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Supplemental Digital Content is available in the text.,Clinical trials have shown cardiovascular benefits and potential risks from sodium glucose cotransporter 2 inhibitors (SGLT2i).,Trials may have limited ability to address individual end points or safety concerns.,We performed a population-based cohort study among patients with type 2 diabetes mellitus with established cardiovascular disease newly initiated on antihyperglycemic agents within the US Department of Defense Military Health System between April 1, 2013, and December 31, 2016.,Incidence rates, hazard ratios (HRs), and 95% confidence intervals (CIs) for time to first composite end point of all-cause mortality and hospitalization for heart failure event, major adverse cardiovascular events (defined as all-cause mortality, nonfatal myocardial infarction, and nonfatal stroke), and individual end points were evaluated using conditional Cox models comparing new SGLT2i users with other antihyperglycemic agents.,The exploratory safety end point was below-knee lower extremity amputation.,Intent-to-treat and on-treatment analyses were performed.,After propensity matching, 25 258 patients were followed for a median of 1.6 years.,Compared with non-SGLT2i, initiation of SGLT2i was associated with a lower rate of all-cause mortality and hospitalization for heart failure (1.73 versus 3.01 events per 100 person-years; HR, 0.57; 95% CI, 0.50-0.65) and major adverse cardiovascular events (2.31 versus 3.45 events per 100 person-years; HR, 0.67; 95% CI, 0.60-0.75).,SGLT2i initiation was also associated with an ≈2-fold higher risk of below-knee lower extremity amputation (0.17 versus 0.09 events per 100 person-years; HR, 1.99; 95% CI, 1.12-3.51).,Because of the disproportionate canagliflozin exposure in the database, the majority of amputations were observed on canagliflozin.,Results were consistent in the on-treatment analysis.,In this high-risk cohort, initiation of SGLT2i was associated with lower risk of all-cause mortality, hospitalization for heart failure, and major adverse cardiovascular events and higher risk of below-knee lower extremity amputation.,Findings underscore the potential benefit and risks to be aware of when initiating SGLT2i.,It remains unclear whether the below-knee lower extremity amputation risk extends across the class of medication, because the study was not powered to make comparisons among individual treatments.

Supplemental Digital Content is available in the text.,Canagliflozin is a sodium glucose cotransporter 2 inhibitor that significantly reduces the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in patients with type 2 diabetes mellitus and elevated cardiovascular risk.,The comparative effects among participants with and without a history of cardiovascular disease (secondary versus primary prevention) were prespecified for evaluation.,The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) randomly assigned 10 142 participants with type 2 diabetes mellitus to canagliflozin or placebo.,The primary prevention cohort comprised individuals ≥50 years of age with ≥2 risk factors for cardiovascular events but with no prior cardiovascular event, and the secondary prevention cohort comprised individuals ≥30 years of age with a prior cardiovascular event.,The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.,Secondary outcomes included heart failure hospitalization and a renal composite (40% reduction in estimated glomerular filtration rate, renal replacement therapy, or renal death).,Primary prevention participants (N=3486; 34%) were younger (63 versus 64 years of age), were more often female (45% versus 31%), and had a longer duration of diabetes mellitus (14 versus 13 years) compared with secondary prevention participants (N=6656; 66%).,The primary end point event rate was higher in the secondary prevention group compared with the primary prevention group (36.9 versus 15.7/1000 patient-years, P<0.001).,In the total cohort, the primary end point was reduced with canagliflozin compared with placebo (26.9 versus 31.5/1000 patient-years; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.97; P<0.001 for noninferiority, P=0.02 for superiority) with no statistical evidence of heterogeneity (interaction P value=0.18) between the primary (HR, 0.98; 95% CI, 0.74-1.30) and secondary prevention (HR, 0.82; 95% CI, 0.72-0.95) cohorts.,Renal outcomes (HR, 0.59; 95% CI, 0.44-0.79 versus HR, 0.63; 95% CI, 0.39-1.02; interaction P value=0.73) and heart failure hospitalization (HR, 0.68; 95% CI, 0.51-0.90 versus HR, 0.64; 95% CI, 0.35-1.15; interaction P value=0.91) were similarly reduced in the secondary and primary prevention cohorts, respectively.,Lower extremity amputations were similarly increased in the secondary and primary prevention cohorts (HR, 2.07; 95% CI, 1.43-3.00 versus HR, 1.52; 95% CI, 0.70-3.29; interaction P value=0.63).,Patients with type 2 diabetes mellitus and prior cardiovascular events had higher rates of cardiovascular outcomes compared with the primary prevention patients.,Canagliflozin reduced cardiovascular and renal outcomes with no statistical evidence of heterogeneity of the treatment effect across the primary and secondary prevention groups.,Additional studies will provide further insights into the effects of canagliflozin in these patient populations.,URL: https://www.clinicaltrials.gov.,Unique identifiers: NCT01032629 and NCT01989754.

The zebrafish (Danio rerio) has become a popular vertebrate model organism to study organ formation and function due to its optical clarity and rapid embryonic development.,The use of genetically modified zebrafish has also allowed identification of new putative therapeutic drugs.,So far, most studies have relied on broad overexpression of transgenes harboring patient-derived mutations or loss-of-function mutants, which incompletely model the human disease allele in terms of expression levels or cell-type specificity of the endogenous gene of interest.,Most human genetically inherited conditions are caused by alleles carrying single nucleotide changes resulting in altered gene function.,Introduction of such point mutations in the zebrafish genome would be a prerequisite to recapitulate human disease but remains challenging to this day.,We present an effective approach to introduce small nucleotide changes in the zebrafish genome.,We generated four different knock-in lines carrying distinct human cardiovascular-disorder-causing missense mutations in their zebrafish orthologous genes by combining CRISPR/Cas9 with a short template oligonucleotide.,Three of these lines carry gain-of-function mutations in genes encoding the pore-forming (Kir6.1, KCNJ8) and regulatory (SUR2, ABCC9) subunits of an ATP-sensitive potassium channel (KATP) linked to Cantú syndrome (CS).,Our heterozygous zebrafish knock-in lines display significantly enlarged ventricles with enhanced cardiac output and contractile function, and distinct cerebral vasodilation, demonstrating the causality of the introduced mutations for CS.,These results demonstrate that introducing patient alleles in their zebrafish orthologs promises a broad application for modeling human genetic diseases, paving the way for new therapeutic strategies using this model organism.,Summary: By using a single-stranded DNA oligonucleotide template in combination with CRISPR/Cas9 in zebrafish, the authors achieved effective germline-transmissible introduction of patient-specific single-nucleotide changes related to cardiovascular disease.

Whole-genome and exome sequencing efforts are increasingly identifying candidate genetic variants associated with human disease.,However, predicting and testing the pathogenicity of a genetic variant remains challenging.,Genome editing allows for the rigorous functional testing of human genetic variants in animal models.,Congenital heart defects (CHDs) are a prominent example of a human disorder with complex genetics.,An inherited sequence variant in the human PBX3 gene (PBX3 p.A136V) has previously been shown to be enriched in a CHD patient cohort, indicating that the PBX3 p.A136V variant could be a modifier allele for CHDs.,Pbx genes encode three-amino-acid loop extension (TALE)-class homeodomain-containing DNA-binding proteins with diverse roles in development and disease, and are required for heart development in mouse and zebrafish.,Here, we used CRISPR-Cas9 genome editing to directly test whether this Pbx gene variant acts as a genetic modifier in zebrafish heart development.,We used a single-stranded oligodeoxynucleotide to precisely introduce the human PBX3 p.A136V variant in the homologous zebrafish pbx4 gene (pbx4 p.A131V).,We observed that zebrafish that are homozygous for pbx4 p.A131V are viable as adults.,However, the pbx4 p.A131V variant enhances the embryonic cardiac morphogenesis phenotype caused by loss of the known cardiac specification factor, Hand2.,Our study is the first example of using precision genome editing in zebrafish to demonstrate a function for a human disease-associated single nucleotide variant of unknown significance.,Our work underscores the importance of testing the roles of inherited variants, not just de novo variants, as genetic modifiers of CHDs.,Our study provides a novel approach toward advancing our understanding of the complex genetics of CHDs.,Summary: This study uses genome editing in zebrafish to demonstrate that a human DNA sequence variant of unknown significance might contribute to the complex genetics of congenital heart defects.

Type 2 Diabetes Mellitus (T2DM) is a well-known comorbidity to COVID-19 and coagulopathies are a common accompaniment to both T2DM and COVID-19.,In addition, patients with COVID-19 are known to develop micro-clots within the lungs.,The rapid detection of COVID-19 uses genotypic testing for the presence of SARS-Cov-2 virus in nasopharyngeal swabs, but it can have a poor sensitivity.,A rapid, host-based physiological test that indicated clotting severity and the extent of clotting pathologies in the individual who was infected or not would be highly desirable.,Platelet poor plasma (PPP) was collected and frozen.,On the day of analysis, PPP samples were thawed and analysed.,We show here that microclots can be detected in the native plasma of twenty COVID-19, as well as ten T2DM patients, without the addition of any clotting agent, and in particular that such clots are amyloid in nature as judged by a standard fluorogenic stain.,Results were compared to ten healthy age-matched individuals.,In COVID-19 plasma these microclots are significantly increased when compared to the levels in T2DM.,This fluorogenic test may provide a rapid and convenient test with 100% sensitivity (P < 0.0001) and is consistent with the recognition that the early detection and prevention of such clotting can have an important role in therapy.

Although the pathophysiology underlying severe COVID19 remains poorly understood, accumulating data suggest that a lung‐centric coagulopathy may play an important role.,Elevated D‐dimer levels which correlated inversely with overall survival were recently reported in Chinese cohort studies.,Critically however, ethnicity has major effects on thrombotic risk, with a 3-4‐fold lower risk in Chinese compared to Caucasians and a significantly higher risk in African‐Americans.,In this study, we investigated COVID19 coagulopathy in Caucasian patients.,Our findings confirm that severe COVID19 infection is associated with a significant coagulopathy that correlates with disease severity.,Importantly however, Caucasian COVID19 patients on low molecular weight heparin thromboprophylaxis rarely develop overt disseminated intravascular coagulation (DIC).,In rare COVID19 cases where DIC does develop, it tends to be restricted to late‐stage disease.,Collectively, these data suggest that the diffuse bilateral pulmonary inflammation observed in COVID19 is associated with a novel pulmonary‐specific vasculopathy termed pulmonary intravascular coagulopathy (PIC) as distinct to DIC.,Given that thrombotic risk is significantly impacted by race, coupled with the accumulating evidence that coagulopathy is important in COVID19 pathogenesis, our findings raise the intriguing possibility that pulmonary vasculopathy may contribute to the unexplained differences that are beginning to emerge highlighting racial susceptibility to COVID19 mortality.

Patients with stroke-like symptoms may be underutilising emergency medical services and avoiding hospitalisation during the COVID-19 pandemic.,We investigated a decline in admissions for stroke and transient ischaemic attack (TIA) and emergency department (ED) stroke alert activations.,We retrospectively compiled total weekly hospital admissions for stroke and TIA between 31 December 2018 and 21 April 2019 versus 30 December 2019 and 19 April 2020 at five US tertiary academic comprehensive stroke centres in cities with early COVID-19 outbreaks in Boston, New York City, Providence and Seattle.,We collected available data on ED stroke alerts, stroke severity using the National Institutes of Health Stroke Scale (NIHSS) and time from symptom onset to hospital arrival.,Compared with 31 December 2018 to 21 April 2019, a decline in stroke/TIA admissions and ED stroke alerts occurred during 30 December 2019 to 19 April 2020 (p trend <0.001 for each).,The declines coincided with state stay-at-home recommendations in late March.,The greatest decline in hospital admissions was observed between 23 March and 19 April 2020, with a 31% decline compared with the corresponding weeks in 2019.,Three of the five centres with 2019 and 2020 stroke alert data had a 46% decline in ED stroke alerts in late March and April 2020, compared with 2019.,Median baseline NIHSS during these 4 weeks was 10 in 2020 and 7 in 2019.,There was no difference in time from symptom onset to hospital arrival.,At these five large academic US hospitals, admissions for stroke and TIA declined during the COVID-19 pandemic.,There was a trend for fewer ED stroke alerts at three of the five centres with available 2019 and 2020 data.,Acute stroke therapies are time-sensitive, so decreased healthcare access or utilisation may lead to more disabling or fatal strokes, or more severe non-neurological complications related to stroke.,Our findings underscore the indirect effects of this pandemic.,Public health officials, hospital systems and healthcare providers must continue to encourage patients with stroke to seek acute care during this crisis.

COVID-19 is an infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).,Apart from respiratory complications, acute cerebrovascular disease (CVD) has been observed in some patients with COVID-19.,Therefore, we described the clinical characteristics, laboratory features, treatment and outcomes of CVD complicating SARS-CoV-2 infection.,Demographic and clinical characteristics, laboratory findings, treatments and clinical outcomes were collected and analysed.,Clinical characteristics and laboratory findings of patients with COVID-19 with or without new-onset CVD were compared.,Of 219 patients with COVID-19, 10 (4.6%) developed acute ischaemic stroke and 1 (0.5%) had intracerebral haemorrhage.,COVID-19 with new onset of CVD were significantly older (75.7±10.8 years vs 52.1±15.3 years, p<0.001), more likely to present with severe COVID-19 (81.8% vs 39.9%, p<0.01) and were more likely to have cardiovascular risk factors, including hypertension, diabetes and medical history of CVD (all p<0.05).,In addition, they were more likely to have increased inflammatory response and hypercoagulable state as reflected in C reactive protein (51.1 (1.3-127.9) vs 12.1 (0.1-212.0) mg/L, p<0.05) and D-dimer (6.9 (0.3-20.0) vs 0.5 (0.1-20.0) mg/L, p<0.001).,Of 10 patients with ischemic stroke; 6 received antiplatelet treatment with aspirin or clopidogrel; and 3 of them died.,The other four patients received anticoagulant treatment with enoxaparin and 2 of them died.,As of 24 March 2020, six patients with CVD died (54.5%).,Acute CVD is not uncommon in COVID-19.,Our findings suggest that older patients with risk factors are more likely to develop CVD.,The development of CVD is an important negative prognostic factor which requires further study to identify optimal management strategy to combat the COVID-19 outbreak.

Patients with COVID-19 have a coagulopathy and high thrombotic risk.,In a cohort of 69 intensive care unit (ICU) patients we investigated for evidence of heparin resistance in those that have received therapeutic anticoagulation. 15 of the patients have received therapeutic anticoagulation with either unfractionated heparin (UFH) or low molecular weight heparin (LMWH), of which full information was available on 14 patients.,Heparin resistance to UFH was documented in 8/10 (80%) patients and sub-optimal peak anti-Xa following therapeutic LMWH in 5/5 (100%) patients where this was measured (some patients received both anticoagulants sequentially).,Spiking plasma from 12 COVID-19 ICU patient samples demonstrated decreased in-vitro recovery of anti-Xa compared to normal pooled plasma.,In conclusion, we have found evidence of heparin resistance in critically unwell COVID-19 patients.,Further studies investigating this are required to determine the optimal thromboprophylaxis in COVID-19 and management of thrombotic episodes.

Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users.

To determine the incidence, patient characteristics, and related events associated with new-onset atrial fibrillation (AF) during a national COVID-19 lockdown.,Using nationwide Danish registries, we included all patients, aged 18-90 years, receiving a new-onset AF diagnosis during the first 3 months of 2019 and 2020.,The main comparison was between patients diagnosed during lockdown (12 March 12-1 April 2020) and patients diagnosed in the corresponding period 1 year previously.,We found a lower incidence of new-onset AF during the 3 weeks of lockdown compared with the corresponding weeks in 2019 [incidence rate ratios with 95% confidence intervals (CIs) for the 3 weeks: 0.66 (0.56-0.78), 0.53 (0.45-0.64), and 0.41 (0.34-0.50)].,There was a 47% drop in total numbers (562 vs.,1053).,Patients diagnosed during lockdown were younger and with a lower CHA2DS2-VASc score, while history of cancer, heart failure, and vascular disease were more prevalent.,During lockdown, 30 (5.3%) patients with new-onset AF suffered an ischaemic stroke and 15 (2.7%) died, compared with 45 (4.3%) and 14 (1.3%) patients during the corresponding 2019 period, respectively.,The adjusted odds ratio of a related event (ischaemic stroke or all-cause death) during lock-down compared with the corresponding weeks was 1.41 (95% CI 0.93-2.12).,Following a national lockdown in Denmark, a 47% drop in registered new-onset AF cases was observed.,In the event of prolonged or subsequent lockdowns, the risk of undiagnosed AF patients developing complications could potentially translate into poorer outcomes in patients with AF during the COVID-19 pandemic.,Graphical Abstract

•There are anecdotal reports of lower stroke rates during the COVID-19 pandemic.,•Our center confirms a local fall in new acute stroke diagnoses during the pandemic.,•This fall is driven by fewer patients presenting with mild symptoms in our network.,•Mild stroke symptoms ought to not be ignored in community practices.,There are anecdotal reports of lower stroke rates during the COVID-19 pandemic.,Our center confirms a local fall in new acute stroke diagnoses during the pandemic.,This fall is driven by fewer patients presenting with mild symptoms in our network.,Mild stroke symptoms ought to not be ignored in community practices.,Although there is evidence to suggest a high rate of cerebrovascular complications in patients with SARS-CoV-2 infection, anecdotal reports indicate a falling rate of new ischemic stroke diagnoses.,We conducted an exploratory single-center analysis to estimate the change in number of new stroke diagnoses in our region, and evaluate the proximate reasons for this change during the COVID-19 pandemic at a tertiary care center in New Jersey.,A Comprehensive Stroke Center prospective cohort was retrospectively analyzed for the number of stroke admissions, demographic features, and short-term outcomes 5 months prior to 3/1/2020 (pre-COVID-19), and in the 6 weeks that followed (COVID-19 period).,The primary outcome was the number of new acute stroke diagnoses before and during the COVID-19 period, as well as the potential reasons for a decline in the number of new diagnoses.,Of the 328 included patients, 53 (16%) presented in the COVID-19 period.,There was a mean fall of 38% in new stroke diagnoses (mean 1.13/day [SD 1.07] from 1.82/day [SD 1.38], p<0.01), which was related to a 59% decline in the number of daily transfers from referral centers (p<0.01), 25% fewer telestroke consultations (p=0.08), and 55% fewer patients presenting directly to our institution by private vehicle (p<0.01) and 29% fewer patients through emergency services (p=0.09).,There was no significant change in the monthly number of strokes due to large vessel occlusion (LVO), however the proportion of new LVOs nearly doubled in the COVID-19 period (38% vs. 21%, p=0.01).,The observations at our tertiary care center corroborate anecdotal reports that the number of new stroke diagnoses is falling, which seems related to a smaller proportion of patients seeking healthcare services for milder symptoms.,These preliminary data warrant validation in larger, multi-center studies.

The COVID‐19 pandemic has become an urgent issue in every country.,Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)‐like massive intravascular clot formation is frequently seen in this cohort.,Therefore, coagulation tests may be considered useful to discriminate severe cases of COVID‐19.,The clinical presentation of COVID‐19‐associated coagulopathy is organ dysfunction primarily, whereas hemorrhagic events are less frequent.,Changes in hemostatic biomarkers represented by increase in D‐dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation.,In comparison with bacterial‐sepsis‐associated coagulopathy/DIC, prolongation of prothrombin time, and activated partial thromboplastin time, and decrease in antithrombin activity is less frequent and thrombocytopenia is relatively uncommon in COVID‐19.,The mechanisms of the coagulopathy are not fully elucidated, however.,It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell death, hypoxia, and endothelial damage are involved.,Bleeding tendency is uncommon, but the incidence of thrombosis in COVID‐19 and the adequacy of current recommendations regarding standard venous thromboembolic dosing are uncertain.

Novel coronavirus disease 2019 (COVID-19) has been associated with an increased risk of arterial and venous thromboembolic (VTE) diseases.,However, there is a limited amount of data regarding the prevention and management of VTE in severe hospitalized COVID-19 patients.,In this article, we review currently available clinical data, and mechanisms for COVID-associated coagulopathy, and propose algorithms for screening, prevention (including extended-duration prophylaxis), and treatment of these patients.,Although these recommendations are subject to change given rapidly evolving data, we provide a framework that can guide clinicians in managing thrombotic complications in this challenging condition.

The effect of implantable cardioverter-defibrillator (ICD) therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes is not fully elucidated.,We examined the effect of ICD therapy on sudden cardiac death, cardiovascular death and all-cause mortality, according to diabetes status at baseline in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT).,The outcomes were analyzed by use of cumulative incidence curves and Cox regressions models.,Of the 1676 patients randomized to an ICD or placebo, 540 (32%) had diabetes at baseline.,Patients with diabetes were slightly older (61 vs 58 years) and were more often in NYHA class III (37% vs 28%).,ICD therapy did not reduce the risk of sudden cardiac death in HFrEF patients with diabetes (HR = 0.85; 95% CI 0.52-1.40); even though these patients had a higher risk of sudden cardiac death compared to patients without diabetes (HR = 1.73 95% CI 1.22-2.47).,By contrast, ICD therapy did reduce sudden cardiac death in HFrEF patients without diabetes (HR = 0.26; 95% CI 0.15-0.46); Pinteraction=0.002.,The findings for cardiovascular and all-cause death were similar.,ICD therapy did not reduce the risk of sudden cardiac death (or, as a consequence, all-cause death) in HFrEF patients with diabetes.,Conversely, an ICD reduced the risk of sudden death in patients without diabetes, irrespective of etiology.,The online version of this article (10.1007/s00392-019-01415-z) contains supplementary material, which is available to authorized users.

Supplemental Digital Content is available in the text.,In the EMPA-REG OUTCOME trial (BI 10773 [Empagliflozin] Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients) in patients with type 2 diabetes mellitus and atherosclerotic cardiovascular disease, in comparison with placebo, empagliflozin reduced the risks of 3-point major adverse cardiovascular events (3-point MACE), cardiovascular and all-cause death, and hospitalization for heart failure.,We investigated whether these effects varied across the spectrum of baseline cardiovascular risk.,Cardiovascular death, all-cause mortality, 3-point MACE, and hospitalization for heart failure in the pooled empagliflozin and placebo groups were analyzed in subgroups by prior myocardial infarction and stroke at baseline, and by estimated baseline cardiovascular risk based on the 10-point TIMI (Thrombolysis In Myocardial Infarction) Risk Score for Secondary Prevention.,Of 7020 patients who received the study drug, 65% had a prior myocardial infarction or stroke, and 12%, 40%, 30%, and 18% were at low, intermediate, high, and highest estimated cardiovascular risk according to TIMI Risk Score for Secondary Prevention (≤2, 3, 4, and ≥5 points, respectively).,In the placebo group, 3-point MACE occurred during the trial in 7.3%, 9.4%, 12.6%, and 20.6% of patients at low, intermediate, high, and highest estimated baseline risk, respectively.,Relative reductions in risk of cardiovascular death, all-cause mortality, 3-point MACE and hospitalization for heart failure with empagliflozin versus placebo were consistent in patients with and without prior myocardial infarction and/or stroke and across subgroups by TIMI Risk Score for Secondary Prevention at baseline (P>0.05 for randomized group-by-subgroup interactions).,Despite all patients having atherosclerotic cardiovascular disease, patients in EMPA-REG OUTCOME demonstrated a broad risk spectrum for cardiovascular events.,Reductions in key cardiovascular outcomes and mortality with empagliflozin versus placebo were consistent across the range of cardiovascular risk.,URL: https://www.clinicaltrials.gov.,Unique identifier: NCT01131676.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting-enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied.,We carried out a population-based case-control study in the Lombardy region of Italy.,A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence.,Information about the use of selected drugs and patients’ clinical profiles was obtained from regional databases of health care use.,Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression.,Among both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women.,The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile.,Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex.,In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease.,However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.

To investigate the prevalence and prognostic impact of right heart failure and right ventricular-arterial uncoupling in Corona Virus Infectious Disease 2019 (COVID-19) complicated by an Acute Respiratory Distress Syndrome (ARDS).,Ninety-four consecutive patients (mean age 64 years) admitted for acute respiratory failure on COVID-19 were enrolled.,Coupling of right ventricular function to the pulmonary circulation was evaluated by a comprehensive trans-thoracic echocardiography with focus on the tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (PASP) ratio,The majority of patients needed ventilatory support, which was noninvasive in 22 and invasive in 37.,There were 25 deaths, all in the invasively ventilated patients.,Survivors were younger (62 ± 13 vs. 68 ± 12 years, p = 0.033), less often overweight or usual smokers, had lower NT-proBNP and interleukin-6, and higher arterial partial pressure of oxygen (PaO2)/fraction of inspired O2 (FIO2) ratio (270 ± 104 vs. 117 ± 57 mmHg, p < 0.001).,In the non-survivors, PASP was increased (42 ± 12 vs. 30 ± 7 mmHg, p < 0.001), while TAPSE was decreased (19 ± 4 vs. 25 ± 4 mm, p < 0.001).,Accordingly, the TAPSE/PASP ratio was lower than in the survivors (0.51 ± 0.22 vs.,0.89 ± 0.29 mm/mmHg, p < 0.001).,At univariate/multivariable analysis, the TAPSE/PASP (HR: 0.026; 95%CI 0.01-0.579; p: 0.019) and PaO2/FIO2 (HR: 0.988; 95%CI 0.988-0.998; p: 0.018) ratios were the only independent predictors of mortality, with ROC-determined cutoff values of 159 mmHg and 0.635 mm/mmHg, respectively.,COVID-19 ARDS is associated with clinically relevant uncoupling of right ventricular function from the pulmonary circulation; bedside echocardiography of TAPSE/PASP adds to the prognostic relevance of PaO2/FIO2 in ARDS on COVID-19.

To assess the prevalence, characteristics and prognostic value of pulmonary hypertension (PH) and right ventricular dysfunction (RVD) in hospitalised, non-intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19).,This single-centre, observational, cross-sectional study included 211 patients with COVID-19 admitted to non-ICU departments who underwent a single transthoracic echocardiography (TTE).,Patients with poor acoustic window (n=11) were excluded.,Clinical, imaging, laboratory and TTE findings were compared in patients with versus without PH (estimated systolic pulmonary artery pressure >35 mm Hg) and with versus without RVD (tricuspid annular plane systolic excursion <17 mm or S wave <9.5 cm/s).,The primary endpoint was in-hospital death or ICU admission.,A total of 200 patients were included in the final analysis (median age 62 (IQR 52-74) years, 65.5% men).,The prevalence of PH and RVD was 12.0% (24/200) and 14.5% (29/200), respectively.,Patients with PH were older and had a higher burden of pre-existing cardiac comorbidities and signs of more severe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (radiological lung involvement, laboratory findings and oxygenation status) compared with those without PH.,Conversely, patients with RVD had a higher burden of pre-existing cardiac comorbidities but no evidence of more severe SARS-CoV-2 infection compared with those without RVD.,The presence of PH was associated with a higher rate of in-hospital death or ICU admission (41.7 vs 8.5%, p<0.001), while the presence of RVD was not (17.2 vs 11.7%, p=0.404).,Among hospitalised non-ICU patients with COVID-19, PH (and not RVD) was associated with signs of more severe COVID-19 and with worse in-hospital clinical outcome.,NCT04318366

Specific clinical risk factors linked to transient ischemic attack (TIA) could affect functional ambulatory outcome following thrombolytic therapy in patients having ischemic stroke with a prior TIA (TIA-ischemic stroke).,This issue was investigated in this study.,We retrospectively analyzed data from 6379 ischemic stroke patients of which 1387 presented with an antecedent TIA prior to onset of stroke.,We used logistic regression model to identify demographic and clinical risk factors that are associated with functional ambulatory outcome in patients with TIA-ischemic stroke treated with thrombolytic therapy.,In a population of TIA-ischemic stroke who received recombinant tissue plasminogen activator, patients with a history of stroke (odds ratio [OR] = 3.229, 95% confidence interval [CI] = 1.494-6.98, P = .003) were associated with increasing odds of improvement in functional ambulation, while the female gender (OR = 0.462, 95% CI = 0.223-0.956, P = .037) was associated with reducing odds of improvement.,In the non-TIA group, dyslipidemia (OR = 1.351, 95% CI = 1.026-1.781, P = .032) and blood glucose (OR = 1.003, 95% CI = 1.0-1.005, P = .041) were associated with the increasing odds of improvement while older patients (OR = 0.989, 95% CI = 0.98-0.999, P = .029) with heart failure (OR = 0.513, 95% CI = 0.326-0.808, P = .004) and higher lipid level (OR = 0.834, 95% CI = 0.728-0.955, P = .009) were associated with reducing odds of improvement in ambulation.,In a population of TIA-ischemic stroke with thrombolytic therapy and a clearly defined TIA without focal ischemic injury, regardless of associated clinical risk factors, a TIA prior to a stroke is not associated with reducing odds of improved ambulatory outcome, except in female patients with TIA-ischemic stroke.

Specific clinical risk factors may contribute to improving or worsening neurological functions in acute ischemic stroke (AIS) patients pre-treated with a combined cholesterol reducer and recombinant tissue plasminogen activator (rtPA) therapy.,In this study, clinical risk factors associated with good or poor presenting neurological symptoms in ischemic stroke patients with prior cholesterol reducer use, specifically a statin and rtPA therapy was investigated.,Retrospective data for baseline clinical and demographic data for patients with AIS taking cholesterol reducers prior to rtPA treatment from January 2010 to June 2016 in a regional stroke center was analyzed.,Improving (NIHSS score ≤ 7) or worsening (NIHSS score > 7) of neurologic functions were the determined measures of treatment outcome.,Multivariate logistic regression models identified demographic and clinical factors associated with worsening or improving neurologic functions.,Adjusted multivariate analysis showed that in an AIS population with a combined rtPA and cholesterol reducer medication history, increasing age (OR = 1.032, 95% CI, 1.015-1.048, P < 0.001) and atrial fibrillation (OR = 1.859, 95% CI, 1.098-3.149, P = 0.021) demonstrated a likely association with worsening neurologic functions, while direct admission (OR = 0.411, 95% CI, 0.246-0.686, P = 0.001) and being Caucasian (OR = 0.496, 95% CI, 0.297-0.827, P = 0.007) showed an association with improving or progressing neurologic functions.,A prior cholesterol reducer, namely a statin, plus rtPA combination may be associated with worsening neurological function for elderly AIS patients with atrial fibrillation, while Caucasians directly admitted to a neurology unit are more likely to show an association with progress or improvements in neurologic functions.,While combining statin with rtPA treatment may facilitate worsening neurologic functions in elderly AIS patients with atrial fibrillation, they should not be denied of this therapy.,The decision to combine statin and rtPA for AIS patients with atrial fibrillation can be done after clinical stabilization following appropriate clinical management.

Coronavirus disease 2019 (COVID-19) has become a global pandemic, affecting millions of people.,However, the relationship between COVID-19 and acute cerebrovascular diseases is unclear.,We aimed to characterize the incidence, risk factors, clinical-radiological manifestations, and outcome of COVID-19-associated stroke.,Three medical databases were systematically reviewed for published articles on acute cerebrovascular diseases in COVID-19 (December 2019-September 2020).,The review protocol was previously registered (PROSPERO ID = CRD42020185476).,Data were extracted from articles reporting ≥5 stroke cases in COVID-19.,We complied with the PRISMA guidelines and used the Newcastle-Ottawa Scale to assess data quality.,Data were pooled using a random-effect model.,Of 2277 initially identified articles, 61 (2.7%) were entered in the meta-analysis.,Out of 108,571 patients with COVID-19, acute CVD occurred in 1.4% (95%CI: 1.0-1.9).,The most common manifestation was acute ischemic stroke (87.4%); intracerebral hemorrhage was less common (11.6%).,Patients with COVID-19 developing acute cerebrovascular diseases, compared to those who did not, were older (pooled median difference = 4.8 years; 95%CI: 1.7-22.4), more likely to have hypertension (OR = 7.35; 95%CI: 1.94-27.87), diabetes mellitus (OR = 5.56; 95%CI: 3.34-9.24), coronary artery disease (OR = 3.12; 95%CI: 1.61-6.02), and severe infection (OR = 5.10; 95%CI: 2.72-9.54).,Compared to individuals who experienced a stroke without the infection, patients with COVID-19 and stroke were younger (pooled median difference = −6.0 years; 95%CI: −12.3 to −1.4), had higher NIHSS (pooled median difference = 5; 95%CI: 3-9), higher frequency of large vessel occlusion (OR = 2.73; 95%CI: 1.63-4.57), and higher in-hospital mortality rate (OR = 5.21; 95%CI: 3.43-7.90).,Acute cerebrovascular diseases are not uncommon in patients with COVID-19, especially in those whom are severely infected and have pre-existing vascular risk factors.,The pattern of large vessel occlusion and multi-territory infarcts suggests that cerebral thrombosis and/or thromboembolism could be possible causative pathways for the disease.

Supplemental Digital Content is available in the text.,The impact of coronavirus disease 2019 (COVID-19) on the occurrence of ischemic stroke has been the subject of increased speculation but has not been confirmed in large observational studies.,We investigated the association between COVID-19 and stroke.,We performed a cross-sectional study involving patients discharged from a healthcare system in New York State, from January to April 2020.,A mixed-effects logistic regression analysis and a propensity score-weighted analysis were used to control for confounders and investigate the association of COVID-19 with ischemic stroke.,Similar techniques were used to detect the impact of concurrent COVID-19 infection on unfavorable outcomes for patients with stroke.,Among 24 808 discharges, 2513 (10.1%) were diagnosed with COVID-19, and 566 (0.2%) presented with acute ischemic stroke.,Patients diagnosed with COVID-19 were at one-quarter the odds of stroke compared with other patients (odds ratio, 0.25 [95% CI, 0.16-0.40]).,This association was consistent in all age groups.,Our results were robust in sensitivity analyses, including propensity score-weighted regression models.,In patients presenting with stroke, concurrent infection with severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) was associated with higher case-fatality (odds ratio, 10.50 [95% CI, 3.54-31.18]) and a trend towards increased occurrence of discharge to rehabilitation (odds ratio, 2.45 [95% CI, 0.81-1.25]).,Using a comprehensive cross-section of patients from a large NY-based healthcare system, we did not identify a positive association between ischemic stroke and COVID-19.,However, patients with stroke with COVID-19 had worse outcomes compared with those without, with over a 9-fold increase in mortality.,Although no definitive conclusions can be reached from our observational study, our data do not support the concerns for an epidemic of stroke in young adults with COVID-19.

Some patients with severe COVID-19 develop prothrombotic autoantibodies that are similar to antiphospholipid antibodies found in autoimmune diseases.,Patients with severe COVID-19 are at high risk for occlusion of blood vessels of all sizes.,This prothrombotic phenotype is reminiscent of patients with lupus and antiphospholipid syndrome, who have long-lived circulating antiphospholipid autoantibodies.,In new work, Zuo et al. measured eight types of antiphospholipid antibodies in serum from patients hospitalized with COVID-19 and found at least one antibody in half of patients.,Antibody levels were associated with neutrophil and coagulation pathway activation.,Purified antibodies from some patients activated neutrophils in vitro and potentiated thrombosis when injected into mice.,Together, these findings suggest that autoantibodies are a potential therapeutic target in severe COVID-19.,Patients with COVID-19 are at high risk for thrombotic arterial and venous occlusions.,Lung histopathology often reveals fibrin-based blockages in the small blood vessels of patients who succumb to the disease.,Antiphospholipid syndrome is an acquired and potentially life-threatening thrombophilia in which patients develop pathogenic autoantibodies targeting phospholipids and phospholipid-binding proteins (aPL antibodies).,Case series have recently detected aPL antibodies in patients with COVID-19.,Here, we measured eight types of aPL antibodies in serum samples from 172 patients hospitalized with COVID-19.,These aPL antibodies included anticardiolipin IgG, IgM, and IgA; anti-β2 glycoprotein I IgG, IgM, and IgA; and anti-phosphatidylserine/prothrombin (aPS/PT) IgG and IgM.,We detected aPS/PT IgG in 24% of serum samples, anticardiolipin IgM in 23% of samples, and aPS/PT IgM in 18% of samples.,Antiphospholipid autoantibodies were present in 52% of serum samples using the manufacturer’s threshold and in 30% using a more stringent cutoff (≥40 ELISA-specific units).,Higher titers of aPL antibodies were associated with neutrophil hyperactivity, including the release of neutrophil extracellular traps (NETs), higher platelet counts, more severe respiratory disease, and lower clinical estimated glomerular filtration rate.,Similar to IgG from patients with antiphospholipid syndrome, IgG fractions isolated from patients with COVID-19 promoted NET release from neutrophils isolated from healthy individuals.,Furthermore, injection of IgG purified from COVID-19 patient serum into mice accelerated venous thrombosis in two mouse models.,These findings suggest that half of patients hospitalized with COVID-19 become at least transiently positive for aPL antibodies and that these autoantibodies are potentially pathogenic.

Since the appearance of the first case of coronavirus disease 2019 (COVID-19) a pandemic has emerged affecting millions of people worldwide.,Although the main clinical manifestations are respiratory, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected.,We present cerebrovascular disease case incidence in hospitalized patients with SARS-CoV-2 infection.,Patients were confirmed by microbiological/serological testing, or on chest CT semiology.,Available data on comorbidity, laboratory parameters, treatment administered, neuroimaging, neuropathological studies and clinical evolution during hospitalization, measured by the modified Rankin scale, were analysed.,A bivariate study was also designed to identify differences between ischaemic and haemorrhagic subtypes.,A statistical model of binary logistic regression and sensitivity analysis was designed to study the influence of independent variables over prognosis.,In our centre, there were 1683 admissions of patients with COVID-19 over 50 days, of which 23 (1.4%) developed cerebrovascular disease.,Within this group of patients, cerebral and chest CT scans were performed in all cases, and MRI in six (26.1%).,Histological samples were obtained in 6/23 cases (two brain biopsies, and four arterial thrombi).,Seventeen patients were classified as cerebral ischaemia (73.9%, with two arterial dissections), five as intracerebral haemorrhage (21.7%), and one leukoencephalopathy of posterior reversible encephalopathy type.,Haemorrhagic patients had higher ferritin levels at the time of stroke (1554.3 versus 519.2, P = 0.004).,Ischaemic strokes were unexpectedly frequent in the vertebrobasilar territory (6/17, 35.3%).,In the haemorrhagic group, a characteristic radiological pattern was identified showing subarachnoid haemorrhage, parieto-occipital leukoencephalopathy, microbleeds and single or multiple focal haematomas.,Brain biopsies performed showed signs of thrombotic microangiopathy and endothelial injury, with no evidence of vasculitis or necrotizing encephalitis.,The functional prognosis during the hospital period was unfavourable in 73.9% (17/23 modified Rankin scale 4-6), and age was the main predictive variable (odds ratio = 1.5; 95% confidence interval 1.012-2.225; P = 0.043).,Our series shows cerebrovascular disease incidence of 1.4% in patients with COVID-19 with high morbidity and mortality.,We describe pathological and radiological data consistent with thrombotic microangiopathy caused by endotheliopathy with a haemorrhagic predisposition.

Supplemental Digital Content is available in the text.,Myocarditis has been recognized as a rare complication of coronavirus disease 2019 (COVID-19) mRNA vaccinations, especially in young adult and adolescent males.,According to the US Centers for Disease Control and Prevention, myocarditis/pericarditis rates are ≈12.6 cases per million doses of second-dose mRNA vaccine among individuals 12 to 39 years of age.,In reported cases, patients with myocarditis invariably presented with chest pain, usually 2 to 3 days after a second dose of mRNA vaccination, and had elevated cardiac troponin levels.,ECG was abnormal with ST elevations in most, and cardiac MRI was suggestive of myocarditis in all tested patients.,There was no evidence of acute COVID-19 or other viral infections.,In 1 case, a cardiomyopathy gene panel was negative, but autoantibody levels against certain self-antigens and frequency of natural killer cells were increased.,Although the mechanisms for development of myocarditis are not clear, molecular mimicry between the spike protein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) and self-antigens, trigger of preexisting dysregulated immune pathways in certain individuals, immune response to mRNA, and activation of immunologic pathways, and dysregulated cytokine expression have been proposed.,The reasons for male predominance in myocarditis cases are unknown, but possible explanations relate to sex hormone differences in immune response and myocarditis, and also underdiagnosis of cardiac disease in women.,Almost all patients had resolution of symptoms and signs and improvement in diagnostic markers and imaging with or without treatment.,Despite rare cases of myocarditis, the benefit-risk assessment for COVID-19 vaccination shows a favorable balance for all age and sex groups; therefore, COVID-19 vaccination is recommended for everyone ≥12 years of age.

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features of myocardial involvement including elevated serum troponin levels and acute heart failure with reduced ejection fraction.,The cardiac pathological changes in these patients with COVID-19 have yet to be well described.,In an international multicentre study, cardiac tissue from the autopsies of 21 consecutive COVID-19 patients was assessed by cardiovascular pathologists.,The presence of myocarditis, as defined by the presence of multiple foci of inflammation with associated myocyte injury, was determined, and the inflammatory cell composition analysed by immunohistochemistry.,Other forms of acute myocyte injury and inflammation were also described, as well as coronary artery, endocardium, and pericardium involvement.,Lymphocytic myocarditis was present in 3 (14%) of the cases.,In two of these cases, the T lymphocytes were CD4 predominant and in one case the T lymphocytes were CD8 predominant.,Increased interstitial macrophage infiltration was present in 18 (86%) of the cases.,A mild pericarditis was present in four cases.,Acute myocyte injury in the right ventricle, most probably due to strain/overload, was present in four cases.,There was a non-significant trend toward higher serum troponin levels in the patients with myocarditis compared with those without myocarditis.,Disrupted coronary artery plaques, coronary artery aneurysms, and large pulmonary emboli were not identified.,In SARS-CoV-2 there are increased interstitial macrophages in a majority of the cases and multifocal lymphocytic myocarditis in a small fraction of the cases.,Other forms of myocardial injury are also present in these patients.,The macrophage infiltration may reflect underlying diseases rather than COVID-19.

The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease (COVID-19) patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are associated with clinical outcomes remains unknown.,COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors.,We observed that patients receiving ACEI or ARB therapy had a lower rate of severe diseases and a trend toward a lower level of IL-6 in peripheral blood.,In addition, ACEI or ARB therapy increased CD3 and CD8 T cell counts in peripheral blood and decreased the peak viral load compared to other antihypertensive drugs.,This evidence supports the benefit of using ACEIs or ARBs to potentially contribute to the improvement of clinical outcomes of COVID-19 patients with hypertension.

Severe acute respiratory-syndrome coronavirus-2 (SARS-CoV-2) host cell infection is mediated by binding to angiotensin-converting enzyme 2 (ACE2).,Systemic dysregulation observed in SARS-CoV was previously postulated to be due to ACE2/angiotensin 1-7 (Ang1-7)/Mas axis downregulation; increased ACE2 activity was shown to mediate disease protection.,Because angiotensin II receptor blockers, ACE inhibitors, and mineralocorticoid receptor antagonists increase ACE2 receptor expression, it has been tacitly believed that the use of these agents may facilitate viral disease; thus, they should not be used in high-risk patients with cardiovascular disease.,Based on the anti-inflammatory benefits of the upregulation of the ACE2/Ang1-7/Mas axis and previously demonstrated benefits of lung function improvement in SARS-CoV infections, it has been hypothesized that the benefits of treatment with renin-angiotensin system inhibitors in SARS-CoV-2 may outweigh the risks and at the very least should not be withheld.,•COVID-19 has been associated with cardiac involvement.,SARS-CoV-2 requires binding to ACE2 in the RAS.,•The ACE2/Ang1-7/Mas pathway counterbalances the RAS, which results in activation of anti-inflammatory pathways.,•ACE inhibitors, ARBs, and MRAs upregulate ACE2 activity and expression.,•More data are required to determine if regulation of ACE2 in patients with cardiovascular disease and COVID-19 would help improve clinical outcomes.,COVID-19 has been associated with cardiac involvement.,SARS-CoV-2 requires binding to ACE2 in the RAS.,The ACE2/Ang1-7/Mas pathway counterbalances the RAS, which results in activation of anti-inflammatory pathways.,ACE inhibitors, ARBs, and MRAs upregulate ACE2 activity and expression.,More data are required to determine if regulation of ACE2 in patients with cardiovascular disease and COVID-19 would help improve clinical outcomes.

Intestinal ischemia-reperfusion (I/R) injury is a life-threatening vascular emergency and has long been a disturbing problem for surgeons.,Oxidative stress is considered a vital factor in I/R injury.,Metformin has anti-oxidative properties and protects against I/R injury.,The present study aimed to investigate whether Metformin protects against intestinal I/R injury and reveal the protective mechanism of Metformin.,I/R injury was induced in mice by temporary superior mesenteric artery occlusion, and Caco-2 cells were subjected to OGD/R to establish an in vitro model.,Different doses of Metformin were administered in vivo and in vitro.,We found that I/R injury led to intestinal barrier disruption and cell death by examining histopathological results and the intestinal barrier index, including TER, tight junction proteins and serum biomarkers.,We confirmed the existence of pyroptosis in intestinal I/R injury.,Moreover, we confirmed the role of pyroptosis in intestinal I/R injury by silencing the gasdermin D (GSDMD).,Then, we confirmed that Metformin treatment protected barrier function against intestinal I/R injury and reduced oxidative stress and the inflammatory response.,Importantly, Metformin reduced pyroptosis-related proteins, including NLRP3, cleaved caspase-1, and the N-terminus of GSDMD.,Knocking down the GSDMD could reversed the protective effects of Metformin, which showed pyroptosis was one of the major cell death pathways controlled by Metformin treatment in setting of intestinal I/R injury.,We also discovered that Metformin suppressed the expression of TXNIP and the interaction between TXNIP and NLRP3.,We performed siRNA knockdown and found that the protective effects were abolished, which further confirmed our findings.,In conclusion, we believe that Metformin protects against intestinal I/R injury in a TXNIP-NLRP3-GSDMD-dependent manner.,•Pyroptosis plays an important role in intestinal I/R injury.,•Metformin protects against intestinal I/R injury in mice.,•Metformin protects Caco-2 cells subjected to OGD/R.,•Metformin inhibits pyroptosis, inflammation and oxidative stress during I/R injury.,•Metformin exerts protective effect through TXNIP-NLRP3-GSDMD pathway.,Pyroptosis plays an important role in intestinal I/R injury.,Metformin protects against intestinal I/R injury in mice.,Metformin protects Caco-2 cells subjected to OGD/R.,Metformin inhibits pyroptosis, inflammation and oxidative stress during I/R injury.,Metformin exerts protective effect through TXNIP-NLRP3-GSDMD pathway.

Emodin has recently been reported to have a powerful antiinflammatory effect, protecting the myocardium against ischemia/reperfusion (I/R) injury.,Pyroptosis is a proinflammatory programmed cell death that is related to many diseases.,The present study investigated the effect of emodin on pyroptosis in cardiomyocytes.,Sprague Dawley rats were randomly divided into sham, I/R, and I/R+Emodin groups.,I/R model was subjected to 30 minutes’ ligation of left anterior descending coronary artery, followed by 2 hours of reperfusion.,Cardiomyocytes were exposed to hypoxic conditions for 1 hour and normoxic conditions for 2 hours.,The level of the pyroptosis was detected by Western blot, real-time PCR analysis, and ELISA.,The level of gasdermin D-N domains was upregulated in cardiomyocytes during I/R or hypoxia/reoxygenation (H/R) treatment.,Moreover, emodin increased the rate of cell survival in vitro and decreased the myocardial infarct size in vivo via suppressing the levels of I/R-induced pyroptosis.,Additionally, the expression of TLR4, MyD88, phospho-IκBα, phospho-NF-κB, and the NLRP3 inflammasome was significantly upregulated in cardiomyocytes subjected to H/R treatment, while emodin suppressed the expression of these proteins.,This study confirms that emodin treatment was able to alleviate myocardial I/R injury and inhibit pyroptosis in vivo and in vitro.,The inhibitory effect of emodin on pyroptosis was mediated by suppressing the TLR4/MyD88/NF-κB/NLRP3 inflammasome pathway.,Therefore, emodin may provide an alternative treatment for myocardial I/R injury.

To delineate the clinical characteristics of patients with coronavirus disease 2019 (covid-19) who died.,Retrospective case series.,Tongji Hospital in Wuhan, China.,Among a cohort of 799 patients, 113 who died and 161 who recovered with a diagnosis of covid-19 were analysed.,Data were collected until 28 February 2020.,Clinical characteristics and laboratory findings were obtained from electronic medical records with data collection forms.,The median age of deceased patients (68 years) was significantly older than recovered patients (51 years).,Male sex was more predominant in deceased patients (83; 73%) than in recovered patients (88; 55%).,Chronic hypertension and other cardiovascular comorbidities were more frequent among deceased patients (54 (48%) and 16 (14%)) than recovered patients (39 (24%) and 7 (4%)).,Dyspnoea, chest tightness, and disorder of consciousness were more common in deceased patients (70 (62%), 55 (49%), and 25 (22%)) than in recovered patients (50 (31%), 48 (30%), and 1 (1%)).,The median time from disease onset to death in deceased patients was 16 (interquartile range 12.0-20.0) days.,Leukocytosis was present in 56 (50%) patients who died and 6 (4%) who recovered, and lymphopenia was present in 103 (91%) and 76 (47%) respectively.,Concentrations of alanine aminotransferase, aspartate aminotransferase, creatinine, creatine kinase, lactate dehydrogenase, cardiac troponin I, N-terminal pro-brain natriuretic peptide, and D-dimer were markedly higher in deceased patients than in recovered patients.,Common complications observed more frequently in deceased patients included acute respiratory distress syndrome (113; 100%), type I respiratory failure (18/35; 51%), sepsis (113; 100%), acute cardiac injury (72/94; 77%), heart failure (41/83; 49%), alkalosis (14/35; 40%), hyperkalaemia (42; 37%), acute kidney injury (28; 25%), and hypoxic encephalopathy (23; 20%).,Patients with cardiovascular comorbidity were more likely to develop cardiac complications.,Regardless of history of cardiovascular disease, acute cardiac injury and heart failure were more common in deceased patients.,Severe acute respiratory syndrome coronavirus 2 infection can cause both pulmonary and systemic inflammation, leading to multi-organ dysfunction in patients at high risk.,Acute respiratory distress syndrome and respiratory failure, sepsis, acute cardiac injury, and heart failure were the most common critical complications during exacerbation of covid-19.

This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury.

Supplemental Digital Content is available in the text.,Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension.,To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19.,This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55-68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57-69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020.,In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19-0.92]; P=0.03).,In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15-0.89]; P=0.03).,Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12-0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension.,Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers.,While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.

The novel coronavirus disease 2019 (COVID-19) has become a global health emergency.,The cumulative number of new confirmed cases and deaths are still increasing out of China.,Independent predicted factors associated with fatal outcomes remain uncertain.,The goal of the current study was to investigate the potential risk factors associated with fatal outcomes from COVID-19 through a multivariate Cox regression analysis and a nomogram model.,A retrospective cohort of 1,590 hospitalized patients with COVID-19 throughout China was established.,The prognostic effects of variables, including clinical features and laboratory findings, were analyzed by using Kaplan-Meier methods and a Cox proportional hazards model.,A prognostic nomogram was formulated to predict the survival of patients with COVID-19.,In this nationwide cohort, nonsurvivors included a higher incidence of elderly people and subjects with coexisting chronic illness, dyspnea, and laboratory abnormalities on admission compared with survivors.,Multivariate Cox regression analysis showed that age ≥ 75 years (hazard ratio [HR], 7.86; 95% CI, 2.44-25.35), age between 65 and 74 years (HR, 3.43; 95% CI, 1.24-9.5), coronary heart disease (HR, 4.28; 95% CI, 1.14-16.13), cerebrovascular disease (HR, 3.1; 95% CI, 1.07-8.94), dyspnea (HR, 3.96; 95% CI, 1.42-11), procalcitonin level > 0.5 ng/mL (HR, 8.72; 95% CI, 3.42-22.28), and aspartate aminotransferase level > 40 U/L (HR, 2.2; 95% CI, 1.1-6.73) were independent risk factors associated with fatal outcome.,A nomogram was established based on the results of multivariate analysis.,The internal bootstrap resampling approach suggested the nomogram has sufficient discriminatory power with a C-index of 0.91 (95% CI, 0.85-0.97).,The calibration plots also showed good consistency between the prediction and the observation.,The proposed nomogram accurately predicted clinical outcomes of patients with COVID-19 based on individual characteristics.,Earlier identification, more intensive surveillance, and appropriate therapy should be considered in patients at high risk.

Vaccination with an adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can result in the rare development of thrombosis with thrombocytopenia mediated by platelet-activating antibodies against platelet factor 4 (PF4).,This is a life-threating condition that may be accompanied by bleeding due to thrombocytopenia with thrombosis of the cerebral venous sinus or splanchnic vein.,Herein, we describe the first fatal case of thrombosis with thrombocytopenia syndrome in Korea, presenting with intracranial hemorrhage caused by cerebral venous sinus thrombosis.,A 33-year-old Korean man received the first dose of the ChAdOx1 nCoV-19 vaccination.,He developed severe headache with vomiting 9 days after the vaccination.,Twelve days after vaccination, he was admitted to the hospital with neurological symptoms and was diagnosed with cerebral venous sinus thrombosis, which was accompanied by intracranial hemorrhage.,Thrombocytopenia and D-dimer elevation were observed, and the result of the PF4 enzyme-linked immunosorbent assay antibody test was reported to be strongly positive.,Despite intensive treatment, including intravenous immunoglobulin injection and endovascular mechanical thrombectomy, the patient died 19 days after vaccination.,Physicians need to be aware of thrombosis with thrombocytopenia syndrome (TTS) in adenoviral vector-vaccinated patients.,Endovascular mechanical thrombectomy might be a useful therapeutic option for the treatment of TTS with cerebral venous sinus thrombosis.

We describe a 30-year-old woman who developed thrombocytopenia and multiple thromboses after she received the ChAdOx1 nCoV-19 vaccine.A maximum 4T HIT score and a positive immunoassay for anti-PF4 antibodies indicated autoimmune HIT as a potential pathogenic mechanism.,We describe a 30-year-old woman who developed thrombocytopenia and multiple thromboses after she received the ChAdOx1 nCoV-19 vaccine.,A maximum 4T HIT score and a positive immunoassay for anti-PF4 antibodies indicated autoimmune HIT as a potential pathogenic mechanism.,Recently, reports of severe thromboses, thrombocytopenia, and hemorrhage in persons vaccinated with the chimpanzee adenovirus-vectored vaccine (ChAdOx1 nCoV-19, AZD1222, Vaxzevria; Oxford/AstraZeneca) against severe acute respiratory syndrome coronavirus 2 have emerged.,We describe an otherwise healthy 30-year-old woman who developed thrombocytopenia, ecchymosis, portal vein thrombosis, and cerebral venous sinus thrombosis the second week after she received the ChAdOx1 nCoV-19 vaccine.,Extensive diagnostic workup for thrombosis predispositions showed heterozygosity for the prothrombin mutation, but no evidence of myeloproliferative neoplasia or infectious or autoimmune diseases.,Her only temporary risk factor was long-term use of oral contraceptive pills (OCPs).,Although both the prothrombin mutation and use of OCPs predispose to portal and cerebral vein thrombosis, the occurrence of multiple thromboses within a short time and the associated pattern of thrombocytopenia and consumption coagulopathy are highly unusual.,A maximum 4T heparin-induced thrombocytopenia (HIT) score and a positive immunoassay for anti-platelet factor 4/heparin antibodies identified autoimmune HIT as a potential pathogenic mechanism.,Although causality has not been established, our case emphasizes the importance of clinical awareness.,Further studies of this potentially new clinical entity have suggested that it should be regarded as a vaccine-induced immune thrombotic thrombocytopenia.

A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting-enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied.,We carried out a population-based case-control study in the Lombardy region of Italy.,A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence.,Information about the use of selected drugs and patients’ clinical profiles was obtained from regional databases of health care use.,Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression.,Among both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women.,The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile.,Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex.,In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease.,However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.

This case series study evaluates the association of underlying cardiovascular disease and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19).,What is the impact of underlying cardiovascular disease (CVD) and myocardial injury on fatal outcomes in patients with coronavirus disease 2019 (COVID-19)?,In this case series study of 187 patients with COVID-19, 27.8% of patients had myocardial injury, which resulted in cardiac dysfunction and arrhythmias.,Myocardial injury has a significant association with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury were relatively favorable.,It is reasonable to triage patients with COVID-19 according to the presence of underlying CVD and evidence of myocardial injury for prioritized treatment and even more aggressive strategies.,Increasing numbers of confirmed cases and mortality rates of coronavirus disease 2019 (COVID-19) are occurring in several countries and continents.,Information regarding the impact of cardiovascular complication on fatal outcome is scarce.,To evaluate the association of underlying cardiovascular disease (CVD) and myocardial injury with fatal outcomes in patients with COVID-19.,This retrospective single-center case series analyzed patients with COVID-19 at the Seventh Hospital of Wuhan City, China, from January 23, 2020, to February 23, 2020.,Analysis began February 25, 2020.,Demographic data, laboratory findings, comorbidities, and treatments were collected and analyzed in patients with and without elevation of troponin T (TnT) levels.,Among 187 patients with confirmed COVID-19, 144 patients (77%) were discharged and 43 patients (23%) died.,The mean (SD) age was 58.50 (14.66) years.,Overall, 66 (35.3%) had underlying CVD including hypertension, coronary heart disease, and cardiomyopathy, and 52 (27.8%) exhibited myocardial injury as indicated by elevated TnT levels.,The mortality during hospitalization was 7.62% (8 of 105) for patients without underlying CVD and normal TnT levels, 13.33% (4 of 30) for those with underlying CVD and normal TnT levels, 37.50% (6 of 16) for those without underlying CVD but elevated TnT levels, and 69.44% (25 of 36) for those with underlying CVD and elevated TnTs.,Patients with underlying CVD were more likely to exhibit elevation of TnT levels compared with the patients without CVD (36 [54.5%] vs 16 [13.2%]).,Plasma TnT levels demonstrated a high and significantly positive linear correlation with plasma high-sensitivity C-reactive protein levels (β = 0.530, P < .001) and N-terminal pro-brain natriuretic peptide (NT-proBNP) levels (β = 0.613, P < .001).,Plasma TnT and NT-proBNP levels during hospitalization (median [interquartile range (IQR)], 0.307 [0.094-0.600]; 1902.00 [728.35-8100.00]) and impending death (median [IQR], 0.141 [0.058-0.860]; 5375 [1179.50-25695.25]) increased significantly compared with admission values (median [IQR], 0.0355 [0.015-0.102]; 796.90 [401.93-1742.25]) in patients who died (P = .001; P < .001), while no significant dynamic changes of TnT (median [IQR], 0.010 [0.007-0.019]; 0.013 [0.007-0.022]; 0.011 [0.007-0.016]) and NT-proBNP (median [IQR], 352.20 [174.70-636.70]; 433.80 [155.80-1272.60]; 145.40 [63.4-526.50]) was observed in survivors (P = .96; P = .16).,During hospitalization, patients with elevated TnT levels had more frequent malignant arrhythmias, and the use of glucocorticoid therapy (37 [71.2%] vs 69 [51.1%]) and mechanical ventilation (31 [59.6%] vs 14 [10.4%]) were higher compared with patients with normal TnT levels.,The mortality rates of patients with and without use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers was 36.8% (7 of 19) and 21.4% (36 of 168) (P = .13).,Myocardial injury is significantly associated with fatal outcome of COVID-19, while the prognosis of patients with underlying CVD but without myocardial injury is relatively favorable.,Myocardial injury is associated with cardiac dysfunction and arrhythmias.,Inflammation may be a potential mechanism for myocardial injury.,Aggressive treatment may be considered for patients at high risk of myocardial injury.

Cardiovascular and arrhythmic events have been reported in hospitalized COVID-19 patients.,However, arrhythmia manifestations and treatment strategies used in these patients have not been well-described.,We sought to better understand the cardiac arrhythmic manifestations and treatment strategies in hospitalized COVID-19 patients through a worldwide cross-sectional survey.,The Heart Rhythm Society (HRS) sent an online survey (via SurveyMonkey) to electrophysiology (EP) professionals (physicians, scientists, and allied professionals) across the globe.,The survey was active from March 27 to April 13, 2020.,A total of 1197 respondents completed the survey with 50% of respondents from outside the USA, representing 76 countries and 6 continents.,Of respondents, 905 (76%) reported having COVID-19-positive patients in their hospital.,Atrial fibrillation was the most commonly reported tachyarrhythmia whereas severe sinus bradycardia and complete heart block were the most common bradyarrhythmias.,Ventricular tachycardia/ventricular fibrillation arrest and pulseless electrical activity were reported by 4.8% and 5.6% of respondents, respectively.,There were 140 of 631 (22.2%) respondents who reported using anticoagulation therapy in all COVID-19-positive patients who did not otherwise have an indication.,One hundred fifty-five of 498 (31%) reported regular use of hydroxychloroquine/chloroquine (HCQ) + azithromycin (AZM); concomitant use of AZM was more common in the USA.,Sixty of 489 respondents (12.3%) reported having to discontinue therapy with HCQ + AZM due to significant QTc prolongation and 20 (4.1%) reported cases of Torsade de Pointes in patients on HCQ/chloroquine and AZM.,Amiodarone was the most common antiarrhythmic drug used for ventricular arrhythmia management.,In this global survey of > 1100 EP professionals regarding hospitalized COVID-19 patients, a variety of arrhythmic manifestations were observed, ranging from benign to potentially life-threatening.,Observed adverse events related to use of HCQ + AZM included prolonged QTc requiring drug discontinuation as well as Torsade de Pointes.,Large prospective studies to better define arrhythmic manifestations as well as the safety of treatment strategies in COVID-19 patients are warranted.,The online version of this article (10.1007/s10840-020-00789-9) contains supplementary material, which is available to authorized users.

Although mortality due to COVID-19 is, for the most part, robustly tracked, its indirect effect at the population level through lockdown, lifestyle changes, and reorganisation of health-care systems has not been evaluated.,We aimed to assess the incidence and outcomes of out-of-hospital cardiac arrest (OHCA) in an urban region during the pandemic, compared with non-pandemic periods.,We did a population-based, observational study using data for non-traumatic OHCA (N=30 768), systematically collected since May 15, 2011, in Paris and its suburbs, France, using the Paris Fire Brigade database, together with in-hospital data.,We evaluated OHCA incidence and outcomes over a 6-week period during the pandemic in adult inhabitants of the study area.,Comparing the 521 OHCAs of the pandemic period (March 16 to April 26, 2020) to the mean of the 3052 total of the same weeks in the non-pandemic period (weeks 12-17, 2012-19), the maximum weekly OHCA incidence increased from 13·42 (95% CI 12·77-14·07) to 26·64 (25·72-27·53) per million inhabitants (p<0·0001), before returning to normal in the final weeks of the pandemic period.,Although patient demographics did not change substantially during the pandemic compared with the non-pandemic period (mean age 69·7 years [SD 17] vs 68·5 [18], 334 males [64·4%] vs 1826 [59·9%]), there was a higher rate of OHCA at home (460 [90·2%] vs 2336 [76·8%]; p<0·0001), less bystander cardiopulmonary resuscitation (239 [47·8%] vs 1165 [63·9%]; p<0·0001) and shockable rhythm (46 [9·2%] vs 472 [19·1%]; p<0·0001), and longer delays to intervention (median 10·4 min [IQR 8·4-13·8] vs 9·4 min [7·9-12·6]; p<0·0001).,The proportion of patients who had an OHCA and were admitted alive decreased from 22·8% to 12·8% (p<0·0001) in the pandemic period.,After adjustment for potential confounders, the pandemic period remained significantly associated with lower survival rate at hospital admission (odds ratio 0·36, 95% CI 0·24-0·52; p<0·0001).,COVID-19 infection, confirmed or suspected, accounted for approximately a third of the increase in OHCA incidence during the pandemic.,A transient two-times increase in OHCA incidence, coupled with a reduction in survival, was observed during the specified time period of the pandemic when compared with the equivalent time period in previous years with no pandemic.,Although this result might be partly related to COVID-19 infections, indirect effects associated with lockdown and adjustment of health-care services to the pandemic are probable.,Therefore, these factors should be taken into account when considering mortality data and public health strategies.,The French National Institute of Health and Medical Research (INSERM)

•RISH harmonization is applicable to multicentre dMRI of elderly subjects with SVD.,•Harmonization removes site-differences in dMRI metrics in matched controls.,•Associations between dMRI metrics and SVD markers in patients are preserved.,•Harmonized scans can be pooled to into a single large dataset to increased power.,RISH harmonization is applicable to multicentre dMRI of elderly subjects with SVD.,Harmonization removes site-differences in dMRI metrics in matched controls.,Associations between dMRI metrics and SVD markers in patients are preserved.,Harmonized scans can be pooled to into a single large dataset to increased power.,Acquisition-related differences in diffusion magnetic resonance imaging (dMRI) hamper pooling of multicentre data to achieve large sample sizes.,A promising solution is to harmonize the raw diffusion signal using rotation invariant spherical harmonic (RISH) features, but this has not been tested in elderly subjects.,Here we aimed to establish if RISH harmonization effectively removes acquisition-related differences in multicentre dMRI of elderly subjects with cerebral small vessel disease (SVD), while preserving sensitivity to disease effects.,Five cohorts of patients with SVD (N = 397) and elderly controls (N = 175) with 3 Tesla MRI on different systems were included.,First, to establish effectiveness of harmonization, the RISH method was trained with data of 13 to 15 age and sex-matched controls from each site.,Fractional anisotropy (FA) and mean diffusivity (MD) were compared in matched controls between sites using tract-based spatial statistics (TBSS) and voxel-wise analysis, before and after harmonization.,Second, to assess sensitivity to disease effects, we examined whether the contrast (effect sizes of FA, MD and peak width of skeletonized MD - PSMD) between patients and controls within each site remained unaffected by harmonization.,Finally, we evaluated the association between white matter hyperintensity (WMH) burden, FA, MD and PSMD using linear regression analyses both within individual cohorts as well as with pooled scans from multiple sites, before and after harmonization.,Before harmonization, significant differences in FA and MD were observed between matched controls of different sites (p < 0.05).,After harmonization these site-differences were removed.,Within each site, RISH harmonization did not alter the effect sizes of FA, MD and PSMD between patients and controls (relative change in Cohen’s d = 4 %) nor the strength of association with WMH volume (relative change in R2 = 2.8 %).,After harmonization, patient data of all sites could be aggregated in a single analysis to infer the association between WMH volume and FA (R2 = 0.62), MD (R2 = 0.64), and PSMD (R2 = 0.60).,We showed that RISH harmonization effectively removes acquisition-related differences in dMRI of elderly subjects while preserving sensitivity to SVD-related effects.,This study provides proof of concept for future multicentre SVD studies with pooled datasets.

To determine whether MRI markers, including diffusion tensor imaging (DTI), can predict cognitive decline and dementia in patients with cerebral small vessel disease (SVD).,In the prospective St George's Cognition and Neuroimaging in Stroke study, multimodal MRI was performed annually for 3 years and cognitive assessments annually for 5 years in a cohort of 99 patients with SVD, defined as symptomatic lacunar stroke and confluent white matter hyperintensities (WMH).,Progression to dementia was determined in all patients.,Progression of WMH, brain volume, lacunes, cerebral microbleeds, and a DTI measure (the normalized peak height of the mean diffusivity histogram distribution) as a marker of white matter microstructural damage were determined.,Over 5 years of follow-up, 18 patients (18.2%) progressed to dementia.,A significant change in all MRI markers, representing deterioration, was observed.,The presence of new lacunes, and rate of increase in white matter microstructural damage on DTI, correlated with both decline in executive function and global functioning.,Growth of WMH and deterioration of white matter microstructure on DTI predicted progression to dementia.,A model including change in MRI variables together with their baseline values correctly classified progression to dementia with a C statistic of 0.85.,This longitudinal prospective study provides evidence that change in MRI measures including DTI, over time durations during which cognitive change is not detectable, predicts cognitive decline and progression to dementia.,It supports the use of MRI measures, including DTI, as useful surrogate biomarkers to monitor disease and assess therapeutic interventions.

Coronavirus disease 2019 (COVID-19) may predispose to venous thromboembolism.,We determined factors independently associated with computed tomography pulmonary angiography (CTPA)-confirmed pulmonary embolism (PE) in hospitalised severe COVID-19 patients.,Among all (n=349) patients hospitalised for COVID-19 in a university hospital in a French region with a high rate of COVID-19, we analysed patients who underwent CTPA for clinical signs of severe disease (oxygen saturation measured by pulse oximetry ≤93% or breathing rate ≥30 breaths·min−1) or rapid clinical worsening.,Multivariable analysis was performed using Firth penalised maximum likelihood estimates.,162 (46.4%) patients underwent CTPA (mean±sd age 65.6±13.0 years; 67.3% male (95% CI 59.5-75.5%).,PE was diagnosed in 44 (27.2%) patients.,Most PEs were segmental and the rate of PE-related right ventricular dysfunction was 15.9%.,By multivariable analysis, the only two significant predictors of CTPA-confirmed PE were D-dimer level and the lack of any anticoagulant therapy (OR 4.0 (95% CI 2.4-6.7) per additional quartile and OR 4.5 (95% CI 1.1-7.4), respectively).,Receiver operating characteristic curve analysis identified a D-dimer cut-off value of 2590 ng·mL−1 to best predict occurrence of PE (area under the curve 0.88, p<0.001, sensitivity 83.3%, specificity 83.8%).,D-dimer level >2590 ng·mL−1 was associated with a 17-fold increase in the adjusted risk of PE.,Elevated D-dimers (>2590 ng·mL−1) and absence of anticoagulant therapy predict PE in hospitalised COVID-19 patients with clinical signs of severity.,These data strengthen the evidence base in favour of systematic anticoagulation, and suggest wider use of D-dimer guided CTPA to screen for PE in acutely ill hospitalised patients with COVID-19.,We studied predictors of pulmonary embolism in severe COVID-19 and found that D-dimer level and lack of any anticoagulant therapy were associated with a 17-fold and four-fold increase in PE, respectively, in COVID-19 patients with clinical signs of severityhttps://bit.ly/2ETfAfo

Little evidence of increased thrombotic risk is available in COVID-19 patients.,Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.,All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included.,Medical history, symptoms, biological data and imaging were prospectively collected.,Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.,150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points).,Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting.,Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO.,Most patients (> 95%) had elevated D-dimer and fibrinogen.,No patient developed disseminated intravascular coagulation.,Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant.,Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs.,2.1%, p < 0.008).,Coagulation parameters significantly differed between the two groups.,Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications.,Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.,The online version of this article (10.1007/s00134-020-06062-x) contains supplementary material, which is available to authorized users.

Some patients with severe COVID-19 develop prothrombotic autoantibodies that are similar to antiphospholipid antibodies found in autoimmune diseases.,Patients with severe COVID-19 are at high risk for occlusion of blood vessels of all sizes.,This prothrombotic phenotype is reminiscent of patients with lupus and antiphospholipid syndrome, who have long-lived circulating antiphospholipid autoantibodies.,In new work, Zuo et al. measured eight types of antiphospholipid antibodies in serum from patients hospitalized with COVID-19 and found at least one antibody in half of patients.,Antibody levels were associated with neutrophil and coagulation pathway activation.,Purified antibodies from some patients activated neutrophils in vitro and potentiated thrombosis when injected into mice.,Together, these findings suggest that autoantibodies are a potential therapeutic target in severe COVID-19.,Patients with COVID-19 are at high risk for thrombotic arterial and venous occlusions.,Lung histopathology often reveals fibrin-based blockages in the small blood vessels of patients who succumb to the disease.,Antiphospholipid syndrome is an acquired and potentially life-threatening thrombophilia in which patients develop pathogenic autoantibodies targeting phospholipids and phospholipid-binding proteins (aPL antibodies).,Case series have recently detected aPL antibodies in patients with COVID-19.,Here, we measured eight types of aPL antibodies in serum samples from 172 patients hospitalized with COVID-19.,These aPL antibodies included anticardiolipin IgG, IgM, and IgA; anti-β2 glycoprotein I IgG, IgM, and IgA; and anti-phosphatidylserine/prothrombin (aPS/PT) IgG and IgM.,We detected aPS/PT IgG in 24% of serum samples, anticardiolipin IgM in 23% of samples, and aPS/PT IgM in 18% of samples.,Antiphospholipid autoantibodies were present in 52% of serum samples using the manufacturer’s threshold and in 30% using a more stringent cutoff (≥40 ELISA-specific units).,Higher titers of aPL antibodies were associated with neutrophil hyperactivity, including the release of neutrophil extracellular traps (NETs), higher platelet counts, more severe respiratory disease, and lower clinical estimated glomerular filtration rate.,Similar to IgG from patients with antiphospholipid syndrome, IgG fractions isolated from patients with COVID-19 promoted NET release from neutrophils isolated from healthy individuals.,Furthermore, injection of IgG purified from COVID-19 patient serum into mice accelerated venous thrombosis in two mouse models.,These findings suggest that half of patients hospitalized with COVID-19 become at least transiently positive for aPL antibodies and that these autoantibodies are potentially pathogenic.

The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide.,However, little is known about the causes of death and the virus's pathologic features.,To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests.,Prospective cohort study.,Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19.,The first 12 consecutive COVID-19-positive deaths.,Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed.,Clinical data and medical course were evaluated.,Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2).,Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively).,Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients.,Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients.,In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.,Limited sample size.,The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy.,Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it.,University Medical Center Hamburg-Eppendorf.,Little is known of the pathologic changes that lead to death in patients with COVID-19.,This study reports the autopsy findings of consecutive patients who died with a diagnosis of COVID-19.

Supplemental Digital Content is available in the text.,A pandemic of historic impact, coronavirus disease 2019 (COVID-19) has potential consequences on the cardiovascular health of millions of people who survive infection worldwide.,Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, can infect the heart, vascular tissues, and circulating cells through ACE2 (angiotensin-converting enzyme 2), the host cell receptor for the viral spike protein.,Acute cardiac injury is a common extrapulmonary manifestation of COVID-19 with potential chronic consequences.,This update provides a review of the clinical manifestations of cardiovascular involvement, potential direct SARS-CoV-2 and indirect immune response mechanisms impacting the cardiovascular system, and implications for the management of patients after recovery from acute COVID-19 infection.

The degree of myocardial injury, as reflected by troponin elevation, and associated outcomes among U.S. hospitalized patients with coronavirus disease-2019 (COVID-19) are unknown.,The purpose of this study was to describe the degree of myocardial injury and associated outcomes in a large hospitalized cohort with laboratory-confirmed COVID-19.,Patients with COVID-19 admitted to 1 of 5 Mount Sinai Health System hospitals in New York City between February 27, 2020, and April 12, 2020, with troponin-I (normal value <0.03 ng/ml) measured within 24 h of admission were included (n = 2,736).,Demographics, medical histories, admission laboratory results, and outcomes were captured from the hospitals’ electronic health records.,The median age was 66.4 years, with 59.6% men.,Cardiovascular disease (CVD), including coronary artery disease, atrial fibrillation, and heart failure, was more prevalent in patients with higher troponin concentrations, as were hypertension and diabetes.,A total of 506 (18.5%) patients died during hospitalization.,In all, 985 (36%) patients had elevated troponin concentrations.,After adjusting for disease severity and relevant clinical factors, even small amounts of myocardial injury (e.g., troponin I >0.03 to 0.09 ng/ml; n = 455; 16.6%) were significantly associated with death (adjusted hazard ratio: 1.75; 95% CI: 1.37 to 2.24; p < 0.001) while greater amounts (e.g., troponin I >0.09 ng/dl; n = 530; 19.4%) were significantly associated with higher risk (adjusted HR: 3.03; 95% CI: 2.42 to 3.80; p < 0.001).,Myocardial injury is prevalent among patients hospitalized with COVID-19; however, troponin concentrations were generally present at low levels.,Patients with CVD are more likely to have myocardial injury than patients without CVD.,Troponin elevation among patients hospitalized with COVID-19 is associated with higher risk of mortality.

To describe a novel England-wide electronic health record (EHR) resource enabling whole population research on covid-19 and cardiovascular disease while ensuring data security and privacy and maintaining public trust.,Data resource comprising linked person level records from national healthcare settings for the English population, accessible within NHS Digital’s new trusted research environment.,EHRs from primary care, hospital episodes, death registry, covid-19 laboratory test results, and community dispensing data, with further enrichment planned from specialist intensive care, cardiovascular, and covid-19 vaccination data.,54.4 million people alive on 1 January 2020 and registered with an NHS general practitioner in England.,Confirmed and suspected covid-19 diagnoses, exemplar cardiovascular conditions (incident stroke or transient ischaemic attack and incident myocardial infarction) and all cause mortality between 1 January and 31 October 2020.,The linked cohort includes more than 96% of the English population.,By combining person level data across national healthcare settings, data on age, sex, and ethnicity are complete for around 95% of the population.,Among 53.3 million people with no previous diagnosis of stroke or transient ischaemic attack, 98 721 had a first ever incident stroke or transient ischaemic attack between 1 January and 31 October 2020, of which 30% were recorded only in primary care and 4% only in death registry records.,Among 53.2 million people with no previous diagnosis of myocardial infarction, 62 966 had an incident myocardial infarction during follow-up, of which 8% were recorded only in primary care and 12% only in death registry records.,A total of 959 470 people had a confirmed or suspected covid-19 diagnosis (714 162 in primary care data, 126 349 in hospital admission records, 776 503 in covid-19 laboratory test data, and 50 504 in death registry records).,Although 58% of these were recorded in both primary care and covid-19 laboratory test data, 15% and 18%, respectively, were recorded in only one.,This population-wide resource shows the importance of linking person level data across health settings to maximise completeness of key characteristics and to ascertain cardiovascular events and covid-19 diagnoses.,Although this resource was initially established to support research on covid-19 and cardiovascular disease to benefit clinical care and public health and to inform healthcare policy, it can broaden further to enable a wide range of research.

Although patients with cardiovascular disease face excess risks of severe illness with coronavirus disease-2019 (COVID-19), there may be indirect consequences of the pandemic on this high-risk patient segment.,This study sought to examine longitudinal trends in hospitalizations for acute cardiovascular conditions across a tertiary care health system.,Acute cardiovascular hospitalizations were tracked between January 1, 2019, and March 31, 2020.,Daily hospitalization rates were estimated using negative binomial models.,Temporal trends in hospitalization rates were compared across the first 3 months of 2020, with the first 3 months of 2019 as a reference.,From January 1, 2019, to March 31, 2020, 6,083 patients experienced 7,187 hospitalizations for primary acute cardiovascular reasons.,There were 43.4% (95% confidence interval [CI]: 27.4% to 56.0%) fewer estimated daily hospitalizations in March 2020 compared with March 2019 (p < 0.001).,The daily rate of hospitalizations did not change throughout 2019 (-0.01% per day [95% CI: -0.04% to +0.02%]; p = 0.50), January 2020 (-0.5% per day [95% CI: -1.6% to +0.5%]; p = 0.31), or February 2020 (+0.7% per day [95% CI: -0.6% to +2.0%]; p = 0.27).,There was significant daily decline in hospitalizations in March 2020 (-5.9% per day [95% CI: -7.6% to -4.3%]; p < 0.001).,Length of stay was shorter (4.8 days [25th to 75th percentiles: 2.4 to 8.3 days] vs.,6.0 days [25th to 75th percentiles: 3.1 to 9.6 days]; p = 0.003) and in-hospital mortality was not significantly different (6.2% vs.,4.4%; p = 0.30) in March 2020 compared with March 2019.,During the first phase of the COVID-19 pandemic, there was a marked decline in acute cardiovascular hospitalizations, and patients who were admitted had shorter lengths of stay.,These data substantiate concerns that acute care of cardiovascular conditions may be delayed, deferred, or abbreviated during the COVID-19 pandemic.

Is Kawasaki disease (KD) associated with droplet- or contact-transmitted infection?,In this cross-sectional study of 17 235 pediatric patients, the number of admissions for KD showed no significant change (27.4% decrease) during quarantine owing to the COVID-19 pandemic, whereas there were significant decreases in numbers of hospital admissions for droplet-transmitted or contact-transmitted respiratory tract infections (75.3% decrease) and gastrointestinal infections (86.3% decrease).,Thus, the ratio of KD admissions to admissions for these infections increased.,These findings suggest that contact or droplet transmission is not a major route for KD development and that KD may be associated with airborne disease.,This cross-sectional study assesses the role of droplet or contact transmission in the etiopathogenesis of Kawasaki disease.,The development of Kawasaki disease (KD) has been suggested to be associated with droplet- or contact-transmitted infection; however, its triggers and transmission modes remain to be determined.,Under an epidemic of SARS-CoV-2, the COVID-19 state of emergency in Japan served as a nationwide social experiment to investigate the impact of quarantine or isolation on the incidence of KD.,To assess the role of droplet or contact transmission in the etiopathogenesis of KD.,This multicenter, longitudinal, cross-sectional study was conducted from 2015 to 2020 at Fukuoka Children’s Hospital and 5 adjacent general hospitals.,The number of admissions for KD and infectious diseases were analyzed.,Participants were pediatric patients admitted to the participating hospitals for KD or infectious diseases.,Quarantine and isolation owing to the COVID-19 state of emergency.,The primary end points were the ratios of patients with KD to patients with respiratory tract or gastrointestinal infections admitted from April to May in 2015 to 2019 and 2020.,A Poisson regression model was used to analyze them.,The study participants included 1649 patients with KD (median [interquartile range] age, 25 [13-43] months; 901 boys [54.6%]) and 15 586 patients with infectious disease (data on age and sex were not available for these patients).,The number of admissions for KD showed no significant change between April and May in 2015 to 2019 vs the same months in 2020 (mean [SD], 24.8 [5.6] vs 18.0 [4.0] admissions per month; 27.4% decrease; adjusted incidence rate ratio [aIRR], 0.73; 95% CI, 0.48-1.10; P = .12).,However, the number of admissions for droplet-transmitted or contact-transmitted respiratory tract infections (mean [SD], 157.6 [14.4] vs 39.0 [15.0] admissions per month; 75.3% decrease; aIRR, 0.25; 95% CI, 0.17-0.35; P < .001) and gastrointestinal infections (mean [SD], 43.8 [12.9] vs 6.0 [2.0] admissions per month; 86.3% decrease; aIRR, 0.14; 95% CI, 0.04-0.43; P < .001) showed significant decreases between April and May in 2015 to 2019 vs the same months in 2020 (total, 12 254 infections).,Thus, the ratio of KD to droplet- or contact-transmitted respiratory tract and gastrointestinal infections incidence in April and May 2020 was significantly increased (ratio, 0.40 vs 0.12; χ21 = 22.76; P < .001).,In this study, the significantly increased incidence of KD compared with respiratory tract and gastrointestinal infections during the COVID-19 state of emergency suggests that contact or droplet transmission is not a major route for KD development and that KD may be associated with airborne infections in most cases.

Epidemiological studies in Kawasaki disease (KD) have suggested infectious aetiology.,During the COVID-19 pandemic, measures for mitigating SARS-CoV-2 transmission also suppress the circulation of other contagious microorganisms.,The primary objective is to compare the number and incidence of KD before and during the COVID-19 pandemic in Japan, and the secondary objective is to investigate temporal association between the KD epidemiology and activities of SARS-CoV-2 and other viral and bacterial infections.,A retrospective cohort study was conducted between 2016 and 2020 in Kobe, Japan.,We collected information of hospitalised KD children in Kobe.,Child population was identified through the resident registry system.,Activity of COVID-19 and 11 other infectious diseases was derived from a public health monitoring system.,Monthly change of KD incidence was analysed using a difference-in-difference regression model.,Throughout the study period, 1027 KD children were identified.,KD had begun to decline in April 2020, coinciding with the beginning of the COVID-19 pandemic.,The number of KD cases (n=66) between April and December 2020 was 40% of the average in the same period in 2016-2019 (165/year).,Annual KD incidence was 315, 300, 353, 347 and 188/100 000 children aged 0-4 years in 2016-2020, respectively.,The difference-in-difference value of KD incidence was significantly reduced in the fourth quarter in 2020 (−15.8, 95% CI −28.0 to −3.5), compared with that in 2016-2019.,Sentinel surveillance showed a marked decrease of all infectious diseases except exanthema subitum after the beginning of the COVID-19 pandemic.,There were 86 COVID-19 cases aged <10 years and no KD children associated with COVID-19.,This study showed that the number and incidence of KD was dramatically reduced during the COVID-19 pandemic in Japan.,This change was temporally associated with decreased activities of various infectious diseases other than COVID-19, supporting the hypothesis of infection-triggered pathogenesis in KD.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets multiple organs and causes severe coagulopathy.,Histopathological organ changes might not only be attributable to a direct virus-induced effect, but also the immune response.,The aims of this study were to assess the duration of viral presence, identify the extent of inflammatory response, and investigate the underlying cause of coagulopathy.,This prospective autopsy cohort study was done at Amsterdam University Medical Centers (UMC), the Netherlands.,With informed consent from relatives, full body autopsy was done on 21 patients with COVID-19 for whom autopsy was requested between March 9 and May 18, 2020.,In addition to histopathological evaluation of organ damage, the presence of SARS-CoV-2 nucleocapsid protein and the composition of the immune infiltrate and thrombi were assessed, and all were linked to disease course.,Our cohort (n=21) included 16 (76%) men, and median age was 68 years (range 41-78).,Median disease course (time from onset of symptoms to death) was 22 days (range 5-44 days).,In 11 patients tested for SARS-CoV-2 tropism, SARS-CoV-2 infected cells were present in multiple organs, most abundantly in the lungs, but presence in the lungs became sporadic with increased disease course.,Other SARS-CoV-2-positive organs included the upper respiratory tract, heart, kidneys, and gastrointestinal tract.,In histological analyses of organs (sampled from nine to 21 patients per organ), an extensive inflammatory response was present in the lungs, heart, liver, kidneys, and brain.,In the brain, extensive inflammation was seen in the olfactory bulbs and medulla oblongata.,Thrombi and neutrophilic plugs were present in the lungs, heart, kidneys, liver, spleen, and brain and were most frequently observed late in the disease course (15 patients with thrombi, median disease course 22 days [5-44]; ten patients with neutrophilic plugs, 21 days [5-44]).,Neutrophilic plugs were observed in two forms: solely composed of neutrophils with neutrophil extracellular traps (NETs), or as aggregates of NETs and platelets..,In patients with lethal COVID-19, an extensive systemic inflammatory response was present, with a continued presence of neutrophils and NETs.,However, SARS-CoV-2-infected cells were only sporadically present at late stages of COVID-19.,This suggests a maladaptive immune response and substantiates the evidence for immunomodulation as a target in the treatment of severe COVID-19.,Amsterdam UMC Corona Research Fund.

Coronavirus disease 2019 (COVID-19) is a pandemic that has affected more than 1.8 million people worldwide, overwhelmed health care systems owing to the high proportion of critical presentations, and resulted in more than 100,000 deaths.,Since the first data analyses in China, elevated cardiac troponin has been noted in a substantial proportion of patients, implicating myocardial injury as a possible pathogenic mechanism contributing to severe illness and mortality.,Accordingly, high troponin levels are associated with increased mortality in patients with COVID-19.,This brief review explores the available evidence regarding the association between COVID-19 and myocardial injury.

A 49-year-old man was admitted to his local hospital with left leg pain and breathing difficulties.,He had negative nasopharyngeal polymerase chain reaction tests for severe acute respiratory syndrome coronavirus 2.,Chest X-ray and Computed tomography pulmonary angiogram displayed typical coronavirus disease 2019 (COVID-19) radiological features as ground-glass opacities and bronchovascular thickening.,His respiratory symptoms resolved after four days of supportive treatment, whereas his left leg became more painful and discolored.,He was referred to our center with acute left leg ischemia. computed tomography angiogram revealed eccentric mural thrombus at the aortic bifurcation, extending into left common iliac and an abrupt occlusion of left popliteal, tibioperoneal, and posterior tibial arteries.,He was treated with catheter-directed thrombolysis for 48-hours that achieved successful revascularization of the ischemic limb with no intervention-related complications.,At six-week follow-up, he showed full recovery.,Our case demonstrates that catheter-directed thrombolysis is a successful and safe treatment option in a COVID-19 patient with acute arterial occlusion.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.

COVID-19 affects millions of patients worldwide, with clinical presentation ranging from isolated thrombosis to acute respiratory distress syndrome (ARDS) requiring ventilator support.,Neutrophil extracellular traps (NETs) originate from decondensed chromatin released to immobilize pathogens, and they can trigger immunothrombosis.,We studied the connection between NETs and COVID-19 severity and progression.,We conducted a prospective cohort study of COVID-19 patients (n = 33) and age- and sex-matched controls (n = 17).,We measured plasma myeloperoxidase (MPO)-DNA complexes (NETs), platelet factor 4, RANTES, and selected cytokines.,Three COVID-19 lung autopsies were examined for NETs and platelet involvement.,We assessed NET formation ex vivo in COVID-19 neutrophils and in healthy neutrophils incubated with COVID-19 plasma.,We also tested the ability of neonatal NET-inhibitory factor (nNIF) to block NET formation induced by COVID-19 plasma.,Plasma MPO-DNA complexes increased in COVID-19, with intubation (P < .0001) and death (P < .0005) as outcome.,Illness severity correlated directly with plasma MPO-DNA complexes (P = .0360), whereas Pao2/fraction of inspired oxygen correlated inversely (P = .0340).,Soluble and cellular factors triggering NETs were significantly increased in COVID-19, and pulmonary autopsies confirmed NET-containing microthrombi with neutrophil-platelet infiltration.,Finally, COVID-19 neutrophils ex vivo displayed excessive NETs at baseline, and COVID-19 plasma triggered NET formation, which was blocked by nNIF.,Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.,•NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.•nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.,NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.,nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.

Recent studies have reported a high prevalence of thrombotic events in coronavirus disease 2019.,However, the significance of thromboembolic complications has not been widely appreciated.,The purpose of this review is to provide current knowledge of this serious problem.,Narrative review.,Online search of published medical literature through PubMed using the term “COVID-19,” “SARS,” “acute respiratory distress syndrome,” “coronavirus,” “coagulopathy,” “thrombus,” and “anticoagulants.”,Articles were chosen for inclusion based on their relevance to coagulopathy and thrombosis in coronavirus disease 2019, and anticoagulant therapy.,Reference lists were reviewed to identify additional relevant articles.,Coronavirus disease 2019 is associated with a strikingly high prevalence of coagulopathy and venous thromboembolism that may contribute to respiratory deterioration.,Monitoring coagulation variables is important, as abnormal coagulation tests are related to adverse outcomes and may necessitate adjuvant antithrombotic interventions.,In the initial phase of the infection, d-dimer and fibrinogen levels are increased, while activated partial prothrombin time, prothrombin time, and platelet counts are often relatively normal.,Increased d-dimer levels three times the upper limit of normal may trigger screening for venous thromboembolism.,In all hospitalized patients, thromboprophylaxis using low-molecular-weight heparin is currently recommended.,The etiology of the procoagulant responses is complex and thought to be a result of specific interactions between host defense mechanisms and the coagulation system.,Although the coagulopathy is reminiscent of disseminated intravascular coagulation and thrombotic microangiopathy, it has features that are markedly distinct from these entities.,Severe acute respiratory syndrome coronavirus 2/coronavirus disease 2019 frequently induces hypercoagulability with both microangiopathy and local thrombus formation, and a systemic coagulation defect that leads to large vessel thrombosis and major thromboembolic complications, including pulmonary embolism in critically ill hospitalized patients. d-dimers and fibrinogen levels should be monitored, and all hospitalized patients should undergo thromboembolism prophylaxis with an increase in therapeutic anticoagulation in certain clinical situations.

Coronavirus disease 2019 (COVID‐19) can lead to systemic coagulation activation and thrombotic complications.,To investigate the incidence of objectively confirmed venous thromboembolism (VTE) in hospitalized patients with COVID‐19.,Single‐center cohort study of 198 hospitalized patients with COVID‐19.,Seventy‐five patients (38%) were admitted to the intensive care unit (ICU).,At time of data collection, 16 (8%) were still hospitalized and 19% had died.,During a median follow‐up of 7 days (IQR, 3‐13), 39 patients (20%) were diagnosed with VTE of whom 25 (13%) had symptomatic VTE, despite routine thrombosis prophylaxis.,The cumulative incidences of VTE at 7, 14 and 21 days were 16% (95% CI, 10‐22), 33% (95% CI, 23‐43) and 42% (95% CI 30‐54) respectively.,For symptomatic VTE, these were 10% (95% CI, 5.8‐16), 21% (95% CI, 14‐30) and 25% (95% CI 16‐36).,VTE appeared to be associated with death (adjusted HR, 2.4; 95% CI, 1.02‐5.5).,The cumulative incidence of VTE was higher in the ICU (26% (95% CI, 17‐37), 47% (95% CI, 34‐58), and 59% (95% CI, 42‐72) at 7, 14 and 21 days) than on the wards (any VTE and symptomatic VTE 5.8% (95% CI, 1.4‐15), 9.2% (95% CI, 2.6‐21), and 9.2% (2.6‐21) at 7, 14, and 21 days).,The observed risk for VTE in COVID‐19 is high, particularly in ICU patients, which should lead to a high level of clinical suspicion and low threshold for diagnostic imaging for DVT or PE.,Future research should focus on optimal diagnostic and prophylactic strategies to prevent VTE and potentially improve survival.

Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.

The Coronavirus Disease 2019 (COVID-19) is now a global pandemic with millions affected and millions more at risk for contracting the infection.,The COVID-19 virus, SARS-CoV-2, affects multiple organ systems, especially the lungs and heart.,Elevation of cardiac biomarkers, particularly high-sensitivity troponin and/or creatine kinase MB, is common in patients with COVID-19 infection.,In our review of clinical analyses, we found that in 26 studies including 11,685 patients, the weighted pooled prevalence of acute myocardial injury was 20% (ranged from 5% to 38% depending on the criteria used).,The plausible mechanisms of myocardial injury include, 1) hyperinflammation and cytokine storm mediated through pathologic T-cells and monocytes leading to myocarditis, 2) respiratory failure and hypoxemia resulting in damage to cardiac myocytes, 3) down regulation of ACE2 expression and subsequent protective signaling pathways in cardiac myocytes, 4) hypercoagulability and development of coronary microvascular thrombosis, 5) diffuse endothelial injury and ‘endotheliitis’ in several organs including the heart, and, 6) inflammation and/or stress causing coronary plaque rupture or supply-demand mismatch leading to myocardial ischemia/infarction.,Cardiac biomarkers can be used to aid in diagnosis as well as risk stratification.,In patients with elevated hs-troponin, clinical context is important and myocarditis as well as stress induced cardiomyopathy should be considered in the differential, along with type I and type II myocardial infarction.,Irrespective of etiology, patients with acute myocardial injury should be prioritized for treatment.,Clinical decisions including interventions should be individualized and carefully tailored after thorough review of risks/benefits.,Given the complex interplay of SARS-CoV-2 with the cardiovascular system, further investigation into potential mechanisms is needed to guide effective therapies.,Randomized trials are urgently needed to investigate treatment modalities to reduce the incidence and mortality associated with COVID-19 related acute myocardial injury.

The aim of this study was to characterize the echocardiographic phenotype of patients with COVID-19 pneumonia and its relation to biomarkers.,Seventy-four patients (59 ± 13 years old, 78% male) admitted with COVID-19 were included after referral for transthoracic echocardiography as part of routine care.,A level 1 British Society of Echocardiography transthoracic echocardiography was used to assess chamber size and function, valvular disease, and likelihood of pulmonary hypertension.,The chief abnormalities were right ventricle (RV) dilatation (41%) and RV dysfunction (27%).,RV impairment was associated with increased D-dimer and C-reactive protein levels.,In contrast, left ventricular function was hyperdynamic or normal in most (89%) patients.

COVID-19 affects millions of patients worldwide, with clinical presentation ranging from isolated thrombosis to acute respiratory distress syndrome (ARDS) requiring ventilator support.,Neutrophil extracellular traps (NETs) originate from decondensed chromatin released to immobilize pathogens, and they can trigger immunothrombosis.,We studied the connection between NETs and COVID-19 severity and progression.,We conducted a prospective cohort study of COVID-19 patients (n = 33) and age- and sex-matched controls (n = 17).,We measured plasma myeloperoxidase (MPO)-DNA complexes (NETs), platelet factor 4, RANTES, and selected cytokines.,Three COVID-19 lung autopsies were examined for NETs and platelet involvement.,We assessed NET formation ex vivo in COVID-19 neutrophils and in healthy neutrophils incubated with COVID-19 plasma.,We also tested the ability of neonatal NET-inhibitory factor (nNIF) to block NET formation induced by COVID-19 plasma.,Plasma MPO-DNA complexes increased in COVID-19, with intubation (P < .0001) and death (P < .0005) as outcome.,Illness severity correlated directly with plasma MPO-DNA complexes (P = .0360), whereas Pao2/fraction of inspired oxygen correlated inversely (P = .0340).,Soluble and cellular factors triggering NETs were significantly increased in COVID-19, and pulmonary autopsies confirmed NET-containing microthrombi with neutrophil-platelet infiltration.,Finally, COVID-19 neutrophils ex vivo displayed excessive NETs at baseline, and COVID-19 plasma triggered NET formation, which was blocked by nNIF.,Thus, NETs triggering immunothrombosis may, in part, explain the prothrombotic clinical presentations in COVID-19, and NETs may represent targets for therapeutic intervention.,•NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.•nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.,NETs contribute to microthrombi through platelet-neutrophil interactions in COVID-19 ARDS.,nNIF blocks NETs induced by COVID-19 plasma and represents a potential therapeutic intervention in COVID-19.

Critically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk.,Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear.,Using platelets from healthy volunteers, non-COVID-19 and COVID-19 patients, as well as wild-type and hACE2 transgenic mice, we evaluated the changes in platelet and coagulation parameters in COVID-19 patients.,We investigated ACE2 expression and direct effect of SARS-CoV-2 virus on platelets by RT-PCR, flow cytometry, Western blot, immunofluorescence, and platelet functional studies in vitro, FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo.,We demonstrated that COVID-19 patients present with increased mean platelet volume (MPV) and platelet hyperactivity, which correlated with a decrease in overall platelet count.,Detectable SARS-CoV-2 RNA in the blood stream was associated with platelet hyperactivity in critically ill patients.,Platelets expressed ACE2, a host cell receptor for SARS-CoV-2, and TMPRSS2, a serine protease for Spike protein priming.,SARS-CoV-2 and its Spike protein directly enhanced platelet activation such as platelet aggregation, PAC-1 binding, CD62P expression, α granule secretion, dense granule release, platelet spreading, and clot retraction in vitro, and thereby Spike protein enhanced thrombosis formation in wild-type mice transfused with hACE2 transgenic platelets, but this was not observed in animals transfused with wild-type platelets in vivo.,Further, we provided evidence suggesting that the MAPK pathway, downstream of ACE2, mediates the potentiating role of SARS-CoV-2 on platelet activation, and that platelet ACE2 expression decreases following SARS-COV-2 stimulation.,SARS-CoV-2 and its Spike protein directly stimulated platelets to facilitate the release of coagulation factors, the secretion of inflammatory factors, and the formation of leukocyte-platelet aggregates.,Recombinant human ACE2 protein and anti-Spike monoclonal antibody could inhibit SARS-CoV-2 Spike protein-induced platelet activation.,Our findings uncovered a novel function of SARS-CoV-2 on platelet activation via binding of Spike to ACE2.,SARS-CoV-2-induced platelet activation may participate in thrombus formation and inflammatory responses in COVID-19 patients.

The COVID-19 pandemic, the result of severe acute respiratory syndrome (SARS)-CoV-2, is a major cause of worldwide mortality with a significant cardiovascular component.,While a number of different cardiovascular histopathologies have been reported at postmortem examination, their incidence is unknown, due to limited numbers of cases in any given study.,A literature review was performed identifying 277 autopsied hearts across 22 separate publications of COVID-19 positive patients.,The median age of the autopsy cohort was 75 and 97.6% had one or more comorbidities.,Initial review of the data indicate that myocarditis was present in 20 hearts (7.2%); however, closer examination of additional reported information revealed that most cases were likely not functionally significant and the true prevalence of myocarditis is likely much lower (<2%).,At least one acute, potentially COVID-19-related cardiovascular histopathologic finding, such as macro or microvascular thrombi, inflammation, or intraluminal megakaryocytes, was reported in 47.8% of cases.,Significant differences in reporting of histopathologic findings occurred between studies indicating strong biases in observations and the need for more consistency in reporting.,In conclusion, across 277 cases, COVID-19-related cardiac histopathological findings, are common, while myocarditis is rare.

We sought to study the impact of COVID‐19 pandemic on the presentation delay, severity, patterns of care, and reasons for delay among patients with ST‐elevation myocardial infarction (STEMI) in a non‐hot‐spot region.,COVID‐19 pandemic has significantly reduced the activations for STEMI in epicenters like Spain.,From January 1, 2020, to April 15, 2020, 143 STEMIs were identified across our integrated 18‐hospital system.,Pre‐ and post‐COVID‐19 cohorts were based on March 23rd, 2020, whenstay‐at‐home orders were initiated in Ohio.,We used presenting heart rate, blood pressure, troponin, new Q‐wave, and left ventricle ejection fraction (LVEF) to assess severity.,Duration of intensive care unit stay, total length of stay, door‐to‐balloon (D2B) time, and radial versus femoral access were used to assess patterns of care.,Post‐COVID‐19 presentation was associated with a lower admission LVEF (45 vs. 50%, p = .015), new Q‐wave, and higher initial troponin; however, these did not reach statistical significance.,Among post‐COVID‐19 patients, those with >12‐hr delay in presentation 31(%) had a longer average D2B time (88 vs. 53 min, p = .033) and higher peak troponin (58 vs.,8.5 ng/ml, p = .03).,Of these, 27% avoided the hospital due to fear of COVID‐19, 18% believed symptoms were COVID‐19 related, and 9% did not want to burden the hospital during the pandemic.,COVID‐19 has remarkably affected STEMI presentation and care.,Patients' fear and confusion about symptoms are integral parts of this emerging public health crisis.

Emerging evidence indicates that both innate and adaptive immunity contribute to hypertension.,Efforts to understand mechanisms of immune activation in hypertension are defining not only new mechanisms of disease but also new therapeutic options for its treatment.,Although systemic hypertension affects a large proportion of the population, its etiology remains poorly defined.,Emerging evidence supports the concept that immune cells become activated and enter target organs, including the vasculature and the kidney, in this disease.,Mediators released by these cells, including reactive oxygen species, metalloproteinases, cytokines, and antibodies promote dysfunction of the target organs and cause damage.,In vessels, these factors enhance constriction, remodeling, and rarefaction.,In the kidney, these mediators increase expression and activation of sodium transporters, and cause interstitial fibrosis and glomerular injury.,Factors common to hypertension, including oxidative stress, increased interstitial sodium, cytokine production, and inflammasome activation promote immune activation in hypertension.,Recent data suggest that isolevuglandin-modified self-proteins in antigen-presenting cells are immunogenic, promoting cytokine production by the cells in which they are formed and T cell activation.,Efforts to prevent and reverse immune activation may prove beneficial in preventing the long-term sequelae of hypertension and its related cardiovascular diseases.

Recent studies suggest a role for T lymphocytes in hypertension.,However, whether T cells contribute to renal sodium retention and salt-sensitive hypertension is unknown.,Here we demonstrate that T cells infiltrate into the kidney of salt-sensitive hypertensive animals.,In particular, CD8+ T cells directly contact the distal convoluted tubule (DCT) in the kidneys of DOCA-salt mice and CD8+ T cell-injected mice, leading to up-regulation of the Na-Cl co-transporter NCC, p-NCC and the development of salt-sensitive hypertension.,Co-culture with CD8+ T cells upregulates NCC in mouse DCT cells via ROS-induced activation of Src kinase, up-regulation of the K+ channel Kir4.1, and stimulation of the Cl− channel ClC-K.,The last event increases chloride efflux, leading to compensatory chloride influx via NCC activation at the cost of increasing sodium retention.,Collectively, these findings provide a mechanism for adaptive immunity involvement in the kidney defect in sodium handling and the pathogenesis of salt-sensitive hypertension.,T cells contribute to development of high blood pressure but their role in salt-sensitive hypertension is less clear.,Liu et al. show that CD8+ T cells upregulate and activate Na-Cl co-transporter NCC in distal convoluted tubules via direct cell-cell contact and ROS-Src activation, leading to Na+ retention and salt-sensitive hypertension.

Supplemental Digital Content is available in the text.,Coronavirus disease 2019 (COVID-19) has led to over 1 million deaths worldwide and has been associated with cardiac complications including cardiac arrhythmias.,The incidence and pathophysiology of these manifestations remain elusive.,In this worldwide survey of patients hospitalized with COVID-19 who developed cardiac arrhythmias, we describe clinical characteristics associated with various arrhythmias, as well as global differences in modulations of routine electrophysiology practice during the pandemic.,We conducted a retrospective analysis of patients hospitalized with COVID-19 infection worldwide with and without incident cardiac arrhythmias.,Patients with documented atrial fibrillation, atrial flutter, supraventricular tachycardia, nonsustained or sustained ventricular tachycardia, ventricular fibrillation, atrioventricular block, or marked sinus bradycardia (heart rate<40 bpm) were classified as having arrhythmia.,Deidentified data was provided by each institution and analyzed.,Data were collected for 4526 patients across 4 continents and 12 countries, 827 of whom had an arrhythmia.,Cardiac comorbidities were common in patients with arrhythmia: 69% had hypertension, 42% diabetes, 30% had heart failure, and 24% had coronary artery disease.,Most had no prior history of arrhythmia.,Of those who did develop an arrhythmia, the majority (81.8%) developed atrial arrhythmias, 20.7% developed ventricular arrhythmias, and 22.6% had bradyarrhythmia.,Regional differences suggested a lower incidence of atrial fibrillation in Asia compared with other continents (34% versus 63%).,Most patients in North America and Europe received hydroxychloroquine, although the frequency of hydroxychloroquine therapy was constant across arrhythmia types.,Forty-three percent of patients who developed arrhythmia were mechanically ventilated and 51% survived to hospital discharge.,Many institutions reported drastic decreases in electrophysiology procedures performed.,Cardiac arrhythmias are common and associated with high morbidity and mortality among patients hospitalized with COVID-19 infection.,There were significant regional variations in the types of arrhythmias and treatment approaches.

Remote monitoring (RM) has significantly transformed the standard of care for patients with cardiac electronic implantable devices.,It provides easy access to valuable information, such as arrhythmic events, acute decompensation manifestations and device‐related issues, without the need of in‐person visits.,Starting March 1st, 332 patients were introduced to an RM program during the Italian lockdown to limit the risk of in‐hospital exposure to severe acute respiratory syndrome‐coronavirus‐2.,Patients were categorized into two groups based on the modality of RM delivery (home [n = 229] vs. office [n = 103] delivered).,The study aimed at assessing the efficacy of the new follow‐up protocol, assessed as mean RM activation time (AT), and the need for technical support.,In addition, patients' acceptance and anxiety status were quantified via the Home Monitoring Acceptance and Satisfaction Questionnaire and the Generalized Anxiety Disorder 7‐item scale.,AT time was less than 48 h in 93% of patients and 7% of them required further technical support.,Despite a higher number of trans‐telephonic technical support in the home‐delivered RM group, mean AT was similar between groups (1.33 ± 0.83 days in home‐delivered vs 1.28 ± 0.81 days in office‐delivered patients; p = .60).,A total of 28 (2.5%) urgent/emergent in‐person examinations were required.,A high degree of patient satisfaction was reached in both groups whereas anxiety status was higher in the office‐delivered group.,The adoption of RM resulted in high patient satisfaction, regardless of the modality of modem delivery; nonetheless, in‐office modem delivery was associated with a higher prevalence of anxiety symptoms.

The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades.,We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies.,While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system.,Risk of severe infection and mortality increase with advancing age and male sex.,Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer.,The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC).,Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes.,This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI).,While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis.,Hence, patients should not discontinue their use.,Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19.,Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19.,Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications.,Preventive measures (social distancing and social isolation) also increase cardiovascular risk.,Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

Studies have reminded that cardiovascular metabolic comorbidities made patients more susceptible to suffer 2019 novel corona virus (2019-nCoV) disease (COVID-19), and exacerbated the infection.,The aim of this analysis is to determine the association of cardiovascular metabolic diseases with the development of COVID-19.,A meta-analysis of eligible studies that summarized the prevalence of cardiovascular metabolic diseases in COVID-19 and compared the incidences of the comorbidities in ICU/severe and non-ICU/severe patients was performed.,Embase and PubMed were searched for relevant studies.,A total of six studies with 1527 patients were included in this analysis.,The proportions of hypertension, cardia-cerebrovascular disease and diabetes in patients with COVID-19 were 17.1%, 16.4% and 9.7%, respectively.,The incidences of hypertension, cardia-cerebrovascular diseases and diabetes were about twofolds, threefolds and twofolds, respectively, higher in ICU/severe cases than in their non-ICU/severe counterparts.,At least 8.0% patients with COVID-19 suffered the acute cardiac injury.,The incidence of acute cardiac injury was about 13 folds higher in ICU/severe patients compared with the non-ICU/severe patients.,Patients with previous cardiovascular metabolic diseases may face a greater risk of developing into the severe condition and the comorbidities can also greatly affect the prognosis of the COVID-19.,On the other hand, COVID-19 can, in turn, aggravate the damage to the heart.

The COVID-19 pandemic has had a profound effect on general health care.,We aimed to evaluate the effect of a nationwide lockdown in France on admissions to hospital for acute myocardial infarction, by patient characteristics and regional prevalence of the pandemic.,In this registry study, we collected data from 21 centres participating in the ongoing French Cohort of Myocardial Infarction Evaluation (FRENCHIE) registry, which collects data from all patients admitted for ST segment elevation myocardial infarction (STEMI) or non-ST segment elevation myocardial infarction (NSTEMI) within 48 h of symptom onset.,We analysed weekly hospital admissions over 8 weeks: the 4 weeks preceding the institution of the lockdown and the 4 weeks following lockdown.,The primary outcome was the change in the number of hospital admissions for all types of acute myocardial infarction, NSTEMI, and STEMI between the 4 weeks before lockdown and the 4 weeks after lockdown.,Comparisons between categorical variables were made using χ2 tests or Fisher's exact tests.,Comparisons of continuous variables were made using Student's t tests or Mann-Whitney tests.,Poisson regression was used to determine the significance of change in hospital admissions over the two periods, after verifying the absence of overdispersion.,Age category, region, and type of acute myocardial infarction (STEMI or NSTEMI) were used as covariables.,The FRENCHIE cohort is registered with ClinicalTrials.gov, NCT04050956.,Between Feb 17 and April 12, 2020, 1167 patients were consecutively admitted within 48 h of acute myocardial infarction (583 with STEMI, 584 with NSTEMI) and were included in the study.,Admissions for acute myocardial infarction decreased between the periods before and after lockdown was instituted, from 686 before to 481 after lockdown (30% decrease; incidence rate ratio 0·69 [95% CI 0·51-0·70]).,Admissions for STEMI decreased from 331 to 252 (24%; 0·72 [0·62-0·85]), and admissions for NSTEMI decreased from 355 to 229 (35%; 0·64 [0·55-0·76]) following institution of the lockdown, with similar trends according to sex, risk factors, and regional prevalence of hospital admissions for COVID-19.,A marked decrease in hospital admissions was observed following the lockdown, irrespective of patient characteristics and regional prevalence of COVID-19.,Health authorities should be aware of these findings, in order to adapt their message if the COVID-19 pandemic persists or recurs, or in case of future major epidemics.,Recherche Hospitalo-Universitaire en Santé iVasc.

The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades.,We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies.,While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system.,Risk of severe infection and mortality increase with advancing age and male sex.,Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer.,The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC).,Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes.,This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI).,While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis.,Hence, patients should not discontinue their use.,Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19.,Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19.,Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications.,Preventive measures (social distancing and social isolation) also increase cardiovascular risk.,Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

Pressure overload induces a transition from cardiac hypertrophy to heart failure, but its underlying mechanisms remain elusive.,Here we reconstruct a trajectory of cardiomyocyte remodeling and clarify distinct cardiomyocyte gene programs encoding morphological and functional signatures in cardiac hypertrophy and failure, by integrating single-cardiomyocyte transcriptome with cell morphology, epigenomic state and heart function.,During early hypertrophy, cardiomyocytes activate mitochondrial translation/metabolism genes, whose expression is correlated with cell size and linked to ERK1/2 and NRF1/2 transcriptional networks.,Persistent overload leads to a bifurcation into adaptive and failing cardiomyocytes, and p53 signaling is specifically activated in late hypertrophy.,Cardiomyocyte-specific p53 deletion shows that cardiomyocyte remodeling is initiated by p53-independent mitochondrial activation and morphological hypertrophy, followed by p53-dependent mitochondrial inhibition, morphological elongation, and heart failure gene program activation.,Human single-cardiomyocyte analysis validates the conservation of the pathogenic transcriptional signatures.,Collectively, cardiomyocyte identity is encoded in transcriptional programs that orchestrate morphological and functional phenotypes.,The mechanisms underlying the transition from cardiac hypertrophy to heart failure following pressure overload are incompletely understood.,Here the authors identify the gene programs encoding the morphological and functional characteristics of cardiomyocytes during the transition from early hypertrophy to heart failure via single-cell transcriptomics, establishing a key role for p53 signalling.

Cardiac regeneration may revolutionize treatment for heart failure but endogenous progenitor-derived cardiomyocytes in the adult mammalian heart are few and pre-existing adult cardiomyocytes divide only at very low rates.,Although candidate genes that control cardiomyocyte cell cycle re-entry have been implicated, expression heterogeneity in the cardiomyocyte stress-response has never been explored.,Here, we show by single nuclear RNA-sequencing of cardiomyocytes from both mouse and human failing, and non-failing adult hearts that sub-populations of cardiomyocytes upregulate cell cycle activators and inhibitors consequent to the stress-response in vivo.,We characterize these subgroups by weighted gene co-expression network analysis and discover long intergenic non-coding RNAs (lincRNA) as key nodal regulators.,KD of nodal lincRNAs affects expression levels of genes related to dedifferentiation and cell cycle, within the same gene regulatory network.,Our study reveals that sub-populations of adult cardiomyocytes may have a unique endogenous potential for cardiac regeneration in vivo.,Adult mammalian cardiomyocytes are predominantly binucleated and unable to divide.,Using single nuclear RNA-sequencing of cardiomyocytes from mouse and human failing and non-failing adult hearts, See et al. show that some cardiomyocytes respond to stress by dedifferentiation and cell cycle re-entry regulated by lncRNAs.

Coronavirus disease 2019 (COVID‐19) is associated with coagulopathy but the optimal prophylactic anticoagulation therapy remains uncertain and may depend on COVID‐19 severity.,To compare outcomes in hospitalized adults with severe COVID‐19 treated with standard prophylactic versus intermediate dose enoxaparin.,We conducted a multi‐center, open‐label, randomized controlled trial comparing standard prophylactic dose versus intermediate dose enoxaparin in adults who were hospitalized with COVID‐19 and admitted to an intensive care unit (ICU) and/or had laboratory evidence of coagulopathy.,Patients were randomly assigned in a 1:1 ratio to receive standard prophylactic dose enoxaparin or intermediate weight‐adjusted dose enoxaparin.,The primary outcome was all‐cause mortality at 30 days.,Secondary outcomes included arterial or venous thromboembolism and major bleeding.,A total of 176 patients (99 males and 77 females) underwent randomization.,In the intention‐to‐treat population, all‐cause mortality at 30 days was 15% for intermediate dose enoxaparin and 21% for standard prophylactic dose enoxaparin (odds ratio, 0.66; 95% confidence interval, 0.30-1.45; P = .31 by Chi‐square test).,Unadjusted Cox proportional hazards modeling demonstrated no significant difference in mortality between intermediate and standard dose enoxaparin (hazard ratio, 0.67; 95% confidence interval, 0.33-1.37; P = .28).,Arterial or venous thrombosis occurred in 13% of patients assigned to intermediate dose enoxaparin and 9% of patients assigned to standard dose enoxaparin.,Major bleeding occurred in 2% of patients in each arm.,In hospitalized adults with severe COVID‐19, standard prophylactic dose and intermediate dose enoxaparin did not differ significantly in preventing death or thrombosis at 30 days.

Coronavirus disease 2019 (COVID-19)-related critical illness and acute illness are associated with a risk of venous thromboembolism (VTE).,These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in decisions about the use of anticoagulation for thromboprophylaxis for patients with COVID-19-related critical illness and acute illness who do not have confirmed or suspected VTE.,ASH formed a multidisciplinary guideline panel and applied strict management strategies to minimize potential bias from conflicts of interest.,The panel included 3 patient representatives.,The McMaster University GRADE Centre supported the guideline-development process, including performing systematic evidence reviews (up to 19 August 2020).,The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients.,The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment.,The panel agreed on 2 recommendations.,The panel issued conditional recommendations in favor of prophylactic-intensity anticoagulation over intermediate-intensity or therapeutic-intensity anticoagulation for patients with COVID-19-related critical illness or acute illness who do not have confirmed or suspected VTE.,These recommendations were based on very low certainty in the evidence, underscoring the need for high-quality, randomized controlled trials comparing different intensities of anticoagulation.,They will be updated using a living recommendation approach as new evidence becomes available.

Hypertrophic cardiomyopathy-causing mutations disrupt a key regulatory off state of myosin in thick filaments.,Hypertrophic cardiomyopathy (HCM) mutations in β-cardiac myosin and myosin binding protein-C (MyBP-C) lead to hypercontractility of the heart, an early hallmark of HCM.,We show that hypercontractility caused by the HCM-causing mutation R663H cannot be explained by changes in fundamental myosin contractile parameters, much like the HCM-causing mutation R403Q.,Using enzymatic assays with purified human β-cardiac myosin, we provide evidence that both mutations cause hypercontractility by increasing the number of functionally accessible myosin heads.,We also demonstrate that the myosin mutation R403Q, but not R663H, ablates the binding of myosin with the C0-C7 fragment of MyBP-C.,Furthermore, addition of C0-C7 decreases the wild-type myosin basal ATPase single turnover rate, while the mutants do not show a similar reduction.,These data suggest that a primary mechanism of action for these mutations is to increase the number of myosin heads functionally available for interaction with actin, which could contribute to hypercontractility.

Supplemental Digital Content is available in the text.,Hypertrophic cardiomyopathy (HCM) is caused by pathogenic variants in sarcomere protein genes that evoke hypercontractility, poor relaxation, and increased energy consumption by the heart and increased patient risks for arrhythmias and heart failure.,Recent studies show that pathogenic missense variants in myosin, the molecular motor of the sarcomere, are clustered in residues that participate in dynamic conformational states of sarcomere proteins.,We hypothesized that these conformations are essential to adapt contractile output for energy conservation and that pathophysiology of HCM results from destabilization of these conformations.,We assayed myosin ATP binding to define the proportion of myosins in the super relaxed state (SRX) conformation or the disordered relaxed state (DRX) conformation in healthy rodent and human hearts, at baseline and in response to reduced hemodynamic demands of hibernation or pathogenic HCM variants.,To determine the relationships between myosin conformations, sarcomere function, and cell biology, we assessed contractility, relaxation, and cardiomyocyte morphology and metabolism, with and without an allosteric modulator of myosin ATPase activity.,We then tested whether the positions of myosin variants of unknown clinical significance that were identified in patients with HCM, predicted functional consequences and associations with heart failure and arrhythmias.,Myosins undergo physiological shifts between the SRX conformation that maximizes energy conservation and the DRX conformation that enables cross-bridge formation with greater ATP consumption.,Systemic hemodynamic requirements, pharmacological modulators of myosin, and pathogenic myosin missense mutations influenced the proportions of these conformations.,Hibernation increased the proportion of myosins in the SRX conformation, whereas pathogenic variants destabilized these and increased the proportion of myosins in the DRX conformation, which enhanced cardiomyocyte contractility, but impaired relaxation and evoked hypertrophic remodeling with increased energetic stress.,Using structural locations to stratify variants of unknown clinical significance, we showed that the variants that destabilized myosin conformations were associated with higher rates of heart failure and arrhythmias in patients with HCM.,Myosin conformations establish work-energy equipoise that is essential for life-long cellular homeostasis and heart function.,Destabilization of myosin energy-conserving states promotes contractile abnormalities, morphological and metabolic remodeling, and adverse clinical outcomes in patients with HCM.,Therapeutic restabilization corrects cellular contractile and metabolic phenotypes and may limit these adverse clinical outcomes in patients with HCM.

Since the appearance of the first case of coronavirus disease 2019 (COVID-19) a pandemic has emerged affecting millions of people worldwide.,Although the main clinical manifestations are respiratory, an increase in neurological conditions, specifically acute cerebrovascular disease, has been detected.,We present cerebrovascular disease case incidence in hospitalized patients with SARS-CoV-2 infection.,Patients were confirmed by microbiological/serological testing, or on chest CT semiology.,Available data on comorbidity, laboratory parameters, treatment administered, neuroimaging, neuropathological studies and clinical evolution during hospitalization, measured by the modified Rankin scale, were analysed.,A bivariate study was also designed to identify differences between ischaemic and haemorrhagic subtypes.,A statistical model of binary logistic regression and sensitivity analysis was designed to study the influence of independent variables over prognosis.,In our centre, there were 1683 admissions of patients with COVID-19 over 50 days, of which 23 (1.4%) developed cerebrovascular disease.,Within this group of patients, cerebral and chest CT scans were performed in all cases, and MRI in six (26.1%).,Histological samples were obtained in 6/23 cases (two brain biopsies, and four arterial thrombi).,Seventeen patients were classified as cerebral ischaemia (73.9%, with two arterial dissections), five as intracerebral haemorrhage (21.7%), and one leukoencephalopathy of posterior reversible encephalopathy type.,Haemorrhagic patients had higher ferritin levels at the time of stroke (1554.3 versus 519.2, P = 0.004).,Ischaemic strokes were unexpectedly frequent in the vertebrobasilar territory (6/17, 35.3%).,In the haemorrhagic group, a characteristic radiological pattern was identified showing subarachnoid haemorrhage, parieto-occipital leukoencephalopathy, microbleeds and single or multiple focal haematomas.,Brain biopsies performed showed signs of thrombotic microangiopathy and endothelial injury, with no evidence of vasculitis or necrotizing encephalitis.,The functional prognosis during the hospital period was unfavourable in 73.9% (17/23 modified Rankin scale 4-6), and age was the main predictive variable (odds ratio = 1.5; 95% confidence interval 1.012-2.225; P = 0.043).,Our series shows cerebrovascular disease incidence of 1.4% in patients with COVID-19 with high morbidity and mortality.,We describe pathological and radiological data consistent with thrombotic microangiopathy caused by endotheliopathy with a haemorrhagic predisposition.

•We demonstrate five consecutive cases of predominantly lobar COVID-19-associated intracerebral haemorrhage (ICH).,•Patients were typically relatively young with a severe, prolonged inflammatory prodrome.,•COVID-19-induced endotheliitis/endotheliopathy may underlie associated cerebrovascular events.,•For the clinician, anticoagulation decisions must balance risk of thrombosis with risk of haemorrhage.,We demonstrate five consecutive cases of predominantly lobar COVID-19-associated intracerebral haemorrhage (ICH).,Patients were typically relatively young with a severe, prolonged inflammatory prodrome.,COVID-19-induced endotheliitis/endotheliopathy may underlie associated cerebrovascular events.,For the clinician, anticoagulation decisions must balance risk of thrombosis with risk of haemorrhage.

COVID‐19 is a systemic infection with a significant impact on the hematopoietic system and hemostasis.,Lymphopenia may be considered as a cardinal laboratory finding, with prognostic potential.,Neutrophil/lymphocyte ratio and peak platelet/lymphocyte ratio may also have prognostic value in determining severe cases.,During the disease course, longitudinal evaluation of lymphocyte count dynamics and inflammatory indices, including LDH, CRP and IL‐6 may help to identify cases with dismal prognosis and prompt intervention in order to improve outcomes.,Biomarkers, such high serum procalcitonin and ferritin have also emerged as poor prognostic factors.,Furthermore, blood hypercoagulability is common among hospitalized COVID‐19 patients.,Elevated D‐Dimer levels are consistently reported, whereas their gradual increase during disease course is particularly associated with disease worsening.,Other coagulation abnormalities such as PT and aPTT prolongation, fibrin degradation products increase, with severe thrombocytopenia lead to life‐threatening disseminated intravascular coagulation (DIC), which necessitates continuous vigilance and prompt intervention.,So, COVID‐19 infected patients, whether hospitalized or ambulatory, are at high risk for venous thromboembolism, and an early and prolonged pharmacological thromboprophylaxis with low molecular weight heparin is highly recommended.,Last but not least, the need for assuring blood donations during the pandemic is also highlighted.

The outbreak of the novel coronavirus in China (SARS‐CoV‐2) that began in December 2019 presents a significant and urgent threat to global health.,This study was conducted to provide the international community with a deeper understanding of this new infectious disease.,Epidemiological, clinical features, laboratory findings, radiological characteristics, treatment, and clinical outcomes of 135 patients in northeast Chongqing were collected and analyzed in this study.,A total of 135 hospitalized patients with COVID‐19 were enrolled.,The median age was 47 years (interquartile range, 36‐55), and there was no significant gender difference (53.3% men).,The majority of patients had contact with people from the Wuhan area.,Forty‐three (31.9%) patients had underlying disease, primarily hypertension (13 [9.6%]), diabetes (12 [8.9%]), cardiovascular disease (7 [5.2%]), and malignancy (4 [3.0%]).,Common symptoms included fever (120 [88.9%]), cough (102 [76.5%]), and fatigue (44 [32.5%]).,Chest computed tomography scans showed bilateral patchy shadows or ground glass opacity in the lungs of all the patients.,All patients received antiviral therapy (135 [100%]) (Kaletra and interferon were both used), antibacterial therapy (59 [43.7%]), and corticosteroids (36 [26.7%]).,In addition, many patients received traditional Chinese medicine (TCM) (124 [91.8%]).,It is suggested that patients should receive Kaletra early and should be treated by a combination of Western and Chinese medicines.,Compared to the mild cases, the severe ones had lower lymphocyte counts and higher plasma levels of Pt, APTT, d‐dimer, lactate dehydrogenase, PCT, ALB, C‐reactive protein, and aspartate aminotransferase.,This study demonstrates the clinic features and therapies of 135 COVID‐19 patients.,Kaletra and TCM played an important role in the treatment of the viral pneumonia.,Further studies are required to explore the role of Kaletra and TCM in the treatment of COVID‐19.,83.7% of the patients had contact history in Wuhan or had been to Wuhan or had contact with people from Wuhan.Common symptoms included fever, cough, and fatigue.,Other symptoms include myalgia, fatigue, dyspnea, anorexia, etc.Common complications of the patients include acute respiratory distress syndrome, acute cardiac injury, acute kidney injury, secondary infection and shock.,ICU patients were more likely to have these complications than non‐ICU patients.Compared with non‐ICU patients, ICU patients had lower lymphocyte count, and higher plasma levels of the Pt, APTT, D‐dimer, LDH, PCT, ALB, CRP, AST.All patients received antiviral therapy (kaletra or interferon), antibacterial therapy and corticosteroid and many received traditional chinese medicine.,It was suggested that patients should use kaletra early.,83.7% of the patients had contact history in Wuhan or had been to Wuhan or had contact with people from Wuhan.,Common symptoms included fever, cough, and fatigue.,Other symptoms include myalgia, fatigue, dyspnea, anorexia, etc.,Common complications of the patients include acute respiratory distress syndrome, acute cardiac injury, acute kidney injury, secondary infection and shock.,ICU patients were more likely to have these complications than non‐ICU patients.,Compared with non‐ICU patients, ICU patients had lower lymphocyte count, and higher plasma levels of the Pt, APTT, D‐dimer, LDH, PCT, ALB, CRP, AST.,All patients received antiviral therapy (kaletra or interferon), antibacterial therapy and corticosteroid and many received traditional chinese medicine.,It was suggested that patients should use kaletra early.

The 2019 novel coronavirus outbreak and its associated disease (coronavirus disease 2019 [COVID-19]) have created a worldwide pandemic.,Early data suggest higher rate of ischemic stroke in severe COVID-19 infection.,We evaluated whether a relationship exists between emergent large vessel occlusion (ELVO) and the ongoing COVID-19 outbreak.,This is a retrospective, observational case series.,Data were collected from all patients who presented with ELVO to the Mount Sinai Health System Hospitals across New York City during the peak 3 weeks of hospitalization and death from COVID-19.,Patients’ demographic, comorbid conditions, cardiovascular risk factors, COVID-19 disease status, and clinical presentation were extracted from the electronic medical record.,Comparison was made between COVID-19 positive and negative cohorts.,The incidence of ELVO stroke was compared with the pre-COVID period.,Forty-five consecutive ELVO patients presented during the observation period.,Fifty-three percent of patients tested positive for COVID-19.,Total patients’ mean (±SD) age was 66 (±17).,Patients with COVID-19 were significantly younger than patients without COVID-19, 59±13 versus 74±17 (odds ratio [95% CI], 0.94 [0.81-0.98]; P=0.004).,Seventy-five percent of patients with COVID-19 were male compared with 43% of patients without COVID-19 (odds ratio [95% CI], 3.99 [1.12-14.17]; P=0.032).,Patients with COVID-19 were less likely to be White (8% versus 38% [odds ratio (95% CI), 0.15 (0.04-0.81); P=0.027]).,In comparison to a similar time duration before the COVID-19 outbreak, a 2-fold increase in the total number of ELVO was observed (estimate: 0.78 [95% CI, 0.47-1.08], P≤0.0001).,More than half of the ELVO stroke patients during the peak time of the New York City’s COVID-19 outbreak were COVID-19 positive, and those patients with COVID-19 were younger, more likely to be male, and less likely to be White.,Our findings also suggest an increase in the incidence of ELVO stroke during the peak of the COVID-19 outbreak.

The COVID-19 pandemic has disrupted established care paths worldwide.,Patient awareness of the pandemic and executive limitations imposed on public life have changed the perception of when to seek care for acute conditions in some cases.,We sought to study whether there is a delay in presentation for acute ischemic stroke patients in the first month of the pandemic in the US.,The interval between last-known-well (LKW) time and presentation of 710 consecutive patients presenting with acute ischemic strokes to 12 stroke centers across the US were extracted from a prospectively maintained quality database.,We analyzed the timing and severity of the presentation in the baseline period from February to March 2019 and compared results with the timeframe of February and March 2020.,There were 320 patients in the 2-month baseline period in 2019, there was a marked decrease in patients from February to March of 2020 (227 patients in February, and 163 patients in March).,There was no difference in the severity of the presentation between groups and no difference in age between the baseline and the COVID period.,The mean interval from LKW to the presentation was significantly longer in the COVID period (603±1035 min) compared with the baseline period (442±435 min, P<0.02).,We present data supporting an association between public awareness and limitations imposed on public life during the COVID-19 pandemic in the US and a delay in presentation for acute ischemic stroke patients to a stroke center.

Supplemental Digital Content is available in the text.,Canagliflozin is a sodium glucose cotransporter 2 inhibitor that significantly reduces the composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke in patients with type 2 diabetes mellitus and elevated cardiovascular risk.,The comparative effects among participants with and without a history of cardiovascular disease (secondary versus primary prevention) were prespecified for evaluation.,The CANVAS Program (Canagliflozin Cardiovascular Assessment Study) randomly assigned 10 142 participants with type 2 diabetes mellitus to canagliflozin or placebo.,The primary prevention cohort comprised individuals ≥50 years of age with ≥2 risk factors for cardiovascular events but with no prior cardiovascular event, and the secondary prevention cohort comprised individuals ≥30 years of age with a prior cardiovascular event.,The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.,Secondary outcomes included heart failure hospitalization and a renal composite (40% reduction in estimated glomerular filtration rate, renal replacement therapy, or renal death).,Primary prevention participants (N=3486; 34%) were younger (63 versus 64 years of age), were more often female (45% versus 31%), and had a longer duration of diabetes mellitus (14 versus 13 years) compared with secondary prevention participants (N=6656; 66%).,The primary end point event rate was higher in the secondary prevention group compared with the primary prevention group (36.9 versus 15.7/1000 patient-years, P<0.001).,In the total cohort, the primary end point was reduced with canagliflozin compared with placebo (26.9 versus 31.5/1000 patient-years; hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.75-0.97; P<0.001 for noninferiority, P=0.02 for superiority) with no statistical evidence of heterogeneity (interaction P value=0.18) between the primary (HR, 0.98; 95% CI, 0.74-1.30) and secondary prevention (HR, 0.82; 95% CI, 0.72-0.95) cohorts.,Renal outcomes (HR, 0.59; 95% CI, 0.44-0.79 versus HR, 0.63; 95% CI, 0.39-1.02; interaction P value=0.73) and heart failure hospitalization (HR, 0.68; 95% CI, 0.51-0.90 versus HR, 0.64; 95% CI, 0.35-1.15; interaction P value=0.91) were similarly reduced in the secondary and primary prevention cohorts, respectively.,Lower extremity amputations were similarly increased in the secondary and primary prevention cohorts (HR, 2.07; 95% CI, 1.43-3.00 versus HR, 1.52; 95% CI, 0.70-3.29; interaction P value=0.63).,Patients with type 2 diabetes mellitus and prior cardiovascular events had higher rates of cardiovascular outcomes compared with the primary prevention patients.,Canagliflozin reduced cardiovascular and renal outcomes with no statistical evidence of heterogeneity of the treatment effect across the primary and secondary prevention groups.,Additional studies will provide further insights into the effects of canagliflozin in these patient populations.,URL: https://www.clinicaltrials.gov.,Unique identifiers: NCT01032629 and NCT01989754.

Previous animal studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1RAs) suppress arterial restenosis, a major complication of angioplasty, presumably through their direct action on vascular smooth muscle cells.,However, the contribution of vascular endothelial cells (VECs) to this process remains unknown.,In addition, the potential interference caused by severe hyperglycemia and optimal treatment regimen remain to be determined.,Nine-week-old male C57BL6 (wild-type) and diabetic db/db mice were randomly divided into vehicle or liraglutide treatment groups (Day 1), and subject to femoral artery wire injuries (Day 3).,The injured arteries were collected on Day 29 for morphometric analysis.,Human umbilical vein endothelial cells (HUVECs) were used for in vitro experiments.,One-way ANOVA, followed by Tukey’s test, was used for comparisons.,In wild-type mice, liraglutide treatment (5.7, 17, or 107 nmol/kg/day) dose-dependently reduced the neointimal area (20, 50, and 65%) without inducing systemic effects, and caused an associated decrease in the percentage of vascular proliferating cells.,However, these effects were completely abolished by the nitric oxide synthase (NOS) inhibitor N-omega-nitro-l-arginine methyl ester.,Next, we investigated the optimal treatment regimen.,Early treatment (Days 1-14) was as effective in reducing the neointimal area and vascular cell proliferation as full treatment (Days 1-29), whereas delayed treatment (Days 15-29) was ineffective.,In HUVECs, liraglutide treatment dose-dependently stimulated NO production, which was dependent on GLP-1R, cAMP, cAMP-dependent protein kinase, AMP-activated protein kinase (AMPK), and NOS.,Subsequently, we investigated the role of liver kinase B (LKB)-1 in this process.,Liraglutide increased the phosphorylation of LKB-1, and siRNA-induced LKB-1 knockdown abolished liraglutide-stimulated NO production.,In severe hyperglycemic db/db mice, liraglutide treatment also suppressed neointimal hyperplasia, which was accompanied by reductions in vascular cell proliferation and density.,Furthermore, liraglutide treatment suppressed hyperglycemia-enhanced vascular inflammation 7 days after arterial injury.,We demonstrate that endothelial cells are targets of liraglutide, and suppress restenosis via endothelial NO.,Furthermore, the protective effects are maintained in severe hyperglycemia.,Our findings provide an evidence base for a future clinical trial to determine whether treatment with GLP-1RAs represents potentially effective pharmacological therapy following angioplasty in patients with diabetes.,The online version of this article (doi:10.1186/s12933-017-0603-x) contains supplementary material, which is available to authorized users.

The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur.,This brief report evaluates cardiovascular complications in the setting of COVID-19 infection.,The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death.,The virus binds and enters through angiotensin-converting enzyme 2 (ACE2).,COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness.,The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events.,Current therapies for COVID-19 may interact with cardiovascular medications.,Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.

Acute respiratory failure and a systemic coagulopathy are critical aspects of the morbidity and mortality characterizing infection with severe acute respiratory distress syndrome-associated coronavirus-2, the etiologic agent of Coronavirus disease 2019 (COVID-19).,We examined skin and lung tissues from 5 patients with severe COVID-19 characterized by respiratory failure (n= 5) and purpuric skin rash (n = 3).,COVID-19 pneumonitis was predominantly a pauci-inflammatory septal capillary injury with significant septal capillary mural and luminal fibrin deposition and permeation of the interalveolar septa by neutrophils.,No viral cytopathic changes were observed and the diffuse alveolar damage (DAD) with hyaline membranes, inflammation, and type II pneumocyte hyperplasia, hallmarks of classic acute respiratory distress syndrome, were not prominent.,These pulmonary findings were accompanied by significant deposits of terminal complement components C5b-9 (membrane attack complex), C4d, and mannose binding lectin (MBL)-associated serine protease (MASP)2, in the microvasculature, consistent with sustained, systemic activation of the complement pathways.,The purpuric skin lesions similarly showed a pauci-inflammatory thrombogenic vasculopathy, with deposition of C5b-9 and C4d in both grossly involved and normally-appearing skin.,In addition, there was co-localization of COVID-19 spike glycoproteins with C4d and C5b-9 in the interalveolar septa and the cutaneous microvasculature of 2 cases examined.,In conclusion, at least a subset of sustained, severe COVID-19 may define a type of catastrophic microvascular injury syndrome mediated by activation of complement pathways and an associated procoagulant state.,It provides a foundation for further exploration of the pathophysiologic importance of complement in COVID-19, and could suggest targets for specific intervention.

To describe the cardiac abnormalities in patients with COVID-19 and identify the characteristics of patients who would benefit most from echocardiography.,In a prospective international survey, we captured echocardiography findings in patients with presumed or confirmed COVID-19 between 3 and 20 April 2020.,Patient characteristics, indications, findings, and impact of echocardiography on management were recorded.,Multivariable logistic regression identified predictors of echocardiographic abnormalities.,A total of 1216 patients [62 (52-71) years, 70% male] from 69 countries across six continents were included.,Overall, 667 (55%) patients had an abnormal echocardiogram.,Left and right ventricular abnormalities were reported in 479 (39%) and 397 (33%) patients, respectively, with evidence of new myocardial infarction in 36 (3%), myocarditis in 35 (3%), and takotsubo cardiomyopathy in 19 (2%).,Severe cardiac disease (severe ventricular dysfunction or tamponade) was observed in 182 (15%) patients.,In those without pre-existing cardiac disease (n = 901), the echocardiogram was abnormal in 46%, and 13% had severe disease.,Independent predictors of left and right ventricular abnormalities were distinct, including elevated natriuretic peptides [adjusted odds ratio (OR) 2.96, 95% confidence interval (CI) 1.75-5.05) and cardiac troponin (OR 1.69, 95% CI 1.13-2.53) for the former, and severity of COVID-19 symptoms (OR 3.19, 95% CI 1.73-6.10) for the latter.,Echocardiography changed management in 33% of patients.,In this global survey, cardiac abnormalities were observed in half of all COVID-19 patients undergoing echocardiography.,Abnormalities were often unheralded or severe, and imaging changed management in one-third of patients.

Up to one-third of COVID-19 patients admitted to intensive care develop an acute cardiomyopathy, which may represent myocarditis or stress cardiomyopathy.,Further, while mortality in older patients with COVID-19 appears related to multi-organ failure complicating acute respiratory distress syndrome (ARDS), the cause of death in younger patients may be related to acute heart failure.,Cardiac involvement needs to be considered early on in critically ill COVID-19 patients, and even after the acute respiratory phase is passing.,This Statement presents a screening algorithm to better identify COVID-19 patients at risk for severe heart failure and circulatory collapse, while balancing the need to protect health care workers and preserve personal protective equipment (PPE).,The significance of serum troponin levels and the role of telemetry and targeted transthoracic echocardiography (TTE) in patient investigation and management are addressed, as are fundamental considerations in the management of acute heart failure in COVID-19 patients.

Children descending from pregnancies complicated by gestational hypertension (GH), preeclampsia (PE) or fetal growth restriction (FGR) have a lifelong cardiovascular risk.,The aim of the study was to verify if pregnancy complications induce postnatal alterations in gene expression of microRNAs associated with cardiovascular/cerebrovascular diseases.,Twenty-nine microRNAs were assessed in peripheral blood, compared between groups, and analyzed in relation to both aspects, the current presence of cardiovascular risk factors and cardiovascular complications and the previous occurrence of pregnancy complications with regard to the clinical signs, dates of delivery, and Doppler ultrasound examination.,The expression profile of miR-21-5p differed between controls and children with a history of uncomplicated pregnancies with abnormal clinical findings.,Abnormal expression profile of multiple microRNAs was found in children affected with GH (miR-1-3p, miR-17-5p, miR-20a-5p, miR-21-5p, miR-23a-3p, miR-26a-5p, miR-29a-3p, miR-103a-3p, miR-125b-5p, miR-126-3p, miR-133a-3p, miR-146a-5p, miR-181a-5p, miR-195-5p, and miR-342-3p), PE (miR-1-3p, miR-20a-5p, miR-20b-5p, miR-103a-3p, miR-133a-3p, miR-342-3p), and FGR (miR-17-5p, miR-126-3p, miR-133a-3p).,The index of pulsatility in the ductus venosus showed a strong positive correlation with miR-210-3p gene expression in children exposed to PE and/or FGR.,Any of changes in epigenome (up-regulation of miR-1-3p and miR-133a-3p) that were induced by pregnancy complications are long-acting and may predispose children affected with GH, PE, or FGR to later development of cardiovascular/cerebrovascular diseases.,Novel epigenetic changes (aberrant expression profile of microRNAs) appeared in a proportion of children that were exposed to GH, PE, or FGR.,Screening of particular microRNAs may stratify a highly risky group of children that might benefit from implementation of early primary prevention strategies.

We investigated the role of microRNAs (miRNA) in endothelial dysfunction in the setting of cardiometabolic disorders represented by type 2 diabetes mellitus (T2DM). miR‐29 was dysregulated in resistance arterioles obtained by biopsy in T2DM patients.,Intraluminal delivery of miR‐29a‐3p or miR‐29b‐3p mimics restored normal endothelium‐dependent vasodilation (EDVD) in T2DM arterioles that otherwise exhibited impaired EDVD.,Intraluminal delivery of anti‐miR‐29b‐3p in arterioles from non‐DM human subjects or rats or targeted mutation of Mir29b‐1/a gene in rats led to impaired EDVD and exacerbation of hypertension in the rats. miR‐29b‐3p mimic increased, while anti‐miR‐29b‐3p or Mir29b‐1/a gene mutation decreased, nitric oxide levels in arterioles.,The mutation of Mir29b‐1/a gene led to preferential differential expression of genes related to nitric oxide including Lypla1.,Lypla1 was a direct target of miR‐29 and could abrogate the effect of miR‐29 in promoting nitric oxide production.,Treatment with Lypla1 siRNA improved EDVD in arterioles obtained from T2DM patients or Mir29b‐1/a mutant rats or treated with anti‐miR‐29b‐3p.,These findings indicate miR‐29 is required for normal endothelial function in humans and animal models and has therapeutic potential for cardiometabolic disorders.

Severe coronavirus disease 2019 (COVID‐19) is characterized by an increased risk of thromboembolic events, with evidence of microthrombosis in the lungs of deceased patients.,To investigate the mechanism of microthrombosis in COVID‐19 progression.,We assessed von Willebrand factor (VWF) antigen (VWF:Ag), VWF ristocetin‐cofactor (VWF:RCo), VWF multimers, VWF propeptide (VWFpp), and ADAMTS13 activity in a cross‐sectional study of 50 patients stratified according to their admission to three different intensity of care units: low (requiring high‐flow nasal cannula oxygenation, n = 14), intermediate (requiring continuous positive airway pressure devices, n = 17), and high (requiring mechanical ventilation, n = 19).,Median VWF:Ag, VWF:RCo, and VWFpp levels were markedly elevated in COVID‐19 patients and increased with intensity of care, with VWF:Ag being 268, 386, and 476 IU/dL; VWF:RCo 216, 334, and 388 IU/dL; and VWFpp 156, 172, and 192 IU/dL in patients at low, intermediate, and high intensity of care, respectively.,Conversely, the high‐to‐low molecular‐weight VWF multimers ratios progressively decreased with increasing intensity of care, as well as median ADAMTS13 activity levels, which ranged from 82 IU/dL for patients at low intensity of care to 62 and 55 IU/dL for those at intermediate and high intensity of care.,We found a significant alteration of the VWF‐ADAMTS13 axis in COVID‐19 patients, with an elevated VWF:Ag to ADAMTS13 activity ratio that was strongly associated with disease severity.,Such an imbalance enhances the hypercoagulable state of COVID‐19 patients and their risk of microthrombosis.

Thirty percent of Covid‐19 patients admitted to intensive care units present with thrombotic complications despite thromboprophylaxis.,Bed rest, obesity, hypoxia, coagulopathy, and acute excessive inflammation are potential mechanisms reported by previous studies.,Better understanding of the underlying mechanisms leading to thrombosis is crucial for developing more appropriate prophylaxis and treatment strategies.,We aimed to assess fibrinolytic activity and thrombin generation in 78 Covid‐19 patients.,Forty‐eight patients admitted to the intensive care unit and 30 patients admitted to the internal medicine department were included in the study.,All patients received thromboprophylaxis.,We measured fibrinolytic parameters (tissue plasminogen activator, PAI‐1, thrombin activatable fibrinolysis inhibitor, alpha2 anti‐plasmin, and tissue plasminogen activator‐modified ROTEM device), thrombin generation, and other coagulation tests (D‐dimer, fibrinogen, factor VIII, antithrombin).,We observed two key findings: a high thrombin generation capacity that remained within normal values despite heparin therapy and a hypofibrinolysis mainly associated with increased PAI‐1 levels.,A modified ROTEM is able to detect both hypercoagulability and hypofibrinolysis simultaneously in Covid‐19 patients with thrombosis.

Glibenclamide is a widely used sulfonylurea drug prescribed to treat type II diabetes mellitus.,Previous studies have demonstrated that glibenclamide has neuroprotective effects in central nervous system injury.,However, the exact mechanism by which glibenclamide acts on the blood-brain barrier (BBB) after intracerebral hemorrhage (ICH) remains unclear.,The purpose of this study was to validate the neuroprotective effects of glibenclamide on ICH and to explore the mechanisms underlying these effects.,We investigated the effects of glibenclamide on experimental ICH using the autologous blood infusion model.,Glibenclamide was administrated either immediately or 2 hr after ICH.,Brain edema was quantified using the wet-dry method 3 days after injury.,BBB integrity was evaluated by Evans Blue extravasation and degradation of the tight junction protein zona occludens‐1 (ZO‐1). mRNA levels of inflammatory cytokines were determined by quantitative polymerase chain reaction.,Activation of the nucleotide‐binding oligomerization domain‐like receptor with a pyrin domain 3 (NLRP3) inflammasome and cell viability were also measured in cerebral microvascular endothelial b.End3 cells exposed to hemin.,Neurological changes were evaluated by the Garcia score and rotarod test.,After ICH, the brain water content, Evans Blue extravasation, and inflammatory cytokines decreased significantly in the ipsilateral hemisphere of the experimental compared to the vehicle group.,Glibenclamide treatment and NLRP3 knockdown significantly reduced hemin‐induced activation of the NLRP3 inflammasome, release of extracellular lactate dehydrogenase, apoptosis, and loss of ZO‐1 in b.End3 cells.,However, NLRP3 knockdown abolished the protective effect of glibenclamide.,Glibenclamide maintained BBB integrity in experimental ICH by inhibiting the activation of the NLRP3 inflammasome in microvessel endothelial cells.,Our findings will contribute to elucidating the pharmacological mechanism of action of glibenclamide and to developing a novel therapy for clinical ICH.

Inflammasomes are involved in diverse inflammatory diseases.,Previous study reported that the neurotransmitter dopamine inhibited NLRP3 inflammasome activation via dopamine D1 receptor (DRD1).,The present study aims to investigate the role of DRD1 on neuroinflammation in intracerebral hemorrhage (ICH) mice and the potential mechanism mediated by NLRP3 inhibition.,One hundred and six male CD-1 mice were subjected to intrastriatal injection of bacterial collagenase or PBS.,A68930 (DRD1 specific agonist) was administered by subcutaneous injection at 1 h after collagenase injection.,Behavioral deficits and brain water content were assayed.,The expression of Iba 1 and MPO levels were measured by immunofluorescence staining.,The expressions of proteins in the DRD1/interferon-beta (IFN-beta)/NLRP3 signaling pathway were evaluated by western blotting.,Activation of the DRD1 by A68930 decreased brain edema and improved behavior at 24 and 72 h of ICH.,A68930 inhibited partly the activation of microglia and the neutrophil infiltration after 24 h of ICH.,IFN-beta, p-STAT1 increased while NLRP3, caspase 1, and IL-1beta decreased after A68930 administration in ICH mice.,DRD1 antagonist and IFN-beta siRNA reversed effects of A68930 on neurological outcome and brain edema.,DRD1 antagonist and IFN-beta siRNA blocked not only A68930-mediated increases of IFN-beta, p-STAT1 but also A68930-mediated decreases of NLRP3, caspase 1, and IL-1beta.,DRD1 activation by A68930 improves neurological outcome through inhibition of NLRP3-mediated inflammation in ICH mice.,The online version of this article (10.1186/s12974-017-1039-7) contains supplementary material, which is available to authorized users.

Supplemental Digital Content is available in the text.,The pandemic caused by the novel coronavirus disease 2019 (COVID-19) has led to an unprecedented paradigm shift in medical care.,We sought to evaluate whether the COVID-19 pandemic may have contributed to delays in acute stroke management at comprehensive stroke centers.,Pooled clinical data of consecutive adult stroke patients from 14 US comprehensive stroke centers (January 1, 2019, to July 31, 2020) were queried.,The rate of thrombolysis for nontransferred patients within the Target: Stroke goal of 60 minutes was compared between patients admitted from March 1, 2019, and July 31, 2019 (pre-COVID-19), and March 1, 2020, to July 31, 2020 (COVID-19).,The time from arrival to imaging and treatment with thrombolysis or thrombectomy, as continuous variables, were also assessed.,Of the 2955 patients who met inclusion criteria, 1491 were admitted during the pre-COVID-19 period and 1464 were admitted during COVID-19, 15% of whom underwent intravenous thrombolysis.,Patients treated during COVID-19 were at lower odds of receiving thrombolysis within 60 minutes of arrival (odds ratio, 0.61 [95% CI, 0.38-0.98]; P=0.04), with a median delay in door-to-needle time of 4 minutes (P=0.03).,The lower odds of achieving treatment in the Target: Stroke goal persisted after adjustment for all variables associated with earlier treatment (adjusted odds ratio, 0.55 [95% CI, 0.35-0.85]; P<0.01).,The delay in thrombolysis appeared driven by the longer delay from imaging to bolus (median, 29 [interquartile range, 18-41] versus 22 [interquartile range, 13-37] minutes; P=0.02).,There was no significant delay in door-to-groin puncture for patients who underwent thrombectomy (median, 83 [interquartile range, 63-133] versus 90 [interquartile range, 73-129] minutes; P=0.30).,Delays in thrombolysis were observed in the months of June and July.,Evaluation for acute ischemic stroke during the COVID-19 period was associated with a small but significant delay in intravenous thrombolysis but no significant delay in thrombectomy time metrics.,Taking steps to reduce delays from imaging to bolus time has the potential to attenuate this collateral effect of the pandemic.

Since the onset of the coronavirus 2019 (COVID-19) pandemic, doctors and public authorities have demonstrated concern about the reduction in quality of care for other health conditions due to social restrictions and lack of resources.,Using a population-based stroke registry, we investigated the impact of the onset of the COVID-19 pandemic in stroke admissions in Joinville, Brazil.,Patients admitted after the onset of COVID-19 restrictions in the city (defined as March 17, 2020) were compared with those admitted in 2019.,We analyzed differences between stroke incidence, types, severity, reperfusion therapies, and time from stroke onset to admission.,Statistical tests were also performed to compare the 30 days before and after COVID-19 to the same period in 2019.,We observed a decrease in total stroke admissions from an average of 12.9/100 000 per month in 2019 to 8.3 after COVID-19 (P=0.0029).,When compared with the same period in 2019, there was a 36.4% reduction in stroke admissions.,There was no difference in admissions for severe stroke (National Institutes of Health Stroke Scale score >8), intraparenchymal hemorrhage, and subarachnoid hemorrhage.,The onset of COVID-19 was correlated with a reduction in admissions for transient, mild, and moderate strokes.,Given the need to prevent the worsening of symptoms and the occurrence of medical complications in these groups, a reorganization of the stroke-care networks is necessary to reduce collateral damage caused by COVID-19.

Three months ago, severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) broke out in Wuhan, China, and spread rapidly around the world.,Severe novel coronavirus pneumonia (NCP) patients have abnormal blood coagulation function, but their venous thromboembolism (VTE) prevalence is still rarely mentioned.,To determine the incidence of VTE in patients with severe NCP.,In this study, 81 severe NCP patients in the intensive care unit (ICU) of Union Hospital (Wuhan, China) were enrolled.,The results of conventional coagulation parameters and lower limb vein ultrasonography of these patients were retrospectively collected and analyzed.,The incidence of VTE in these patients was 25% (20/81), of which 8 patients with VTE events died.,The VTE group was different from the non‐VTE group in age, lymphocyte counts, activated partial thromboplastin time (APTT), D‐dimer, etc.,If 1.5 µg/mL was used as the D‐dimer cut‐off value to predicting VTE, the sensitivity was 85.0%, the specificity was 88.5%, and the negative predictive value (NPV) was 94.7%.,The incidence of VTE in patients with severe NCP is 25% (20/81), which may be related to poor prognosis.,The significant increase of D‐dimer in severe NCP patients is a good index for identifying high‐risk groups of VTE.

A novel coronavirus severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) caused pneumonia, Coronavirus Disease 2019 (COVID-19), broke out in Wuhan, China in December 2019, and spread all over the world.,Patients with COVID-19 showed huge differences in the hospital stay, progression, and prognosis.,As reported, the comorbidities may play an important role in COVID-19.,Here, we aim to address the role of cardiovascular disease (CVD) in the progression and prognosis of COVID-19.,Eighty-three confirmed COVID-19 patients were divided into CVD (n = 42) and non-CVD (n = 41) group according to their medical history.,Medical records including demographic data, medical history, clinical characteristics, laboratory examinations, chest computed tomography (CT), and treatment measures were collected, analyzed, and compared between the two groups.,COVID-19 patients with CVD showed (1) more severe pathological changes in the lungs, (2) elevated injury-related enzymes including α-hydroxybutyrate dehydrogenase (HDBH), lactic dehydrogenase (LDH), γ-glutamyltransferase (GGT), creatine kinase (CK), and alanine aminotransferase (ALT), (3) significantly increased uncontrolled inflammation related markers, such as c-reactive protein (CRP), interleukin (IL)-6, serum ferritin, erythrocyte sedimentation rate (ESR), and serum amyloid A (SAA), (4) serious hypercoagulable status reflected by increased D-dimer and serum fibrinogen (FIB), and (5) higher mortality, compared to COVID-19 patients without CVD.,Our data indicated that CVD is a strong risk factor for rapid progression and bad prognosis of COVID-19.,More intensive medical care should be applied to patients with CVD to prevent rapid deterioration of the disease.,•The COVID-19 patients with CVD experienced more severe pneumonia.,•The COVID-19 patients with CVD showed more tissue injury-related enzymes release.,•The COVID-19 patients with CVD were at higher risk of cytokine storm.,•The COVID-19 patients with CVD were at higher risk of hypercoagulable state.,•CVD is a risk factor for the progression and prognosis of COVID-19.,The COVID-19 patients with CVD experienced more severe pneumonia.,The COVID-19 patients with CVD showed more tissue injury-related enzymes release.,The COVID-19 patients with CVD were at higher risk of cytokine storm.,The COVID-19 patients with CVD were at higher risk of hypercoagulable state.,CVD is a risk factor for the progression and prognosis of COVID-19.

The novel coronavirus disease 2019 (COVID-19) pandemic is still spreading across the world.,Although the pandemic has an all-round impact on medical work, the degree of its impact on endovascular thrombectomy (EVT) for patients with acute ischemic stroke (AIS) is unclear.,We continuously included AIS patients with large artery occlusion who underwent EVT in a comprehensive stroke center before and during the Wuhan shutdown.,The protected code stroke (PCS) for screening and treating AIS patients was established during the pandemic.,The efficacy and safety outcomes including the rate of successful reperfusion (defined as modified Thrombolysis In Cerebral Infarction (mTICI) graded 2b or 3) and time intervals for reperfusion were compared between two groups: pre-pandemic and pandemic.,A total of 55 AIS patients who received EVT were included.,The baseline characteristics were comparable between the two groups.,The time from hospital arrival to puncture (174 vs 125.5 min; p=0.002) and time from hospital arrival to reperfusion (213 vs 172 min; p=0.047) were significantly prolonged in the pandemic group compared with the pre-pandemic group.,The rate of successful reperfusion was not significantly different between the two groups (85.7% (n=18) vs 88.2% (n=30); OR 0.971, 95% CI 0.785 to 1.203; p=1.000).,The results of this study suggest a proper PCS algorithm which combines the COVID-19 screening and protection measures could decrease the impact of the disease on the clinical outcomes of EVT for AIS patients to the lowest extent possible during the pandemic.

Hyperacute assessment and management of patients with stroke, termed code stroke, is a time-sensitive and high-stakes clinical scenario.,In the context of the current coronavirus disease 2019 (COVID-19) pandemic caused by the SARS-CoV-2 virus, the ability to deliver timely and efficacious care must be balanced with the risk of infectious exposure to the clinical team.,Furthermore, rapid and effective stroke care remains paramount to achieve maximal functional recovery for those needing admission and to triage care appropriately for those who may be presenting with neurological symptoms but have an alternative diagnosis.,Available resources, COVID-19-specific infection prevention and control recommendations, and expert consensus were used to identify clinical screening criteria for patients and provide the required nuanced considerations for the healthcare team, thereby modifying the conventional code stroke processes to achieve a protected designation.,A protected code stroke algorithm was developed.,Features specific to prenotification and clinical status of the patient were used to define precode screening.,These include primary infectious symptoms, clinical, and examination features.,A focused framework was then developed with regard to a protected code stroke.,We outline the specifics of personal protective equipment use and considerations thereof including aspects of crisis resource management impacting team role designation and human performance factors during a protected code stroke.,We introduce the concept of a protected code stroke during a pandemic, as in the case of COVID-19, and provide a framework for key considerations including screening, personal protective equipment, and crisis resource management.,These considerations and suggested algorithms can be utilized and adapted for local practice.

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is prone to being complicated with various cardiovascular, cerebrovascular and metabolic conditions.,OSAHS, due to its multifactorial nature, entails individualized and comprehensive treatment.,So far, no well-established diagnostic criteria for the disease are available.,In recent years, miRNA has been shown to be a sensitive biomarker suggestive of the progression and prognosis of many diseases.,In this study, we examined some serum miRNAs in healthy OSAHS (OSAHS patients without complication) and OSAHS with arterial hypertension, with an attempt to understand the potential effects on the disease, improve the diagnosis of OSAHS and find OSAHS-related diagnostic markers.,Against various diagnostic criteria, participants were divided into three groups: healthy OSAHS, OSAHS with arterial hypertension and healthy controls.,Their serum miRNA profiles were assessed by microarray technology, and then differentially expressed miRNAs were verified by quantitative real-time PCR (qRT-PCR).,The receiver operating characteristic (ROC) curves of miRNAs were constructed and the areas under the curve (AUC) were calculated.,Meanwhile, the miRNAs were subjected to logistic regression analysis.,The target genes were bioinformatically assessed, their functions and signaling pathways further determined and eventually an miRNA-gene network was established.,Analysis with the miRNA array exhibited that, compared with the control group, 12 differentially expressed miRNAs were found in healthy OSAHS, and 33 were found in OSAHS with arterial hypertension.,The expression of miR-126-3p, let-7d-5p, miR-7641 and miR-1233-5p, miR-320b, miR-145-5p, miR-107, miR-26a-5p were validated by using qRT-PCR.,Bioinformatics analysis predicted that the potential target genes of these miRNAs might be involved in metabolism, and the regulation of endothelial cells and nervous system.,Moreover, the ROC analysis showed that the using miR-145-5p and let-7d-5p in combination can identify the healthy OSAHS, presence of miR-126-3p, miR-26a-5p and miR-107 was well indicative of OSAHS with arterial hypertension.,A cluster of dysregulation miRNAs have been found to be involved in the development of OSAHS patients.,Moreover, these miRNAs might be used to be potential diagnostic and early warning markers.

Circulating miRNAs are proposed as a biomarker of heart disease.,This study evaluated whether circulating miRNAs could be used as a biomarker for childhood dilated cardiomyopathy (CDCM).,A total of 28 participants were enrolled in a discovery set, including patients with CDCM (n = 16) and healthy children (n = 12).,The cardiac function of patients with CDCM was characterized by echocardiography and serum miRNA profiles of all participants were assessed by miRNA sequencing.,After miRNA profiling, we quantitatively confirmed 148 regulated miRNAs in patients with CDCM compared with healthy subjects, and none were downregulated.,Validation of candidate miRNAs was assessed by quantitative real-time polymerase chain reaction in other patients with CDCM (n = 30) and healthy controls (n = 16).,A unique signature comprising mir-142-5p, mir-143-3p, mir-27b-3p, and mir-126-3p differentiated patients with CDCM from healthy subjects.,Importantly, we observed an increase in mir-126-3p or let-7g in parallel with a robust decrease in the ejection fraction in patients with CDCM, which could differentiate heart failure patients from non-heart failure patients with CDCM.,Moreover, mir-126-3p and let-7g were significantly negatively associated with the left ventricular ejection fraction.,This study shows that a signature of four serum miRNAs may be a potential biomarker for diagnosing CDCM and assessing heart failure.

Coronavirus disease 2019 (COVID-19) may cause myocardial injury and myocarditis, and reports of persistent cardiac pathology after COVID-19 have raised concerns of long-term cardiac consequences.,We aimed to assess the presence of abnormal cardiovascular resonance imaging (CMR) findings in patients recovered from moderate-to-severe COVID-19, and its association with markers of disease severity in the acute phase.,Fifty-eight (49%) survivors from the prospective COVID MECH study, underwent CMR median 175 [IQR 105-217] days after COVID-19 hospitalization.,Abnormal CMR was defined as left ventricular ejection fraction (LVEF) <50% or myocardial scar by late gadolinium enhancement.,CMR indices were compared to healthy controls (n = 32), and to circulating biomarkers measured during the index hospitalization.,Abnormal CMR was present in 12 (21%) patients, of whom 3 were classified with major pathology (scar and LVEF <50% or LVEF <40%).,There was no difference in the need of mechanical ventilation, length of hospital stay, and vital signs between patients with vs without abnormal CMR after 6 months.,Severe acute respiratory syndrome coronavirus 2 viremia and concentrations of inflammatory biomarkers during the index hospitalization were not associated with persistent CMR pathology.,Cardiac troponin T and N-terminal pro-B-type natriuretic peptide concentrations on admission, were higher in patients with CMR pathology, but these associations were not significant after adjusting for demographics and established cardiovascular disease.,CMR pathology 6 months after moderate-to-severe COVID-19 was present in 21% of patients and did not correlate with severity of the disease.,Cardiovascular biomarkers during COVID-19 were higher in patients with CMR pathology, but with no significant association after adjusting for confounders.,COVID MECH Study ClinicalTrials.gov Identifier: NCT04314232

Magnetic resonance (MR) studies suggested cardiac involvement post‐Covid‐19 in a significant subset of affected individuals, including athletes.,This brings serious clinical concerns regarding the potential need for in‐depth cardiac screening in athletes after Covid‐19 before return to play.,The aim of this study was to gain further insight into the relation between Covid‐19 and cardiac involvement in professional athletes.,This was a retrospective cohort study, in which 26 consecutive elite athletes (national team, Olympians, top national league players; median age 24 years, interquartile range [IQR] 21-27, 81% female) were included.,At 1.5 T including balanced steady‐state free precession cine imaging, T1 and T2‐mapping using Myomaps software (Siemens), dark‐blood T2‐weighted images with fat suppression, and late gadolinium enhancement (LGE) with phase‐sensitive inversion recovery sequence were used.,The athletes had mainly asymptomatic or mild course of the disease (77%).,They were scanned after a median of 32 days (IQR 22-62 days) from the diagnosis.,MR data were reviewed by three independent observers, each with >10 years cardiac MR experience.,Native T1, T2, extracellular volume, and T2 signal intensity ratio were calculated.,Diagnosis of acute myocarditis was based on modified Lake Louise criteria.,Statistical analyses used were Pearson correlation and Bland-Altman repeatability analysis.,At the time of MR the athletes had no pathologic electrocardiogram abnormalities or elevated troponin levels.,MR did not reveal any case of acute myocarditis.,Cardiac abnormalities were found in five (19%) athletes, including four athletes presenting borderline signs of isolated myocardial edema and one athlete showing nonischemic LGE with pleural and pericardial effusion.,Another athlete had signs of persistent lung congestion without cardiac involvement.,We have shown that in a small group of elite athletes with mainly asymptomatic to mild Covid‐19, lack of electrocardiographic changes, and normal troponin concentration 1-2 months after the diagnosis, there were no signs of acute myocarditis, but 19% of athletes had some abnormalities as assessed by cardiac MR.,4,3

In the recent outbreak of COVID-19 pandemic, increased D-dimer levels and high rates of venous thromboembolic events were reported.,We aimed to compare coagulation parameters on admission between COVID-19 patients and non-COVID-19 patients with acute respiratory insufficiency and to describe VTE diagnosed at entry.,In this single-centre, observational retrospective study consecutive patients admitted for fever and acute respiratory failure were included.,Patients underwent laboratory tests, arterial blood gas, chest X-ray, point of care ultrasound (POCUS), limited compression ultrasonography of the lower limbs (L-CUS), chest CT-scan if necessary, and swab test for COVID-19.,Of 324 patients, 50% had COVID-19.,COVID19 patients had significantly lower mean white blood cells, neutrophils, platelet count, and pCT values, and significantly higher CRP, LDH, and ferritin levels than non-COVID19 patients.,D-dimer was increased in 86.5% COVID19 patients and in 84.9% non-COVID19 patients; mean values were similar (2185 ng/mL and 2814 ng/mL, respectively, p = n.s.).,After multivariate analysis, results were unchanged (Odds Ratio 1.00 95%CI: 0.99-1.00, p = 0.21).,PT and aPTT values were also similar between the two groups, fibrinogen levels were higher in COVID19 than in non-COVID19 patients (684 and 496 mg/dL, respectively, p < 0.0001).,Five patients had asymptomatic proximal deep vein thrombosis detected by L-CUS (3 COVID19) and 2 patients had symptomatic pulmonary embolism (both non-COVID19).,D-dimer levels were similarly increased in patients with and without SARS-CoV 2 related disease.,There were few cases of asymptomatic deep vein thrombosis or symptomatic pulmonary embolism at first day of admission, similarly distributed between COVID19 patients and non-COVID19 patients.,•High D-dimer levels are associated with an increased risk of venous thromboembolism in COVID-19 patients•High D-dimer levels can be detected in most patients with acute respiratory failure, not only associated with SARS-CoV 2•The prevalence of deep venous thrombosis on admission was similar between patients with and without COVID-19•Patients with COVID-19 had significantly higher levels of CRP, LDH and ferritin than patients without COVID-19,High D-dimer levels are associated with an increased risk of venous thromboembolism in COVID-19 patients,High D-dimer levels can be detected in most patients with acute respiratory failure, not only associated with SARS-CoV 2,The prevalence of deep venous thrombosis on admission was similar between patients with and without COVID-19,Patients with COVID-19 had significantly higher levels of CRP, LDH and ferritin than patients without COVID-19

Acute respiratory distress syndrome development in patients with coronavirus disease 2019 (COVID-19) pneumonia is associated with a high mortality rate and is the main cause of death in patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection [1].,Myocardial injury has also been reported to be significantly associated with fatal outcome, with a 37% mortality rate in patients without prior cardiovascular disease but elevated troponin levels [2].,A D-dimer level of >1 μg·mL−1 has been clearly identified as a risk factor for poor outcome in SARS-Cov-2 infection [3], with recent reports highlighting a high incidence of thrombotic events in intensive care unit (ICU) patients [4].,A normal D-dimer level allows the safe exclusion of pulmonary embolism (PE) in outpatients with a low or intermediate clinical probability of PE, but there is no recommendation to use D-dimer as a positive marker of thrombosis because of lack of specificity.,This study reports an overall 24% (95% CI 17-32%) cumulative incidence of pulmonary embolism in patients with COVID-19 pneumonia, 50% (30-70%) in ICU and 18% (12-27%) in other patientshttps://bit.ly/35s7hjm

Coronavirus disease 2019 (COVID-19) predisposes to arterial and venous thromboembolic complications.,We describe the clinical presentation, management, and outcomes of acute arterial ischemia and concomitant infection at the epicenter of cases in the United States.,Patients with confirmed COVID-19 infection between March 1, 2020 and May 15, 2020 with an acute arterial thromboembolic event were reviewed.,Data collected included demographics, anatomical location of the thromboembolism, treatments, and outcomes.,Over the 11-week period, the Northwell Health System cared for 12,630 hospitalized patients with COVID-19.,A total of 49 patients with arterial thromboembolism and confirmed COVID-19 were identified.,The median age was 67 years (58-75) and 37 (76%) were men.,The most common preexisting conditions were hypertension (53%) and diabetes (35%).,The median D-dimer level was 2,673 ng/mL (723-7,139).,The distribution of thromboembolic events included upper 7 (14%) and lower 35 (71%) extremity ischemia, bowel ischemia 2 (4%), and cerebral ischemia 5 (10%).,Six patients (12%) had thrombus in multiple locations.,Concomitant deep vein thrombosis was found in 8 patients (16%).,Twenty-two (45%) patients presented with signs of acute arterial ischemia and were subsequently diagnosed with COVID-19.,The remaining 27 (55%) developed ischemia during hospitalization.,Revascularization was performed in 13 (27%) patients, primary amputation in 5 (10%), administration of systemic tissue‐ plasminogen activator in 3 (6%), and 28 (57%) were treated with systemic anticoagulation only.,The rate of limb loss was 18%.,Twenty-one patients (46%) died in the hospital.,Twenty-five (51%) were successfully discharged, and 3 patients are still in the hospital.,While the mechanism of thromboembolic events in patients with COVID-19 remains unclear, the occurrence of such complication is associated with acute arterial ischemia which results in a high limb loss and mortality.

With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke.,However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19.,We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic.,We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls).,In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls).,During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke.,Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P=0.003) and historical controls (25.0%, P<0.001).,When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels.,When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate.,Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls.,We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19.,Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased.,Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.

The risk of pulmonary embolism (PE) in patients with Coronavirus Disease 2019 (COVID-19) is recognized.,The prevalence of PE in patients with respiratory deterioration at the Emergency Department (ED), the regular ward, and the Intensive Care Unit (ICU) are not well-established.,We aimed to investigate how often PE was present in individuals with COVID-19 and respiratory deterioration in different settings, and whether or not disease severity as measured by CT-severity score (CTSS) was related to the occurrence of PE.,Between April 6th and May 3rd, we enrolled 60 consecutive adult patients with confirmed COVID-19 from the ED, regular ward and ICU who met the pre-specified criteria for respiratory deterioration.,A total of 24 (24/60: 40% (95% CI: 28-54%)) patients were diagnosed with PE, of whom 6 were in the ED (6/23: 26% (95% CI: 10-46%)), 8 in the regular ward (8/24: 33% (95% CI: 16-55%)), and 10 in the ICU (10/13: 77% (95% CI: 46-95%)).,CTSS (per unit) was not associated with the occurrence of PE (age and sex-adjusted OR 1.06 (95%CI 0.98-1.15)).,The number of PE diagnosis among patients with COVID-19 and respiratory deterioration was high; 26% in the ED, 33% in the regular ward and 77% in the ICU respectively.,In our cohort CTSS was not associated with the occurrence of PE.,Based on the high number of patients diagnosed with PE among those scanned we recommend a low threshold for performing computed tomography angiography in patients with COVID-19 and respiratory deterioration.,•The high prevalence of pulmonary embolism in COVID-19 is not limited to the ICU•Respiratory deterioration in COVID-19 patients should prompt a low threshold CTPA•Regular thromboprophylaxis may be insufficient to prevent PE in COVID-19 patients,The high prevalence of pulmonary embolism in COVID-19 is not limited to the ICU,Respiratory deterioration in COVID-19 patients should prompt a low threshold CTPA,Regular thromboprophylaxis may be insufficient to prevent PE in COVID-19 patients

To evaluate the prevalence of acute pulmonary embolism (APE) in non-hospitalized COVID-19 patients referred to CT pulmonary angiography (CTPA) by the emergency department.,From March 14 to April 6, 2020, 72 non-hospitalized patients referred by the emergency department to CTPA for COVID-19 pneumonia were retrospectively identified.,Relevant clinical and laboratory data and CT scan findings were collected for each patient.,CTPA scans were reviewed by two radiologists to determinate the presence or absence of APE.,Clinical classification, lung involvement of COVID-19 pneumonia, and CT total severity score were compared between APE group and non-APE group.,APE was identified in 13 (18%) CTPA scans.,The mean age and D-dimer of patients from the APE group were higher in comparison with those from the non-APE group (74.4 vs.,59.6 years, p = 0.008, and 7.29 vs.,3.29 μg/ml, p = 0.011).,There was no significant difference between APE and non-APE groups concerning clinical type, COVID-19 pneumonia lung lesions (ground-glass opacity: 85% vs. 97%; consolidation: 69% vs. 68%; crazy paving: 38% vs. 37%; linear reticulation: 69% vs.,78%), CT severity score (6.3 vs.,7.1, p = 0.365), quality of CTPA (1.8 vs.,2.0, p = 0.518), and pleural effusion (38% vs. 19%, p = 0.146).,Non-hospitalized patients with COVID-19 pneumonia referred to CT scan by the emergency departments are at risk of APE.,The presence of APE was not limited to severe or critical clinical type of COVID-19 pneumonia.,• Acute pulmonary embolism was found in 18% of non-hospitalized COVID-19 patients referred by the emergency department to CTPA.,Two (15%) patients had main, four (30%) lobar, and seven (55%) segmental acute pulmonary embolism.,• Five of 13 (38%) patients with acute pulmonary embolism had a moderate clinical type.,• Severity and radiological features of COVID-19 pneumonia showed no significant difference between patients with or without acute pulmonary embolism.

Biological considerations suggest that renin-angiotensin system inhibitors might influence the severity of COVID-19.,We aimed to evaluate whether continuing versus discontinuing renin-angiotensin system inhibitors (angiotensin-converting enzyme inhibitors or angiotensin receptor blockers) affects outcomes in patients admitted to hospital with COVID-19.,The REPLACE COVID trial was a prospective, randomised, open-label trial done at 20 large referral hospitals in seven countries worldwide.,Eligible participants were aged 18 years and older who were admitted to hospital with COVID-19 and were receiving a renin-angiotensin system inhibitor before admission.,Individuals with contraindications to continuation or discontinuation of renin-angiotensin system inhibitor therapy were excluded.,Participants were randomly assigned (1:1) to continuation or discontinuation of their renin-angiotensin system inhibitor using permuted block randomisation, with allocation concealed using a secure web-based randomisation system.,The primary outcome was a global rank score in which participants were ranked across four hierarchical tiers incorporating time to death, duration of mechanical ventilation, time on renal replacement or vasopressor therapy, and multiorgan dysfunction during the hospitalisation.,Primary analyses were done in the intention-to-treat population.,The REPLACE COVID trial is registered with ClinicalTrials.gov, NCT04338009.,Between March 31 and Aug 20, 2020, 152 participants were enrolled and randomly assigned to either continue or discontinue renin-angiotensin system inhibitor therapy (continuation group n=75; discontinuation group n=77).,Mean age of participants was 62 years (SD 12), 68 (45%) were female, mean body-mass index was 33 kg/m2 (SD 8), and 79 (52%) had diabetes.,Compared with discontinuation of renin-angiotensin system inhibitors, continuation had no effect on the global rank score (median rank 73 [IQR 40-110] for continuation vs 81 [38-117] for discontinuation; β-coefficient 8 [95% CI −13 to 29]).,There were 16 (21%) of 75 participants in the continuation arm versus 14 (18%) of 77 in the discontinuation arm who required intensive care unit admission or invasive mechanical ventilation, and 11 (15%) of 75 participants in the continuation group versus ten (13%) of 77 in the discontinuation group died. 29 (39%) participants in the continuation group and 28 (36%) participants in the discontinuation group had at least one adverse event (χ2 test of adverse events between treatment groups p=0·77).,There was no difference in blood pressure, serum potassium, or creatinine during follow-up across the two groups.,Consistent with international society recommendations, renin-angiotensin system inhibitors can be safely continued in patients admitted to hospital with COVID-19.,REPLACE COVID Investigators, REPLACE COVID Trial Social Fundraising Campaign, and FastGrants.

The COVID-19 pandemic is an unprecedented healthcare emergency causing mortality and illness across the world.,Although primarily affecting the lungs, the SARS-CoV-2 virus also affects the cardiovascular system.,In addition to cardiac effects, e.g. myocarditis, arrhythmias, and myocardial damage, the vasculature is affected in COVID-19, both directly by the SARS-CoV-2 virus, and indirectly as a result of a systemic inflammatory cytokine storm.,This includes the role of the vascular endothelium in the recruitment of inflammatory leucocytes where they contribute to tissue damage and cytokine release, which are key drivers of acute respiratory distress syndrome (ARDS), in disseminated intravascular coagulation, and cardiovascular complications in COVID-19.,There is also evidence linking endothelial cells (ECs) to SARS-CoV-2 infection including: (i) the expression and function of its receptor angiotensin-converting enzyme 2 (ACE2) in the vasculature; (ii) the prevalence of a Kawasaki disease-like syndrome (vasculitis) in COVID-19; and (iii) evidence of EC infection with SARS-CoV-2 in patients with fatal COVID-19.,Here, the Working Group on Atherosclerosis and Vascular Biology together with the Council of Basic Cardiovascular Science of the European Society of Cardiology provide a Position Statement on the importance of the endothelium in the underlying pathophysiology behind the clinical presentation in COVID-19 and identify key questions for future research to address.,We propose that endothelial biomarkers and tests of function (e.g. flow-mediated dilatation) should be evaluated for their usefulness in the risk stratification of COVID-19 patients.,A better understanding of the effects of SARS-CoV-2 on endothelial biology in both the micro- and macrovasculature is required, and endothelial function testing should be considered in the follow-up of convalescent COVID-19 patients for early detection of long-term cardiovascular complications.

The COVID‐19 pandemic has become an urgent issue in every country.,Based on recent reports, the most severely ill patients present with coagulopathy, and disseminated intravascular coagulation (DIC)‐like massive intravascular clot formation is frequently seen in this cohort.,Therefore, coagulation tests may be considered useful to discriminate severe cases of COVID‐19.,The clinical presentation of COVID‐19‐associated coagulopathy is organ dysfunction primarily, whereas hemorrhagic events are less frequent.,Changes in hemostatic biomarkers represented by increase in D‐dimer and fibrin/fibrinogen degradation products indicate the essence of coagulopathy is massive fibrin formation.,In comparison with bacterial‐sepsis‐associated coagulopathy/DIC, prolongation of prothrombin time, and activated partial thromboplastin time, and decrease in antithrombin activity is less frequent and thrombocytopenia is relatively uncommon in COVID‐19.,The mechanisms of the coagulopathy are not fully elucidated, however.,It is speculated that the dysregulated immune responses orchestrated by inflammatory cytokines, lymphocyte cell death, hypoxia, and endothelial damage are involved.,Bleeding tendency is uncommon, but the incidence of thrombosis in COVID‐19 and the adequacy of current recommendations regarding standard venous thromboembolic dosing are uncertain.

Coronavirus disease 2019 (COVID-19) represents a public health crisis of pandemic proportions.,Caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the symptoms most commonly reported include cough, fever and shortness of breath, but extra-pulmonary symptoms may also be present, such as neurological and gastroenterological manifestations.,Endothelial cell dysfunction and impaired microcirculatory function contribute markedly to life-threatening complications of COVID-19, such as venous thromboembolic disease and multiple organ involvementhttps://bit.ly/3cZMjKV

A potential association between the use of angiotensin-receptor blockers (ARBs) and angiotensin-converting-enzyme (ACE) inhibitors and the risk of coronavirus disease 2019 (Covid-19) has not been well studied.,We carried out a population-based case-control study in the Lombardy region of Italy.,A total of 6272 case patients in whom infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed between February 21 and March 11, 2020, were matched to 30,759 beneficiaries of the Regional Health Service (controls) according to sex, age, and municipality of residence.,Information about the use of selected drugs and patients’ clinical profiles was obtained from regional databases of health care use.,Odds ratios and 95% confidence intervals for associations between drugs and infection, with adjustment for confounders, were estimated by means of logistic regression.,Among both case patients and controls, the mean (±SD) age was 68±13 years, and 37% were women.,The use of ACE inhibitors and ARBs was more common among case patients than among controls, as was the use of other antihypertensive and non-antihypertensive drugs, and case patients had a worse clinical profile.,Use of ARBs or ACE inhibitors did not show any association with Covid-19 among case patients overall (adjusted odds ratio, 0.95 [95% confidence interval {CI}, 0.86 to 1.05] for ARBs and 0.96 [95% CI, 0.87 to 1.07] for ACE inhibitors) or among patients who had a severe or fatal course of the disease (adjusted odds ratio, 0.83 [95% CI, 0.63 to 1.10] for ARBs and 0.91 [95% CI, 0.69 to 1.21] for ACE inhibitors), and no association between these variables was found according to sex.,In this large, population-based study, the use of ACE inhibitors and ARBs was more frequent among patients with Covid-19 than among controls because of their higher prevalence of cardiovascular disease.,However, there was no evidence that ACE inhibitors or ARBs affected the risk of COVID-19.

There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).,We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive.,Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class.,A difference of at least 10 percentage points was prespecified as a substantial difference.,Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness.,A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness.,There was no association between any single medication class and an increased likelihood of a positive test.,None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive.,We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) associates with a considerable high rate of mortality and represents currently the most important concern in global health.,The risk of more severe clinical manifestation of COVID-19 is higher in males and steeply raised with age but also increased by the presence of chronic comorbidities.,Among the latter, early reports suggested that arterial hypertension associates with higher susceptibility to SARS-CoV-2 infection, more severe course and increased COVID-19-related deaths.,Furthermore, experimental studies suggested that key pathophysiological hypertension mechanisms, such as activation of the renin-angiotensin system (RAS), may play a role in COVID-19.,In fact, ACE2 (angiotensin-converting-enzyme 2) is the pivotal receptor for SARS-CoV-2 to enter host cells and provides thus a link between COVID-19 and RAS.,It was thus anticipated that drugs modulating the RAS including an upregulation of ACE2 may increase the risk for infection with SARS-CoV-2 and poorer outcomes in COVID-19.,Since the use of RAS-blockers, ACE inhibitors or angiotensin receptor blockers, represents the backbone of recommended antihypertensive therapy and intense debate about their use in the COVID-19 pandemic has developed.,Currently, a direct role of hypertension, independent of age and other comorbidities, as a risk factor for the SARS-COV-2 infection and COVID-19 outcome, particularly death, has not been established.,Similarly, both current experimental and clinical studies do not support an unfavorable effect of RAS-blockers or other classes of first line blood pressure lowering drugs in COVID-19.,Here, we review available data on the role of hypertension and its management on COVID-19.,Conversely, some aspects as to how the COVID-19 affects hypertension management and impacts on future developments are also briefly discussed.,COVID-19 has and continues to proof the critical importance of hypertension research to address questions that are important for global health.

There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).,We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive.,Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class.,A difference of at least 10 percentage points was prespecified as a substantial difference.,Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness.,A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness.,There was no association between any single medication class and an increased likelihood of a positive test.,None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive.,We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.

The influence of the COVID-19 pandemic on attendance to out-of-hospital cardiac arrest (OHCA) has only been described in city or regional settings.,The impact of COVID-19 across an entire country with a high infection rate is yet to be explored.,The study uses data from 8629 cases recorded in two time-series (2017/2018 and 2020) of the Spanish national registry.,Data from a non-COVID-19 period and the COVID-19 period (February 1st-April 30th 2020) were compared.,During the COVID-19 period, data a further analysis comparing non-pandemic and pandemic weeks (defined according to the WHO declaration on March 11th, 2020) was conducted.,The chi-squared analysis examined differences in OHCA attendance and other patient and resuscitation characteristics.,Multivariate logistic regression examined survival likelihood to hospital admission and discharge.,The multilevel analysis examined the differential effects of regional COVID-19 incidence on these same outcomes.,During the COVID-19 period, the incidence of resuscitation attempts declined and survival to hospital admission (OR = 1.72; 95%CI = 1.46-2.04; p < 0.001) and discharge (OR = 1.38; 95%CI = 1.07-1.78; p = 0.013) fell compared to the non-COVID period.,This pattern was also observed when comparing non-pandemic weeks and pandemic weeks.,COVID-19 incidence impinged significantly upon outcomes regardless of regional variation, with low, medium, and high incidence regions equally affected.,The pandemic, irrespective of its incidence, seems to have particularly impeded the pre-hospital phase of OHCA care.,Present findings call for the need to adapt out-of-hospital care for periods of serious infection risk.,ISRCTN10437835.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy.,The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020.,Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease.,Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease.,Mean age was 67 ± 12 years, and 80 (81%) patients were males.,No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients.,During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock.,Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08-5.09).,The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively).,Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates.

In this systematic review and meta-analysis, we aimed to explore the association between cardiac injury and mortality, the need for intensive care unit (ICU) care, acute respiratory distress syndrome (ARDS), and severe coronavirus disease 2019 (COVID-19) in patients with COVID-19 pneumonia.,We performed a comprehensive literature search from several databases.,Definition of cardiac injury follows that of the included studies, which includes highly sensitive cardiac troponin I (hs-cTnl) >99th percentile.The primary outcome was mortality, and the secondary outcomes were ARDS, the need for ICU care, and severe COVID-19.,ARDS and severe COVID-19 were defined per the World Health Organization (WHO) interim guidance of severe acute respiratory infection (SARI) of COVID-19.,There were a total of 2389 patients from 13 studies.,This meta-analysis showed that cardiac injury was associated with higher mortality (RR 7.95 [5.12, 12.34], p < 0.001; I2: 65%).,Cardiac injury was associated with higher need for ICU care (RR 7.94 [1.51, 41.78], p = 0.01; I2: 79%), and severe COVID-19 (RR 13.81 [5.52, 34.52], p < 0.001; I2: 0%).,The cardiac injury was not significant for increased risk of ARDS (RR 2.57 [0.96, 6.85], p = 0.06; I2: 84%).,The level of hs-cTnI was higher in patients with primary + secondary outcome (mean difference 10.38 pg/mL [4.44, 16.32], p = 0.002; I2: 0%).,Cardiac injury is associated with mortality, need for ICU care, and severity of disease in patients with COVID-19.

Identifying people at risk of cardiovascular diseases (CVD) is a cornerstone of preventative cardiology.,Risk prediction models currently recommended by clinical guidelines are typically based on a limited number of predictors with sub-optimal performance across all patient groups.,Data-driven techniques based on machine learning (ML) might improve the performance of risk predictions by agnostically discovering novel risk predictors and learning the complex interactions between them.,We tested (1) whether ML techniques based on a state-of-the-art automated ML framework (AutoPrognosis) could improve CVD risk prediction compared to traditional approaches, and (2) whether considering non-traditional variables could increase the accuracy of CVD risk predictions.,Using data on 423,604 participants without CVD at baseline in UK Biobank, we developed a ML-based model for predicting CVD risk based on 473 available variables.,Our ML-based model was derived using AutoPrognosis, an algorithmic tool that automatically selects and tunes ensembles of ML modeling pipelines (comprising data imputation, feature processing, classification and calibration algorithms).,We compared our model with a well-established risk prediction algorithm based on conventional CVD risk factors (Framingham score), a Cox proportional hazards (PH) model based on familiar risk factors (i.e, age, gender, smoking status, systolic blood pressure, history of diabetes, reception of treatments for hypertension and body mass index), and a Cox PH model based on all of the 473 available variables.,Predictive performances were assessed using area under the receiver operating characteristic curve (AUC-ROC).,Overall, our AutoPrognosis model improved risk prediction (AUC-ROC: 0.774, 95% CI: 0.768-0.780) compared to Framingham score (AUC-ROC: 0.724, 95% CI: 0.720-0.728, p < 0.001), Cox PH model with conventional risk factors (AUC-ROC: 0.734, 95% CI: 0.729-0.739, p < 0.001), and Cox PH model with all UK Biobank variables (AUC-ROC: 0.758, 95% CI: 0.753-0.763, p < 0.001).,Out of 4,801 CVD cases recorded within 5 years of baseline, AutoPrognosis was able to correctly predict 368 more cases compared to the Framingham score.,Our AutoPrognosis model included predictors that are not usually considered in existing risk prediction models, such as the individuals’ usual walking pace and their self-reported overall health rating.,Furthermore, our model improved risk prediction in potentially relevant sub-populations, such as in individuals with history of diabetes.,We also highlight the relative benefits accrued from including more information into a predictive model (information gain) as compared to the benefits of using more complex models (modeling gain).,Our AutoPrognosis model improves the accuracy of CVD risk prediction in the UK Biobank population.,This approach performs well in traditionally poorly served patient subgroups.,Additionally, AutoPrognosis uncovered novel predictors for CVD disease that may now be tested in prospective studies.,We found that the “information gain” achieved by considering more risk factors in the predictive model was significantly higher than the “modeling gain” achieved by adopting complex predictive models.

Current approaches to predict cardiovascular risk fail to identify many people who would benefit from preventive treatment, while others receive unnecessary intervention.,Machine-learning offers opportunity to improve accuracy by exploiting complex interactions between risk factors.,We assessed whether machine-learning can improve cardiovascular risk prediction.,Prospective cohort study using routine clinical data of 378,256 patients from UK family practices, free from cardiovascular disease at outset.,Four machine-learning algorithms (random forest, logistic regression, gradient boosting machines, neural networks) were compared to an established algorithm (American College of Cardiology guidelines) to predict first cardiovascular event over 10-years.,Predictive accuracy was assessed by area under the ‘receiver operating curve’ (AUC); and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) to predict 7.5% cardiovascular risk (threshold for initiating statins).,24,970 incident cardiovascular events (6.6%) occurred.,Compared to the established risk prediction algorithm (AUC 0.728, 95% CI 0.723-0.735), machine-learning algorithms improved prediction: random forest +1.7% (AUC 0.745, 95% CI 0.739-0.750), logistic regression +3.2% (AUC 0.760, 95% CI 0.755-0.766), gradient boosting +3.3% (AUC 0.761, 95% CI 0.755-0.766), neural networks +3.6% (AUC 0.764, 95% CI 0.759-0.769).,The highest achieving (neural networks) algorithm predicted 4,998/7,404 cases (sensitivity 67.5%, PPV 18.4%) and 53,458/75,585 non-cases (specificity 70.7%, NPV 95.7%), correctly predicting 355 (+7.6%) more patients who developed cardiovascular disease compared to the established algorithm.,Machine-learning significantly improves accuracy of cardiovascular risk prediction, increasing the number of patients identified who could benefit from preventive treatment, while avoiding unnecessary treatment of others.

The aim was to assess coronary atherosclerosis, plaque morphology and associations to cardiovascular risk factors and epicardial adipose tissue (EAT) in patients with long duration of type 1 diabetes mellitus (T1DM).,Eighty-eight patients with ≥ 45 year T1DM duration and 60 controls underwent coronary CT angiography (CCTA) for evaluation of coronary artery plaque volume (total, calcified or mixed/soft), coronary artery calcification score (CAC) and EAT.,Plaques were detected in 75 (85%) T1DM patients and 28 (47%) controls, p < 0.01.,Median (interquartile range) plaque volume (mm3) in T1DM vs. controls was: 21.0 (1.0-66.0) vs.,0.2 (0.0-7.1), p < 0.01 for calcified, 0.0 (0.0-8.7) vs.,0.0 (0.0-0.0), p < 0.01 for soft/mixed and 29.5 (3.9-95.8) vs.,0.4 (0.0-7.4), p < 0.01 for total plaque volume.,Median CAC was 128 (13-671) vs.,1 (0.0-39.0), p < 0.01 in T1DM vs. controls.,Median EAT volume did not differ between the groups; 52.3 (36.1-65.5) cm3 vs.,55 (38.3-79.6), p = 0.20.,No association between CAC or plaque volumes and EAT were observed.,Low time-weighted LDL-cholesterol and HbA1c for 30 years were associated with having plaque volume < 25th percentile, OR (95% CI) 0.18 (0.05-0.70), p = 0.01 and 0.45 (0.20-1.00), p < 0.05, respectively.,Time-weighted LDL-c was linearly associated with CAC (beta 0.82 (95% CI 0.03-1.62), p = 0.04) and total plaque volume (beta 0.77 (95% CI 0.19-1.36), p = 0.01).,Long-term survivors of T1DM have a higher prevalence of coronary atherosclerosis compared to controls.,Low LDL-cholesterol and HbA1c over time have a protective effect on coronary atherosclerosis.,EAT volume was not associated with coronary atherosclerosis in T1DM patients.

Coronary artery inflammation inhibits adipogenesis in adjacent perivascular fat.,A novel imaging biomarker-the perivascular fat attenuation index (FAI)-captures coronary inflammation by mapping spatial changes of perivascular fat attenuation on coronary computed tomography angiography (CTA).,However, the ability of the perivascular FAI to predict clinical outcomes is unknown.,In the Cardiovascular RISk Prediction using Computed Tomography (CRISP-CT) study, we did a post-hoc analysis of outcome data gathered prospectively from two independent cohorts of consecutive patients undergoing coronary CTA in Erlangen, Germany (derivation cohort) and Cleveland, OH, USA (validation cohort).,Perivascular fat attenuation mapping was done around the three major coronary arteries-the proximal right coronary artery, the left anterior descending artery, and the left circumflex artery.,We assessed the prognostic value of perivascular fat attenuation mapping for all-cause and cardiac mortality in Cox regression models, adjusted for age, sex, cardiovascular risk factors, tube voltage, modified Duke coronary artery disease index, and number of coronary CTA-derived high-risk plaque features.,Between 2005 and 2009, 1872 participants in the derivation cohort underwent coronary CTA (median age 62 years [range 17-89]).,Between 2008 and 2016, 2040 patients in the validation cohort had coronary CTA (median age 53 years [range 19-87]).,Median follow-up was 72 months (range 51-109) in the derivation cohort and 54 months (range 4-105) in the validation cohort.,In both cohorts, high perivascular FAI values around the proximal right coronary artery and left anterior descending artery (but not around the left circumflex artery) were predictive of all-cause and cardiac mortality and correlated strongly with each other.,Therefore, the perivascular FAI measured around the right coronary artery was used as a representative biomarker of global coronary inflammation (for prediction of cardiac mortality, hazard ratio [HR] 2·15, 95% CI 1·33-3·48; p=0·0017 in the derivation cohort, and 2·06, 1·50-2·83; p<0·0001 in the validation cohort).,The optimum cutoff for the perivascular FAI, above which there is a steep increase in cardiac mortality, was ascertained as −70·1 Hounsfield units (HU) or higher in the derivation cohort (HR 9·04, 95% CI 3·35-24·40; p<0·0001 for cardiac mortality; 2·55, 1·65-3·92; p<0·0001 for all-cause mortality).,This cutoff was confirmed in the validation cohort (HR 5·62, 95% CI 2·90-10·88; p<0·0001 for cardiac mortality; 3·69, 2·26-6·02; p<0·0001 for all-cause mortality).,Perivascular FAI improved risk discrimination in both cohorts, leading to significant reclassification for all-cause and cardiac mortality.,The perivascular FAI enhances cardiac risk prediction and restratification over and above current state-of-the-art assessment in coronary CTA by providing a quantitative measure of coronary inflammation.,High perivascular FAI values (cutoff ≥-70·1 HU) are an indicator of increased cardiac mortality and, therefore, could guide early targeted primary prevention and intensive secondary prevention in patients.,British Heart Foundation, and the National Institute of Health Research Oxford Biomedical Research Centre.

Data on the impact of COVID‐19 in chronic heart failure (CHF) patients and its potential to trigger acute heart failure (AHF) are lacking.,The aim of this work was to study characteristics, cardiovascular outcomes and mortality in patients with confirmed COVID‐19 infection and a prior diagnosis of heart failure (HF).,Further aims included the identification of predictors and prognostic implications for AHF decompensation during hospital admission and the determination of a potential correlation between the withdrawal of HF guideline‐directed medical therapy (GDMT) and worse outcomes during hospitalization.,Data for a total of 3080 consecutive patients with confirmed COVID‐19 infection and follow‐up of at least 30 days were analysed.,Patients with a previous history of CHF (n = 152, 4.9%) were more prone to the development of AHF (11.2% vs.,2.1%; P < 0.001) and had higher levels of N‐terminal pro brain natriuretic peptide.,In addition, patients with previous CHF had higher mortality rates (48.7% vs.,19.0%; P < 0.001).,In contrast, 77 patients (2.5%) were diagnosed with AHF, which in the vast majority of cases (77.9%) developed in patients without a history of HF.,Arrhythmias during hospital admission and CHF were the main predictors of AHF.,Patients developing AHF had significantly higher mortality (46.8% vs.,19.7%; P < 0.001).,Finally, the withdrawal of beta‐blockers, mineralocorticoid receptor antagonists and angiotensin‐converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant increase in in‐hospital mortality.,Patients with COVID‐19 have a significant incidence of AHF, which is associated with very high mortality rates.,Moreover, patients with a history of CHF are prone to developing acute decompensation after a COVID‐19 diagnosis.,The withdrawal of GDMT was associated with higher mortality.,Heart failure in COVID‐19 patients: prevalence, incidence and prognostic implications.

To compare demographic characteristics, clinical presentation, and outcomes of patients with and without concomitant cardiac disease, hospitalized for COVID-19 in Brescia, Lombardy, Italy.,The study population includes 99 consecutive patients with COVID-19 pneumonia admitted to our hospital between 4 March and 25 March 2020.,Fifty-three patients with a history of cardiac disease were compared with 46 without cardiac disease.,Among cardiac patients, 40% had a history of heart failure, 36% had atrial fibrillation, and 30% had coronary artery disease.,Mean age was 67 ± 12 years, and 80 (81%) patients were males.,No differences were found between cardiac and non-cardiac patients except for higher values of serum creatinine, N-terminal probrain natriuretic peptide, and high sensitivity troponin T in cardiac patients.,During hospitalization, 26% patients died, 15% developed thrombo-embolic events, 19% had acute respiratory distress syndrome, and 6% had septic shock.,Mortality was higher in patients with cardiac disease compared with the others (36% vs. 15%, log-rank P = 0.019; relative risk 2.35; 95% confidence interval 1.08-5.09).,The rate of thrombo-embolic events and septic shock during the hospitalization was also higher in cardiac patients (23% vs. 6% and 11% vs. 0%, respectively).,Hospitalized patients with concomitant cardiac disease and COVID-19 have an extremely poor prognosis compared with subjects without a history of cardiac disease, with higher mortality, thrombo-embolic events, and septic shock rates.

An increased risk of venous thromboembolism (VTE) in patients with COVID-19 pneumonia admitted to intensive care unit (ICU) has been reported.,Whether COVID-19 increases the risk of VTE in non-ICU wards remains unknown.,We aimed to evaluate the burden of asymptomatic deep vein thrombosis (DVT) in COVID-19 patients with elevated D-dimer levels.,In this prospective study consecutive patients hospitalized in non-intensive care units with diagnosis of COVID-19 pneumonia and D-dimer > 1000 ng/ml were screened for asymptomatic DVT with complete compression doppler ultrasound (CCUS).,The study was approved by the Institutional Ethics Committee.,The study comprised 156 patients (65.4% male).,All but three patients received standard doses of thromboprophylaxis.,Median days of hospitalization until CCUS was 9 (IQR 5-17).,CCUS was positive for DVT in 23 patients (14.7%), of whom only one was proximal DVT.,Seven patients (4.5%) had bilateral distal DVT.,Patients with DVT had higher median D-dimer levels: 4527 (IQR 1925-9144) ng/ml vs 2050 (IQR 1428-3235) ng/ml; p < 0.001.,D-dimer levels > 1570 ng/ml were associated with asymptomatic DVT (OR 9.1; CI 95% 1.1-70.1).,D-dimer showed an acceptable discriminative capacity (area under the ROC curve 0.72, 95% CI 0.61-0.84).,In patients admitted with COVID-19 pneumonia and elevated D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.,•An increased risk of VTE in patients with COVID-19 pneumonia admitted to intensive care unit has been reported.,•The most consistent hemostatic abnormalities with COVID-19 include mild thrombocytopenia and increased D-dimer levels.,•In COVID-19 patients with high D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,•Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.,An increased risk of VTE in patients with COVID-19 pneumonia admitted to intensive care unit has been reported.,The most consistent hemostatic abnormalities with COVID-19 include mild thrombocytopenia and increased D-dimer levels.,In COVID-19 patients with high D-dimer levels, the incidence of asymptomatic DVT is similar to that described in other series.,Higher cut-off levels for D-dimer might be necessary for the diagnosis of DVT in COVID-19 patients.

Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.

There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).,We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive.,Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class.,A difference of at least 10 percentage points was prespecified as a substantial difference.,Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness.,A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness.,There was no association between any single medication class and an increased likelihood of a positive test.,None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive.,We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.

This document is an update to the 2013 publication of the Society for Cardiovascular Magnetic Resonance (SCMR) Board of Trustees Task Force on Standardized Protocols.,Concurrent with this publication, 3 additional task forces will publish documents that should be referred to in conjunction with the present document.,The first is a document on the Clinical Indications for CMR, an update of the 2004 document.,The second task force will be updating the document on Reporting published by that SCMR Task Force in 2010.,The 3rd task force will be updating the 2013 document on Post-Processing.,All protocols relative to congenital heart disease are covered in a separate document.,The section on general principles and techniques has been expanded as more of the techniques common to CMR have been standardized.,A section on imaging in patients with devices has been added as this is increasingly seen in day-to-day clinical practice.,The authors hope that this document continues to standardize and simplify the patient-based approach to clinical CMR.,It will be updated at regular intervals as the field of CMR advances.

Coronavirus disease 2019 (COVID-19) has become a global pandemic, affecting millions of people.,However, the relationship between COVID-19 and acute cerebrovascular diseases is unclear.,We aimed to characterize the incidence, risk factors, clinical-radiological manifestations, and outcome of COVID-19-associated stroke.,Three medical databases were systematically reviewed for published articles on acute cerebrovascular diseases in COVID-19 (December 2019-September 2020).,The review protocol was previously registered (PROSPERO ID = CRD42020185476).,Data were extracted from articles reporting ≥5 stroke cases in COVID-19.,We complied with the PRISMA guidelines and used the Newcastle-Ottawa Scale to assess data quality.,Data were pooled using a random-effect model.,Of 2277 initially identified articles, 61 (2.7%) were entered in the meta-analysis.,Out of 108,571 patients with COVID-19, acute CVD occurred in 1.4% (95%CI: 1.0-1.9).,The most common manifestation was acute ischemic stroke (87.4%); intracerebral hemorrhage was less common (11.6%).,Patients with COVID-19 developing acute cerebrovascular diseases, compared to those who did not, were older (pooled median difference = 4.8 years; 95%CI: 1.7-22.4), more likely to have hypertension (OR = 7.35; 95%CI: 1.94-27.87), diabetes mellitus (OR = 5.56; 95%CI: 3.34-9.24), coronary artery disease (OR = 3.12; 95%CI: 1.61-6.02), and severe infection (OR = 5.10; 95%CI: 2.72-9.54).,Compared to individuals who experienced a stroke without the infection, patients with COVID-19 and stroke were younger (pooled median difference = −6.0 years; 95%CI: −12.3 to −1.4), had higher NIHSS (pooled median difference = 5; 95%CI: 3-9), higher frequency of large vessel occlusion (OR = 2.73; 95%CI: 1.63-4.57), and higher in-hospital mortality rate (OR = 5.21; 95%CI: 3.43-7.90).,Acute cerebrovascular diseases are not uncommon in patients with COVID-19, especially in those whom are severely infected and have pre-existing vascular risk factors.,The pattern of large vessel occlusion and multi-territory infarcts suggests that cerebral thrombosis and/or thromboembolism could be possible causative pathways for the disease.

•Stroke cases continue to rise in the COVID-19 pandemic.,•Stroke presents late in severe COVID-19 patients and early in mild cases.,•Patients with large vessel occlusion were younger and had higher NIHSS.,•Hypercoagulability and inflammation in COVID-19 are related to stroke.,•Other cause should be considered as a stroke etiology in COVID-19 patients.,Stroke cases continue to rise in the COVID-19 pandemic.,Stroke presents late in severe COVID-19 patients and early in mild cases.,Patients with large vessel occlusion were younger and had higher NIHSS.,Hypercoagulability and inflammation in COVID-19 are related to stroke.,Other cause should be considered as a stroke etiology in COVID-19 patients.,Coronavirus disease 2019 has been associated with stroke, particular characteristics of these patients are not fully understood.,The adequate management of these patients depends on the comprehension of factors such as temporality, clinical presentation and etiology.,We hypothesize there is an important temporal relationship between COVID-19 severity and stroke onset.,a systematic review of the available literature was conducted using Pubmed and Scopus, studies reporting patients with Coronavirus disease 19 and stroke were included.,Clinical, sociodemographic and laboratory characteristics of patients were extracted and analyzed.,Forty-seven studies and 176 patients were included, with a mean age of 63.1 years (SD= 16 n=122), most of them were males (63.2% n=171).,The most frequent etiology was cryptogenic 40.9% n=66), and a mean National Institute of Health Stroke Scale of 14.4 points was found (SD= 8.6 n=73).,Large vessel occlusion was reported in 65.9% patients (n=91) and these patients were younger with greater stroke severity.,D-dimer, C-reactive protein, fibrinogen, ferritin and lactate dehydrogenase were elevated in most patients with reported findings.,Most patients had severe Coronavirus disease 2019.,The mean time from onset of respiratory symptoms to stroke was 9 days (SD=9.9), the shortest time was noted in those with mild and moderate disease.,There is a trend between the severity of Coronavirus disease 2019 and time to stroke onset.,Also, age and stroke severity were found to be related to the development of large vessel occlusion.,Inflammation and hypercoagulability markers are elevated in this disease, we propose to not discard hypercoagulability secondary to severe acute respiratory syndrome-coronavirus-2 as an underlying cause of stroke in these patients.

Hypertensive disorders of pregnancy (HDP) lead to the death of approximately 30,000 women annually, and the identification of biomarkers to predict their onset before symptom occurrence is crucial.,Here, we aimed to identify the first-trimester maternal serum biomarkers for predicting early-onset HDP via a comprehensive metabolomic analysis.,This study was conducted by the Fukushima Regional Center as an adjunct study to the Japan Environment and Children’s Study.,The study comprised 12 patients with early-onset HDP and 12 control subjects with healthy pregnancy whose medical background information was matched with that of the patients by propensity-score matching.,Capillary electrophoresis and mass spectrometry-based quantitative analysis of charged metabolites were performed with the first-trimester maternal serum samples.,Welch’s t-test was used to analyse metabolite peak areas in the two groups.,A total of 166 charged metabolites were identified.,The peak area of N-dimethylglycine and S-methylcysteine was significantly higher in the first-trimester serum of patients with early-onset HDP than in the controls.,Conversely, the peak area of munic acid was significantly decreased in the serum of patients with early-onset HDP.,Although we identified potential biomarkers for the prediction and diagnosis of early-onset HDP, no clear marker was identified because of a low statistical power.

Determining the appropriate preconception care to reduce the occurrence of hypertensive disorder of pregnancy (HDP) remains a challenge in modern obstetrics.,This study aimed to examine the association between pre-pregnancy calcium (Ca) intake and HDP in normotensive primiparas.,We used data from the Japan Environment Children’s study (JECS), which is the largest birth cohort study.,A total of 33,894 normotensive Japanese primiparas were recruited for JECS between January 2011 and March 2014.,Participants were categorized into five groups according to pre-pregnancy Ca intake quintiles (Q1 and Q5 were the lowest and highest Ca intake groups, respectively) to compare their basic background and obstetrics outcome.,Multiple logistic regressions were performed to identify the effect of pre-pregnancy Ca intake on HDP, early onset HDP, and late-onset HDP, using Ca intake thresholds of 500, 550, 650, 700, 1000, 1500, and 1500 mg.,We found significant differences in maternal background among the Ca intake groups; in particular, there were more participants with low socioeconomic status, indicated by low education level and low household income, and smokers in the lowest Ca intake group.,Multiple logistic regression did not show any significant difference with regard to HDP, early onset HDP, and late-onset HDP in each Ca intake threshold.,Despite considerable recommendations concerning Ca intake for women of reproductive age, the present study indicates that pre-pregnancy Ca intake was not associated with an increased risk of new-onset hypertension among primiparas during pregnancy.,Further studies examining the effect of other pre-pregnancy dietary factors on obstetric outcomes should be considered in the formulation of earlier preventive strategies for primiparas.

Few data are available on the rate and characteristics of thromboembolic complications in hospitalized patients with COVID-19.,We studied consecutive symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02.2020-10.04.2020).,The primary outcome was any thromboembolic complication, including venous thromboembolism (VTE), ischemic stroke, and acute coronary syndrome (ACS)/myocardial infarction (MI).,Secondary outcome was overt disseminated intravascular coagulation (DIC).,We included 388 patients (median age 66 years, 68% men, 16% requiring intensive care [ICU]).,Thromboprophylaxis was used in 100% of ICU patients and 75% of those on the general ward.,Thromboembolic events occurred in 28 (7.7% of closed cases; 95%CI 5.4%-11.0%), corresponding to a cumulative rate of 21% (27.6% ICU, 6.6% general ward).,Half of the thromboembolic events were diagnosed within 24 h of hospital admission.,Forty-four patients underwent VTE imaging tests and VTE was confirmed in 16 (36%).,Computed tomography pulmonary angiography (CTPA) was performed in 30 patients, corresponding to 7.7% of total, and pulmonary embolism was confirmed in 10 (33% of CTPA).,The rate of ischemic stroke and ACS/MI was 2.5% and 1.1%, respectively.,Overt DIC was present in 8 (2.2%) patients.,The high number of arterial and, in particular, venous thromboembolic events diagnosed within 24 h of admission and the high rate of positive VTE imaging tests among the few COVID-19 patients tested suggest that there is an urgent need to improve specific VTE diagnostic strategies and investigate the efficacy and safety of thromboprophylaxis in ambulatory COVID-19 patients.,•COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,•We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,•Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,•Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,•There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.,COVID-19 is characterized by coagulation activation and endothelial dysfunction.,Few data are available on thromboembolic complications.,We studied symptomatic patients with laboratory-proven COVID-19 admitted to a university hospital in Milan, Italy (13.02-10.04.2020).,Venous and arterial thromboembolic events occurred in 8% of hospitalized patients (cumulative rate 21.0%) and 50% of events were diagnosed within 24 h of hospital admission.,Forty-four (11% of total) patients underwent VTE imaging tests; 16 were positive (36% of tests), suggesting underestimation of thromboembolic complications.,There is an urgent need to investigate VTE diagnostic strategies and the impact of thromboprophylaxis in ambulatory COVID-19 patients.

COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.

The use of renin-angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), was alleged to cause a more severe course of novel coronavirus disease 2019 (COVID-19).,We systematically reviewed the published studies to assess the association of RAS inhibitors with mortality as well as disease severity in COVID-19 patients.,A systematic literature search was performed to retrieve relevant original studies investigating mortality and severity (severe/critical disease) in COVID-19 patients with and without exposure to RAS inhibitors.,A total of 59 original studies were included for qualitative synthesis.,Twenty-four studies that reported adjusted effect sizes (24 studies reported mortality outcomes and 16 studies reported disease severity outcomes), conducted in RAS inhibitor-exposed and unexposed groups, were pooled in random-effects models to estimate overall risk.,Quality assessment of studies revealed that most of the studies included were of fair quality.,The use of an ACEI/ARB in COVID-19 patients was significantly associated with lower odds (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.56-0.95; n = 18,749) or hazard (hazard ratio [HR] = 0.75, 95% CI 0.60-0.95; n = 26,598) of mortality compared with non-use of ACEI/ARB.,However, the use of an ACEI/ARB was non-significantly associated with lower odds (OR = 0.91, 95% CI 0.75-1.10; n = 7446) or hazard (HR = 0.73, 95% CI 0.33-1.66; n = 6325) of developing severe/critical disease compared with non-use of an ACEI/ARB.,Since there was no increased risk of harm, the use of RAS inhibitors for hypertension and other established clinical indications can be maintained in COVID-19 patients.,The online version of this article (10.1007/s40256-020-00439-5) contains supplementary material, which is available to authorized users.

It remains unknown whether the treatment of hypertension influences the mortality of patients diagnosed with coronavirus disease 2019 (COVID-19).,This is a retrospective observational study of all patients admitted with COVID-19 to Huo Shen Shan Hospital.,The hospital was dedicated solely to the treatment of COVID-19 in Wuhan, China.,Hypertension and the treatments were stratified according to the medical history or medications administrated prior to the infection.,Among 2877 hospitalized patients, 29.5% (850/2877) had a history of hypertension.,After adjustment for confounders, patients with hypertension had a two-fold increase in the relative risk of mortality as compared with patients without hypertension [4.0% vs.,1.1%, adjusted hazard ratio (HR) 2.12, 95% confidence interval (CI) 1.17-3.82, P = 0.013].,Patients with a history of hypertension but without antihypertensive treatment (n = 140) were associated with a significantly higher risk of mortality compared with those with antihypertensive treatments (n = 730) (7.9% vs.,3.2%, adjusted HR 2.17, 95% CI 1.03-4.57, P = 0.041).,The mortality rates were similar between the renin-angiotensin-aldosterone system (RAAS) inhibitor (4/183) and non-RAAS inhibitor (19/527) cohorts (2.2% vs.,3.6%, adjusted HR 0.85, 95% CI 0.28-2.58, P = 0.774).,However, in a study-level meta-analysis of four studies, the result showed that patients with RAAS inhibitor use tend to have a lower risk of mortality (relative risk 0.65, 95% CI 0.45-0.94, P = 0.20).,While hypertension and the discontinuation of antihypertensive treatment are suspected to be related to increased risk of mortality, in this retrospective observational analysis, we did not detect any harm of RAAS inhibitors in patients infected with COVID-19.,However, the results should be considered as exploratory and interpreted cautiously.

There is concern about the potential of an increased risk related to medications that act on the renin-angiotensin-aldosterone system in patients exposed to coronavirus disease 2019 (Covid-19), because the viral receptor is angiotensin-converting enzyme 2 (ACE2).,We assessed the relation between previous treatment with ACE inhibitors, angiotensin-receptor blockers, beta-blockers, calcium-channel blockers, or thiazide diuretics and the likelihood of a positive or negative result on Covid-19 testing as well as the likelihood of severe illness (defined as intensive care, mechanical ventilation, or death) among patients who tested positive.,Using Bayesian methods, we compared outcomes in patients who had been treated with these medications and in untreated patients, overall and in those with hypertension, after propensity-score matching for receipt of each medication class.,A difference of at least 10 percentage points was prespecified as a substantial difference.,Among 12,594 patients who were tested for Covid-19, a total of 5894 (46.8%) were positive; 1002 of these patients (17.0%) had severe illness.,A history of hypertension was present in 4357 patients (34.6%), among whom 2573 (59.1%) had a positive test; 634 of these patients (24.6%) had severe illness.,There was no association between any single medication class and an increased likelihood of a positive test.,None of the medications examined was associated with a substantial increase in the risk of severe illness among patients who tested positive.,We found no substantial increase in the likelihood of a positive test for Covid-19 or in the risk of severe Covid-19 among patients who tested positive in association with five common classes of antihypertensive medications.

Angiotensin converting enzyme 2 (ACE2) is an endogenous regulator of the renin angiotensin system.,Increased circulating ACE2 predicts adverse outcomes in patients with heart failure (HF), but it is unknown if elevated plasma ACE2 activity predicts major adverse cardiovascular events (MACE) in patients with obstructive coronary artery disease (CAD).,We prospectively recruited patients with obstructive CAD (defined as ≥50% stenosis of the left main coronary artery and/or ≥70% stenosis in ≥ 1 other major epicardial vessel on invasive coronary angiography) and measured plasma ACE2 activity.,Patients were followed up to determine if circulating ACE2 activity levels predicted the primary endpoint of MACE (cardiovascular mortality, HF or myocardial infarction).,We recruited 79 patients with obstructive coronary artery disease.,The median (IQR) plasma ACE2 activity was 29.3 pmol/ml/min [21.2-41.2].,Over a median follow up of 10.5 years [9.6-10.8years], MACE occurred in 46% of patients (36 events).,On Kaplan-Meier analysis, above-median plasma ACE2 activity was associated with MACE (log-rank test, p = 0.035) and HF hospitalisation (p = 0.01).,After Cox multivariable adjustment, log ACE2 activity remained an independent predictor of MACE (hazard ratio (HR) 2.4, 95% confidence interval (CI) 1.24-4.72, p = 0.009) and HF hospitalisation (HR: 4.03, 95% CI: 1.42-11.5, p = 0.009).,Plasma ACE2 activity independently increased the hazard of adverse long-term cardiovascular outcomes in patients with obstructive CAD.

To investigate the characteristics and clinical significance of myocardial injury in patients with severe coronavirus disease 2019 (COVID-19).,We enrolled 671 eligible hospitalized patients with severe COVID-19 from 1 January to 23 February 2020, with a median age of 63 years.,Clinical, laboratory, and treatment data were collected and compared between patients who died and survivors.,Risk factors of death and myocardial injury were analysed using multivariable regression models.,A total of 62 patients (9.2%) died, who more often had myocardial injury (75.8% vs.,9.7%; P < 0.001) than survivors.,The area under the receiver operating characteristic curve of initial cardiac troponin I (cTnI) for predicting in-hospital mortality was 0.92 [95% confidence interval (CI), 0.87-0.96; sensitivity, 0.86; specificity, 0.86; P < 0.001].,The single cut-off point and high level of cTnI predicted risk of in-hospital death, hazard ratio (HR) was 4.56 (95% CI, 1.28-16.28; P = 0.019) and 1.25 (95% CI, 1.07-1.46; P = 0.004), respectively.,In multivariable logistic regression, senior age, comorbidities (e.g. hypertension, coronary heart disease, chronic renal failure, and chronic obstructive pulmonary disease), and high level of C-reactive protein were predictors of myocardial injury.,The risk of in-hospital death among patients with severe COVID-19 can be predicted by markers of myocardial injury, and was significantly associated with senior age, inflammatory response, and cardiovascular comorbidities.

Coronavirus disease-2019 (COVID-19), a viral respiratory illness caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), may predispose patients to thrombotic disease, both in the venous and arterial circulations, because of excessive inflammation, platelet activation, endothelial dysfunction, and stasis.,In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy.,Moreover, during a time with much focus on COVID-19, it is critical to consider how to optimize the available technology to care for patients without COVID-19 who have thrombotic disease.,Herein, the authors review the current understanding of the pathogenesis, epidemiology, management, and outcomes of patients with COVID-19 who develop venous or arterial thrombosis, of those with pre-existing thrombotic disease who develop COVID-19, or those who need prevention or care for their thrombotic disease during the COVID-19 pandemic.,•COVID-19 may predispose patients to arterial and venous thrombosis.,•Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,•Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,•The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.,COVID-19 may predispose patients to arterial and venous thrombosis.,Initial series suggest the common occurrence of venous thromboembolic disease in patients with severe COVID-19.,The optimal preventive strategy warrants further investigation.,Drug-drug interactions between antiplatelet agents and anticoagulants with investigational COVID-19 therapies should be considered.,The available technology should be used optimally to care for patients without COVID-19 who have thrombotic disease during the pandemic.

Emerging evidence shows that severe coronavirus disease 2019 (COVID-19) can be complicated by a significant coagulopathy, that likely manifests in the form of both microthrombosis and VTE.,This recognition has led to the urgent need for practical guidance regarding prevention, diagnosis, and treatment of VTE.,A group of approved panelists developed key clinical questions by using the PICO (Population, Intervention, Comparator, Outcome) format that addressed urgent clinical questions regarding the prevention, diagnosis, and treatment of VTE in patients with COVID-19.,MEDLINE (via PubMed or Ovid), Embase, and Cochrane Controlled Register of Trials were systematically searched for relevant literature, and references were screened for inclusion.,Validated evaluation tools were used to grade the level of evidence to support each recommendation.,When evidence did not exist, guidance was developed based on consensus using the modified Delphi process.,The systematic review and critical analysis of the literature based on 13 Population, Intervention, Comparator, Outcome questions resulted in 22 statements.,Very little evidence exists in the COVID-19 population.,The panel thus used expert consensus and existing evidence-based guidelines to craft the guidance statements.,The evidence on the optimal strategies to prevent, diagnose, and treat VTE in patients with COVID-19 is sparse but rapidly evolving.

•SARS-CoV-2 may impair host antiviral response, causing subsequent hyperinflammation.,•SARS-CoV-2 likely deranges the renin angiotensin aldosterone system (RAAS).,•Hyperinflammation and RAAS imbalance may drive acute lung injury and coagulopathy.,•RAAS imbalance impairs fibrinolysis, which can result in relative hypofibrinolysis.,•This can lead widespread immunothrombosis, contributing to multi-organ damage.,SARS-CoV-2 may impair host antiviral response, causing subsequent hyperinflammation.,SARS-CoV-2 likely deranges the renin angiotensin aldosterone system (RAAS).,Hyperinflammation and RAAS imbalance may drive acute lung injury and coagulopathy.,RAAS imbalance impairs fibrinolysis, which can result in relative hypofibrinolysis.,This can lead widespread immunothrombosis, contributing to multi-organ damage.,Early clinical evidence suggests that severe cases of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), are frequently characterized by hyperinflammation, imbalance of renin-angiotensin-aldosterone system, and a particular form of vasculopathy, thrombotic microangiopathy, and intravascular coagulopathy.,In this paper, we present an immunothrombosis model of COVID-19.,We discuss the underlying pathogenesis and the interaction between multiple systems, resulting in propagation of immunothrombosis, which through investigation in the coming weeks, may lead to both an improved understanding of COVID-19 pathophysiology and identification of innovative and efficient therapeutic targets to reverse the otherwise unfavorable clinical outcome of many of these patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children.,A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation.,The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology.,We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C.,We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage.,Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.,•Hyperinflammation in MIS-C differs from that of acute COVID-19•T cell subsets discriminate Kawasaki disease patients from MIS-C•IL-17A drives Kawasaki but not MIS-C hyperinflammation•Global profiling reveals candidate autoantibodies with pathogenic potential,Hyperinflammation in MIS-C differs from that of acute COVID-19,T cell subsets discriminate Kawasaki disease patients from MIS-C,IL-17A drives Kawasaki but not MIS-C hyperinflammation,Global profiling reveals candidate autoantibodies with pathogenic potential,A systems immunology approach describes how multisystem inflammatory syndrome in children (MIS-C) is distinct from Kawasaki disease as well as the cytokine storm associated with severe COVID-19 in terms of its molecular and immune profiles.

The Bergamo province, which is extensively affected by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemic, is a natural observatory of virus manifestations in the general population.,In the past month we recorded an outbreak of Kawasaki disease; we aimed to evaluate incidence and features of patients with Kawasaki-like disease diagnosed during the SARS-CoV-2 epidemic.,All patients diagnosed with a Kawasaki-like disease at our centre in the past 5 years were divided according to symptomatic presentation before (group 1) or after (group 2) the beginning of the SARS-CoV-2 epidemic.,Kawasaki- like presentations were managed as Kawasaki disease according to the American Heart Association indications.,Kawasaki disease shock syndrome (KDSS) was defined by presence of circulatory dysfunction, and macrophage activation syndrome (MAS) by the Paediatric Rheumatology International Trials Organisation criteria.,Current or previous infection was sought by reverse-transcriptase quantitative PCR in nasopharyngeal and oropharyngeal swabs, and by serological qualitative test detecting SARS-CoV-2 IgM and IgG, respectively.,Group 1 comprised 19 patients (seven boys, 12 girls; aged 3·0 years [SD 2·5]) diagnosed between Jan 1, 2015, and Feb 17, 2020.,Group 2 included ten patients (seven boys, three girls; aged 7·5 years [SD 3·5]) diagnosed between Feb 18 and April 20, 2020; eight of ten were positive for IgG or IgM, or both.,The two groups differed in disease incidence (group 1 vs group 2, 0·3 vs ten per month), mean age (3·0 vs 7·5 years), cardiac involvement (two of 19 vs six of ten), KDSS (zero of 19 vs five of ten), MAS (zero of 19 vs five of ten), and need for adjunctive steroid treatment (three of 19 vs eight of ten; all p<0·01).,In the past month we found a 30-fold increased incidence of Kawasaki-like disease.,Children diagnosed after the SARS-CoV-2 epidemic began showed evidence of immune response to the virus, were older, had a higher rate of cardiac involvement, and features of MAS.,The SARS-CoV-2 epidemic was associated with high incidence of a severe form of Kawasaki disease.,A similar outbreak of Kawasaki-like disease is expected in countries involved in the SARS-CoV-2 epidemic.,None.

The use of renin-angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), was alleged to cause a more severe course of novel coronavirus disease 2019 (COVID-19).,We systematically reviewed the published studies to assess the association of RAS inhibitors with mortality as well as disease severity in COVID-19 patients.,A systematic literature search was performed to retrieve relevant original studies investigating mortality and severity (severe/critical disease) in COVID-19 patients with and without exposure to RAS inhibitors.,A total of 59 original studies were included for qualitative synthesis.,Twenty-four studies that reported adjusted effect sizes (24 studies reported mortality outcomes and 16 studies reported disease severity outcomes), conducted in RAS inhibitor-exposed and unexposed groups, were pooled in random-effects models to estimate overall risk.,Quality assessment of studies revealed that most of the studies included were of fair quality.,The use of an ACEI/ARB in COVID-19 patients was significantly associated with lower odds (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.56-0.95; n = 18,749) or hazard (hazard ratio [HR] = 0.75, 95% CI 0.60-0.95; n = 26,598) of mortality compared with non-use of ACEI/ARB.,However, the use of an ACEI/ARB was non-significantly associated with lower odds (OR = 0.91, 95% CI 0.75-1.10; n = 7446) or hazard (HR = 0.73, 95% CI 0.33-1.66; n = 6325) of developing severe/critical disease compared with non-use of an ACEI/ARB.,Since there was no increased risk of harm, the use of RAS inhibitors for hypertension and other established clinical indications can be maintained in COVID-19 patients.,The online version of this article (10.1007/s40256-020-00439-5) contains supplementary material, which is available to authorized users.

The dysfunction of the renin-angiotensin system (RAS) has been observed in coronavirus infection disease (COVID-19) patients, but whether RAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II type 1 receptor blockers (ARBs), are associated with clinical outcomes remains unknown.,COVID-19 patients with hypertension were enrolled to evaluate the effect of RAS inhibitors.,We observed that patients receiving ACEI or ARB therapy had a lower rate of severe diseases and a trend toward a lower level of IL-6 in peripheral blood.,In addition, ACEI or ARB therapy increased CD3 and CD8 T cell counts in peripheral blood and decreased the peak viral load compared to other antihypertensive drugs.,This evidence supports the benefit of using ACEIs or ARBs to potentially contribute to the improvement of clinical outcomes of COVID-19 patients with hypertension.

Aortic aneurysm is a life-threatening disease due to the risk of aortic rupture.,The only curative treatment available relies on surgical approaches; drug-based therapies are lacking, highlighting an unmet need for clinical practice.,Abdominal aortic aneurysm (AAA) is frequently associated with atherosclerosis and cardiovascular risk factors including male sex, age, smoking, hypertension, and dyslipidaemia.,Thoracic aortic aneurysm (TAA) is more often linked to genetic disorders of the extracellular matrix and the contractile apparatus but also share similar cardiovascular risk factors.,Intriguingly, a large body of evidence points to an inverse association between diabetes and both AAA and TAA.,A better understanding of the mechanisms underlying the negative association between diabetes and aortic aneurysm could help the development of innovative diagnostic and therapeutic approaches to tackle the disease.,Here, we summarize current knowledge on the relationship between glycaemic parameters, diabetes, and the development of aortic aneurysm.,Cellular and molecular pathways that underlie the protective effect of diabetes itself and its treatment are reviewed and discussed, along with their potential implications for clinical translation.

Medial degeneration associated with thoracic aortic aneurysm and acute aortic dissection was originally described by Erdheim as a noninflammatory lesion related to the loss of smooth muscle cells and elastic fibre fragmentation in the media.,Recent evidences propose the strong role of a chronic immune/inflammatory process in aneurysm evocation and progression.,The coexistence of inflammatory cells with markers of apoptotic vascular cell death in the media of ascending aorta with aneurysms and type A dissections raises the possibility that activated T cells and macrophages may contribute to the elimination of smooth muscle cells and degradation of the matrix.,On the other hand, several inflammatory pathways (including TGF-β, TLR-4 interferon-γ, chemokines, and interferon-γ) seem to be involved in the medial degeneration related to aged and dilated aorta.,This is an overview on thoracic aortic aneurysm as an emerging inflammatory disease.

An increase in out-of-hospital cardiac arrest (OHCA) incidence has been reported in the very early phase of the COVID-19 epidemic, but a clear demonstration of a correlation between the increased incidence of OHCA and COVID-19 is missing so far.,We aimed to verify whether there is an association between the OHCA difference compared with 2019 and the COVID-19 epidemic curve.,We included all the consecutive OHCAs which occurred in the Provinces of Lodi, Cremona, Pavia, and Mantova in the 2 months following the first documented case of COVID-19 in the Lombardia Region and compared them with those which occurred in the same time frame in 2019.,The cumulative incidence of COVID-19 from 21 February to 20 April 2020 in the study territory was 956 COVID-19/100 000 inhabitants and the cumulative incidence of OHCA was 21 cases/100 000 inhabitants, with a 52% increase as compared with 2019 (490 OHCAs in 2020 vs. 321 in 2019).,A strong and statistically significant correlation was found between the difference in cumulative incidence of OHCA between 2020 and 2019 per 100 000 inhabitants and the COVID-19 cumulative incidence per 100 000 inhabitants both for the overall territory (ρ 0.87, P < 0.001) and for each province separately (Lodi: ρ 0.98, P < 0.001; Cremona: ρ 0.98, P < 0.001; Pavia: ρ 0.87, P < 0.001; Mantova: ρ 0.81, P < 0.001).,The increase in OHCAs in 2020 is significantly correlated to the COVID-19 pandemic and is coupled with a reduction in short-term outcome.,Government and local health authorities should seriously consider our results when planning healthcare strategies to face the epidemic, especially considering the expected recurrent outbreaks.,Graphical Abstract

This cross-sectional study describes the characteristics associated with outpatient cardiac arrests and death during the coronavirus disease 2019 pandemic in New York City.,What characteristics are associated with out-of-hospital cardiac arrests and death during the COVID-19 pandemic in New York City?,In this population-based cross-sectional study of 5325 patients with out-of-hospital cardiac arrests, the number undergoing resuscitation was 3-fold higher during the 2020 COVID-19 period compared with during the comparison period in 2019.,Patients with out-of-hospital cardiac arrest during 2020 were older, less likely to be white, and more likely to have specific comorbidities and substantial reductions in return and sustained return of spontaneous circulation.,Identifying patients at risk for out-of-hospital cardiac arrest and death during the COVID-19 pandemic should lead to interventions in the outpatient setting to help reduce out-of-hospital deaths.,Risk factors for out-of-hospital death due to novel coronavirus disease 2019 (COVID-19) are poorly defined.,From March 1 to April 25, 2020, New York City, New York (NYC), reported 17 118 COVID-19-related deaths.,On April 6, 2020, out-of-hospital cardiac arrests peaked at 305 cases, nearly a 10-fold increase from the prior year.,To describe the characteristics (race/ethnicity, comorbidities, and emergency medical services [EMS] response) associated with outpatient cardiac arrests and death during the COVID-19 pandemic in NYC.,This population-based, cross-sectional study compared patients with out-of-hospital cardiac arrest receiving resuscitation by the NYC 911 EMS system from March 1 to April 25, 2020, compared with March 1 to April 25, 2019.,The NYC 911 EMS system serves more than 8.4 million people.,The COVID-19 pandemic.,Characteristics associated with out-of-hospital arrests and the outcomes of out-of-hospital cardiac arrests.,A total of 5325 patients were included in the main analysis (2935 men [56.2%]; mean [SD] age, 71 [18] years), 3989 in the COVID-19 period and 1336 in the comparison period.,The incidence of nontraumatic out-of-hospital cardiac arrests in those who underwent EMS resuscitation in 2020 was 3 times the incidence in 2019 (47.5/100 000 vs 15.9/100 000).,Patients with out-of-hospital cardiac arrest during 2020 were older (mean [SD] age, 72 [18] vs 68 [19] years), less likely to be white (611 of 2992 [20.4%] vs 382 of 1161 [32.9%]), and more likely to have hypertension (2134 of 3989 [53.5%] vs 611 of 1336 [45.7%]), diabetes (1424 of 3989 [35.7%] vs 348 of 1336 [26.0%]), and physical limitations (2259 of 3989 [56.6%] vs 634 of 1336 [47.5%]).,Compared with 2019, the odds of asystole increased in the COVID-19 period (odds ratio [OR], 3.50; 95% CI, 2.53-4.84; P < .001), as did the odds of pulseless electrical activity (OR, 1.99; 95% CI, 1.31-3.02; P = .001).,Compared with 2019, the COVID-19 period had substantial reductions in return of spontaneous circulation (ROSC) (727 of 3989 patients [18.2%] vs 463 of 1336 patients [34.7%], P < .001) and sustained ROSC (423 of 3989 patients [10.6%] vs 337 of 1336 patients [25.2%], P < .001), with fatality rates exceeding 90%.,These associations remained statistically significant after adjustment for potential confounders (OR for ROSC, 0.59 [95% CI, 0.50-0.70; P < .001]; OR for sustained ROSC, 0.53 [95% CI, 0.43-0.64; P < .001]).,In this population-based, cross-sectional study, out-of-hospital cardiac arrests and deaths during the COVID-19 pandemic significantly increased compared with the same period the previous year and were associated with older age, nonwhite race/ethnicity, hypertension, diabetes, physical limitations, and nonshockable presenting rhythms.,Identifying patients with the greatest risk for out-of-hospital cardiac arrest and death during the COVID-19 pandemic should allow for early, targeted interventions in the outpatient setting that could lead to reductions in out-of-hospital deaths.

Many long non-coding RNAs (lncRNAs), including lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), are involved in various cardiac diseases.,We evaluated the effects of tag single nucleotide polymorphisms (tag-SNPs) on MALAT1 gene in a Chinese population of children with congenital heart disease (CHD).,In the present study, 713 CHD patients and 730 gender- and age-matched children without CHD were genotyped for MALAT1 tag-SNPs rs11227209, rs619586, and rs3200401.,Further investigation of SNP’s function was performed by luciferase assay.,Statistical analyses, including uni- and multivariate logistic regression were performed to quantitate the association between these tag SNPs and CHD.,We discovered that MALAT1 rs619586 GG allele was significantly associated with lower risk of CHD (odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.59-0.92, P=0.014) in additive model.,Functional investigation indicated that G allele of rs619586 could trigger higher expression of MALAT1.,We demonstrated that the functional MALAT1 polymorphism rs619586 A>G was significantly associated with CHD susceptibility in Chinese population, potentially via regulating MALAT1 expression.

Long noncoding RNAs (lncRNAs) represent a large subgroup of RNAs that are longer than 200 nucleotides and have no apparent protein coding potential.,They have diverse functions in different biological processes by regulating chromatin remodeling or protein translation.,This review summarizes the recent progress of lncRNAs in angiogenesis and vascular diseases.,A general overview of lncRNA functional mechanisms will be introduced.,A list of lncRNAs, which are termed “Angio-LncRs”, including MALAT1, MANTIS, PUNISHER, MEG3, MIAT, SENCR and GATA6-AS, will be discussed regarding their expression, regulation, function and mechanism of action in angiogenesis.,Implications of lncRNAs in vascular diseases, such as atherosclerosis, hypertension, vascular retinopathies and tumor angiogenesis will also be discussed.

Whether dipeptidyl peptidase-4 inhibitor (DPP4i) is associated with a lower risk of new-onset atrial fibrillation (AF) in patients with diabetes remains unclear.,This study aimed to evaluate the risk of AF associated with use of DPP4i among a longitudinal cohort of patients with diabetes.,Over a 3-year period, 480,000 patients with diabetes were analyzed utilizing Taiwan’s National Health Insurance Research Database and 90,880 patients taking metformin as first-line therapy were enrolled.,Patients were further divided into two groups: (1) DPP4i users: those taking DPP4i and (2) non-DPP4i users: those prescribed other hypoglycemic agents (HAs) as second-line drug.,Study end point was defined by diagnosis of AF, addition of any third-line HA, or the end of the study period (December 31, 2013), whichever came first.,A total of 16,017 DPP4i users and 74,863 non-DPP4i users were eligible for the study.,For the DPP4i group, most patients were prescribed sitagliptin (n = 12,180; 76%).,Among the non-DPP4i group, most patients took sulfonylurea (n = 60,606; 81%) as their second-line medication.,DPP4i users were associated with a lower risk of new-onset AF compared with non-DPP4i users after propensity-score weighting (hazard ratio 0.65; P < 0.0001).,Subgroup analysis showed that DPP4i user were associated with a lower risk of new-onset AF compared with non-DPP4i users in most subgroups.,Multivariate analysis indicated that use of DPP4i was associated with lower risk of new-onset AF and age > 65 years, presence of hypertension, and ischemic heart disease were independent risk factors for new-onset AF.,Among patients with diabetes prescribed with metformin, the patients with DPP4i as second HA were associated with a lower risk of AF compared with the patients with other drugs as second HAs in real-world practice.,The online version of this article (10.1186/s12933-017-0640-5) contains supplementary material, which is available to authorized users.

Accumulating evidence suggests that thiazolidinediones (TZDs) may exert protective effects in atrial fibrillation (AF).,The present meta-analysis investigated the association between TZD use and the incidence of AF in diabetic patients.,Electronic databases were searched until December 2016.,Of the 346 initially identified records, 3 randomized clinical trials (RCTs) and 4 observational studies with 130,854 diabetic patients were included in the final analysis.,Pooled analysis of the included studies demonstrated that patients treated with TZDs had approximately 30% lower risk of developing AF compared to controls [odds ratio (OR): 0.73, 95% confidence interval (CI): 0.62 to 0.87, p = 0.0003].,This association was consistently observed for both new onset AF (OR =0.77, p = 0.002) and recurrent AF (OR =0.41, p = 0.002), pioglitazone use (OR =0.56, p = 0.04) but not rosiglitazone use (OR =0.78, p = 0.12).,The association between TZD use and AF incidence was not significant in the pooled analysis of three RCTs (OR =0.77, 95% CI = 0.53-1.12, p = 0.17), but was significantly in the pooled analysis of the four observational studies (OR =0.71, p = 0.0003).,This meta-analysis suggests that TZDs may confer protection against AF in the setting of diabetes mellitus (DM).,This class of drugs can be used as upstream therapy for DM patients to prevent the development of AF.,Further large-scale RCTs are needed to determine whether TZDs use could prevent AF in the setting of DM.

Critically ill patients diagnosed with COVID-19 may develop a pro-thrombotic state that places them at a dramatically increased lethal risk.,Although platelet activation is critical for thrombosis and is responsible for the thrombotic events and cardiovascular complications, the role of platelets in the pathogenesis of COVID-19 remains unclear.,Using platelets from healthy volunteers, non-COVID-19 and COVID-19 patients, as well as wild-type and hACE2 transgenic mice, we evaluated the changes in platelet and coagulation parameters in COVID-19 patients.,We investigated ACE2 expression and direct effect of SARS-CoV-2 virus on platelets by RT-PCR, flow cytometry, Western blot, immunofluorescence, and platelet functional studies in vitro, FeCl3-induced thrombus formation in vivo, and thrombus formation under flow conditions ex vivo.,We demonstrated that COVID-19 patients present with increased mean platelet volume (MPV) and platelet hyperactivity, which correlated with a decrease in overall platelet count.,Detectable SARS-CoV-2 RNA in the blood stream was associated with platelet hyperactivity in critically ill patients.,Platelets expressed ACE2, a host cell receptor for SARS-CoV-2, and TMPRSS2, a serine protease for Spike protein priming.,SARS-CoV-2 and its Spike protein directly enhanced platelet activation such as platelet aggregation, PAC-1 binding, CD62P expression, α granule secretion, dense granule release, platelet spreading, and clot retraction in vitro, and thereby Spike protein enhanced thrombosis formation in wild-type mice transfused with hACE2 transgenic platelets, but this was not observed in animals transfused with wild-type platelets in vivo.,Further, we provided evidence suggesting that the MAPK pathway, downstream of ACE2, mediates the potentiating role of SARS-CoV-2 on platelet activation, and that platelet ACE2 expression decreases following SARS-COV-2 stimulation.,SARS-CoV-2 and its Spike protein directly stimulated platelets to facilitate the release of coagulation factors, the secretion of inflammatory factors, and the formation of leukocyte-platelet aggregates.,Recombinant human ACE2 protein and anti-Spike monoclonal antibody could inhibit SARS-CoV-2 Spike protein-induced platelet activation.,Our findings uncovered a novel function of SARS-CoV-2 on platelet activation via binding of Spike to ACE2.,SARS-CoV-2-induced platelet activation may participate in thrombus formation and inflammatory responses in COVID-19 patients.

An important feature of severe acute respiratory syndrome coronavirus 2 pathogenesis is COVID-19-associated coagulopathy, characterised by increased thrombotic and microvascular complications.,Previous studies have suggested a role for endothelial cell injury in COVID-19-associated coagulopathy.,To determine whether endotheliopathy is involved in COVID-19-associated coagulopathy pathogenesis, we assessed markers of endothelial cell and platelet activation in critically and non-critically ill patients admitted to the hospital with COVID-19.,In this single-centre cross-sectional study, hospitalised adult (≥18 years) patients with laboratory-confirmed COVID-19 were identified in the medical intensive care unit (ICU) or a specialised non-ICU COVID-19 floor in our hospital.,Asymptomatic, non-hospitalised controls were recruited as a comparator group for biomarkers that did not have a reference range.,We assessed markers of endothelial cell and platelet activation, including von Willebrand Factor (VWF) antigen, soluble thrombomodulin, soluble P-selectin, and soluble CD40 ligand, as well as coagulation factors, endogenous anticoagulants, and fibrinolytic enzymes.,We compared the level of each marker in ICU patients, non-ICU patients, and controls, where applicable.,We assessed correlations between these laboratory results with clinical outcomes, including hospital discharge and mortality.,Kaplan-Meier analysis was used to further explore the association between biochemical markers and survival.,68 patients with COVID-19 were included in the study from April 13 to April 24, 2020, including 48 ICU and 20 non-ICU patients, as well as 13 non-hospitalised, asymptomatic controls.,Markers of endothelial cell and platelet activation were significantly elevated in ICU patients compared with non-ICU patients, including VWF antigen (mean 565% [SD 199] in ICU patients vs 278% [133] in non-ICU patients; p<0·0001) and soluble P-selectin (15·9 ng/mL [4·8] vs 11·2 ng/mL [3·1]; p=0·0014).,VWF antigen concentrations were also elevated above the normal range in 16 (80%) of 20 non-ICU patients.,We found mortality to be significantly correlated with VWF antigen (r = 0·38; p=0·0022) and soluble thrombomodulin (r = 0·38; p=0·0078) among all patients.,In all patients, soluble thrombomodulin concentrations greater than 3·26 ng/mL were associated with lower rates of hospital discharge (22 [88%] of 25 patients with low concentrations vs 13 [52%] of 25 patients with high concentrations; p=0·0050) and lower likelihood of survival on Kaplan-Meier analysis (hazard ratio 5·9, 95% CI 1·9-18·4; p=0·0087).,Our findings show that endotheliopathy is present in COVID-19 and is likely to be associated with critical illness and death.,Early identification of endotheliopathy and strategies to mitigate its progression might improve outcomes in COVID-19.,This work was supported by a gift donation from Jack Levin to the Benign Hematology programme at Yale, and the National Institutes of Health.

Supplemental Digital Content is available in the text.,Pulmonary thrombosis is observed in severe acute respiratory syndrome coronavirus 2 pneumonia.,Aim was to investigate whether subpopulations of platelets were programmed to procoagulant and inflammatory activities in coronavirus disease 2019 (COVID-19) patients with pneumonia, without comorbidities predisposing to thromboembolism.,Overall, 37 patients and 28 healthy subjects were studied.,Platelet-leukocyte aggregates, platelet-derived microvesicles, the expression of P-selectin, and active fibrinogen receptor on platelets were quantified by flow cytometry.,The profile of 45 cytokines, chemokines, and growth factors released by platelets was defined by immunoassay.,The contribution of platelets to coagulation factor activity was selectively measured.,Numerous platelet-monocyte (mean±SE, 67.9±4.9%, n=17 versus 19.4±3.0%, n=22; P<0.0001) and platelet-granulocyte conjugates (34.2±4.04% versus 8.6±0.7%; P<0.0001) were detected in patients.,Resting patient platelets had similar levels of P-selectin (10.9±2.6%, n=12) to collagen-activated control platelets (8.7±1.5%), which was not further increased by collagen activation on patient platelets (12.4±2.5%, P=nonsignificant).,The agonist-stimulated expression of the active fibrinogen receptor was reduced by 60% in patients (P<0.0001 versus controls).,Cytokines (IL [interleukin]-1α, IL-1β, IL-1RA, IL-4, IL-10, IL-13, IL, 17, IL-27, IFN [interferon]-α, and IFN-γ), chemokines (MCP-1/CCL2 [monocyte chemoattractant protein 1]), and growth factors (VEGF [vascular endothelial growth factor]-A/D) were released in significantly larger amounts upon stimulation of COVID-19 platelets.,Platelets contributed to increased fibrinogen, VWF (von Willebrand factor), and factor XII in COVID-19 patients.,Patients (28.5±0.7 s, n=32), unlike controls (31.6±0.5 s, n=28; P<0.001), showed accelerated factor XII-dependent coagulation.,Platelets in COVID-19 pneumonia are primed to spread proinflammatory and procoagulant activities in systemic circulation.

Since the onset of the global pandemic in early 2020, coronavirus disease 2019 (COVID-19) has posed a multitude of challenges to health care systems worldwide.,In order to combat these challenges and devise appropriate therapeutic strategies, it becomes of paramount importance to elucidate the pathophysiology of this illness.,Coronavirus disease 2019, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), is characterized by a dysregulated immune system and hypercoagulability.,COVID-associated coagulopathy (CAC) was recognized based on profound d-dimer elevations and evidence of microthrombi and macrothrombi, both in venous and arterial systems.,The underlying mechanisms associated with CAC have been suggested, but not clearly defined.,The model of immunothrombosis illustrates the elaborate crosstalk between the innate immune system and coagulation.,The rendering of a procoagulant state in COVID-19 involves the interplay of many innate immune pathways.,The SARS-CoV2 virus can directly infect immune and endothelial cells, leading to endothelial injury and dysregulation of the immune system.,Activated leukocytes potentiate a procoagulant state via release of intravascular tissue factor, platelet activation, NETosis, and inhibition of anticoagulant mechanisms.,Additional pathways of specific relevance in CAC include cytokine release and complement activation.,All these mechanisms have recently been reported in COVID-19.,Immunothrombosis provides a comprehensive perspective of the several synergistic pathways pertinent to the pathogenesis of CAC.

This study sought to explore the spectrum of cardiac abnormalities in student athletes who returned to university campus in July 2020 with uncomplicated coronavirus disease 2019 (COVID-19).,There is limited information on cardiovascular involvement in young individuals with mild or asymptomatic COVID-19.,Screening echocardiograms were performed in 54 consecutive student athletes (mean age 19 years; 85% male) who had positive results of reverse transcription polymerase chain reaction nasal swab testing of the upper respiratory tract or immunoglobulin G antibodies against severe acute respiratory syndrome coronavirus type 2.,Sequential cardiac magnetic resonance imaging was performed in 48 (89%) subjects.,A total of 16 (30%) athletes were asymptomatic, whereas 36 (66%) and 2 (4%) athletes reported mild and moderate COVID-19 related symptoms, respectively.,For the 48 athletes completing both imaging studies, abnormal findings were identified in 27 (56.3%) individuals.,This included 19 (39.5%) athletes with pericardial late enhancements with associated pericardial effusion.,Of the individuals with pericardial enhancements, 6 (12.5%) had reduced global longitudinal strain and/or an increased native T1.,One patient showed myocardial enhancement, and reduced left ventricular ejection fraction or reduced global longitudinal strain with or without increased native T1 values was also identified in an additional 7 (14.6%) individuals.,Native T2 findings were normal in all subjects, and no specific imaging features of myocardial inflammation were identified.,Hierarchical clustering of left ventricular regional strain identified 3 unique myopericardial phenotypes that showed significant association with the cardiac magnetic resonance findings (p = 0.03).,More than 1 in 3 previously healthy college athletes recovering from COVID-19 infection showed imaging features of a resolving pericardial inflammation.,Although subtle changes in myocardial structure and function were identified, no athlete showed specific imaging features to suggest an ongoing myocarditis.,Further studies are needed to understand the clinical implications and long-term evolution of these abnormalities in uncomplicated COVID-19.

Parametric mapping techniques provide a non-invasive tool for quantifying tissue alterations in myocardial disease in those eligible for cardiovascular magnetic resonance (CMR).,Parametric mapping with CMR now permits the routine spatial visualization and quantification of changes in myocardial composition based on changes in T1, T2, and T2*(star) relaxation times and extracellular volume (ECV).,These changes include specific disease pathways related to mainly intracellular disturbances of the cardiomyocyte (e.g., iron overload, or glycosphingolipid accumulation in Anderson-Fabry disease); extracellular disturbances in the myocardial interstitium (e.g., myocardial fibrosis or cardiac amyloidosis from accumulation of collagen or amyloid proteins, respectively); or both (myocardial edema with increased intracellular and/or extracellular water).,Parametric mapping promises improvements in patient care through advances in quantitative diagnostics, inter- and intra-patient comparability, and relatedly improvements in treatment.,There is a multitude of technical approaches and potential applications.,This document provides a summary of the existing evidence for the clinical value of parametric mapping in the heart as of mid 2017, and gives recommendations for practical use in different clinical scenarios for scientists, clinicians, and CMR manufacturers.

Coronavirus disease-2019 (COVID-19) is thought to predispose patients to thrombotic disease.,To date there are few reports of ST-segment elevation myocardial infarction (STEMI) caused by type 1 myocardial infarction in patients with COVID-19.,The aim of this study was to describe the demographic, angiographic, and procedural characteristics alongside clinical outcomes of consecutive cases of COVID-19-positive patients with STEMI compared with COVID-19-negative patients.,This was a single-center, observational study of 115 consecutive patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention at Barts Heart Centre between March 1, 2020, and May 20, 2020.,Patients with STEMI presenting with concurrent COVID-19 infection had higher levels of troponin T and lower lymphocyte count, but elevated D-dimer and C-reactive protein.,There were significantly higher rates of multivessel thrombosis, stent thrombosis, higher modified thrombus grade post first device with consequently higher use of glycoprotein IIb/IIIa inhibitors and thrombus aspiration.,Myocardial blush grade and left ventricular function were significantly lower in patients with COVID-19 with STEMI.,Higher doses of heparin to achieve therapeutic activated clotting times were also noted.,Importantly, patients with STEMI presenting with COVID-19 infection had a longer in-patient admission and higher rates of intensive care admission.,In patients presenting with STEMI and concurrent COVID-19 infection, there is a strong signal toward higher thrombus burden and poorer outcomes.,This supports the need for establishing COVID-19 status in all STEMI cases.,Further work is required to understand the mechanism of increased thrombosis and the benefit of aggressive antithrombotic therapy in selected cases.

ST-segment elevation myocardial infarction (STEMI) is a fatal cardiovascular emergency requiring rapid reperfusion treatment.,During the coronavirus disease-2019 (COVID-19) pandemic, medical professionals need to strike a balance between providing timely treatment for STEMI patients and implementing infection control procedures to prevent nosocomial spread of COVID-19 among health care workers and other vulnerable cardiovascular patients.,This study evaluates the impact of the COVID-19 outbreak and China Chest Pain Center’s modified STEMI protocol on the treatment and prognosis of STEMI patients in China.,Based on the data of 28,189 STEMI patients admitted to 1,372 Chest Pain Centers in China between December 27, 2019 and February 20, 2020, the study analyzed how the COVID-19 outbreak and China Chest Pain Center’s modified STEMI protocol influenced the number of admitted STEMI cases, reperfusion strategy, key treatment time points, and in-hospital mortality and heart failure for STEMI patients.,The COVID-19 outbreak reduced the number of STEMI cases reported to China Chest Pain Centers.,Consistent with China Chest Pain Center’s modified STEMI protocol, the percentage of patients undergoing primary percutaneous coronary intervention declined while the percentage of patients undergoing thrombolysis increased.,With an average delay of approximately 20 min for reperfusion therapy, the rate of in-hospital mortality and in-hospital heart failure increased during the outbreak, but the rate of in-hospital hemorrhage remained stable.,There were reductions in STEMI patients’ access to care, delays in treatment timelines, changes in reperfusion strategies, and an increase of in-hospital mortality and heart failure during the COVID-19 pandemic in China.

Coronavirus disease 2019 (COVID-19) is a rapidly expanding global pandemic caused by severe acute respiratory syndrome coronavirus 2, resulting in significant morbidity and mortality.,A substantial minority of patients hospitalized develop an acute COVID-19 cardiovascular syndrome, which can manifest with a variety of clinical presentations but often presents as an acute cardiac injury with cardiomyopathy, ventricular arrhythmias, and hemodynamic instability in the absence of obstructive coronary artery disease.,The cause of this injury is uncertain but is suspected to be related to myocarditis, microvascular injury, systemic cytokine-mediated injury, or stress-related cardiomyopathy.,Although histologically unproven, severe acute respiratory syndrome coronavirus 2 has the potential to directly replicate within cardiomyocytes and pericytes, leading to viral myocarditis.,Systemically elevated cytokines are also known to be cardiotoxic and have the potential to result in profound myocardial injury.,Prior experience with severe acute respiratory syndrome coronavirus 1 has helped expedite the evaluation of several promising therapies, including antiviral agents, interleukin-6 inhibitors, and convalescent serum.,Management of acute COVID-19 cardiovascular syndrome should involve a multidisciplinary team including intensive care specialists, infectious disease specialists, and cardiologists.,Priorities for managing acute COVID-19 cardiovascular syndrome include balancing the goals of minimizing healthcare staff exposure for testing that will not change clinical management with early recognition of the syndrome at a time point at which intervention may be most effective.,This article aims to review the best available data on acute COVID-19 cardiovascular syndrome epidemiology, pathogenesis, diagnosis, and treatment.,From these data, we propose a surveillance, diagnostic, and management strategy that balances potential patient risks and healthcare staff exposure with improvement in meaningful clinical outcomes.

The coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 that has significant implications for the cardiovascular care of patients.,First, those with COVID-19 and pre-existing cardiovascular disease have an increased risk of severe disease and death.,Second, infection has been associated with multiple direct and indirect cardiovascular complications including acute myocardial injury, myocarditis, arrhythmias, and venous thromboembolism.,Third, therapies under investigation for COVID-19 may have cardiovascular side effects.,Fourth, the response to COVID-19 can compromise the rapid triage of non-COVID-19 patients with cardiovascular conditions.,Finally, the provision of cardiovascular care may place health care workers in a position of vulnerability as they become hosts or vectors of virus transmission.,We hereby review the peer-reviewed and pre-print reports pertaining to cardiovascular considerations related to COVID-19 and highlight gaps in knowledge that require further study pertinent to patients, health care workers, and health systems.,•Patients with pre-existing CVD appear to have worse outcomes with COVID-19.,•CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care.,•Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV medications.,•Health care workers and health systems should take measures to ensure safety while providing high-quality care for COVID-19 patients.,Patients with pre-existing CVD appear to have worse outcomes with COVID-19.,CV complications include biomarker elevations, myocarditis, heart failure, and venous thromboembolism, which may be exacerbated by delays in care.,Therapies under investigation for COVID-19 may have significant drug-drug interactions with CV medications.,Health care workers and health systems should take measures to ensure safety while providing high-quality care for COVID-19 patients.

Unlike most noninvasive imaging modalities, coronary computed tomography angiography can characterize subtypes of atherosclerotic plaque.,The purpose of this study was to investigate the prognostic implications of adverse coronary plaque characteristics in patients with suspected coronary artery disease.,In this SCOT-HEART (Scottish COmputed Tomography of the HEART Trial) post hoc analysis, the presence of adverse plaque (positive remodeling or low attenuation plaque), obstructive disease, and coronary artery calcification within 15 coronary segments was assessed on coronary computed tomography angiography of 1,769 patients who were followed-up for 5 years.,Among study participants (mean age 58 ± 10 years; 56% male), 608 (34%) patients had 1 or more adverse plaque features.,Coronary heart disease death or nonfatal myocardial infarction was 3 times more frequent in patients with adverse plaque (n = 25 of 608 [4.1%] vs. n = 16 of 1,161 [1.4%]; p < 0.001; hazard ratio [HR]: 3.01; 95% confidence interval (CI): 1.61 to 5.63; p = 0.001) and was twice as frequent in those with obstructive disease (n = 22 of 452 [4.9%] vs. n = 16 of 671 [2.4%]; p = 0.024; HR: 1.99; 95% CI: 1.05 to 3.79; p = 0.036).,Patients with both obstructive disease and adverse plaque had the highest event rate, with a 10-fold increase in coronary heart disease death or nonfatal myocardial infarction compared with patients with normal coronary arteries (HR: 11.50; 95% CI: 3.39 to 39.04; p < 0.001).,However, these associations were not independent of coronary artery calcium score, a surrogate measure of coronary plaque burden.,Adverse coronary plaque characteristics and overall calcified plaque burden confer an increased risk of coronary heart disease death or nonfatal myocardial infarction.,(Scottish COmputed Tomography of the HEART Trial [SCOT-HEART]; NCT01149590)

Coronary artery inflammation inhibits adipogenesis in adjacent perivascular fat.,A novel imaging biomarker-the perivascular fat attenuation index (FAI)-captures coronary inflammation by mapping spatial changes of perivascular fat attenuation on coronary computed tomography angiography (CTA).,However, the ability of the perivascular FAI to predict clinical outcomes is unknown.,In the Cardiovascular RISk Prediction using Computed Tomography (CRISP-CT) study, we did a post-hoc analysis of outcome data gathered prospectively from two independent cohorts of consecutive patients undergoing coronary CTA in Erlangen, Germany (derivation cohort) and Cleveland, OH, USA (validation cohort).,Perivascular fat attenuation mapping was done around the three major coronary arteries-the proximal right coronary artery, the left anterior descending artery, and the left circumflex artery.,We assessed the prognostic value of perivascular fat attenuation mapping for all-cause and cardiac mortality in Cox regression models, adjusted for age, sex, cardiovascular risk factors, tube voltage, modified Duke coronary artery disease index, and number of coronary CTA-derived high-risk plaque features.,Between 2005 and 2009, 1872 participants in the derivation cohort underwent coronary CTA (median age 62 years [range 17-89]).,Between 2008 and 2016, 2040 patients in the validation cohort had coronary CTA (median age 53 years [range 19-87]).,Median follow-up was 72 months (range 51-109) in the derivation cohort and 54 months (range 4-105) in the validation cohort.,In both cohorts, high perivascular FAI values around the proximal right coronary artery and left anterior descending artery (but not around the left circumflex artery) were predictive of all-cause and cardiac mortality and correlated strongly with each other.,Therefore, the perivascular FAI measured around the right coronary artery was used as a representative biomarker of global coronary inflammation (for prediction of cardiac mortality, hazard ratio [HR] 2·15, 95% CI 1·33-3·48; p=0·0017 in the derivation cohort, and 2·06, 1·50-2·83; p<0·0001 in the validation cohort).,The optimum cutoff for the perivascular FAI, above which there is a steep increase in cardiac mortality, was ascertained as −70·1 Hounsfield units (HU) or higher in the derivation cohort (HR 9·04, 95% CI 3·35-24·40; p<0·0001 for cardiac mortality; 2·55, 1·65-3·92; p<0·0001 for all-cause mortality).,This cutoff was confirmed in the validation cohort (HR 5·62, 95% CI 2·90-10·88; p<0·0001 for cardiac mortality; 3·69, 2·26-6·02; p<0·0001 for all-cause mortality).,Perivascular FAI improved risk discrimination in both cohorts, leading to significant reclassification for all-cause and cardiac mortality.,The perivascular FAI enhances cardiac risk prediction and restratification over and above current state-of-the-art assessment in coronary CTA by providing a quantitative measure of coronary inflammation.,High perivascular FAI values (cutoff ≥-70·1 HU) are an indicator of increased cardiac mortality and, therefore, could guide early targeted primary prevention and intensive secondary prevention in patients.,British Heart Foundation, and the National Institute of Health Research Oxford Biomedical Research Centre.

Coronavirus disease 2019 (COVID-19) is a clinical syndrome caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Patients with severe disease show hyperactivation of the immune system, which can affect multiple organs besides the lungs.,Here, we propose that SARS-CoV-2 infection induces a process known as immunothrombosis, in which activated neutrophils and monocytes interact with platelets and the coagulation cascade, leading to intravascular clot formation in small and larger vessels.,Microthrombotic complications may contribute to acute respiratory distress syndrome (ARDS) and other organ dysfunctions.,Therapeutic strategies aimed at reducing immunothrombosis may therefore be useful.,Several antithrombotic and immunomodulating drugs have been proposed as candidates to treat patients with SARS-CoV-2 infection.,The growing understanding of SARS-CoV-2 infection pathogenesis and how it contributes to critical illness and its complications may help to improve risk stratification and develop targeted therapies to reduce the acute and long-term consequences of this disease.,Here, the authors propose that SARS-CoV-2 induces a prothrombotic state, with dysregulated immunothrombosis in lung microvessels and endothelial injury, which drive the clinical manifestations of severe COVID-19.,They discuss potential antithrombotic and immunomodulating drugs that are being considered in the treatment of patients with COVID-19.

Novel coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state, characterized by abnormal coagulation parameters and by increased incidence of cardiovascular complications.,With this study, we aimed to investigate the activation state and the expression of transmembrane proteins in platelets of hospitalized COVID-19 patients.,We investigated transmembrane proteins expression with a customized mass cytometry panel of 21 antibodies.,Platelets of 8 hospitalized COVID-19 patients not requiring intensive care support and without pre-existing conditions were compared to platelets of healthy controls (11 donors) with and without in vitro stimulation with thrombin receptor-activating peptide (TRAP).,Mass cytometry of non-stimulated platelets detected an increased surface expression of activation markers P-Selectin (0.67 vs.,1.87 median signal intensity for controls vs. patients, p = 0.0015) and LAMP-3 (CD63, 0.37 vs.,0.81, p = 0.0004), the GPIIb/IIIa complex (4.58 vs.,5.03, p < 0.0001) and other adhesion molecules involved in platelet activation and platelet-leukocyte interactions.,Upon TRAP stimulation, mass cytometry detected a higher expression of P-selectin in COVID-19 samples compared to controls (p < 0.0001).,However, we observed a significantly reduced capacity of COVID-19 platelets to increase the expression of activation markers LAMP-3 and P-Selectin upon stimulation with TRAP.,We detected a hyperactivated phenotype in platelets during SARS-CoV-2 infection, consisting of highly expressed platelet activation markers, which might contribute to the hypercoagulopathy observed in COVID-19.,In addition, several transmembrane proteins were more highly expressed compared to healthy controls.,These findings support research projects investigating antithrombotic and antiplatelet treatment regimes in COVID-19 patients, and provide new insights on the phenotypical platelet expression during SARS-CoV-2 infection.

Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described.,In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020.,Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors.,We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death.,191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients).,Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03-1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61-12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64-128·55; p=0·0033) on admission.,Median duration of viral shedding was 20·0 days (IQR 17·0-24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors.,The longest observed duration of viral shedding in survivors was 37 days.,The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage.,Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future.,Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

The novel coronavirus disease (COVID-19) outbreak, caused by SARS-CoV-2, represents the greatest medical challenge in decades.,We provide a comprehensive review of the clinical course of COVID-19, its comorbidities, and mechanistic considerations for future therapies.,While COVID-19 primarily affects the lungs, causing interstitial pneumonitis and severe acute respiratory distress syndrome (ARDS), it also affects multiple organs, particularly the cardiovascular system.,Risk of severe infection and mortality increase with advancing age and male sex.,Mortality is increased by comorbidities: cardiovascular disease, hypertension, diabetes, chronic pulmonary disease, and cancer.,The most common complications include arrhythmia (atrial fibrillation, ventricular tachyarrhythmia, and ventricular fibrillation), cardiac injury [elevated highly sensitive troponin I (hs-cTnI) and creatine kinase (CK) levels], fulminant myocarditis, heart failure, pulmonary embolism, and disseminated intravascular coagulation (DIC).,Mechanistically, SARS-CoV-2, following proteolytic cleavage of its S protein by a serine protease, binds to the transmembrane angiotensin-converting enzyme 2 (ACE2) -a homologue of ACE-to enter type 2 pneumocytes, macrophages, perivascular pericytes, and cardiomyocytes.,This may lead to myocardial dysfunction and damage, endothelial dysfunction, microvascular dysfunction, plaque instability, and myocardial infarction (MI).,While ACE2 is essential for viral invasion, there is no evidence that ACE inhibitors or angiotensin receptor blockers (ARBs) worsen prognosis.,Hence, patients should not discontinue their use.,Moreover, renin-angiotensin-aldosterone system (RAAS) inhibitors might be beneficial in COVID-19.,Initial immune and inflammatory responses induce a severe cytokine storm [interleukin (IL)-6, IL-7, IL-22, IL-17, etc.] during the rapid progression phase of COVID-19.,Early evaluation and continued monitoring of cardiac damage (cTnI and NT-proBNP) and coagulation (D-dimer) after hospitalization may identify patients with cardiac injury and predict COVID-19 complications.,Preventive measures (social distancing and social isolation) also increase cardiovascular risk.,Cardiovascular considerations of therapies currently used, including remdesivir, chloroquine, hydroxychloroquine, tocilizumab, ribavirin, interferons, and lopinavir/ritonavir, as well as experimental therapies, such as human recombinant ACE2 (rhACE2), are discussed.

The new coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has caused more than 210 000 deaths worldwide.,However, little is known about the causes of death and the virus's pathologic features.,To validate and compare clinical findings with data from medical autopsy, virtual autopsy, and virologic tests.,Prospective cohort study.,Autopsies performed at a single academic medical center, as mandated by the German federal state of Hamburg for patients dying with a polymerase chain reaction-confirmed diagnosis of COVID-19.,The first 12 consecutive COVID-19-positive deaths.,Complete autopsy, including postmortem computed tomography and histopathologic and virologic analysis, was performed.,Clinical data and medical course were evaluated.,Results: Median patient age was 73 years (range, 52 to 87 years), 75% of patients were male, and death occurred in the hospital (n = 10) or outpatient sector (n = 2).,Coronary heart disease and asthma or chronic obstructive pulmonary disease were the most common comorbid conditions (50% and 25%, respectively).,Autopsy revealed deep venous thrombosis in 7 of 12 patients (58%) in whom venous thromboembolism was not suspected before death; pulmonary embolism was the direct cause of death in 4 patients.,Postmortem computed tomography revealed reticular infiltration of the lungs with severe bilateral, dense consolidation, whereas histomorphologically diffuse alveolar damage was seen in 8 patients.,In all patients, SARS-CoV-2 RNA was detected in the lung at high concentrations; viremia in 6 of 10 and 5 of 12 patients demonstrated high viral RNA titers in the liver, kidney, or heart.,Limited sample size.,The high incidence of thromboembolic events suggests an important role of COVID-19-induced coagulopathy.,Further studies are needed to investigate the molecular mechanism and overall clinical incidence of COVID-19-related death, as well as possible therapeutic interventions to reduce it.,University Medical Center Hamburg-Eppendorf.,Little is known of the pathologic changes that lead to death in patients with COVID-19.,This study reports the autopsy findings of consecutive patients who died with a diagnosis of COVID-19.

The coronavirus disease of 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,While systemic inflammation and pulmonary complications can result in significant morbidity and mortality, cardiovascular complications may also occur.,This brief report evaluates cardiovascular complications in the setting of COVID-19 infection.,The current COVID-19 pandemic has resulted in over one million infected worldwide and thousands of death.,The virus binds and enters through angiotensin-converting enzyme 2 (ACE2).,COVID-19 can result in systemic inflammation, multiorgan dysfunction, and critical illness.,The cardiovascular system is also affected, with complications including myocardial injury, myocarditis, acute myocardial infarction, heart failure, dysrhythmias, and venous thromboembolic events.,Current therapies for COVID-19 may interact with cardiovascular medications.,Emergency clinicians should be aware of these cardiovascular complications when evaluating and managing the patient with COVID-19.

Risk factors for pulmonary embolism in patients with coronavirus disease 2019 include obesity, an elevated d-dimer value, elevated C-reactive protein level, and a rising d-dimer value over time.

Aim of the study is to evaluate the incidence of DVT in COVID-19 patients and its correlation with the severity of the disease and with clinical and laboratory findings.,234 symptomatic patients with COVID-19, diagnosed according to the World Health Organization guidelines, were included in the study.,The severity of the disease was classified as moderate, severe and critical.,Doppler ultrasound (DUS) was performed in all patients.,DUS findings, clinical, laboratory’s and therapeutic variables were investigated by contingency tables, Pearson chi square test and by Student t test and Fisher's exact test.,ROC curve analysis was applied to study significant continuous variables.,Overall incidence of DVT was 10.7% (25/234): 1.6% (1/60) among moderate cases, 13.8% (24/174) in severely and critically ill patients.,Prolonged bedrest and intensive care unit admission were significantly associated with the presence of DVT (19.7%).,Fraction of inspired oxygen, P/F ratio, respiratory rate, heparin administration, D-dimer, IL-6, ferritin and CRP showed correlation with DVT.,DUS may be considered a useful and valid tool for early identification of DVT.,In less severely affected patients, DUS as screening of DVT might be unnecessary.,High rate of DVT found in severe patients and its correlation with respiratory parameters and some significant laboratory findings suggests that these can be used as a screening tool for patients who should be getting DUS.

The purpose of this study was to evaluate in-hospital outcomes among patients with a history of heart failure (HF) hospitalized with coronavirus disease-2019 (COVID-19).,Cardiometabolic comorbidities are common in patients with severe COVID-19.,Patients with HF may be particularly susceptible to COVID-19 complications.,The Premier Healthcare Database was used to identify patients with at least 1 HF hospitalization or 2 HF outpatient visits between January 1, 2019, and March 31, 2020, who were subsequently hospitalized between April and September 2020.,Baseline characteristics, health care resource utilization, and mortality rates were compared between those hospitalized with COVID-19 and those hospitalized with other causes.,Predictors of in-hospital mortality were identified in HF patients hospitalized with COVID-19 by using multivariate logistic regression.,Among 1,212,153 patients with history of HF, 132,312 patients were hospitalized from April 1, 2020, to September 30, 2020.,A total of 23,843 patients (18.0%) were hospitalized with acute HF, 8,383 patients (6.4%) were hospitalized with COVID-19, and 100,068 patients (75.6%) were hospitalized with alternative reasons.,Hospitalization with COVID-19 was associated with greater odds of in-hospital mortality as compared with hospitalization with acute HF; 24.2% of patients hospitalized with COVID-19 died in-hospital compared to 2.6% of those hospitalized with acute HF.,This association was strongest in April (adjusted odds ratio [OR]: 14.48; 95% confidence interval [CI]:12.25 to 17.12) than in subsequent months (adjusted OR: 10.11; 95% CI: 8.95 to 11.42; pinteraction <0.001).,Among patients with HF hospitalized with COVID-19, male sex (adjusted OR: 1.26; 95% CI: 1.13 to 1.40) and morbid obesity (adjusted OR: 1.25; 95% CI: 1.07 to 1.46) were associated with greater odds of in-hospital mortality, along with age (adjusted OR: 1.35; 95% CI: 1.29 to 1.42 per 10 years) and admission earlier in the pandemic.,Patients with HF hospitalized with COVID-19 are at high risk for complications, with nearly 1 in 4 dying during hospitalization.

Although the direct toll of COVID-19 in the United States has been substantial, concerns have also arisen about the indirect effects of the pandemic.,Hospitalizations for acute cardiovascular conditions have declined, raising concern that patients may be avoiding hospitals because of fear of contracting severe acute respiratory syndrome- coronavirus-2 (SARS-CoV-2).,Other factors, including strain on health care systems, may also have had an indirect toll.,This investigation aimed to evaluate whether population-level deaths due to cardiovascular causes increased during the COVID-19 pandemic.,The authors conducted an observational cohort study using data from the National Center for Health Statistics to evaluate the rate of deaths due to cardiovascular causes after the onset of the pandemic in the United States, from March 18, 2020, to June 2, 2020, relative to the period immediately preceding the pandemic (January 1, 2020 to March 17, 2020).,Changes in deaths were compared with the same periods in the previous year.,There were 397,042 cardiovascular deaths from January 1, 2020, to June 2, 2020.,Deaths caused by ischemic heart disease increased nationally after the onset of the pandemic in 2020, compared with changes over the same period in 2019 (ratio of the relative change in deaths per 100,000 in 2020 vs.,2019: 1.11, 95% confidence interval: 1.04 to 1.18).,An increase was also observed for deaths caused by hypertensive disease (1.17, 95% confidence interval: 1.09 to 1.26), but not for heart failure, cerebrovascular disease, or other diseases of the circulatory system.,New York City experienced a large relative increase in deaths caused by ischemic heart disease (2.39, 95% confidence interval: 1.39 to 4.09) and hypertensive diseases (2.64, 95% confidence interval: 1.52 to 4.56) during the pandemic.,More modest increases in deaths caused by these conditions occurred in the remainder of New York State, New Jersey, Michigan, and Illinois but not in Massachusetts or Louisiana.,There was an increase in deaths caused by ischemic heart disease and hypertensive diseases in some regions of the United States during the initial phase of the COVID-19 pandemic.,These findings suggest that the pandemic may have had an indirect toll on patients with cardiovascular disease.

During the peak phase of the COVID-19 pandemic, alterations of standard operating procedures were necessary for health systems to protect patients and healthcare workers and ensure access to vital hospital resources.,As the peak phase passes, re-activation plans are required to safely manage increasing clinical volumes.,In the context of cardiovascular magnetic resonance (CMR), re-activation objectives include continued performance of urgent CMR studies and resumption of CMR in patients with semi-urgent and elective indications in an environment that is safe for both patients and health care workers.

What are the cardiovascular effects in unselected patients with recent coronavirus disease 2019 (COVID-19)?,In this cohort study including 100 patients recently recovered from COVID-19 identified from a COVID-19 test center, cardiac magnetic resonance imaging revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), which was independent of preexisting conditions, severity and overall course of the acute illness, and the time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.,This cohort study evaluates the presence of myocardial injury in unselected patients recently recovered from coronavirus disease 2019 (COVID-19).,Coronavirus disease 2019 (COVID-19) continues to cause considerable morbidity and mortality worldwide.,Case reports of hospitalized patients suggest that COVID-19 prominently affects the cardiovascular system, but the overall impact remains unknown.,To evaluate the presence of myocardial injury in unselected patients recently recovered from COVID-19 illness.,In this prospective observational cohort study, 100 patients recently recovered from COVID-19 illness were identified from the University Hospital Frankfurt COVID-19 Registry between April and June 2020.,Recent recovery from severe acute respiratory syndrome coronavirus 2 infection, as determined by reverse transcription-polymerase chain reaction on swab test of the upper respiratory tract.,Demographic characteristics, cardiac blood markers, and cardiovascular magnetic resonance (CMR) imaging were obtained.,Comparisons were made with age-matched and sex-matched control groups of healthy volunteers (n = 50) and risk factor-matched patients (n = 57).,Of the 100 included patients, 53 (53%) were male, and the mean (SD) age was 49 (14) years.,The median (IQR) time interval between COVID-19 diagnosis and CMR was 71 (64-92) days.,Of the 100 patients recently recovered from COVID-19, 67 (67%) recovered at home, while 33 (33%) required hospitalization.,At the time of CMR, high-sensitivity troponin T (hsTnT) was detectable (greater than 3 pg/mL) in 71 patients recently recovered from COVID-19 (71%) and significantly elevated (greater than 13.9 pg/mL) in 5 patients (5%).,Compared with healthy controls and risk factor-matched controls, patients recently recovered from COVID-19 had lower left ventricular ejection fraction, higher left ventricle volumes, and raised native T1 and T2.,A total of 78 patients recently recovered from COVID-19 (78%) had abnormal CMR findings, including raised myocardial native T1 (n = 73), raised myocardial native T2 (n = 60), myocardial late gadolinium enhancement (n = 32), or pericardial enhancement (n = 22).,There was a small but significant difference between patients who recovered at home vs in the hospital for native T1 mapping (median [IQR], 1119 [1092-1150] ms vs 1141 [1121-1175] ms; P = .008) and hsTnT (4.2 [3.0-5.9] pg/dL vs 6.3 [3.4-7.9] pg/dL; P = .002) but not for native T2 mapping.,None of these measures were correlated with time from COVID-19 diagnosis (native T1: r = 0.07; P = .47; native T2: r = 0.14; P = .15; hsTnT: r = −0.07; P = .50).,High-sensitivity troponin T was significantly correlated with native T1 mapping (r = 0.33; P < .001) and native T2 mapping (r = 0.18; P = .01).,Endomyocardial biopsy in patients with severe findings revealed active lymphocytic inflammation.,Native T1 and T2 were the measures with the best discriminatory ability to detect COVID-19-related myocardial pathology.,In this study of a cohort of German patients recently recovered from COVID-19 infection, CMR revealed cardiac involvement in 78 patients (78%) and ongoing myocardial inflammation in 60 patients (60%), independent of preexisting conditions, severity and overall course of the acute illness, and time from the original diagnosis.,These findings indicate the need for ongoing investigation of the long-term cardiovascular consequences of COVID-19.

To assess the utility of human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as an in vitro proarrhythmia model, we evaluated the concentration dependence and sources of variability of electrophysiologic responses to 28 drugs linked to low, intermediate, and high torsades de pointes (TdP) risk categories using two commercial cell lines and standardized protocols in a blinded multisite study using multielectrode array or voltage-sensing optical approaches.,Logistical and ordinal linear regression models were constructed using drug responses as predictors and TdP risk categories as outcomes.,Three of seven predictors (drug-induced arrhythmia-like events and prolongation of repolarization at either maximum tested or maximal clinical exposures) categorized drugs with reasonable accuracy (area under the curve values of receiver operator curves ~0.8). hiPSC-CM line, test site, and platform had minimal influence on drug categorization.,These results demonstrate the utility of hiPSCCMs to detect drug-induced proarrhythmic effects as part of the evolving Comprehensive In Vitro Proarrhythmia Assay paradigm.

Fulfilling the potential of human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes for studying conduction and arrhythmogenesis requires development of multicellular models and methods for long-term repeated tissue phenotyping.,We generated confluent hiPSC-derived cardiac cell sheets (hiPSC-CCSs), expressing the genetically encoded voltage indicator ArcLight.,ArcLight-based optical mapping allowed generation of activation and action-potential duration (APD) maps, which were validated by mapping the same hiPSC-CCSs with the voltage-sensitive dye, Di-4-ANBDQBS.,ArcLight mapping allowed long-term assessment of electrical remodeling in the hiPSC-CCSs and evaluation of drug-induced conduction slowing (carbenoxolone, lidocaine, and quinidine) and APD prolongation (quinidine and dofetilide).,The latter studies also enabled step-by-step depiction of drug-induced arrhythmogenesis ("torsades de pointes in the culture dish") and its prevention by MgSO4 and rapid pacing.,Phase-mapping analysis allowed biophysical characterization of spiral waves induced in the hiPSC-CCSs and their termination by electrical cardioversion and overdrive pacing.,In conclusion, ArcLight mapping of hiPSC-CCSs provides a powerful tool for drug testing and arrhythmia investigation.,•Optical mapping of hiPSC-derived cardiac cell sheets expressing ArcLight•Evaluating effects of drugs and time (weeks) on conduction and APD•Mapping drug-induced TdP and electrically induced spiral waves (rotors)•Evaluating interventions aiming to prevent or terminate arrhythmias in the model,Optical mapping of hiPSC-derived cardiac cell sheets expressing ArcLight,Evaluating effects of drugs and time (weeks) on conduction and APD,Mapping drug-induced TdP and electrically induced spiral waves (rotors),Evaluating interventions aiming to prevent or terminate arrhythmias in the model,Shaheen and Shiti et al. combine hiPSC-CMs, two-dimensional cardiac tissue models, and optical mapping of a genetically encoded voltage indicator (ArcLight) to enable both short-term and repeated tissue electrophysiological phenotyping (over weeks).,This allowed tracking of electrophysiological tissue remodeling over time; drug effects on conduction, repolarization, and pro-arrhythmia; and investigation of arrhythmia mechanisms and treatments.

A new type of pneumonia caused by a novel coronavirus SARS-CoV-2 outbreaks recently in China and spreads into many other countries.,This disease, named as COVID-19, is similar to patients infected by SARS-CoV and MERS-CoV, and nearly 20% of patients developed severe condition.,Cardiac injury is a prevalent complication of severe patients, exacerbating the disease severity in coronavirus disease 2019 (COVID-19) patients.,Angiotensin-converting enzyme 2 (ACE2), the key host cellular receptor of SARS-CoV-2, has been identified in multiple organs, but its cellular distribution in human heart is not illuminated clearly.,This study performed the first state-of-art single cell atlas of adult human heart, and revealed that pericytes with high expression of ACE2 might act as the target cardiac cell of SARS-CoV-2.,The pericytes injury due to virus infection may result in capillary endothelial cells dysfunction, inducing microvascular dysfunction.,And patients with basic heart failure disease showed increased ACE2 expression at both mRNA and protein levels, meaning that if infected by the virus these patients may have higher risk of heart attack and critically ill condition.,The finding of this study explains the high rate of severe cases among COVID-19 patients with basic cardiovascular disease; and these results also perhaps provide important reference to clinical treatment of cardiac injury among severe patients infected by SARS-CoV-2.

Angiotensin converting enzyme-2 (ACE2) receptors mediate the entry into the cell of three strains of coronavirus: SARS-CoV, NL63 and SARS-CoV-2.,ACE2 receptors are ubiquitous and widely expressed in the heart, vessels, gut, lung (particularly in type 2 pneumocytes and macrophages), kidney, testis and brain.,ACE2 is mostly bound to cell membranes and only scarcely present in the circulation in a soluble form.,An important salutary function of membrane-bound and soluble ACE2 is the degradation of angiotensin II to angiotensin1-7.,Consequently, ACE2 receptors limit several detrimental effects resulting from binding of angiotensin II to AT1 receptors, which include vasoconstriction, enhanced inflammation and thrombosis.,The increased generation of angiotensin1-7 also triggers counter-regulatory protective effects through binding to G-protein coupled Mas receptors.,Unfortunately, the entry of SARS-CoV2 into the cells through membrane fusion markedly down-regulates ACE2 receptors, with loss of the catalytic effect of these receptors at the external site of the membrane.,Increased pulmonary inflammation and coagulation have been reported as unwanted effects of enhanced and unopposed angiotensin II effects via the ACE→Angiotensin II→AT1 receptor axis.,Clinical reports of patients infected with SARS-CoV-2 show that several features associated with infection and severity of the disease (i.e., older age, hypertension, diabetes, cardiovascular disease) share a variable degree of ACE2 deficiency.,We suggest that ACE2 down-regulation induced by viral invasion may be especially detrimental in people with baseline ACE2 deficiency associated with the above conditions.,The additional ACE2 deficiency after viral invasion might amplify the dysregulation between the ‘adverse’ ACE→Angiotensin II→AT1 receptor axis and the ‘protective’ ACE2→Angiotensin1-7→Mas receptor axis.,In the lungs, such dysregulation would favor the progression of inflammatory and thrombotic processes triggered by local angiotensin II hyperactivity unopposed by angiotensin1-7.,In this setting, recombinant ACE2, angiotensin1-7 and angiotensin II type 1 receptor blockers could be promising therapeutic approaches in patients with SARS-CoV-2 infection.

We aim to characterize the incidence, risk for mortality, and identify risk factors for mortality in patients presenting with hemorrhage and COVID-19.,This retrospective cohort study included a cohort of patients admitted to one of three major hospitals of our healthcare network including, an academic medical center and comprehensive stroke center, which accepts transfers for complex cases from eight community hospitals, during March 1 to May 1, 2020.,All patients that received imaging of the neuroaxis and had positive PCR testing for COVID-19 were identified and reviewed by an attending neuroradiologist.,Demographics and comorbidities were recorded.,Biomarkers were recorded from the day of the hemorrhagic event.,Vital signs from the day of the hemorrhagic event mechanical ventilation orders at admission were recorded.,Imaging findings were divided into 5 subtypes; acute subdural hematoma (SDH), subarachnoid hemorrhage (SAH), multi-compartmental hemorrhage (MCH), multi-focal intracerebral hemorrhage (MFH), and focal intracerebral hemorrhage (fICH).,Outcomes were recorded as non-routine discharge and mortality.,We found a total of 35 out of 5227 patients with COVID-19 that had hemorrhage of some kind.,Mortality for the entire cohort was 45.7 % (n = 16).,SDH patients had a mortality rate of 35.3 % (n = 6), SAH had a mortality of 50 % (n = 1), MCH patients had a mortality of 71.4 % (n = 5), MFH patients had a mortality of 50 % (n = 2), fICH patients had a mortality of 40 % (n = 2).,Patients with severe pulmonary COVID requiring mechanical ventilation (OR 10.24 [.43−243.12] p = 0.015), with INR > 1.2 on the day of the hemorrhagic event (OR 14.36 [1.69−122.14] p = 0.015], and patients presenting with spontaneous vs. traumatic hemorrhage (OR 6.11 [.31−118.89] p = 0.023) had significantly higher risk for mortality.,Hemorrhagic presentations with COVID-19 are a rare but serious way in which the illness can manifest.,It is important for neurosurgeons to realize that patients can present with these findings without primary pulmonary symptoms, and that severe pulmonary symptoms, elevated INR, and spontaneous hemorrhagic presentations is associated with increased risk for mortality.

Severe acute respiratory syndrome coronavirus 2, coronavirus disease 2019 (COVID-19)-induced infection can be associated with a coagulopathy, findings consistent with infection-induced inflammatory changes as observed in patients with disseminated intravascular coagulopathy (DIC).,The lack of prior immunity to COVID-19 has resulted in large numbers of infected patients across the globe and uncertainty regarding management of the complications that arise in the course of this viral illness.,The lungs are the target organ for COVID-19; patients develop acute lung injury that can progress to respiratory failure, although multiorgan failure can also occur.,The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen-degradation products, whereas abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations.,Coagulation test screening, including the measurement of D-dimer and fibrinogen levels, is suggested.,COVID-19-associated coagulopathy should be managed as it would be for any critically ill patient, following the established practice of using thromboembolic prophylaxis for critically ill hospitalized patients, and standard supportive care measures for those with sepsis-induced coagulopathy or DIC.,Although D-dimer, sepsis physiology, and consumptive coagulopathy are indicators of mortality, current data do not suggest the use of full-intensity anticoagulation doses unless otherwise clinically indicated.,Even though there is an associated coagulopathy with COVID-19, bleeding manifestations, even in those with DIC, have not been reported.,If bleeding does occur, standard guidelines for the management of DIC and bleeding should be followed.

Emerging reports of rare neurological complications associated with COVID-19 infection and vaccinations are leading to regulatory, clinical and public health concerns.,We undertook a self-controlled case series study to investigate hospital admissions from neurological complications in the 28 days after a first dose of ChAdOx1nCoV-19 (n = 20,417,752) or BNT162b2 (n = 12,134,782), and after a SARS-CoV-2-positive test (n = 2,005,280).,There was an increased risk of Guillain-Barré syndrome (incidence rate ratio (IRR), 2.90; 95% confidence interval (CI): 2.15-3.92 at 15-21 days after vaccination) and Bell’s palsy (IRR, 1.29; 95% CI: 1.08-1.56 at 15-21 days) with ChAdOx1nCoV-19.,There was an increased risk of hemorrhagic stroke (IRR, 1.38; 95% CI: 1.12-1.71 at 15-21 days) with BNT162b2.,An independent Scottish cohort provided further support for the association between ChAdOx1nCoV and Guillain-Barré syndrome (IRR, 2.32; 95% CI: 1.08-5.02 at 1-28 days).,There was a substantially higher risk of all neurological outcomes in the 28 days after a positive SARS-CoV-2 test including Guillain-Barré syndrome (IRR, 5.25; 95% CI: 3.00-9.18).,Overall, we estimated 38 excess cases of Guillain-Barré syndrome per 10 million people receiving ChAdOx1nCoV-19 and 145 excess cases per 10 million people after a positive SARS-CoV-2 test.,In summary, although we find an increased risk of neurological complications in those who received COVID-19 vaccines, the risk of these complications is greater following a positive SARS-CoV-2 test.,A self-controlled case series analysis of nearly 32 million people in England shows an increased risk of rare neurological complications in those who received COVID-19 vaccines and following SARS-CoV-2 infection.,The results highlight 38 excess cases of Guillain-Barré syndrome per 10 million ChAdOx1nCoV-19 vaccinations.

With the spread of coronavirus disease 2019 (COVID-19) during the current worldwide pandemic, there is mounting evidence that patients affected by the illness may develop clinically significant coagulopathy with thromboembolic complications including ischemic stroke.,However, there is limited data on the clinical characteristics, stroke mechanism, and outcomes of patients who have a stroke and COVID-19.,We conducted a retrospective cohort study of consecutive patients with ischemic stroke who were hospitalized between March 15, 2020, and April 19, 2020, within a major health system in New York, the current global epicenter of the pandemic.,We compared the clinical characteristics of stroke patients with a concurrent diagnosis of COVID-19 to stroke patients without COVID-19 (contemporary controls).,In addition, we compared patients to a historical cohort of patients with ischemic stroke discharged from our hospital system between March 15, 2019, and April 15, 2019 (historical controls).,During the study period in 2020, out of 3556 hospitalized patients with diagnosis of COVID-19 infection, 32 patients (0.9%) had imaging proven ischemic stroke.,Cryptogenic stroke was more common in patients with COVID-19 (65.6%) as compared to contemporary controls (30.4%, P=0.003) and historical controls (25.0%, P<0.001).,When compared with contemporary controls, COVID-19 positive patients had higher admission National Institutes of Health Stroke Scale score and higher peak D-dimer levels.,When compared with historical controls, COVID-19 positive patients were more likely to be younger men with elevated troponin, higher admission National Institutes of Health Stroke Scale score, and higher erythrocyte sedimentation rate.,Patients with COVID-19 and stroke had significantly higher mortality than historical and contemporary controls.,We observed a low rate of imaging-confirmed ischemic stroke in hospitalized patients with COVID-19.,Most strokes were cryptogenic, possibly related to an acquired hypercoagulability, and mortality was increased.,Studies are needed to determine the utility of therapeutic anticoagulation for stroke and other thrombotic event prevention in patients with COVID-19.

Stroke, the third leading cause of death and disability worldwide, is undergoing a change in perspective with the emergence of new ideas on neurodegeneration.,The concept that stroke is a disorder solely of blood vessels has been expanded to include the effects of a detrimental interaction between glia, neurons, vascular cells, and matrix components, which is collectively referred to as the neurovascular unit.,Following the acute stroke, the majority of which are ischemic, there is secondary neuroinflammation that both promotes further injury, resulting in cell death, but conversely plays a beneficial role, by promoting recovery.,The proinflammatory signals from immune mediators rapidly activate resident cells and influence infiltration of a wide range of inflammatory cells (neutrophils, monocytes/macrophages, different subtypes of T cells, and other inflammatory cells) into the ischemic region exacerbating brain damage.,In this review, we discuss how neuroinflammation has both beneficial as well as detrimental roles and recent therapeutic strategies to combat pathological responses.,Here, we also focus on time-dependent entry of immune cells to the ischemic area and the impact of other pathological mediators, including oxidative stress, excitotoxicity, matrix metalloproteinases (MMPs), high-mobility group box 1 (HMGB1), arachidonic acid metabolites, mitogen-activated protein kinase (MAPK), and post-translational modifications that could potentially perpetuate ischemic brain damage after the acute injury.,Understanding the time-dependent role of inflammatory factors could help in developing new diagnostic, prognostic, and therapeutic neuroprotective strategies for post-stroke inflammation.

Nod-like receptor protein 3 (NLRP3) inflammasome is a crucial factor in mediating inflammatory responses after cerebral ischemia/reperfusion (I/R), but the cellular location of NLRP3 inflammasome in cerebral I/R has yet come to a conclusion, and there is still no specific evidence to state the relationship between mitochondria and the NLRP3 inflammasome in cerebral I/R.,In the present study, we detected the cellular localization of NLRP3 inflammasomes in a transient middle cerebral artery occlusion (tMCAO) rat model and a transwell co-culture cell system under oxygen-glucose deprivation/reoxygenation (OGD/R) conditions.,Then, we investigated the relationship between mitochondrial dysfunction and the activation of NLRP3 inflammasomes in different cell types after OGD/R and cerebral I/R injury.,Our results showed that NLRP3 inflammasomes were first activated in microglia soon after cerebral I/R injury onset and then were expressed in neurons and microvascular endothelial cells later, but they were mainly in neurons.,Furthermore, mitochondrial dysfunction played an important role in activating NLRP3 inflammasomes in microglia after OGD/R, and mitochondrial protector could inhibit the activation of NLRP3 inflammasomes in cerebral I/R rats.,Our findings may provide novel insights into the cell type-dependent activation of NLRP3 inflammasomes at different stages of cerebral I/R injury and the role of mitochondrial dysfunction in activating the NLRP3 inflammasome pathway.,The online version of this article (10.1186/s12974-018-1282-6) contains supplementary material, which is available to authorized users.

Acute stroke remains a medical emergency even during the COVID-19 pandemic.,Most patients with COVID-19 infection present with constitutional and respiratory symptoms; while others present with atypical gastrointestinal, cardiovascular, or neurological manifestations.,Here we present a series of four patients with COVID-19 that presented with acute stroke.,We searched the hospital databases for patients that presented with acute stroke and concomitant features of suspected COVID-19 infection.,All patients who had radiographic evidence of stroke and PCR-confirmed COVID-19 infection were included in the study.,Patients admitted to the hospital with PCR- confirmed COVID-19 disease whose hospital course was complicated with acute stroke while inpatient were excluded from the study.,Retrospective patient data were obtained from electronic medical records.,Informed consent was obtained.,We identified four patients who presented with radiographic confirmation of acute stroke and PCR-confirmed SARS-CoV-2 infection.,We elucidate the clinical characteristics, imaging findings, and the clinical course.,Timely assessment and hyperacute treatment is the key to minimize mortality and morbidity of patients with acute stroke.,Stroke teams should be wary of the fact that COVID-19 patients can present with cerebrovascular accidents and should don appropriate personal protective equipment in every suspected patient.,Further studies are urgently needed to improve current understandings of neurological pathology in the setting of COVID-19 infection.

COVID-19 may predispose to both venous and arterial thromboembolism due to excessive inflammation, hypoxia, immobilisation and diffuse intravascular coagulation.,Reports on the incidence of thrombotic complications are however not available.,We evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction or systemic arterial embolism in all COVID-19 patients admitted to the ICU of 2 Dutch university hospitals and 1 Dutch teaching hospital.,We studied 184 ICU patients with proven COVID-19 pneumonia of whom 23 died (13%), 22 were discharged alive (12%) and 139 (76%) were still on the ICU on April 5th 2020.,All patients received at least standard doses thromboprophylaxis.,The cumulative incidence of the composite outcome was 31% (95%CI 20-41), of which CTPA and/or ultrasonography confirmed VTE in 27% (95%CI 17-37%) and arterial thrombotic events in 3.7% (95%CI 0-8.2%).,PE was the most frequent thrombotic complication (n = 25, 81%).,Age (adjusted hazard ratio (aHR) 1.05/per year, 95%CI 1.004-1.01) and coagulopathy, defined as spontaneous prolongation of the prothrombin time > 3 s or activated partial thromboplastin time > 5 s (aHR 4.1, 95%CI 1.9-9.1), were independent predictors of thrombotic complications.,The 31% incidence of thrombotic complications in ICU patients with COVID-19 infections is remarkably high.,Our findings reinforce the recommendation to strictly apply pharmacological thrombosis prophylaxis in all COVID-19 patients admitted to the ICU, and are strongly suggestive of increasing the prophylaxis towards high-prophylactic doses, even in the absence of randomized evidence.