Datasets:

GleghornLab

/

abstract_domain_cvd

like 0

Follow

Gleghorn Lab 8

Previous studies found that low vitamin D levels were modestly associated with risk of stroke and poor functional outcome after stroke.,In addition, vitamin D deficiency has been linked with cognitive decline.,Our study aimed to explore the potential relationship between vitamin D levels in the short-term acute phase of ischemic stroke and cognitive impairment at 1 month.,In total, 354 ischemic stroke patients were consecutively enrolled in the study and received 1-month follow-up.,The serum levels of vitamin D were measured within 24 hours after admission.,Cognitive function was evaluated by the Mini-Mental State Examination (MMSE) at 1 month after acute ischemic stroke.,Cognitive impairment was defined according to different education levels.,According to MMSE scores, 114 participants (32.2%) had cognitive impairment at 1 month.,Patients with vitamin D deficiency were more likely to have cognitive impairment than those with vitamin D insufficiency and vitamin D sufficiency (P<0.001).,After adjusting for potential confounders in our Cox proportional hazards model, vitamin D deficiency was independently associated with the development of cognitive impairment in acute ischemic stroke patients.,Independent of established risk factors, vitamin D deficiency in the short-term phase of ischemic stroke was associated with a higher incidence of 1-month cognitive impairment.

In recent years, accumulating evidence has supported the hypothesis that lower vitamin D status is associated with several known risk factors of stroke.,However, the relationship between vitamin D and stroke is still uncertain.,To explore if there was an association between vitamin D status and the risk of stroke, a systematic review and a meta-analysis were conducted by searching three databases: Pubmed, Embase, and the Cochrane Library.,Following the application of inclusion and exclusion criteria, the relative risk estimates of all the included studies were pooled together to compare the risk of stroke between the lowest and the highest category of vitamin D.,The Newcastle-Ottawa Scale (NOS) and the Cochrane Risk of Bias Tool were used to assess the risk of bias, and the publication bias was detected by using a funnel plot and Egger’s test.,Nineteen studies were included and the pooled relative risk was 1.62 (95% CI: 1.34-1.96).,Further analysis found that vitamin D status was associated with ischemic stroke (relative risk = 2.45, 95% CI: 1.56-3.86), but not with hemorrhagic stroke (relative risk = 2.50, 95% CI: 0.87-7.15).,In conclusion, our meta-analysis supported the hypothesis that lower vitamin D status was associated with an increased risk of ischemic stroke.,Further studies are required to confirm this association and to explore the association among different subtypes.

COVID-19 raises D-dimer (DD) levels even in the absence of pulmonary embolism (PE), resulting in an increase in computed tomography pulmonary angiogram (CTPA) requests.,Our purpose is to determine whether there are differences between DD values in PE-positive and PE-negative COVID-19 patients and, if so, to establish a new cutoff value which accurately determines when a CTPA is needed.,This study retrospectively analyzed all COVID-19 patients who underwent a CTPA due to suspected PE between March 1 and April 30, 2020, at Ramón y Cajal University Hospital, Madrid (Spain).,DD level comparisons between PE-positive and PE-negative groups were made using Student’s t test.,The optimal DD cutoff value to predict PE risk in COVID-19 patients was calculated in the ROC curve.,Two hundred forty-two patients were included in the study.,One hundred fifty-one (62%) were men and the median age was 68 years (IQR 55-78).,An increase of DD (median 3260; IQR 1203-9625 ng/mL) was detected in 205/242 (96%) patients. 73/242 (30%) of the patients were diagnosed with PE on CTPA.,The DD median value was significantly higher (p < .001) in the PE-positive group (7872, IQR 3150-22,494 ng/mL) compared with the PE-negative group (2009, IQR 5675-15,705 ng/mL).,The optimal cutoff value for DD to predict PE was 2903 ng/mL (AUC was 0.76 [CI 95% 0.69-0.83], sensitivity 81%).,The overall mortality rate was 16% (39/242).,A higher threshold (2903 ng/mL) for D-dimer could predict the risk of PE in COVID-19 patients with a sensitivity of 81%.

The aim of this study was to describe clinical, imaging, and laboratory features of acute pulmonary embolism (APE) in patients with COVID-19 associated pneumonia.,Patients with COVID-19 associated pneumonia who underwent a computed tomography pulmonary artery (CTPA) scan for suspected APE were retrospectively studied.,Laboratory data and CTPA images were collected.,Imaging characteristics were analyzed descriptively.,Laboratory data were analyzed and compared between patients with and without APE.,A series of 25 COVID-19 patients who underwent CTPA between January 2020 and February 2020 were enrolled.,The median D-dimer level founded in these 25 patients was 6.06 μg/mL (interquartile range [IQR] 1.90-14.31 μg/mL).,Ten (40%) patients with APE had a significantly higher level of D-dimer (median, 11.07 μg/mL; IQR, 7.12-21.66 vs median, 2.44 μg/mL; IQR, 1.68-8.34, respectively, P = .003), compared with the 15 (60%) patients without APE.,No significant differences in other laboratory data were found between patients with and without APE.,Among the 10 patients with APE, 6 (60%) had a bilateral pulmonary embolism, while 4 had a unilateral embolism.,The thrombus-prone sites were the right lower lobe (70%), the left upper lobe (60%), both upper lobe (40%) and the right middle lobe (20%).,The thrombus was partially or completely absorbed after anticoagulant therapy in 3 patients who underwent a follow-up CTPA.,Patients with COVID-19 associated pneumonia have a risk of developing APE during the disease.,When the D-dimer level abnormally increases in patients with COVID-19 pneumonia, CTPA should be performed to detect and assess the severity of APE.

Coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has rapidly evolved into a sweeping pandemic.,Its major manifestation is in the respiratory tract, and the general extent of organ involvement and the microscopic changes in the lungs remain insufficiently characterised.,Autopsies are essential to elucidate COVID‐19‐associated organ alterations.,This article reports the autopsy findings of 21 COVID‐19 patients hospitalised at the University Hospital Basel and at the Cantonal Hospital Baselland, Switzerland.,An in‐corpore technique was performed to ensure optimal staff safety.,The primary cause of death was respiratory failure with exudative diffuse alveolar damage and massive capillary congestion, often accompanied by microthrombi despite anticoagulation.,Ten cases showed superimposed bronchopneumonia.,Further findings included pulmonary embolism (n = 4), alveolar haemorrhage (n = 3), and vasculitis (n = 1).,Pathologies in other organ systems were predominantly attributable to shock; three patients showed signs of generalised and five of pulmonary thrombotic microangiopathy.,Six patients were diagnosed with senile cardiac amyloidosis upon autopsy.,Most patients suffered from one or more comorbidities (hypertension, obesity, cardiovascular diseases, and diabetes mellitus).,Additionally, there was an overall predominance of males and individuals with blood group A (81% and 65%, respectively).,All relevant histological slides are linked as open‐source scans in supplementary files.,This study provides an overview of postmortem findings in COVID‐19 cases, implying that hypertensive, elderly, obese, male individuals with severe cardiovascular comorbidities as well as those with blood group A may have a lower threshold of tolerance for COVID‐19.,This provides a pathophysiological explanation for higher mortality rates among these patients.

We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals.,In answering questions raised regarding our study, we updated our database and repeated all analyses.,We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.,We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%).,The median follow-up duration increased from 7 to 14 days.,All patients received pharmacological thromboprophylaxis.,The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%).,The majority of thrombotic events were PE (65/75; 87%).,In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92).,Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12).,Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).,In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.

Hypertesion is the leading cause of morbidity and mortality, worldwide, and its prevalence has been increasing in several countries, including Italy.,To assess hypertension prevalence, awareness, treatment, and control in a real-world sample of adults with self-reported diabetes compared with nondiabetic individuals.,Following the 2018 World Hypertension Day, a nationwide, cross-sectional epidemiological survey on cardiovascular risk factors (“Abbasso la Pressione!”),in 3956 Italian pharmacies enrolled 47217 self-presenting volunteers (≥ 18 years).,Participants underwent standardized blood pressure (BP) measurements and answered a questionnaire on cardiovascular risk factors and lifestyle habits.,Questions included if they had an established diagnosis of diabetes, hypertension or were on a BP medication.,Hypertension prevalence was defined as systolic BP ≥ 140 and/or diastolic BP ≥ 90 mmHg.,A double definition for hypertension control based on the recent European and US guidelines on hypertension was applied.,Diabetic individuals (N = 5695, 12%) had higher rates of hypertension prevalence (80% vs.,54.7%, p < 0.001), awareness (85.6% vs 77.3%, p < 0.001) and treatment (85.8% vs.,76.7%, p < 0.001), but lower hypertension control rates (36.1% vs.,39.6% according to the 2018 European guidelines, p < 0.001; 25.4% vs 30.8% according to the 2017 US guidelines, p < 0.001) than nondiabetics.,Diabetic participants tended to be older, sedentary, overweight/obese, dyslipidemic men, with higher 10-years cardiovascular risk than nondiabetics (p < 0.001).,Uncontrolled hypertension was associated with male gender, diabetes, body mass index, unhealthy lifestyle habits, and older age.,Elevated hypertension awareness and treatment rates in diabetic adults do not translate into adequate BP control in the real world.,Concomitant unfavorable metabolic features and unhealthy lifestyle habits might contribute to this observation.

Antihypertensive medicines are effective in reducing adverse cardiovascular events.,Our aim was to compare hypertension awareness, treatment, and control, and how they have changed over time, in high-income countries.,We used data from people aged 40-79 years who participated in 123 national health examination surveys from 1976 to 2017 in 12 high-income countries: Australia, Canada, Finland, Germany, Ireland, Italy, Japan, New Zealand, South Korea, Spain, the UK, and the USA.,We calculated the proportion of participants with hypertension, which was defined as systolic blood pressure of 140 mm Hg or more, or diastolic blood pressure of 90 mm Hg or more, or being on pharmacological treatment for hypertension, who were aware of their condition, who were treated, and whose hypertension was controlled (ie, lower than 140/90 mm Hg).,Data from 526 336 participants were used in these analyses.,In their most recent surveys, Canada, South Korea, Australia, and the UK had the lowest prevalence of hypertension, and Finland the highest.,In the 1980s and early 1990s, treatment rates were at most 40% and control rates were less than 25% in most countries and age and sex groups.,Over the time period assessed, hypertension awareness and treatment increased and control rate improved in all 12 countries, with South Korea and Germany experiencing the largest improvements.,Most of the observed increase occurred in the 1990s and early-mid 2000s, having plateaued since in most countries.,In their most recent surveys, Canada, Germany, South Korea, and the USA had the highest rates of awareness, treatment, and control, whereas Finland, Ireland, Japan, and Spain had the lowest.,Even in the best performing countries, treatment coverage was at most 80% and control rates were less than 70%.,Hypertension awareness, treatment, and control have improved substantially in high-income countries since the 1980s and 1990s.,However, control rates have plateaued in the past decade, at levels lower than those in high-quality hypertension programmes.,There is substantial variation across countries in the rates of hypertension awareness, treatment, and control.,Wellcome Trust and WHO.

This study aimed to develop and validate deep-learning-based artificial intelligence algorithm for predicting mortality of AHF (DAHF).,12,654 dataset from 2165 patients with AHF in two hospitals were used as train data for DAHF development, and 4759 dataset from 4759 patients with AHF in 10 hospitals enrolled to the Korean AHF registry were used as performance test data.,The endpoints were in-hospital, 12-month, and 36-month mortality.,We compared the DAHF performance with the Get with the Guidelines-Heart Failure (GWTG-HF) score, Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score, and other machine-learning models by using the test data.,Area under the receiver operating characteristic curve of the DAHF were 0.880 (95% confidence interval, 0.876-0.884) for predicting in-hospital mortality; these results significantly outperformed those of the GWTG-HF (0.728 [0.720-0.737]) and other machine-learning models.,For predicting 12- and 36-month endpoints, DAHF (0.782 and 0.813) significantly outperformed MAGGIC score (0.718 and 0.729).,During the 36-month follow-up, the high-risk group, defined by the DAHF, had a significantly higher mortality rate than the low-risk group(p<0.001).,DAHF predicted the in-hospital and long-term mortality of patients with AHF more accurately than the existing risk scores and other machine-learning models.

Whereas heart failure (HF) is a complex clinical syndrome, conventional approaches to its management have treated it as a singular disease, leading to inadequate patient care and inefficient clinical trials.,We hypothesized that applying advanced analytics to a large cohort of HF patients would improve prognostication of outcomes, identify distinct patient phenotypes, and detect heterogeneity in treatment response.,The Swedish Heart Failure Registry is a nationwide registry collecting detailed demographic, clinical, laboratory, and medication data and linked to databases with outcome information.,We applied random forest modeling to identify predictors of 1‐year survival.,Cluster analysis was performed and validated using serial bootstrapping.,Association between clusters and survival was assessed with Cox proportional hazards modeling and interaction testing was performed to assess for heterogeneity in response to HF pharmacotherapy across propensity‐matched clusters.,Our study included 44 886 HF patients enrolled in the Swedish Heart Failure Registry between 2000 and 2012.,Random forest modeling demonstrated excellent calibration and discrimination for survival (C‐statistic=0.83) whereas left ventricular ejection fraction did not (C‐statistic=0.52): there were no meaningful differences per strata of left ventricular ejection fraction (1‐year survival: 80%, 81%, 83%, and 84%).,Cluster analysis using the 8 highest predictive variables identified 4 clinically relevant subgroups of HF with marked differences in 1‐year survival.,There were significant interactions between propensity‐matched clusters (across age, sex, and left ventricular ejection fraction and the following medications: diuretics, angiotensin‐converting enzyme inhibitors, β‐blockers, and nitrates, P<0.001, all).,Machine learning algorithms accurately predicted outcomes in a large data set of HF patients.,Cluster analysis identified 4 distinct phenotypes that differed significantly in outcomes and in response to therapeutics.,Use of these novel analytic approaches has the potential to enhance effectiveness of current therapies and transform future HF clinical trials.

Patients with COVID-19 seem to be prone to the development of arrhythmias.,The objective of this trial was to determine the characteristics, clinical significance and therapeutic consequences of these arrhythmias in COVID-19 patients requiring intensive care unit (ICU) treatment.,A total of 113 consecutive patients (mean age 64.1 ± 14.3 years, 30 (26.5%) female) with positive PCR testing for SARS-CoV2 as well as radiographically confirmed pulmonary involvement admitted to the ICU from March to May 2020 were included and observed for a cumulative time of 2321 days.,Fifty episodes of sustained atrial tachycardias, five episodes of sustained ventricular arrhythmias and thirty bradycardic events were documented.,Sustained new onset atrial arrhythmias were associated with hemodynamic deterioration in 13 cases (35.1%).,Patients with new onset atrial arrhythmias were older, showed higher levels of Hs-Troponin and NT-proBNP, and a more severe course of disease.,The 5 ventricular arrhythmias (two ventricular tachycardias, two episodes of ventricular fibrillation, and one torsade de pointes tachycardia) were observed in 4 patients.,All episodes could be terminated by immediate defibrillation/cardioversion.,Five bradycardic events were associated with hemodynamic deterioration.,Precipitating factors could be identified in 19 of 30 episodes (63.3%), no patient required cardiac pacing.,Baseline characteristics were not significantly different between patients with or without bradycardic events.,Relevant arrhythmias are common in severely ill ICU patients with COVID-19.,They are associated with worse courses of disease and require specific treatment.,This makes daily close monitoring of telemetric data mandatory in this patient group.

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.

Supplemental Digital Content is available in the text.,We aimed to investigate the acute stroke presentations during the coronavirus disease 2019 (COVID-19) pandemic.,The data were obtained from a health system with 19 emergency departments in northeast Ohio in the United States.,Baseline period from January 1 to March 8, 2020, was compared with the COVID period from March 9, to April 2, 2020.,The variables included were total daily stroke alerts across the hospital emergency departments, thrombolysis, time to presentation, stroke severity, time from door-to-imaging, time from door-to-needle in thrombolysis, and time from door-to-puncture in thrombectomy.,The 2 time periods were compared using nonparametric statistics and Poisson regression.,Nine hundred two stroke alerts during the period across the emergency departments were analyzed.,Total daily stroke alerts decreased from median, 10 (interquartile range, 8-13) during baseline period to median, 8 (interquartile range, 4-10, P=0.001) during COVID period.,Time to presentation, stroke severity, and time to treatment were unchanged.,COVID period was associated with decrease in stroke alerts with rate ratio of 0.70 (95% CI, 0.60-0.28).,Thrombolysis also decreased with rate ratio, 0.52 (95% CI, 0.28-0.97) but thrombectomy remained unchanged rate ratio, 0.93 (95% CI, 0.52-1.62),We observed a significant decrease in acute stroke presentations by ≈30% across emergency departments at the time of surge of COVID-19 cases.,This observation could be attributed to true decline in stroke incidence or patients not seeking medical attention for emergencies during the pandemic.

A high incidence of thrombotic events, particularly deep vein thrombosis and pulmonary embolism, has been clearly documented in COVID-19 patients.,In addition, small series of patients with coronary, cerebrovascular and peripheral arterial thrombotic events have also been reported, but their true incidence and consequences are not well described, and constitute the objective of this study.,From February 1st to April 21st, 2020, 2115 COVID-19 patients were treated at Hospital Universitario Fundación Alcorcón (Madrid, Spain), and 1419 were eventually admitted.,Patient characteristics and outcomes were collected by reviewing their electronic medical records.,Fourteen patients had a systemic arterial thrombotic event, which represents a 1% incidence in relation to the total number of hospitalized patients.,Three patients suffered an acute coronary syndrome, two with persistent ST-segment elevation, one of whom was treated invasively, and one with transient ST-segment elevation.,Eight patients had a cerebrovascular event.,Six suffered an acute ischemic stroke and two a transient ischemic attack, 50% of them had a Rankin score ≥ 3 at discharge.,Three additional patients had a limb thrombotic event, all of them infrapopliteal, and were managed conservatively.,All three cases developed necrosis of the toes, two of them with bilateral involvement.,The hospitalization death rate of patients with an arterial event was 28.6%.,Although COVID-19 may favor the occurrence of thrombotic events, the destabilization and thrombosis of arterial atherosclerotic plaques do not seem to be a frequent mechanism which warrants the need for specific systematic preventive measures.

Diabetic retinopathy is a common complication of diabetes mellitus, which appears in one third of all diabetic patients and is a prominent cause of vision loss.,First discovered as a microvascular disease, intensive research in the field identified inflammation and neurodegeneration to be part of diabetic retinopathy.,Microglia, the resident monocytes of the retina, are activated due to a complex interplay between the different cell types of the retina and diverse pathological pathways.,The trigger for developing diabetic retinopathy is diabetes-induced hyperglycemia, accompanied by leukostasis and vascular leakages.,Transcriptional changes in activated microglia, mediated via the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) and extracellular signal-regulated kinase (ERK) signaling pathways, results in release of various pro-inflammatory mediators, including cytokines, chemokines, caspases and glutamate.,Activated microglia additionally increased proliferation and migration.,Among other consequences, these changes in microglia severely affected retinal neurons, causing increased apoptosis and subsequent thinning of the nerve fiber layer, resulting in visual loss.,New potential therapeutics need to interfere with these diabetic complications even before changes in the retina are diagnosed, to prevent neuronal apoptosis and blindness in patients.

Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and is the leading cause of blindness in young adults.,Oxidative stress has been implicated as a critical cause of DR.,Metabolic abnormalities induced by high-glucose levels are involved in the development of DR and appear to be influenced by oxidative stress.,The imbalance between reactive oxygen species (ROS) production and the antioxidant defense system activates several oxidative stress-related mechanisms that promote the pathogenesis of DR.,The damage caused by oxidative stress persists for a considerable time, even after the blood glucose concentration has returned to a normal level.,Animal experiments have proved that the use of antioxidants is a beneficial therapeutic strategy for the treatment of DR, but more data are required from clinical trials.,The aims of this review are to highlight the improvements to our understanding of the oxidative stress-related mechanisms underlying the development of DR and provide a summary of the main antioxidant therapy strategies used to treat the disease.

A high incidence of thrombotic events, particularly deep vein thrombosis and pulmonary embolism, has been clearly documented in COVID-19 patients.,In addition, small series of patients with coronary, cerebrovascular and peripheral arterial thrombotic events have also been reported, but their true incidence and consequences are not well described, and constitute the objective of this study.,From February 1st to April 21st, 2020, 2115 COVID-19 patients were treated at Hospital Universitario Fundación Alcorcón (Madrid, Spain), and 1419 were eventually admitted.,Patient characteristics and outcomes were collected by reviewing their electronic medical records.,Fourteen patients had a systemic arterial thrombotic event, which represents a 1% incidence in relation to the total number of hospitalized patients.,Three patients suffered an acute coronary syndrome, two with persistent ST-segment elevation, one of whom was treated invasively, and one with transient ST-segment elevation.,Eight patients had a cerebrovascular event.,Six suffered an acute ischemic stroke and two a transient ischemic attack, 50% of them had a Rankin score ≥ 3 at discharge.,Three additional patients had a limb thrombotic event, all of them infrapopliteal, and were managed conservatively.,All three cases developed necrosis of the toes, two of them with bilateral involvement.,The hospitalization death rate of patients with an arterial event was 28.6%.,Although COVID-19 may favor the occurrence of thrombotic events, the destabilization and thrombosis of arterial atherosclerotic plaques do not seem to be a frequent mechanism which warrants the need for specific systematic preventive measures.

This case series reports a systematic assessment of deep vein thrombosis among patients in an intensive care unit in France with severe coronavirus disease 2019 (COVID-19).

A high incidence of thrombotic events, particularly deep vein thrombosis and pulmonary embolism, has been clearly documented in COVID-19 patients.,In addition, small series of patients with coronary, cerebrovascular and peripheral arterial thrombotic events have also been reported, but their true incidence and consequences are not well described, and constitute the objective of this study.,From February 1st to April 21st, 2020, 2115 COVID-19 patients were treated at Hospital Universitario Fundación Alcorcón (Madrid, Spain), and 1419 were eventually admitted.,Patient characteristics and outcomes were collected by reviewing their electronic medical records.,Fourteen patients had a systemic arterial thrombotic event, which represents a 1% incidence in relation to the total number of hospitalized patients.,Three patients suffered an acute coronary syndrome, two with persistent ST-segment elevation, one of whom was treated invasively, and one with transient ST-segment elevation.,Eight patients had a cerebrovascular event.,Six suffered an acute ischemic stroke and two a transient ischemic attack, 50% of them had a Rankin score ≥ 3 at discharge.,Three additional patients had a limb thrombotic event, all of them infrapopliteal, and were managed conservatively.,All three cases developed necrosis of the toes, two of them with bilateral involvement.,The hospitalization death rate of patients with an arterial event was 28.6%.,Although COVID-19 may favor the occurrence of thrombotic events, the destabilization and thrombosis of arterial atherosclerotic plaques do not seem to be a frequent mechanism which warrants the need for specific systematic preventive measures.

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.

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.

Thrombosis and inflammation may contribute to morbidity and mortality among patients with coronavirus disease 2019 (Covid-19).,We hypothesized that therapeutic-dose anticoagulation would improve outcomes in critically ill patients with Covid-19.,In an open-label, adaptive, multiplatform, randomized clinical trial, critically ill patients with severe Covid-19 were randomly assigned to a pragmatically defined regimen of either therapeutic-dose anticoagulation with heparin or pharmacologic thromboprophylaxis in accordance with local usual care.,The primary outcome was organ support-free days, evaluated on an ordinal scale that combined in-hospital death (assigned a value of −1) and the number of days free of cardiovascular or respiratory organ support up to day 21 among patients who survived to hospital discharge.,The trial was stopped when the prespecified criterion for futility was met for therapeutic-dose anticoagulation.,Data on the primary outcome were available for 1098 patients (534 assigned to therapeutic-dose anticoagulation and 564 assigned to usual-care thromboprophylaxis).,The median value for organ support-free days was 1 (interquartile range, −1 to 16) among the patients assigned to therapeutic-dose anticoagulation and was 4 (interquartile range, −1 to 16) among the patients assigned to usual-care thromboprophylaxis (adjusted proportional odds ratio, 0.83; 95% credible interval, 0.67 to 1.03; posterior probability of futility [defined as an odds ratio <1.2], 99.9%).,The percentage of patients who survived to hospital discharge was similar in the two groups (62.7% and 64.5%, respectively; adjusted odds ratio, 0.84; 95% credible interval, 0.64 to 1.11).,Major bleeding occurred in 3.8% of the patients assigned to therapeutic-dose anticoagulation and in 2.3% of those assigned to usual-care pharmacologic thromboprophylaxis.,In critically ill patients with Covid-19, an initial strategy of therapeutic-dose anticoagulation with heparin did not result in a greater probability of survival to hospital discharge or a greater number of days free of cardiovascular or respiratory organ support than did usual-care pharmacologic thromboprophylaxis.,(REMAP-CAP, ACTIV-4a, and ATTACC ClinicalTrials.gov numbers, NCT02735707, NCT04505774, NCT04359277, and NCT04372589.)

Cardiac fibroblasts are the primary cell type responsible for deposition of extracellular matrix in the heart, providing support to the contracting myocardium and contributing to a myriad of physiological signaling processes.,Despite the importance of fibrosis in processes of wound healing, excessive fibroblast proliferation and activation can lead to pathological remodeling, driving heart failure and the onset of arrhythmias.,Our understanding of the mechanisms driving the cardiac fibroblast activation and proliferation is expanding, and evidence for their direct and indirect effects on cardiac myocyte function is accumulating.,In this review, we focus on the importance of the fibroblast‐to‐myofibroblast transition and the cross talk of cardiac fibroblasts with cardiac myocytes.,We also consider the current use of models used to explore these questions.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in humans.,Several risk factors promote AF, among which diabetes mellitus has emerged as one of the most important.,The growing recognition that obesity, diabetes and AF are closely intertwined disorders has spurred major interest in uncovering their mechanistic links.,In this article we provide an update on the growing evidence linking oxidative stress and inflammation to adverse atrial structural and electrical remodeling that leads to the onset and maintenance of AF in the diabetic heart.,We then discuss several therapeutic strategies to improve atrial excitability by targeting pathways that control oxidative stress and inflammation.

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.

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.

This study investigated continued and discontinued use of angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) during hospitalization of 614 hypertensive laboratory-confirmed COVID-19 patients.,Demographics, comorbidities, vital signs, laboratory data, and ACEi/ARB usage were analyzed.,To account for confounders, patients were substratified by whether they developed hypotension and acute kidney injury (AKI) during the index hospitalization.,Mortality (22% vs 17%, P > .05) and intensive care unit (ICU) admission (26% vs 12%, P > .05) rates were not significantly different between non-ACEi/ARB and ACEi/ARB groups.,However, patients who continued ACEi/ARBs in the hospital had a markedly lower ICU admission rate (12% vs 26%; P = .001; odds ratio [OR] = 0.347; 95% confidence interval [CI], .187-.643) and mortality rate (6% vs 28%; P = .001; OR = 0.215; 95% CI, .101-.455) compared to patients who discontinued ACEi/ARB.,The odds ratio for mortality remained significantly lower after accounting for development of hypotension or AKI.,These findings suggest that continued ACEi/ARB use in hypertensive COVID-19 patients yields better clinical outcomes.,In hypertensive patients with COVID-19, in-hospital continuation of ACE inhibitors or ARBs is associated with lower rates of mortality and intensive care admission in the absence of hypotension or acute kidney injury.

To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease.,To assess the association between renin-angiotensin system inhibitors (RASIs) and disease progression and critical outcomes.,All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study.,The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission.,Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint.,Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2.,Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32-54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61-84)].,A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU.,Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age.,After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02-2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class.,This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents.,We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome.,Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.

Hypercoagulability and thromboembolism are prominent features of severe COVID‐19, and ongoing anticoagulant use might be protective.,We conducted a nationwide register‐based cohort study in Sweden, February through May, 2020, to assess whether ongoing direct oral anticoagulant (DOAC) use was associated with reduced risk of hospital admission for laboratory‐confirmed COVID‐19, or a composite of intensive care unit (ICU) admission or death due to laboratory‐confirmed COVID‐19.,DOAC use (n = 103 703) was not associated with reduced risk of hospital admission for COVID‐19 (adjusted hazard ratio [aHR] [95% confidence interval] 1.00 [0.75-1.33] vs. nonuse atrial fibrillation comparator [n = 36 875]; and aHR 0.94 [0.80-1.10] vs. nonuse cardiovascular disease comparator [n = 355 699]), or ICU admission or death due to COVID‐19 (aHRs 0.76 [0.51-1.12], and 0.90 [0.71-1.15], respectively).,Ongoing DOAC use was not associated with reduced risk of severe COVID‐19, indicating that prognosis would not be modified by early outpatient DOAC initiation.

The recent emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the ensuing global pandemic has presented a health emergency of unprecedented magnitude.,Recent clinical data has highlighted that coronavirus disease 2019 (COVID-19) is associated with a significant risk of thrombotic complications ranging from microvascular thrombosis, venous thromboembolic disease, and stroke.,Importantly, thrombotic complications are markers of severe COVID-19 and are associated with multiorgan failure and increased mortality.,The evidence to date supports the concept that the thrombotic manifestations of severe COVID-19 are due to the ability of SARS-CoV-2 to invade endothelial cells via ACE-2 (angiotensin-converting enzyme 2), which is expressed on the endothelial cell surface.,However, in patients with COVID-19 the subsequent endothelial inflammation, complement activation, thrombin generation, platelet, and leukocyte recruitment, and the initiation of innate and adaptive immune responses culminate in immunothrombosis, ultimately causing (micro)thrombotic complications, such as deep vein thrombosis, pulmonary embolism, and stroke.,Accordingly, the activation of coagulation (eg, as measured with plasma D-dimer) and thrombocytopenia have emerged as prognostic markers in COVID-19.,Given thrombotic complications are central determinants of the high mortality rate in COVID-19, strategies to prevent thrombosis are of critical importance.,Several antithrombotic drugs have been proposed as potential therapies to prevent COVID-19-associated thrombosis, including heparin, FXII inhibitors, fibrinolytic drugs, nafamostat, and dipyridamole, many of which also possess pleiotropic anti-inflammatory or antiviral effects.,The growing awareness and mechanistic understanding of the prothrombotic state of COVID-19 patients are driving efforts to more stringent diagnostic screening for thrombotic complications and to the early institution of antithrombotic drugs, for both the prevention and therapy of thrombotic complications.,The shifting paradigm of diagnostic and treatment strategies holds significant promise to reduce the burden of thrombotic complications and ultimately improve the prognosis for patients with COVID-19.

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.

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.

It is unknown if there are cardiac abnormalities in participants recovered from COVID-19 without cardiac symptoms and those who have normal biomarkers and normal ECGs.,To evaluate cardiac involvement in participants recovered from COVID-19 without clinical evidence of cardiac involvement using cardiac MRI,In this prospective observational cohort study, 40 participants recovered from COVID-19 with moderate(n=24) or severe(n=16) pneumonia and no cardiovascular medical history, without cardiac symptoms, with normal ECG, normal serological cardiac enzyme levels, and discharged > 90 days between May and September 2020.,Demographic characteristics, serum cardiac enzymes, and cardiac MRI were obtained.,Cardiac function, native T1, ECV and Two-dimensional (2D) strain were quantitatively evaluated and compared with controls (n = 25).,The Comparison among the 3 groups were performed using one-way analysis of variance (ANOVA) with Bonferroni corrected post-hoc comparisons(for normal distribution) or Kruskal-Wallis tests with post-hoc pairwise comparisons(for non-normal distribution).,Forty participants (54±12 years; 24 men) enrolled with a mean time between admission and CMR of 158 ±18 days and discharge and CMR examination of 124 ±17 days.,There was no LV and RV size or functional differences among participants recovered from COVID-19 and healthy controls.,Only one (3%) participants had positive LGE located at the mid inferior wall.,Global ECV values were elevated in both participants recovered from COVID-19 with moderate or severe pneumonia, compared to the healthy controls [median ECV (IQR)], [29.7% (28.0%-32.9%), versus 31.4% (29.3%-34.0%), versus 25.0% (23.7%-26.0%); both p<.001].,The 2D-global LV longitudinal stains (GLS) were reduced in both groups of participants [COVID-19 moderate group,-12.5%(-10.7%--15.5%), COVID-19 severe group, -12.5%(-8.7%--15.4%) compared to healthy control group -15.4%(-14.6%-17.6%), p=.002 and p=.001, respectively].,CMR myocardial tissue and strain imaging parameters suggest that a proportion of participants recovered from COVID-19 had subclinical myocardial abnormalities detectable months after recovery.

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.

This cross-sectional study compares trends in out-of-hospital cardiac arrests and fatalities in the Detroit area during the COVID-19 pandemic with year-earlier events for the same period.

The purpose of this study was to evaluate the potential impact of the coronavirus disease-2019 (COVID-19) pandemic on out-of-hospital cardiac arrest (OHCA) responses and outcomes in 2 U.S. communities with relatively low infection rates.,Studies in areas with high COVID-19 infection rates indicate that the pandemic has had direct and indirect effects on community responses to OHCA and negative impacts on survival.,Data from areas with lower infection rates are lacking.,Cases of OHCA in Multnomah County, Oregon, and Ventura County, California, with attempted resuscitation by emergency medical services (EMS) from March 1 to May 31, 2020, and from March 1 to May 31, 2019, were evaluated.,In a comparison of 231 OHCA in 2019 to 278 in 2020, the proportion of cases receiving bystander cardiopulmonary resuscitation (CPR) was lower in 2020 (61% to 51%, respectively; p = 0.02), and bystander use of automated external defibrillators (AEDs) declined (5% to 1%, respectively; p = 0.02).,EMS response time increased (6.6 ± 2.0 min to 7.6 ± 3.0 min, respectively; p < 0.001), and fewer OHCA cases survived to hospital discharge (14.7% to 7.9%, respectively; p = 0.02).,Incidence rates did not change significantly (p > 0.07), and coronavirus infection rates were low (Multnomah County, 143/100,000; Ventura County, 127/100,000 as of May 31) compared to rates of ∼1,600 to 3,000/100,000 in the New York City region at that time.,The community response to OHCA was altered from March to May 2020, with less bystander CPR, delays in EMS response time, and reduced survival from OHCA.,These results highlight the pandemic’s indirect negative impact on OHCA, even in communities with relatively low incidence of COVID-19 infection, and point to potential opportunities for countering the impact.

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.

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.

Children presenting with hypertrophic cardiomyopathy (HCM) in infancy are reported to have a poor prognosis, but this heterogeneous group has not been systematically characterized.,This study aimed to describe the aetiology, phenotype, and outcomes of infantile HCM in a well‐characterized multicentre European cohort.,Of 301 children diagnosed with infantile HCM between 1987 and 2019 presenting to 17 European centres [male n = 187 (62.1%)], underlying aetiology was non‐syndromic (n = 138, 45.6%), RASopathy (n = 101, 33.6%), or inborn error of metabolism (IEM) (n = 49, 16.3%).,The most common reasons for presentation were symptoms (n = 77, 29.3%), which were more prevalent in those with syndromic disease (n = 62, 61.4%, P < 0.001), and an isolated murmur (n = 75, 28.5%).,One hundred and sixty‐one (53.5%) had one or more co‐morbidities.,Genetic testing was performed in 163 (54.2%) patients, with a disease‐causing variant identified in 115 (70.6%).,Over median follow‐up of 4.1 years, 50 (16.6%) underwent one or more surgical interventions; 15 (5.0%) had an arrhythmic event (6 in the first year of life); and 48 (15.9%) died, with an overall 5 year survival of 85%.,Predictors of all‐cause mortality were an underlying diagnosis of IEM [hazard ratio (HR) 4.4, P = 0.070], cardiac symptoms (HR 3.2, P = 0.005), and impaired left ventricular systolic function (HR 3.0, P = 0.028).,This large, multicentre study of infantile HCM describes a complex cohort of patients with a diverse phenotypic spectrum and clinical course.,Although overall outcomes were poor, this was largely related to underlying aetiology emphasizing the importance of comprehensive aetiological investigations, including genetic testing, in infantile HCM.

Childhood-onset hypertrophic cardiomyopathy (HCM) is far less common than adult-onset disease, thus natural history is not well characterized.,We aim to describe the characteristics and outcomes of childhood-onset HCM.,We performed an observational cohort study of 7677 HCM patients from the Sarcomeric Human Cardiomyopathy Registry (SHaRe).,Hypertrophic cardiomyopathy patients were stratified by age at diagnosis [<1 year (infancy), 1-18 years (childhood), >18 years (adulthood)] and assessed for composite endpoints reflecting heart failure (HF), life-threatening ventricular arrhythmias, atrial fibrillation (AF), and an overall composite that also included stroke and death.,Stratifying by age of diagnosis, 184 (2.4%) patients were diagnosed in infancy; 1128 (14.7%) in childhood; and 6365 (82.9%) in adulthood.,Childhood-onset HCM patients had an ∼2%/year event rate for the overall composite endpoint, with ventricular arrhythmias representing the most common event in the 1st decade following baseline visit, but HF and AF becoming more common by the end of the 2nd decade.,Sarcomeric variants were more common in childhood-onset HCM (63%) and carried a worse prognosis than non-sarcomeric disease, including a greater than two-fold increased risk of HF [HRadj 2.39 (1.36-4.20), P = 0.003] and 67% increased risk of the overall composite outcome [HRadj 1.67 (1.16-2.41), P = 0.006].,When compared with adult-onset HCM, childhood-onset was 36% more likely to develop life-threatening ventricular arrhythmias [HRadj 1.36 (1.03-1.80)] and twice as likely to require transplant or ventricular assist device [HRadj 1.99 (1.23-3.23)].,Patients with childhood-onset HCM are more likely to have sarcomeric disease, carry a higher risk of life-threatening ventricular arrythmias, and have greater need for advanced HF therapies.,These findings provide insight into the natural history of disease and can help inform clinical risk stratification.,Natural history of sarcomeric HCM may differ depending on age of diagnosis with HCM.,Natural history of sarcomeric HCM may differ depending on age of diagnosis with HCM.

We recently reported a high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 admitted to the intensive care units (ICUs) of three Dutch hospitals.,In answering questions raised regarding our study, we updated our database and repeated all analyses.,We re-evaluated the incidence of the composite outcome of symptomatic acute pulmonary embolism (PE), deep-vein thrombosis, ischemic stroke, myocardial infarction and/or systemic arterial embolism in all COVID-19 patients admitted to the ICUs of 2 Dutch university hospitals and 1 Dutch teaching hospital from ICU admission to death, ICU discharge or April 22nd 2020, whichever came first.,We studied the same 184 ICU patients as reported on previously, of whom a total of 41 died (22%) and 78 were discharged alive (43%).,The median follow-up duration increased from 7 to 14 days.,All patients received pharmacological thromboprophylaxis.,The cumulative incidence of the composite outcome, adjusted for competing risk of death, was 49% (95% confidence interval [CI] 41-57%).,The majority of thrombotic events were PE (65/75; 87%).,In the competing risk model, chronic anticoagulation therapy at admission was associated with a lower risk of the composite outcome (Hazard Ratio [HR] 0.29, 95%CI 0.091-0.92).,Patients diagnosed with thrombotic complications were at higher risk of all-cause death (HR 5.4; 95%CI 2.4-12).,Use of therapeutic anticoagulation was not associated with all-cause death (HR 0.79, 95%CI 0.35-1.8).,In this updated analysis, we confirm the very high cumulative incidence of thrombotic complications in critically ill patients with COVID-19 pneumonia.

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 Lombardy region suffered severely during the acute phase of the coronavirus disease 2019 outbreak in Italy (Mar-Apr 2020) with 16,000 diagnosed coronavirus disease 2019-related deaths (49% of the total coronavirus disease 2019-related deaths in Italy).,In the area surrounding Pavia during the critical stage of the outbreak (Mar-Apr 2020), 1,225 of the documented 4,200 deaths were related to coronavirus disease 2019 infection, with a mortality rate of 181/100,000 inhabitants and an increase in deaths of 138% compared with the same period during previous years.,Our aim was to report the experience of the Department of Vascular Surgery of Pavia (Lombardy, Italy), including the lessons learned and future perspectives regarding the management of coronavirus disease 2019 patients who developed severe acute ischemia with impending lower limb loss or deep vein thrombosis.,We carried out a retrospective data collection of coronavirus disease 2019 patients with severe acute ischemia of the lower limbs or deep vein thrombosis, which we observed in our department during the period March 1, 2020, to April 30, 2020.,Primary outcomes of the analysis were postoperative mortality for all patients and amputation rates only in those coronavirus disease 2019 patients suffering from acute lower limb ischemia.,Secondary outcomes were the prevalence of the disease among admitted coronavirus disease 2019 patients, and any possible correlation among inflammatory parameters, thrombolytic status, and the presence of acute ischemia or deep vein thrombosis.,We observed 38 patients (28 male) with severe coronavirus disease 2019 infection (6 with lower limb arterial thrombosis and 32 with deep vein thrombosis).,The median patient age was 64 years (range 30-94 y).,In the arterial group, 3 had thrombosis on plaque and 3 on healthy arteries (“simple” arterial thrombosis).,All underwent operative or hybrid (open/endo) revascularization; 1 patient died from major organ failure and 1 patient underwent major amputation.,In the deep vein thrombosis group, 9 (28%) patients died from major organ failure, despite aggressive medical therapy.,In patients with simple arterial thrombosis and those with deep vein thrombosis, we observed a decrease in inflammatory parameters (C-reactive protein) and in D-dimer and fibrinogen after aggressive therapy (P <.001).,Our study confirms that critically ill, coronavirus disease 2019 patients who develop arterial and deep vein thrombosis have a high risk of mortality, but, if treated properly, there is an improvement in overall survival, especially in patients of 60 years of age or younger.

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.

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.

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.

A patient with coronavirus disease 19 (COVID‐19) developed acute myocardial infarction (AMI) complicated by extensive coronary thrombosis and cardiogenic shock.,She underwent percutaneous coronary intervention and placement of a mechanical circulatory support device but subsequently died from shock.,This report illustrates the challenges in managing patients with COVID‐19, AMI, and cardiogenic shock.

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.

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.

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 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.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects host cells through ACE2 receptors, leading to coronavirus disease (COVID-19)-related pneumonia, while also causing acute myocardial injury and chronic damage to the cardiovascular system.,Therefore, particular attention should be given to cardiovascular protection during treatment for COVID-19.

Previous reports suggest that the use of angiotensin‐converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) may upregulate angiotensin‐converting enzyme 2 receptors and increase severe acute respiratory syndrome coronavirus 2 infectivity.,We evaluated the association between ACEI or ARB use and coronavirus disease 2019 (COVID‐19) infection among patients with hypertension.,We identified patients with hypertension as of March 1, 2020 (index date) from Kaiser Permanente Southern California.,Patients who received ACEIs, ARBs, calcium channel blockers, beta blockers, thiazide diuretics (TD), or no therapy were identified using outpatient pharmacy data covering the index date.,Outcome of interest was a positive reverse transcription polymerase chain reaction test for COVID‐19 between March 1 and May 6, 2020.,Patient sociodemographic and clinical characteristics were identified within 1 year preindex date.,Among 824 650 patients with hypertension, 16 898 (2.0%) were tested for COVID‐19.,Of those tested, 1794 (10.6%) had a positive result.,Overall, exposure to ACEIs or ARBs was not statistically significantly associated with COVID‐19 infection after propensity score adjustment (odds ratio [OR], 1.06; 95% CI, 0.90-1.25) for ACEIs versus calcium channel blockers/beta blockers/TD; OR, 1.10; 95% CI, 0.91-1.31 for ARBs versus calcium channel blockers/beta blockers/TD).,The associations between ACEI use and COVID‐19 infection varied in different age groups (P‐interaction=0.03).,ACEI use was associated with lower odds of COVID‐19 among those aged ≥85 years (OR, 0.30; 95% CI, 0.12-0.77).,Use of no antihypertensive medication was significantly associated with increased odds of COVID‐19 infection compared with calcium channel blockers/beta blockers/TD (OR, 1.32; 95% CI, 1.11-1.56).,Neither ACEI nor ARB use was associated with increased likelihood of COVID‐19 infection.,Decreased odds of COVID‐19 infection among adults ≥85 years using ACEIs warrants further investigation.

Association of renin-angiotensin system inhibitors with risk of death in patients with hypertension (HTN) and coronavirus disease 2019 (COVID-19) is not well characterized.,The aim of this study was to evaluate the outcomes of patients with HTN and COVID-19 with respect to different chronic antihypertensive drug intake.,We performed a retrospective, observational study from a large cohort of patients with HTN and with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection admitted to the Emergency Rooms (ER) of the Piacenza Hospital network from February 21, 2020 to March 20, 2020.,There were 1050 patients admitted to the ERs of the Piacenza Hospital network with COVID-19.,HTN was present in 590 patients [median age, 76.2 years (IQR 68.2-82.6)]; 399 (66.1%) patients were male.,Of them, 248 patients were chronically treated with ACEi, 181 with ARBs, and 161 with other drugs (O-drugs) including beta blockers, diuretics and calcium-channel inhibitors.,With respect to the antihypertensive use, there was no difference between comorbid conditions.,During a follow-up of 38 days (IQR 7.0-46.0), 256 patients (43.4%) died, without any difference stratifying for antihypertensive drugs.,Of them, 107 (43.1%) were in ACEi group vs 67 (37%) in ARBs group vs 82 (50.7%) in O-drugs group, (log-rank test: p = 0.066).,In patients with HTN and COVID-19, neither ACEi nor ARBs were independently associated with mortality.,After adjusting for potential confounders in risk prediction, the rate of death was similar.,Our data confirm Specialty Societal recommendations, suggesting that treatment with ACEIs or ARBs should not be discontinued because of COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic brought about abrupt changes in the way health care is delivered, and the impact of transitioning outpatient clinic visits to telehealth visits on processes of care and outcomes is unclear.,We evaluated ordering patterns during cardiovascular telehealth clinic visits in the Duke University Health System between March 15 and June 30, 2020 and 30-day outcomes compared with in-person visits in the same time frame in 2020 and in 2019.,Within the Duke University Health System, there was a 33.1% decrease in the number of outpatient cardiovascular visits conducted in the first 15 weeks of the COVID-19 pandemic, compared with the same time period in 2019.,As a proportion of total visits initially booked, 53% of visits were cancelled in 2020 compared to 35% in 2019.,However, patients with cancelled visits had similar demographics and comorbidities in 2019 and 2020.,Telehealth visits comprised 9.3% of total visits initially booked in 2020, with younger and healthier patients utilizing telehealth compared with those utilizing in-person visits.,Compared with in-person visits in 2020, telehealth visits were associated with fewer new (31.6% for telehealth vs 44.6% for in person) or refill (12.9% vs 15.6%, respectively) medication prescriptions, electrocardiograms (4.3% vs 31.4%), laboratory orders (5.9% vs 21.8%), echocardiograms (7.3% vs 98%), and stress tests (4.4% vs 6.6%).,When adjusted for age, race, and insurance status, those who had a telehealth visit or cancelled their visit were less likely to have an emergency department or hospital encounter within 30 days compared with those who had in-person visits (adjusted rate ratios (aRR) 0.76 [95% 0.65, 0.89] and aRR 0.71 [95% 0.65, 0.78], respectively).,In response to the perceived risks of routine medical care affected by the COVID-19 pandemic, different phenotypes of patients chose different types of outpatient cardiology care.,A better understanding of these differences could help define necessary and appropriate mode of care for cardiology patients.

To examine the impact of COVID‐19 on acute heart failure (AHF) hospitalization rates, clinical characteristics and management of patients admitted to a tertiary Heart Failure Unit in London during the peak of the pandemic.,Data from King's College Hospital, London, reported to the National Heart Failure Audit for England and Wales, between 2 March-19 April 2020 were compared both to a pre‐COVID cohort and the corresponding time periods in 2017 to 2019 with respect to absolute hospitalization rates.,Furthermore, we performed detailed comparison of patients hospitalized during the COVID‐19 pandemic and patients presenting in the same period in 2019 with respect to clinical characteristics and management during the index admission.,A significantly lower admission rate for AHF was observed during the study period compared to all other included time periods.,Patients admitted during the COVID‐19 pandemic had higher rates of New York Heart Association III or IV symptoms (96% vs.,77%, P = 0.03) and severe peripheral oedema (39% vs.,14%, P = 0.01).,We did not observe any differences in inpatient management, including place of care and pharmacological management of heart failure with reduced ejection fraction.,Incident AHF hospitalization significantly declined in our centre during the COVID‐19 pandemic, but hospitalized patients had more severe symptoms at admission.,Further studies are needed to investigate whether the incidence of AHF declined or patients did not present to hospital while the national lockdown and social distancing restrictions were in place.,From a public health perspective, it is imperative to ascertain whether this will be associated with worse long‐term outcomes.

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.

The aim of this study was to identify factors associated with the death of patients with COVID-19 pneumonia caused by the novel coronavirus SARS-CoV-2.,All clinical and laboratory parameters were collected prospectively from a cohort of patients with COVID-19 pneumonia who were hospitalised to Wuhan Pulmonary Hospital (Wuhan City, Hubei Province, China) between 25 December 2019 and 7 February 2020.,Univariate and multivariate logistic regression was performed to investigate the relationship between each variable and the risk of death of COVID-19 pneumonia patients.,In total, 179 patients with COVID-19 pneumonia (97 male and 82 female) were included in the present prospective study, of whom 21 died.,Univariate and multivariate logistic regression analysis revealed that age ≥65 years (OR 3.765, 95% CI 1.146-17.394; p=0.023), pre-existing concurrent cardiovascular or cerebrovascular diseases (OR 2.464, 95% CI 0.755-8.044; p=0.007), CD3+CD8+ T-cells ≤75 cells·μL−1 (OR 3.982, 95% CI 1.132-14.006; p<0.001) and cardiac troponin I ≥0.05 ng·mL−1 (OR 4.077, 95% CI 1.166-14.253; p<0.001) were associated with an increase in risk of mortality from COVID-19 pneumonia.,In a sex-, age- and comorbid illness-matched case-control study, CD3+CD8+ T-cells ≤75 cells·μL−1 and cardiac troponin I ≥0.05 ng·mL−1 remained as predictors for high mortality from COVID-19 pneumonia.,We identified four risk factors: age ≥65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells ≤75 cells·μL−1 and cardiac troponin I ≥0.05 ng·mL−1.,The latter two factors, especially, were predictors for mortality of COVID-19 pneumonia patients.,These data showed that age ≥65 years, pre-existing concurrent cardiovascular or cerebrovascular diseases, CD3+CD8+ T-cells ≤75 cells·μL−1 and cardiac troponin I ≥0.05 ng·mL−1 were four risk factors predicting high mortality of COVID-19 pneumonia patientshttps://bit.ly/2Rh6Nqv

Expanding from China around the world, coronavirus 2019 (COVID-19) is the disease caused by severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2).,COVID-19 primarily manifests by hypoxic normo-hypocapnia with preserved lung compliance [1].,In the absence of targeted treatment, sub-intensive clinicians support patients with noninvasive ventilation and anti-inflammatory/anti-viral agents waiting for status improvement.,Angiotensin-converting enzyme (ACE)2, highly expressed on the external membrane of lungs, heart, kidney and gastrointestinal tract cells, displays the binding site for the spike protein of SARS-CoV-2 [2].,ACE2, identified as a counterpart of the Renin-Angiotensin-Aldosterone System (RAAS), converts angiotensin (Ang) II to Ang-(1-7) and Ang I to Ang-(1-9).,ACE2 activity induces vasodilatation and reduces cell growth and inflammatory response.,In COVID-19 patients respiratory failure is associated with increased systemic blood pressure, conceivably due to the modulation of the renin-angiotensin-aldosterone system by SARS-CoV-2 infectionhttps://bit.ly/3cINsHB

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.

WNT signaling is an elaborate and complex collection of signal transduction pathways mediated by multiple signaling molecules.,WNT signaling is critically important for developmental processes, including cell proliferation, differentiation and tissue patterning.,Little WNT signaling activity is present in the cardiovascular system of healthy adults, but reactivation of the pathway is observed in many pathologies of heart and blood vessels.,The high prevalence of these pathologies and their significant contribution to human disease burden has raised interest in WNT signaling as a potential target for therapeutic intervention.,In this review, we first will focus on the constituents of the pathway and their regulation and the different signaling routes.,Subsequently, the role of WNT signaling in cardiovascular development is addressed, followed by a detailed discussion of its involvement in vascular and cardiac disease.,After highlighting the crosstalk between WNT, transforming growth factor-β and angiotensin II signaling, and the emerging role of WNT signaling in the regulation of stem cells, we provide an overview of drugs targeting the pathway at different levels.,From the combined studies we conclude that, despite the sometimes conflicting experimental data, a general picture is emerging that excessive stimulation of WNT signaling adversely affects cardiovascular pathology.,The rapidly increasing collection of drugs interfering at different levels of WNT signaling will allow the evaluation of therapeutic interventions in the pathway in relevant animal models of cardiovascular diseases and eventually in patients in the near future, translating the outcomes of the many preclinical studies into a clinically relevant context.

Dickkopf‐3 (DKK3) is a negative regulator of the Wnt/β‐catenin signaling pathway, which is involved in inflammation.,However, little is known about the relationship between DKK3 expression and the progression of atherosclerosis.,The aim of the present study was to define the role of DKK3 and its potential mechanism in the development of atherosclerosis.,Immunofluorescence analysis showed that DKK3 was strongly expressed in macrophages of atherosclerotic plaques from patients with coronary heart disease and in hyperlipidemic mice.,The expression level was significantly increased in atherogenesis.,DKK3−/−ApoE−/− mice exhibited a significant decrease in atherosclerotic lesions in the entire aorta, aortic sinus, and brachiocephalic arteries.,Transplantation of bone marrow from DKK3−/−ApoE−/− mice into lethally irradiated ApoE−/− recipients resulted in a reduction of atherosclerotic lesions, compared with the lesions in recipients transplanted with ApoE−/− donor cells, suggesting that the effect of DKK3 deficiency was largely mediated by bone marrow-derived cells.,A reduction in the necrotic core size, accompanied by increased collagen content and smooth muscle cells and decreased accumulation of macrophages and lipids, contributed to the stability of plaques in DKK3−/−ApoE−/− mice.,Furthermore, multiple proinflammatory cytokines exhibited marked decreases in DKK3−/−ApoE−/− mice.,Finally, we observed that DKK3 ablation increased β‐catenin expression in the nuclei of macrophages both in vivo and in vitro.,DKK3 expression in macrophages is involved in the pathogenesis of atherosclerosis through modulation of inflammation and inactivation of the Wnt/β‐catenin pathway.

Coagulopathy is a common abnormality in patients with COVID‐19.,However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID‐19 patients.,Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID‐19 patients.,We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care.,A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID‐19.,Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis.,Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation.,Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration.,From March 19 to April 11, 2020, 26 consecutive patients with severe COVID‐19 were screened for VTE.,Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation.,The overall rate of VTE in patients was 69%.,The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03).,Surprisingly, we found a high rate of thromboembolic events in COVID‐19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms.,Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID‐19 patients.

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.

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is now a global pandemic with the highest number of affected individuals in the modern era.,Not only is the infection inflicting significant morbidity and mortality, but there has also been a significant strain to the health care system and the economy.,COVID-19 typically presents as viral pneumonia, occasionally leading to acute respiratory distress syndrome (ARDS) and death.,However, emerging evidence suggests that it has a significant impact on the cardiovascular (CV) system by direct myocardial damage, severe systemic inflammatory response, hypoxia, right heart strain secondary to ARDS and lung injury, and plaque rupture secondary to inflammation.,Primary cardiac manifestations include acute myocarditis, myocardial infarction, arrhythmia, and abnormal clotting.,Several consensus documents have been released to help manage CV disease during this pandemic.,In this review, we summarize key cardiac manifestations, their management, and future implications.

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.

Cardiovascular complications, including myocardial infarction, ischemic stroke, and pulmonary embolism, represent an important source of adverse outcomes in coronavirus disease-2019 (COVID-19).,To assess the frequency of arterial and venous thromboembolic disease, risk factors, prevention and management patterns, and outcomes in patients with COVID-19, the authors designed a multicenter, observational cohort study.,We analyzed a retrospective cohort of 1,114 patients with COVID-19 diagnosed through our Mass General Brigham integrated health network.,The total cohort was analyzed by site of care: intensive care (n = 170); hospitalized nonintensive care (n = 229); and outpatient (n = 715).,The primary study outcome was a composite of adjudicated major arterial or venous thromboembolism.,Patients with COVID-19 were 22.3% Hispanic/Latinx and 44.2% non-White.,Cardiovascular risk factors of hypertension (35.8%), hyperlipidemia (28.6%), and diabetes (18.0%) were common.,Prophylactic anticoagulation was prescribed in 89.4% of patients with COVID-19 in the intensive care cohort and 84.7% of those in the hospitalized nonintensive care setting.,Frequencies of major arterial or venous thromboembolism, major cardiovascular adverse events, and symptomatic venous thromboembolism were highest in the intensive care cohort (35.3%, 45.9%, and 27.0 %, respectively) followed by the hospitalized nonintensive care cohort (2.6%, 6.1%, and 2.2%, respectively) and the outpatient cohort (0% for all).,Major arterial or venous thromboembolism, major adverse cardiovascular events, and symptomatic venous thromboembolism occurred with high frequency in patients with COVID-19, especially in the intensive care setting, despite a high utilization rate of thromboprophylaxis.

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.

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.

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.

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.

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.

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.

Coronavirus disease 2019 (COVID-19) is a global pandemic that is wreaking havoc on the health and economy of much of human civilization.,Electrophysiologists have been impacted personally and professionally by this global catastrophe.,In this joint article from representatives of the Heart Rhythm Society, the American College of Cardiology, and the American Heart Association, we identify the potential risks of exposure to patients, allied healthcare staff, industry representatives, and hospital administrators.,We also describe the impact of COVID-19 on cardiac arrhythmias and methods of triage based on acuity and patient comorbidities.,We provide guidance for managing invasive and noninvasive electrophysiology procedures, clinic visits, and cardiac device interrogations.,In addition, we discuss resource conservation and the role of telemedicine in remote patient care along with management strategies for affected patients.

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.

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.

Enteroviral cardiomyopathy is a life-threatening disease, and detection of enterovirus (EV) RNA in the initial endomyocardial biopsy is associated with adverse prognosis and increased mortality.,Some patients with EV infection may spontaneously eliminate the virus and recover, whereas those with virus persistence deteriorate and progress to heart failure.,Interferon-beta (IFN-β) therapy eliminates the virus, resulting in increased survival of treated patients.,CCR5 is expressed on antigen-presenting cells (both macrophages and dendritic cells) and immune effector cells (T-lymphocytes with memory/effector phenotype and natural killer cells).,Its 32-bp deletion (CCR5del32) is the most frequent human coding sequence mutation.,This study addresses the correlation of CCR5 polymorphism to the clinical course of EV infection and the necessity for IFN-β treatment.,We examined 97 consecutive patients with chronic/inflammatory cardiomyopathy and biopsy-proven EV infection and reliable information on clinical outcomes by CCr5 genotyping.,These data were evaluated in relation to virus persistence in follow-up biopsies and survival rates over a 15-year period.,Genotyping revealed a strong correlation between the CCR5del32 genotype and spontaneous virus clearance with improved outcomes.,All patients with CCR5del32 eliminated EV spontaneously and none of them died within the observed period.,In the group of untreated CCR5 wildtype patients, 33% died (Kaplan-Meier log-rank p = 0.010).,However, CCR5 wildtype individuals treated with IFN-β are more likely to survive than without therapy (Kaplan-Meier log-rank p = 0.004) in identical proportions to individuals with the CCR5del32 genotype.,These data suggest that CCR5 genotyping is a novel predictive genetic marker for the clinical course of human EV cardiomyopathies.,Hereby clinicians can identify those EV positive individuals who will eliminate the virus spontaneously based on CCR5 phenotype and those patients with CCR5 wildtype genotype who would be eligible for immediate antiviral IFN-β treatment to minimize irreversible cardiac damage.,The online version of this article (10.1186/s12967-018-1610-8) contains supplementary material, which is available to authorized users.

Myocarditis is an inflammatory disease of the cardiac muscle mainly caused by viral infection.,Due to the diverse clinical presentation of myocarditis, accurate diagnosis demands simultaneous histologic, immunohistochemical and molecular biological workup of endomyocardial biopsies (EMBs) as defined by the position statement of the Working Group on Myocardial and Pericardial Diseases of the European Society of Cardiology on myocarditis.,Endomyocardial biopsy-based analysis of viral transcriptional activity, mRNA expression, epigenetics and region-specific protein expression analysis via imaging mass spectrometry have led to the identification of novel potential diagnostic criteria, markers with prognostic value and therapeutic targets for the treatment of viral myocarditis, opening new avenues for novel therapies, including cell therapies, as well as the use of established treatment options, be it from other indications.,Under certain clinical scenarios EMB-based analysis is required to come to a tailored individualized therapy that improves symptoms and prognosis of patients with acute and chronic viral-driven cardiac inflammation.

The increase in the incidence of cardiovascular diseases (CVDs) and kidney disease has stimulated research for strategies that could prevent, rather than just treat, both interconnected disorders.,Resveratrol, a polyphenolic compound with pleiotropic biofunctions, has shown health benefits.,Emerging epidemiological data supports that early life environmental insults are regarded as increased risks of developing CVDs and kidney disease in adulthood.,Conversely, both disorders could be reversed or postponed by shifting interventions from adulthood to earlier stage by so-called reprogramming.,The purpose of this review is first to highlight current epidemiological studies linking cardiovascular and renal programming to resulting CVD and kidney disease of developmental origins.,This will be followed by a summary of how resveratrol could exert a positive influence on CVDs and kidney disease.,This review also presents an overview of the evidence documenting resveratrol as a reprogramming agent to protect against CVD and kidney disease of developmental origins from animal studies and to outline the advances in understanding the underlying molecular mechanisms.,Overall, this review reveals the need for future research to further clarify the reprogramming effects of resveratrol before clinical translation.

The renin-angiotensin-aldosterone system (RAAS) is implicated in hypertension and kidney disease.,The developing kidney can be programmed by various early-life insults by so-called renal programming, resulting in hypertension and kidney disease in adulthood.,This theory is known as developmental origins of health and disease (DOHaD).,Conversely, early RAAS-based interventions could reverse program processes to prevent a disease from occurring by so-called reprogramming.,In the current review, we mainly summarize (1) the current knowledge on the RAAS implicated in renal programming; (2) current evidence supporting the connections between the aberrant RAAS and other mechanisms behind renal programming, such as oxidative stress, nitric oxide deficiency, epigenetic regulation, and gut microbiota dysbiosis; and (3) an overview of how RAAS-based reprogramming interventions may prevent hypertension and kidney disease of developmental origins.,To accelerate the transition of RAAS-based interventions for prevention of hypertension and kidney disease, an extended comprehension of the RAAS implicated in renal programming is needed, as well as a greater focus on further clinical translation.

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.

The aim of this study was to investigate whether right ventricular longitudinal strain (RVLS) was independently predictive of higher mortality in patients with coronavirus disease-2019 (COVID-19).,RVLS obtained from 2-dimensional speckle-tracking echocardiography has been recently demonstrated to be a more accurate and sensitive tool to estimate right ventricular (RV) function.,The prognostic value of RVLS in patients with COVID-19 remains unknown.,One hundred twenty consecutive patients with COVID-19 who underwent echocardiographic examinations were enrolled in our study.,Conventional RV functional parameters, including RV fractional area change, tricuspid annular plane systolic excursion, and tricuspid tissue Doppler annular velocity, were obtained.,RVLS was determined using 2-dimensional speckle-tracking echocardiography.,RV function was categorized in tertiles of RVLS.,Compared with patients in the highest RVLS tertile, those in the lowest tertile were more likely to have higher heart rate; elevated levels of D-dimer and C-reactive protein; more high-flow oxygen and invasive mechanical ventilation therapy; higher incidence of acute heart injury, acute respiratory distress syndrome, and deep vein thrombosis; and higher mortality.,After a median follow-up period of 51 days, 18 patients died.,Compared with survivors, nonsurvivors displayed enlarged right heart chambers, diminished RV function, and elevated pulmonary artery systolic pressure.,Male sex, acute respiratory distress syndrome, RVLS, RV fractional area change, and tricuspid annular plane systolic excursion were significant univariate predictors of higher risk for mortality (p < 0.05 for all).,A Cox model using RVLS (hazard ratio: 1.33; 95% confidence interval [CI]: 1.15 to 1.53; p < 0.001; Akaike information criterion = 129; C-index = 0.89) was found to predict higher mortality more accurately than a model with RV fractional area change (Akaike information criterion = 142, C-index = 0.84) and tricuspid annular plane systolic excursion (Akaike information criterion = 144, C-index = 0.83).,The best cutoff value of RVLS for prediction of outcome was −23% (AUC: 0.87; p < 0.001; sensitivity, 94.4%; specificity, 64.7%).,RVLS is a powerful predictor of higher mortality in patients with COVID-19.,These results support the application of RVLS to identify higher risk patients with 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.

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.

As our understanding of the complications of coronavirus disease-2019 (COVID-19) evolve, subclinical cardiac pathology such as myocarditis, pericarditis, and right ventricular dysfunction in the absence of significant clinical symptoms represents a concern.,The potential implications of these findings in athletes are significant given the concern that exercise, during the acute phase of viral myocarditis, may exacerbate myocardial injury and precipitate malignant ventricular arrhythmias.,Such concerns have led to the development and publication of expert consensus documents aimed at providing guidance for the evaluation of athletes after contracting COVID-19 in order to permit safe return to play.,Cardiac imaging is at the center of these evaluations.,This review seeks to evaluate the current evidence regarding COVID-19-associated cardiovascular disease and how multimodality imaging may be useful in the screening and clinical evaluation of athletes with suspected cardiovascular complications of infection.,Guidance is provided with diagnostic “red flags” that raise the suspicion of pathology.,Specific emphasis is placed on the unique challenges posed in distinguishing athletic cardiac remodeling from subclinical cardiac disease.,The strengths and limitations of different imaging modalities are discussed and an approach to return to play decision making for athletes post-COVID-19, as informed by multimodality imaging, is provided.

Inflammatory cardiomyopathy, characterized by inflammatory cell infiltration into the myocardium and a high risk of deteriorating cardiac function, has a heterogeneous aetiology.,Inflammatory cardiomyopathy is predominantly mediated by viral infection, but can also be induced by bacterial, protozoal or fungal infections as well as a wide variety of toxic substances and drugs and systemic immune-mediated diseases.,Despite extensive research, inflammatory cardiomyopathy complicated by left ventricular dysfunction, heart failure or arrhythmia is associated with a poor prognosis.,At present, the reason why some patients recover without residual myocardial injury whereas others develop dilated cardiomyopathy is unclear.,The relative roles of the pathogen, host genomics and environmental factors in disease progression and healing are still under discussion, including which viruses are active inducers and which are only bystanders.,As a consequence, treatment strategies are not well established.,In this Review, we summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with a special focus on virus-induced and virus-associated myocarditis.,Furthermore, we identify knowledge gaps, appraise the available experimental models and propose future directions for the field.,The current knowledge and open questions regarding the cardiovascular effects associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are also discussed.,This Review is the result of scientific cooperation of members of the Heart Failure Association of the ESC, the Heart Failure Society of America and the Japanese Heart Failure Society.,In this Review, Tschöpe and colleagues summarize and evaluate the available evidence on the pathogenesis, diagnosis and treatment of myocarditis and inflammatory cardiomyopathy, with special focus on virus-induced and virus-associated myocarditis.,The authors also identify knowledge gaps, appraise available experimental models and propose future directions for the field.,The role of specific viruses, immune cells and autoimmunity in the pathogenesis of myocarditis and inflammatory cardiomyopathy is still incompletely understood, and advanced animal and cell models are required for future research.Advanced animal models that take into account immune experience and exposure to environmental factors and in vitro models with immune cell interactions are needed to facilitate better clinical translation of the findings.Improved standardization of available invasive and noninvasive diagnostic tools and a consensus on their specific use are needed to allow specific diagnosis and stratification of patient cohorts for the implementation of aetiology-based therapies.To develop aetiology-based therapies, the efficacy of many existing, repurposed or emerging therapies needs to be evaluated in large, controlled, randomized trials.,The role of specific viruses, immune cells and autoimmunity in the pathogenesis of myocarditis and inflammatory cardiomyopathy is still incompletely understood, and advanced animal and cell models are required for future research.,Advanced animal models that take into account immune experience and exposure to environmental factors and in vitro models with immune cell interactions are needed to facilitate better clinical translation of the findings.,Improved standardization of available invasive and noninvasive diagnostic tools and a consensus on their specific use are needed to allow specific diagnosis and stratification of patient cohorts for the implementation of aetiology-based therapies.,To develop aetiology-based therapies, the efficacy of many existing, repurposed or emerging therapies needs to be evaluated in large, controlled, randomized trials.

To estimate prevalence and clustering of cardiovascular risk factors (CRFs), and investigate the association between relevant characteristics and CRF clustering among adults in eastern China.,Community-based cross-sectional study.,Data were collected by interview survey, physical measurements and laboratory examinations from the 2011 Nanjing Chronic Disease and Risk Factor Surveillance.,A representative sample of 41 072 residents aged ≥18 years volunteered to participate in the survey, with a response rate of 91.3%.,We excluded 1232 subjects due to missing data or having a history of cardiovascular diseases; a total of 39 840 participants were included in the analysis.,Prevalence and clustering of five major CRFs including hypertension, diabetes, dyslipidaemia, overweight or obesity and current smoking.,Of 39 840 participants (mean age 47.9±16.2 years), 17 964 (45.1%) were men and 21 876 (54.9%) were women.,The weighted prevalence of CRFs ranged between 6.2% for diabetes and 35.6% for overweight or obesity.,The proportion of CRFs tended to be higher in men, the elderly, participants who lost a life partner, or lived in rural areas, or had lower level of education and total annual income.,Overall, 30.1% and 35.2% of participants had one and at least two CRFs, respectively.,Multivariate logistic regression revealed that men, older age, loss of a life partner, lower level of socioeconomic status, rural areas, insufficient physical activity or unhealthy diets were positively associated with CVD risk factor clustering, compared with their counterparts.,High regional prevalence of hypertension, dyslipidaemia, overweight or obesity and their clustering are present in Nanjing.,The Nanjing government should develop effective public health policies at the regional level especially for high-risk groups, such as enhancing the public’s health awareness, organising health promotion programmes, implementing smoke-free law, producing healthy nutrient foods, providing free or low-cost public sports and fitness facilities.

To assess the relationship between risk factor clusters and cardiovascular disease (CVD) incidence in Asian and Caucasian populations and to estimate the burden of CVD attributable to each cluster.,Asia Pacific Cohort Studies Collaboration.,Individual participant data from 34 population-based cohorts, involving 314 024 participants without a history of CVD at baseline.,Clusters were 11 possible combinations of four individual risk factors (current smoking, overweight, blood pressure (BP) and total cholesterol).,Cox regression models were used to obtain adjusted HRs and 95% CIs for CVD associated with individual risk factors and risk factor clusters.,Population-attributable fractions (PAFs) were calculated.,During a mean follow-up of 7 years, 6203 CVD events were recorded.,The ranking of HRs and PAFs was similar for Australia and New Zealand (ANZ) and Asia; clusters including BP consistently showed the highest HRs and PAFs.,The BP-smoking cluster had the highest HR for people with two risk factors: 4.13 (3.56 to 4.80) for Asia and 3.07 (2.23 to 4.23) for ANZ.,Corresponding PAFs were 24% and 11%, respectively.,For individuals with three risk factors, the BP-smoking-cholesterol cluster had the highest HR (4.67 (3.92 to 5.57) for Asia and 3.49 (2.69 to 4.53) for ANZ).,Corresponding PAFs were 13% and 10%.,Risk factor clusters act similarly on CVD risk in Asian and Caucasian populations.,Clusters including elevated BP were associated with the highest excess risk of CVD.

A remarkably high incidence of venous thromboembolism (VTE) has been reported among critically ill patients with COVID‐19 assisted in the intensive care unit (ICU).,However, VTE burden among non‐ICU patients hospitalized for COVID‐19 that receive guideline‐recommended thromboprophylaxis is unknown.,To determine the incidence of VTE among non‐ICU patients hospitalized for COVID‐19 that receive pharmacological thromboprophylaxis.,We performed a systematic screening for the diagnosis of deep vein thrombosis (DVT) by lower limb vein compression ultrasonography (CUS) in consecutive non‐ICU patients hospitalized for COVID‐19, independent of the presence of signs or symptoms of DVT.,All patients were receiving pharmacological thromboprophylaxis with either enoxaparin or fondaparinux.,The population that we screened consisted of 84 consecutive patients, with a mean age of 67.6 ± 13.5 years and a mean Padua Prediction Score of 5.1 ± 1.6.,Seventy‐two patients (85.7%) had respiratory insufficiency, required oxygen supplementation, and had reduced mobility or were bedridden.,In this cohort, we found 10 cases of DVT, with an incidence of 11.9% (95% confidence interval [CI] 4.98‐18.82).,Of these, 2 were proximal DVT (incidence rate 2.4%, 95% CI −0.87‐5.67) and 8 were distal DVT (incidence rate 9.5%, 95% CI 3.23‐5.77).,Significant differences between subjects with and without DVT were D‐dimer > 3000 µg/L (P < .05), current or previous cancer (P < .05), and need of high flow nasal oxygen therapy and/or non‐invasive ventilation (P < .01).,DVT may occur among non‐ICU patients hospitalized for COVID‐19, despite guideline‐recommended thromboprophylaxis.

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.

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.

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.

Although coronavirus disease 2019 (COVID-19) predominantly disrupts the respiratory system, there is accumulating experience that the disease, particularly in its more severe manifestations, also affects the cardiovascular system.,Cardiovascular risk factors and chronic cardiovascular conditions are prevalent among patients affected by COVID-19 and associated with adverse outcomes.,However, whether pre-existing cardiovascular disease is an independent determinant of higher mortality risk with COVID-19 remains uncertain.,Acute cardiac injury, manifest by increased blood levels of cardiac troponin, electrocardiographic abnormalities, or myocardial dysfunction, occurs in up to ~60% of hospitalized patients with severe COVID-19.,Potential contributors to acute cardiac injury in the setting of COVID-19 include (1) acute changes in myocardial demand and supply due to tachycardia, hypotension, and hypoxemia resulting in type 2 myocardial infarction; (2) acute coronary syndrome due to acute atherothrombosis in a virally induced thrombotic and inflammatory milieu; (3) microvascular dysfunction due to diffuse microthrombi or vascular injury; (4) stress-related cardiomyopathy (Takotsubo syndrome); (5) nonischemic myocardial injury due to a hyperinflammatory cytokine storm; or (6) direct viral cardiomyocyte toxicity and myocarditis.,Diffuse thrombosis is emerging as an important contributor to adverse outcomes in patients with COVID-19.,Practitioners should be vigilant for cardiovascular complications of COVID-19.,Monitoring may include serial cardiac troponin and natriuretic peptides, along with fibrinogen, D-dimer, and inflammatory biomarkers.,Management decisions should rely on the clinical assessment for the probability of ongoing myocardial ischemia, as well as alternative nonischemic causes of injury, integrating the level of suspicion for COVID-19.

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.

We describe the first case of acute cardiac injury directly linked to myocardial localization of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) in a 69‐year‐old patient with flu‐like symptoms rapidly degenerating into respiratory distress, hypotension, and cardiogenic shock.,The patient was successfully treated with venous‐arterial extracorporeal membrane oxygenation (ECMO) and mechanical ventilation.,Cardiac function fully recovered in 5 days and ECMO was removed.,Endomyocardial biopsy demonstrated low‐grade myocardial inflammation and viral particles in the myocardium suggesting either a viraemic phase or, alternatively, infected macrophage migration from the lung.

Background: Cardiac damage is frequently referred to in patients with SARS-CoV-2, is usually diagnosed by enzyme elevations, and is generally thought to be due to underlying coronary artery disease.,There are references to cardiomyopathies accompanying coronavirus, but there has been no histologic confirmation.,Case report: A previously healthy 17 year male old presented in full cardiac arrest to the emergency department after a 2 day history of headache, dizziness, nausea and vomiting.,Autopsy demonstrated an enlarged flabby heart with eosinophilic myocarditis.,There was no interstitial pneumonia or diffuse alveolar damage.,Postmortem nasopharyngeal swabs detected severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) known to cause coronavirus disease 2019 (COVID-19).,No other cause for the eosinophilic myocarditis was elucidated.,Conclusion: Like other viruses, SARS-CoV-2 may be associated with fulminant myocarditis.

Supplemental Digital Content is Available in the Text.,South Africa faces a dual burden of HIV/AIDS and noncommunicable diseases.,In 2011, a pilot integrated chronic disease management (ICDM) model was introduced by the National Health Department into selected primary health care (PHC) facilities.,The objective of this study was to assess the effectiveness of the ICDM model in controlling patients' CD4 counts (>350 cells/mm3) and blood pressure [BP (<140/90 mm Hg)] in PHC facilities in the Bushbuckridge municipality, South Africa.,A controlled interrupted time-series study was conducted using the data from patients' clinical records collected multiple times before and after the ICDM model was initiated in PHC facilities in Bushbuckridge.,Patients ≥18 years were recruited by proportionate sampling from the pilot (n = 435) and comparing (n = 443) PHC facilities from 2011 to 2013.,Health outcomes for patients were retrieved from facility records for 30 months.,We performed controlled segmented regression to model the monthly averages of individuals' propensity scores using autoregressive moving average model at 5% significance level.,The pilot facilities had 6% greater likelihood of controlling patients' CD4 counts than the comparison facilities (coefficient = 0.057; 95% confidence interval: 0.056 to 0.058; P < 0.001).,Compared with the comparison facilities, the pilot facilities had 1.0% greater likelihood of controlling patients' BP (coefficient = 0.010; 95% confidence interval: 0.003 to 0.016; P = 0.002).,Application of the model had a small effect in controlling patients' CD4 counts and BP, but showed no overall clinical benefit for the patients; hence, the need to more extensively leverage the HIV program for hypertension treatment.

Many patients on antiretroviral therapy (ART) in Malawi have or will develop non-communicable diseases (NCDs).,The current capacity of ART sites to provide care for NCDs is not known.,This study aimed to assess the capacity of ART sites to provide care for hypertension and diabetes in rural Malawi.,Twenty-five health centres and five hospitals in two rural districts in northern Malawi.,A cross-sectional survey was performed between March and May 2014 at all facilities.,Qualitative interviews were held with three NCD coordinators.,Treatment of hypertension and diabetes was predominantly hospital-based.,Sixty percent of hospitals had at least one clinician and one nurse trained in NCD care, whereas 5% of health centres had a clinician and 8% had a nurse trained in NCD care.,Hundred percent of hospitals and 92% of health centres had uninterrupted supply of hydrochlorothiazide in the previous 6 months, but only 40% of hospitals and no health centres had uninterrupted supply of metformin.,Hundred percent of hospitals and 80% of health centres had at least one blood pressure machine, and 80% of hospitals and 32% of health centres had one glucometer.,Screening for hypertension amongst ART patients was only conducted at one hospital and no health centres.,At health centres, integrated NCD and ART care was more common, with 48% (12/25) providing ART and NCD treatment in the same consultation.,The results reflect the status of the initial stages of the Malawi NCD programme at sites currently providing ART care.

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.

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.

Intracerebral hemorrhage (ICH) can be a devastating complication of coronavirus disease (COVID-19).,We aimed to assess risk factors associated with ICH in this population.,We performed a retrospective cohort study of adult patients admitted to NYU Langone Health system between March 1 and April 27 2020 with a positive nasopharyngeal swab polymerase chain reaction test result and presence of primary nontraumatic intracranial hemorrhage or hemorrhagic conversion of ischemic stroke on neuroimaging.,Patients with intracranial procedures, malignancy, or vascular malformation were excluded.,We used regression models to estimate odds ratios and 95% confidence intervals (OR, 95% CI) of the association between ICH and covariates.,We also used regression models to determine association between ICH and mortality.,Among 3824 patients admitted with COVID-19, 755 patients had neuroimaging and 416 patients were identified after exclusion criteria were applied.,The mean (standard deviation) age was 69.3 (16.2), 35.8% were women, and 34.9% were on therapeutic anticoagulation.,ICH occurred in 33 (7.9%) patients.,Older age, non-Caucasian race, respiratory failure requiring mechanical ventilation, and therapeutic anticoagulation were associated with ICH on univariate analysis (p < 0.01 for each variable).,In adjusted regression models, anticoagulation use was associated with a five-fold increased risk of ICH (OR 5.26, 95% CI 2.33-12.24, p < 0.001).,ICH was associated with increased mortality (adjusted OR 2.6, 95 % CI 1.2-5.9).,Anticoagulation use is associated with increased risk of ICH in patients with COVID-19.,Further investigation is required to elucidate underlying mechanisms and prevention strategies in this population.,The online version of this article (10.1007/s11239-020-02288-0) contains supplementary material, which is available to authorized users.

To investigate the incidence and spectrum of neuroimaging findings and their prognostic role in hospitalized COVID-19 patients in New York City.,This is a retrospective cohort study of 3218 COVID-19 confirmed patients admitted to a major healthcare system (three hospitals) in New York City between March 1, 2020 and April 13, 2020.,Clinical data were extracted from electronic medical records, and particularly data of all neurological symptoms were extracted from the imaging reports.,Four neuroradiologists evaluated all neuroimaging studies for acute neuroimaging findings related to COVID-19.,14.1% of admitted COVID-19 patients had neuroimaging and this accounted for only 5.5% of the total imaging studies.,Acute stroke was the most common finding on neuro-imaging, seen in 92.5% of patients with positive neuro-imaging studies, and present in 1.1% of hospitalized COVID-19 patients.,Patients with acute large ischemic and hemorrhagic stroke had much higher mortality risk adjusted for age, BMI and hypertension compared to those COVID-19 patients without neuroimaging.,(Odds Ratio 6.02 by LR; Hazard Ratio 2.28 by CRR).,Our study demonstrates acute stroke is the most common neuroimaging finding among hospitalized COVID-19 patients.,Detection of an acute stroke is a strong prognostic marker of poor outcome.,Our study also highlights the fact there is limited use of neuroimaging in these patients due to multiple logistical constraints.

Woven EndoBridge (WEB; Sequent Medical) treatment is an innovative endovascular approach for treatment of wide-neck bifurcation aneurysms.,Initial studies have shown high safety with good efficacy at short term confirmed by trials conducted in United States (WEB-Intrasaccular Therapy) and in Europe (WEB Clinical Assessment of Intrasaccular Aneurysm Therapy [WEBCAST], French Observatory, and WEBCAST-2).,To report the 2-yr clinical and anatomical results of WEB treatment in the combined population of 3 European trials.,In a French Observatory, 2-yr clinical and anatomical data were collected.,In WEBCAST and WEBCAST-2, 2-yr follow-up was optional, and data were collected when follow-up was performed.,Aneurysm occlusion was evaluated using a 3-grade scale: complete occlusion, neck remnant, and aneurysm remnant.,The population for safety was 138/168 patients (82.1%), including 89 females (64.5%), with mean age of 55.5 ± 10.2 yr.,The population for efficacy was 121/169 aneurysms (71.6%).,Aneurysm locations were middle cerebral artery in 65/121 aneurysms (53.7%), anterior-communicating artery in 25/121 (20.7%), basilar artery in 17/121 (14.0%), and internal carotid artery terminus in 14/121 (11.6%).,No clinically relevant adverse events occurred between years 1 and 2.,At 2 yr, complete occlusion was observed in 62/121 (51.2%) aneurysms, neck remnant in 36/121 (29.8%) aneurysms, and aneurysm remnant in 23/121 (19.0%) aneurysms.,The global retreatment rate at 2 yr was 9.3%.,This analysis confirms the high safety profile of WEB treatment at 2 yr.,Aneurysm occlusion is generally stable at 2 yr, and the retreatment rate between 1 yr and 2 yr is low (2.0%).,Graphical Abstract

Flow disruption with the WEB is an innovative endovascular approach for treatment of wide-neck bifurcation aneurysms.,Initial studies have shown a low complication rate with good efficacy.,To report clinical and anatomical results of the WEB treatment in the cumulative population of three Good Clinical Practice (GCP) studies: WEBCAST (WEB Clinical Assessment of Intrasaccular Aneurysm), French Observatory, and WEBCAST-2.,WEBCAST, French Observatory, and WEBCAST-2 are single-arm, prospective, multicenter, GCP studies dedicated to the evaluation of WEB treatment.,Clinical data were independently evaluated.,Postoperative and 1-year aneurysm occlusion was independently evaluated using the 3-grade scale: complete occlusion, neck remnant, and aneurysm remnant.,The cumulative population comprised 168 patients with 169 aneurysms, including 112 female subjects (66.7%).,The patients' ages ranged between 27 and 77 years (mean 55.5±10.2 years).,Aneurysm locations were middle cerebral artery in 86/169 aneurysms (50.9%), anterior communicating artery in 36/169 (21.3%), basilar artery in 30/169 (17.8%), and internal carotid artery terminus in 17/169 (10.1%).,The aneurysm was ruptured in 14/169 (8.3%).,There was no mortality at 1 month and procedure/device-related morbidity was 1.2% (2/168).,At 1 year, complete aneurysm occlusion was observed in 81/153 aneurysms (52.9%), neck remnant in 40/153 aneurysms (26.1%), and aneurysm remnant in 32/153 aneurysms (20.9%).,Re-treatment was carried out in 6.9%.,This series is at the moment the largest prospective, multicenter, GCP series of patients with aneurysms treated with WEB.,It shows the high safety and good mid-term efficacy of this treatment.,French Observatory: Unique identifier (NCT18069); WEBCAST and WEBCAST-2: Unique identifier (NCT01778322).

The aim of this document is to provide specific recommendations on the use of cardiovascular magnetic resonance (CMR) protocols in the era of the COVID-19 pandemic.,In patients without COVID-19, standard CMR protocols should be used based on clinical indication as usual.,Protocols used in patients who have known / suspected active COVID-19 or post COVID-19 should be performed based on the specific clinical question with an emphasis on cardiac function and myocardial tissue characterization.,Short and dedicated protocols are recommended.

A 60-year-old male patient with coronavirus disease-2019 showed new onset ST-segment elevation in V1-V2 leads on electrocardiogram and cardiac enzyme elevation in intensive care unit.,He had a history of type 2 diabetes mellitus, hypertension, and dyslipidemia.,He was receiving mechanical ventilation and veno-venous extracorporeal membrane oxygenation treatment for severe hypoxia.,Two-D echocardiogram showed regional wall motion abnormalities.,We performed primary percutaneous coronary intervention for acute myocardial infarction complicating cardiogenic shock under hemodynamic support.,He expired on the 16th day of admission because of cardiogenic shock and multi-organ failure.,Active surveillance and intensive treatment strategy are important for saving lives of COVID-19 patients with acute myocardial infarction.

Fatty acid-binding protein 4 (FABP4) acts as a novel adipokine, and elevated FABP4 concentration is associated with obesity, insulin resistance and atherosclerosis.,Dipeptidyl peptidase-4 (DPP-4) inhibitors, a class of antidiabetic drugs, have distinct structures among the drugs, possibly leading to a drug class effect and each drug effect.,Sitagliptin, a DPP-4 inhibitor, has been reported to decrease FABP4 concentration in drug-naïve and sulfonylurea-treated patients with type 2 diabetes mellitus.,Anagliptin, another DPP-4 inhibitor, was shown to decrease low-density lipoprotein cholesterol (LDL-C) level to a greater extent than that by sitagliptin in the Randomized Evaluation of Anagliptin vs.,Sitagliptin On low-density lipoproteiN cholesterol in diabetes (REASON) trial.,As a sub-analysis study using data obtained from the REASON trial, we investigated the effects of treatment with anagliptin (n = 148, male/female: 89/59) and treatment with sitagliptin (n = 159, male/female: 93/66) for 52 weeks on FABP4 concentration in patients with type 2 diabetes mellitus at a high risk for cardiovascular events who were receiving statin therapy.,The DPP-4 inhibitor had been administered in 82% of the patients in the anagliptin group and 81% of the patients in sitagliptin group prior to randomization.,Serum FABP4 level was significantly decreased by 7.9% by treatment with anagliptin (P = 0.049) and was not significantly decreased by treatment with sitagliptin (P = 0.660).,Change in FABP4 level was independently associated with basal FABP4 level and changes in waist circumference and creatinine after adjustment of age, sex and the treatment group.,Anagliptin decreases serum FABP4 concentration independent of change in hemoglobin A1c or LDL-C in patients with type 2 diabetes mellitus and dyslipidemia who are on statin therapy.,Trial registration ClinicalTrials.gov number NCT02330406.,Registered January 5, 2015, https://clinicaltrials.gov/ct2/show/NCT02330406

Fatty acid‐binding protein 4 (FABP4) is expressed in adipocytes, macrophages, and endothelial cells of capillaries but not arteries.,FABP4 is secreted from adipocytes in association with lipolysis, and an elevated circulating FABP4 level is associated with obesity, insulin resistance, and atherosclerosis.,However, little is known about the link between FABP4 and endovascular injury.,We investigated the involvement of ectopic FABP4 expression in endothelial cells in neointima hyperplasia after vascular injury.,Femoral arteries of 8‐week‐old male mice were subjected to wire‐induced vascular injury.,After 4 weeks, immunofluorescence staining showed that FABP4 was ectopically expressed in endothelial cells of the hyperplastic neointima.,Neointima formation determined by intima area and intima to media ratio was significantly decreased in FABP4‐defficient mice compared with that in wild‐type mice.,Adenovirus‐mediated overexpression of FABP4 in human coronary artery endothelial cells (HCAECs) in vitro increased inflammatory cytokines and decreased phosphorylation of nitric oxide synthase 3.,Furthermore, FABP4 was secreted from HCAECs.,Treatment of human coronary smooth muscle cells or HCAECs with the conditioned medium of Fabp4‐overexpressed HCAECs or recombinant FABP4 significantly increased gene expression of inflammatory cytokines and proliferation‐ and adhesion‐related molecules in cells, promoted cell proliferation and migration of human coronary smooth muscle cells, and decreased phosphorylation of nitric oxide synthase 3 in HCAECs, which were attenuated in the presence of an anti‐FABP4 antibody.,Ectopic expression and secretion of FABP4 in vascular endothelial cells contribute to neointima formation after vascular injury.,Suppression of ectopic FABP4 in the vascular endothelium would be a novel strategy against post‐angioplasty vascular restenosis.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of an ongoing pandemic, with increasing deaths worldwide.,To date, documentation of the histopathological features in fatal cases of the disease caused by SARS-CoV-2 (COVID-19) has been scarce due to sparse autopsy performance and incomplete organ sampling.,We aimed to provide a clinicopathological report of severe COVID-19 cases by documenting histopathological changes and evidence of SARS-CoV-2 tissue tropism.,In this case series, patients with a positive antemortem or post-mortem SARS-CoV-2 result were considered eligible for enrolment.,Post-mortem examinations were done on 14 people who died with COVID-19 at the King County Medical Examiner's Office (Seattle, WA, USA) and Snohomish County Medical Examiner's Office (Everett, WA, USA) in negative-pressure isolation suites during February and March, 2020.,Clinical and laboratory data were reviewed.,Tissue examination was done by light microscopy, immunohistochemistry, electron microscopy, and quantitative RT-PCR.,The median age of our cohort was 73·5 years (range 42-84; IQR 67·5-77·25).,All patients had clinically significant comorbidities, the most common being hypertension, chronic kidney disease, obstructive sleep apnoea, and metabolic disease including diabetes and obesity.,The major pulmonary finding was diffuse alveolar damage in the acute or organising phases, with five patients showing focal pulmonary microthrombi.,Coronavirus-like particles were detected in the respiratory system, kidney, and gastrointestinal tract.,Lymphocytic myocarditis was observed in one patient with viral RNA detected in the tissue.,The primary pathology observed in our cohort was diffuse alveolar damage, with virus located in the pneumocytes and tracheal epithelium.,Microthrombi, where observed, were scarce and endotheliitis was not identified.,Although other non-pulmonary organs showed susceptibility to infection, their contribution to the pathogenesis of SARS-CoV-2 infection requires further examination.,None.

COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital.,Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes.,We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020.,The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h.,Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation.,All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet-fibrin thrombi (in 33 cases).,The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases).,Electron microscopy revealed that viral particles were predominantly located in the pneumocytes.,The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses.,Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent.,Importantly, the presence of platelet-fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy.,None.

To report the methods and findings of two complete autopsies of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive individuals who died in Oklahoma (United States) in March 2020.,Complete postmortem examinations were performed according to standard procedures in a negative-pressure autopsy suite/isolation room using personal protective equipment, including N95 masks, eye protection, and gowns.,The diagnosis of coronavirus disease 2019 (COVID-19) was confirmed by real-time reverse transcriptase polymerase chain reaction testing on postmortem swabs.,A 77-year-old obese man with a history of hypertension, splenectomy, and 6 days of fever and chills died while being transported for medical care.,He tested positive for SARS-CoV-2 on postmortem nasopharyngeal and lung parenchymal swabs.,Autopsy revealed diffuse alveolar damage and chronic inflammation and edema in the bronchial mucosa.,A 42-year-old obese man with a history of myotonic dystrophy developed abdominal pain followed by fever, shortness of breath, and cough.,Postmortem nasopharyngeal swab was positive for SARS-CoV-2; lung parenchymal swabs were negative.,Autopsy showed acute bronchopneumonia with evidence of aspiration.,Neither autopsy revealed viral inclusions, mucus plugging in airways, eosinophils, or myocarditis.,SARS-CoV-2 testing can be performed at autopsy.,Autopsy findings such as diffuse alveolar damage and airway inflammation reflect true virus-related pathology; other findings represent superimposed or unrelated processes.

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.

Hypercoagulability may be a key mechanism of death in patients with COVID-19.,This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival.,Hypercoagulability may be a key mechanism of death in patients with COVID-19.,This cohort study evaluated the incidence of venous thromboembolism and major bleeding in critically ill patients with COVID-19 and examined the observational effect of early therapeutic anticoagulation on survival.,Hypercoagulability may be a key mechanism of death in patients with coronavirus disease 2019 (COVID-19).,To evaluate the incidence of venous thromboembolism (VTE) and major bleeding in critically ill patients with COVID-19 and examine the observational effect of early therapeutic anticoagulation on survival.,In a multicenter cohort study of 3239 critically ill adults with COVID-19, the incidence of VTE and major bleeding within 14 days after intensive care unit (ICU) admission was evaluated.,A target trial emulation in which patients were categorized according to receipt or no receipt of therapeutic anticoagulation in the first 2 days of ICU admission was done to examine the observational effect of early therapeutic anticoagulation on survival.,A Cox model with inverse probability weighting to adjust for confounding was used.,67 hospitals in the United States.,Adults with COVID-19 admitted to a participating ICU.,Time to death, censored at hospital discharge, or date of last follow-up.,Among the 3239 patients included, the median age was 61 years (interquartile range, 53 to 71 years), and 2088 (64.5%) were men.,A total of 204 patients (6.3%) developed VTE, and 90 patients (2.8%) developed a major bleeding event.,Independent predictors of VTE were male sex and higher D-dimer level on ICU admission.,Among the 2809 patients included in the target trial emulation, 384 (11.9%) received early therapeutic anticoagulation.,In the primary analysis, during a median follow-up of 27 days, patients who received early therapeutic anticoagulation had a similar risk for death as those who did not (hazard ratio, 1.12 [95% CI, 0.92 to 1.35]).,Observational design.,Among critically ill adults with COVID-19, early therapeutic anticoagulation did not affect survival in the target trial emulation.,None.

Because of the high risk of thrombotic complications (TCs) during SARS-CoV-2 infection, several scientific societies have proposed to increase the dose of preventive anticoagulation, although arguments in favor of this strategy are inconsistent.,What is the incidence of TC in critically ill patients with COVID-19 and what is the relationship between the dose of anticoagulant therapy and the incidence of TC?,All consecutive patients referred to eight French ICUs for COVID-19 were included in this observational study.,Clinical and laboratory data were collected from ICU admission to day 14, including anticoagulation status and thrombotic and hemorrhagic events.,The effect of high-dose prophylactic anticoagulation (either at intermediate or equivalent to therapeutic dose), defined using a standardized protocol of classification, was assessed using a time-varying exposure model using inverse probability of treatment weight.,Of 538 patients included, 104 patients experienced a total of 122 TCs with an incidence of 22.7% (95% CI, 19.2%-26.3%).,Pulmonary embolism accounted for 52% of the recorded TCs.,High-dose prophylactic anticoagulation was associated with a significant reduced risk of TC (hazard ratio, 0.81; 95% CI, 0.66-0.99) without increasing the risk of bleeding (HR, 1.11; 95% CI, 0.70-1.75).,High-dose prophylactic anticoagulation is associated with a reduction in thrombotic complications in critically ill patients with COVID-19 without an increased risk of hemorrhage.,Randomized controlled trials comparing prophylaxis with higher doses of anticoagulants are needed to confirm these results.,ClinicalTrials.gov; No.: NCT04405869; URL: www.clinicaltrials.gov

Coronavirus disease 2019 (COVID-19), currently a worldwide pandemic, is a viral illness caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,The suspected contribution of thrombotic events to morbidity and mortality in COVID-19 patients has prompted a search for novel potential options for preventing COVID-19-associated thrombotic disease.,In this article by the Global COVID-19 Thrombosis Collaborative Group, we describe novel dosing approaches for commonly used antithrombotic agents (especially heparin-based regimens) and the potential use of less widely used antithrombotic drugs in the absence of confirmed thrombosis.,Although these therapies may have direct antithrombotic effects, other mechanisms of action, including anti-inflammatory or antiviral effects, have been postulated.,Based on survey results from this group of authors, we suggest research priorities for specific agents and subgroups of patients with COVID-19.,Further, we review other agents, including immunomodulators, that may have antithrombotic properties.,It is our hope that the present document will encourage and stimulate future prospective studies and randomized trials to study the safety, efficacy, and optimal use of these agents for prevention or management of thrombosis in COVID-19.

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.

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.

As an acute febrile and inflammatory disease, Kawasaki disease (KD) could develop Kawasaki disease shock syndrome (KDSS) sometimes.,However its pathogenesis was still not well known.,This study was to learn more about the clinical features and evaluate the role of cytokines in the pathogenesis of KDSS.,We collected clinical and laboratory data retrospectively for all patients with KDSS(KDSS, n = 27)who were hospitalized at our hospital from Jan 2014 to Oct 2017.,For patient with KDSS, we randomly identified 43 patients with KD as control subjects (KD, n = 43).,Clinical features, laboratory evaluations were collected.,Cytokines IL-2, IL-4, IL-6, IL-10, TNF-α and IFN-γ in serum were assayed using flow cytometric bead array.,The patients with KDSS were older age (43.41 ± 31.42 vs 28.81 ± 21.51 months, P < 0.05), longer duration of fever (10.63 ± 5.12 vs 6.98 ± 2.45 days, P < 0.05), higher WBC count, neutrophils, CRP, ESR, PCT and D-dimer, and lower hemoglobin and albumin, more severe hyponatremia and hypokalemia, more refractory to IVIG therapy, more coronary artery abnormalities (CAAs), aseptic meningitis, and longer duration of hospitalization than patients with KD (all P < 0.05).,The levels of serum IL-6 [184.1 (27.7-2577.3) vs 54.1 (4-425) pg/ml], IL-10 [42.6 (5-236.7) vs 9.4 (3-94) pg/ml], TNF-α [2.6 (1.0-23.4) vs 2.1 (1-6) pg/ml] and IFN-γ [18.3 (4.5-94.4) vs 6.7 (2-56) pg/ml] in KDSS patients were significant higher than KD patients (all P < 0.05).,ROC curves showed that 66.7 pg/ml of IL-6, 20.85 pg/ml of IL-10 and 8.35 pg/ml of IFN-γ had sensitivity and specificity for identifying KDSS as 85.2 and 62.8%; 66.7 and 83.7%; 74.1 and 74.4% respectively.,No fatality was recorded in this series.,KDSS were characteristic as more cytokine production and prone to developing IVIG non-responsiveness and CAAs.,KD patients with IL-6 above 66.7 pg/ml, IL-10 above 20.85 pg/ml, and IFN-γ above 8.35 pg/ml suggested higher risk for KDSS.

Preapproval trials showed that messenger RNA (mRNA)-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations.,An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse events is needed.,We used data from the largest health care organization in Israel to evaluate the safety of the BNT162b2 mRNA vaccine.,For each potential adverse event, in a population of persons with no previous diagnosis of that event, we individually matched vaccinated persons to unvaccinated persons according to sociodemographic and clinical variables.,Risk ratios and risk differences at 42 days after vaccination were derived with the use of the Kaplan-Meier estimator.,To place these results in context, we performed a similar analysis involving SARS-CoV-2-infected persons matched to uninfected persons.,The same adverse events were studied in the vaccination and SARS-CoV-2 infection analyses.,In the vaccination analysis, the vaccinated and control groups each included a mean of 884,828 persons.,Vaccination was most strongly associated with an elevated risk of myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2).,SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis (risk ratio, 18.28; 95% CI, 3.95 to 25.12; risk difference, 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8) and of additional serious adverse events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia.,In this study in a nationwide mass vaccination setting, the BNT162b2 vaccine was not associated with an elevated risk of most of the adverse events examined.,The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons).,The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection.,(Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.)

Clinical trials of the BNT162b2 vaccine, revealed efficacy and safety.,We report six cases of myocarditis, which occurred shortly after BNT162b2 vaccination.,Patients were identified upon presentation to the emergency department with symptoms of chest pain/discomfort.,In all study patients, we excluded past and current COVID-19.,Routine clinical and laboratory investigations for common etiologies of myocarditis were performed.,Laboratory tests also included troponin and C-reactive protein levels.,The diagnosis of myocarditis was established after cardiac MRI.,Five patients presented after the second and one after the first dose of the vaccine.,All patients were males with a median age of 23 years.,Myocarditis was diagnosed in all patients, there was no evidence of COVID-19 infection.,Laboratory assays excluded concomitant infection; autoimmune disorder was considered unlikely.,All patients responded to the BNT162b2 vaccine.,The clinical course was mild in all six patients.,Our report of myocarditis after BNT162b2 vaccination may be possibly considered as an adverse reaction following immunization.,We believe our information should be interpreted with caution and further surveillance is warranted.

•We evaluated ECG features of patients hospitalized for COVID-19 pneumonia.,•New ECG abnormalities reflected a wide spectrum of cardiovascular complications.,•The most common manifestations were signs of pericarditis and atrial fibrillation.,•ECG abnormalities showed a late onset from hospitalization.,•ECG abnormalities seem to follow a separate course from the respiratory infection.,We evaluated ECG features of patients hospitalized for COVID-19 pneumonia.,New ECG abnormalities reflected a wide spectrum of cardiovascular complications.,The most common manifestations were signs of pericarditis and atrial fibrillation.,ECG abnormalities showed a late onset from hospitalization.,ECG abnormalities seem to follow a separate course from the respiratory infection.,.,The electrocardiographic (ECG) changes which may occur during hospitalization for COVID-19 have not yet been comprehensively assessed.,.,We examined 50 patients admitted to hospital with proven COVID-19 pneumonia.,At entry, all patients underwent a detailed clinical examination, 12-lead ECG, laboratory tests and arterial blood gas test.,ECG was also recorded at discharge and in case of worsening clinical conditions.,.,Mean age of patients was 64 years and 72% were men.,At baseline, 30% of patients had ST-T abnormalities, and 33% had left ventricular hypertrophy.,During hospitalization, 26% of patients developed new ECG abnormalities which included atrial fibrillation, ST-T changes, tachy-brady syndrome, and changes consistent with acute pericarditis.,One patient was transferred to intensive care unit for massive pulmonary embolism with right bundle branch block, and another for non-ST segment elevation myocardial infarction.,Patients free of ECG changes during hospitalization were more likely to be treated with antiretrovirals (68% vs 15%, p = 0.001) and hydroxychloroquine (89% vs 62%, p = 0.026) versus those who developed ECG abnormalities after admission.,Most measurable ECG features at discharge did not show significant changes from baseline (all p>0.05) except for a slightly decrease in Cornell voltages (13±6 vs 11±5 mm; p = 0.0001) and a modest increase in the PR interval.,The majority (54%) of patients with ECG abnormalities had 2 prior consecutive negative nasopharyngeal swabs.,ECG abnormalities were first detected after an average of about 30 days from symptoms’ onset (range 12-51 days).,.,ECG abnormalities during hospitalization for COVID-19 pneumonia reflect a wide spectrum of cardiovascular complications, exhibit a late onset, do not progress in parallel with pulmonary abnormalities and may occur after negative nasopharyngeal swabs.

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.

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.

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.

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.

Fingolimod (Gilenya®) is approved for relapsing forms of multiple sclerosis in the USA.,Owing to transient heart-rate effects when initiating fingolimod, eligible patients undergo precautionary baseline assessment and first-dose observation (FDO) for ≥6 h.,Prior to 2014, FDO was undertaken only in clinics.,As the FDO period is short, and fingolimod has accumulated evidence of a positive benefit:risk ratio, an in-home treatment-initiation program, Gilenya@Home, was developed to offer a convenient alternative.,Cardiac parameters and adverse events (AEs) were recorded by healthcare professionals performing fingolimod FDOs in the US Gilenya@Home program or in US Gilenya Assessment Network clinics.,Anonymized data were collated retrospectively from the first 34 months in the home setting and from 78 months in clinics; data are reported descriptively.,Satisfaction with Gilenya@Home was rated by patients using a 7-item questionnaire that considered aspects such as ease of scheduling, courtesy, and competency.,Data were captured as part of standard care from 5573 patients initiating fingolimod in-home (October 2014 to July 2017) and from 15,025 patients initiating in-clinic (July 2010 to December 2016).,In the Gilenya@Home questionnaire, 91.7% of 1848 respondents rated their overall satisfaction as “very good,” and 7.6% rated their satisfaction as “good.”,AEs were reported for 30.7 and 32.6% of in-home and in-clinic patients, respectively.,In total, 557 in-home (10.0%) and 398 in-clinic (2.6%) patients were monitored for > 6 h; 15 (0.3%) in-home and 129 (0.9%) in-clinic patients were transferred to an emergency room for overnight monitoring.,The mean (standard deviation) heart rate (HR; bpm) pre-FDO was 74.8 (12.2) in-home and 74.2 (11.3) in-clinic; reduction in HR at 6 h postdose was 10.6 (12.0) and 6.3 (9.6), respectively.,New-onset first-degree atrioventricular block was experienced by 132 (2.4%) in-home and 74 (0.5%) in-clinic patients, and Wenckebach (Mobitz type I) second-degree atrioventricular block by four (0.07%) and nine (0.1%) patients, with no cases of third-degree atrioventricular block.,A substantial number of patients have initiated fingolimod at home, reporting very high levels of satisfaction.,Gilenya@Home was as rigorous as the clinic setting in detecting cardiovascular events.,Overall, FDO safety outcomes were similar with Gilenya@Home and in-clinic.

COVID-19 is a deadly pulmonary disease with peculiar characteristics, which include variable clinical course and thrombophilia.,A thorough understanding of the pathological correlates of the disease is still missing.,Here we report the systematic analysis of 41 consecutive post-mortem samples from individuals who died of COVID-19.,Histological analysis is complemented by immunohistochemistry for cellular and viral antigens and the detection of viral genomes by in situ RNA hybridization.,COVID-19 is characterized by extensive alveolar damage (41/41 of patients) and thrombosis of the lung micro- and macro-vasculature (29/41, 71%).,Thrombi were in different stages of organization, consistent with their local origin.,Pneumocytes and endothelial cells contained viral RNA even at the later stages of the disease.,An additional feature was the common presence of a large number of dysmorphic pneumocytes, often forming syncytial elements (36/41, 87%).,Despite occasional detection of virus-positive cells, no overt signs of viral infection were detected in other organs, which showed non-specific alterations.,COVID-19 is a unique disease characterized by extensive lung thrombosis, long-term persistence of viral RNA in pneumocytes and endothelial cells, along with the presence of infected cell syncytia.,Several of COVID-19 features might be consequent to the persistence of virus-infected cells for the duration of the disease.,This work was supported by a King's Together Rapid COVID-19 Call grant from King's College London.,MG is supported by the European Research Council (ERC) Advanced Grant 787971 “CuRE” and by Programme Grant RG/19/11/34633 from the British Heart Foundation.

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.

According to a report on the worldwide trends in blood pressure from 1975 to 2015, mean blood pressure is increasing in low and middle income countries while it is either decreasing or stabilizing in high income countries.,Few studies have been published on the prevalence of hypertension in Ethiopia demonstrating an increased trend; however, these studies had small sample size and were limited to participants older than 35 years; which left the burden among adolescents and young adults unaddressed.,The aim of this study was to assess prevalence of hypertension (HTN) and associated factors in Gondar city.,A population based cross-sectional study was conducted among 3227 individuals in Gondar city.,A multistage cluster random sampling was used.,The Kish method from World Health Organization (WHO) STEPS instrument of random sampling method was used for selecting one individual older than or equal to 18 years from each household.,WHO and International Diabetic Association (IDA) criterion was used to classify HTN.,The overall prevalence of HTN was 27.,4% [95% CI: (25.,8-28.9)].,The prevalence for participants in the age group of ≥35 years was 36.,1%.,It consistently increased from 9.5% in the age group of 18-25 years to 46.3% in the age group of ≥65 years (P-value < 0.,001).,Only 47% of the participants had ever had any kind of blood pressure measurement.,Being elderly (AOR = 5.,56; 95% CI: 3.,71-8. 35), obese (AOR =2.,62; 95%CI: 1.,70-4. 03), widowed (AOR = 1.,87; 95%CI: 1.,27-2. 75), separated (AOR = 1.,87; 95%CI: 1.,27-2. 75), daily alcohol user (AOR = 1.,51; 95%CI: 1.,02-2. 23), male gender (AOR = 1.,42; 95%CI: 1.,18-1. 72) and born in urban area (AOR = 1.,31; 95%CI: 1.,10-1. 56) were found to be independently associated with HTN.,There is a high prevalence of hypertension in Gondar city and is showing increasing trend compared to previous reports.,Interventions to raise awareness and to improve both capacity and accessibility of facilities for screening hypertension are highly recommended.

Hypertension is a major risk factor of cardiovascular diseases which are the leading causes of deaths from chronic non-communicable diseases in Ethiopia.,However, little is documented in the issue.,Therefore, this study aimed to assess the prevalence, associated factors, awareness, treatment and control of hypertension among adults 18 years old or above in Aksum town, Tigray region, North Ethiopia.,A sequential quantitative-qualitative study was conducted among adults aged 18 years and above in Aksum town.,A multi stage sampling procedure was used to select the study participants for the quantitative study whilst convenience sampling technique was used for the qualitative part.,A pre-tested and structured questionnaire was used to collect quantitative data, and an interview guide was used to collect the qualitative data.,The logistic regression model was fitted to identify factors independently associated with hypertension using SPSS Version 20.,P-values of < 0.05 were considered statistically significant.,For the qualitative data, iterative hearing of the discussions verbatim interpretation was followed by categorizing similar ideas into themes and finally triangulated with the quantitative results.,The overall prevalence of hypertension was 16.5% (95% CI: 13.4, 20.0).,Awareness, treatment and control of hypertension were 43%, 2.1% and 18.2%, respectively.,Being unable to read and write [AOR = 4.73, 95% CI:1.11, 20.23], not consuming fruit [AOR = 4.31, 95% CI:1.74, 10.66], being physically inactive [AOR = 20.11, 95% CI:8.75, 6.20], not knowing physical inactivity is a risk factor of hypertension [AOR = 3.57, 95% CI: 1.69, 7.69] and being overweight/obese [AOR = 9.2, 95% CI:4.54, 18.67] were significantly associated with hypertension.,Remarkably, all identified hypertensive cases were linked to the nearby hospital for confirmation of diagnosis, care and follow-up and all of them were found to be hypertensive.,This suggests that implementing primary health care approach integrated with the urban health extension package may be effective in the prevention and control of hypertension in poor settings.,Prevalence of hypertension among adults was very high, but awareness, treatment and control of hypertension was very low.,Being unable to read and write, not consuming fruit, being physically inactive, overweight/obesity and not knowing physical inactivity is a risk factor for hypertension were independently associated with hypertension.,Policy makers need to consider integrating prevention and control of hypertension with health extension package.,Appropriate information, education and communication strategies should also be designed and implemented to avoid unhealthy lifestyles and promote healthy practices.

Neovascularization and vascular remodeling are functionally important for brain repair after stroke.,We show that neutrophils accumulate in the peri-infarct cortex during all stages of ischemic stroke.,Neutrophils producing intravascular and intraparenchymal neutrophil extracellular traps (NETs) peak at 3-5 days.,Neutrophil depletion reduces blood-brain barrier (BBB) breakdown and enhances neovascularization at 14 days.,Peptidylarginine deiminase 4 (PAD4), an enzyme essential for NET formation, is upregulated in peri-ischemic brains.,Overexpression of PAD4 induces an increase in NET formation that is accompanied by reduced neovascularization and increased BBB damage.,Disruption of NETs by DNase 1 and inhibition of NET formation by genetic ablation or pharmacologic inhibition of PAD increases neovascularization and vascular repair and improves functional recovery.,Furthermore, PAD inhibition reduces stroke-induced STING-mediated production of IFN-β, and STING knockdown and IFN receptor-neutralizing antibody treatment reduces BBB breakdown and increases vascular plasticity.,Collectively, our results indicate that NET release impairs vascular remodeling during stroke recovery.,Following ischemic insult, neovascularization and vascular remodelling play an essential part in the repair of brain damage.,Here the authors show that neutrophil extracellular traps serve a detrimental role in the regeneration process, limiting the functional recovery of the brain post injury.

Regulation of neural inflammation is considered as a vital therapeutic target in ischemic stroke.,All-trans retinoic acid (atRA), a potent immune modulator, has raised interest in the field of stroke therapy.,However, the immunological mechanisms for atRA-mediated neuroprotection remain elusive.,The current study evaluated the impact of atRA on post-stroke neural inflammation and elucidated the mechanisms involved in the regulation of related neutrophil functions.,atRA was prophylactically administered to mice 1 day before transient middle cerebral artery occlusion (tMCAO, 1 h) and repeated daily immediately after reperfusion for 3 days.,Stroke outcomes, neutrophil polarization, and formation of neutrophil extracellular traps (NETs) in the stroke lesion were assessed.,Neutrophil depletion was induced with anti-Ly6G antibodies.,Primary neutrophil cultures were used to explore the mechanisms of atRA treatment.,Prophylactic atRA treatment reduced infarct volumes and neurological deficits at 1 day after tMCAO.,Post-stroke neural inflammation was attenuated and neutrophil accumulation in lesion was downregulated. atRA treatment skewed neutrophil toward N2 phenotype which facilitated its clearance by macrophage and inhibited NETs formation.,The functions of neutrophil were indispensable in the protective effects of atRA and were associated with suppression to STAT1 signaling by atRA.,Administration of atRA after stroke still provided efficient protection to cerebral ischemia.,atRA displays potent therapeutic efficacy in ischemic stroke by attenuating neural inflammation.,Treatment of atRA impeded neutrophil accumulation, favored N2 polarization, and forbade NETs formation in ischemic lesion.,STAT1 signaling played a decisive role in the mechanisms of atRA-afforded regulation to neutrophil.,The online version of this article (10.1186/s12974-019-1557-6) contains supplementary material, which is available to authorized users.

Supplemental Digital Content is available in the text.,Many patients with heart failure and reduced ejection fraction (HFrEF) have chronic kidney disease that complicates pharmacological management and is associated with worse outcomes.,We assessed the safety and efficacy of dapagliflozin in patients with HFrEF, according to baseline kidney function, in the DAPA-HF trial (Dapagliflozin and Prevention of Adverse-outcomes in Heart Failure).,We also examined the effect of dapagliflozin on kidney function after randomization.,Patients who have HFrEF with or without type 2 diabetes and an estimated glomerular filtration rate (eGFR) ≥30 mL·min-1·1.73 m-2 were enrolled in DAPA-HF.,We calculated the incidence of the primary outcome (cardiovascular death or worsening heart failure) according to eGFR category at baseline (<60 and ≥60 mL·min-1·1.73 m-2) and used eGFR at baseline as a continuous measure, as well.,Secondary cardiovascular outcomes and a prespecified composite renal outcome (≥50% sustained decline eGFR, end-stage renal disease, or renal death) were also examined, along with a decline in eGFR over time.,Of 4742 patients with a baseline eGFR, 1926 (41%) had eGFR <60 mL·min-1·1.73 m-2.,The effect of dapagliflozin on the primary and secondary outcomes did not differ by eGFR category or examining eGFR as a continuous measurement.,The hazard ratio (95% CI) for the primary end point in patients with chronic kidney disease was 0.71 (0.59-0.86) versus 0.77 (0.64-0.93) in those with an eGFR ≥60 mL·min-1·1.73 m-2 (interaction P=0.54).,The composite renal outcome was not reduced by dapagliflozin (hazard ratio=0.71 [95% CI, 0.44-1.16]; P=0.17) but the rate of decline in eGFR between day 14 and 720 was less with dapagliflozin, -1.09 (-1.40 to -0.77) versus placebo -2.85 (-3.17 to -2.53) mL·min-1·1.73 m-2 per year (P<0.001).,This was observed in those with and without type 2 diabetes (P for interaction=0.92).,Baseline kidney function did not modify the benefits of dapagliflozin on morbidity and mortality in HFrEF, and dapagliflozin slowed the rate of decline in eGFR, including in patients without diabetes.,URL: https://www.clinicaltrials.gov; Unique identifier: NCT03036124.

Supplemental Digital Content is available in the text.,Reduction in cardiovascular death and hospitalization for heart failure (HHF) was recently reported with the sodium-glucose cotransporter-2 inhibitor (SGLT-2i) empagliflozin in patients with type 2 diabetes mellitus who have atherosclerotic cardiovascular disease.,We compared HHF and death in patients newly initiated on any SGLT-2i versus other glucose-lowering drugs in 6 countries to determine if these benefits are seen in real-world practice and across SGLT-2i class.,Data were collected via medical claims, primary care/hospital records, and national registries from the United States, Norway, Denmark, Sweden, Germany, and the United Kingdom.,Propensity score for SGLT-2i initiation was used to match treatment groups.,Hazard ratios for HHF, death, and their combination were estimated by country and pooled to determine weighted effect size.,Death data were not available for Germany.,After propensity matching, there were 309 056 patients newly initiated on either SGLT-2i or other glucose-lowering drugs (154 528 patients in each treatment group).,Canagliflozin, dapagliflozin, and empagliflozin accounted for 53%, 42%, and 5% of the total exposure time in the SGLT-2i class, respectively.,Baseline characteristics were balanced between the 2 groups.,There were 961 HHF cases during 190 164 person-years follow-up (incidence rate, 0.51/100 person-years).,Of 215 622 patients in the United States, Norway, Denmark, Sweden, and the United Kingdom, death occurred in 1334 (incidence rate, 0.87/100 person-years), and HHF or death in 1983 (incidence rate, 1.38/100 person-years).,Use of SGLT-2i, versus other glucose-lowering drugs, was associated with lower rates of HHF (hazard ratio, 0.61; 95% confidence interval, 0.51-0.73; P<0.001); death (hazard ratio, 0.49; 95% confidence interval, 0.41-0.57; P<0.001); and HHF or death (hazard ratio, 0.54; 95% confidence interval, 0.48-0.60; P<0.001) with no significant heterogeneity by country.,In this large multinational study, treatment with SGLT-2i versus other glucose-lowering drugs was associated with a lower risk of HHF and death, suggesting that the benefits seen with empagliflozin in a randomized trial may be a class effect applicable to a broad population of patients with type 2 diabetes mellitus in real-world practice.,URL: http://www.clinicaltrials.gov.,Unique identifier: NCT02993614.

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.

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.

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes.,The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes.,A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke.,Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy.,Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies.,The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity.,They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study.,It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury.

The cardiac microvascular system ischemia/reperfusion injury following percutaneous coronary intervention is a clinical thorny problem.,This study explores the mechanisms by which ischemia/reperfusion injury induces cardiac microcirculation collapse.,In wild‐type mice, mitochondrial fission factor (Mff) expression increased in response to acute microvascular ischemia/reperfusion injury.,Compared with wild‐type mice, homozygous Mff‐deficient (Mffgt) mice exhibited a smaller infarcted area, restored cardiac function, improved blood flow, and reduced microcirculation perfusion defects.,Histopathology analysis demonstrated that cardiac microcirculation endothelial cells (CMECs) in Mffgt mice had an intact endothelial barrier, recovered phospho‐endothelial nitric oxide synthase production, opened lumen, undivided mitochondrial structures, and less CMEC death.,In vitro, Mff‐deficient CMECs (derived from Mffgt mice or Mff small interfering RNA-treated) demonstrated less mitochondrial fission and mitochondrial‐dependent apoptosis compared with cells derived from wild‐type mice.,The loss of Mff inhibited mitochondrial permeability transition pore opening via blocking the oligomerization of voltage‐dependent anion channel 1 and subsequent hexokinase 2 separation from mitochondria.,Moreover, Mff deficiency reduced the cyt‐c leakage into the cytoplasm by alleviating cardiolipin oxidation resulting from damage to the electron transport chain complexes and mitochondrial reactive oxygen species overproduction.,This evidence clearly illustrates that microcirculatory ischemia/reperfusion injury can be attributed to Mff‐dependent mitochondrial fission via voltage‐dependent anion channel 1/hexokinase 2-mediated mitochondrial permeability transition pore opening and mitochondrial reactive oxygen species/cardiolipin involved cyt‐c release.

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.

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 association of pulmonary embolism (PE) with deep vein thrombosis (DVT) in patients with coronavirus disease 2019 (COVID-19) remains unclear, and the diagnostic accuracy of D-dimer tests for PE is unknown.,To conduct meta-analysis of the study-level incidence of PE and DVT and to evaluate the diagnostic accuracy of D-dimer tests for PE from multicenter individual patient data.,A systematic literature search identified studies evaluating the incidence of PE or DVT in patients with COVID-19 from January 1, 2020, to June 15, 2020.,These outcomes were pooled using a random-effects model and were further evaluated using metaregression analysis.,The diagnostic accuracy of D-dimer tests for PE was estimated on the basis of individual patient data using the summary receiver operating characteristic curve.,Twenty-seven studies with 3342 patients with COVID-19 were included in the analysis.,The pooled incidence rates of PE and DVT were 16.5% (95% CI: 11.6, 22.9; I2 = 0.93) and 14.8% (95% CI: 8.5, 24.5; I2 = 0.94), respectively.,PE was more frequently found in patients who were admitted to the intensive care unit (ICU) (24.7% [95% CI: 18.6, 32.1] vs 10.5% [95% CI: 5.1, 20.2] in those not admitted to the ICU) and in studies with universal screening using CT pulmonary angiography.,DVT was present in 42.4% of patients with PE.,D-dimer tests had an area under the receiver operating characteristic curve of 0.737 for PE, and D-dimer levels of 500 and 1000 μg/L showed high sensitivity (96% and 91%, respectively) but low specificity (10% and 24%, respectively).,Pulmonary embolism (PE) and deep vein thrombosis (DVT) occurred in 16.5% and 14.8% of patients with coronavirus disease 2019 (COVID-19), respectively, and more than half of patients with PE lacked DVT.,The cutoffs of D-dimer levels used to exclude PE in preexisting guidelines seem applicable to patients with COVID-19.,© RSNA, 2020,Supplemental material is available for this article.,See also the editorial by Woodard in this issue.

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.

Heightened inflammation, dysregulated immunity, and thrombotic events are characteristic of hospitalized COVID‐19 patients.,Given that platelets are key regulators of thrombosis, inflammation, and immunity they represent prime candidates as mediators of COVID‐19‐associated pathogenesis.,The objective of this study was to understand the contribution of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) to the platelet phenotype via phenotypic (activation, aggregation) and transcriptomic characterization.,In a cohort of 3915 hospitalized COVID‐19 patients, we analyzed blood platelet indices collected at hospital admission.,Following adjustment for demographics, clinical risk factors, medication, and biomarkers of inflammation and thrombosis, we find platelet count, size, and immaturity are associated with increased critical illness and all‐cause mortality.,Bone marrow, lung tissue, and blood from COVID‐19 patients revealed the presence of SARS‐CoV‐2 virions in megakaryocytes and platelets.,Characterization of COVID‐19 platelets found them to be hyperreactive (increased aggregation, and expression of P‐selectin and CD40) and to have a distinct transcriptomic profile characteristic of prothrombotic large and immature platelets.,In vitro mechanistic studies highlight that the interaction of SARS‐CoV‐2 with megakaryocytes alters the platelet transcriptome, and its effects are distinct from the coronavirus responsible for the common cold (CoV‐OC43).,Platelet count, size, and maturity associate with increased critical illness and all‐cause mortality among hospitalized COVID‐19 patients.,Profiling tissues and blood from COVID‐19 patients revealed that SARS‐CoV‐2 virions enter megakaryocytes and platelets and associate with alterations to the platelet transcriptome and activation profile.

Progressive respiratory failure is seen as a major cause of death in severe acute respiratory syndrome coronavirus 2 (SARS-Cov-2)-induced infection.,Relatively little is known about the associated morphologic and molecular changes in the circulation of these patients.,In particular, platelet and erythrocyte pathology might result in severe vascular issues, and the manifestations may include thrombotic complications.,These thrombotic pathologies may be both extrapulmonary and intrapulmonary and may be central to respiratory failure.,Previously, we reported the presence of amyloid microclots in the circulation of patients with coronavirus disease 2019 (COVID-19).,Here, we investigate the presence of related circulating biomarkers, including C-reactive protein (CRP), serum ferritin, and P-selectin.,These biomarkers are well-known to interact with, and cause pathology to, platelets and erythrocytes.,We also study the structure of platelets and erythrocytes using fluorescence microscopy (using the markers PAC-1 and CD62PE) and scanning electron microscopy.,Thromboelastography and viscometry were also used to study coagulation parameters and plasma viscosity.,We conclude that structural pathologies found in platelets and erythrocytes, together with spontaneously formed amyloid microclots, may be central to vascular changes observed during COVID-19 progression, including thrombotic microangiopathy, diffuse intravascular coagulation, and large-vessel thrombosis, as well as ground-glass opacities in the lungs.,Consequently, this clinical snapshot of COVID-19 strongly suggests that it is also a true vascular disease and considering it as such should form an essential part of a clinical treatment regime.

The spread of the novel coronavirus SARS-CoV-2 and the guidance from authorities for social distancing and media reporting lead to significant uncertainty in Germany.,Concerns have been expressed regarding the underdiagnosing of harmful diseases.,We explored the rates of emergency presentations for acute coronary syndrome (ACS) and acute cerebrovascular events (ACVE) before and after spread of SARS-CoV-2.,We analyzed all-cause visits at a tertiary university emergency department and admissions for ACS and ACVE before (calendar weeks 1-9, 2020) and after (calendar weeks 10-16, 2020) the first coronavirus disease (COVID-19) case in the region of the Saarland, Germany.,The data were compared with the same period of the previous year.,In 2020 an average of 346 patients per week presented at the emergency department whereas in 2019 an average of 400 patients presented up to calendar week 16 (p = 0.018; whole year 2019 = 395 patients per week).,After the first COVID-19 diagnosis in the region, emergency department visit volume decreased by 30% compared with the same period in 2019 (p = 0.0012).,Admissions due to ACS decreased by 41% (p = 0.0023 for all; Δ − 71% (p = 0.007) for unstable angina, Δ − 25% (p = 0.42) for myocardial infarction with ST-elevation and Δ − 17% (p = 0.28) without ST-elevation) compared with the same period in 2019 and decreased from 142 patients in calendar weeks 1-9 to 62 patients in calendar weeks 10-16.,ACVE decreased numerically by 20% [p = 0.25 for all; transient ischemic attack: Δ − 32% (p = 0.18), ischemic stroke: Δ − 23% (p = 0.48), intracerebral haemorrhage: Δ + 57% (p = 0.4)].,There was no significant change in ACVE per week (p = 0.7) comparing calendar weeks 1-9 (213 patients) and weeks 10-16 (147 patients).,Testing of 3756 samples was performed to detect 58 SARS-CoV-2 positive patients (prevalence 1,54%, thereof one patient with myocardial and two with cerebral ischemia) up to calendar week 16 in 2020.,The COVID-19 pandemic was associated with a significant decrease in all-cause admission and admissions due to cardiovascular events in the emergency department.,Regarding acute cerebrovascular events there was a numerical decrease but no significant difference.

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.

The possible effects of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) on COVID-19 disease severity have generated considerable debate.,We performed a single-center, retrospective analysis of hospitalized adult COVID-19 patients in Wuhan, China, who had definite clinical outcome (dead or discharged) by February 15, 2020.,Patients on anti-hypertensive treatment with or without ACEI/ARB were compared on their clinical characteristics and outcomes.,The medical records from 702 patients were screened.,Among the 101 patients with a history of hypertension and taking at least one anti-hypertensive medication, 40 patients were receiving ACEI/ARB as part of their regimen, and 61 patients were on antihypertensive medication other than ACEI/ARB.,We observed no statistically significant differences in percentages of in-hospital mortality (28% vs.,34%, P = 0.46), ICU admission (20% vs.,28%, P = 0.37) or invasive mechanical ventilation (18% vs.,26%, P = 0.31) between patients with or without ACEI/ARB treatment.,Further multivariable adjustment of age and gender did not provide evidence for a significant association between ACEI/ARB treatment and severe COVID-19 outcomes.,Our findings confirm the lack of an association between chronic receipt of renin-angiotensin system antagonists and severe outcomes of COVID-19.,Patients should continue previous anti-hypertensive therapy until further evidence is available.

To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease.,To assess the association between renin-angiotensin system inhibitors (RASIs) and disease progression and critical outcomes.,All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study.,The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission.,Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint.,Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2.,Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32-54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61-84)].,A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU.,Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age.,After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02-2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class.,This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents.,We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome.,Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.

Initial reports on COVID-19 described children as largely spared from severe manifestations, with only 2-6% of children requiring intensive care treatment.,However, since mid-April 2020, clusters of pediatric cases of severe systemic hyperinflammation and shock epidemiologically linked with COVID-19 have been reported.,This condition was named as SARS-Cov-2-associated multisystem inflammatory syndrome in children and showed similarities to Kawasaki disease.,Here, we present a narrative review of cases reported in literature and we discuss the clinical acute and follow-up management of these patients.,Patients with SARS-Cov-2-associated multisystem inflammatory syndrome frequently presented with persistent fever, gastrointestinal symptoms, polymorphic rash, conjunctivitis, and mucosal changes.,Elevated inflammatory markers and evidence of cytokine storm were frequently observed.,A subset of these patients also presented with hypotension and shock (20-100%) from either acute myocardial dysfunction or systemic hyperinflammation/vasodilation.,Coronary artery dilation or aneurysms have been described in 6-24%, and arrhythmias in 7-60%.,Cardiac support, immunomodulation, and anticoagulation are the key aspects for the management of the acute phase.,Long-term structured follow-up of these patients is required due to the unclear prognosis and risk of progression of cardiac manifestations.,Conclusion: Multisystem inflammatory syndrome is a novel syndrome related to SARS-CoV-2 infection.,Evidence is still scarce but rapidly emerging in the literature.,Cardiac manifestations are frequent, including myocardial and coronary involvement, and need to be carefully identified and monitored over time.What is Known:• Multisystem inflammatory syndrome in children (MIS-C) has been described associated with SARS-CoV-2.,What is New:• Patients with MIS-C often present with fever, gastrointestinal symptoms, and shock.,• Cardiac involvement is found in a high proportion of these patients, including ventricular dysfunction, coronary artery dilation or aneurysm, and arrhythmias.,• Management is based on expert consensus and includes cardiac support, immunomodulatory agents, and anticoagulation.,• Long-term follow-up is required due to the unclear prognosis and risk of progression of cardiac manifestation.,What is Known:,• Multisystem inflammatory syndrome in children (MIS-C) has been described associated with SARS-CoV-2.,What is New:,• Patients with MIS-C often present with fever, gastrointestinal symptoms, and shock.,• Cardiac involvement is found in a high proportion of these patients, including ventricular dysfunction, coronary artery dilation or aneurysm, and arrhythmias.,• Management is based on expert consensus and includes cardiac support, immunomodulatory agents, and anticoagulation.,• Long-term follow-up is required due to the unclear prognosis and risk of progression of cardiac manifestation.,The online version of this article (10.1007/s00431-020-03766-6) contains supplementary material, which is available to authorized users.

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.

Ambiguity exists in relation to the role of physical activity (PA) for cardiovascular disease (CVD) risk reduction.,We examined the interplay between PA dimensions and more conventional CVD risk factors to assess which PA dimensions were associated with the first CVD event and whether subgroup differences exist.,A total of 1449 individuals [median age 65.8 (IQR: 61.2, 70.7) years] with low to high risk of type 2 diabetes and free from CVD from the Danish ADDITION-PRO study were included for survival analysis.,PA was measured by individually calibrated heart rate and movement sensing for 7 consecutive days.,The associations of different PA dimensions (PA energy expenditure, time spent in light-, moderate- and vigorous intensity PA), sedentary time and other conventional CVD risk factors with the first CVD event were examined by tree-structured survival analysis.,Baseline information was linked to data on the first CVD event (ischemic heart disease, ischemic stroke, heart failure, atrial flutter/fibrillation and atherosclerotic disease) and mortality obtained from Danish registers.,During a median follow-up time of 5.5 (IQR: 5.1-6.1) years, a total of 201 individuals (13.9%) developed CVD.,Overall CVD incidence rate was 2.6/100 person-years.,PA energy expenditure above 43 kJ/kg/day was associated with lower rates of CVD events among participants ≤ 70 years and with HbA1c ≤ 5.7% (39 mmol/mol), systolic blood pressure ≤ 156 mmHg and albumin creatinine ratio ≤ 70 (incidence rates 0.0-0.8/100 person-years).,Any type of PA resulting in increased PA energy expenditure may over time be the best prevention strategy to uphold reduced risk of CVD.,The online version of this article (10.1186/s12933-018-0769-x) contains supplementary material, which is available to authorized users.

Exercise training is considered a cornerstone in the management of type 2 diabetes, which is associated with impaired endothelial function.,However, the association of exercise training with endothelial function in type 2 diabetes patients has not been fully understood.,This meta-analysis aimed to investigate their associations with focus on exercise types.,Databases were searched up to January 2018 for studies evaluating the influences of exercise training with durations ≥ 8 weeks on endothelial function assessed by flow-mediated dilation (FMD) among type 2 diabetes patients or between type 2 diabetics and non-diabetics.,Data were pooled using random-effects models to obtain the weighted mean differences (WMDs) and 95% confidence intervals (CIs).,Sixteen databases were included.,Exercise training resulted in an overall improvement in FMD by 1.77% (95% CI 0.94-2.59%) in type 2 diabetes patients.,Specifically, both aerobic and combined aerobic and resistance exercise increased FMD by 1.21% (95% CI 0.23-2.19%) and 2.49% (95% CI 1.17-3.81%), respectively; but resistance exercise only showed a trend.,High-intensity interval aerobic exercise did not significantly improve FMD over moderate-intensity continuous exercise.,Notably, the improvement in FMD among type 2 diabetes patients was smaller compared with non-diabetics in response to exercise training (WMD − 0.72%, 95% CI − 1.36 to − 0.08%) or specifically to aerobic exercise (WMD − 0.65%, 95% CI − 1.31 to 0.01%).,Exercise training, in particular aerobic and combined exercise, improves endothelial function in type 2 diabetes patients, but such an improvement appears to be weakened compared with non-diabetics.,Trial registration PROSPERO CRD42018087376,The online version of this article (10.1186/s12933-018-0711-2) contains supplementary material, which is available to authorized users.

Observational data suggest an acquired prothrombotic state may contribute to the pathophysiology of COVID-19.,These data include elevated D-dimers observed among many COVID-19 patients.,We present a retrospective analysis of admission D-dimer, and D-dimer trends, among 1065 adult hospitalized COVID-19 patients, across 6 New York Hospitals.,The primary outcome was all-cause mortality.,Secondary outcomes were intubation and venous thromboembolism (VTE).,Three-hundred-thirteen patients (29.4%) died, 319 (30.0%) required intubation, and 30 (2.8%) had diagnosed VTE.,Using Cox proportional-hazard modeling, each 1 μg/ml increase in admission D-dimer level was associated with a hazard ratio (HR) of 1.06 (95%CI 1.04-1.08, p < 0.0001) for death, 1.08 (95%CI 1.06-1.10, p < 0.0001) for intubation, and 1.08 (95%CI 1.03-1.13, p = 0.0087) for VTE.,Time-dependent receiver-operator-curves for admission D-dimer as a predictor of death, intubation, and VTE yielded areas-under-the-curve of 0.694, 0.621, and 0.565 respectively.,Joint-latent-class-modeling identified distinct groups of patients with respect to D-dimer trend.,Patients with stable D-dimer trajectories had HRs of 0.29 (95%CI 0.17-0.49, p < 0.0001) and 0.22 (95%CI 0.10-0.45, p = 0.0001) relative to those with increasing D-dimer trajectories, for the outcomes death and intubation respectively.,Patients with low-increasing D-dimer trajectories had a multivariable HR for VTE of 0.18 (95%CI 0.05-0.68, p = 0.0117) relative to those with high-decreasing D-dimer trajectories.,Time-dependent receiver-operator-curves for D-dimer trend as a predictor of death, intubation, and VTE yielded areas-under-the-curve of 0.678, 0.699, and 0.722 respectively.,Although admission D-dimer levels, and D-dimer trends, are associated with outcomes in COVID-19, they have limited performance characteristics as prognostic tests.,•We present a retrospective analysis of admission D-dimer, and D-dimer trends, among adults hospitalized for COVID-19.•1065 inpatients from 6 hospitals were included; outcomes included mortality, intubation, and VTE.,•Admission D-dimers and D-dimer trends were associated with outcomes in COVID-19.,•However, D-dimer levels and trends were limited prognostic tests in COVID-19.,•The role of D-dimer levels in COVID-19 clinical decision making remains unclear.,We present a retrospective analysis of admission D-dimer, and D-dimer trends, among adults hospitalized for COVID-19.,1065 inpatients from 6 hospitals were included; outcomes included mortality, intubation, and VTE.,Admission D-dimers and D-dimer trends were associated with outcomes in COVID-19.,However, D-dimer levels and trends were limited prognostic tests in COVID-19.,The role of D-dimer levels in COVID-19 clinical decision making remains unclear.

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.

The aim of this document is to provide specific recommendations on the use of cardiovascular magnetic resonance (CMR) protocols in the era of the COVID-19 pandemic.,In patients without COVID-19, standard CMR protocols should be used based on clinical indication as usual.,Protocols used in patients who have known / suspected active COVID-19 or post COVID-19 should be performed based on the specific clinical question with an emphasis on cardiac function and myocardial tissue characterization.,Short and dedicated protocols are recommended.

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.

Coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become pandemic, with substantial mortality.,To evaluate the pathologic changes of organ systems and the clinicopathologic basis for severe and fatal outcomes.,Prospective autopsy study.,Single pathology department.,11 deceased patients with COVID-19 (10 of whom were selected at random for autopsy).,Systematic macroscopic, histopathologic, and viral analysis (SARS-CoV-2 on real-time polymerase chain reaction assay), with correlation of pathologic and clinical features, including comorbidities, comedication, and laboratory values.,Patients' age ranged from 66 to 91 years (mean, 80.5 years; 8 men, 3 women).,Ten of the 11 patients received prophylactic anticoagulant therapy; venous thromboembolism was not clinically suspected antemortem in any of the patients.,Both lungs showed various stages of diffuse alveolar damage (DAD), including edema, hyaline membranes, and proliferation of pneumocytes and fibroblasts.,Thrombosis of small and mid-sized pulmonary arteries was found in various degrees in all 11 patients and was associated with infarction in 8 patients and bronchopneumonia in 6 patients.,Kupffer cell proliferation was seen in all patients, and chronic hepatic congestion in 8 patients.,Other changes in the liver included hepatic steatosis, portal fibrosis, lymphocytic infiltrates and ductular proliferation, lobular cholestasis, and acute liver cell necrosis, together with central vein thrombosis.,Additional frequent findings included renal proximal tubular injury, focal pancreatitis, adrenocortical hyperplasia, and lymphocyte depletion of spleen and lymph nodes.,Viral RNA was detectable in pharyngeal, bronchial, and colonic mucosa but not bile.,The sample was small.,COVID-19 predominantly involves the lungs, causing DAD and leading to acute respiratory insufficiency.,Death may be caused by the thrombosis observed in segmental and subsegmental pulmonary arterial vessels despite the use of prophylactic anticoagulation.,Studies are needed to further understand the thrombotic complications of COVID-19, together with the roles for strict thrombosis prophylaxis, laboratory, and imaging studies and early anticoagulant therapy for suspected pulmonary arterial thrombosis or thromboembolism.,None.,The clinicopathological basis for morbidity and mortality with SARS-CoV-2 infection is not well understood.,This study reports the clinical and autopsy findings of patients who died of COVID-19.

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.

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.

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.

Genetic testing in hypertrophic cardiomyopathy (HCM) has long relied on Sanger sequencing of sarcomeric genes.,The advent of next-generation sequencing (NGS) has catalyzed routine testing of additional genes of dubious HCM-causing potential.,We used 19 years of genetic testing results to define a reliable set of genes implicated in Mendelian HCM and assess the value of expanded NGS panels.,We dissected genetic testing results from 1,198 single-center HCM probands and devised a widely applicable score to identify which genes yield effective results in the diagnostic setting.,Compared with early panels targeting only fully validated sarcomeric HCM genes, expanded NGS panels allow the prompt recognition of probands with HCM-mimicking diseases.,Scoring by “diagnostic effectiveness” highlighted that PLN should also be routinely screened besides historically validated genes for HCM and its mimics.,The additive value of expanded panels in HCM genetic testing lies in the systematic screening of genes associated with HCM mimics, requiring different patient management.,Only variants in a limited set of genes are highly actionable and interpretable in the clinic, suggesting that larger panels offer limited additional sensitivity.,A score estimating the relative effectiveness of a given gene’s inclusion in diagnostic panels is proposed.

The “super-relaxed state” (SRX) of myosin represents a ‘reserve’ of motors in the heart.,Myosin heads in the SRX are bound to the thick filament and have a very low ATPase rate.,Changes in the SRX are likely to modulate cardiac contractility.,We previously demonstrated that the SRX is significantly reduced in mouse cardiomyocytes lacking cardiac myosin binding protein-C (cMyBP-C).,Here, we report the effect of mutations in the cMyBP-C gene (MYBPC3) using samples from human patients with hypertrophic cardiomyopathy (HCM).,Left ventricular (LV) samples from 11 HCM patients were obtained following myectomy surgery to relieve LV outflow tract obstruction.,HCM samples were genotyped as either MYBPC3 mutation positive (MYBPC3mut) or negative (HCMsmn) and were compared to eight non-failing donor hearts.,Compared to donors, only MYBPC3mut samples display a significantly diminished SRX, characterised by a decrease in both the number of myosin heads in the SRX and the lifetime of ATP turnover.,These changes were not observed in HCMsmn samples.,There was a positive correlation (p < 0.01) between the expression of cMyBP-C and the proportion of myosin heads in the SRX state, suggesting cMyBP-C modulates and maintains the SRX.,Phosphorylation of the myosin regulatory light chain in MYBPC3mut samples was significantly decreased compared to the other groups, suggesting a potential mechanism to compensate for the diminished SRX.,We conclude that by altering both contractility and sarcomeric energy requirements, a reduced SRX may be an important disease mechanism in patients with MYBPC3 mutations.

Patients suffering from cardiovascular autonomic failure often develop neurogenic supine hypertension (nSH), i.e., high blood pressure (BP) in the supine position, which falls in the upright position owing to impaired autonomic regulation.,A committee was formed to reach consensus among experts on the definition and diagnosis of nSH in the context of cardiovascular autonomic failure.,As a first and preparatory step, a systematic search of PubMed-indexed literature on nSH up to January 2017 was performed.,Available evidence derived from this search was discussed in a consensus expert round table meeting in Innsbruck on February 16, 2017.,Statements originating from this meeting were further discussed by representatives of the American Autonomic Society and the European Federation of Autonomic Societies and are summarized in the document presented here.,The final version received the endorsement of the European Academy of Neurology and the European Society of Hypertension.,In patients with neurogenic orthostatic hypotension, nSH is defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, measured after at least 5 min of rest in the supine position.,Three severity degrees are recommended: mild, moderate and severe. nSH may also be present during nocturnal sleep, with reduced-dipping, non-dipping or rising nocturnal BP profiles with respect to mean daytime BP values.,Home BP monitoring and 24-h-ambulatory BP monitoring provide relevant information for a customized clinical management.,The establishment of expert-based criteria to define nSH should standardize diagnosis and allow a better understanding of its epidemiology, prognosis and, ultimately, treatment.

Neurogenic orthostatic hypotension (nOH) is common in patients with neurodegenerative disorders such as Parkinson’s disease, multiple system atrophy, pure autonomic failure, dementia with Lewy bodies, and peripheral neuropathies including amyloid or diabetic neuropathy.,Due to the frequency of nOH in the aging population, clinicians need to be well informed about its diagnosis and management.,To date, studies of nOH have used different outcome measures and various methods of diagnosis, thereby preventing the generation of evidence-based guidelines to direct clinicians towards ‘best practices’ when treating patients with nOH and associated supine hypertension.,To address these issues, the American Autonomic Society and the National Parkinson Foundation initiated a project to develop a statement of recommendations beginning with a consensus panel meeting in Boston on November 7, 2015, with continued communications and contributions to the recommendations through October of 2016.,This paper summarizes the panel members’ discussions held during the initial meeting along with continued deliberations among the panel members and provides essential recommendations based upon best available evidence as well as expert opinion for the (1) screening, (2) diagnosis, (3) treatment of nOH, and (4) diagnosis and treatment of associated supine hypertension.,The online version of this article (doi:10.1007/s00415-016-8375-x) contains supplementary material, which is available to authorized users.

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.

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.

Approximately 5.1 million Israelis had been fully immunized against coronavirus disease 2019 (Covid-19) after receiving two doses of the BNT162b2 messenger RNA vaccine (Pfizer-BioNTech) by May 31, 2021.,After early reports of myocarditis during adverse events monitoring, the Israeli Ministry of Health initiated active surveillance.,We retrospectively reviewed data obtained from December 20, 2020, to May 31, 2021, regarding all cases of myocarditis and categorized the information using the Brighton Collaboration definition.,We analyzed the occurrence of myocarditis by computing the risk difference for the comparison of the incidence after the first and second vaccine doses (21 days apart); by calculating the standardized incidence ratio of the observed-to-expected incidence within 21 days after the first dose and 30 days after the second dose, independent of certainty of diagnosis; and by calculating the rate ratio 30 days after the second dose as compared with unvaccinated persons.,Among 304 persons with symptoms of myocarditis, 21 had received an alternative diagnosis.,Of the remaining 283 cases, 142 occurred after receipt of the BNT162b2 vaccine; of these cases, 136 diagnoses were definitive or probable.,The clinical presentation was judged to be mild in 129 recipients (95%); one fulminant case was fatal.,The overall risk difference between the first and second doses was 1.76 per 100,000 persons (95% confidence interval [CI], 1.33 to 2.19), with the largest difference among male recipients between the ages of 16 and 19 years (difference, 13.73 per 100,000 persons; 95% CI, 8.11 to 19.46).,As compared with the expected incidence based on historical data, the standardized incidence ratio was 5.34 (95% CI, 4.48 to 6.40) and was highest after the second dose in male recipients between the ages of 16 and 19 years (13.60; 95% CI, 9.30 to 19.20).,The rate ratio 30 days after the second vaccine dose in fully vaccinated recipients, as compared with unvaccinated persons, was 2.35 (95% CI, 1.10 to 5.02); the rate ratio was again highest in male recipients between the ages of 16 and 19 years (8.96; 95% CI, 4.50 to 17.83), with a ratio of 1 in 6637.,The incidence of myocarditis, although low, increased after the receipt of the BNT162b2 vaccine, particularly after the second dose among young male recipients.,The clinical presentation of myocarditis after vaccination was usually mild.

To determine the frequency and pattern of cardiac complications in patients hospitalised with coronavirus disease (COVID-19).,CAPACITY-COVID is an international patient registry established to determine the role of cardiovascular disease in the COVID-19 pandemic.,In this registry, data generated during routine clinical practice are collected in a standardised manner for patients with a (highly suspected) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection requiring hospitalisation.,For the current analysis, consecutive patients with laboratory confirmed COVID-19 registered between 28 March and 3 July 2020 were included.,Patients were followed for the occurrence of cardiac complications and pulmonary embolism from admission to discharge.,In total, 3011 patients were included, of which 1890 (62.8%) were men.,The median age was 67 years (interquartile range 56-76); 937 (31.0%) patients had a history of cardiac disease, with pre-existent coronary artery disease being most common (n=463, 15.4%).,During hospitalisation, 595 (19.8%) patients died, including 16 patients (2.7%) with cardiac causes.,Cardiac complications were diagnosed in 349 (11.6%) patients, with atrial fibrillation (n=142, 4.7%) being most common.,The incidence of other cardiac complications was 1.8% for heart failure (n=55), 0.5% for acute coronary syndrome (n=15), 0.5% for ventricular arrhythmia (n=14), 0.1% for bacterial endocarditis (n=4) and myocarditis (n=3), respectively, and 0.03% for pericarditis (n=1).,Pulmonary embolism was diagnosed in 198 (6.6%) patients.,This large study among 3011 hospitalised patients with COVID-19 shows that the incidence of cardiac complications during hospital admission is low, despite a frequent history of cardiovascular disease.,Long-term cardiac outcomes and the role of pre-existing cardiovascular disease in COVID-19 outcome warrants further investigation.

Hypertension is one of the most powerful modifiable risk factors for cardiovascular disease.,It is usually asymptomatic and therefore essential to measure blood pressure regularly for the detection of hypertension.,Home blood pressure monitoring (HBPM) is recognized as a valuable tool to monitor blood pressure and facilitate effective diagnosis of hypertension.,It is useful to identify the masked or white‐coat hypertension.,There is also increasing evidence that supports the role of HBPM in guiding antihypertensive treatment, and improving treatment compliance and hypertension control.,In addition, HBPM has also shown prognostic value in predicting cardiovascular events.,Despite these benefits, the use of HBPM in many parts of Asia has been reported to be low.,An expert panel comprising 12 leading experts from 10 Asian countries/regions convened to share their perspectives on the realities of HBPM.,This article provides an expert summary of the current status of HBPM and the key factors hindering its use.,It also describes HBPM‐related initiatives in the respective countries/regions and presents strategies that could be implemented to better support the use of HBPM in the management of hypertension.

Supplemental Digital Content is available in the text.,Ambulatory and home blood pressure (BP) monitoring parameters are better predictors of cardiovascular events than are office BP monitoring parameters, but there is a lack of robust data and little information on heart failure (HF) risk.,The JAMP study (Japan Ambulatory Blood Pressure Monitoring Prospective) used the same ambulatory BP monitoring device, measurement schedule, and diary-based approach to data processing across all study centers and determined the association between both nocturnal hypertension and nighttime BP dipping patterns and the occurrence of cardiovascular events, including HF, in patients with hypertension.,This practitioner-based, nationwide, multicenter, prospective, observational study included patients with at least 1 cardiovascular risk factor, mostly hypertension, and free of symptomatic cardiovascular disease at baseline.,All patients underwent 24-hour ambulatory BP monitoring at baseline.,Patients were followed annually to determine the occurrence of primary end point cardiovascular events (atherosclerotic cardiovascular disease and HF).,A total of 6,359 patients (68.6±11.7 years of age, 48% men) were included in the final analysis.,During a mean±SD follow-up of 4.5±2.4 years, there were 306 cardiovascular events (119 stroke, 99 coronary artery disease, 88 HF).,Nighttime systolic BP was significantly associated with the risk of atherosclerotic cardiovascular disease and HF (hazard ratio adjusted for demographic and clinical risk factors per 20-mm Hg increase: 1.18 [95% CI, 1.02-1.37], P=0.029; and 1.25 [95% CI, 1.00-1.55], P=0.048, respectively).,Disrupted circadian BP rhythm (riser pattern, nighttime BP higher than daytime BP) was significantly associated with higher overall cardiovascular disease risk (1.48 [95% CI, 1.05-2.08]; P=0.024), and especially HF (2.45 [95% CI, 1.34-4.48]; P=0.004) compared with normal circadian rhythm.,Nighttime BP levels and a riser pattern were independently associated with the total cardiovascular event rate, in particular for HF.,These findings suggest the importance of antihypertensive strategies targeting nighttime systolic BP.,URL: https://www.umin.ac.jp/ctr/; Unique identifier: UMIN000020377.

In our registry, 90-day postdischarge VTE, ATE, and ACM rates were 1.55%, 1.71%, and 4.83%, respectively.Discharge anticoagulants, mostly prophylactic doses, were associated with 46% decrease in major thromboembolism or ACM composite end point.,In our registry, 90-day postdischarge VTE, ATE, and ACM rates were 1.55%, 1.71%, and 4.83%, respectively.,Discharge anticoagulants, mostly prophylactic doses, were associated with 46% decrease in major thromboembolism or ACM composite end point.,Thromboembolic events, including venous thromboembolism (VTE) and arterial thromboembolism (ATE), and mortality from subclinical thrombotic events occur frequently in coronavirus disease 2019 (COVID-19) inpatients.,Whether the risk extends postdischarge has been controversial.,Our prospective registry included consecutive patients with COVID-19 hospitalized within our multihospital system from 1 March to 31 May 2020.,We captured demographics, comorbidities, laboratory parameters, medications, postdischarge thromboprophylaxis, and 90-day outcomes.,Data from electronic health records, health informatics exchange, radiology database, and telephonic follow-up were merged.,Primary outcome was a composite of adjudicated VTE, ATE, and all-cause mortality (ACM).,Principal safety outcome was major bleeding (MB).,Among 4906 patients (53.7% male), mean age was 61.7 years.,Comorbidities included hypertension (38.6%), diabetes (25.1%), obesity (18.9%), and cancer history (13.1%).,Postdischarge thromboprophylaxis was prescribed in 13.2%.,VTE rate was 1.55%; ATE, 1.71%; ΑCM, 4.83%; and MB, 1.73%.,Composite primary outcome rate was 7.13% and significantly associated with advanced age (odds ratio [OR], 3.66; 95% CI, 2.84-4.71), prior VTE (OR, 2.99; 95% CI, 2.00-4.47), intensive care unit (ICU) stay (OR, 2.22; 95% CI, 1.78-2.93), chronic kidney disease (CKD; OR, 2.10; 95% CI, 1.47-3.0), peripheral arterial disease (OR, 2.04; 95% CI, 1.10-3.80), carotid occlusive disease (OR, 2.02; 95% CI, 1.30-3.14), IMPROVE-DD VTE score ≥4 (OR, 1.51; 95% CI, 1.06-2.14), and coronary artery disease (OR, 1.50; 95% CI, 1.04-2.17).,Postdischarge anticoagulation was significantly associated with reduction in primary outcome (OR, 0.54; 95% CI, 0.47-0.81).,Postdischarge VTE, ATE, and ACM occurred frequently after COVID-19 hospitalization.,Advanced age, cardiovascular risk factors, CKD, IMPROVE-DD VTE score ≥4, and ICU stay increased risk.,Postdischarge anticoagulation reduced risk by 46%.

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.

Both arterial and venous thrombotic events of the extremities occur in coronavirus disease 2019 (COVID-19) infection, but the etiology of these events remains unclear.,This study sought to evaluate pathology specimens of COVID-19-positive patients postamputation, who were found to have Rutherford 3 acute limb ischemia requiring amputation.,A retrospective review was performed of all vascular surgery emergency room and inpatient consultations in patients who presented to the Mount Sinai Health System from March 26, 2020, to May 10, 2020.,Pathology specimens were examined using hematoxylin and eosin stain.,The specimens were assessed for the following: inflammatory cells associated with endothelium/apoptotic bodies, mononuclear cells, small vessel congestion, and lymphocytic endotheliitis.,Of the specimens evaluated, 2 patients with a known history of peripheral vascular disease were excluded.,Inflammatory cells associated with endothelium/apoptotic bodies were seen in all 4 patients and in 4 of 5 specimens.,Mononuclear cells were found in 2 of 4 patients.,Small vessel congestion was seen in all patients.,Lymphocytic endotheliitis was seen in 1 of 4 patients.,This study shows endotheliitis in amputation specimens of four patients with COVID-19 disease and Rutherford Class 3 acute limb ischemia.,The findings in these patients is more likely an infectious angiitis because of COVID-19.

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.

Emerging data indicate an increased risk of cerebrovascular events with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and highlight the potential impact of coronavirus disease (COVID‐19) on the management and outcomes of acute stroke.,We conducted a systematic review and meta‐analysis to evaluate the aforementioned considerations.,We performed a meta‐analysis of observational cohort studies reporting on the occurrence and/or outcomes of patients with cerebrovascular events in association with their SARS‐CoV‐2 infection status.,We used a random‐effects model.,Summary estimates were reported as odds ratios (ORs) and corresponding 95% confidence intervals (CIs).,We identified 18 cohort studies including 67,845 patients.,Among patients with SARS‐CoV‐2, 1.3% (95% CI = 0.9-1.6%, I 2 = 87%) were hospitalized for cerebrovascular events, 1.1% (95% CI = 0.8-1.3%, I 2 = 85%) for ischemic stroke, and 0.2% (95% CI = 0.1-0.3%, I 2 = 64%) for hemorrhagic stroke.,Compared to noninfected contemporary or historical controls, patients with SARS‐CoV‐2 infection had increased odds of ischemic stroke (OR = 3.58, 95% CI = 1.43-8.92, I 2 = 43%) and cryptogenic stroke (OR = 3.98, 95% CI = 1.62-9.77, I 2 = 0%).,Diabetes mellitus was found to be more prevalent among SARS‐CoV‐2 stroke patients compared to noninfected historical controls (OR = 1.39, 95% CI = 1.00-1.94, I 2 = 0%).,SARS‐CoV‐2 infection status was not associated with the likelihood of receiving intravenous thrombolysis (OR = 1.42, 95% CI = 0.65-3.10, I 2 = 0%) or endovascular thrombectomy (OR = 0.78, 95% CI = 0.35-1.74, I 2 = 0%) among hospitalized ischemic stroke patients during the COVID‐19 pandemic.,Odds of in‐hospital mortality were higher among SARS‐CoV‐2 stroke patients compared to noninfected contemporary or historical stroke patients (OR = 5.60, 95% CI = 3.19-9.80, I 2 = 45%).,SARS‐CoV‐2 appears to be associated with an increased risk of ischemic stroke, and potentially cryptogenic stroke in particular.,It may also be related to an increased mortality risk.,ANN NEUROL 2021;89:380-388

Concerns regarding potential neurological complications of COVID-19 are being increasingly reported, primarily in small series.,Larger studies have been limited by both geography and specialty.,Comprehensive characterisation of clinical syndromes is crucial to allow rational selection and evaluation of potential therapies.,The aim of this study was to investigate the breadth of complications of COVID-19 across the UK that affected the brain.,During the exponential phase of the pandemic, we developed an online network of secure rapid-response case report notification portals across the spectrum of major UK neuroscience bodies, comprising the Association of British Neurologists (ABN), the British Association of Stroke Physicians (BASP), and the Royal College of Psychiatrists (RCPsych), and representing neurology, stroke, psychiatry, and intensive care.,Broad clinical syndromes associated with COVID-19 were classified as a cerebrovascular event (defined as an acute ischaemic, haemorrhagic, or thrombotic vascular event involving the brain parenchyma or subarachnoid space), altered mental status (defined as an acute alteration in personality, behaviour, cognition, or consciousness), peripheral neurology (defined as involving nerve roots, peripheral nerves, neuromuscular junction, or muscle), or other (with free text boxes for those not meeting these syndromic presentations).,Physicians were encouraged to report cases prospectively and we permitted recent cases to be notified retrospectively when assigned a confirmed date of admission or initial clinical assessment, allowing identification of cases that occurred before notification portals were available.,Data collected were compared with the geographical, demographic, and temporal presentation of overall cases of COVID-19 as reported by UK Government public health bodies.,The ABN portal was launched on April 2, 2020, the BASP portal on April 3, 2020, and the RCPsych portal on April 21, 2020.,Data lock for this report was on April 26, 2020.,During this period, the platforms received notification of 153 unique cases that met the clinical case definitions by clinicians in the UK, with an exponential growth in reported cases that was similar to overall COVID-19 data from UK Government public health bodies.,Median patient age was 71 years (range 23-94; IQR 58-79).,Complete clinical datasets were available for 125 (82%) of 153 patients. 77 (62%) of 125 patients presented with a cerebrovascular event, of whom 57 (74%) had an ischaemic stroke, nine (12%) an intracerebral haemorrhage, and one (1%) CNS vasculitis. 39 (31%) of 125 patients presented with altered mental status, comprising nine (23%) patients with unspecified encephalopathy and seven (18%) patients with encephalitis.,The remaining 23 (59%) patients with altered mental status fulfilled the clinical case definitions for psychiatric diagnoses as classified by the notifying psychiatrist or neuropsychiatrist, and 21 (92%) of these were new diagnoses.,Ten (43%) of 23 patients with neuropsychiatric disorders had new-onset psychosis, six (26%) had a neurocognitive (dementia-like) syndrome, and four (17%) had an affective disorder. 18 (49%) of 37 patients with altered mental status were younger than 60 years and 19 (51%) were older than 60 years, whereas 13 (18%) of 74 patients with cerebrovascular events were younger than 60 years versus 61 (82%) patients older than 60 years.,To our knowledge, this is the first nationwide, cross-specialty surveillance study of acute neurological and psychiatric complications of COVID-19.,Altered mental status was the second most common presentation, comprising encephalopathy or encephalitis and primary psychiatric diagnoses, often occurring in younger patients.,This study provides valuable and timely data that are urgently needed by clinicians, researchers, and funders to inform immediate steps in COVID-19 neuroscience research and health policy.,None.

Sodium glucose co-transporter 2 inhibitor (SGLT2i), a new class of anti-diabetic drugs acting on inhibiting glucose resorption by kidneys, is shown beneficial in reduction of heart failure hospitalization and cardiovascular mortality.,The mechanisms remain unclear.,We hypothesized that SGLT2i, empagliflozin can improve cardiac hemodynamics in non-diabetic hypertensive heart failure.,The hypertensive heart failure model had been created by feeding spontaneous hypertensive rats (SHR) with high fat diet for 32 weeks (total n = 13).,Half SHRs were randomized to be administered with SGLT2i, empagliflozin at 20 mg/kg/day for 12 weeks.,After evaluation of electrocardiography and echocardiography, invasive hemodynamic study was performed and followed by blood sample collection and tissue analyses.,Empagliflozin exhibited cardiac (improved atrial and ventricular remodeling) and renal protection, while plasma glucose level was not affected.,Empagliflozin normalized both end-systolic and end-diastolic volume in SHR, in parallel with parameters in echocardiographic evaluation.,Empagliflozin also normalized systolic dysfunction, in terms of the reduced maximal velocity of pressure incline and the slope of end-systolic pressure volume relationship in SHR.,In histological analysis, empagliflozin significantly attenuated cardiac fibrosis in both atrial and ventricular tissues.,The upregulation of atrial and ventricular expression of PPARα, ACADM, natriuretic peptides (NPPA and NPPB), and TNF-α in SHR, was all restored by treatment of empagliflozin.,Empagliflozin improves hemodynamics in our hypertensive heart failure rat model, associated with renal protection, attenuated cardiac fibrosis, and normalization of HF genes.,Our results contribute some understanding of the pleiotropic effects of empagliflozin on improving heart function.

Metabolic syndrome (MetS) is a prevalent risk factor for cardiac dysfunction.,Although SGLT2-inhibitors have important cardioprotective effects in hyperglycemia, their underlying mechanisms are complex and not completely understood.,Therefore, we examined mechanisms of a SGLT2-inhibitor dapagliflozin (DAPA)-related cardioprotection in overweight insulin-resistant MetS-rats comparison with insulin (INSU), behind its glucose-lowering effect.,A 28-week high-carbohydrate diet-induced MetS-rats received DAPA (5 mg/kg), INSU (0.15 mg/kg) or vehicle for 2 weeks.,To validate MetS-induction, we monitored all animals weekly by measuring body weight, blood glucose and HOMO-IR index, electrocardiograms, heart rate, systolic and diastolic pressures.,DAPA-treatment of MetS-rats significantly augmented the increased blood pressure, prolonged Q-R interval, and low heart rate with depressed left ventricular function and relaxation of the aorta.,Prolonged-action potentials were preserved with DAPA-treatment, more prominently than INSU-treatment, at most, through the augmentation in depressed voltage-gated K+-channel currents.,DAPA, more prominently than INSU-treatment, preserved the depolarized mitochondrial membrane potential, and altered mitochondrial protein levels such as Mfn-1, Mfn-2, and Fis-1 as well as provided significant augmentation in cytosolic Ca2+-homeostasis.,Furthermore, DAPA also induced significant augmentation in voltage-gated Na+-currents and intracellular pH, and the cellular levels of increased oxidative stress, protein-thiol oxidation and ADP/ATP ratio in cardiomyocytes from MetS rats.,Moreover, DAPA-treatment normalized the increases in the mRNA level of SGLT2 in MetS-rat heart.,Overall, our data provided a new insight into DAPA-associated cardioprotection in MetS rats, including suppression of prolonged ventricular-repolarization through augmentation of mitochondrial function and oxidative stress followed by improvement of fusion-fission proteins, out of its glucose-lowering effect.,The online version of this article (10.1186/s12933-018-0790-0) contains supplementary material, which is available to authorized users.

Although myocarditis and pericarditis were not observed as adverse events in coronavirus disease 2019 (COVID-19) vaccine trials, there have been numerous reports of suspected cases following vaccination in the general population.,We undertook a self-controlled case series study of people aged 16 or older vaccinated for COVID-19 in England between 1 December 2020 and 24 August 2021 to investigate hospital admission or death from myocarditis, pericarditis and cardiac arrhythmias in the 1-28 days following adenovirus (ChAdOx1, n = 20,615,911) or messenger RNA-based (BNT162b2, n = 16,993,389; mRNA-1273, n = 1,006,191) vaccines or a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test (n = 3,028,867).,We found increased risks of myocarditis associated with the first dose of ChAdOx1 and BNT162b2 vaccines and the first and second doses of the mRNA-1273 vaccine over the 1-28 days postvaccination period, and after a SARS-CoV-2 positive test.,We estimated an extra two (95% confidence interval (CI) 0, 3), one (95% CI 0, 2) and six (95% CI 2, 8) myocarditis events per 1 million people vaccinated with ChAdOx1, BNT162b2 and mRNA-1273, respectively, in the 28 days following a first dose and an extra ten (95% CI 7, 11) myocarditis events per 1 million vaccinated in the 28 days after a second dose of mRNA-1273.,This compares with an extra 40 (95% CI 38, 41) myocarditis events per 1 million patients in the 28 days following a SARS-CoV-2 positive test.,We also observed increased risks of pericarditis and cardiac arrhythmias following a positive SARS-CoV-2 test.,Similar associations were not observed with any of the COVID-19 vaccines, apart from an increased risk of arrhythmia following a second dose of mRNA-1273.,Subgroup analyses by age showed the increased risk of myocarditis associated with the two mRNA vaccines was present only in those younger than 40.,A self-controlled case series using individual-patient-level data from over 38 million people aged 16 years and over, reveals an increased risk of myocarditis within a week of receiving a first dose of ChAdOx1, BNT162b2 and mRNA-1273 vaccines, which was further increased after a second dose of either mRNA vaccine.,SARS-CoV-2 infection was associated with even greater risk of myocarditis, as well as pericarditis and cardiac arrhythmia.

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.

An important manifestation of severe COVID-19 is the ARDS-like lung injury that is associated with vascular endothelialitis, thrombosis, and angiogenesis.,The intravascular innate immune system (IIIS), including the complement, contact, coagulation, and fibrinolysis systems, which is crucial for recognizing and eliminating microorganisms and debris in the body, is likely to be involved in the pathogenesis of COVID-19 ARDS.,Biomarkers for IIIS activation were studied in the first 66 patients with COVID-19 admitted to the ICU in Uppsala University Hospital, both cross-sectionally on day 1 and in 19 patients longitudinally for up to a month, in a prospective study.,IIIS analyses were compared with biochemical parameters and clinical outcome and survival.,Blood cascade systems activation leading to an overreactive conjunct thromboinflammation was demonstrated, reflected in consumption of individual cascade system components, e.g., FXII, prekallikrein, and high molecular weight kininogen and in increased levels of activation products, e.g., C4d, C3a, C3d,g, sC5b-9, TAT, and D-dimer.,Strong associations were found between the blood cascade systems and organ damage, illness severity scores, and survival.,We show that critically ill COVID-19 patients display a conjunct activation of the IIIS that is linked to organ damage of the lung, heart, kidneys, and death.,We present evidence that the complement and in particular the kallikrein/kinin system is strongly activated and that both systems are prognostic markers of the outcome of the patients suggesting their role in driving the inflammation.,Already licensed kallikrein/kinin inhibitors are potential drugs for treatment of critically ill patients with COVID-19.

The COVID-19 pandemic has led to extensive morbidity and mortality throughout the world.,Clinical features that drive SARS-CoV-2 pathogenesis in humans include inflammation and thrombosis, but the mechanistic details underlying these processes remain to be determined.,In this study, we demonstrate endothelial disruption and vascular thrombosis in histopathologic sections of lungs from both humans and rhesus macaques infected with SARS-CoV-2.,To define key molecular pathways associated with SARS-CoV-2 pathogenesis in macaques, we performed transcriptomic analyses of bronchoalveolar lavage and peripheral blood and proteomic analyses of serum.,We observed macrophage infiltrates in lung and upregulation of macrophage, complement, platelet activation, thrombosis, and proinflammatory markers, including C-reactive protein, MX1, IL-6, IL-1, IL-8, TNFα, and NF-κB.,These results suggest a model in which critical interactions between inflammatory and thrombosis pathways lead to SARS-CoV-2-induced vascular disease.,Our findings suggest potential therapeutic targets for COVID-19.,Aid et al. show that SARS-CoV-2 causes endothelial disruption and vascular thrombosis in both human and rhesus macaques lungs by inducing an upregulation of proinflammatory cytokines.,Using an approach that combines histopathology and multiomics in macaques, they show the progression to vascular disease over time, which involves complement, macrophage, cytokine, and thrombosis cascades.

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.

Cardiovascular disease (CVD) presents a global health burden, despite recent advances in management.,CVD can originate from early life by so-called “developmental origins of health and disease” (DOHaD).,Epidemiological and experimental evidence supports that early-life insults can induce programming of later CVD.,Underlying the DOHaD concept, early intervention may offset programming process to prevent the development of CVD, namely reprogramming.,Oxidative stress and nutrient sensing signals have been considered to be major mechanisms of cardiovascular programming, while the interplay between these two mechanisms have not been examined in detail.,This review summarizes current evidence that supports the link between oxidative stress and nutrient sensing signaling to cardiovascular programming, with an emphasis on the l-arginine-asymmetric dimethylarginine (ADMA)-nitric oxide (NO) pathway.,This review provides an overview of evidence from human studies supporting fetal programming of CVD, insight from animal models of cardiovascular programming and oxidative stress, impact of the l-arginine-ADMA-NO pathway in cardiovascular programming, the crosstalk between l-arginine metabolism and nutrient sensing signals, and application of reprogramming interventions to prevent the programming of CVD.,A greater understanding of the mechanisms underlying cardiovascular programming is essential to developing early reprogramming interventions to combat the globally growing epidemic of CVD.

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.

Coronavirus disease 2019 (COVID-19) is a viral infection that can, in severe cases, result in cytokine storm, systemic inflammatory response and coagulopathy that is prognostic of poor outcomes.,While some, but not all, laboratory findings appear similar to sepsis-associated disseminated intravascular coagulopathy (DIC), COVID-19- induced coagulopathy (CIC) appears to be more prothrombotic than hemorrhagic.,It has been postulated that CIC may be an uncontrolled immunothrombotic response to COVID-19, and there is growing evidence of venous and arterial thromboembolic events in these critically ill patients.,Clinicians around the globe are challenged with rapidly identifying reasonable diagnostic, monitoring and anticoagulant strategies to safely and effectively manage these patients.,Thoughtful use of proven, evidence-based approaches must be carefully balanced with integration of rapidly emerging evidence and growing experience.,The goal of this document is to provide guidance from the Anticoagulation Forum, a North American organization of anticoagulation providers, regarding use of anticoagulant therapies in patients with COVID-19.,We discuss in-hospital and post-discharge venous thromboembolism (VTE) prevention, treatment of suspected but unconfirmed VTE, laboratory monitoring of COVID-19, associated anticoagulant therapies, and essential elements for optimized transitions of care specific to patients with COVID-19.

The role of renin-angiotensin-aldosterone system (RAAS) inhibitors, notably angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs), in the COVID-19 pandemic has not been fully evaluated.,With an increasing number of COVID-19 cases worldwide, it is imperative to better understand the impact of RAAS inhibitors in hypertensive COVID patients.,PubMed, Embase and the pre-print database Medrxiv were searched, and studies with data on patients on ACEi/ARB with COVID-19 were included.,Random effects models were used to estimate the pooled mean difference with 95% confidence interval using Open Meta[Analyst] software.,A total of 28,872 patients were included in this meta-analysis.,The use of any RAAS inhibition for any conditions showed a trend to lower risk of death/critical events (OR 0.671, CI 0.435 to 1.034, p = 0.071).,Within the hypertensive cohort, however, there was a significant lower association with deaths (OR 0.664, CI 0.458 to 0.964, p = 0.031) or the combination of death/critical outcomes (OR 0.670, CI 0.495 to 0.908, p = 0.010).,There was no significant association of critical/death outcomes within ACEi vs non-ACEi (OR 1.008, CI 0.822 to 1.235, p = 0.941) and ARB vs non-ARB (OR 0.946, CI 0.735 to 1.218, p = 0.668).,This is the largest meta-analysis including critical events and mortality data on patients prescribed ACEi/ARB and found evidence of beneficial effects of chronic ACEi/ARB use especially in hypertensive cohort with COVID-19.,As such, we would strongly encourage patients to continue with RAAS inhibitor pharmacotherapy during the COVID-19 pandemic.,The online version of this article (10.1007/s11883-020-00880-6) contains supplementary material, which is available to authorized users.

To describe the characteristics of patients hospitalized with COVID-19 (including their long-term at-home medication use), and compare them with regard to the course of the disease.,To assess the association between renin-angiotensin system inhibitors (RASIs) and disease progression and critical outcomes.,All consecutive hospitalized patients with laboratory-confirmed COVID-19 in a university hospital in Amiens (France) were included in this study.,The primary composite endpoint was admission to an intensive care unit (ICU) or death before ICU admission.,Univariable and multivariable logistic regression models were used to identify factors associated with the composite endpoint.,Between 28 February 2020 and 30 March 2020, a total of 499 local patients tested positive for SARS-CoV-2.,Of these, 231 were not hospitalized {males 33%; median [interquartile range (IQR)] age: 44 (32-54)}, and 268 were hospitalized [males 58%; median (IQR) age: 73 (61-84)].,A total of 116 patients met the primary endpoint: 47 died before ICU admission, and 69 were admitted to the ICU.,Patients meeting the primary endpoint were more likely than patients not meeting the primary endpoint to have coronary heart disease and to have been taking RASIs; however, the two subsets of patients did not differ with regard to median age.,After adjustment for other associated variables, the risk of meeting the composite endpoint was 1.73 times higher (odds ratio 1.73, 95% confidence interval 1.02-2.93) in patients treated at baseline with a RASI than in patients not treated with this drug class.,This association was confirmed when the analysis was restricted to patients treated with antihypertensive agents.,We highlighted a potential safety signal for RASIs, the long-term use of which was independently associated with a higher risk of severe COVID-19 and a poor outcome.,Due to the widespread use of this important drug class, formal proof based on clinical trials is needed to better understand the association between RASIs and complications of COVID-19.

Renin-angiotensin-aldosterone system inhibitors (RAASi) improve outcomes in cardiorenal disease but concerns have been raised over increased risk of incident hospitalization and death from coronavirus disease 2019 (COVID‐19).,We investigated the association between use of angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARBs) or mineralocorticoid receptor antagonists (MRAs) and COVID‐19 hospitalization/death in a large nationwide population.,Patients with hypertension, heart failure, diabetes, kidney disease, or ischaemic heart disease registered in the Swedish National Patient Registry until 1 February 2020 were included and followed until 31 May 2020.,COVID‐19 cases were defined based on hospitalization/death for COVID‐19.,Multivariable logistic and Cox regressions were fitted to investigate the association between ACEi/ARB and MRA and risk of hospitalization/death for COVID‐19 in the overall population, and of all‐cause mortality in COVID‐19 cases.,We performed consistency analysis to quantify the impact of potential unmeasured confounding.,Of 1 387 746 patients (60% receiving ACEi/ARB and 5.8% MRA), 7146 (0.51%) had incident hospitalization/death from COVID‐19.,After adjustment for 45 variables, ACEi/ARB use was associated with a reduced risk of hospitalization/death for COVID‐19 (odds ratio 0.86, 95% confidence interval 0.81-0.91) in the overall population, and with reduced mortality in COVID‐19 cases (hazard ratio 0.89, 95% confidence interval 0.82-0.96).,MRA use was not associated with risk of any outcome.,Consistency analysis showed that unmeasured confounding would need to be large for there to be harmful signals associated with RAASi use.,In a 1.4 million nationwide cohort, use of RAASi was not associated with increased risk of hospitalization for or death from COVID‐19.

Coronavirus disease 2019 (Covid-19) has rapidly infected millions of people worldwide.,Recent studies suggest that racial minorities and patients with comorbidities are at higher risk of Covid-19.,In this study, we analyzed the effects of clinical, regional, and genetic factors on Covid-19 positive status.,The UK Biobank is a longitudinal cohort study that recruited participants from 2006 to 2010 from throughout the United Kingdom.,Covid-19 test results were provided to UK Biobank starting on March 16, 2020.,The main outcome measure in this study was Covid-19 positive status, determined by the presence of any positive test for a single individual.,Clinical risk factors were derived from UK Biobank at baseline, and regional risk factors were imputed using census features local to each participant’s home zone.,We used robust adjusted Poisson regression with clustering by testing laboratory to estimate relative risk.,Blood types were derived using genetic variants rs8176719 and rs8176746, and genomewide tests of association were conducted using logistic-Firth hybrid regression.,This prospective cohort study included 397,064 UK Biobank participants, of whom 968 tested positive for Covid-19.,The unadjusted relative risk of Covid-19 for Black participants was 3.66 (95% CI 2.83-4.74), compared to White participants.,Adjusting for Townsend deprivation index alone reduced the relative risk to 2.44 (95% CI 1.86-3.20).,Comorbidities that significantly increased Covid-19 risk included chronic obstructive pulmonary disease (adjusted relative risk [ARR] 1.64, 95% CI 1.18-2.27), ischemic heart disease (ARR 1.48, 95% CI 1.16-1.89), and depression (ARR 1.32, 95% CI 1.03-1.70).,There was some evidence that angiotensin converting enzyme inhibitors (ARR 1.48, 95% CI 1.13-1.93) were associated with increased risk of Covid-19.,Each standard deviation increase in the number of total individuals living in a participant’s locality was associated with increased risk of Covid-19 (ARR 1.14, 95% CI 1.08-1.20).,Analyses of genetically inferred blood types confirmed that participants with type A blood had increased odds of Covid-19 compared to participants with type O blood (odds ratio [OR] 1.16, 95% CI 1.01-1.33).,A meta-analysis of genomewide association studies across ancestry groups did not reveal any significant loci.,Study limitations include confounding by indication, bias due to limited information on early Covid-19 test results, and inability to accurately gauge disease severity.,When assessing the association of Black race with Covid-19, adjusting for deprivation reduced the relative risk of Covid-19 by 33%.,In the context of sociological research, these findings suggest that discrimination in the labor market may play a role in the high relative risk of Covid-19 for Black individuals.,In this study, we also confirmed the association of blood type A with Covid-19, among other clinical and regional factors.

Coagulopathy is a common abnormality in patients with COVID‐19.,However, the exact incidence of venous thromboembolic event is unknown in anticoagulated, severe COVID‐19 patients.,Systematic assessment of venous thromboembolism (VTE) using complete duplex ultrasound (CDU) in anticoagulated COVID‐19 patients.,We performed a retrospective study in 2 French intensive care units (ICU) where CDU is performed as a standard of care.,A CDU from thigh to ankle at selected sites with Doppler waveforms and images was performed early during ICU stay in patients admitted with COVID‐19.,Anticoagulation dose was left to the discretion of the treating physician based on the individual risk of thrombosis.,Patients were classified as treated with prophylactic anticoagulation or therapeutic anticoagulation.,Pulmonary embolism was systematically searched in patients with persistent hypoxemia or secondary deterioration.,From March 19 to April 11, 2020, 26 consecutive patients with severe COVID‐19 were screened for VTE.,Eight patients (31%) were treated with prophylactic anticoagulation, whereas 18 patients (69%) were treated with therapeutic anticoagulation.,The overall rate of VTE in patients was 69%.,The proportion of VTE was significantly higher in patients treated with prophylactic anticoagulation when compared with the other group (100% vs 56%, respectively, P = .03).,Surprisingly, we found a high rate of thromboembolic events in COVID‐19 patients treated with therapeutic anticoagulation, with 56% of VTE and 6 pulmonary embolisms.,Our results suggest considering both systematic screening of VTE and early therapeutic anticoagulation in severe ICU COVID‐19 patients.

The novel coronavirus strain known as SARS-CoV-2 has rapidly spread around the world creating distinct challenges to the healthcare workforce.,Coagulopathy contributing to significant morbidity in critically ill patients with SARS-CoV-2 has now been well documented.,We discuss two cases selected from patients requiring critical care in April 2020 in New York City with a unique clinical course.,Both cases reveal significant thrombotic events noted on imaging during their hospital course.,Obtaining serial inflammatory markers in conjunction with anti-phospholipid antibody testing revealed clinically significant Antiphospholipid syndrome (APS).,This case series reviews the details preceding APS observed in SARS-CoV-2 and aims to report findings that could potentially further our understanding of the disease.

Preapproval trials showed that messenger RNA (mRNA)-based vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a good safety profile, yet these trials were subject to size and patient-mix limitations.,An evaluation of the safety of the BNT162b2 mRNA vaccine with respect to a broad range of potential adverse events is needed.,We used data from the largest health care organization in Israel to evaluate the safety of the BNT162b2 mRNA vaccine.,For each potential adverse event, in a population of persons with no previous diagnosis of that event, we individually matched vaccinated persons to unvaccinated persons according to sociodemographic and clinical variables.,Risk ratios and risk differences at 42 days after vaccination were derived with the use of the Kaplan-Meier estimator.,To place these results in context, we performed a similar analysis involving SARS-CoV-2-infected persons matched to uninfected persons.,The same adverse events were studied in the vaccination and SARS-CoV-2 infection analyses.,In the vaccination analysis, the vaccinated and control groups each included a mean of 884,828 persons.,Vaccination was most strongly associated with an elevated risk of myocarditis (risk ratio, 3.24; 95% confidence interval [CI], 1.55 to 12.44; risk difference, 2.7 events per 100,000 persons; 95% CI, 1.0 to 4.6), lymphadenopathy (risk ratio, 2.43; 95% CI, 2.05 to 2.78; risk difference, 78.4 events per 100,000 persons; 95% CI, 64.1 to 89.3), appendicitis (risk ratio, 1.40; 95% CI, 1.02 to 2.01; risk difference, 5.0 events per 100,000 persons; 95% CI, 0.3 to 9.9), and herpes zoster infection (risk ratio, 1.43; 95% CI, 1.20 to 1.73; risk difference, 15.8 events per 100,000 persons; 95% CI, 8.2 to 24.2).,SARS-CoV-2 infection was associated with a substantially increased risk of myocarditis (risk ratio, 18.28; 95% CI, 3.95 to 25.12; risk difference, 11.0 events per 100,000 persons; 95% CI, 5.6 to 15.8) and of additional serious adverse events, including pericarditis, arrhythmia, deep-vein thrombosis, pulmonary embolism, myocardial infarction, intracranial hemorrhage, and thrombocytopenia.,In this study in a nationwide mass vaccination setting, the BNT162b2 vaccine was not associated with an elevated risk of most of the adverse events examined.,The vaccine was associated with an excess risk of myocarditis (1 to 5 events per 100,000 persons).,The risk of this potentially serious adverse event and of many other serious adverse events was substantially increased after SARS-CoV-2 infection.,(Funded by the Ivan and Francesca Berkowitz Family Living Laboratory Collaboration at Harvard Medical School and Clalit Research Institute.)

Reports of ChAdOx1 vaccine-associated thrombocytopenia and vascular adverse events have led to some countries restricting its use.,Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis.,An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0-27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41-13.83), with an estimated incidence of 1.13 (0.62-1.63) cases per 100,000 doses.,An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29-3.02)).,There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12-1.34) 0-27 d after vaccination, with an SCCS RR of 0.97 (0.93-1.02).,For hemorrhagic events 0-27 d after vaccination, the aRR was 1.48 (1.12-1.96), with an SCCS RR of 0.95 (0.82-1.11).,A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events.,The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication.,Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1.,No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.,New data from the EAVE II cohort in Scotland suggests that a first dose of the ChAdOx1 nCoV-19 vaccine might be associated with a small increase in the risk of idiopathic thrombocytopenic purpura between 0 and 27 d after vaccination.

Supplemental Digital Content is available in the text.,Patients with coronavirus disease 2019 (COVID-19) have a high rate of thrombosis.,We hypothesized that severe acute respiratory syndrome coronavirus 2 infection leads to induction of TF (tissue factor) expression and increased levels of circulating TF-positive extracellular vesicles (EV) that may drive thrombosis.,We measured levels of plasma EV TF activity in 100 patients with COVID-19 with moderate and severe disease and 28 healthy controls.,Levels of EV TF activity were significantly higher in patients with COVID-19 compared with controls.,In addition, levels of EV TF activity were associated with disease severity and mortality.,Finally, levels of EV TF activity correlated with several plasma markers, including D-dimer, which has been shown to be associated with thrombosis in patients with COVID-19.,Our results indicate that severe acute respiratory syndrome coronavirus 2 infection induces the release of TF-positive EVs into the circulation that are likely to contribute to thrombosis in patients with COVID-19.,EV TF activity was also associated with severity and mortality.

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.

Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may benefit most.,This individual patient data (IPD) meta-analysis was performed to better understand the effectiveness of BP self-monitoring to lower BP and control hypertension.,Medline, Embase, and the Cochrane Library were searched for randomised trials comparing self-monitoring to no self-monitoring in hypertensive patients (June 2016).,Two reviewers independently assessed articles for eligibility and the authors of eligible trials were approached requesting IPD.,Of 2,846 articles in the initial search, 36 were eligible.,IPD were provided from 25 trials, including 1 unpublished study.,Data for the primary outcomes-change in mean clinic or ambulatory BP and proportion controlled below target at 12 months-were available from 15/19 possible studies (7,138/8,292 [86%] of randomised participants).,Overall, self-monitoring was associated with reduced clinic systolic blood pressure (sBP) compared to usual care at 12 months (−3.2 mmHg, [95% CI −4.9, −1.6 mmHg]).,However, this effect was strongly influenced by the intensity of co-intervention ranging from no effect with self-monitoring alone (−1.0 mmHg [−3.3, 1.2]), to a 6.1 mmHg (−9.0, −3.2) reduction when monitoring was combined with intensive support.,Self-monitoring was most effective in those with fewer antihypertensive medications and higher baseline sBP up to 170 mmHg.,No differences in efficacy were seen by sex or by most comorbidities.,Ambulatory BP data at 12 months were available from 4 trials (1,478 patients), which assessed self-monitoring with little or no co-intervention.,There was no association between self-monitoring and either lower clinic or ambulatory sBP in this group (clinic −0.2 mmHg [−2.2, 1.8]; ambulatory 1.1 mmHg [−0.3, 2.5]).,Results for diastolic blood pressure (dBP) were similar.,The main limitation of this work was that significant heterogeneity remained.,This was at least in part due to different inclusion criteria, self-monitoring regimes, and target BPs in included studies.,Self-monitoring alone is not associated with lower BP or better control, but in conjunction with co-interventions (including systematic medication titration by doctors, pharmacists, or patients; education; or lifestyle counselling) leads to clinically significant BP reduction which persists for at least 12 months.,The implementation of self-monitoring in hypertension should be accompanied by such co-interventions.,In an individual patient data meta-analysis of randomized trials, Katherine Tucker and colleagues examine the evidence for the effectiveness of self-monitoring of blood pressure in hypertension.

Oral anticoagulation prevents ischemic strokes in patients with atrial fibrillation (AF).,Early detection of AF and subsequent initiation of oral anticoagulation help to prevent strokes in AF patients.,Implanted cardiac pacemakers and defibrillators allow seamless detection of atrial high rate episodes (AHRE), but the best antithrombotic therapy in patients with AHRE is not known.,Stroke risk is higher in pacemaker patients with AHRE than in those without, but the available data also show that stroke risk in patients with AHRE is lower than in patients with AF.,Furthermore, only a minority of patients with AHRE will develop AF, many strokes occur without a temporal relation to AHRE, and AHRE can reflect other arrhythmias than AF or artifacts.,An adequately powered controlled trial of oral anticoagulation in patients with AHRE is needed.,The Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High rate episodes (NOAH-AFNET 6 ) trial tests whether oral anticoagulation with edoxaban is superior to prevent the primary efficacy outcome of stroke or cardiovascular death compared with aspirin or no antithrombotic therapy based on evidence-based indications.,The primary safety outcome will be major bleeding.,NOAH-AFNET 6 will randomize 3,400 patients with AHRE, but without documented AF, aged ≥65 years with at least 1 other stroke risk factor, to oral anticoagulation therapy (edoxaban) or no anticoagulation.,All patients will be followed until the end of this investigator-driven, prospective, parallel-group, randomized, event-driven, double-blind, multicenter phase IIIb trial.,Patients will be censored when they develop AF and offered open-label anticoagulation.,The sponsor is the Atrial Fibrillation NETwork (AFNET).,The trial is supported by the DZHK (German Centre for Cardiovascular Research), the BMBF (German Ministry of Education and Research), and Daiichi Sankyo Europe.,NOAH-AFNET 6 will provide robust information on the effect of oral anticoagulation in patients with atrial high rate episodes detected by implanted devices.,Image 1

Regular exercise has multiple benefits for physical and mental health, including the body’s ability to combat infections.,The current COVID-19 pandemic and the social distancing measures employed to curtail the impact of the infection are likely to reduce the amount of usual physical activity being performed by most individuals, including habitual exercisers.,The uncertainties relating to the impact of the SARS-CoV-2 virus on the heart may cause increased anxiety, particularly in athletes who need to sustain a vigorous exercise regime in order to maintain their skills and fitness in preparation for return to competition after a short re-training period.,The aim of this document is to provide practical answers to pertinent questions being posed by the sporting community, in an attempt to offer reassurance, promote safe participation in exercise during as well as after the COVID-19 pandemic and provide a framework of management for physicians caring for athletes.

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.