The coronavirus disease 2019 (COVID-19) pandemic has impacted healthcare communities across the globe on an unprecedented scale. Patients have had diverse clinical outcomes, but those developing COVID-19-related coagulopathy have shown a disproportionately worse outcome. This narrative review summarizes current evidence regarding the epidemiology, clinical features, known and presumed pathophysiology-based models, and treatment guidance regarding COVID-19 coagulopathy.

Background: Whilst the link between aging and thrombogenicity in atrial fibrillation (AF) is well established, the cellular underlying mechanisms are unknown. In AF, the role of senescence in tissue remodeling and prothrombotic state remains unclear. Aims: We investigated the link between AF and senescence by comparing the expression of senescence markers (p53 and p16), with prothrombotic and inflammatory proteins in right atrial appendages from patients in AF and sinus rhythm (SR). Methods: The right atrial appendages of 147 patients undergoing open-heart surgery were harvested. Twenty-one non-valvular AF patients, including paroxysmal (PAF) or permanent AF (PmAF), were matched with 21 SR patients according to CHA2DS2-VASc score and treatment. Protein expression was assessed by tissue lysates Western blot analysis. Results: The expression of p53, p16, and tissue factor (TF) was significantly increased in AF compared to SR (0.91 ± 0.31 vs. 0.58 ± 0.31, p = 0.001; 0.76 ± 0.32 vs. 0.35 ± 0.18, p = 0.0001; 0.88 ± 0.32 vs. 0.68 ± 0.29, p = 0.045, respectively). Expression of endothelial NO synthase (eNOS) was lower in AF (0.25 ± 0.15 vs. 0.35 ± 0.12, p = 0.023). There was a stepwise increase of p53, p16, TF, matrix metalloproteinase-9, and an eNOS progressive decrease between SR, PAF, and PmAF. AF was the only predictive factor of p53 and p16 elevation in multivariate analysis. Conclusions: The study brought new evidence indicating that AF progression is strongly related to human atrial senescence burden and points at a link between senescence, thrombogenicity, endothelial dysfunction and atrial remodeling.

The recent outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 has been declared a public health emergency of international concern. COVID-19 may present as acute respiratory distress syndrome in severe cases, and patients with pre-existing cardiovascular comorbidities are reported to be the most vulnerable. Notably, acute myocardial injury, determined by elevated high-sensitivity troponin levels, is commonly observed in severe cases, and is strongly associated with mortality. Therefore, understanding the effects of COVID-19 on the cardiovascular system is essential for providing comprehensive medical care for critically ill patients. In this review, we summarize the rapidly evolving data and highlight the cardiovascular considerations related to COVID-19.

Background: Besides its well-known functions in hemostasis, thrombin plays a role in various non-hemostatic biological and pathophysiologic processes. We examined the potential of thrombin to promote premature atrial endothelial cells (ECs) senescence. Methods and Results: Primary ECs were isolated from porcine atrial tissue. Endothelial senescence was assessed by measuring beta-galactosidase (SA-β-gal) activity using flow cytometry, oxidative stress using the redox-sensitive probe dihydroethidium, protein level by Western blot, and matrix metalloproteinases (MMPs) activity using zymography. Atrial endothelial senescence was induced by thrombin at clinically relevant concentrations. Thrombin induced the up-regulation of p53, a key regulator in cellular senescence and of p21 and p16, two cyclin-dependent kinase inhibitors. Nicotinamide adenine dinucleotide phosphate NADPH oxidase, cyclooxygenases and the mitochondrial respiration complex contributed to oxidative stress and senescence. Enhanced expression levels of vascular cell adhesion molecule (VCAM)-1, tissue factor, transforming growth factor (TGF)-β and MMP-2 and 9 characterized the senescence-associated secretory phenotype of atrial ECs. In addition, the pro-senescence endothelial response to thrombin was associated with an overexpression of both angiotensin converting enzyme and AT1 receptors and was inhibited by perindoprilat and losartan. Conclusions: Thrombin promotes premature ageing and senescence of atrial ECs and may pave the way to deleterious remodeling of atrial tissue by a local up-regulation of the angiotensin system and by promoting pro-inflammatory, pro-thrombotic, pro-fibrotic and pro-remodeling responses. Hence, targeting thrombin and/or angiotensin systems may efficiently prevent atrial endothelial senescence.

Background: Bedside diagnosis between Takotsubo syndrome (TTS) and ST elevation (STEMI) and non-ST elevation (NSTEMI) myocardial infarction remains challenging. We sought to determine a cardiac biomarker profile to enable their early distinction. Methods: 1100 patients (TTS n = 314, STEMI n = 452, NSTEMI n = 334) were enrolled in two centers. Baseline clinical and biological characteristics were compared between groups. Results: At admission, cut-off values of BNP (B-type natriuretic peptide)/TnI (Troponin I) ratio of 54 and 329 distinguished respectively STEMI from NSTEMI, and NSTEMI from TTS. Best differentiation was obtained by the use of BNP/TnI ratio at peak (cut-of values of 6 and 115 discriminated respectively STEMI from NSTEMI, and NSTEMI from TTS). We developed a score including five parameters (age, gender, history of psychiatric disorders, LVEF, and BNP/TnI ratio at admission) enabling good distinction between TTS and STEMI (77% specificity and 92% sensitivity, AUC 0.93). For the distinction between TTS and NSTEMI, a four variables score (gender, history of psychiatric disorders, LVEF, and BNP at admission) achieved a good diagnostic performance (89% sensitivity, 85% specificity, AUC 0.94). Conclusion: A distinctive cardiac biomarker profile enables at an early stage a differentiation between TTS and ACS. A four (NSTEMI) or five variables score (STEMI) permitted a better discrimination.

The impact of antithrombotic regimen and platelet inhibition extent on subclinical leaflet thrombosis (SLT) detected by cardiac multidetector computed tomography (MDCT) after transcatheter aortic valve replacement (TAVR) is not well established. Hypoattenuation affecting motion (HAM) has been proposed as a surrogate marker of SLT, and is characterized by hypoattenuated leaflet thickening (HALT) and concomitant reduction in leaflet motion (RELM). We sought to investigate (i) the prevalence of HAM and HALT after TAVR detected by MDCT, (ii) the predictors of SLT, (iii) the impact of oral anticoagulant (OAC) and platelet inhibition extent assessed by platelet reactivity index vasodilator stimulated phosphoprotein (PRI-VASP) and closure time adenosine diphosphate (CT-ADP) on SLT. Of 187 consecutive patients who underwent TAVR from 1 August 2017 to 31 March 2018, 90 of them had cardiac CT at relevant follow-up. Clinical, biological, echocardiographic, procedural characteristics and treatments were collected before, at discharge, and 1 year after TAVR. P2Y₁₂ platelet inhibition extent and primary haemostasis disorders were investigated using platelet PRI-VASP and CT-ADP point-of-care assays. Eighty-five post-TAVR CTs out of 90 were ranked for clarity and assessed with sufficient diagnostic quality. HAM was evidenced in 13 patients (15.3%) and HALT in 30 patients (35%). Procedural characteristics, including aortic valve calcium score, annulus size, or procedural heparin regimens, were equivalent between groups. Likewise, no impact of P2Y₁₂ inhibition (PRI-VASP) nor primary haemostasis disorders (CT-ADP) on SLT could be evidenced. No impact of SLT on valve deterioration evaluated by transthoracic echocardiography (TTE) and clinical events could be established at 12 months follow-up. By multivariate analysis, lack of oral anticoagulant therapy at discharge (HR 12.130 CI 95% (1.394–150.582); p = 0.028) and higher haemoglobin levels were evidenced as the sole independent predictors of SLT. In four patients with HAM, MDCT follow-up was obtained after initiation of OAC therapy and showed a complete regression of HAM. SLT was evidenced in a sizeable proportion of patients treated by TAVR and was mainly determined by the lack of oral anticoagulant therapy. Conversely, no impact of platelet inhibition extent on SLT could be evidenced.