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The use of circulating biomarkers for heart failure (HF) is engrained in contemporary cardiovascular practice and provides objective information about various pathophysiological pathways associated with HF syndrome.,However, biomarker profiles differ considerably among women and men.,For instance, in the general population, markers of cardiac stretch (natriuretic peptides) and fibrosis (galectin‐3) are higher in women, whereas markers of cardiac injury (cardiac troponins) and inflammation (sST2) are higher in men.,Such differences may reflect sex‐specific pathogenic processes associated with HF risk, but may also arise as a result of differences in sex hormone profiles and fat distribution.,From a clinical perspective, sex‐related differences in biomarker levels may affect the objectivity of biomarkers in HF management because what is considered to be ‘normal’ in one sex may not be so in the other.,The objectives of this review are, therefore: (i) to examine the sex‐specific dynamics of clinically relevant HF biomarkers in the general population, as well as in HF patients; (ii) to discuss the overlap between sex‐related and obesity‐related effects, and (iii) to identify knowledge gaps to stimulate research on sex‐related differences in HF.

Heart failure with preserved ejection fraction (HFpEF) affects more women than men, suggesting gender to play a major role in disease evolution.,However, studies investigating gender differences in HFpEF are limited.,In the present study we aimed to describe gender differences in a well-characterized HFpEF cohort.,Consecutive HFpEF patients underwent invasive hemodynamic assessment, cardiac magnetic resonance imaging and exercise testing.,Study endpoints were: cardiac death, a combined endpoint of HF hospitalization or cardiac death and all-cause death.,260 HFpEF patients were prospectively enrolled.,Men were more compromised with regard to exercise capacity and had significantly more co-morbidities.,Men had more pronounced pulmonary vascular disease with higher diastolic pressure gradients and a lower right ventricular EF.,During follow-up, 9.2% experienced cardiac death, 33.5% the combined endpoint and 17.3% all-cause death.,Male gender was independently associated with cardiac death, but neither with the combined endpoint nor with all-cause mortality.,We detected clear gender differences in HFpEF patients.,Cardiac death was more common among men, but not all-cause death.,While men are more prone to develop a right heart phenotype and die from HFpEF, women are more likely to die with HFpEF.

More than 2,000,000 individuals worldwide have had coronavirus 2019 disease infection (COVID-19), yet there is no effective medical therapy.,Multiple off-label and investigational drugs, such as chloroquine and hydroxychloroquine, have gained broad interest due to positive pre-clinical data and are currently used for treatment of COVID-19.,However, some of these medications have potential cardiac adverse effects.,This is important because up to one-third of patients with COVID-19 have cardiac injury, which can further increase the risk of cardiomyopathy and arrhythmias.,Adverse effects of chloroquine and hydroxychloroquine on cardiac function and conduction are broad and can be fatal.,Both drugs have an anti-arrhythmic property and are proarrhythmic.,The American Heart Association has listed chloroquine and hydroxychloroquine as agents which can cause direct myocardial toxicity.,Similarly, other investigational drugs such as favipiravir and lopinavir/ritonavir can prolong QT interval and cause Torsade de Pointes.,Many antibiotics commonly used for the treatment of patients with COVID-19, for instance azithromycin, can also prolong QT interval.,This review summarizes evidenced-based data regarding potential cardiac adverse effects due to off-label and investigational drugs including chloroquine and hydroxychloroquine, antiviral therapy, monoclonal antibodies, as well as common antibiotics used for the treatment of COVID-19.,The article focuses on practical points and offers a point-of-care protocol for providers who are taking care of patients with COVID-19 in an inpatient and outpatient setting.,The proposed protocol is taking into consideration that resources during the pandemic are limited.

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

Infection by the 2019 novel coronavirus (COVID-19) has been reportedly associated with a high risk of thrombotic complications.,So far information is scarce and rapidly emerging.,We conducted a scoping review using a single engine search for studies assessing thrombosis and coagulopathy in COVID-19 patients.,Additional studies were identified by secondary review and alert services.,Studies reported the occurrence of venous thromboembolism and stroke in approximately 20% and 3% of patients, respectively.,A higher frequency seems to be present in severely ill patients, in particular those admitted to intensive care units.,The thrombotic risk is elevated despite the use of anticoagulant prophylaxis but optimal doses of anticoagulation are not yet defined.,Although an increase of biomarkers such as D-dimer has been consistently reported in severely ill COVID-19, the optimal cut-off level and prognostic value are not known.,A number of pressing issues were identified by this review, including defining the true incidence of VTE in COVID patients, developing algorithms to identify those susceptible to develop thrombotic complications and severe disease, determining the role of biomarkers and/or scoring systems to stratify patients' risk, designing adequate and feasible diagnostic protocols for PE, establishing the optimal thromboprophylaxis strategy, and developing uniform diagnostic and reporting criteria.,•Thrombotic events, venous and arterial are frequent in COVID-19, more so in critically ill patients.,•Valid biomarkers to define risk and prognosis are still lacking.,•Anticoagulant prophylaxis is needed in all patients.,•The role of higher doses of anticoagulants in all patients is unclear.,•There is a need to develop standard clinical definitions, common data elements, and standard reporting criteria.,Thrombotic events, venous and arterial are frequent in COVID-19, more so in critically ill patients.,Valid biomarkers to define risk and prognosis are still lacking.,Anticoagulant prophylaxis is needed in all patients.,The role of higher doses of anticoagulants in all patients is unclear.,There is a need to develop standard clinical definitions, common data elements, and standard reporting criteria.

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.

Supplemental Digital Content is available in the text.,Shelter-in-place (SIP) orders implemented to mitigate severe acute respiratory syndrome coronavirus 2 spread may inadvertently discourage patient care-seeking behavior for critical conditions like acute ischemic stroke.,We aimed to compare temporal trends in volume of acute stroke alerts, patient characteristics, telestroke care, and short-term outcomes pre- and post-SIP orders.,We conducted a cohort study in 21 stroke centers of an integrated healthcare system serving 4.4+ million members across Northern California.,We included adult patients who presented with suspected acute stroke and were evaluated by telestroke between January 1, 2019, and May 9, 2020.,SIP orders announced the week of March 15, 2020, created pre (January 1, 2019, to March 14, 2020) and post (March 15, 2020, to May 9, 2020) cohort for comparison.,Main outcomes were stroke alert volumes and inpatient mortality for stroke.,Stroke alert weekly volume post-SIP (mean, 98 [95% CI, 92-104]) decreased significantly compared with pre-SIP (mean, 132 [95% CI, 130-136]; P<0.001).,Stroke discharges also dropped, in concordance with acute stroke alerts decrease.,In total, 9120 patients were included: 8337 in pre- and 783 in post-SIP cohorts.,There were no differences in patient demographics.,Compared with pre-SIP, post-SIP patients had higher National Institutes of Health Stroke Scale scores (P=0.003), lower comorbidity score (P<0.001), and arrived more often by ambulance (P<0.001).,Post-SIP, more patients had large vessel occlusions (P=0.03), and there were fewer stroke mimics (P=0.001).,Discharge outcomes were similar for post-SIP and pre-SIP cohorts.,In this cohort study, regional stroke alert and ischemic stroke discharge volumes decreased significantly in the early COVID-19 pandemic.,Compared with pre-SIP, the post-SIP population showed no significant demographic differences but had lower comorbidity scores, more severe strokes, and more large vessel occlusions.,The inpatient mortality was similar in both cohorts.,Further studies are needed to understand the causes and implications of care avoidance to patients and healthcare systems.

Since the outbreak of the COVID-19 epidemic which in our region, Veneto (Italy), dates back to February, we were confronted with several challenges, but with a constant aim of keeping our Stroke Unit COVID-free.,For this reason, in addition to creating a dedicated hot-spot as a pre-triage just outside the Emergency Department, together with the Neuroradiology Unit we obtained a mobile CT unit that could be used by COVID-positive or COVID-suspected patients.,Furthermore, thanks to the collaboration with colleagues from different specialties (Infectious Disease, Internal Medicine, Intensive Care, Emergency Medicine), dedicated areas for COVID patients were activated.,This led to a substantial change of our acute stoke management pathway.,As the number of COVID patients increased, and the WHO declared a state of pandemic, this new stroke pathway has been fully tested.,We would like to share our experience and send a clear message to keep a high attention on stroke as an emergency condition, because we have observed a decreased number of patients with minor strokes and TIAs, longer onset-to-door and door-to-treatment times for major strokes, and a reduced number of transfers from spokes.,We strongly believe that the general population and family doctors are rightly focused on COVID.,However, to remain at home with stroke symptoms does not mean to “stay safe at home”.

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

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

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

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.

This cohort study examines the characteristics and outcomes of patients for whom transcatheter aortic valve replacement (TAVR) was deferred because of the coronavirus disease 2019 (COVID-19) pandemic.

To describe the place and causes of acute cardiovascular death during the COVID-19 pandemic.,Retrospective cohort of adult (age ≥18 years) acute cardiovascular deaths (n=5 87 225) in England and Wales, from 1 January 2014 to 30 June 2020.,The exposure was the COVID-19 pandemic (from onset of the first COVID-19 death in England, 2 March 2020).,The main outcome was acute cardiovascular events directly contributing to death.,After 2 March 2020, there were 28 969 acute cardiovascular deaths of which 5.1% related to COVID-19, and an excess acute cardiovascular mortality of 2085 (+8%).,Deaths in the community accounted for nearly half of all deaths during this period.,Death at home had the greatest excess acute cardiovascular deaths (2279, +35%), followed by deaths at care homes and hospices (1095, +32%) and in hospital (50, +0%).,The most frequent cause of acute cardiovascular death during this period was stroke (10 318, 35.6%), followed by acute coronary syndrome (ACS) (7 098, 24.5%), heart failure (6 770, 23.4%), pulmonary embolism (2 689, 9.3%) and cardiac arrest (1 328, 4.6%).,The greatest cause of excess cardiovascular death in care homes and hospices was stroke (715, +39%), compared with ACS (768, +41%) at home and cardiogenic shock (55, +15%) in hospital.,The COVID-19 pandemic has resulted in an inflation in acute cardiovascular deaths, nearly half of which occurred in the community and most did not relate to COVID-19 infection suggesting there were delays to seeking help or likely the result of undiagnosed 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.

Coagulopathy in COVID-19 is a burning issue and strategies to prevent thromboembolic events are debated and highly heterogeneous.,The objective was to determine incidence and risk factors of venous thromboembolism (VTE) in COVID-19 inpatients receiving thromboprophylaxis.,In this retrospective French cohort study, patients hospitalized in medical wards non-ICU with confirmed COVID-19 and adequate thromboprophylaxis were included.,A systematic low limb venous duplex ultrasonography was performed at hospital discharge or earlier if deep venous thrombosis (DVT) was clinically suspected.,Chest angio-CT scan was performed when pulmonary embolism (PE) was suspected.,Of 71 patients, 16 developed VTE (22.5%) and 7 PE (10%) despite adequate thromboprophylaxis.,D-dimers at baseline were significantly higher in patients with DVT (p < 0.001).,Demographics, comorbidities, disease manifestations, severity score, and other biological parameters, including inflammatory markers, were similar in patients with and without VTE.,The negative predictive value of a baseline D-dimer level < 1.0 µg/ml was 90% for VTE and 98% for PE.,The positive predictive value for VTE was 44% and 67% for D-dimer level ≥ 1.0 µg/ml and ≥ 3 µg/ml, respectively.,The association between D-dimer level and VTE risk increased by taking into account the latest available D-dimer level prior to venous duplex ultrasonography for the patients with monitoring of D-dimer.,Despite thromboprophylaxis, the risk of VTE is high in COVID-19 non-ICU inpatients.,Increased D-dimer concentrations of more than 1.0 μg/ml predict the risk of venous thromboembolism.,D-dimer level-guided aggressive thromboprophylaxis regimens using higher doses of heparin should be evaluated in prospective studies.

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.

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

Cardiovascular diseases (CVDs) are the most common cause of non-communicable disease mortality in sub-Saharan African (SSA) countries.,Gaps in knowledge of CVD conditions and their risk factors are important barriers in effective prevention and treatment.,Yet, evidence on the awareness and knowledge level of CVD and associated risk factors among populations of SSA is scarce.,This review aimed to synthesize available evidence of the level of knowledge of and perceptions towards CVDs and risk factors in the SSA region.,Five databases were searched for publications up to December 2016.,Narrative synthesis was conducted for knowledge level of CVDs, knowledge of risk factors and clinical signs, factors influencing knowledge of CVDs and source of health information on CVDs.,The review was registered with Prospero (CRD42016049165).,Of 2212 titles and abstracts screened, 45 full-text papers were retrieved and reviewed and 20 were included: eighteen quantitative and two qualitative studies.,Levels of knowledge and awareness for CVD and risk factors were generally low, coupled with poor perception.,Most studies reported less than half of their study participants having good knowledge of CVDs and/or risk factors.,Proportion of participants who were unable to identify a single risk factor and clinical symptom for CVDs ranged from 1.8% in a study among hospital staff in Nigeria to a high of 73% in a population-based survey in Uganda and 7% among University staff in Nigeria to 75.1% in a general population in Uganda respectively.,High educational attainment and place of residence had a significant influence on the levels of knowledge for CVDs among SSA populations.,Low knowledge of CVDs, risk factors and clinical symptoms is strongly associated with the low levels of educational attainment and rural residency in the region.,These findings provide useful information for implementers of interventions targeted at the prevention and control of CVDs, and encourages them to incorporate health promotion and awareness campaigns in order to enhance knowledge and awareness of CVDs in the region.

Adequate awareness of cardiovascular diseases (CVD) and their risk factors may help reduce the population’s exposure to modifiable risk factors and thereby contribute to prevention and control strategies.,There is limited data on knowledge among the general population in sub-Saharan Africa regarding CVD and risk factors.,We aimed to assess the population awareness (and associated factors) of CVD types and risk factors in Buea, Cameroon.,This was a community-based cross-sectional study conducted in 2016 among randomly selected adults (>18 years).,Data on socio-demographic characteristics, knowledge about CVD types, their risk factors and warning signs for CVD events (stroke and heart attack) were acquired using a self-administered questionnaire.,Logistic regression analysis was used to investigate factors associated with moderate-to-good knowledge.,Of the 1162 participants (61.7% women, mean age 32 years), 52.5% had overall poor knowledge (mean score 12.1 on total of 25) on CVD with only about a quarter correctly identifying types of CVD.,Overall, 36, 63 and 45% were unaware of CVD risk factors, warning signs of heart attack and stroke respectively.,In multivariable analysis; high level of education (aOR = 2.26 (1.69-3.02), p < 0.0001), high monthly income (aOR = 1.64 (1.07-2.51), p = 0.023), having a family history of CVD (aOR = 1.59 (1.21-2.09), p = 0.001) and being a former smoker (aOR = 1.11 (1.02-1.95), p = 0.043) were associated with moderate-to-good knowledge.,There exists a significant gap in population awareness about CVDs in Cameroon and this is similar to previous reports.,Cost-effective community health education interventions taking into account socioeconomic status may be beneficial in this setting.

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

COVID-19 predisposes patients to a prothrombotic state with demonstrated microvascular involvement.,The degree of hypercoagulability appears to correlate with outcomes; however, optimal criteria to assess for the highest-risk patients for thrombotic events remain unclear; we hypothesized that deranged thromboelastography measurements of coagulation would correlate with thromboembolic events.,Patients admitted to an ICU with COVID-19 diagnoses who had thromboelastography analyses performed were studied.,Conventional coagulation assays, d-dimer levels, and viscoelastic measurements were analyzed using a receiver operating characteristic curve to predict thromboembolic outcomes and new-onset renal failure.,Forty-four patients with COVID-19 were included in the analysis.,Derangements in coagulation laboratory values, including elevated d-dimer, fibrinogen, prothrombin time, and partial thromboplastin time, were confirmed; viscoelastic measurements showed an elevated maximum amplitude and low lysis of clot at 30 minutes.,A complete lack of lysis of clot at 30 minutes was seen in 57% of patients and predicted venous thromboembolic events with an area under the receiver operating characteristic curve of 0.742 (p = 0.021).,A d-dimer cutoff of 2,600 ng/mL predicted need for dialysis with an area under the receiver operating characteristic curve of 0.779 (p = 0.005).,Overall, patients with no lysis of clot at 30 minutes and a d-dimer > 2,600 ng/mL had a venous thromboembolic event rate of 50% compared with 0% for patients with neither risk factor (p = 0.008), and had a hemodialysis rate of 80% compared with 14% (p = 0.004).,Fibrinolysis shutdown, as evidenced by elevated d-dimer and complete failure of clot lysis at 30 minutes on thromboelastography predicts thromboembolic events and need for hemodialysis in critically ill patients with COVID-19.,Additional clinical trials are required to ascertain the need for early therapeutic anticoagulation or fibrinolytic therapy to address this state of fibrinolysis shutdown.

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

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.

Since the body of evidence addressing the coagulation derangements caused by Coronavirus disease (COVID-19) has been constantly growing, we investigated whether pre-hospitalization oral anticoagulation (OAC) or in-hospital heparin treatment could have a protective role among COVID-19 patients.,In this cohort study, consecutive COVID-19 patients admitted to four different Italian Institutions were enrolled.,Baseline demographic, clinical, laboratory, and radiological characteristics, as well as in-hospital treatment and outcomes were evaluated.,The primary outcome was mortality.,A total of 844 COVID-19 patients were enrolled as study cohort, n = 65 (7.7%) taking OACs prior to hospitalization.,Regarding clinical outcomes, OAC patients developed acute hypoxemic respiratory failure (AHRF) more frequently than non-OAC patients as well as presenting a higher mortality rate (44.6% vs 19.8%, p < 0.001).,At overall multivariate logistical regression, use of heparin (n = 394, 46.6%) was associated with a better chance of survival to hospital discharge (OR 0.60 [0.38-0.94], p < 0.001), in particular in patients with AHRF, with no association found with the use of OACs.,In a sub-analysis, the highest mortality rate was found for AHRF patients when heparin was not administered.,In our cohort, OACs appeared to be ineffective in reducing mortality rate, while heparin resulted to be a useful treatment when lung disease was sufficiently severe, potentially suggesting a crucial role of microthrombosis in severe COVID-19.,Due to the relatively small number of COVID-19 patients treated with OACs included in our analysis and their higher number of comorbidities, larger studies are needed in order to confirm our findings.,•Evidence on a prothrombotic asset caused by COVID-19 has been constantly growing.,•In our cohort, OACs appeared to be ineffective in reducing mortality rate.,•Heparin resulted to be a useful treatment when lung disease was sufficiently severe.,•Microthrombosis may have a crucial role in COVID-19.,•Due to the relatively small sample size of OAC patients included, larger studies are needed.,Evidence on a prothrombotic asset caused by COVID-19 has been constantly growing.,In our cohort, OACs appeared to be ineffective in reducing mortality rate.,Heparin resulted to be a useful treatment when lung disease was sufficiently severe.,Microthrombosis may have a crucial role in COVID-19.,Due to the relatively small sample size of OAC patients included, larger studies are needed.

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 19 (COVID‐19) is a rapidly evolving pandemic caused by the coronavirus Sars‐CoV‐2.,Clinically manifest central nervous system symptoms have been described in COVID‐19 patients and could be the consequence of commonly associated vascular pathology, but the detailed neuropathological sequelae remain largely unknown.,A total of six cases, all positive for Sars‐CoV‐2, showed evidence of cerebral petechial hemorrhages and microthrombi at autopsy.,Two out of six patients showed an elevated risk for disseminated intravascular coagulopathy according to current criteria and were excluded from further analysis.,In the remaining four patients, the hemorrhages were most prominent at the grey and white matter junction of the neocortex, but were also found in the brainstem, deep grey matter structures and cerebellum.,Two patients showed vascular intramural inflammatory infiltrates, consistent with Sars‐CoV‐2‐associated endotheliitis, which was associated by elevated levels of the Sars‐CoV‐2 receptor ACE2 in the brain vasculature.,Distribution and morphology of patchy brain microbleeds was clearly distinct from hypertension‐related hemorrhage, critical illness‐associated microbleeds and cerebral amyloid angiopathy, which was ruled out by immunohistochemistry.,Cerebral microhemorrhages in COVID‐19 patients could be a consequence of Sars‐ CoV‐2‐induced endotheliitis and more general vasculopathic changes and may correlate with an increased risk of vascular encephalopathy.,Clinically manifest central nervous system symptoms are common in COVID‐19 patients but their causes are still unknown.,We present here four patients who tested positive for Sars‐CoV‐2 with cerebral haemorrhages which were most prominent at the grey and white matter junction of the neocortex and the brainstem.,We present evidence of intracerebral endotheliitis in COVID‐19 patients which could predispose to more general vasculopathic changes and may correlate with an increased risk of vascular encephalopathy.

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

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

To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs).,We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019.,We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001).,The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7-32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3-70.3; P < 0.001).,Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191).,A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%).,The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7-6.6; P < 0.001].,A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1-2.8; P = 0.009).,Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates.,This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies.

Electrocardiographic characteristics in COVID‐19‐related mortality have not yet been reported, particularly in racial/ethnic minorities.,We reviewed demographics, laboratory and cardiac tests, medications, and cardiac rhythm proximate to death or initiation of comfort care for patients hospitalized with a positive SARS‐CoV‐2 reverse‐transcriptase polymerase chain reaction in three New York City hospitals between March 1 and April 3, 2020 who died.,We described clinical characteristics and compared factors contributing toward arrhythmic versus nonarrhythmic death.,Of 1258 patients screened, 133 died and were enrolled.,Of these, 55.6% (74/133) were male, 69.9% (93/133) were racial/ethnic minorities, and 88.0% (117/133) had cardiovascular disease.,The last cardiac rhythm recorded was VT or fibrillation in 5.3% (7/133), pulseless electrical activity in 7.5% (10/133), unspecified bradycardia in 0.8% (1/133), and asystole in 26.3% (35/133).,Most 74.4% (99/133) died receiving comfort measures only.,The most common abnormalities on admission electrocardiogram included abnormal QRS axis (25.8%), atrial fibrillation/flutter (14.3%), atrial ectopy (12.0%), and right bundle branch block (11.9%).,During hospitalization, an additional 17.6% developed atrial ectopy, 14.7% ventricular ectopy, 10.1% atrial fibrillation/flutter, and 7.8% a right ventricular abnormality.,Arrhythmic death was confirmed or suspected in 8.3% (11/133) associated with age, coronary artery disease, asthma, vasopressor use, longer admission corrected QT interval, and left bundle branch block (LBBB).,Conduction, rhythm, and electrocardiographic abnormalities were common during COVID‐19‐related hospitalization.,Arrhythmic death was associated with age, coronary artery disease, asthma, longer admission corrected QT interval, LBBB, ventricular ectopy, and usage of vasopressors.,Most died receiving comfort measures.

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.

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

Coronavirus disease 2019 (COVID-19) has been demonstrated to be the cause of pneumonia.,Nevertheless, it has not been reported as the cause of acute myocarditis or fulminant myocarditis.,A 63-year-old male was admitted with pneumonia and cardiac symptoms.,He was genetically confirmed as having COVID-19 according to sputum testing on the day of admission.,He also had elevated troponin I (Trop I) level (up to 11.37 g/L) and diffuse myocardial dyskinesia along with a decreased left ventricular ejection fraction (LVEF) on echocardiography.,The highest level of interleukin-6 was 272.40 pg/ml.,Bedside chest radiographs showed typical ground-glass changes indicative of viral pneumonia.,Laboratory test results for viruses that cause myocarditis were all negative.,The patient conformed to the diagnostic criteria of the Chinese expert consensus statement for fulminant myocarditis.,After receiving antiviral therapy and mechanical life support, Trop I was reduced to 0.10 g/L, and interleukin-6 was reduced to 7.63 pg/mL.,Moreover, the LVEF of the patient gradually recovered to 68%.,The patient died of aggravation of secondary infection on the 33rd day of hospitalization.,COVID-19 patients may develop severe cardiac complications such as myocarditis and heart failure.,This is the first report of COVID-19 complicated with fulminant myocarditis.,The mechanism of cardiac pathology caused by COVID-19 needs further study.

There has been significant controversy regarding the effects of pre‐hospitalization use of renin‐angiotensin system (RAS) inhibitors on the prognosis of hypertensive COVID‐19 patients.,We retrospectively assessed 2,297 hospitalized COVID‐19 patients at Tongji Hospital in Wuhan, China, from January 10th to March 30th, 2020; and identified 1,182 patients with known hypertension on pre‐hospitalization therapy.,We compared the baseline characteristics and in‐hospital mortality between hypertensive patients taking RAS inhibitors (N=355) versus non‐RAS inhibitors (N=827).,Of the 1,182 hypertensive patients (median age 68 years, 49.1% male), 12/355 (3.4%) patients died in the RAS inhibitors group vs.,95/827 (11.5%) patients in the non‐RAS inhibitors group (p<0.0001).,Adjusted hazard ratio for mortality was 0.28 (95% CI 0.15‐0.52, p<0.0001) at 45 days in the RAS inhibitors group compared with non‐RAS inhibitors group.,Similar findings were observed when patients taking angiotensin receptor blockers (N=289) or angiotensin converting enzyme inhibitors (N=66) were separately compared with non‐RAS inhibitors group.,The RAS inhibitors group compared with non‐RAS inhibitors group had lower levels of C‐reactive protein (median 13.5 vs.,24.4 pg/mL; p=0.007) and interleukin‐6 (median 6.0 vs.,8.5 pg/mL; p=0.026) on admission.,The protective effect of RAS inhibitors on mortality was confirmed in a meta‐analysis of published data when our data were added to previous studies (odd ratio 0.44, 95% CI 0.29-0.65, p<0.0001).,In a large single center retrospective analysis we observed a protective effect of pre‐hospitalization use of RAS inhibitors on mortality in hypertensive COVID‐19 patients; which might be associated with reduced inflammatory response.

To investigate possible relationships between pre-existing medical conditions (including common comorbidities and chronic medications) and risk for suffering COVID-19 disease in middle-aged and older adults.,Population-based retrospective cohort study.,Twelve primary care centres (PCCs) in Tarragona (Spain).,79 083 people (77 676 community-dwelling and 1407 nursing-home residents), who were all individuals aged >50 years affiliated to the 12 participating PCCs.,Baseline cohort characteristics (age, sex, vaccinations, comorbidities and chronic medications) were established at study start (1st.,March 2020) and primary outcome was time to COVID-19 confirmed by PCR among cohort members throughout the epidemic period (from 1st.,March 2020 to 23rd.,May 2020).,Risk for suffering COVID-19 was evaluated by Cox regression, estimating multivariable HRs adjusted for age, sex, comorbidities and medications use.,During the study period, 2324 cohort members were PCR-tested, with 1944 negative and 380 positive results, which means an incidence of 480.5 PCR-confirmed COVID-19 cases per 100 000 persons-period.,Assessing the total study cohort, only age (HR 1.02; 95% CI 1.01 to 1.03; p=0.002), nursing-home residence (HR 21.83; 95% CI 16.66 to 28.61; p<0.001) and receiving diuretics (HR 1.35; 95% CI 1.04 to 1.76; p=0.026) appeared independently associated with increased risk.,Smoking (HR 0.62; 95% CI 0.41 to 0.93; p=0.022), ACE inhibitors (HR 0.68; 95% CI 0.47 to 0.99; p=0.046) and antihistamine (HR 0.47; 95% CI 0.22 to 1.01; p=0.052) were associated with a lower risk.,Among community-dwelling individuals, cancer (HR 1.52; 95% CI 1.03 to 2.24; p=0.035), chronic respiratory disease (HR 1.82; 95% CI 1.08 to 3.07; p=0.025) and cardiac disease (HR 1.53; 95% CI 1.06 to 2.19; p=0.021) emerged to be also associated with an increased risk.,Receiving ACE inhibitors (HR 0.66; 95% CI 0.44 to 0.99; p=0.046) and influenza vaccination (HR 0.63; 95% CI 0.44 to 0.91; p=0.012) was associated with decreased risk.,Age, nursing-home residence and multiple comorbidities appear predisposing for COVID-19.,Conversely, receiving ACE inhibitors, antihistamine and influenza vaccination could be protective, which should be closely investigated in further studies specifically focused on these concerns.

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability.,This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019.,GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019.,Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019.,The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period.,The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019.,The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019.,Cardiovascular diseases remain the leading cause of disease burden in the world.,CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries.,There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.,•The burden of CVD, in number of DALYs and deaths, continues to increase globally.,•CVD burden attributable to modifiable risk factors continues to increase globally.,•Countries should invest in existing cost-effective public health programs and clinical interventions to target modifiable risks, promote healthy aging across the lifespan, and reduce disability and premature death due to CVD.,The burden of CVD, in number of DALYs and deaths, continues to increase globally.,CVD burden attributable to modifiable risk factors continues to increase globally.,Countries should invest in existing cost-effective public health programs and clinical interventions to target modifiable risks, promote healthy aging across the lifespan, and reduce disability and premature death due to CVD.

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.

Coronavirus disease 2019 (COVID-19) has caused a global pandemic in just a few months, causing millions infected.,Nearly 20% of COVID-19 patients present severe coagulation abnormalities, which may occur in almost all of the severe and critical ill COVID-19 cases.,Concomitant venous thromboembolism (VTE), a potential cause of unexplained deaths, has been frequently reported in COVID-19 cases, but its management is still challenging due to the complexity between antithrombotic therapy and coagulation disorders.,Based on frontline practical experience and comprehensive literature review, here a panel of experts and physicians from China and Europe developed an evidence and opinion-based consensus on the prophylaxis and management of VTE associated with COVID-19.,This statement aims for clinicians treating COVID-19 and provides practical recommendations in detailed situations, for example, how to choose thromboprophylactic measures for patients with diverse severity of disease and bleeding risk, or which kind of anticoagulant should be prescribed.,With limited experience on COVID19-associated VTE, this expert consensus statement should be helpful for clinicians worldwide with specific suggestions.

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.

Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals.,Extensive studies have revealed that SARS-CoV-2 shares many biological features with SARS-CoV, the zoonotic virus that caused the 2002 outbreak of severe acute respiratory syndrome, including the system of cell entry, which is triggered by binding of the viral spike protein to angiotensin-converting enzyme 2.,Clinical studies have also reported an association between COVID-19 and cardiovascular disease.,Pre-existing cardiovascular disease seems to be linked with worse outcomes and increased risk of death in patients with COVID-19, whereas COVID-19 itself can also induce myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism.,Potential drug-disease interactions affecting patients with COVID-19 and comorbid cardiovascular diseases are also becoming a serious concern.,In this Review, we summarize the current understanding of COVID-19 from basic mechanisms to clinical perspectives, focusing on the interaction between COVID-19 and the cardiovascular system.,By combining our knowledge of the biological features of the virus with clinical findings, we can improve our understanding of the potential mechanisms underlying COVID-19, paving the way towards the development of preventative and therapeutic solutions.,The presence of cardiovascular comorbidities is linked with worse outcomes in patients with coronavirus disease 2019 (COVID-19), and COVID-19 can induce cardiovascular damage.,In this Review, Wu and colleagues summarize the latest mechanistic and clinical studies that contribute to our current understanding of COVID-19-related cardiovascular disease.,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), shares many biological features with SARS-CoV, the virus that causes severe acute respiratory syndrome, owing to 80% genomic sequence identity.The interaction between the viral spike (S) protein and angiotensin-converting enzyme 2, which triggers entry of the virus into host cells, is likely to be involved in the cardiovascular manifestations of COVID-19.,The presence of underlying cardiovascular comorbidities in patients with COVID-19 is associated with high mortality.COVID-19 can cause cardiovascular disorders, including myocardial injury, arrhythmias, acute coronary syndrome and venous thromboembolism.Several medications used for the treatment of COVID-19 have uncertain safety and efficacy profiles.,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), shares many biological features with SARS-CoV, the virus that causes severe acute respiratory syndrome, owing to 80% genomic sequence identity.,The interaction between the viral spike (S) protein and angiotensin-converting enzyme 2, which triggers entry of the virus into host cells, is likely to be involved in the cardiovascular manifestations of COVID-19.,The presence of underlying cardiovascular comorbidities in patients with COVID-19 is associated with high mortality.,COVID-19 can cause cardiovascular disorders, including myocardial injury, arrhythmias, acute coronary syndrome and venous thromboembolism.,Several medications used for the treatment of COVID-19 have uncertain safety and efficacy profiles.

This retrospective case-control study was aimed at identifying potential independent predictors of severe/lethal COVID-19, including the treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) and/or Angiotensin II Receptor Blockers (ARBs).,All adults with SARS-CoV-2 infection in two Italian provinces were followed for a median of 24 days.,ARBs and/or ACEi treatments, and hypertension, diabetes, cancer, COPD, renal and major cardiovascular diseases (CVD) were extracted from clinical charts and electronic health records, up to two years before infection.,The sample consisted of 1603 subjects (mean age 58.0y; 47.3% males): 454 (28.3%) had severe symptoms, 192 (12.0%) very severe or lethal disease (154 deaths; mean age 79.3 years; 70.8% hypertensive, 42.2% with CVD).,The youngest deceased person aged 44 years.,Among hypertensive subjects (n = 543), the proportion of those treated with ARBs or ACEi were 88.4%, 78.7% and 80.6% among patients with mild, severe and very severe/lethal disease, respectively.,At multivariate analysis, no association was observed between therapy and disease severity (Adjusted OR for very severe/lethal COVID-19: 0.87; 95% CI: 0.50-1.49).,Significant predictors of severe disease were older age (with AORs largely increasing after 70 years of age), male gender (AOR: 1.76; 1.40-2.23), diabetes (AOR: 1.52; 1.05-2.18), CVD (AOR: 1.88; 1.32-2.70) and COPD (AOR: 1.88; 1.11-3.20).,Only gender, age and diabetes also predicted very severe/lethal disease.,No association was found between COVID-19 severity and treatment with ARBs and/or ACEi, supporting the recommendation to continue medication for all patients unless otherwise advised by their physicians.

Previous studies have demonstrated that no-option angiitis-induced critical limb ischemia (NO-AICLI) could be significantly improved by transplantation of peripheral blood-derived stem cells (PBDSCs).,Additionally, a randomized controlled trial (RCT) recently conducted by us suggested that peripheral blood-derived purified CD34+ cells (PCCs) were not inferior to non-purified peripheral blood mononuclear cells (PBMNCs) at limb salvage in treatment of NO-AICLI.,However, most of these clinical trials whether RCT or single-arm studies were characterized with a small sample size and absence of long-term outcomes.,To analyze long-term clinical outcomes of PBDSCs transplantation for NO-AICLI, we reviewed clinical data of patients with NO-AICLI receiving PBDSCs transplantation at our center during the past decade.,Meanwhile, we first compared the long-term safety and efficacy of intramuscular transplantation of PCCs versus PBMNCs in a sizable number of patients with NO-AICLI.,From May 2009 to December 2019, a total of 160 patients with NO-AICLI patients were treated by PBDSCs transplantation (82 with PCCs, 78 with PBMNCs) at our center.,Baseline characteristics between two groups were similar.,Up to June 2020, the mean follow-up period was 46.6 ± 35.3 months.,No critical adverse events were observed in either group.,There was one death during the follow-up period.,A total of eight major amputations occurred.,The cumulative major amputation-free survival (MAFS) rate at 5 years after PBDSCs transplantation was 94.4%, without difference between two groups (P = .855).,Wound healing, rest pain, pain-free walking time, ankle-brachial index, transcutaneous oxygen pressure, and quality of life (QoL) also significantly improved after PBDSCs transplantation.,Autologous PBDSCs intramuscular transplantation could significantly decrease the major amputation rates and improve the QoL in patients with NO-AICLI.,Long-term observation of a large sample of patients confirmed that the clinical benefits of PBDSCs transplantation were durable, without difference between the PCCs and PBMNCs groups.

For patients with thromboangiitis obliterans (TAO), revascularization with bypass or angioplasty is frequently not feasible due to the poor outflow of the distal small vessels.,We evaluated the long-term results of our experience treating patients with TAO with autologous bone marrow-derived mononuclear cells (ABMMNCs) to determine the safety and efficacy of ABMMNC therapy in patients with critical limb ischemia due to TAO.,This was a retrospective chart review from a single university hospital vascular surgery center between January 2005 and July 2006.,Patients were treated with smoking cessation and either aspirin (100 mg/day) alone or aspirin and ABMMNC injection according to patient preference.,Groups were compared for demographics, clinical characteristics, and short-term and long-term results.,Of 59 patients with TAO who were treated, 19 patients elected aspirin alone and 40 patients elected aspirin and ABMMNC injection.,No patients suffered perioperative complications and 49 (83%) patients remained smoke-free for 10 years.,The 10-year amputation-free survival was 85.3% (29/34) in patients treated with ABMMNCs compared to 40% (6/15) in patients treated with aspirin alone (p = 0.0019).,Ulcer area (p < 0.0001), toe-brachial index (TBI; p < 0.0001), transcutaneous oxygen pressure (TcPO2; p < 0.0001), and pain score (p < 0.0001) were also significantly improved with ABMMNC treatment, although there was no difference in mean ankle-brachial index (ABI; p = 0.806).,In patients with critical limb ischemia due to TAO, ABMMNC treatment was safe and effective.,ABMMNC treatment significantly improved amputation-free survival, ulcer healing, and pain, although there is no difference in ABI compared to treatment with aspirin alone.

Understanding the epidemiology and clinical course of multisystem inflammatory syndrome in children (MIS-C) and its temporal association with coronavirus disease 2019 (Covid-19) is important, given the clinical and public health implications of the syndrome.,We conducted targeted surveillance for MIS-C from March 15 to May 20, 2020, in pediatric health centers across the United States.,The case definition included six criteria: serious illness leading to hospitalization, an age of less than 21 years, fever that lasted for at least 24 hours, laboratory evidence of inflammation, multisystem organ involvement, and evidence of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) based on reverse-transcriptase polymerase chain reaction (RT-PCR), antibody testing, or exposure to persons with Covid-19 in the past month.,Clinicians abstracted the data onto standardized forms.,We report on 186 patients with MIS-C in 26 states.,The median age was 8.3 years, 115 patients (62%) were male, 135 (73%) had previously been healthy, 131 (70%) were positive for SARS-CoV-2 by RT-PCR or antibody testing, and 164 (88%) were hospitalized after April 16, 2020.,Organ-system involvement included the gastrointestinal system in 171 patients (92%), cardiovascular in 149 (80%), hematologic in 142 (76%), mucocutaneous in 137 (74%), and respiratory in 131 (70%).,The median duration of hospitalization was 7 days (interquartile range, 4 to 10); 148 patients (80%) received intensive care, 37 (20%) received mechanical ventilation, 90 (48%) received vasoactive support, and 4 (2%) died.,Coronary-artery aneurysms (z scores ≥2.5) were documented in 15 patients (8%), and Kawasaki’s disease-like features were documented in 74 (40%).,Most patients (171 [92%]) had elevations in at least four biomarkers indicating inflammation.,The use of immunomodulating therapies was common: intravenous immune globulin was used in 144 (77%), glucocorticoids in 91 (49%), and interleukin-6 or 1RA inhibitors in 38 (20%).,Multisystem inflammatory syndrome in children associated with SARS-CoV-2 led to serious and life-threatening illness in previously healthy children and adolescents.,(Funded by the Centers for Disease Control and Prevention.)

We report on the presentation and course of 33 children with multisystem inflammatory syndrome in children and confirmed severe acute respiratory syndrome coronavirus 2 infection.,Hemodynamic instability and cardiac dysfunction were prominent findings, with most patients exhibiting rapid resolution following anti-inflammatory therapy.

The impact of atrial arrhythmias on coronavirus disease 2019 (COVID‐19)‐associated outcomes are unclear.,We sought to identify prevalence, risk factors and outcomes associated with atrial arrhythmias among patients hospitalized with COVID‐19.,An observational cohort study of 1053 patients with severe acute respiratory syndrome coronavirus 2 infection admitted to a quaternary care hospital and a community hospital was conducted.,Data from electrocardiographic and telemetry were collected to identify atrial fibrillation (AF) or atrial flutter/tachycardia (AFL).,The association between atrial arrhythmias and 30‐day mortality was assessed with multivariable analysis.,Mean age of patients was 62 ± 17 years and 62% were men.,Atrial arrhythmias were identified in 166 (15.8%) patients, with AF in 154 (14.6%) patients and AFL in 40 (3.8%) patients.,Newly detected atrial arrhythmias occurred in 101 (9.6%) patients.,Age, male sex, prior AF, renal disease, and hypoxia on presentation were independently associated with AF/AFL occurrence.,Compared with patients without AF/AFL, patients with AF/AFL had significantly higher levels of troponin, B‐type natriuretic peptide, C‐reactive protein, ferritin and d‐dimer.,Mortality was significantly higher among patients with AF/AFL (39.2%) compared to patients without (13.4%; p < .001).,After adjustment for age and co‐morbidities, AF/AFL (adjusted odds ratio [OR]: 1.93; p = .007) and newly detected AF/AFL (adjusted OR: 2.87; p < .001) were independently associated with 30‐day mortality.,Atrial arrhythmias are common among patients hospitalized with COVID‐19.,The presence of AF/AFL tracked with markers of inflammation and cardiac injury.,Atrial arrhythmias were independently associated with increased mortality.

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.

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

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.

Individual studies have reported widely variable rates for VTE and bleeding among hospitalized patients with coronavirus disease 2019 (COVID-19).,What is the incidence of VTE and bleeding among hospitalized patients with COVID-19?,In this systematic review and meta-analysis, 15 standard sources and COVID-19-specific sources were searched between January 1, 2020, and July 31, 2020, with no restriction according to language.,Incidence estimates were pooled by using random effects meta-analyses.,Heterogeneity was evaluated by using the I2 statistic, and publication bias was assessed by using the Begg and Egger tests.,The pooled incidence was 17.0% (95% CI, 13.4-20.9) for VTE, 12.1% (95% CI, 8.4-16.4) for DVT, 7.1% (95% CI, 5.3-9.1) for pulmonary embolism (PE), 7.8% (95% CI, 2.6-15.3) for bleeding, and 3.9% (95% CI, 1.2-7.9) for major bleeding.,In subgroup meta-analyses, the incidence of VTE was higher when assessed according to screening (33.1% vs 9.8% by clinical diagnosis), among patients in the ICU (27.9% vs 7.1% in the ward), in prospective studies (25.5% vs 12.4% in retrospective studies), and with the inclusion of catheter-associated thrombosis/isolated distal DVTs and isolated subsegmental PEs.,The highest pooled incidence estimate of bleeding was reported for patients receiving intermediate- or full-dose anticoagulation (21.4%) and the lowest in the only prospective study that assessed bleeding events (2.7%).,Among hospitalized patients with COVID-19, the overall estimated pooled incidence of VTE was 17.0%, with higher rates with routine screening, inclusion of distal DVT, and subsegmental PE, in critically ill patients and in prospective studies.,Bleeding events were observed in 7.8% of patients and were sensitive to use of escalated doses of anticoagulants and nature of data collection.,Additional studies are required to ascertain the significance of various thrombotic events and to identify strategies to improve patient outcomes.,PROSPERO; No.: CRD42020198864; URL: https://www.crd.york.ac.uk/prospero/.

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.

The viral load of asymptomatic SAR-COV-2 positive (ASAP) persons has been equal to that of symptomatic patients.,On the other hand, there are no reports of ST-elevation myocardial infarction (STEMI) outcomes in ASAP patients.,Therefore, we evaluated thrombus burden and thrombus viral load and their impact on microvascular bed perfusion in the infarct area (myocardial blush grade, MBG) in ASAP compared to SARS-COV-2 negative (SANE) STEMI patients.,This was an observational study of 46 ASAP, and 130 SANE patients admitted with confirmed STEMI treated with primary percutaneous coronary intervention and thrombus aspiration.,The primary endpoints were thrombus dimension + thrombus viral load effects on MBG after PPCI.,The secondary endpoints during hospitalization were major adverse cardiovascular events (MACEs).,MACEs are defined as a composite of cardiovascular death, nonfatal acute AMI, and heart failure during hospitalization.,In the study population, ASAP vs.,SANE showed a significant greater use of GP IIb/IIIa inhibitors and of heparin (p < 0.05), and a higher thrombus grade 5 and thrombus dimensions (p < 0.05).,Interestingly, ASAP vs.,SANE patients had lower MBG and left ventricular function (p < 0.001), and 39 (84.9%) of ASAP patients had thrombus specimens positive for SARS-COV-2.,After PPCI, a MBG 2-3 was present in only 26.1% of ASAP vs.,97.7% of SANE STEMI patients (p < 0.001).,Notably, death and nonfatal AMI were higher in ASAP vs.,SANE patients (p < 0.05).,Finally, in ASAP STEMI patients the thrombus viral load was a significant determinant of thrombus dimension independently of risk factors (p < 0.005).,Thus, multiple logistic regression analyses evidenced that thrombus SARS-CoV-2 infection and dimension were significant predictors of poorer MBG in STEMI patients.,Intriguingly, in ASAP patients the female vs. male had higher thrombus viral load (15.53 ± 4.5 vs.,30.25 ± 5.51 CT; p < 0.001), and thrombus dimension (4.62 ± 0.44 vs 4.00 ± 1.28 mm2; p < 0.001).,ASAP vs.,SANE patients had a significantly lower in-hospital survival for MACE following PPCI (p < 0.001).,In ASAP patients presenting with STEMI, there is strong evidence towards higher thrombus viral load, dimension, and poorer MBG.,These data support the need to reconsider ASAP status as a risk factor that may worsen STEMI outcomes.

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

Atherogenic index of plasma (AIP) has been reported to be associated with cardiovascular diseases.,However no study has yet systematically evaluated the association between AIP and obesity and its advantage in obesity prediction compared with conventional lipid components.,A total of 6465 participants aged over 30 years were included in this study.,Blood lipid components including triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were measured, and AIP was calculated as log10(TG/HDL-C).,Pearson correlation analyses, multivariable logistic analyses and predictive analyses were used to evaluate the association and discrimination ability between AIP, four conventional lipid profiles and obesity.,Subjects in the higher quartiles of AIP all had a significantly increased risk of obesity compared with those in the lowest quartile (P for trend< 0.01).,AIP showed a stronger association with obesity than the conventional lipid components as the pearson coefficient reached up to 0.372 and the adjusted odds ratio was 5.55.,Using AIP rather than HDL-C and TG significantly improved risk prediction for obesity (AUC improvement = 0.011, P = 0.011; Continuous net reclassification index = 29.55%, P < 0.01; Category net reclassification index = 6.06%; Integrated discrimination improvement = 0.68%, P < 0.01).,Higher AIP level was positively and strongly associated with obesity.,AIP is a novel and better biomarker associated with obesity.,Controlling the AIP level would be more helpful for the prevention of obesity.

The correlation between the atherogenic index of plasma (AIP) and waist circumference (WC) remains unknown.,A total of 5351 middle-aged men living in Southeastern China were surveyed using the random stratified cluster sampling method.,A WC of 90 cm or greater was indicative of abdominal obesity, and AIP was calculated as follows: log [triglyceride (TG)/high-density lipoprotein-cholesterol (HDL-C)].,(1) A significantly higher AIP was observed in subjects with abdominal obesity than in those without abdominal obesity (P < 0·001).,(2) Multivariate logistic regression analysis revealed an odds ratio of 1·93, 2·59 and 2·76 for abnormal AIP levels for the second, third and fourth WC quartiles, respectively (all P < 0·001) compared to the first WC quartile as a reference.,(3) There was a linear correlation between WC and AIP, and a 1·0 cm increase in WC resulted in a 0·0175 rise in AIP.,For AIP corresponding to moderate risk (0·12-0·21), WC was 85-90 cm; for AIP corresponding to high risk (> 0·21), WC was >90 cm.,AIP of 0·12-0·21 or >0·21 indicates a likelihood of borderline abdominal obesity or abdominal obesity, respectively, and the combination of WC and AIP may increase the specificity and sensitivity for detection of abdominal obesity in clinical practice.,The results suggest that AIP may be used as a reference to estimate abdominal obesity.

The purpose of this study was to detect cardiovascular changes after mild severe acute respiratory syndrome-coronavirus-2 infection.,Concern exists that mild coronavirus disease 2019 may cause myocardial and vascular disease.,Participants were recruited from COVIDsortium, a 3-hospital prospective study of 731 health care workers who underwent first-wave weekly symptom, polymerase chain reaction, and serology assessment over 4 months, with seroconversion in 21.5% (n = 157).,At 6 months post-infection, 74 seropositive and 75 age-, sex-, and ethnicity-matched seronegative control subjects were recruited for cardiovascular phenotyping (comprehensive phantom-calibrated cardiovascular magnetic resonance and blood biomarkers).,Analysis was blinded, using objective artificial intelligence analytics where available.,A total of 149 subjects (mean age 37 years, range 18 to 63 years, 58% women) were recruited.,Seropositive infections had been mild with case definition, noncase definition, and asymptomatic disease in 45 (61%), 18 (24%), and 11 (15%), respectively, with 1 person hospitalized (for 2 days).,Between seropositive and seronegative groups, there were no differences in cardiac structure (left ventricular volumes, mass, atrial area), function (ejection fraction, global longitudinal shortening, aortic distensibility), tissue characterization (T1, T2, extracellular volume fraction mapping, late gadolinium enhancement) or biomarkers (troponin, N-terminal pro-B-type natriuretic peptide).,With abnormal defined by the 75 seronegatives (2 SDs from mean, e.g., ejection fraction <54%, septal T1 >1,072 ms, septal T2 >52.4 ms), individuals had abnormalities including reduced ejection fraction (n = 2, minimum 50%), T1 elevation (n = 6), T2 elevation (n = 9), late gadolinium enhancement (n = 13, median 1%, max 5% of myocardium), biomarker elevation (borderline troponin elevation in 4; all N-terminal pro-B-type natriuretic peptide normal).,These were distributed equally between seropositive and seronegative individuals.,Cardiovascular abnormalities are no more common in seropositive versus seronegative otherwise healthy, workforce representative individuals 6 months post-mild severe acute respiratory syndrome-coronavirus-2 infection.

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.

Widespread consumption of high-fructose and high-fat diets relates to the global epidemic of hypertension.,Hypertension may originate from early life by a combination of prenatal and postnatal nutritional insults.,We examined whether maternal high-fructose diet increases vulnerability to post-weaning high-fructose or high-fat diets induced hypertension in adult offspring and determined the underlying mechanisms.,Pregnant Sprague-Dawley rats received regular chow (ND) or chow supplemented with 60% fructose (HFR) during the entire pregnancy and lactation periods.,Male offspring were onto either the regular chow, 60% fructose, or high-fat diet (HFA) from weaning to 12 weeks of age and assigned to four groups: ND/ND, HFR/ND, HFR/HFR, and HFR/HFA.,Maternal high-fructose diet exacerbates post-weaning high-fat diet-induced programmed hypertension.,Post-weaning high-fructose and high-fat diets similarly reduced Sirt4, Prkaa2, Prkag2, Ppara, Pparb, and Ppargc1a mRNA expression in offspring kidneys exposed to maternal high-fructose intake.,Additionally, post-weaning high-fat diet significantly reduced renal mRNA levels of Ulk1, Atg5, and Nrf2 and induced greater oxidative stress than did high-fructose diet.,Although maternal high-fructose intake increases soluble epoxide hydrolase (SEH) expression in the kidney, which was restored by post-weaning high-fructose and high-fat diets.,Maternal high-fructose diet programs differential vulnerability to developing hypertension in male offspring in response to post-weaning high-fructose and high-fat diets.,Our data implicated that specific therapy targeting on nutrient sensing signals, oxidative stress, and SEH may be a promising approach to prevent hypertension in children and mothers exposed to high-fructose and high-fat consumption.

Recently, the potential role of gut microbiome in metabolic diseases has been revealed, especially in cardiovascular diseases.,Hypertension is one of the most prevalent cardiovascular diseases worldwide, yet whether gut microbiota dysbiosis participates in the development of hypertension remains largely unknown.,To investigate this issue, we carried out comprehensive metagenomic and metabolomic analyses in a cohort of 41 healthy controls, 56 subjects with pre-hypertension, 99 individuals with primary hypertension, and performed fecal microbiota transplantation from patients to germ-free mice.,Compared to the healthy controls, we found dramatically decreased microbial richness and diversity, Prevotella-dominated gut enterotype, distinct metagenomic composition with reduced bacteria associated with healthy status and overgrowth of bacteria such as Prevotella and Klebsiella, and disease-linked microbial function in both pre-hypertensive and hypertensive populations.,Unexpectedly, the microbiome characteristic in pre-hypertension group was quite similar to that in hypertension.,The metabolism changes of host with pre-hypertension or hypertension were identified to be closely linked to gut microbiome dysbiosis.,And a disease classifier based on microbiota and metabolites was constructed to discriminate pre-hypertensive and hypertensive individuals from controls accurately.,Furthermore, by fecal transplantation from hypertensive human donors to germ-free mice, elevated blood pressure was observed to be transferrable through microbiota, and the direct influence of gut microbiota on blood pressure of the host was demonstrated.,Overall, our results describe a novel causal role of aberrant gut microbiota in contributing to the pathogenesis of hypertension.,And the significance of early intervention for pre-hypertension was emphasized.,The online version of this article (doi:10.1186/s40168-016-0222-x) contains supplementary material, which is available to authorized users.

The mainstay of control of the coronavirus disease 2019 (Covid-19) pandemic is vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Within a year, several vaccines have been developed and millions of doses delivered.,Reporting of adverse events is a critical postmarketing activity.,We report findings in 23 patients who presented with thrombosis and thrombocytopenia 6 to 24 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca).,On the basis of their clinical and laboratory features, we identify a novel underlying mechanism and address the therapeutic implications.,In the absence of previous prothrombotic medical conditions, 22 patients presented with acute thrombocytopenia and thrombosis, primarily cerebral venous thrombosis, and 1 patient presented with isolated thrombocytopenia and a hemorrhagic phenotype.,All the patients had low or normal fibrinogen levels and elevated d-dimer levels at presentation.,No evidence of thrombophilia or causative precipitants was identified.,Testing for antibodies to platelet factor 4 (PF4) was positive in 22 patients (with 1 equivocal result) and negative in 1 patient.,On the basis of the pathophysiological features observed in these patients, we recommend that treatment with platelet transfusions be avoided because of the risk of progression in thrombotic symptoms and that the administration of a nonheparin anticoagulant agent and intravenous immune globulin be considered for the first occurrence of these symptoms.,Vaccination against SARS-CoV-2 remains critical for control of the Covid-19 pandemic.,A pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, can occur after the administration of the ChAdOx1 nCoV-19 vaccine.,Rapid identification of this rare syndrome is important because of the therapeutic implications.

Heparin-induced thrombocytopenia/thrombosis (HIT) is a serious immune reaction to heparins, characterized by thrombocytopenia and often severe thrombosis with high morbidity and mortality.,HIT is mediated by IgG antibodies against heparin/platelet factor 4 antigenic complexes.,These complexes are thought to activate platelets leading to thrombocytopenia and thrombosis.,Here we show that HIT immune complexes induce NETosis via interaction with FcγRIIa on neutrophils and through neutrophil-platelet association.,HIT immune complexes induce formation of thrombi containing neutrophils, extracellular DNA, citrullinated histone H3 and platelets in a microfluidics system and in vivo, while neutrophil depletion abolishes thrombus formation.,Absence of PAD4 or PAD4 inhibition with GSK484 abrogates thrombus formation but not thrombocytopenia, suggesting they are induced by separate mechanisms.,NETs markers and neutrophils undergoing NETosis are present in HIT patients.,Our findings demonstrating the involvement of NETosis in thrombosis will modify the current concept of HIT pathogenesis and may lead to new therapeutic strategies.,The pathogenesis of heparin-induced thrombocytopenia and thrombosis (HIT) is mediated by heparin-reactive autoantibodies binding to platelets (thrombocytes).,Here the authors show neutrophil activation and NETosis are elevated in patients with HIT, and are essential for thrombosis in HIT mouse models.

A compelling body of evidence points to pulmonary thrombosis and thromboembolism as a key feature of COVID-19.,As the pandemic spread across the globe over the past few months, a timely call to arms was issued by a team of clinicians to consider the prospect of long-lasting pulmonary fibrotic damage and plan for structured follow-up.,However, the component of post-thrombotic sequelae has been less widely considered.,Although the long-term outcomes of COVID-19 are not known, should pulmonary vascular sequelae prove to be clinically significant, these have the potential to become a public health problem.,In this Personal View, we propose a proactive follow-up strategy to evaluate residual clot burden, small vessel injury, and potential haemodynamic sequelae.,A nuanced and physiological approach to follow-up imaging that looks beyond the clot, at the state of perfusion of lung tissue, is proposed as a key triage tool, with the potential to inform therapeutic strategies.

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

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

A novel coronavirus disease (COVID-19) in Wuhan has caused an outbreak and become a major public health issue in China and great concern from international community.,Myocarditis and myocardial injury were suspected and may even be considered as one of the leading causes for death of COVID-19 patients.,Therefore, we focused on the condition of the heart, and sought to provide firsthand evidence for whether myocarditis and myocardial injury were caused by COVID-19.,We enrolled patients with confirmed diagnosis of COVID-19 retrospectively and collected heart-related clinical data, mainly including cardiac imaging findings, laboratory results and clinical outcomes.,Serial tests of cardiac markers were traced for the analysis of potential myocardial injury/myocarditis.,112 COVID-19 patients were enrolled in our study.,There was evidence of myocardial injury in COVID-19 patients and 14 (12.5%) patients had presented abnormalities similar to myocarditis.,Most of patients had normal levels of troponin at admission, that in 42 (37.5%) patients increased during hospitalization, especially in those that died.,Troponin levels were significantly increased in the week preceding the death.,15 (13.4%) patients have presented signs of pulmonary hypertension.,Typical signs of myocarditis were absent on echocardiography and electrocardiogram.,The clinical evidence in our study suggested that myocardial injury is more likely related to systemic consequences rather than direct damage by the 2019 novel coronavirus.,The elevation in cardiac markers was probably due to secondary and systemic consequences and can be considered as the warning sign for recent adverse clinical outcomes of the patients.,•The evidence from clinical standpoint and front-line data in Wuhan for COVID-19.,•The novel coronavirus in COVID-19 less likely caused myocardial injury directly.,•Elevation in cardiac markers is the warning sign of adverse outcomes for COVID-19.,The evidence from clinical standpoint and front-line data in Wuhan for COVID-19.,The novel coronavirus in COVID-19 less likely caused myocardial injury directly.,Elevation in cardiac markers is the warning sign of adverse outcomes for COVID-19.

Curcumin has anti-inflammatory, antioxidative, anticarcinogenic, and cardiovascular protective effects.,Our study is aimed at evaluating the effects of pretreatment with curcumin nanoparticles (CCNP) compared to conventional curcumin (CC) on isoproterenol (ISO) induced myocardial infarction (MI) in rats.,Fifty-six Wistar-Bratislava white rats were randomly divided into eight groups of seven rats each.,Curcumin and curcumin nanoparticles were given by gavage in three different doses (100 mg/kg body weight (bw), 150 mg/kg bw, and 200 mg/kg bw) for 15 days.,The MI was induced on day 13 using 100 mg/kg bw ISO administered twice, with the second dose 24 h after the initial dose.,The blood samples were taken 24 h after the last dose of ISO.,The antioxidant, anti-inflammatory, and cardioprotective effects were evaluated in all groups.,All doses of CC and CCNP offered a cardioprotective effect by preventing creatine kinase-MB leakage from cardiomyocytes, with the best result for CCNP.,All the oxidative stress parameters were significantly improved after CCNP compared to CC pretreatment.,CCNP was more efficient than CC in limiting the increase in inflammatory cytokine levels (such as TNF-α, IL-6, IL-1α, IL-1β, MCP-1, and RANTES) after MI.,MMP-2 and MMP-9 levels decreased more after pretreatment with CCNP than with CC.,CCNP better prevented myocardial necrosis and reduced interstitial edema and neutrophil infiltration than CC, on histopathological examination.,Therefore, improving the bioactivity of curcumin by nanotechnology may help limit cardiac injury after myocardial infarction.

Disrupting the costimulatory CD40-CD40L dyad reduces atherosclerosis, but can result in immune suppression.,The authors recently identified small molecule inhibitors that block the interaction between CD40 and tumor necrosis factor receptor-associated factor (TRAF) 6 (TRAF-STOPs), while leaving CD40-TRAF2/3/5 interactions intact, thereby preserving CD40-mediated immunity.,This study evaluates the potential of TRAF-STOP treatment in atherosclerosis.,The effects of TRAF-STOPs on atherosclerosis were investigated in apolipoprotein E deficient (Apoe−/−) mice.,Recombinant high-density lipoprotein (rHDL) nanoparticles were used to target TRAF-STOPs to macrophages.,TRAF-STOP treatment of young Apoe−/− mice reduced atherosclerosis by reducing CD40 and integrin expression in classical monocytes, thereby hampering monocyte recruitment.,When Apoe−/− mice with established atherosclerosis were treated with TRAF-STOPs, plaque progression was halted, and plaques contained an increase in collagen, developed small necrotic cores, and contained only a few immune cells.,TRAF-STOP treatment did not impair “classical” immune pathways of CD40, including T-cell proliferation and costimulation, Ig isotype switching, or germinal center formation, but reduced CD40 and β2-integrin expression in inflammatory monocytes.,In vitro testing and transcriptional profiling showed that TRAF-STOPs are effective in reducing macrophage migration and activation, which could be attributed to reduced phosphorylation of signaling intermediates of the canonical NF-κB pathway.,To target TRAF-STOPs specifically to macrophages, TRAF-STOP 6877002 was incorporated into rHDL nanoparticles.,Six weeks of rHDL-6877002 treatment attenuated the initiation of atherosclerosis in Apoe−/− mice.,TRAF-STOPs can overcome the current limitations of long-term CD40 inhibition in atherosclerosis and have the potential to become a future therapeutic for atherosclerosis.

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

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.

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

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

We report 3 patients with coronavirus disease who had a decline in respiratory status during their hospital course that responded well to intravenous steroids and interleukin-6 receptor antagonist therapy.,These patients later showed development of persistent hypoxia with increased levels of d-dimer levels and were given a diagnosis of pulmonary embolisms.

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

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

Supplemental Digital Content is available in the text.,The European Society of Cardiology recommends a 0/1-hour algorithm for rapid rule-out and rule-in of non-ST-segment elevation myocardial infarction using high-sensitivity cardiac troponin (hs-cTn) concentrations irrespective of renal function.,Because patients with renal dysfunction (RD) frequently present with increased hs-cTn concentrations even in the absence of non-ST-segment elevation myocardial infarction, concern has been raised regarding the performance of the 0/1-hour algorithm in RD.,In a prospective multicenter diagnostic study enrolling unselected patients presenting with suspected non-ST-segment elevation myocardial infarction to the emergency department, we assessed the diagnostic performance of the European Society of Cardiology 0/1-hour algorithm using hs-cTnT and hs-cTnI in patients with RD, defined as an estimated glomerular filtration rate <60 mL/min/1.73 m2, and compared it to patients with normal renal function.,The final diagnosis was centrally adjudicated by 2 independent cardiologists using all available information, including cardiac imaging.,Safety was quantified as sensitivity in the rule-out zone, accuracy as the specificity in the rule-in zone, and efficacy as the proportion of the overall cohort assigned to either rule-out or rule-in based on the 0- and 1-hour sample.,Among 3254 patients, RD was present in 487 patients (15%).,The prevalence of non-ST-segment elevation myocardial infarction was substantially higher in patients with RD compared with patients with normal renal function (31% versus 13%, P<0.001).,Using hs-cTnT, patients with RD had comparable sensitivity of rule-out (100.0% [95% confidence interval {CI}, 97.6-100.0] versus 99.2% [95% CI, 97.6-99.8]; P=0.559), lower specificity of rule-in (88.7% [95% CI, 84.8-91.9] versus 96.5% [95% CI, 95.7-97.2]; P<0.001), and lower overall efficacy (51% versus 81%, P<0.001), mainly driven by a much lower percentage of patients eligible for rule-out (18% versus 68%, P<0.001) compared with patients with normal renal function.,Using hs-cTnI, patients with RD had comparable sensitivity of rule-out (98.6% [95% CI, 95.0-99.8] versus 98.5% [95% CI, 96.5-99.5]; P=1.0), lower specificity of rule-in (84.4% [95% CI, 79.9-88.3] versus 91.7% [95% CI, 90.5-92.9]; P<0.001), and lower overall efficacy (54% versus 76%, P<0.001; proportion ruled out, 18% versus 58%, P<0.001) compared with patients with normal renal function.,In patients with RD, the safety of the European Society of Cardiology 0/1-hour algorithm is high, but specificity of rule-in and overall efficacy are decreased.,Modifications of the rule-in and rule-out thresholds did not improve the safety or overall efficacy of the 0/1-hour algorithm.,URL: https://www.clinicaltrials.gov.,Unique identifier: NCT00470587.

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.

Atrial fibrillation (AF) has been shown to be associated with an increased risk of dementia as well as Alzheimer disease in observational studies.,Whether this association reflects causal association is still unclear.,The purpose of this study was to examine the causal association of AF with Alzheimer disease.,We used a 2‐sample Mendelian randomization approach to evaluate the causal effect of AF on Alzheimer disease.,Summary data on the association of single nucleotide polymorphisms with AF were obtained from a recently published genome‐wide association study with up to 1 030 836 individuals and data on single nucleotide polymorphism‐Alzheimer disease association from another genome‐wide association study with up to 455 258 individuals.,AF was mainly diagnosed according to International Classification of Diseases, Ninth Revision (ICD‐9 or ICD‐10) and Alzheimer disease was mainly diagnosed according to clinical criteria (eg, National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association [NINCDS‐ADRDA] criteria).,Effect estimates were calculated using the inverse‐variance weighted method.,The Mendelian randomization analysis showed nonsignificant association of genetically predicted AF with risk of Alzheimer disease (odds ratio=1.002, 95% CI: 0.996-1.009, P=0.47) using 93 single nucleotide polymorphisms as the instruments.,Mendelian randomization‐Egger indicated no evidence of genetic pleiotropy (intercept=0.0002, 95% CI: −0.001 to 0.001, P=0.70).,This Mendelian randomization analysis found no evidence to support causal association between AF and Alzheimer disease.

Previous studies have found ischemic stroke is associated with atrial fibrillation.,However, the causal association between ischemic stroke and atrial fibrillation is not clear.,Furthermore, the network relationship among ischemic stroke, atrial fibrillation and its risk factors need further attention.,This study aims to examine the potential causal association between ischemic stroke and atrial fibrillation and further to explore potential mediators in the causal pathway from ischemic stroke to atrial fibrillation.,Summary statistics from the ISGC (case = 10,307 and control = 19,326) were used as ischemic stroke genetic instruments, AFGen Consortium data (case = 65,446 and control = 522,744) were used for atrial fibrillation, and other consortia data were used for potential mediators (fasting insulin, white blood cell count, procalcitonin, systolic and diastolic blood pressure, body mass index, waist circumference, and height).,Under the framework of network Mendelian randomization, two-sample Mendelian randomization study was performed using summary statistics from several genome-wide association studies.,Inverse-variance weighted method was performed to estimate causal effect.,Blood pressure mediates the causal pathways from ischemic stroke to atrial fibrillation.,The total odds ratio of ischemic stroke on atrial fibrillation was 1.05 (95% confidence interval [CI], 1.02 to 1.07; P = 1.3 × 10−5).,One-unit increase of genetically determined ischemic stroke was associated with 0.02 (DBP: 95% CI, 0.001 to 0.034, P = 0.029; SBP: 95% CI, 0.006 to 0.034, P = 0.003) upper systolic and diastolic blood pressure levels.,Higher genetically determined systolic and diastolic blood pressure levels were associated with higher atrial fibrillation risk (DBP: RR, 1.18; 95% CI, 1.03 to 1.35; P = 0.012.,SBP: RR, 1.18; 95% CI, 1.01 to 1.38; P = 0.04).,Specially, we also found the bidirectional causality between blood pressure and ischemic stroke.,Our study provided a strong evidence that raised blood pressure in stroke patients increases the risk of atrial fibrillation and active acute blood pressure lowering can improve the outcome in ischemic stroke patients.

Vaccine-induced thrombotic thrombocytopenia with cerebral venous thrombosis is a syndrome recently described in young adults within two weeks from the first dose of the ChAdOx1 nCoV-19 vaccine.,Here we report two cases of malignant middle cerebral artery (MCA) infarct and thrombocytopenia 9-10 days following ChAdOx1 nCoV-19 vaccination.,The two cases arrived in our facility around the same time but from different geographical areas, potentially excluding epidemiological links; meanwhile, no abnormality was found in the respective vaccine batches.,Patient 1 was a 57-year-old woman who underwent decompressive craniectomy despite two prior, successful mechanical thrombectomies.,Patient 2 was a 55-year-old woman who developed a fatal bilateral malignant MCA infarct.,Both patients manifested pulmonary and portal vein thrombosis and high level of antibodies to platelet factor 4-polyanion complexes.,None of the patients had ever received heparin in the past before stroke onset.,Our observations of rare arterial thrombosis may contribute to assessment of possible adverse effects associated with COVID-19 vaccination.,Vaccination is an effective strategy in suppressing COVID-19 pandemic, but rare adverse effects have been reported, including cerebral venous thrombosis.,Here the authors report two cases of middle cerebral artery infarct within 9-10 days following ChAdOx1 nCov-19 vaccination that also manifest pulmonary and portal vein thrombosis.

We describe the first Danish case of presumed inflammatory and thrombotic response to vaccination with an adenoviral (ChAdOx1) vector‐based COVID‐19 vaccine (AZD1222).,The case describes a 60‐year‐old woman who was admitted with intractable abdominal pain 7 days after receiving the vaccine.,Computed tomography of the abdomen revealed bilateral adrenal hemorrhages.,On the following day, she developed a massive right‐sided ischemic stroke and magnetic resonance imaging angiography showed occlusion of the right internal carotid artery.,The ischemic area was deemed too large to offer reperfusion therapy.,During admission, blood tests showed a remarkable drop in platelet counts from 118,000 to 5000 per μl and a substantial increase in D‐dimer.,The patient died on the sixth day of hospitalization.,Blood tests revealed platelet factor 4 reactive antibodies, imitating what is seen in heparin‐induced thrombocytopenia.,This may be a novel immune‐mediated response to the vaccine.

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.

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

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.

The cardiac microvascular system, which is primarily composed of monolayer endothelial cells, is the site of blood supply and nutrient exchange to cardiomyocytes.,However, microvascular ischemia/reperfusion injury (IRI) following percutaneous coronary intervention is a woefully neglected topic, and few strategies are available to reverse such pathologies.,Here, we studied the effects of melatonin on microcirculation IRI and elucidated the underlying mechanism.,Melatonin markedly reduced infarcted area, improved cardiac function, restored blood flow, and lower microcirculation perfusion defects.,Histological analysis showed that cardiac microcirculation endothelial cells (CMEC) in melatonin‐treated mice had an unbroken endothelial barrier, increased endothelial nitric oxide synthase expression, unobstructed lumen, reduced inflammatory cell infiltration, and less endothelial damage.,In contrast, AMP‐activated protein kinase α (AMPKα) deficiency abolished the beneficial effects of melatonin on microvasculature.,In vitro, IRI activated dynamin‐related protein 1 (Drp1)‐dependent mitochondrial fission, which subsequently induced voltage‐dependent anion channel 1 (VDAC1) oligomerization, hexokinase 2 (HK2) liberation, mitochondrial permeability transition pore (mPTP) opening, PINK1/Parkin upregulation, and ultimately mitophagy‐mediated CMEC death.,However, melatonin strengthened CMEC survival via activation of AMPKα, followed by p‐Drp1S616 downregulation and p‐Drp1S37 upregulation, which blunted Drp1‐dependent mitochondrial fission.,Suppression of mitochondrial fission by melatonin recovered VDAC1‐HK2 interaction that prevented mPTP opening and PINK1/Parkin activation, eventually blocking mitophagy‐mediated cellular death.,In summary, this study confirmed that melatonin protects cardiac microvasculature against IRI.,The underlying mechanism may be attributed to the inhibitory effects of melatonin on mitochondrial fission‐VDAC1‐HK2‐mPTP‐mitophagy axis via activation of AMPKα.

Kawasaki disease (KD) is a prevalent pediatric disease worldwide and can cause coronary artery aneurysm as a severe complication.,Typically, DNA methylation is thought to repress the expression of nearby genes.,However, the cases in which DNA methylation promotes gene expression have been reported.,In addition, globally, to what extent DNA methylation affects gene expression and how it contributes to the pathogenesis of KD are not yet well understood.,To address these important biological questions, we enrolled subjects, collected DNA and RNA samples from the subjects’ total white blood cells, and performed DNA methylation (M450K) and gene expression (HTA 2.0) microarray assays.,By analyzing the variation ratios of CpG beta values (methylation percentage) and gene expression intensities, we first concluded that the CpG markers close (− 1500 bp to + 500 bp) to the transcription start sites had higher variation ratios, reflecting significant regulation capacities.,Next, we observed that, globally speaking, gene expression was modestly negatively correlated (correlation rho ≈ − 0.2) with the DNA methylation status of both upstream and downstream CpG markers in the promoter region.,Third, we found that specific CpG markers were hypo-methylated in disease samples compared with healthy samples and hyper-methylated in convalescent samples compared with disease samples, promoting and repressing S100A genes’ expressions, respectively.,Finally, using an in vitro cell model, we demonstrated that S100A family proteins enhanced leukocyte transendothelial migration in KD.,This is the first study to integrate genome-wide DNA methylation with gene expression assays in KD and showed that the S100A family plays important roles in the pathogenesis of KD.,The online version of this article (10.1186/s13148-018-0557-1) contains supplementary material, which is available to authorized users.

Oxidative stress has recently been shown to play an important role in the development of arteriosclerosis in patients with Kawasaki disease (KD); however, no study has investigated this association in early childhood patients with KD.,In this study, we evaluated prospectively the association between the levels of oxidative stress and the endothelial function in early childhood patients with KD.,We compared the derivatives of reactive oxygen metabolites (ROM), flow-mediated dilatation (FMD), and biological characteristics in a population of 50 children: 10 patients with KD and coronary artery lesions (CAL) (group 1), 15 KD patients without CAL (group 2), and 25 healthy age- and sex-matched children (group 3).,The median age of all KD children at study enrollment was 6.8 (IQR 4.4-8.2) years.,ROM levels were significantly higher in group 1 (p < 0.001) and group 2 (p = 0.004) than in group 3.,The %FMD of group 1 (p < 0.001) and group 2 (p = 0.026) was significantly lower than that of group 3.,There was a significant negative correlation between ROM and %FMD (r = − 0.60, p < 0.001).,A multiple linear regression analysis identified ln-ROM (standardized coefficient = − 0.403, p = 0.043) and total fever duration (standardized coefficient = − 0.413, p = 0.038) as significant determinants of %FMD in the patients with KD.,Our study suggests that oxidative stress is strongly associated with endothelial dysfunction in early childhood patients with KD.,Furthermore, we found that the longer the fever duration, the higher the risk of oxidative stress-induced endothelial dysfunction in these children.

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

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.

Takotsubo syndrome (TTS) is an acute heart failure, typically triggered by high adrenaline during physical or emotional stress.,It is distinguished from myocardial infarction (MI) by a characteristic pattern of ventricular basal hypercontractility with hypokinesis of apical segments, and in the absence of culprit coronary occlusion.,We aimed to understand whether recently discovered circulating biomarkers miR-16 and miR-26a, which differentiate TTS from MI at presentation, were mechanistically involved in the pathophysiology of TTS.,miR-16 and miR-26a were co-overexpressed in rats with AAV and TTS induced with an adrenaline bolus.,Untreated isolated rat cardiomyocytes were transfected with pre-/anti-miRs and functionally assessed.,Ventricular basal hypercontraction and apical depression were accentuated in miR-transfected animals after induction of TTS.,In vitro miR-16 and/or miR-26a overexpression in isolated apical (but not basal), cardiomyocytes produced strong depression of contraction, with loss of adrenaline sensitivity.,They also enhanced the initial positive inotropic effect of adrenaline in basal cells.,Decreased contractility after TTS-miRs was reproduced in non-failing human apical cardiomyocytes.,Bioinformatic profiling of miR targets, followed by expression assays and functional experiments, identified reductions of CACNB1 (L-type calcium channel Cavβ subunit), RGS4 (regulator of G-protein signalling 4), and G-protein subunit Gβ (GNB1) as underlying these effects.,miR-16 and miR-26a sensitize the heart to TTS-like changes produced by adrenaline.,Since these miRs have been associated with anxiety and depression, they could provide a mechanism whereby priming of the heart by previous stress causes an increased likelihood of TTS in the future.,Graphical Abstract

Takotsubo syndrome (TTS) is a poorly recognized heart disease that was initially regarded as a benign condition.,Recently, it has been shown that TTS may be associated with severe clinical complications including death and that its prevalence is probably underestimated.,Since current guidelines on TTS are lacking, it appears timely and important to provide an expert consensus statement on TTS.,The clinical expert consensus document part I summarizes the current state of knowledge on clinical presentation and characteristics of TTS and agrees on controversies surrounding TTS such as nomenclature, different TTS types, role of coronary artery disease, and etiology.,This consensus also proposes new diagnostic criteria based on current knowledge to improve diagnostic accuracy.

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

The COVID-19 pandemic's impact on stroke care is two-fold - direct impact of the infection and indirect impact on non-COVID-19 diseases.,Anecdotal evidence and clinical observation suggest that there is a decrease in the number of patients presenting with stroke during the pandemic.,We aim to understand the impact of the COVID-19 pandemic on the utilization of stroke emergency services on a single comprehensive stroke center (CSC).,We performed a retrospective analysis of a prospectively maintained database and compared all emergency department (ED) encounters, acute stroke admissions (including TIA), and thrombectomy cases admitted in March 2017-2019 to patients admitted in March 2020 at a comprehensive stroke center.,Number of total ED encounters (22%, p=0.005), acute ischemic strokes (40%, p=0.001), and TIAs (60%, p=0.163) decreased between March of 2017-2019 compared to March of 2020.,The number of patients undergoing EVT in March 2020 was comparable to March 2017-2019 (p=0.430).,A pandemic-related stay-at-home policy reduces the utilization of stroke emergency services at a CSC.,This effect appears to be more prominent for ED encounters, all stroke admissions and TIAs, and less impactful for severe strokes.,Given the relatively low prevalence of COVID-19 cases in our region, this decrement is likely related to healthcare seeking behavior rather than capacity saturation.

The severe acute respiratory syndrome-coronavirus-2 outbreak has rapidly reached pandemic proportions and has become a major threat to global health.,Although the predominant clinical feature of coronavirus disease-2019 (COVID-19) is an acute respiratory syndrome of varying severity, ranging from mild symptomatic interstitial pneumonia to acute respiratory distress syndrome, the cardiovascular system can be involved in several ways.,As many as 40% of patients hospitalized with COVID-19 have histories of cardiovascular disease, and current estimates report a proportion of myocardial injury in patients with COVID-19 of up to 12%.,Multiple pathways have been suggested to explain this finding and the related clinical scenarios, encompassing local and systemic inflammatory responses and oxygen supply-demand imbalance.,From a clinical point of view, cardiac involvement during COVID-19 may present a wide spectrum of severity, ranging from subclinical myocardial injury to well-defined clinical entities (myocarditis, myocardial infarction, pulmonary embolism, and heart failure), whose incidence and prognostic implications are currently largely unknown because of a significant lack of imaging data.,Integrated heart and lung multimodality imaging plays a central role in different clinical settings and is essential in the diagnosis, risk stratification, and management of patients with COVID-19.,The aims of this review are to summarize imaging-oriented pathophysiological mechanisms of lung and cardiac involvement in COVID-19 and to provide a guide for integrated imaging assessment in these patients.,•Cardiac involvement is present in up to 12% of patients with COVID-19.,•Multimodality imaging is essential in different clinical settings in COVID-19.,•Multimodality imaging is useful in diagnosis, risk stratification, and management.,•Strategies for preventing viral transmission during examinations must be adopted.,Cardiac involvement is present in up to 12% of patients with COVID-19.,Multimodality imaging is essential in different clinical settings in COVID-19.,Multimodality imaging is useful in diagnosis, risk stratification, and management.,Strategies for preventing viral transmission during examinations must be adopted.

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.

Biological cardiac injury related to the Severe Acute Respiratory Syndrome Coronavirus-2 infection has been associated with excess mortality.,However, its functional impact remains unknown.,The aim of our study was to explore the impact of biological cardiac injury on myocardial functions in patients with COVID-19. 31 patients with confirmed COVID-19 (CoV+) and 16 controls (CoV−) were prospectively included in this observational study.,Demographic data, laboratory findings, comorbidities, treatments and myocardial function assessed by transthoracic echocardiography were collected and analysed in CoV+ with (TnT+) and without (TnT−) elevation of troponin T levels and compared with CoV−.,Among CoV+, 13 (42%) exhibited myocardial injury.,CoV+/TnT + patients were older, had lower diastolic arterial pressure and were more likely to have hypertension and chronic renal failure compared with CoV+/TnT−.,The control group was comparable except for an absence of biological inflammatory syndrome.,Left ventricular ejection fraction and global longitudinal strain were not different among the three groups.,There was a trend of decreased myocardial work and increased peak systolic tricuspid annular velocity between the CoV− and CoV + patients, which became significant when comparing CoV− and CoV+/TnT+ (2167 ± 359 vs. 1774 ± 521%/mmHg, P = 0.047 and 14 ± 3 vs. 16 ± 3 cm/s, P = 0.037, respectively).,There was a decrease of global work efficiency from CoV− (96 ± 2%) to CoV+/TnT− (94 ± 4%) and then CoV+/TnT+ (93 ± 3%, P = 0.042).,In conclusion, biological myocardial injury in COVID 19 has low functional impact on left ventricular systolic function.

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

Emerging evidence has identified the association between gut microbiota and various diseases, including cardiovascular diseases (CVDs).,Altered intestinal flora composition has been described in detail in CVDs, such as hypertension, atherosclerosis, myocardial infarction, heart failure, and arrhythmia.,In contrast, the importance of fermentation metabolites, such as trimethylamine N-oxide (TMAO), short-chain fatty acids (SCFAs), and secondary bile acid (BA), has also been implicated in CVD development, prevention, treatment, and prognosis.,The potential mechanisms are conventionally thought to involve immune regulation, host energy metabolism, and oxidative stress.,However, numerous types of programmed cell death, including apoptosis, autophagy, pyroptosis, ferroptosis, and clockophagy, also serve as a key link in microbiome-host cross talk.,In this review, we introduced and summarized the results from recent studies dealing with the relationship between gut microbiota and cardiac disorders, highlighting the role of programmed cell death.,We hope to shed light on microbiota-targeted therapeutic strategies in CVD management.

The intestine is colonized by a considerable community of microorganisms that cohabits within the host and plays a critical role in maintaining host homeostasis.,Recently, accumulating evidence has revealed that the gut microbial ecology plays a pivotal role in the occurrence and development of cardiovascular disease (CVD).,Moreover, the effects of imbalances in microbe-host interactions on homeostasis can lead to the progression of CVD.,Alterations in the composition of gut flora and disruptions in gut microbial metabolism are implicated in the pathogenesis of CVD.,Furthermore, the gut microbiota functions like an endocrine organ that produces bioactive metabolites, including trimethylamine/trimethylamine N‐oxide, short‐chain fatty acids and bile acids, which are also involved in host health and disease via numerous pathways.,Thus, the gut microbiota and its metabolic pathways have attracted growing attention as a therapeutic target for CVD treatment.,The fundamental purpose of this review was to summarize recent studies that have illustrated the complex interactions between the gut microbiota, their metabolites and the development of common CVD, as well as the effects of gut dysbiosis on CVD risk factors.,Moreover, we systematically discuss the normal physiology of gut microbiota and potential therapeutic strategies targeting gut microbiota to prevent and treat CVD.,The fundamental purpose of this review is to summarize recent studies on illustrating the complex interactions between the gut microbiota, their metabolites and the development of common CVD, as well as the effects of gut dysbiosis on CVD risk factors.,Moreover, we systematically discuss the normal physiology of gut microbiota and potential therapeutic strategies targeting gut microbiota to prevent and treat CVD.

Venous thromboembolism (VTE) may complicate the course of Coronavirus Disease 2019 (COVID-19).,To evaluate the incidence of VTE in patients with COVID-19.,MEDLINE, EMBASE, and PubMed were searched up to 24th June 2020 for studies that evaluated the incidence of VTE, including pulmonary embolism (PE) and/or deep vein thrombosis (DVT), in patients with COVID-19.,Pooled proportions with corresponding 95% confidence intervals (CI) and prediction intervals (PI) were calculated by random-effect meta-analysis.,3487 patients from 30 studies were included.,Based on very low-quality evidence due to heterogeneity and risk of bias, the incidence of VTE was 26% (95% PI, 6%-66%).,PE with or without DVT occurred in 12% of patients (95% PI, 2%-46%) and DVT alone in 14% (95% PI, 1%-75%).,Studies using standard algorithms for clinically suspected VTE reported PE in 13% of patients (95% PI, 2%-57%) and DVT in 6% (95% PI, 0%-60%), compared to 11% (95% PI, 2%-46%) and 24% (95% PI, 2%-85%) in studies using other diagnostic strategies or patient sampling.,In patients admitted to intensive care units, VTE occurred in 24% (95% PI, 5%-66%), PE in 19% (95% PI, 6%-47%), and DVT alone in 7% (95% PI, 0%-69%).,Corresponding values in general wards were respectively 9% (95% PI, 0%-94%), 4% (95% PI, 0%-100%), and 7% (95% CI, 1%-49%).,VTE represents a frequent complication in hospitalized COVID-19 patients and often occurs as PE.,The threshold for clinical suspicion should be low to trigger prompt diagnostic testing.,•Incidence of venous thromboembolism (VTE) in Coronavirus Disease-2019 (COVID-19) is unclear.,•A total of 3487 patients with COVID-19 were included in 30 observational studies.,•VTE incidence varied due to differences in diagnostic protocols and hospital setting.,•VTE risk was higher in intensive care units, but seemed also substantial in general wards despite prophylaxis.,Incidence of venous thromboembolism (VTE) in Coronavirus Disease-2019 (COVID-19) is unclear.,A total of 3487 patients with COVID-19 were included in 30 observational studies.,VTE incidence varied due to differences in diagnostic protocols and hospital setting.,VTE risk was higher in intensive care units, but seemed also substantial in general wards despite prophylaxis.

COVID‐19 is associated with increased risk of venous thromboembolic events (VTE).,However, there is significant heterogeneity in the thromboembolic phenotypes of COVID‐19 patients (deep vein thrombosis, pulmonary embolism/thrombosis).,The latter might be partly attributed to the variation in VTE risk factors in COVID‐19 patients including: (i) patients’ characteristics; (ii) hospitalization conditions and interventions; and (iii) SARS‐CoV‐2‐specific factors (coagulopathy, endothelial injury/microthrombosis).,Furthermore, there is methodological heterogeneity in relation to the assessment of VTE (indications for screening, diagnostic methodology, etc).,Physicians should be aware of the increased VTE risk, strongly consider VTE screening, and use thromboprophylaxis in all hospitalized patients.

Ischemic preconditioning (IPC) and ischemic postconditioning (IPoC) are currently among the most efficient strategies protecting the heart against ischemia/reperfusion injury.,However, the effect of IPC and IPoC on functional recovery following ischemia/reperfusion is less clear, particularly with regard to the specific receptor‐mediated signaling of the postischemic heart.,The current article examines the effect of IPC or IPoC on the regulation and coupling of β‐adrenergic receptors and their effects on postischemic left ventricular function.,The β‐adrenergic signal transduction was analyzed in 3‐month‐old Wistar rats for each of the intervention strategies (Sham, ischemia/reperfusion, IPC, IPoC) immediately and 7 days after myocardial infarction.,Directly after the infarction a cardioprotective potential was demonstrated for both IPC and IPoC: the infarct size was reduced, apoptosis and production of reactive oxygen species were lowered, and the myocardial tissue was preserved.,Seven days after myocardial ischemia, only IPC hearts showed significant functional improvement.,Along with a deterioration in fractional shortening, IPoC hearts no longer responded adequately to β‐adrenergic stimulation.,The stabilization of β‐adrenergic receptor kinase‐2 via increased phosphorylation of Mdm2 (an E3‐ubiquitin ligase) was responsible for desensitization of β‐adrenergic receptors and identified as a characteristic specific to IPoC hearts.,Immediately after myocardial infarction, rapid and transient activation of β‐adrenergic receptor kinase‐2 may be an appropriate means to protect the injured heart from excessive stress.,In the long term, however, induction and stabilization of β‐adrenergic receptor kinase‐2, with the resultant loss of positive inotropic function, leads to the functional picture of heart failure.

Despite advances in myocardial reperfusion therapies, acute myocardial ischaemia/reperfusion injury and consequent ischaemic heart failure represent the number one cause of morbidity and mortality in industrialized societies.,Although different therapeutic interventions have been shown beneficial in preclinical settings, an effective cardioprotective or regenerative therapy has yet to be successfully introduced in the clinical arena.,Given the complex pathophysiology of the ischaemic heart, large scale, unbiased, global approaches capable of identifying multiple branches of the signalling networks activated in the ischaemic/reperfused heart might be more successful in the search for novel diagnostic or therapeutic targets.,High-throughput techniques allow high-resolution, genome-wide investigation of genetic variants, epigenetic modifications, and associated gene expression profiles.,Platforms such as proteomics and metabolomics (not described here in detail) also offer simultaneous readouts of hundreds of proteins and metabolites.,Isolated omics analyses usually provide Big Data requiring large data storage, advanced computational resources and complex bioinformatics tools.,The possibility of integrating different omics approaches gives new hope to better understand the molecular circuitry activated by myocardial ischaemia, putting it in the context of the human ‘diseasome’.,Since modifications of cardiac gene expression have been consistently linked to pathophysiology of the ischaemic heart, the integration of epigenomic and transcriptomic data seems a promising approach to identify crucial disease networks.,Thus, the scope of this Position Paper will be to highlight potentials and limitations of these approaches, and to provide recommendations to optimize the search for novel diagnostic or therapeutic targets for acute ischaemia/reperfusion injury and ischaemic heart failure in the post-genomic era.

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 P2Y12 receptor is a key player in platelet activation and a major target for antithrombotic drugs.,The beneficial effects of P2Y12 receptor antagonists might, however, not be restricted to the primary and secondary prevention of arterial thrombosis.,Indeed, it has been established that platelet activation also has an essential role in inflammation.,Additionally, nonplatelet P2Y12 receptors present in immune cells and vascular smooth muscle cells might be effective players in the inflammatory response.,This review will investigate the biological and clinical impact of P2Y12 receptor inhibition beyond its platelet-driven antithrombotic effects, focusing on its anti-inflammatory role.,We will discuss the potential molecular and cellular mechanisms of P2Y12-mediated inflammation, including cytokine release, platelet-leukocyte interactions and neutrophil extracellular trap formation.,Then we will summarize the current evidence on the beneficial effects of P2Y12 antagonists during various clinical inflammatory diseases, especially during sepsis, acute lung injury, asthma, atherosclerosis, and cancer.

We summarize the cardiovascular risks associated with Covid-19 pandemic, discussing the risks for both infected and non-infected patients.

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.

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.

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.

Liraglutide is an antidiabetic agent with cardioprotective effect.,The purpose of this study is to test efficacy of liraglutide to improve diabetic cardiomyopathy in patients with diabetes mellitus type 2 (DM2) without cardiovascular disease.,Patients with DM2 were randomly assigned to receive liraglutide 1.8 mg/day or placebo in this double-blind trial of 26 weeks.,Primary outcome measures were LV diastolic function (early (E) and late (A) transmitral peak flow rate, E/A ratio, early deceleration peak (Edec), early peak mitral annular septal tissue velocity (Ea) and estimated LV filling pressure (E/Ea), and systolic function (stroke volume, ejection fraction, cardiac output, cardiac index and peak ejection rate) assessed with CMR.,Intention-to-treat analysis of between-group differences was performed using ANCOVA.,Mean estimated treatment differences (95% confidence intervals) are reported.,23 patients were randomized to liraglutide and 26 to placebo.,As compared with placebo, liraglutide significantly reduced E (− 56 mL/s (− 91 to − 21)), E/A ratio (− 0.17 (− 0.27 to − 0.06)), Edec (− 0.9 mL/s2 * 10−3 (− 1.3 to − 0.2)) and E/Ea (− 1.8 (− 3.0 to − 0.6)), without affecting A (3 mL/s (− 35 to 41)) and Ea (0.4 cm/s (− 0.9 to 1.4)).,Liraglutide reduced stroke volume (− 9 mL (− 16 to − 2)) and ejection fraction (− 3% (− 6 to − 0.1)), but did not change cardiac output (− 0.4 L/min (− 0.9 to 0.2)), cardiac index (− 0.1 L/min/m2 (− 0.4 to 0.1)) and peak ejection rate (− 46 mL/s (− 95 to 3)).,Liraglutide reduced early LV diastolic filling and LV filling pressure, thereby unloading the left ventricle.,LV systolic function reduced and remained within normal range.,Future studies are needed to investigate if liraglutide-induced left ventricular unloading slows progression of diabetic cardiomyopathy into symptomatic stages.,Trial registration ClinicalTrials.gov: NCT01761318.

Multiple bloodglucose-lowering agents have been linked to cardiovascular events.,Preliminary studies showed improvement in left ventricular (LV) function during glucagon-like peptide-1 receptor agonist administration.,Underlying mechanisms, however, are unclear.,The purpose of this study was to investigate myocardial perfusion and oxidative metabolism in type 2 diabetic (T2DM) patients with LV systolic dysfunction as compared to healthy controls.,Furthermore, effects of 26-weeks of exenatide versus insulin glargine administration on cardiac function, perfusion and oxidative metabolism in T2DM patients with LV dysfunction were explored.,Twenty-six T2DM patients with LV systolic dysfunction (cardiac magnetic resonance (CMR) derived LV ejection fraction (LVEF) of 47 ± 13%) and 10 controls (LVEF of 59 ± 4%, P < 0.01 as compared to patients) were analyzed.,Both myocardial perfusion during adenosine-induced hyperemia (P < 0.01), and coronary flow reserve (P < 0.01), measured by [15O]H2O positron emission tomography (PET), were impaired in T2DM patients as compared to healthy controls.,Myocardial oxygen consumption and myocardial efficiency, measured using [11C]acetate PET and CMR derived stroke volume, were not different between the groups.,Eleven patients in the exenatide group and 12 patients in the insulin glargine group completed the trial.,Systemic metabolic control was improved after both treatments, although, no changes in cardiac function, perfusion and metabolism were seen after exenatide or insulin glargine.,T2DM patients with LV systolic dysfunction did not have altered myocardial efficiency as compared to healthy controls.,Exenatide or insulin glargine had no effects on cardiac function, perfusion or oxidative metabolism.,Trial registration NCT00766857

Acute ischemic stroke may occur in patients with coronavirus disease 2019 (COVID-19), but risk factors, in-hospital events, and outcomes are not well studied in large cohorts.,We identified risk factors, comorbidities, and outcomes in patients with COVID-19 with or without acute ischemic stroke and compared with patients without COVID-19 and acute ischemic stroke.,We analyzed the data from 54 health care facilities using the Cerner deidentified COVID-19 dataset.,The dataset included patients with an emergency department or inpatient encounter with discharge diagnoses codes that could be associated to suspicion of or exposure to COVID-19 or confirmed COVID-19.,A total of 103 (1.3%) patients developed acute ischemic stroke among 8163 patients with COVID-19.,Among all patients with COVID-19, the proportion of patients with hypertension, diabetes, hyperlipidemia, atrial fibrillation, and congestive heart failure was significantly higher among those with acute ischemic stroke.,Acute ischemic stroke was associated with discharge to destination other than home or death (relative risk, 2.1 [95% CI, 1.6-2.4]; P<0.0001) after adjusting for potential confounders.,A total of 199 (1.0%) patients developed acute ischemic stroke among 19 513 patients without COVID-19.,Among all ischemic stroke patients, COVID-19 was associated with discharge to destination other than home or death (relative risk, 1.2 [95% CI, 1.0-1.3]; P=0.03) after adjusting for potential confounders.,Acute ischemic stroke was infrequent in patients with COVID-19 and usually occurs in the presence of other cardiovascular risk factors.,The risk of discharge to destination other than home or death increased 2-fold with occurrence of acute ischemic stroke in patients with COVID-19.

Anecdotal reports and clinical observations have recently emerged suggesting a relationship between COVID-19 disease and stroke, highlighting the possibility that infected individuals may be more susceptible to cerebrovascular events.,In this review we draw on emerging studies of the current pandemic and data from earlier, viral epidemics, to describe possible mechanisms by which SARS-CoV-2 may influence the prevalence of stroke, with a focus on the thromboinflammatory pathways, which may be perturbed.,Some of these potential mechanisms are not novel but are, in fact, long-standing hypotheses linking stroke with preceding infection that are yet to be confirmed.,The current pandemic may present a renewed opportunity to better understand the relationship between infection and stroke and possible underlying mechanisms.

Neuroplasticity is a natural process occurring in the brain for the entire life.,Stroke is the leading cause of long term disability and a huge medical and financial problem throughout the world.,Research conducted over the past decade focused mainly on neuroprotection in the acute phase of stroke while very little studies target the chronic stage.,Recovery after stroke depends on the ability of our brain to reestablish the structural and functional organization of neurovascular networks.,Combining adjuvant therapies and drugs may enhance the repair processes and restore impaired brain functions.,Currently, there are some drugs and rehabilitative strategies that can facilitate brain repair and improve clinical effect even years after stroke onset.,Moreover, some of the compounds such as citicoline, fluoxetine, niacin, levodopa, etc. are already in clinical use or are being trialed in clinical issues.,Many studies are also testing cell therapies; in our review, we focused on studies where cells have been implemented at the early stage of stroke.,Next, we discuss pharmaceutical interventions.,In this section, we selected methods of cognitive, behavioral, and physical rehabilitation as well as adjuvant interventions for neuroprotection including noninvasive brain stimulation and extremely low-frequency electromagnetic field.,The modern rehabilitation represents a new model of physical interventions with the limited therapeutic window up to six months after stroke.,However, previous studies suggest that the time window for stroke recovery is much longer than previously thought.,This review attempts to present the progress in neuroprotective strategies, both pharmacological and non-pharmacological that can stimulate the endogenous neuroplasticity in post-stroke patients.

Ischemic stroke is one of the leading causes of mortality and disability worldwide.,However, there is a current lack of effective therapies available.,As the resident macrophages of the brain, microglia can monitor the microenvironment and initiate immune responses.,In response to various brain injuries, such as ischemic stroke, microglia are activated and polarized into the proinflammatory M1 phenotype or the anti-inflammatory M2 phenotype.,The immunomodulatory molecules, such as cytokines and chemokines, generated by these microglia are closely associated with secondary brain damage or repair, respectively, following ischemic stroke.,It has been shown that M1 microglia promote secondary brain damage, whilst M2 microglia facilitate recovery following stroke.,In addition, autophagy is also reportedly involved in the pathology of ischemic stroke through regulating the activation and function of microglia.,Therefore, this review aimed to provide a comprehensive overview of microglia activation, their functions and changes, and the modulators of these processes, including transcription factors, membrane receptors, ion channel proteins and genes, in ischemic stroke.,The effects of autophagy on microglia polarization in ischemic stroke were also reviewed.,Finally, future research areas of ischemic stroke and the implications of the current knowledge for the development of novel therapeutics for ischemic stroke were identified.

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

Since December 2019, a new coronavirus, named SARS-CoV-2, has spread globally, affecting >200 000 people worldwide with the so-called COVID-19 disease.,The scientific community is actively and constantly working to identify the mechanisms involved in the diffusion of this virus and the pathogenesis of the infection, with its most frequent and severe complication, namely interstitial pneumonia.,To date, SARS-CoV-2 is known to enter the host cells via the angiotensin-converting enzyme 2 protein.,For this reason, the hypothesis that drugs capable of increasing the expression of this protein may have a role in the spread of the virus and in the symptomatology of affected patients has taken hold.,The purpose of this Editorial is to briefly show the evidence currently available in this regard and to provide ideas for future research.

Coronavirus disease 2019 (COVID-19) causes a hypercoagulable state.,Several autopsy studies have found microthrombi in pulmonary circulation.,In this randomized, open-label, phase II study, we randomized COVID-19 patients requiring mechanical ventilation to receive either therapeutic enoxaparin or the standard anticoagulant thromboprophylaxis.,We evaluated the gas exchange over time through the ratio of partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) at baseline, 7, and 14 days after randomization, the time until successful liberation from mechanical ventilation, and the ventilator-free days.,Ten patients were assigned to the therapeutic enoxaparin and ten patients to prophylactic anticoagulation.,There was a statistically significant increase in the PaO2/FiO2 ratio over time in the therapeutic group (163 [95% confidence interval - CI 133-193] at baseline, 209 [95% CI 171-247] after 7 days, and 261 [95% CI 230-293] after 14 days), p = 0.0004.,In contrast, we did not observe this improvement over time in the prophylactic group (184 [95% CI 146-222] at baseline, 168 [95% CI 142-195] after 7 days, and 195 [95% CI 128-262] after 14 days), p = 0.487.,Patients of the therapeutic group had a higher ratio of successful liberation from mechanical ventilation (hazard ratio: 4.0 [95% CI 1.035-15.053]), p = 0.031 and more ventilator-free days (15 days [interquartile range IQR 6-16] versus 0 days [IQR 0-11]), p = 0.028 when compared to the prophylactic group.,Therapeutic enoxaparin improves gas exchange and decreases the need for mechanical ventilation in severe COVID-19.,REBEC RBR-949z6v.,•COVID-19 is associated with microthrombi in pulmonary circulation.,•We randomized severe COVID-19 patients to receive either therapeutic enoxaparin or the standard thromboprophylaxis.,•Therapeutic enoxaparin resulted in improved gas exchange over time.,•Larger clinical trial is urgently needed to evaluate the anticoagulant therapy in severe COVID-19.,COVID-19 is associated with microthrombi in pulmonary circulation.,We randomized severe COVID-19 patients to receive either therapeutic enoxaparin or the standard thromboprophylaxis.,Therapeutic enoxaparin resulted in improved gas exchange over time.,Larger clinical trial is urgently needed to evaluate the anticoagulant therapy in severe COVID-19.

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

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

Coronavirus disease 2019 (COVID-19) is a pandemic respiratory disease with serious public health risk and has taken the world off-guard with its rapid spread.,As the COVID-19 pandemic intensifies, overwhelming the healthcare system and the medical community, current practice for the management of acute ischemic stroke (AIS) will require modification, and guidelines should be relaxed while maintaining high standard quality of care.,The aim of these suggestions is to avoid contributing to the rapid spread of COVID-19 as well as to conserve what are likely to be very limited resources (including personnel, intensive care/hospital beds as well as physicians) while maintaining high quality care for patients with AIS.,We present our recommendations for the management of acute stroke during the COVID-19 pandemics.

The mainstay of control of the coronavirus disease 2019 (Covid-19) pandemic is vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).,Within a year, several vaccines have been developed and millions of doses delivered.,Reporting of adverse events is a critical postmarketing activity.,We report findings in 23 patients who presented with thrombosis and thrombocytopenia 6 to 24 days after receiving the first dose of the ChAdOx1 nCoV-19 vaccine (AstraZeneca).,On the basis of their clinical and laboratory features, we identify a novel underlying mechanism and address the therapeutic implications.,In the absence of previous prothrombotic medical conditions, 22 patients presented with acute thrombocytopenia and thrombosis, primarily cerebral venous thrombosis, and 1 patient presented with isolated thrombocytopenia and a hemorrhagic phenotype.,All the patients had low or normal fibrinogen levels and elevated d-dimer levels at presentation.,No evidence of thrombophilia or causative precipitants was identified.,Testing for antibodies to platelet factor 4 (PF4) was positive in 22 patients (with 1 equivocal result) and negative in 1 patient.,On the basis of the pathophysiological features observed in these patients, we recommend that treatment with platelet transfusions be avoided because of the risk of progression in thrombotic symptoms and that the administration of a nonheparin anticoagulant agent and intravenous immune globulin be considered for the first occurrence of these symptoms.,Vaccination against SARS-CoV-2 remains critical for control of the Covid-19 pandemic.,A pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, can occur after the administration of the ChAdOx1 nCoV-19 vaccine.,Rapid identification of this rare syndrome is important because of the therapeutic implications.

Ischemic stroke is caused by a thromboembolic occlusion of cerebral arteries.,Treatment is focused on fast and efficient removal of the occluding thrombus, either via intravenous thrombolysis or via endovascular thrombectomy.,Recanalization, however, is not always successful and factors contributing to failure are not completely understood.,Although the occluding thrombus is the primary target of acute treatment, little is known about its internal organization and composition.,The aim of this study, therefore, was to better understand the internal organization of ischemic stroke thrombi on a molecular and cellular level.,A total of 188 thrombi were collected from endovascularly treated ischemic stroke patients and analyzed histologically for fibrin, red blood cells (RBC), von Willebrand factor (vWF), platelets, leukocytes and DNA, using bright field and fluorescence microscopy.,Our results show that stroke thrombi are composed of two main types of areas: RBC-rich areas and platelet-rich areas.,RBC-rich areas have limited complexity as they consist of RBC that are entangled in a meshwork of thin fibrin.,In contrast, platelet-rich areas are characterized by dense fibrin structures aligned with vWF and abundant amounts of leukocytes and DNA that accumulate around and in these platelet-rich areas.,These findings are important to better understand why platelet-rich thrombi are resistant to thrombolysis and difficult to retrieve via thrombectomy, and can guide further improvements of acute ischemic stroke therapy.

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.

Since its recognition in December 2019, covid-19 has rapidly spread globally causing a pandemic.,Pre-existing comorbidities such as hypertension, diabetes, and cardiovascular disease are associated with a greater severity and higher fatality rate of covid-19.,Furthermore, COVID-19 contributes to cardiovascular complications, including acute myocardial injury as a result of acute coronary syndrome, myocarditis, stress-cardiomyopathy, arrhythmias, cardiogenic shock, and cardiac arrest.,The cardiovascular interactions of COVID-19 have similarities to that of severe acute respiratory syndrome, Middle East respiratory syndrome and influenza.,Specific cardiovascular considerations are also necessary in supportive treatment with anticoagulation, the continued use of renin-angiotensin-aldosterone system inhibitors, arrhythmia monitoring, immunosuppression or modulation, and mechanical circulatory support.

COVID-19 is associated with both venous and arterial thrombotic complications.,While prophylactic anticoagulation is now widely recommended for hospitalized patients with COVID-19, the effectiveness and safety of thromboprophylaxis in outpatients with COVID-19 has not been established.,PREVENT-HD is a double-blind, placebo-controlled, pragmatic, event-driven phase 3 trial to evaluate the efficacy and safety of rivaroxaban in symptomatic outpatients with laboratory-confirmed COVID-19 at risk for thrombotic events, hospitalization, and death.,Several challenges posed by the pandemic have necessitated innovative approaches to clinical trial design, start-up, and conduct.,Participants are randomized in a 1:1 ratio, stratified by time from COVID-19 confirmation, to either rivaroxaban 10 mg once daily or placebo for 35 days.,The primary efficacy end point is a composite of symptomatic venous thromboembolism, myocardial infarction, ischemic stroke, acute limb ischemia, non-central nervous system systemic embolization, all-cause hospitalization, and all-cause mortality.,The primary safety end point is fatal and critical site bleeding according to the International Society on Thrombosis and Haemostasis definition.,Enrollment began in August 2020 and is expected to enroll approximately 4,000 participants to yield the required number of end point events.,PREVENT-HD is a pragmatic trial evaluating the efficacy and safety of the direct oral anticoagulant rivaroxaban in the outpatient setting to reduce major venous and arterial thrombotic events, hospitalization, and mortality associated with COVID-19.

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

While pulmonary embolism (PE) appears to be a major issue in COVID-19, data remain sparse.,We aimed to describe the risk factors and baseline characteristics of patients with PE in a cohort of COVID-19 patients.,In a retrospective multicentre observational study, we included consecutive patients hospitalized for COVID-19.,Patients without computed tomography pulmonary angiography (CTPA)-proven PE diagnosis and those who were directly admitted to an intensive care unit (ICU) were excluded.,Among 1240 patients (58.1% men, mean age 64 ± 17 years), 103 (8.3%) patients had PE confirmed by CTPA.,The ICU transfer and mechanical ventilation were significantly higher in the PE group (for both P < 0.001).,In an univariable analysis, traditional venous thrombo-embolic risk factors were not associated with PE (P > 0.05), while patients under therapeutic dose anticoagulation before hospitalization or prophylactic dose anticoagulation introduced during hospitalization had lower PE occurrence [odds ratio (OR) 0.40, 95% confidence interval (CI) 0.14-0.91, P = 0.04; and OR 0.11, 95% CI 0.06-0.18, P < 0.001, respectively].,In a multivariable analysis, the following variables, also statistically significant in univariable analysis, were associated with PE: male gender (OR 1.03, 95% CI 1.003-1.069, P = 0.04), anticoagulation with a prophylactic dose (OR 0.83, 95% CI 0.79-0.85, P < 0.001) or a therapeutic dose (OR 0.87, 95% CI 0.82-0.92, P < 0.001), C-reactive protein (OR 1.03, 95% CI 1.01-1.04, P = 0.001), and time from symptom onset to hospitalization (OR 1.02, 95% CI 1.006-1.038, P = 0.002).,PE risk factors in the COVID-19 context do not include traditional thrombo-embolic risk factors but rather independent clinical and biological findings at admission, including a major contribution to inflammation.,Graphical Abstract

Coronavirus disease 2019 (COVID-19) pneumonia is associated to systemic hyper-inflammation and abnormal coagulation profile.,D-dimer elevation is particularly frequent, and values higher than 1μg/mL have been associated with disease severity and in-hospital mortality.,Previous retrospective studies found a high pulmonary embolism (PE) prevalence, however, it should be highlighted that diagnoses were only completed when PE was clinically suspected.,Single-center prospective cohort study.,Between April 6th and April 17th 2020, consecutive confirmed cases of COVID-19 pneumonia with D-dimer >1 μg/mL underwent computed tomography pulmonary angiography (CTPA) to investigate the presence and magnitude of PE.,Demographic and laboratory data, comorbidities, CTPA scores, administered treatments, and, clinical outcomes were analysed and compared between patients with and without PE.,Thirty consecutive patients (11 women) were included.,PE was diagnosed in 15 patients (50%).,In patients with PE, emboli were located mainly in segmental arteries (86%) and bilaterally (60%).,Patients with PE were significantly older (median age 67.0 (IQR 63.0-73.0) vs.,57.0 (IQR 48.0-69.0) years, p = .048) and did not differ in sex or risk factors for thromboembolic disease from the non-PE group.,D-dimer, platelet count, and, C reactive protein values were significantly higher among PE patients.,D-dimer values correlated with the radiologic magnitude of PE (p<0.001).,Patients with COVID-19 pneumonia and D-dimer values higher than 1 μg/mL presented a high prevalence of PE, regardless of clinical suspicion.,We consider that these findings could contribute to improve the prognosis of patients with COVID-19 pneumonia, by initiating anticoagulant therapy when a PE is found.

White matter injury (WMI) is associated with motor deficits and cognitive dysfunctions in subarachnoid hemorrhage (SAH) patients.,Therapeutic strategy targeting WMI would likely improve the neurological outcomes after SAH.,Low-density lipoprotein receptor-related protein-1 (LRP1), a scavenger receptor of apolipoprotein E (apoE), is able to modulate microglia polarization towards anti-inflammatory M2 phenotypes during inflammatory and oxidative insult.,In the present study, we investigated the effects of LRP1 activation on WMI and underlying mechanisms of M2 microglial polarization in a rat model of SAH.,Two hundred and seventeen male Sprague Dawley rats (weight 280-330 g) were used.,SAH was induced by endovascular perforation.,LPR1 ligand, apoE-mimic peptide COG1410 was administered intraperitoneally.,Microglial depletion kit liposomal clodronate (CLP), LPR1 siRNA or PI3K inhibitor were administered intracerebroventricularly.,Post-SAH assessments included neurobehavioral tests, brain water content, immunohistochemistry, Golgi staining, western blot and co-immunoprecipitation.,SAH induced WMI shown as the accumulation of amyloid precursor protein and neurofilament heavy polypeptide as well as myelin loss.,Microglial depletion by CLP significantly suppressed WMI after SAH.,COG1410 reduced brain water content, increased the anti-inflammatory M2 microglial phenotypes, attenuated WMI and improved neurological function after SAH.,LRP1 was bound with endogenous apoE and intracellular adaptor protein Shc1.,The benefits of COG1410 were reversed by LPR1 siRNA or PI3K inhibitor.,LRP1 activation attenuated WMI and improved neurological function by modulating M2 microglial polarization at least in part through Shc1/PI3K/Akt signaling in a rat model of SAH.,The apoE-mimic peptide COG1410 may serve as a promising treatment in the management of SAH patients.,fx1,•LRP1 was significantly increased over 72 h after SAH.,•Microglial depletion attenuates WMI at early phase after SAH.,•Activation of LRP1 attenuates WMI by modulating microglial M2 polarization.,•Activation of Shc1/PI3K/Akt signaling pathway underlines the effects of LRP1 mediated microglial polarization modulation.,LRP1 was significantly increased over 72 h after SAH.,Microglial depletion attenuates WMI at early phase after SAH.,Activation of LRP1 attenuates WMI by modulating microglial M2 polarization.,Activation of Shc1/PI3K/Akt signaling pathway underlines the effects of LRP1 mediated microglial polarization modulation.

Oxidative stress and neuronal apoptosis have been demonstrated to be key features in early brain injury (EBI) after subarachnoid hemorrhage (SAH).,Previous studies have indicated that Mas receptor activation initiates an anti-oxidative and anti-apoptotic role in the brain.,However, whether Mas activation can attenuate oxidative stress and neuronal apoptosis after SAH remains unknown.,To investigate the beneficial effect of Mas on oxidative stress injury and neuronal apoptosis induced by SAH, a total of 196 rats were subjected to an endovascular perforation model of SAH.,AVE 0991 (AVE), a selective agonist of Mas, was administered intranasally 1 h after SAH induction.,A779, a selective inhibitor of Mas, and small interfering ribonucleic acid (siRNA) for UCP-2 were administered by intracerebroventricular (i.c.v) injection at 1 h and 48 h before SAH induction respectively.,Neurological tests, immunofluorescence, TUNEL, Fluoro-Jade C, DHE staining, and Western blot experiments were performed.,We found that Mas activation with AVE significantly improved neurobehavioral scores and reduced oxidative stress and neuronal apoptosis in SAH+AVE group compared with SAH+vehicle group.,Moreover, AVE treatment significantly promoted phosphorylation of CREB and the expression UCP-2, as well as upregulated expression of Bcl-2 and downregulation of Romo-1 and Bax.,The protective effects of AVE were reversed by i.c.v injection of A779 and UCP-2 siRNA in SAH+AVE+A779 and SAH+AVE+UCP-2 siRNA groups, respectively.,In conclusion, our data provides evidence that Mas activation with AVE reduces oxidative stress injury and neuronal apoptosis through Mas/PKA/p-CREB/UCP-2 pathway after SAH.,Furthermore, our study indicates that Mas may be a novel therapeutic treatment target in early brain injury of SAH.,fx1,•Mas axis of brain RAS was suppressed after SAH.,•AVE 0991 reduces neuronal apoptosis and degeneration induced by SAH.,•AVE 0991 improves neurological impairments after SAH.,•The anti-apoptotic effect of AVE 0991 was mediated through Mas/PKA/CREB/UCP-2 pathway.,Mas axis of brain RAS was suppressed after SAH.,AVE 0991 reduces neuronal apoptosis and degeneration induced by SAH.,AVE 0991 improves neurological impairments after SAH.,The anti-apoptotic effect of AVE 0991 was mediated through Mas/PKA/CREB/UCP-2 pathway.

Myriad manifestations of cardiovascular involvement have been described in patients with coronavirus disease 2019 (COVID-19), but there have been no reports of COVID-19 affecting the cardiac conduction system.,The PR interval on the electrocardiogram (ECG) normally shortens with increasing heart rate (HR).,The case of a patient with COVID-19 manifesting Mobitz type 1 atrioventricular (AV) block that normalized as the patient’s condition improved prompted us to investigate PR interval behavior in patients with COVID-19.,The purpose of this study was to characterize PR interval behavior in hospitalized patients with COVID-19 and to correlate that behavior with clinical outcomes.,This study was a cross-sectional cohort analysis of confirmed COVID-19 cases (March 26, 2020, to April 25, 2020).,We reviewed pre-COVID-19 and COVID-19 ECGs to characterize AV conduction by calculating the PR interval to HR (PR:HR) slope.,Clinical endpoints were death or need for endotracheal intubation.,ECGs from 75 patients (246 pre-COVID-19 ECGs and 246 COVID-19 ECGs) were analyzed for PR:HR slope.,Of these patients, 38 (50.7%) showed the expected PR interval shortening with increasing HR (negative PR:HR slope), whereas 37 (49.3%) showed either no change (8 with PR:HR slope = 0) or paradoxical PR interval prolongation (29 with positive PR:HR slope) with increasing HR.,Patients without PR interval shortening were more likely to die (11/37 [29.7%] vs 3/38 [7.9%]; P = .019) or require endotracheal intubation (16/37 [43.2%] vs 8/38 [21.1%]; P = .05) compared to patients with PR interval shortening.,Half of patients with COVID-19 showed abnormal PR interval behavior (paradoxical prolongation or lack of shortening) with increasing HR.,This finding was associated with increased risk of death and need for endotracheal intubation.

There is no known effective therapy for patients with coronavirus disease 2019 (COVID-19).,Initial reports suggesting the potential benefit of hydroxychloroquine/azithromycin (HY/AZ) have resulted in massive adoption of this combination worldwide.,However, while the true efficacy of this regimen is unknown, initial reports have raised concerns about the potential risk of QT interval prolongation and induction of torsade de pointes (TdP).,The purpose of this study was to assess the change in corrected QT (QTc) interval and arrhythmic events in patients with COVID-19 treated with HY/AZ.,This is a retrospective study of 251 patients from 2 centers who were diagnosed with COVID-19 and treated with HY/AZ.,We reviewed electrocardiographic tracings from baseline and until 3 days after the completion of therapy to determine the progression of QTc interval and the incidence of arrhythmia and mortality.,The QTc interval prolonged in parallel with increasing drug exposure and incompletely shortened after its completion.,Extreme new QTc interval prolongation to >500 ms, a known marker of high risk of TdP, had developed in 23% of patients.,One patient developed polymorphic ventricular tachycardia suspected as TdP, requiring emergent cardioversion.,Seven patients required premature termination of therapy.,The baseline QTc interval of patients exhibiting extreme QTc interval prolongation was normal.,The combination of HY/AZ significantly prolongs the QTc interval in patients with COVID-19.,This prolongation may be responsible for life-threatening arrhythmia in the form of TdP.,This risk mandates careful consideration of HY/AZ therapy in light of its unproven efficacy.,Strict QTc interval monitoring should be performed if the regimen is given.

Supplemental Digital Content is available in the text.,We aimed to investigate the rate of hospital admissions for cerebrovascular events and of revascularization treatments for acute ischemic stroke in Italy during the coronavirus disease 2019 (COVID-19) outbreak.,The Italian Stroke Organization performed a multicenter study involving 93 Italian Stroke Units.,We collected information on hospital admissions for cerebrovascular events from March 1 to March 31, 2020 (study period), and from March 1 to March 31, 2019 (control period).,Ischemic strokes decreased from 2399 in 2019 to 1810 in 2020, with a corresponding hospitalization rate ratio (RR) of 0.75 ([95% CI, 0.71-0.80] P<0.001); intracerebral hemorrhages decreased from 400 to 322 (hospitalization RR, 0.81 [95% CI, 0.69-0.93]; P=0.004), and transient ischemic attacks decreased from 322 to 196 (hospitalization RR, 0.61 [95% CI, 0.51-0.73]; P<0.001).,Hospitalizations decreased in Northern, Central, and Southern Italy.,Intravenous thrombolyses decreased from 531 (22.1%) in 2019 to 345 in 2020 (19.1%; RR, 0.86 [95% CI, 0.75-0.99]; P=0.032), while primary endovascular procedures increased in Northern Italy (RR, 1.61 [95% CI, 1.13-2.32]; P=0.008).,We found no correlation (P=0.517) between the hospitalization RRs for all strokes or transient ischemic attack and COVID-19 incidence in the different areas.,Hospitalizations for stroke or transient ischemic attacks across Italy were reduced during the worst period of the COVID-19 outbreak.,Intravenous thrombolytic treatments also decreased, while endovascular treatments remained unchanged and even increased in the area of maximum expression of the outbreak.,Limited hospitalization of the less severe patients and delays in hospital admission, due to overcharge of the emergency system by COVID-19 patients, may explain these data.

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

•Fever and cough are the most common symptoms in patients with COVID-19.,•The most prevalent comorbidities are hypertension and diabetes which are associated with the severity of COVID-19.,•ARDS and ACI may be the main obstacles to treatment recovery for patients.,•The case severe rate and mortality is lower than that of SARS and MERS.,Fever and cough are the most common symptoms in patients with COVID-19.,The most prevalent comorbidities are hypertension and diabetes which are associated with the severity of COVID-19.,ARDS and ACI may be the main obstacles to treatment recovery for patients.,The case severe rate and mortality is lower than that of SARS and MERS.,Since being first reported in Wuhan, China, in December 8, 2019, the outbreak of the novel coronavirus, now known as COVID-19, has spread globally.,Some case studies regarding the characteristics and outcome of patients with COVID-19 have been published recently.,We conducted a meta-analysis to evaluate the risk factors of COVID-19.,Medline, SinoMed, EMBASE, and Cochrane Library were searched for clinical and epidemiological studies on confirmed cases of COVID-19.,The incidence of fever, cough, fatigue, and dyspnea symptoms were 85.6 % (95CI 81.3-89.9 %), 65.7 % (95CI 60.1-71.4 %), 42.4 % (95CI 32.2-52.6 %) and 21.4 % (95CI 15.3-27.5 %).,The prevalence of diabetes was 7.7 % (95CI 6.1-9.3 %), hypertension was 15.6 % (95CI 12.6-18.6 %), cardiovascular disease was 4.7 % (95CI 3.1-6.2 %), and malignancy was 1.2 % (95CI 0.5-1.8 %).,The complications, including ARDS risk, ranged from 5.6-13.2 %, with the pooled estimate of ARDS risk at 9.4 %, ACI at 5.8 % (95CI 0.7-10.8 %), AKI at 2.1 % (95CI 0.6-3.7 %), and shock at 4.7 % (95CI 0.9-8.6 %).,The risks of severity and mortality ranged from 12.6 to 23.5% and from 2.0 to 4.4 %, with pooled estimates at 18.0 and 3.2 %, respectively.,The percentage of critical cases in diabetes and hypertension was 44.5 % (95CI 27.0-61.9 %) and 41.7 % (95CI 26.4-56.9 %), respectively.,Fever is the most common symptom in patients with COVID-19.,The most prevalent comorbidities are hypertension and diabetes which are associated with the severity of COVID-19.,ARDS and ACI may be the main obstacles for patients to treatment recovery.,The case severe rate and mortality is lower than that of SARS and MERS.

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

The incidence of pulmonary embolism (PE) is high during severe Coronavirus Disease 2019 (COVID-19).,We aimed to identify predictive and prognostic factors of PE in non-ICU hospitalized COVID-19 patients.,In the retrospective multicenter observational CLOTVID cohort, we enrolled patients with confirmed RT-PCR COVID-19 who were hospitalized in a medicine ward and also underwent a CT pulmonary angiography for a PE suspicion.,Baseline data, laboratory biomarkers, treatments, and outcomes were collected.,Predictive and prognostics factors of PE were identified by using logistic multivariate and by Cox regression models, respectively.,A total of 174 patients were enrolled, among whom 86 (median [IQR] age of 66 years [55-77]) had post-admission PE suspicion, with 30/86 (34.9%) PE being confirmed.,PE occurrence was independently associated with the lack of long-term anticoagulation or thromboprophylaxis (OR [95%CI], 72.3 [3.6-4384.8]) D-dimers ≥ 2000 ng/mL (26.3 [4.1-537.8]) and neutrophils ≥ 7.0 G/L (5.8 [1.4-29.5]).,The presence of these two biomarkers was associated with a higher risk of PE (p = 0.0002) and death or ICU transfer (HR [95%CI], 12.9 [2.5-67.8], p < 0.01).,In hospitalized non-ICU severe COVID-19 patients with clinical PE suspicion, the lack of anticoagulation, D-dimers ≥ 2000 ng/mL, neutrophils ≥ 7.0 G/L, and these two biomarkers combined might be useful predictive markers of PE and prognosis, respectively.

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.

Autopsies of deceased with a confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can provide important insights into the novel disease and its course.,Furthermore, autopsies are essential for the correct statistical recording of the coronavirus disease 2019 (COVID-19) deaths.,In the northern German Federal State of Hamburg, all deaths of Hamburg citizens with ante- or postmortem PCR-confirmed SARS-CoV-2 infection have been autopsied since the outbreak of the pandemic in Germany.,Our evaluation provides a systematic overview of the first 80 consecutive full autopsies.,A proposal for the categorisation of deaths with SARS-CoV-2 infection is presented (category 1: definite COVID-19 death; category 2: probable COVID-19 death; category 3: possible COVID-19 death with an equal alternative cause of death; category 4: SARS-CoV-2 detection with cause of death not associated to COVID-19).,In six cases, SARS-CoV-2 infection was diagnosed postmortem by a positive PCR test in a nasopharyngeal or lung tissue swab.,In the other 74 cases, SARS-CoV-2 infection had already been known antemortem.,The deceased were aged between 52 and 96 years (average 79.2 years, median 82.4 years).,In the study cohort, 34 deceased were female (38%) and 46 male (62%).,Overall, 38% of the deceased were overweight or obese.,All deceased, except for two women, in whom no significant pre-existing conditions were found autoptically, had relevant comorbidities (in descending order of frequency): (1) diseases of the cardiovascular system, (2) lung diseases, (3) central nervous system diseases, (4) kidney diseases, and (5) diabetes mellitus.,A total of 76 cases (95%) were classified as COVID-19 deaths, corresponding to categories 1-3.,Four deaths (5%) were defined as non-COVID-19 deaths with virus-independent causes of death.,In eight cases, pneumonia was combined with a fulminant pulmonary artery embolism.,Peripheral pulmonary artery embolisms were found in nine other cases.,Overall, deep vein thrombosis has been found in 40% of the cases.,This study provides the largest overview of autopsies of SARS-CoV-2-infected patients presented so far.

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) increases the risk of several non-pulmonary complications such as acute myocardial injury, renal failure or thromboembolic events.,A possible unifying explanation for these phenomena may be the presence of profound endothelial dysfunction and injury.,This review provides an overview on the association of endothelial dysfunction with COVID-19 and its therapeutic implications.,Endothelial dysfunction is a common feature of the key comorbidities that increase risk for severe COVID-19 such as hypertension, obesity, diabetes mellitus, coronary artery disease or heart failure.,Preliminary studies indicate that vascular endothelial cells can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and evidence of widespread endothelial injury and inflammation is found in advanced cases of COVID-19.,Prior evidence has established the crucial role of endothelial cells in maintaining and regulating vascular homeostasis and blood coagulation.,Aggravation of endothelial dysfunction in COVID-19 may therefore impair organ perfusion and cause a procoagulatory state resulting in both macro- and microvascular thrombotic events.,Angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs) and statins are known to improve endothelial dysfunction.,Data from smaller observational studies and other viral infections suggests a possible beneficial effect in COVID-19.,Other treatments that are currently under investigation for COVID-19 may also act by improving endothelial dysfunction in patients.,Focusing therapies on preventing and improving endothelial dysfunction could improve outcomes in COVID-19.,Several clinical trials are currently underway to explore this concept.,Image 1,•New evidence implicates endothelial dysfunction in the pathophysiology of COVID-19.,•It may explain complications such as multi-organ damage or thrombotic events.,•Targeted interventions such as RAS inhibitors or statins may improve outcomes.,•Studies on interventions that affect endothelial dysfunction are underway in COVID-19.,New evidence implicates endothelial dysfunction in the pathophysiology of COVID-19.,It may explain complications such as multi-organ damage or thrombotic events.,Targeted interventions such as RAS inhibitors or statins may improve outcomes.,Studies on interventions that affect endothelial dysfunction are underway in 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.

Supplemental Digital Content is available in the text.,RAASi (renin-angiotensin-aldosterone system inhibitors) are suggested as possible treatment option in the early phase of severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection.,A meta-analysis investigating the possible detrimental effects of RAASi on the severity of (SARS-CoV-2) infection showed that ambulatory use of RAASi, by hospitalized patients, has a neutral effect.,It is, however, conceivable that this observation is biased by the fact that antihypertensive medications, are often discontinued at or during admission in hospitalized patients with SARS-CoV-2.,We, therefore, investigated the effect of discontinuation of antihypertensive medications, in hospitalized patients with SARS-CoV-2.,We performed a retrospective observational study on 1584 hospitalized patients with SARS-CoV-2 from 10 participating hospitals in the Netherlands.,Differences in the outcome (severity of disease or death) between the groups in which medications were either continued or discontinued during the course of hospitalization were assessed using logistic regression models.,Discontinuation of angiotensin receptor blockers, ACE (angiotensin-converting enzyme) inhibitors and β-blockers, even when corrected for sex, age, and severity of symptoms during admission, resulted in a 2 to 4× higher risk of dying from SARS-CoV-2 infection (odds ratio [95% CI]); angiotensin receptor blockers 2.65 [1.17-6.04], ACE inhibitor (2.28 [1.15-4.54]), and β-blocker (3.60 [1.10-10.27]).,In conclusion, discontinuation of at-home ACE inhibitor, angiotensin receptor blockers, or β-blocker in patients hospitalized for a SARS-CoV-2 infection was associated with an increased risk of dying, whereas discontinuation of calcium channel blockers and diuretics was not.

Supplemental Digital Content is available in the text.,Patients with coronavirus disease 2019 (COVID-19) who develop cardiac injury are reported to experience higher rates of malignant cardiac arrhythmias.,However, little is known about these arrhythmias-their frequency, the underlying mechanisms, and their impact on mortality.,We extracted data from a registry (NCT04358029) regarding consecutive inpatients with confirmed COVID-19 who were receiving continuous telemetric ECG monitoring and had a definitive disposition of hospital discharge or death.,Between patients who died versus discharged, we compared a primary composite end point of cardiac arrest from ventricular tachycardia/fibrillation or bradyarrhythmias such as atrioventricular block.,Among 800 patients with COVID-19 at Mount Sinai Hospital with definitive dispositions, 140 patients had telemetric monitoring, and either died (52) or were discharged (88).,The median (interquartile range) age was 61 years (48-74); 73% men; and ethnicity was White in 34%.,Comorbidities included hypertension in 61%, coronary artery disease in 25%, ventricular arrhythmia history in 1.4%, and no significant comorbidities in 16%.,Compared with discharged patients, those who died had elevated peak troponin I levels (0.27 versus 0.02 ng/mL) and more primary end point events (17% versus 4%, P=0.01)-a difference driven by tachyarrhythmias.,Fatal tachyarrhythmias invariably occurred in the presence of severe metabolic imbalance, while atrioventricular block was largely an independent primary event.,Hospitalized patients with COVID-19 who die experience malignant cardiac arrhythmias more often than those surviving to discharge.,However, these events represent a minority of cardiovascular deaths, and ventricular tachyarrhythmias are mainly associated with severe metabolic derangement.,URL: https://www.clinicaltrials.gov; Unique identifier: NCT04358029.

Venous thromboembolism (VTE) has emerged as an important issue in patients with COVID-19.,The purpose of this study is to identify the incidence of VTE and mortality in COVID-19 patients initially presenting to a large health system.,Our retrospective study included adult patients (excluding patients presenting with obstetric/gynecologic conditions) across a multihospital health system in the New York Metropolitan Region from March 1-April 27, 2020.,VTE and mortality rates within 8 h of assessment were described.,In 10,871 adults with COVID-19, 118 patients (1.09%) were diagnosed with symptomatic VTE (101 pulmonary embolism, 17 deep vein thrombosis events) and 28 patients (0.26%) died during initial assessment.,Among these 146 patients, 64.4% were males, 56.8% were 60 years or older, 15.1% had a BMI > 35, and 11.6% were admitted to the intensive care unit.,Comorbidities included hypertension (46.6%), diabetes (24.7%), hyperlipidemia (14.4%), chronic lung disease (12.3%), coronary artery disease (11.0%), and prior VTE (7.5%).,Key medications included corticosteroids (22.6%), statins (21.2%), antiplatelets (20.6%), and anticoagulants (20.6%).,Highest D-Dimer was greater than six times the upper limit of normal in 51.4%.,Statin and antiplatelet use were associated with decreased VTE or mortality (each p < 0.01).,In COVID-19 patients who initially presented to a large multihospital health system, the overall symptomatic VTE and mortality rate was over 1.0%.,Statin and antiplatelet use were associated with decreased VTE or mortality.,The potential benefits of antithrombotics in high risk COVID-19 patients during the pre-hospitalization period deserves study.

Those who are infected with Severe Acute Respiratory Syndrome‐related CoronaVirus‐2 are theoretically at increased risk of venous thromboembolism during self‐isolation if they have reduced mobility or are dehydrated.,Should patients develop coronavirus disease (COVID‐19) pneumonia requiring hospital admission for treatment of hypoxia, the risk for thromboembolic complications increases greatly.,These thromboembolic events are the result of at least two distinct mechanisms - microvascular thrombosis in the pulmonary system (immunothrombosis) and hospital‐associated venous thromboembolism.,Since pregnancy is a prothrombotic state, there is concern regarding the potentially increased risk of thrombotic complications among pregnant women with COVID‐19.,To date, however, pregnant women do not appear to have a substantially increased risk of thrombotic complications related to COVID‐19.,Nevertheless, several organizations have vigilantly issued pregnancy‐specific guidelines for thromboprophylaxis in COVID‐19.,Discrepancies between these guidelines reflect the altruistic wish to protect patients and lack of high‐quality evidence available to inform clinical practice.,Low molecular weight heparin (LMWH) is the drug of choice for thromboprophylaxis in pregnant women with COVID‐19.,However, its utility in non‐pregnant patients is only established against venous thromboembolism, as LMWH may have little or no effect on immunothrombosis.,Decisions about initiation and duration of prophylactic anticoagulation in the context of pregnancy and COVID‐19 must take into consideration disease severity, outpatient vs inpatient status, temporal relation between disease occurrence and timing of childbirth, and the underlying prothrombotic risk conferred by additional comorbidities.,There is currently no evidence to recommend the use of intermediate or therapeutic doses of LMWH in thromboprophylaxis, which may increase bleeding risk without reducing thrombotic risk in pregnant patients with COVID‐19.,Likewise, there is no evidence to comment on the role of low‐dose aspirin in thromboprophylaxis or of anti‐cytokine and antiviral agents in preventing immunothrombosis.,These unanswered questions are being studied within the context of clinical trials.

Objective: This study summarizes and compares clinical and laboratory characteristics of 34 patients admitted to the intensive care unit (ICU) for complications from coronavirus disease 2019 (COVID-19) at the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China from Jan. 22 to Mar.,5, 2020.,Methods: A total of 34 patients were divided into two groups, including those who required noninvasive ventilation (NIV) and invasive mechanical ventilation (IMV) with additional extracorporeal membrane oxygenation (ECMO) in 11 patients.,Clinical features of COVID-19 patients were described and the parameters of clinical characteristics between the two groups were compared.,Results: The rates of the acute cardiac and kidney complications were higher in IMV cases than those in NIV cases.,Most patients had lymphocytopenia on admission, with lymphocyte levels dropping progressively on the following days, and the more severe lymphopenia developed in the IMV group.,In both groups, T lymphocyte counts were below typical lower limit norms compared to B lymphocytes.,On admission, both groups had higher than expected amounts of plasma interleukin-6 (IL-6), which over time declined more in NIV patients.,The prothrombin time was increased and the levels of platelet, hemoglobin, blood urea nitrogen (BUN), D-dimer, lactate dehydrogenase (LDH), and IL-6 were higher in IMV cases compared with NIV cases during hospitalization.,Conclusions: Data showed that the rates of complications, dynamics of lymphocytopenia, and changes in levels of platelet, hemoglobin, BUN, D-dimer, LDH and IL-6, and prothrombin time in these ICU patients were significantly different between IMV and NIV cases.

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.

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.

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.

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

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

COVID-19 is a complex disease targeting many organs.,Previous studies highlight COVID-19 as a probable risk factor for acute cardiovascular complications.,We aimed to quantify the risk of acute myocardial infarction and ischaemic stroke associated with COVID-19 by analysing all COVID-19 cases in Sweden.,This self-controlled case series (SCCS) and matched cohort study was done in Sweden.,The personal identification numbers of all patients with COVID-19 in Sweden from Feb 1 to Sept 14, 2020, were identified and cross-linked with national inpatient, outpatient, cancer, and cause of death registers.,The controls were matched on age, sex, and county of residence in Sweden.,International Classification of Diseases codes for acute myocardial infarction or ischaemic stroke were identified in causes of hospital admission for all patients with COVID-19 in the SCCS and all patients with COVID-19 and the matched control individuals in the matched cohort study.,The SCCS method was used to calculate the incidence rate ratio (IRR) for first acute myocardial infarction or ischaemic stroke following COVID-19 compared with a control period.,The matched cohort study was used to determine the increased risk that COVID-19 confers compared with the background population of increased acute myocardial infarction or ischaemic stroke in the first 2 weeks following COVID-19.,86 742 patients with COVID-19 were included in the SCCS study, and 348 481 matched control individuals were also included in the matched cohort study.,When day of exposure was excluded from the risk period in the SCCS, the IRR for acute myocardial infarction was 2·89 (95% CI 1·51-5·55) for the first week, 2·53 (1·29-4·94) for the second week, and 1·60 (0·84-3·04) in weeks 3 and 4 following COVID-19.,When day of exposure was included in the risk period, IRR was 8·44 (5·45-13·08) for the first week, 2·56 (1·31-5·01) for the second week, and 1·62 (0·85-3·09) for weeks 3 and 4 following COVID-19.,The corresponding IRRs for ischaemic stroke when day of exposure was excluded from the risk period were 2·97 (1·71-5·15) in the first week, 2·80 (1·60-4·88) in the second week, and 2·10 (1·33-3·32) in weeks 3 and 4 following COVID-19; when day of exposure was included in the risk period, the IRRs were 6·18 (4·06-9·42) for the first week, 2·85 (1·64-4·97) for the second week, and 2·14 (1·36-3·38) for weeks 3 and 4 following COVID-19.,In the matched cohort analysis excluding day 0, the odds ratio (OR) for acute myocardial infarction was 3·41 (1·58-7·36) and for stroke was 3·63 (1·69-7·80) in the 2 weeks following COVID-19.,When day 0 was included in the matched cohort study, the OR for acute myocardial infarction was 6·61 (3·56-12·20) and for ischaemic stroke was 6·74 (3·71-12·20) in the 2 weeks following COVID-19.,Our findings suggest that COVID-19 is a risk factor for acute myocardial infarction and ischaemic stroke.,This indicates that acute myocardial infarction and ischaemic stroke represent a part of the clinical picture of COVID-19, and highlights the need for vaccination against COVID-19.,Central ALF-funding and Base Unit ALF-Funding, Region Västerbotten, Sweden; Strategic funding during 2020 from the Department of Clinical Microbiology, Umeå University, Sweden; Stroke Research in Northern Sweden; The Laboratory for Molecular Infection Medicine Sweden.

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.

To investigate the association between SARS-CoV-2 vaccination and myocarditis or myopericarditis.,Population based cohort study.,Denmark.,4 931 775 individuals aged 12 years or older, followed from 1 October 2020 to 5 October 2021.,The primary outcome, myocarditis or myopericarditis, was defined as a combination of a hospital diagnosis of myocarditis or pericarditis, increased troponin levels, and a hospital stay lasting more than 24 hours.,Follow-up time before vaccination was compared with follow-up time 0-28 days from the day of vaccination for both first and second doses, using Cox proportional hazards regression with age as an underlying timescale to estimate hazard ratios adjusted for sex, comorbidities, and other potential confounders.,During follow-up, 269 participants developed myocarditis or myopericarditis, of whom 108 (40%) were 12-39 years old and 196 (73%) were male.,Of 3 482 295 individuals vaccinated with BNT162b2 (Pfizer-BioNTech), 48 developed myocarditis or myopericarditis within 28 days from the vaccination date compared with unvaccinated individuals (adjusted hazard ratio 1.34 (95% confidence interval 0.90 to 2.00); absolute rate 1.4 per 100 000 vaccinated individuals within 28 days of vaccination (95% confidence interval 1.0 to 1.8)).,Adjusted hazard ratios among female participants only and male participants only were 3.73 (1.82 to 7.65) and 0.82 (0.50 to 1.34), respectively, with corresponding absolute rates of 1.3 (0.8 to 1.9) and 1.5 (1.0 to 2.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively.,The adjusted hazard ratio among 12-39 year olds was 1.48 (0.74 to 2.98) and the absolute rate was 1.6 (1.0 to 2.6) per 100 000 vaccinated individuals within 28 days of vaccination.,Among 498 814 individuals vaccinated with mRNA-1273 (Moderna), 21 developed myocarditis or myopericarditis within 28 days from vaccination date (adjusted hazard ratio 3.92 (2.30 to 6.68); absolute rate 4.2 per 100 000 vaccinated individuals within 28 days of vaccination (2.6 to 6.4)).,Adjusted hazard ratios among women only and men only were 6.33 (2.11 to 18.96) and 3.22 (1.75 to 5.93), respectively, with corresponding absolute rates of 2.0 (0.7 to 4.8) and 6.3 (3.6 to 10.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively.,The adjusted hazard ratio among 12-39 year olds was 5.24 (2.47 to 11.12) and the absolute rate was 5.7 (3.3 to 9.3) per 100 000 vaccinated individuals within 28 days of vaccination.,Vaccination with mRNA-1273 was associated with a significantly increased risk of myocarditis or myopericarditis in the Danish population, primarily driven by an increased risk among individuals aged 12-39 years, while BNT162b2 vaccination was only associated with a significantly increased risk among women.,However, the absolute rate of myocarditis or myopericarditis after SARS-CoV-2 mRNA vaccination was low, even in younger age groups.,The benefits of SARS-CoV-2 mRNA vaccination should be taken into account when interpreting these findings.,Larger multinational studies are needed to further investigate the risks of myocarditis or myopericarditis after vaccination within smaller subgroups.

The risk of acute myocarditis associated with COVID-19 mRNA vaccination has garnered intense (social) media attention.,However, myocarditis after COVID-19 mRNA vaccination is rare and usually resolves within days or weeks.,Moreover, the risks of hospitalization and death associated with COVID-19 are greater than the risk associated with COVID-19 vaccination.,Therefore, COVID-19 vaccination should be recommended in adolescents and adults.

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.

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 ischemic stroke may occur in patients with coronavirus disease 2019 (COVID-19), but risk factors, in-hospital events, and outcomes are not well studied in large cohorts.,We identified risk factors, comorbidities, and outcomes in patients with COVID-19 with or without acute ischemic stroke and compared with patients without COVID-19 and acute ischemic stroke.,We analyzed the data from 54 health care facilities using the Cerner deidentified COVID-19 dataset.,The dataset included patients with an emergency department or inpatient encounter with discharge diagnoses codes that could be associated to suspicion of or exposure to COVID-19 or confirmed COVID-19.,A total of 103 (1.3%) patients developed acute ischemic stroke among 8163 patients with COVID-19.,Among all patients with COVID-19, the proportion of patients with hypertension, diabetes, hyperlipidemia, atrial fibrillation, and congestive heart failure was significantly higher among those with acute ischemic stroke.,Acute ischemic stroke was associated with discharge to destination other than home or death (relative risk, 2.1 [95% CI, 1.6-2.4]; P<0.0001) after adjusting for potential confounders.,A total of 199 (1.0%) patients developed acute ischemic stroke among 19 513 patients without COVID-19.,Among all ischemic stroke patients, COVID-19 was associated with discharge to destination other than home or death (relative risk, 1.2 [95% CI, 1.0-1.3]; P=0.03) after adjusting for potential confounders.,Acute ischemic stroke was infrequent in patients with COVID-19 and usually occurs in the presence of other cardiovascular risk factors.,The risk of discharge to destination other than home or death increased 2-fold with occurrence of acute ischemic stroke in patients with COVID-19.

COVID-19 is a multi-system infection which predominantly affects the respiratory system, but also causes systemic inflammation, endothelialitis and thrombosis.,The consequences of this include renal dysfunction, hepatitis and stroke.,In this systematic review, we aimed to evaluate the epidemiology, clinical course, and outcomes of patients who suffer from stroke as a complication of COVID-19.,We conducted a systematic review of all studies published between November 1, 2019 and July 8, 2020 which reported on patients who suffered from stroke as a complication of COVID-19.,326 studies were screened, and 30 studies reporting findings from 55,176 patients including 899 with stroke were included.,The average age of patients who suffered from stroke as a complication of COVID-19 was 65.5 (Range: 40.4-76.4 years).,The average incidence of stroke as a complication of COVID-19 was 1.74% (95% CI: 1.09% to 2.51%).,The average mortality of stroke in COVID-19 patients was 31.76% (95% CI: 17.77% to 47.31%).,These patients also had deranged clinical parameters including deranged coagulation profiles, liver function tests, and full blood counts.,Although stroke is an uncommon complication of COVID-19, when present, it often results in significant morbidity and mortality.,In COVID-19 patients, stroke was associated with older age, comorbidities, and severe illness.

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.

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.

Association of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) use with coronavirus disease 2019 (COVID-19) remains controversial.,We aimed to investigate the impact of ACEI/ARB use on all-cause mortality in severe COVID-19 patients with hypertension.,We enrolled 650 COVID-19 patients from Changsha and Wuhan city between 17 January 2020 and 8 March 2020.,Demographic, clinical characteristics, and outcomes were collected.,Multivariable analysis and propensity-score matching were performed to assess the impact of ACEI/ARB therapy on mortality.,Among the 650 patients, 126 who had severe COVID-19 concomitant with hypertension were analyzed.,The average age was 66 years and 56 (44.4%) were men.,There were 37 ACEI/ARB users and 21 in-hospital deaths (mortality rate, 16.7%).,Male sex (odds ratio [OR], 5.13; 95% confidence interval [CI], 1.75 to 17.8), but not ACEI/ARB use (OR, 1.09; 95%CI, 0.31 to 3.43), was an independent risk factor for mortality in severe COVID-19 patients with hypertension.,After propensity-score matching, 60 severe COVID-19 patients were included and no significant correlation between use of ACEI/ARB and mortality was observed.,There was no significant association of ACEI/ARB use with mortality in severe COVID-19 patients with hypertension.,These findings support the continuation of ACEI/ARB therapy for such patients.

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

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

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.

Obesity is a well-established independent risk factor for hypertension and other cardiometabolic disorders.,However, the best anthropometric index of obesity that predicts or associates strongly with hypertension and related conditions remains controversial and inconclusive.,This study compared the performance of eight anthropometric indices of obesity: body mass index (BMI), ponderal index (PI), waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR), waist-height ratio (WHtR), body adiposity index (BAI) and conicity index (CI) as correlates and potential predictors of risk of hypertension and prehypertension in a Nigerian population, and also the possible effect of combining two or more indices in that regard.,This church-based, cross-sectional study was conducted in Anambra state, south-eastern Nigeria from 2012 to 2013.,A total of 912 persons (436 male and 476 female) drawn randomly from three major cities (Awka, Onitsha and Nnewi) in the state participated in the study.,Information on demography, medical history and lifestyle were obtained using a well-structured and validated questionnaire.,The systolic/diastolic blood pressure and anthropometric measurements were taken by well-trained personnel.,The resulting data were analysed using descriptive statistics, logistic regression, Poisson regression and receiver operating characteristic curve analysis.,The mean values of all the anthropometric indices studied increased from normotension, through prehypertension to hypertension in both genders.,BMI, WC, HC and CI were significantly higher (p < 0.05) in females than males.,All the anthropometric indices studied were significantly (p < 0.001 except for CI) correlated with systolic and diastolic blood pressure.,BMI, WHtR, WC and PI (with higher correlation coefficients for blood pressure) showed the best potential potential to predict hypertension and prehypertension in the study: BMI (cut-off = 24.49, AUC = 0.698; cut-off = 23.62, AUC = 0.659), WHtR (cut-off = 0.55, AUC = 0.682; cut-off = 0.5, AUC = 0.636), WC (cut-off = 91.44, AUC = 0.692; cut-off = 82.55, AUC = 0.645), PI (cut-off = 14.45, AUC = 0.670; cut-off = 13.69, AUC = 0.639), in males; and BMI (cut-off = 24.44, AUC = 0.622; cut-off = 28.01, AUC = 0.609), WHtR (cut-off = 0.51, AUC = 0.624; cut-off = 0.6, AUC = 0.572), WC (cut-off = 96.62, AUC = 0.616; cut-off = 96.52, AUC = 0.584), PI (cut-off = 16.38, AUC = 0.619; cut-off = 17.65, AUC = 0.599), in females for hypertension and prehypertension, respectively.,In predicting hypertension risk, WC and WHtR did not significantly improve the performance of BMI in the models when included using our decision rule.,Overall, CI had a very poor discriminatory power for both conditions in this study.,BMI, WHtR, WC and PI emerged the best predictors of hypertension risk, and BMI, WC and PI of prehypertension risk in this study.,The combination of high-performing anthropometric indices in a model did not improve their performance.,Therefore we recommend the simultaneous but independent use of BMI and either WC or WHtR for predicting hypertension, and BMI and WC for prehypertension risk, bearing in mind that both types of index (abdominal and general obesity) account for different forms of obesity.

We comparatively assessed the performance of six simple obesity indices to identify adults with cardiovascular disease (CVD) risk factors in a diverse and contemporary South Asian population.,8,892 participants aged 20-60 years in 2010-2011 were analyzed.,Six obesity indices were examined: body mass index (BMI), waist circumference (WC), waist-height ratio (WHtR), waist-hip ratio (WHR), log of the sum of triceps and subscapular skin fold thickness (LTS), and percent body fat derived from bioelectric impedance analysis (BIA).,We estimated models with obesity indices specified as deciles and as continuous linear variables to predict prevalent hypertension, diabetes, and high cholesterol and report associations (prevalence ratios, PRs), discrimination (area-under-the-curve, AUCs), and calibration (index χ2).,We also examined a composite unhealthy cardiovascular profile score summarizing glucose, lipids, and blood pressure.,No single obesity index consistently performed statistically significantly better than the others across the outcome models.,Based on point estimates, WHtR trended towards best performance in classifying diabetes (PR = 1.58 [1.45-1.72], AUC = 0.77, men; PR = 1.59 [1.47-1.71], AUC = 0.80, women) and hypertension (PR = 1.34 [1.26,1.42], AUC = 0.70, men; PR = 1.41 [1.33,1.50], AUC = 0.78, women).,WC (mean difference = 0.24 SD [0.21-0.27]) and WHtR (mean difference = 0.24 SD [0.21,0.28]) had the strongest associations with the composite unhealthy cardiovascular profile score in women but not in men.,WC and WHtR were the most useful indices for identifying South Asian adults with prevalent diabetes and hypertension.,Collection of waist circumference data in South Asian health surveys will be informative for population-based CVD surveillance efforts.

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

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

The coronavirus disease 2019 (COVID‐19) shows high morbidity and mortality, particularly in patients with concomitant cardiovascular diseases.,Some of these patients are under oral anticoagulation (OAC) at admission, but to date, there are no data on the clinical profile, prognosis and risk factors of such patients during hospitalization for COVID‐19.,Subanalysis of the international ‘real‐world’ HOPE COVID‐19 registry.,All patients with prior OAC at hospital admission for COVID‐19 were suitable for the study.,All‐cause mortality was the primary endpoint.,From 1002 patients included, 110 (60.9% male, median age of 81.5 [IQR 75‐87] years, median Short‐Form Charlson Comorbidity Index [CCI] of 1 [IQR 1‐3]) were on OAC at admission, mainly for atrial fibrillation and venous thromboembolism.,After propensity score matching, 67.9% of these patients died during hospitalization, which translated into a significantly higher mortality risk compared to patients without prior OAC (HR 1.53, 95% CI 1.08‐2.16).,After multivariate Cox regression analysis, respiratory insufficiency during hospitalization (HR 6.02, 95% CI 2.18‐16.62), systemic inflammatory response syndrome (SIRS) during hospitalization (HR 2.29, 95% CI 1.34‐3.91) and the Short‐Form CCI (HR 1.24, 95% CI 1.03‐1.49) were the main risk factors for mortality in patients on prior OAC.,Compared to patients without prior OAC, COVID‐19 patients on OAC therapy at hospital admission showed lower survival and higher mortality risk.,In these patients on OAC therapy, the prevalence of several comorbidities is high.,Respiratory insufficiency and SIRS during hospitalization, as well as higher comorbidity, pointed out those anticoagulated patients with increased mortality risk.

Thromboembolic disease is common in coronavirus disease-2019 (COVID-19).,There is limited evidence on the association of in-hospital anticoagulation (AC) with outcomes and postmortem findings.,The purpose of this study was to examine association of AC with in-hospital outcomes and describe thromboembolic findings on autopsies.,This retrospective analysis examined the association of AC with mortality, intubation, and major bleeding.,Subanalyses were also conducted on the association of therapeutic versus prophylactic AC initiated ≤48 h from admission.,Thromboembolic disease was contextualized by premortem AC among consecutive autopsies.,Among 4,389 patients, median age was 65 years with 44% women.,Compared with no AC (n = 1,530; 34.9%), therapeutic AC (n = 900; 20.5%) and prophylactic AC (n = 1,959; 44.6%) were associated with lower in-hospital mortality (adjusted hazard ratio [aHR]: 0.53; 95% confidence interval [CI]: 0.45 to 0.62 and aHR: 0.50; 95% CI: 0.45 to 0.57, respectively), and intubation (aHR: 0.69; 95% CI: 0.51 to 0.94 and aHR: 0.72; 95% CI: 0.58 to 0.89, respectively).,When initiated ≤48 h from admission, there was no statistically significant difference between therapeutic (n = 766) versus prophylactic AC (n = 1,860) (aHR: 0.86; 95% CI: 0.73 to 1.02; p = 0.08).,Overall, 89 patients (2%) had major bleeding adjudicated by clinician review, with 27 of 900 (3.0%) on therapeutic, 33 of 1,959 (1.7%) on prophylactic, and 29 of 1,530 (1.9%) on no AC.,Of 26 autopsies, 11 (42%) had thromboembolic disease not clinically suspected and 3 of 11 (27%) were on therapeutic AC.,AC was associated with lower mortality and intubation among hospitalized COVID-19 patients.,Compared with prophylactic AC, therapeutic AC was associated with lower mortality, although not statistically significant.,Autopsies revealed frequent thromboembolic disease.,These data may inform trials to determine optimal AC regimens.

Cardiac complications, including clinically suspected myocarditis, have been described in novel coronavirus disease 2019.,Here, we review current data on suspected myocarditis in the course of severe acute respiratory syndrome novel coronavirus-2 (SARS-CoV-2) infection.,Hypothetical mechanisms to explain the pathogenesis of troponin release in patients with novel coronavirus disease 2019 include direct virus-induced myocardial injury (ie, viral myocarditis), systemic hyperinflammatory response (ie, cytokine storm), hypoxemia, downregulation of angiotensin-converting enzyme 2, systemic virus-induced endothelialitis, and type 1 and type 2 myocardial infarction.,To date, despite the fact that millions of SARS-CoV-2 infections have been diagnosed worldwide, there is no definitive proof that SARS-CoV-2 is a novel cardiotropic virus causing direct cardiomyocyte damage.,Diagnosis of viral myocarditis should be based on the molecular assessment of endomyocardial biopsy or autopsy by polymerase chain reaction or in-situ hybridization.,Blood, sputum, or nasal and throat swab virology testing are insufficient and do not correlate with the myocardial involvement of a given pathogen.,Data from endomyocardial biopsies and autopsies in clinically suspected SARS-CoV-2 myocarditis are scarce.,Overall, current clinical epidemiologic data do not support the hypothesis that viral myocarditis is caused by SARS-CoV-2, or that it is common.,More endomyocardial biopsy and autopsy data are also needed for a better understanding of pathogenesis of clinically suspected myocarditis in the course of SARS-CoV-2 infection, which may include virus-negative immune-mediated or already established subclinical autoimmune forms, triggered or accelerated by the hyperinflammatory state of severe novel coronavirus disease 2019.

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

In December 2019, the world started to face a new pandemic situation, the severe acute respiratory syndrome‐coronavirus 2 (SARS‐CoV‐2).,Although coronavirus disease (COVID‐19) clinical manifestations are mainly respiratory, major cardiac complications are being reported.,Cardiac manifestations etiology seems to be multifactorial, comprising direct viral myocardial damage, hypoxia, hypotension, enhanced inflammatory status, ACE2‐receptors downregulation, drug toxicity, endogenous catecholamine adrenergic status, among others.,Studies evaluating patients with COVID‐19 presenting cardiac injury markers show that it is associated with poorer outcomes, and arrhythmic events are not uncommon.,Besides, drugs currently used to treat the COVID‐19 are known to prolong the QT interval and can have a proarrhythmic propensity.,This review focus on COVID‐19 cardiac and arrhythmic manifestations and, in parallel, makes an appraisal of other virus epidemics as SARS‐CoV, Middle East respiratory syndrome coronavirus, and H1N1 influenza.

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.

What are the contemporary clinical characteristics, management, and in-hospital outcomes in patients with acute stroke and transient ischemic attack in China?,In this quality improvement study that included more than 1 million admissions, in-hospital management measures and outcomes varied by type of cerebrovascular event and hospital level of care.,Temporal improvements from 2015 to 2019 were also observed.,Although improvements were seen over time, these findings suggest that ongoing support for evidence-based care is needed.,Stroke represents a significant burden on the health care system of China.,The Chinese Stroke Center Alliance was launched in 2015 to monitor and improve care quality and outcomes for patients with acute stroke and transient ischemic attack (TIA).,To evaluate the clinical characteristics, management, and in-hospital clinical outcomes and complications among patients with stroke or TIA in China.,This quality improvement study assessed stroke or TIA admissions to 1476 participating hospitals in the Chinese Stroke Center Alliance between August 1, 2015, and July 31, 2019.,Stroke types and calendar year.,Eleven guideline-based admission or discharge management measures and 2 summary measures: an all-or-none binary outcome and a composite score (range, 0 [nonadherence] to 1 [perfect adherence]) for adherence to evidence-based stroke and TIA care and in-hospital clinical outcomes, including death or discharge against medical advice (DAMA), major adverse cardiovascular events (MACEs), including ischemic stroke, hemorrhagic stroke, TIA, or myocardial infarction; and in-hospital complications.,Of 1 006 798 patients with stroke or TIA (mean [SD] age, 65.7 [12.2] years; 383 500 [38.1%] female), 838 229 (83.3%) had an ischemic stroke, 64 929 (6.4%) had TIA, 85 705 (8.5%) had intracerebral hemorrhage (ICH), and 11 241 (1.1%) had subarachnoid hemorrhage (SAH).,Management measures varied by cerebrovascular event type, with the mean (SD) composite score ranging from 0.57 (0.31) in SAH to 0.83 (0.24) in TIA.,Poor outcomes and complications were highest among patients with SAH (21.9%; 95% CI, 21.0%-22.8% in-hospital death or DAMA; 9.6%; 95% CI, 9.1%-10.2% MACEs; and 31.4%; 95% CI, 30.6%-32.3% in-hospital complications) and patients with ICH (17.2%; 95% CI, 16.9%-17.5% in-hospital death or DAMA; 9.3%; 95% CI, 9.1%-9.5% MACEs; and 31.3%; 95% CI, 31.0%-31.6% in-hospital complications), followed by patients with ischemic stroke (6.1%; 95% CI, 6.0%-6.1% in-hospital death or DAMA; 6.3%; 95% CI, 6.3%-6.4% MACEs; and 12.8%; 95% CI, 12.7%-12.9% in-hospital complications), and lowest in patients with TIA (5.0%; 95% CI, 4.8%-5.2% in-hospital death or DAMA; 2.4%; 95% CI, 2.3%-2.5% MACEs; and 0.8%; 95% CI, 0.7%-0.8% in-hospital complications).,Temporal improvements in management measures were observed from 2015 to 2019, especially in administration of intravenous recombinant tissue plasminogen activator (+60.3% relatively; 95% CI, 52.9%-70.5%), dysphagia screening (+14.7% relatively; 95% CI, 14.0%-15.6%), and use of anticoagulants for atrial fibrillation (+31.4% relatively; 95% CI, 25.7%-37.3%).,Temporal improvements in in-hospital death or DAMA (−9.7% relatively; 95% CI, −9.6% to −8.5%) and complications (−27.1% relatively; 95% CI, −28.6% to −25.3) were also observed.,In this quality improvement study, performance measure adherence and poor outcomes and complications varied by cerebrovascular event type; although there were substantial improvements over time, these results suggest that support for the use of evidence-based practices is needed.,This quality improvement study examines variations in and temporal trends of performance measures and in-hospital outcomes in patients with stroke or transient ischemic attack in the Chinese Stroke Center Alliance program.

China faces the greatest challenge from stroke in the world.,The death rate for cerebrovascular diseases in China was 149.49 per 100 000, accounting for 1.57 million deaths in 2018.,It ranked third among the leading causes of death behind malignant tumours and heart disease.,The age-standardised prevalence and incidence of stroke in 2013 were 1114.8 per 100 000 population and 246.8 per 100 000 person-years, respectively.,According to the Global Burden of Disease Study 2017, the years of life lost (YLLs) per 100 000 population for stroke increased by 14.6%; YLLs due to stroke rose from third highest among all causes in 1990 to the highest in 2017.,The absolute numbers and rates per 100 000 population for all-age disability-adjusted life years (DALYs) for stroke increased substantially between 1990 and 2017, and stroke was the leading cause of all-age DALYs in 2017.,The main contributors to cerebrovascular diseases include behavioural risk factors (smoking and alcohol use) and pre-existing conditions (hypertension, diabetes mellitus, dyslipidaemia and atrial fibrillation (AF)).,The most prevalent risk factors among stroke survivors were hypertension (63.0%-84.2%) and smoking (31.7%-47.6%).,The least prevalent was AF (2.7%-7.4%).,The prevalences for major risk factors for stroke are high and most have increased over time.,Based on the latest national epidemiological data, 26.6% of adults aged ≥15 years (307.6 million adults) smoked tobacco products.,For those aged ≥18 years, age-adjusted prevalence of hypertension was 25.2%; adjusted prevalence of hypercholesterolaemia was 5.8%; and the standardised prevalence of diabetes was 10.9%.,For those aged ≥40 years, the standardised prevalence of AF was 2.31%.,Data from the Hospital Quality Monitoring System showed that 3 010 204 inpatients with stroke were admitted to 1853 tertiary care hospitals during 2018.,Of those, 2 466 785 (81.9%) were ischaemic strokes (ISs); 447 609 (14.9%) were intracerebral haemorrhages (ICHs); and 95 810 (3.2%) were subarachnoid haemorrhages (SAHs).,The average age of patients admitted was 66 years old, and nearly 60% were male.,A total of 1555 (0.1%), 2774 (0.6%) and 1347 (1.4%) paediatric strokes (age <18 years) were identified among IS, ICH and SAH, respectively.,Over one-third (1 063 892 (35.3%)) of the patients were covered by urban resident basic medical insurance, followed by urban employee basic medical insurance (699 513 (23.2%)) and new rural cooperative medical schema (489 361 (16.3%)).,The leading risk factor was hypertension (67.4% for IS, 77.2% for ICH and 49.1% for SAH), and the leading comorbidity was pneumonia or pulmonary infection (10.1% for IS, 31.4% for ICH and 25.2% for SAH).,In-hospital death/discharge against medical advice rate was 8.3% for stroke inpatients, ranging from 5.8% for IS to 19.5% for ICH.,The median and IQR of length of stay was 10.0 (7.0-14.0) days, ranging from 10.0 (7.0-13.0) in IS to 14.0 (8.0-22.0) in SAH.,Data from the Chinese Stroke Center Alliance demonstrated that the composite scores of guideline-recommended key performance indicators for patients with IS, ICH and SAH were 0.77±0.21, 0.72±0.28 and 0.59±0.32, respectively.

Hypertension is a common comorbidity in hospitalized patients with COVID-19 infection.,This study aimed to estimate the risks of adverse events associated with in-hospital blood pressure (BP) control and the effects of angiotensin II receptor blocker (ARB) prescription in COVID-19 patients with concomitant hypertension.,In this retrospective cohort study, the anonymized medical records of COVID-19 patients were retrieved from an acute field hospital in Wuhan, China.,Clinical data, drug prescriptions, and laboratory investigations were collected for individual patients with diagnosed hypertension on admission.,Cox proportional hazards models were used to estimate the risks of adverse outcomes associated with BP control during the hospital stay.,Of 803 hypertensive patients, 67 (8.3%) were admitted to the ICU, 30 (3.7%) had respiratory failure, 26 (3.2%) had heart failure, and 35 (4.8%) died.,After adjustment for confounders, the significant predictors of heart failure were average systolic blood pressure (SBP) (hazard ratio (HR) per 10 mmHg 1.89, 95% confidence interval (CI): 1.15, 3.13) and pulse pressure (HR per 10 mmHg 2.71, 95% CI: 1.39, 5.29).,The standard deviations of SBP and diastolic BP were independently associated with mortality and ICU admission.,The risk estimates of poor BP control were comparable between patients receiving ARBs and those not receiving ARBs, with the only exception of a high risk of heart failure in the non-ARB group.,Poor BP control was independently associated with higher risks of adverse outcomes of COVID-19.,ARB drugs did not increase the risks of adverse events in hypertensive patients.

Coronavirus disease 2019 (COVID-19), caused by a strain of coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has become a global pandemic that has affected the lives of billions of individuals.,Extensive studies have revealed that SARS-CoV-2 shares many biological features with SARS-CoV, the zoonotic virus that caused the 2002 outbreak of severe acute respiratory syndrome, including the system of cell entry, which is triggered by binding of the viral spike protein to angiotensin-converting enzyme 2.,Clinical studies have also reported an association between COVID-19 and cardiovascular disease.,Pre-existing cardiovascular disease seems to be linked with worse outcomes and increased risk of death in patients with COVID-19, whereas COVID-19 itself can also induce myocardial injury, arrhythmia, acute coronary syndrome and venous thromboembolism.,Potential drug-disease interactions affecting patients with COVID-19 and comorbid cardiovascular diseases are also becoming a serious concern.,In this Review, we summarize the current understanding of COVID-19 from basic mechanisms to clinical perspectives, focusing on the interaction between COVID-19 and the cardiovascular system.,By combining our knowledge of the biological features of the virus with clinical findings, we can improve our understanding of the potential mechanisms underlying COVID-19, paving the way towards the development of preventative and therapeutic solutions.,The presence of cardiovascular comorbidities is linked with worse outcomes in patients with coronavirus disease 2019 (COVID-19), and COVID-19 can induce cardiovascular damage.,In this Review, Wu and colleagues summarize the latest mechanistic and clinical studies that contribute to our current understanding of COVID-19-related cardiovascular disease.,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), shares many biological features with SARS-CoV, the virus that causes severe acute respiratory syndrome, owing to 80% genomic sequence identity.The interaction between the viral spike (S) protein and angiotensin-converting enzyme 2, which triggers entry of the virus into host cells, is likely to be involved in the cardiovascular manifestations of COVID-19.,The presence of underlying cardiovascular comorbidities in patients with COVID-19 is associated with high mortality.COVID-19 can cause cardiovascular disorders, including myocardial injury, arrhythmias, acute coronary syndrome and venous thromboembolism.Several medications used for the treatment of COVID-19 have uncertain safety and efficacy profiles.,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), shares many biological features with SARS-CoV, the virus that causes severe acute respiratory syndrome, owing to 80% genomic sequence identity.,The interaction between the viral spike (S) protein and angiotensin-converting enzyme 2, which triggers entry of the virus into host cells, is likely to be involved in the cardiovascular manifestations of COVID-19.,The presence of underlying cardiovascular comorbidities in patients with COVID-19 is associated with high mortality.,COVID-19 can cause cardiovascular disorders, including myocardial injury, arrhythmias, acute coronary syndrome and venous thromboembolism.,Several medications used for the treatment of COVID-19 have uncertain safety and efficacy profiles.

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS).,The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion.,Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years.,Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n=35,182).,Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (padj=6.73×10−6).,Novel reciprocal case-control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion.,Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes.,No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia.,These findings suggest that in addition to conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present.

The 22q11.2 deletion syndrome (22q11.2DS) is associated with an increased risk for psychiatric disorders.,Although most of the 22q11.2DS patients have a 3.0-Mb deletion, existing mouse models only mimic a minor mutation of 22q11.2DS, a 1.5-Mb deletion.,The role of the genes existing outside the 1.5-Mb deletion in psychiatric symptoms of 22q11.2DS is unclear.,In this study, we generated a mouse model that reproduced the 3.0-Mb deletion of the 22q11.2DS (Del(3.0 Mb)/ +) using the CRISPR/Cas9 system.,Ethological and physiological phenotypes of adult male mutants were comprehensively evaluated by visual-evoked potentials, circadian behavioral rhythm, and a series of behavioral tests, such as measurement of locomotor activity, prepulse inhibition, fear-conditioning memory, and visual discrimination learning.,As a result, Del(3.0 Mb)/ + mice showed reduction of auditory prepulse inhibition and attenuated cue-dependent fear memory, which is consistent with the phenotypes of existing 22q11.2DS models.,In addition, Del(3.0 Mb)/ + mice displayed an impaired early visual processing that is commonly seen in patients with schizophrenia.,Meanwhile, unlike the existing models, Del(3.0 Mb)/ + mice exhibited hypoactivity over several behavioral tests, possibly reflecting the fatigability of 22q11.2DS patients.,Lastly, Del(3.0 Mb)/ + mice displayed a faster adaptation to experimental jet lag as compared with wild-type mice.,Our results support the validity of Del(3.0 Mb)/ + mice as a schizophrenia animal model and suggest that our mouse model is a useful resource to understand pathogenic mechanisms of schizophrenia and other psychiatric disorders associated with 22q11.2DS.

COVID-19 is a complex disease targeting many organs.,Previous studies highlight COVID-19 as a probable risk factor for acute cardiovascular complications.,We aimed to quantify the risk of acute myocardial infarction and ischaemic stroke associated with COVID-19 by analysing all COVID-19 cases in Sweden.,This self-controlled case series (SCCS) and matched cohort study was done in Sweden.,The personal identification numbers of all patients with COVID-19 in Sweden from Feb 1 to Sept 14, 2020, were identified and cross-linked with national inpatient, outpatient, cancer, and cause of death registers.,The controls were matched on age, sex, and county of residence in Sweden.,International Classification of Diseases codes for acute myocardial infarction or ischaemic stroke were identified in causes of hospital admission for all patients with COVID-19 in the SCCS and all patients with COVID-19 and the matched control individuals in the matched cohort study.,The SCCS method was used to calculate the incidence rate ratio (IRR) for first acute myocardial infarction or ischaemic stroke following COVID-19 compared with a control period.,The matched cohort study was used to determine the increased risk that COVID-19 confers compared with the background population of increased acute myocardial infarction or ischaemic stroke in the first 2 weeks following COVID-19.,86 742 patients with COVID-19 were included in the SCCS study, and 348 481 matched control individuals were also included in the matched cohort study.,When day of exposure was excluded from the risk period in the SCCS, the IRR for acute myocardial infarction was 2·89 (95% CI 1·51-5·55) for the first week, 2·53 (1·29-4·94) for the second week, and 1·60 (0·84-3·04) in weeks 3 and 4 following COVID-19.,When day of exposure was included in the risk period, IRR was 8·44 (5·45-13·08) for the first week, 2·56 (1·31-5·01) for the second week, and 1·62 (0·85-3·09) for weeks 3 and 4 following COVID-19.,The corresponding IRRs for ischaemic stroke when day of exposure was excluded from the risk period were 2·97 (1·71-5·15) in the first week, 2·80 (1·60-4·88) in the second week, and 2·10 (1·33-3·32) in weeks 3 and 4 following COVID-19; when day of exposure was included in the risk period, the IRRs were 6·18 (4·06-9·42) for the first week, 2·85 (1·64-4·97) for the second week, and 2·14 (1·36-3·38) for weeks 3 and 4 following COVID-19.,In the matched cohort analysis excluding day 0, the odds ratio (OR) for acute myocardial infarction was 3·41 (1·58-7·36) and for stroke was 3·63 (1·69-7·80) in the 2 weeks following COVID-19.,When day 0 was included in the matched cohort study, the OR for acute myocardial infarction was 6·61 (3·56-12·20) and for ischaemic stroke was 6·74 (3·71-12·20) in the 2 weeks following COVID-19.,Our findings suggest that COVID-19 is a risk factor for acute myocardial infarction and ischaemic stroke.,This indicates that acute myocardial infarction and ischaemic stroke represent a part of the clinical picture of COVID-19, and highlights the need for vaccination against COVID-19.,Central ALF-funding and Base Unit ALF-Funding, Region Västerbotten, Sweden; Strategic funding during 2020 from the Department of Clinical Microbiology, Umeå University, Sweden; Stroke Research in Northern Sweden; The Laboratory for Molecular Infection Medicine Sweden.

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.

COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis.,Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age.,The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19.,VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves.,For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk.,For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH.

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

A 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.

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.

Reports of widespread thromboses and disseminated intravascular coagulation (DIC) in patients with coronavirus disease 19 (COVID-19) have been rapidly increasing in number.,Key features of this disorder include a lack of bleeding risk, only mildly low platelet counts, elevated plasma fibrinogen levels, and detection of both severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and complement components in regions of thrombotic microangiopathy (TMA).,This disorder is not typical DIC.,Rather, it might be more similar to complement-mediated TMA syndromes, which are well known to rheumatologists who care for patients with severe systemic lupus erythematosus or catastrophic antiphospholipid syndrome.,This perspective has critical implications for treatment.,Anticoagulation and antiviral agents are standard treatments for DIC but are gravely insufficient for any of the TMA disorders that involve disorders of complement.,Mediators of TMA syndromes overlap with those released in cytokine storm, suggesting close connections between ineffective immune responses to SARS-CoV-2, severe pneumonia and life-threatening microangiopathy.,A subset of patients with coronavirus disease 19 (COVID-19) develop a thrombotic disorder that resembles a virally induced, complement-mediated thrombotic microangiopathy.,Here, the authors present the theory and evidence for this disease model and discuss important considerations for treatment.

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.

To quantify rates of organ specific dysfunction in individuals with covid-19 after discharge from hospital compared with a matched control group from the general population.,Retrospective cohort study.,NHS hospitals in England.,47 780 individuals (mean age 65, 55% men) in hospital with covid-19 and discharged alive by 31 August 2020, exactly matched to controls from a pool of about 50 million people in England for personal and clinical characteristics from 10 years of electronic health records.,Rates of hospital readmission (or any admission for controls), all cause mortality, and diagnoses of respiratory, cardiovascular, metabolic, kidney, and liver diseases until 30 September 2020.,Variations in rate ratios by age, sex, and ethnicity.,Over a mean follow-up of 140 days, nearly a third of individuals who were discharged from hospital after acute covid-19 were readmitted (14 060 of 47 780) and more than 1 in 10 (5875) died after discharge, with these events occurring at rates four and eight times greater, respectively, than in the matched control group.,Rates of respiratory disease (P<0.001), diabetes (P<0.001), and cardiovascular disease (P<0.001) were also significantly raised in patients with covid-19, with 770 (95% confidence interval 758 to 783), 127 (122 to 132), and 126 (121 to 131) diagnoses per 1000 person years, respectively.,Rate ratios were greater for individuals aged less than 70 than for those aged 70 or older, and in ethnic minority groups compared with the white population, with the largest differences seen for respiratory disease (10.5 (95% confidence interval 9.7 to 11.4) for age less than 70 years v 4.6 (4.3 to 4.8) for age ≥70, and 11.4 (9.8 to 13.3) for non-white v 5.2 (5.0 to 5.5) for white individuals).,Individuals discharged from hospital after covid-19 had increased rates of multiorgan dysfunction compared with the expected risk in the general population.,The increase in risk was not confined to the elderly and was not uniform across ethnicities.,The diagnosis, treatment, and prevention of post-covid syndrome requires integrated rather than organ or disease specific approaches, and urgent research is needed to establish the risk factors.

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.

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

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

Coronavirus disease 2019 (COVID-19) causes a hypercoagulable state.,Several autopsy studies have found microthrombi in pulmonary circulation.,In this randomized, open-label, phase II study, we randomized COVID-19 patients requiring mechanical ventilation to receive either therapeutic enoxaparin or the standard anticoagulant thromboprophylaxis.,We evaluated the gas exchange over time through the ratio of partial pressure of arterial oxygen (PaO2) to the fraction of inspired oxygen (FiO2) at baseline, 7, and 14 days after randomization, the time until successful liberation from mechanical ventilation, and the ventilator-free days.,Ten patients were assigned to the therapeutic enoxaparin and ten patients to prophylactic anticoagulation.,There was a statistically significant increase in the PaO2/FiO2 ratio over time in the therapeutic group (163 [95% confidence interval - CI 133-193] at baseline, 209 [95% CI 171-247] after 7 days, and 261 [95% CI 230-293] after 14 days), p = 0.0004.,In contrast, we did not observe this improvement over time in the prophylactic group (184 [95% CI 146-222] at baseline, 168 [95% CI 142-195] after 7 days, and 195 [95% CI 128-262] after 14 days), p = 0.487.,Patients of the therapeutic group had a higher ratio of successful liberation from mechanical ventilation (hazard ratio: 4.0 [95% CI 1.035-15.053]), p = 0.031 and more ventilator-free days (15 days [interquartile range IQR 6-16] versus 0 days [IQR 0-11]), p = 0.028 when compared to the prophylactic group.,Therapeutic enoxaparin improves gas exchange and decreases the need for mechanical ventilation in severe COVID-19.,REBEC RBR-949z6v.,•COVID-19 is associated with microthrombi in pulmonary circulation.,•We randomized severe COVID-19 patients to receive either therapeutic enoxaparin or the standard thromboprophylaxis.,•Therapeutic enoxaparin resulted in improved gas exchange over time.,•Larger clinical trial is urgently needed to evaluate the anticoagulant therapy in severe COVID-19.,COVID-19 is associated with microthrombi in pulmonary circulation.,We randomized severe COVID-19 patients to receive either therapeutic enoxaparin or the standard thromboprophylaxis.,Therapeutic enoxaparin resulted in improved gas exchange over time.,Larger clinical trial is urgently needed to evaluate the anticoagulant therapy in severe COVID-19.

Coronavirus Disease 2019 (COVID‐19) is responsible for a worldwide pandemic, with a high rate of morbidity and mortality.,The increasing evidence of an associated relevant prothrombotic coagulopathy has resulted in an increasing use of antithrombotic doses higher than usual in COVID‐19 patients.,Information on the benefit/risk ratio of this approach is still lacking.,To assess the incidence of relevant bleeding complications in association with the antithrombotic strategy and its relationship with the amount of drug.,Consecutive COVID‐19 patients admitted between February and April 2020 were included in a retrospective analysis.,Major bleedings (MB) and clinically relevant non‐major bleeding (CRNMB) were obtained from patient medical records and were adjudicated by an independent committee.,Of the 324 patients who were recruited, 240 had been treated with prophylactic doses and 84 with higher doses of anticoagulants.,The rate of the composite endpoint of MB or CRNMB was 6.9 per 100‐person/months in patients who had been given prophylactic doses, and 26.4 per 100‐person/months in those who had been prescribed higher doses (hazard ratio, 3.89; 95% confidence interval, 1.90‐7.97).,The corresponding rates for overall mortality were 12.2 and 20.1 per 100‐person/months, respectively.,The rate of relevant bleeding events was high in patients treated with (sub)therapeutic doses of anticoagulants.,In the latter group, overall mortality did not differ from that of patients treated with standard prophylactic doses and was even higher.,Our result does not support a strategy of giving (sub)therapeutic doses of anticoagulants in non‐critically ill patients with COVID‐19.

Periodontitis is an independent risk factor for cardiovascular disease, but the mechanistic link is not fully understood.,In atherosclerotic cardiovascular disease, monocytes can adopt a persistent hyperresponsive phenotype, termed trained immunity.,We hypothesized that periodontitis-associated bacteria can induce trained immunity in monocytes, which subsequently accelerate atherosclerosis development.,We combined in vitro experiments on human primary monocytes and in vivo techniques in patients with periodontitis to test this hypothesis.,Adherent peripheral blood mononuclear cells (PBMCs) were transiently exposed in vitro to Porphyromonas gingivalis for 24 hours, and restimulated with lipopolysaccharide (LPS) or Pam3CysK4 (P3C) six days later, to measure interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) production.,In an exploratory observational study, patients with severe periodontitis (63 ± 6 years, n=14) and control subjects with no-to-mild periodontitis (54 ± 10 years, n=14) underwent venipuncture and 2’-deoxy-2’-[18F]fluoro-D-glucose positron-emission-tomography ([18F]FDG PET/CT) scanning.,When adherent peripheral blood mononuclear cells (PBMCs) were transiently exposed in vitro to Porphyromonas gingivalis for 24 hours, and restimulated with LPS or P3C six days later, IL-6 and TNFα production was significantly increased (TNFα/P3C, p<0.01).,Circulating leukocytes, IL-6 and interleukin-1 receptor antagonist (IL-1Ra) concentrations were generally higher in patients compared to controls (leukocytes: p<0.01; IL-6: p=0.08; IL-1Ra: p=0.10).,Cytokine production capacity in PBMCs after 24h stimulation revealed no differences between groups.,[18F]FDG PET/CT imaging showed a trend for increased [18F]FDG-uptake in the periodontium [mean standard uptake value (SUVmean), p=0.11] and in femur bone marrow (SUVmean, p=0.06), but no differences were observed for vascular inflammation.,Positive correlations between severity of periodontitis, measured by The Dutch Periodontal Screening Index and pocket depth, with circulating inflammatory markers and tissue inflammation were found.,P. gingivalis induces long-term activation of human monocytes in vitro (trained immunity).,Patients with severe periodontitis did have signs of increased systemic inflammation and hematopoietic tissue activation.,However, their circulating monocytes did not show a hyperresponsive phenotype.,Together we suggest that trained immunity might contribute to local periodontal inflammation which warrants further investigation.

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability.,This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019.,GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019.,Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019.,The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period.,The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019.,The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019.,Cardiovascular diseases remain the leading cause of disease burden in the world.,CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries.,There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.,•The burden of CVD, in number of DALYs and deaths, continues to increase globally.,•CVD burden attributable to modifiable risk factors continues to increase globally.,•Countries should invest in existing cost-effective public health programs and clinical interventions to target modifiable risks, promote healthy aging across the lifespan, and reduce disability and premature death due to CVD.,The burden of CVD, in number of DALYs and deaths, continues to increase globally.,CVD burden attributable to modifiable risk factors continues to increase globally.,Countries should invest in existing cost-effective public health programs and clinical interventions to target modifiable risks, promote healthy aging across the lifespan, and reduce disability and premature death due to CVD.