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Introduction: Corticosteroid therapy has been demonstrated to improve prognosis and reduce mortality in patients with severe Coronavirus Disease 2019 (COVID-19) infection by attenuating the exaggerated inflammatory response that emerges in the late phase of infection. However, its impact on patients with pre-existing cardiovascular disease, who are at higher risk of complications, has not been specifically studied. The aim of this study is to evaluate the effect of corticosteroid therapy on mortality and long-term COVID-19 symptoms in this high-risk population. Methods: We analyzed the prospective registry HOPE-2. Patients with previous cardiovascular disease were selected, and 18-month all-cause death was defined as the primary endpoint. Long-term COVID-19 symptoms were considered as secondary endpoints. A total of 1188 patients with previous heart disease were included, of which 453 received corticosteroid treatment. Propensity score matching analysis in a 1:1 fashion was performed based on baseline variables that exhibited a p-value < 0.05 in the univariant analysis and outcome variables that defined corticosteroid use, with a final matched population of 796 patients. Results: In patients with pre-existing heart disease, corticosteroid treatment was not associated with differences in 18-month all-cause mortality (p = 0.52). However, a shorter duration of hospitalization (median: 8 days [IQR: 4–14] and 11 days [IQR: 7–18]; p < 0.001) was observed in patients who received corticosteroids. No significant differences in long-term COVID-19 symptoms were observed between the two groups. Conclusions: In patients with pre-existing heart disease, the absence of a clear harmful effect suggests that the positive effects of corticosteroids may be offset by their potential adverse effects which could contribute to the persistence of long COVID symptoms. This finding may reflect a differential response to corticosteroids in this high-risk subgroup, highlighting the need for further studies to clarify the role of this therapy in such patients.

Background: Acute cardiac injury (ACI) after COVID-19 has been linked with unfavorable clinical outcomes, but data on the clinical impact of elevated cardiac troponin on discharge during follow-up are scarce. Our objective is to elucidate the clinical outcome of patients with elevated troponin on discharge after surviving a COVID-19 hospitalization. Methods: We conducted an analysis in the prospective registry HOPE-2 (NCT04778020). Only patients discharged alive were selected for analysis, and all-cause death on follow-up was considered as the primary endpoint. As a secondary endpoint, we established any long-term COVID-19 symptoms. HOPE-2 stopped enrolling patients on 31 December 2021, with 9299 patients hospitalized with COVID-19, of which 1805 were deceased during the acute phase. Finally, 2382 patients alive on discharge underwent propensity score matching by relevant baseline variables in a 1:3 fashion, from 56 centers in 8 countries. Results: Patients with elevated troponin experienced significantly higher all-cause death during follow-up (log-rank = 27.23, p < 0.001), and had a higher chance of experiencing long-term COVID-19 cardiovascular symptoms. Specifically, fatigue and dyspnea (57.7% and 62.8%, with p-values of 0.009 and <0.001, respectively) are among the most common. Conclusions: After surviving the acute phase, patients with elevated troponin on discharge present increased mortality and long-term COVID-19 symptoms over time, which is clinically relevant in follow-up visits.

Background: Heart disease is linked to worse acute outcomes after coronavirus disease 2019 (COVID-19), although long-term outcomes and prognostic factor data are lacking. We aim to characterize the outcomes and the impact of underlying heart diseases after surviving COVID-19 hospitalization. Methods: We conducted an analysis of the prospective registry HOPE-2 (Health Outcome Predictive Evaluation for COVID-19-2, NCT04778020). We selected patients discharged alive and considered the primary end-point all-cause mortality during follow-up. As secondary main end-points, we included any readmission or any post-COVID-19 symptom. Clinical features and follow-up events are compared between those with and without cardiovascular disease. Factors with p < 0.05 in the univariate analysis were entered into the multivariate analysis to determine independent prognostic factors. Results: HOPE-2 closed on 31 December 2021, with 9299 patients hospitalized with COVID-19, and 1805 died during this acute phase. Finally, 7014 patients with heart disease data were included in the present analysis, from 56 centers in 8 countries. Heart disease (+) patients were older (73 vs. 58 years old), more frequently male (63 vs. 56%), had more comorbidities than their counterparts, and suffered more frequently from post-COVID-19 complications and higher mortality (OR heart disease: 2.63, 95% CI: 1.81–3.84). Vaccination was found to be an independent protector factor (HR all-cause death: 0.09; 95% CI: 0.04–0.19). Conclusions: After surviving the acute phase, patients with underlying heart disease continue to present a more complex clinical profile and worse outcomes including increased mortality. The COVID-19 vaccine could benefit survival in patients with heart disease during follow-up.

Background COVID‐19 is an infectious illness, featured by an increased risk of thromboembolism. However, no standard antithrombotic therapy is currently recommended for patients hospitalized with COVID‐19. The aim of this study was to evaluate safety and efficacy of additional therapy with aspirin over prophylactic anticoagulation (PAC) in patients hospitalized with COVID‐19 and its impact on survival. Methods and Results A total of 8168 patients hospitalized for COVID‐19 were enrolled in a multicenter‐international prospective registry (HOPE COVID‐19). Clinical data and in‐hospital complications, including mortality, were recorded. Study population included patients treated with PAC or with PAC and aspirin. A comparison of clinical outcomes between patients treated with PAC versus PAC and aspirin was performed using an adjusted analysis with propensity score matching. Of 7824 patients with complete data, 360 (4.6%) received PAC and aspirin and 2949 (37.6%) PAC. Propensity‐score matching yielded 298 patients from each group. In the propensity score‐matched population, cumulative incidence of in‐hospital mortality was lower in patients treated with PAC and aspirin versus PAC (15% versus 21%, Log Rank P =0.01). At multivariable analysis in propensity matched population of patients with COVID‐19, including age, sex, hypertension, diabetes, kidney failure, and invasive ventilation, aspirin treatment was associated with lower risk of in‐hospital mortality (hazard ratio [HR], 0.62; [95% CI 0.42–0.92], P =0.018). Conclusions Combination PAC and aspirin was associated with lower mortality risk among patients hospitalized with COVID‐19 in a propensity score matched population compared to PAC alone.

Abstract Background Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) uses angiotensin-converting enzyme 2 (ACE2) receptor as a means to enter the host. High density of ACE2 receptor in vascular endothelial cells may explain why vascular complications related to endothelial dysfunction occur in COVID-19. However, in vivo assessment of vascular endothelial function during COVID-19 has not been reported. Objective To investigate the vascular endothelial function and its temporal changes in COVID-19 patients. Methods In this prospective blinded study, systemic endothelial function was assessed using plethysmography-derived peripheral arterial tonometry (PAT). The reactive hyperemia index (LnRHI), a measure of endothelium-mediated hyperaemia, and the augmentation index, a measure of arterial vascular stiffness, were measured in 102 individuals across three study groups using PAT: group 1 (active infection), constituted by 20 patients hospitalised due to acute COVID-19; group 2 (past infection), constituted by 52 patients who had recovered from COVID-19; and group 3 (controls), constituted by 30 healthcare workers not infected by SARS-CoV-2. Additionally, among group 1, PAT assessment was repeated in 14 patients several weeks after recovery from acute COVID-19. PAT studies were analysed at a blinded fashion with respect to the assigned study group. Results Lower resting PAT amplitude was found in acute COVID-19 patients compared to the other groups (ratio of arterial tone signal between hyperemia to resting condition was 1.5 [interquartile range, 1.1] in group 1, 1.3 [0.3] in group 2 and 1.2 [0.3] in group 3, p=0.041). On the contrary, no significant differences between groups were found with respect to the hyperemic PAT amplitude (867.9 [486.1] in group 1, 944.7 [748.1] in group 2 and 819.3 [639.6] in group 3, p=0.444). Due to the lower resting PAT amplitude, there was a paradoxically significantly increased LnRHI during acute COVID-19 compared to past infection and controls (0.73 [0.32] vs. 0.53 [0.31] vs. 0.44 [0.23], respectively; p=0.013) (Figure A). Furthermore, among group 1 patients, LnRHI normalised markedly from acute COVID-19 to past infection stage (0.73 [0.32] vs. 0.49 [0.28], respectively; p=0.005) (Figure B). Augmentation index was significantly higher during acute COVID-19 compared to past COVID-19 and controls (9.6 [19.1] in group 1, 6.97 [18.6] in group 2 and −0.35 [20.53] in group 3; p=0.045 for COVID groups vs. controls). Conclusions Non-invasive assessment of systemic vascular endothelial function with PAT revealed significant differences between subjects with acute COVID-19, past COVID-19 and controls. Lower baseline PAT amplitude and high augmentation index suggest vasoconstriction at rest during the acute phase of COVID-19. These findings open new research opportunities to investigate the prognostic value of PAT in COVID-19 patients. Funding Acknowledgement Type of funding sources: None.

Background Standard therapy for COVID-19 is continuously evolving. Autopsy studies showed high prevalence of platelet-fibrin-rich microthrombi in several organs. The aim of the study was therefore to evaluate the safety and efficacy of antiplatelet therapy (APT) in hospitalised patients with COVID-19 and its impact on survival. Methods 7824 consecutive patients with COVID-19 were enrolled in a multicentre international prospective registry (Health Outcome Predictive Evaluation-COVID-19 Registry). Clinical data and in-hospital complications were recorded. Data on APT, including aspirin and other antiplatelet drugs, were obtained for each patient. Results During hospitalisation, 730 (9%) patients received single APT (93%, n=680) or dual APT (7%, n=50). Patients treated with APT were older (74±12 years vs 63±17 years, p<0.01), more frequently male (68% vs 57%, p<0.01) and had higher prevalence of diabetes (39% vs 16%, p<0.01). Patients treated with APT showed no differences in terms of in-hospital mortality (18% vs 19%, p=0.64), need for invasive ventilation (8.7% vs 8.5%, p=0.88), embolic events (2.9% vs 2.5% p=0.34) and bleeding (2.1% vs 2.4%, p=0.43), but had shorter duration of mechanical ventilation (8±5 days vs 11±7 days, p=0.01); however, when comparing patients with APT versus no APT and no anticoagulation therapy, APT was associated with lower mortality rates (log-rank p<0.01, relative risk 0.79, 95% CI 0.70 to 0.94). On multivariable analysis, in-hospital APT was associated with lower mortality risk (relative risk 0.39, 95% CI 0.32 to 0.48, p<0.01). Conclusions APT during hospitalisation for COVID-19 could be associated with lower mortality risk and shorter duration of mechanical ventilation, without increased risk of bleeding. Trial registration number NCT04334291.

AbstractObjectivesTo assess the Usefulness of oral anticoagulation therapy (OAT) in patients with coronary artery aneurysm (CAA).BackgroundData on the most adequate antithrombotic CAA management is lacking.MethodsPatients included in CAAR (Coronary Artery Aneurysm Registry, Clinical Trials.gov: NCT02563626) were selected. Patients were divided in OAT and non‐OAT groups, according to anticoagulation status at discharge and 2:1 propensity score matching with replacement was performed. The primary endpoint of the analysis was a composite and mutual exclusive endpoint of myocardial infarction, unstable angina (UA), and aneurysm thrombosis (coronary ischemic endpoint). Net adverse clinical events, major adverse cardiovascular events, their single components, cardiovascular death, re‐hospitalizations for heart failure, stroke, aneurysm thrombosis, and bleeding were the secondary ones.ResultsOne thousand three hundred thirty‐one patients were discharged without OAT and 211 with OAT. In the propensity‐matched sample (390 patients in the non‐OAT group, 195 patients in the OAT group), after 3 years of median follow‐up (interquartile range 1–6 years), the rate of the primary endpoint (coronary ischemic endpoint) was significantly less in the OAT group as compared to non‐OAT group (8.7 vs. 17.2%, respectively; p = .01), driven by a significant reduction in UA (4.6 vs. 10%, p < .01) and aneurysm thrombosis (0 vs. 3.1%, p = .03), along with a non‐significant reduction in MI (4.1 vs. 7.7%, p = .13). A non‐significant increase in bleedings, mainly BARC type 1 (55%), was found in the OAT‐group (10.3% in the non‐OAT vs. 6.2% in the OAT group, p = .08).ConclusionOAT decreases the composite endpoint of UA, myocardial infarction, and aneurysm thrombosis in patients with CAA, despite a non‐significant higher risk of bleeding.

Background and Purpose— We aimed to assess if renal function can aid in risk stratification for ischemic stroke or transient ischemic attack (TIA) recurrence and death in patients with embolic stroke of undetermined source (ESUS). Methods— We pooled 12 ESUS datasets from Europe and America. Renal function was evaluated using the estimated glomerular filtration rate (eGFR) and analyzed in continuous, binary, and categorical way. Cox-regression analyses assessed if renal function was independently associated with the risk for ischemic stroke/TIA recurrence and death. The Kaplan-Meier product limit method estimated the cumulative probability of ischemic stroke/TIA recurrence and death. Results— In 1530 patients with ESUS followed for 3260 patient-years, there were 237 recurrences (15.9%) and 201 deaths (13.4%), corresponding to 7.3 ischemic stroke/TIA recurrences and 5.6 deaths per 100 patient-years, respectively. Renal function was not associated with the risk for ischemic stroke/TIA recurrence when forced into the final multivariate model, regardless if it was analyzed as continuous (hazard ratio, 1.00; 95% CI, 0.99–1.00 for every 1 mL/min), binary (hazard ratio, 1.27; 95% CI, 0.87–1.73) or categorical covariate (likelihood-ratio test 2.59, P =0.63 for stroke recurrence). The probability of ischemic stroke/TIA recurrence across stages of renal function was 11.9% for eGFR ≥90, 16.6% for eGFR 60–89, 21.7% for eGFR 45–59, 19.2% for eGFR 30–44, and 24.9% for eGFR <30 (likelihood-ratio test 2.59, P =0.63). The results were similar for the outcome of death. Conclusions— The present study is the largest pooled individual patient-level ESUS dataset, and does not provide evidence that renal function can be used to stratify the risk of ischemic stroke/TIA recurrence or death in patients with ESUS.

AbstractBackgroundTranscatheter aortic valve replacement (TAVR) is typically performed under general anesthesia (GA). However, there is increasing data supporting the safety of performing TAVR under local anesthesia/conscious sedation (LA). We performed a meta‐analysis to gain better understanding of the safety and efficacy of LA versus GA in patients with severe aortic stenosis undergoing TAVR.Methods and ResultsWe comprehensively searched EMBASE, PubMed, and Web of Science. Effect sizes were summarized using risk ratios (RRs) difference of the mean (DM), and 95% CIs (confidence intervals) for dichotomous and continuous variables respectively. Twenty‐six studies and 10,572 patients were included in the meta‐analysis. The use of LA for TAVR was associated with lower overall 30‐day mortality (RR, 0.73; 95% CI, 0.57–0.93; P = 0.01), use of inotropic/vasopressor drugs (RR, 0.45; 95% CI, 0.28–0.72; P < 0.001), hospital length of stay (LOS) (DM, −2.09; 95% CI, −3.02 to −1.16; P < 0.001), intensive care unit LOS (DM, −0.18; 95% CI, −0.31 to −0.04; P = 0.01), procedure time (DM, −25.02; 95% CI, −32.70 to −17.35; P < 0.001); and fluoroscopy time (DM, −1.63; 95% CI, −3.02 to −0.24; P = 0.02). No differences were observed between LA and GA for stroke, cardiovascular mortality, myocardial infarction, permanent pacemaker implantation, acute kidney injury, paravalvular leak, vascular complications, major bleeding, procedural success, conduction abnormalities, and annular rupture.ConclusionOur meta‐analysis suggests that use of LA for TAVR is associated with a lower 30‐day mortality, shorter procedure time, fluoroscopy time, ICU LOS, hospital length of stay, and reduced need for inotropic support.

Coronary artery aneurysm is defined as a coronary dilation that exceeds the diameter of adjacent segments or the diameter of the patient's largest normal coronary vessel by 1.5×. It is an uncommon disease that has been diagnosed with increasing frequency since the widespread appearance of coronary angiography. The published incidence varies from 1.5% to 5%, suggesting male dominance and a predilection for the right coronary artery. Although several causes have been described, atherosclerosis accounts for ≥50% of coronary aneurysms in adults. Reported complications include thrombosis and distal embolization, rupture, and vasospasm, causing ischemia, heart failure, or arrhythmias. The natural history and prognosis remain unknown, as definitive data are scarce. Controversies persist regarding the use of medical management (antithrombotic therapy) or interventional/surgical procedures. Only some case reports or small case series are available about this condition. The Coronary Artery Aneurysm Registry (CAAR; http://www.ClinicalTrials.gov NCT02563626) is a multicenter international ambispective registry that aims to provide insights on anatomic, epidemiologic, and clinical aspects of this substantially unknown entity. In addition, the registry will assess management strategies (conservative, interventional, or surgical) and their short‐ and long‐term results in a large cohort of patients.Clinical Trial registration: ClinicalTrials.gov. Unique identifier: NCT02563626.