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Aims: The objective of the study was to determine the effect of renin-angiotensin system inhibitors (RASI) on the survival of subgroups of patients with aortic stenosis after transcatheter aortic valve implantation (TAVI) and to assess the impact of types and dosages of RASI on outcomes., Methods and Results: This single-centre, retrospective analysis included 2862 patients (n = 2227 with RASI and n = 635 without RASI) after successful TAVI. Propensity score matching established comparable patient populations (n = 625 per group). Survival was analysed by Kaplan-Meier curves and Cox regression and was corrected for baseline, procedural, and medical parameters. Self-reported adherence to RASI therapy 3 months after hospital discharge was 94%. Three-year all-cause mortality rates were 12.3% and 20.2% for patients with or without RASI, respectively (log-rank <0.001). In the matched study populations, mortality rates were 14.2% vs. 20.0% (log-rank <0.03). RASI was particularly beneficial in patients with ejection fraction <40% [adjusted hazard ratio (HR) and 95% confidence interval 0.50 (0.29-0.87)], EuroScore II ≥4% [HR 0.47 (0.35-0.65)], or low-flow, low-gradient aortic stenosis [HR 0.53 (0.31-0.93)] who were also on beta-blockers and statins. An association between discharge dosage and survival was observed, with HR 0.75 (0.58-0.96) and 0.57 (0.44-0.72) for patients on <50% and ≥50% target dose, respectively. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) reduced mortality rates similarly (13.9% vs. 9.8%, log-rank 0.103)., Conclusions: The beneficial association between RASI after TAVI and improved survival during follow-up is particularly evident in high-risk patients and may be dose dependent. No superiority was noted in the effectiveness of ACEI or ARB., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aim: Presepsin is a sensitive biomarker for the diagnosis and estimation of prognosis in septic patients. The prognostic role of presepsin in patients undergoing transcatheter aortic valve implantation (TAVI) has never been investigated. Patients, materials & methods: In 343 patients, presepsin and N-terminal pro-B-type natriuretic peptide were measured before TAVI. One-year all-cause mortality was used as outcome measure. Results: Patients with high presepsin levels were more likely to succumb than patients with low presepsin values (16.9% vs 12.3%; p = 0.015). Elevated presepsin remained a significant predictor of 1-year all-cause mortality (odds ratio: 2.2 [95% CI: 1.12-4.29]; p = 0.022) after adjustment. N-terminal pro-B-type natriuretic peptide did not predict 1-year all-cause mortality. Conclusion: Elevated baseline presepsin levels are an independent predictor of 1-year mortality in TAVI patients.

Objective: The present study was designed to investigate the dynamics of right atrial pressure (RAP) and mid-regional pro-atrial natriuretic peptide (MR-proANP) during physical exercise in patients with chronic thromboembolic pulmonary hypertension (CTEPH) and to determine whether these parameters might serve as a tool to measure exercise-dependent atrial stress as an indicator of right heart failure., Methods: This prospective observational cohort study included 100 CTEPH patients who underwent right heart catheterization during physical exercise (eRHC). Blood samples for MR-proANP measurement were taken prior, during, and after eRHC. MR-proANP levels were correlated to RAP levels at rest, at peak exercise (eRAP), and during recovery. RAP at rest ≤7 mmHg was defined as normal and eRAP >15 mmHg as suggestive of right heart failure., Results: During eRHC mean RAP increased from 6 mmHg (standard deviation, SD 4) to 16 mmHg (SD 7; p < 0.001). MR-proANP levels and dynamics correlated with RAP at rest (r s  = 0.61; p < 0.001) and at peak exercise (r s  = 0.66; p < 0.001). Logistic regression analysis revealed the peak MR-proANP level (B = 0.058; p = 0.004) and the right atrial area (B = 0.389; p < 0.001) to be associated with eRAP dynamics. A peak MR-proANP level ≥139 pmol/L (AUC = 0.81) and recovery level ≥159 pmol/L (AUC = 0.82) predicted an eRAP >15 mmHg. Physical exercise unmasked right heart failure in 39% of patients with normal RAP at rest; these patients were also characterized by a more distinct increase in MR-proANP levels (p = 0.005) and higher peak (p < 0.001) and recovery levels (p < 0.001)., Conclusions: RAP and MR-proANP dynamics unmask manifest and latent right heart failure in CTEPH patients., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: The gold standard treatment of patients with chronic thromboembolic pulmonary hypertension (CTEPH) is pulmonary endarterectomy (PEA). Little is known about the influence of advanced age on surgical outcome. Therefore, the aim of this study was to investigate the impact of patient's age on postoperative morbidity, mortality, and quality of life in a German referral center., Methods: Prospectively collected data from 386 consecutive patients undergoing PEA between 01/2014 and 12/2016 were analyzed. Patients were divided into three groups according to their age: group 1: ≤ 50 years, group 2: > 50 ≤ 70 years, group 3: > 70 years., Results: After PEA, distinct improvements in pulmonary hemodynamics, physical capacity (World Health Organization [WHO] functional class and 6-minute walking distance) and quality of life were found in all groups. There were more complications in elderly patients with longer time of invasive ventilation, intensive care, and in-hospital stay. However, the in-hospital mortality was comparable (0% in group 1, 2.6% in group 2, and 2.1% in group 3 [ p  = 0.326]). Furthermore, the all-cause mortality at 1 year was 1.1% in group 1, 3.2% in group 2, and 6.3% in group 3 ( p  = 0.122)., Conclusions: PEA is an effective treatment for CTEPH patients of all ages accompanied by low perioperative and 1-year mortality. CTEPH patients in advanced age carefully selected by thorough preoperative evaluation should be offered PEA in expert centers to improve quality of life, symptoms, and pulmonary hemodynamics., Competing Interests: CBW has received speaker fees and/or consultant honoraria from Actelion, AOP Orphan Pharmaceuticals AG, Bayer AG, BTG, MSD, and Pfizer.DB has nothing to disclose.KA has nothing to disclose.HAG has reported receiving fees for serving as a board member for Bellerophon Pulse Technologies, Medscape, OMT, UCB Celltech, and Web MD Global; receiving consultancy fees and fees for serving on a steering committee for Actelion Pharmaceuticals, Bayer, Gilead Sciences, GlaxoSmithKline, Merck, Novartis, and Pfizer; receiving lecture fees from Actelion Pharmaceuticals, Bayer, GlaxoSmithKline, Merck, Novartis, and Pfizer; and receiving grant support from Actelion Pharmaceuticals, Bayer, Novartis, and Pfizer.ML reports consultant and speaker fees from Actelion, Bayer, Thermo Fisher Scientific, Daiichi-Sankyo, MSD and Bristol-Myers Squibb-Pfizer, project funding from Thermo Fisher Scientific and institutional funding from the German Federal Ministry of Education and Research (BMBF 01EO1003 and 01EO1503).CL has received speaker fees from Abbott, Astra Zeneca, Bayer, Berlin-Chemie, Boehringer Ingelheim, Daiichi Sankyo, Elixir Medical, and Pfizer.DP has received speaker fees from AstraZeneca, and Kerckhoff-Forschungs GmbH, and received grant support from Johnson & Johnson and Medtronic.EM has received speaker fees and/or honoraria for consultations from Actelion, Bayer, GSK, MSD, and Pfizer.SDK has nothing to disclose.SG has received speaker fees from Actelion, Bayer, GSK, MSD and Pfizer., (Thieme. All rights reserved.)

Background: This study analyzed the utility of soluble ST2 (sST2) and GDF-15 as biomarkers of right ventricular (RV) function in patients with pulmonary hypertension (PH). Methods: GDF-15 and sST2 serum concentrations were measured in patients with PH (n = 628), dilated cardiomyopathy (n = 31) and left ventricular hypertrophy (n = 47), and in healthy controls (n = 61). Results: Median sST2 and GDF-15 levels in patients with left ventricular hypertrophy were higher than in patients with PH and dilated cardiomyopathy. In tertile analysis GDF-15 >1363 pg/ml and sST2 >38 ng/ml were associated with higher N-terminal pro-brain natriuretic peptide, RV systolic dysfunction, RV-pulmonary arterial uncoupling and hemodynamic impairment. Conclusion: GDF-15 and sST2 are potential biomarkers of RV dysfunction in patients with PH.

Aims: To establish the safety and efficacy of different dual antiplatelet therapy (DAPT) combinations in patients with acute coronary syndrome (ACS) according to their baseline ischaemic and bleeding risk estimated with a machine learning derived model [machine learning-based prediction of adverse events following an acute coronary syndrome (PRAISE) score]., Methods and Results: Incidences of death, re-acute myocardial infarction (re-AMI), and Bleeding Academic Research Consortium 3-5 bleeding with aspirin plus different P2Y12 inhibitors (clopidogrel or potent P2Y12 inhibitors: ticagrelor or prasugrel) were appraised among patients of the PRAISE data set grouped in four subcohorts: low-to-moderate ischaemic and bleeding risk; low-to-moderate ischaemic risk and high bleeding risk; high ischaemic risk and low-to-moderate bleeding risk; and high ischaemic and bleeding risk. Hazard ratios (HRs) for the outcome measures were derived with inverse probability of treatment weighting adjustment. Among patients with low-to-moderate bleeding risk, clopidogrel was associated with higher rates of re-AMI in those at low-to-moderate ischaemic risk [HR 1.69, 95% confidence interval (CI) 1.16-2.51; P = 0.006] and increased risk of death (HR 3.2, 1.45-4.21; P = 0.003) and re-AMI (HR 2.23, 1.45-3.41; P < 0.001) in those at high ischaemic risk compared with prasugrel or ticagrelor, without a difference in the risk of major bleeding. Among patients with high bleeding risk, clopidogrel showed comparable risk of death, re-AMI, and major bleeding vs. potent P2Y12 inhibitors, regardless of the baseline ischaemic risk., Conclusion: Among ACS patients with non-high risk of bleeding, the use of potent P2Y12 inhibitors is associated with a lower risk of death and recurrent ischaemic events, without bleeding excess. Patients deemed at high bleeding risk may instead be safely addressed to a less intensive DAPT strategy with clopidogrel., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Balloon pulmonary angioplasty (BPA) is an emerging interventional treatment for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) that targets subsegmental branches of the pulmonary artery. As the reported complication rates are high, the aim of the present study was to evaluate the effects of certain complications on the outcome after treatment., Methods: From March 2014 to December 2019, a total of 235 patients with inoperable CTEPH underwent BPA. Of these patients, 140 were included who completed a follow-up examination 6 months after the last intervention; another 2 patients deceased due to complications of BPA., Results: A high baseline pulmonary vascular resistance (PVR) >6.6 WU correlated with a higher rate of complications (mostly pulmonary artery perforations). Wire perforation during BPA did not correlate with worse outcome in terms of PVR reduction. The complication rate per intervention decreased from 21% to 14% during the 5 year period of the study., Conclusions: Complications are frequently observed in BPA, but the mortality rate is very low in expert centers. Importantly, the occurrence of complications does not portend a worse outcome., (Copyright © 2022 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Whether the access site influences the comparative efficacy and safety of ticagrelor and prasugrel in patients with acute coronary syndrome (ACS) undergoing invasive treatment strategy remains unstudied., Methods: This post-hoc analysis included ACS patients undergoing invasive treatment via radial or femoral access and randomized to either ticagrelor or prasugrel in the ISAR-REACT 5 trial. The primary efficacy endpoint was the composite of death, myocardial infarction (MI) or stroke, safety endpoint was BARC 3 to 5 bleeding. Outcomes were assessed out to 12 months after randomization., Results: Out of 4018 patients, 3984 underwent invasive treatment via radial or femoral access. 1479 had coronary angiography via radial access (ticagrelor, N = 748; prasugrel, N = 731) and 2505 via femoral access (ticagrelor, N = 1245; prasugrel, N = 1260). There was no interaction between access route and assignment to either ticagrelor or prasugrel regarding the primary efficacy or safety endpoints (P for interaction≥0.616). In the radial group, the primary efficacy endpoint (7.6% versus 5.8%, HR: 1.32 [0.88-1.97], P = 0.151) and the safety endpoint (4.3% versus 3.0%, HR: 1.36, [0.73-1.31], P = 0.300) were not statistically different in patients receiving either ticagrelor or prasugrel. In the femoral group, the primary efficacy endpoint occurred more frequently in patients assigned to ticagrelor as compared to prasugrel (10.3% versus 7.3%, HR: 1.44 [1.10-1.88], P = 0.006) without significant difference in terms of safety endpoint (6.4% versus 5.8%, HR: 1.14, [0.81-1.60], P = 0.470)., Conclusions: In patients with ACS undergoing an invasive treatment strategy, the access route does not influence the comparative efficacy and safety of ticagrelor and prasugrel., Clinical Trial Registration: NCT01944800., (Copyright © 2021. Published by Elsevier Inc.)

Epicardial fat tissue (EFT) is a highly metabolically active fat depot surrounding the heart and coronary arteries that is related to early atherosclerosis and adverse cardiac events. We aimed to investigate the relationship between the amount of EFT and preexisting cardiac conduction abnormalities (CCAs) and the need for new postinterventional pacemaker in patients with severe aortic stenosis planned for transcatheter aortic valve implantation (TAVI). A total of 560 consecutive patients (54% female) scheduled for TAVI were included in this retrospective study. EFT volume was measured via a fully automated artificial intelligence software (QFAT) using computed tomography (CT) performed before TAVI. Baseline CCAs [first-degree atrioventricular (AV) block, right bundle branch block (RBBB), and left bundle branch block (LBBB)] were diagnosed according to 12-lead ECG before TAVI. Aortic valve calcification was determined by the Agatston score assessed in the pre-TAVI CT. The median EFT volume was 129.5 ml [IQR 94-170]. Baseline first-degree AV block was present in 17%, RBBB in 10.4%, and LBBB in 10.2% of the overall cohort. In adjusted logistic regression analysis, higher EFT volume was associated with first-degree AV block (OR 1.006 [95% CI 1.002-1.010]; p = 0.006) and the need for new pacemaker implantation after TAVI (OR 1.005 [95% CI 1.0-1.01]; p = 0.035) but not with the presence of RBBB or LBBB. EFT volume did not correlate with the Agatston score of the aortic valve. Greater EFT volume is associated independently with preexisting first-degree AV block and new pacemaker implantation in patients undergoing TAVI. It may play a causative role in degenerative processes and the susceptibility of the AV conduction system., (© 2021. The Author(s).)

Left ventricular (LV) longitudinal, circumferential, and radial motion can be measured using feature tracking of cardiac magnetic resonance (CMR) images. The aim of our study was to detect differences in LV mechanics between patients with dilated cardiomyopathy (DCM) and ischemic cardiomyopathy (ICM) who were matched using a propensity score-based model. Between April 2017 and October 2019, 1224 patients were included in our CMR registry, among them 141 with ICM and 77 with DCM. Propensity score matching was used to pair patients based on their indexed end-diastolic volume (EDVi), ejection fraction (EF), and septal T1 relaxation time (psmatch2 module L Feature tracking provided six parameters for global longitudinal, circumferential, and radial strain with corresponding strain rates in each group. Strain parameters were compared between matched pairs of ICM and DCM patients using paired t tests. Propensity score matching yielded 72 patients in each group (DCM mean age 58.6 ± 11.6 years, 15 females; ICM mean age 62.6 ± 13.2 years, 11 females, p = 0.084 and 0.44 respectively; LV-EF 32.2 ± 13.5% vs. 33.8 ± 12.1%, p = 0.356; EDVi 127.2 ± 30.7 ml/m 2 vs. 121.1 ± 41.8 ml/m 2 , p = 0.251; native T1 values 1165 ± 58 ms vs. 1167 ± 70 ms, p = 0.862). There was no difference in global longitudinal strain between DCM and ICM patients (- 10.9 ± 5.5% vs. - 11.2 ± 4.7%, p = 0.72), whereas in DCM patients there was a significant reduction in global circumferential strain (- 10.0 ± 4.5% vs. - 12.2 ± 4.7%, p = 0.002) and radial strain (17.1 ± 8.51 vs. 21.2 ± 9.7%, p = 0.039). Our data suggest that ICM and DCM patients have inherently different myocardial mechanics, even if phenotypes are similar. Our data show that GCS is significantly more impaired in DCM patients. This feature may help in more thoroughly characterizing cardiomyopathy patients., (© 2021. The Author(s).)

The aim of this study was to evaluate the cartilage intermediate layer protein 1 (CILP1) as a biomarker of right ventricular dysfunction in patients with ischemic cardiomyopathy (ICM). CILP1 plasma concentrations were measured in 98 patients with ICM and 30 controls without any cardiac abnormalities. All participants underwent cardiac magnetic resonance imaging. Median CILP1 concentrations were higher in ICM than in controls. In the tertile analysis, low right ventricular ejection fraction (RVEF) and high right ventricular end-systolic volume index and N-terminal pro-brain natriuretic peptide (NT-proBNP) were associated with higher CILP1 levels in ICM. However, there were no associations between CILP1 concentrations and left ventricular (LV) parameters in this group. In receiver-operating characteristic (ROC) analysis CILP1 was a good predictor of RVEF < 40% with an optimal cut-off value of 3545 pg/ml in ICM, whereas it was not predictive of LV ejection fraction (LVEF) < 40% (area under the curve [AUC] = 0.57) There was no significant difference between the ROC curves of CILP1 (AUC = 0.72) and NT-proBNP (AUC = 0.77) for RVEF < 40% ( p  = 0.42). In multivariable regression analysis, RVEF was the only independent predictor of elevated CILP1. CILP1 and LVEF were the only independent predictors of RVEF < 40% in ICM. Our analysis demonstrates the potential role of CILP1 as a novel cardiac biomarker of prognostically relevant RV dysfunction in patients with ICM., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Authors. Pulmonary Circulation published by Wiley Periodicals LLC on behalf of the Pulmonary Vascular Research Institute.)

Introduction: Mechanical circulatory support (MCS) devices are increasingly used as a treatment option in resuscitation or in patients with cardiogenic shock (CS). Prophylactic implantation in high-risk percutaneous coronary interventions (HRPCI) is another upcoming indication. The i-cor ECG-synchronized cardiac assist device combines the hemodynamic support of a veno-arterial extracorporeal membrane oxygenation (VA-ECMO) with the ability to generate a pulsatile flow and thus decreasing adverse effects of VA-ECMO on myocardial function. Aim of this study was to obtain data concerning feasibility, safety and outcomes in both indications., Methods: A total of 47 patients (34 HRPCI, 13 CS) were included in nine German centers and participated in this study. Demographic and clinical parameters, procedural as well as follow-up data were prospectively recorded and analyzed., Results: Device implantation and initiation of ECG-synchronized cardiac assist was technical successful in all cases and no failures of the consoles or disposable parts were observed. Furthermore, intended percutaneous coronary interventions and successful weaning from cardiac assist was achieved in 97.1% of HRPCI patients. We observed a 30d-survival of 94.1% in the HRPCI group and 69.2% in the CS group. Main complications in both groups were bleeding events (14.7% HRPCI, 23.1% CS) and critical limb ischemia (2.9% HRPCI, 38.5% CS)., Conclusion: The i-cor ECG-synchronized cardiac assist device appears safe and feasible showing clinical outcomes comparable to existing data in the setting of high-risk percutaneous coronary interventions and acute cardiogenic shock. Further prospective trials are warranted to identify optimal patient and interventional characteristics that will benefit most of this novel kind of mechanical circulatory support., (© 2021 International Center for Artificial Organs and Transplantation and Wiley Periodicals LLC.)

Purpose: The aim of this study was to assess effects of balloon pulmonary angioplasty (BPA) on right ventricular (RV) mechanical dysfunction in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH) via MRI., Method: MRI at 1.5 Tesla and right heart catheterization were performed before and 6 months after BPA in 30 CTEPH patients (mean age 63.4 ± 10.6 years; 17 female). Feature-tracking strain analysis, including global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain, was performed and compared with right ventricular function, myocardial remodelling (assessed by native T1 times), and pulmonary haemodynamics (mean pulmonary arterial pressure and pulmonary vascular resistance)., Results: RVEF (35.9% to 48.4%) increased and mPAP (42.1 mmHg to 33.1 mmHg) and PVR (551.8 to 377.7 dyn∙s/cm 5 ) decreased after BPA (all p < 0.0001). Moreover, RV strain increased (GLS -19.9 to -24.0%, p = 0.0003; GCS -9.4 to -11.0%, p = 0.0022; GRS 38.2 to 50.7%, p = 0.001) and septal native area-adjusted T1 time (AA-T1) decreased (1019.4 to 988.7 ms, p < 0.0001). GLS revealed the best correlations with RVEF (before BPA r = -0.75; after BPA r = -0.54), mPAP (r = 0.36; r = 0.52), PVR (r = 0.49; r = 0.48), and AA-T1 (r = 0.44; 0.19)., Conclusion: RV mechanical dysfunction, pulmonary haemodynamics, and myocardial remodelling are markedly improved by BPA. Moreover, RV strain values showed good correlations with RV function, pulmonary haemodynamics, and myocardial remodelling. Therefore, strain analysis might provide new insights regarding therapy outcome, monitoring, and prognosis., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: The five-item PRECISE-DAPT, integrating age, haemoglobin, white-blood-cell count, creatinine clearance, and prior bleeding, predicts bleeding risk in patients on dual antiplatelet therapy (DAPT) after stent implantation. We sought to assess whether the bleeding risk prediction offered by the PRECISE-DAPT remains valid among patients receiving ticagrelor monotherapy from 1 month onwards after coronary stenting instead of standard DAPT and having or not having centrally adjudicated bleeding endpoints., Methods and Results: The PRECISE-DAPT was calculated in 14 928 and 7134 patients from GLOBAL LEADERS and GLASSY trials, respectively. The ability of the score to predict Bleeding Academic Research Consortium 3 or 5 bleeding was assessed and compared among patients on ticagrelor monotherapy (experimental strategy) or standard DAPT (reference strategy) from 1 month after drug-eluting stent implantation. Bleeding endpoints were investigator-reported or centrally adjudicated in GLOBAL LEADERS and GLASSY, respectively. At 2 years, the c-indexes for the score among patients treated with the experimental or reference strategy were 0.67 [95% confidence interval (CI): 0.63-0.71] vs. 0.63 (95% CI: 0.59-0.67) in GLOBAL LEADERS (P = 0.27), and 0.67 (95% CI: 0.61-0.73) vs. 0.66 (95% CI: 0.61-0.72) in GLASSY (P = 0.88). Decision curve analysis showed net benefit using the PRECISE-DAPT to guide bleeding risk assessment under both treatment strategies. Results were consistent between investigator-reported and adjudicated endpoints and using the simplified four-item PRECISE-DAPT., Conclusion: The PRECISE-DAPT offers a prediction model that proved similarly effective to predict clinically relevant bleeding among patients on ticagrelor monotherapy from 1 month after coronary stenting compared with standard DAPT and appears to be unaffected by the presence or absence of adjudicated bleeding endpoints., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

Background: Myocardial infarction is a frequent cause of out-of-hospital cardiac arrest. However, the benefits of early coronary angiography and revascularization in resuscitated patients without electrocardiographic evidence of ST-segment elevation are unclear., Methods: In this multicenter trial, we randomly assigned 554 patients with successfully resuscitated out-of-hospital cardiac arrest of possible coronary origin to undergo either immediate coronary angiography (immediate-angiography group) or initial intensive care assessment with delayed or selective angiography (delayed-angiography group). All the patients had no evidence of ST-segment elevation on postresuscitation electrocardiography. The primary end point was death from any cause at 30 days. Secondary end points included a composite of death from any cause or severe neurologic deficit at 30 days., Results: A total of 530 of 554 patients (95.7%) were included in the primary analysis. At 30 days, 143 of 265 patients (54.0%) in the immediate-angiography group and 122 of 265 patients (46.0%) in the delayed-angiography group had died (hazard ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.63; P = 0.06). The composite of death or severe neurologic deficit occurred more frequently in the immediate-angiography group (in 164 of 255 patients [64.3%]) than in the delayed-angiography group (in 138 of 248 patients [55.6%]), for a relative risk of 1.16 (95% CI, 1.00 to 1.34). Values for peak troponin release and for the incidence of moderate or severe bleeding, stroke, and renal-replacement therapy were similar in the two groups., Conclusions: Among patients with resuscitated out-of-hospital cardiac arrest without ST-segment elevation, a strategy of performing immediate angiography provided no benefit over a delayed or selective strategy with respect to the 30-day risk of death from any cause. (Funded by the German Center for Cardiovascular Research; TOMAHAWK ClinicalTrials.gov number, NCT02750462.)., (Copyright © 2021 Massachusetts Medical Society.)

Background: In chronic thromboembolic pulmonary hypertension, right heart failure determines outcome. Balloon pulmonary angioplasty therapy allows right heart recovery, which can be monitored by cardiac magnetic resonance imaging. This study evaluates whether cardiac biomarkers (NT-proBNP, MR-proANP, sST2, and PAPP-A) are associated with cardiac magnetic resonance imaging findings prior to and after balloon pulmonary angioplasty therapy., Methods: This observational cohort study enrolled 22 chronic thromboembolic pulmonary hypertension patients who underwent balloon pulmonary angioplasty therapy and completed a six-month follow-up including cardiac magnetic resonance imaging. Biomarker levels were compared with findings for right heart morphology and function derived from cardiac magnetic resonance imaging., Results: Pulmonary hemodynamics improved after balloon pulmonary angioplasty therapy [pulmonary vascular resistance: 7.7 (6.0-9.0) vs. 4.7 (3.5-5.5) wood units, p < 0.001; mean pulmonary artery pressure 41 (38-47) vs. 32 (28-37) mmHg, p < 0.001]. Cardiac magnetic resonance imaging findings indicated right heart maladaptation at baseline and recovery after therapy [right ventricular end-diastolic volume 192 (141-229) ml vs. 143 (128-172) ml, p = 0.002; right ventricular end-systolic volume 131 (73-157) ml vs. 77 (61-99) ml (p < 0.001); right ventricular ejection fraction (RVEF) 34 (28-41) % vs. 52 (41-54) %; p < 0.001]. Biomarker level cut-offs [NT-proBNP 347 ng/L (area under the curve (AUC) 0.91), MR-proANP 230 pg/L (AUC 0.78), PAPP-A 14.5 mU/L (AUC 0.81), and sST2 48.0 ng/ml (AUC 0.88)] indicated a RVEF ≤ 35% at baseline. The dynamics of NT-proBNP (rs = -0.79; p < 0.001), MR-proANP (rs = -0.80; p < 0.001), and sST2 (rs = -0.49; p = 0.02) correlated inversely with the improvement in RVEF after therapy. A relative decrease of NT-proBNP < 53% (AUC 0.86) and MR-proANP < 24% (AUC 0.82) indicated a limited RVEF response., Conclusions: In chronic thromboembolic pulmonary hypertension patients, cardiac magnetic resonance imaging findings illustrate right heart failure and recovery after balloon pulmonary angioplasty therapy. Cardiac biomarker levels correlate with right heart parameters at baseline and their dynamics after therapy., (© The Author(s) 2021.)

Background: Defective angiogenesis, incomplete thrombus revascularisation and fibrosis are considered critical pathomechanisms of chronic thromboembolic pulmonary hypertension (CTEPH) after pulmonary embolism. Angiopoietin-2 (ANGPT2) has been shown to regulate angiogenesis, but its importance for thrombus resolution and remodelling is unknown., Methods: ANGPT2 plasma concentrations were measured in patients with CTEPH (n=68) and acute pulmonary embolism (n=84). Tissue removed during pulmonary endarterectomy (PEA) for CTEPH was analysed (immuno)histologically. A mouse model of inferior vena cava ligation was used to study the kinetics of venous thrombus resolution in wild-type mice receiving recombinant ANGPT2 via osmotic pumps, and in transgenic mice overexpressing ANGPT2 in endothelial cells., Results: Circulating ANGPT2 levels were higher in CTEPH patients compared to patients with idiopathic pulmonary arterial hypertension and healthy controls, and decreased after PEA. Plasma ANGPT2 levels were elevated in patients with pulmonary embolism and diagnosis of CTEPH during follow-up. Histological analysis of PEA specimens confirmed increased ANGPT2 expression, and low levels of phosphorylated TIE2 were observed in regions with early-organised pulmonary thrombi, myofibroblasts and fibrosis. Microarray and high-resolution microscopy analysis could localise ANGPT2 overexpression to endothelial cells, and hypoxia and transforming growth factor-β1 were identified as potential stimuli. Gain-of-function experiments in mice demonstrated that exogenous ANGPT2 administration and transgenic endothelial ANGPT2 overexpression resulted in delayed venous thrombus resolution, and thrombi were characterised by lower TIE2 phosphorylation and fewer microvessels., Conclusion: Our findings suggest that ANGPT2 delays venous thrombus resolution and that overexpression of ANGPT2 contributes to thrombofibrosis and may thus support the transition from pulmonary embolism to CTEPH., Competing Interests: Conflict of interest: L. Hobohm reports personal fees for lectures from MSD and Actelion, outside the submitted work. Conflict of interest: S. Kölmel has nothing to disclose. Conflict of interest: C. Niemann has nothing to disclose. Conflict of interest: P. Kümpers has nothing to disclose. Conflict of interest: V.J. Krieg has nothing to disclose. Conflict of interest: M.L. Bochenek has nothing to disclose. Conflict of interest: A.H. Lukasz has nothing to disclose. Conflict of interest: Y. Reiss has nothing to disclose. Conflict of interest: K-H. Plate has nothing to disclose. Conflict of interest: C. Liebetrau reports personal fees for lectures and consultancy from AstraZeneca, Bayer, Berlin Chemie, Boehringer Ingelheim, Daiichi-Sankyo, Pfizer–Bristol-Myers Squibb and Thermo-Fisher, outside the submitted work. Conflict of interest: C.B. Wiedenroth reports personal fees for lectures and consultancy from Actelion, Bayer, Pfizer, BTG and MSD, outside the submitted work. Conflict of interest: S. Guth reports personal fees for lectures and consultancy from Actelion, Bayer, GlaxoSmithKline, Pfizer and MSD, outside the submitted work. Conflict of interest: T. Münzel has nothing to disclose. Conflict of interest: G. Hasenfuß reports personal fees for lectures and consultancy from AstraZeneca, Corvia, Impulse Dynamics, Novartis, Servier, Berlin Chemie and Vifor Pharma; and editor honoraria from Springer International Publishing AG. Conflict of interest: P. Wenzel has nothing to disclose. Conflict of interest: E. Mayer reports personal fees for lectures and consultancy from Actelion, Bayer, MSD and Pfizer, outside the submitted work. Conflict of interest: S.V. Konstantinides reports grants from German Federal Ministry of Education and Research (BMBF 01EO1003 and BMBF 01EO1503), during the conduct of the study; personal fees for consultancy and lectures from Bayer, Boehringer Ingelheim, Daiichi-Sankyo, MSD and Pfizer–Bristol-Myers Squibb; and institutional grants from Actelion, Bayer, Boehringer Ingelheim, Daiichi-Sankyo and Pfizer–Bristol-Myers Squibb, outside the submitted work. Conflict of interest: K. Schäfer has nothing to disclose. Conflict of interest: M. Lankeit reports grants from German Federal Ministry of Education and Research (BMBF 01EO1003 and 01EO1503), during the conduct of the study; personal fees for consultancy and lectures from Actelion, Bayer, BRAHMS–Thermo-Fisher Scientific, Daiichi-Sankyo, MSD and Pfizer–Bristol-Myers Squibb, and research funding from BRAHMS–Thermo-Fisher Scientific., (Copyright ©The authors 2021. For reproduction rights and permissions contact permissions@ersnet.org.)

Purpose: Higher risk of bleeding with ticagrelor over clopidogrel in elderly patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) has been suggested. We assessed the incidence of major bleedings (MB), reinfarction (re-MI), and all-cause death to evaluate safety and efficacy of ticagrelor versus clopidogrel in such population., Methods: Real-world registries RENAMI and BleeMACS were merged. The pooled cohort was divided into two groups, clopidogrel versus ticagrelor. Statistical analysis considered patients <75 versus ≥75 years old. Endpoints were BARC 3-5 MB, re-MI, and all-cause death at 1-year follow-up. The study included 16,653 patients (13,153 < 75 and 3500 ≥ 75 years). Ticagrelor was underused in elderly patients (16.3% versus 20.8%, P < 0.001). Using propensity score matching (PSM), two treatment groups of 1566 patients were included in the final analysis., Results: Ticagrelor was able to prevent re-MI (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.2-0.6; P < 0.001) and all-cause death (HR, 0.60; 95% CI, 0.4-0.9; P = 0.026) irrespective of age. In patients ≥75 years, ticagrelor reduced all-cause death (HR, 0.32; 95% CI, 0.1-0.8; P = 0.012) and re-MI (HR, 0.25; 95% CI, 0.1-1.1, P = 0.072). Moreover, even with the limit of the low number of events, ticagrelor did not significantly increase the incidence of MB (HR, 1.49; 95% CI, 0.70-3.0; P = 0.257). At multiple Cox regression, age (HR, 1.03; 95% CI, 1.02-1.05; P < 0.001) resulted an independent risk factor for bleeding., Conclusion: In our study, reflecting the results from two large retrospective, real-world registries, Ticagrelor did not significantly increase MB compared with clopidogrel in elderly patients with ACS treated with PCI, while significantly improving 1-year survival. Further studies on elderly patients are suggested., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

The main aim of this study was to assess the prognostic utility of TAPSE/PASP as an echocardiographic parameter of maladaptive RV remodeling in cardiomyopathy patients using cardiac magnetic resonance (CMR) imaging. Furthermore, we sought to compare TAPSE/PASP to TAPSE. The association of the echocardiographic parameters TAPSE/PASP and TAPSE with CMR parameters of RV and LV remodeling was evaluated in 111 patients with ischemic and non-ischemic cardiomyopathy and cut-off values for maladaptive RV remodeling were defined. In a second step, the prognostic value of TAPSE/PASP and its cut-off value were analyzed regarding mortality in a validation cohort consisting of 221 patients with ischemic and non-ischemic cardiomyopathy. A low TAPSE/PASP (<0.38 mm/mmHg) and TAPSE (<16 mm) were associated with a lower RVEF and a long-axis RV global longitudinal strain (GLS) as well as higher RVESVI, RVEDVI and NT-proBNP. A low TAPSE/PASP, but not TAPSE, was associated with a lower LVEF and long-axis LV GLS, and a higher LVESVI, LVEDVI and T1 relaxation time at the interventricular septum and the RV insertion points. Furthermore, in the validation cohort, low TAPSE/PASP was associated with a higher mortality and TAPSE/PASP was an independent predictor of mortality. TAPSE/PASP is a predictor of maladaptive RV and LV remodeling associated with poor outcomes in cardiomyopathy patients.

Background: Blunted left ventricular hemodynamics reflected by a low stroke volume index (SVI) ≤35 mL/m 2 body surface area (low flow [LF]) in patients with severe aortic stenosis (AS) are associated with worse outcomes even after correction of afterload by transcatheter aortic valve implantation (TAVI). These patients can have a low or high transvalvular mean pressure gradient (MPG). We investigated the impact of the pre-interventional MPG on outcomes after TAVI., Methods: Patients with LF AS were classified into those with normal (EF ≥ 50%; LF/NEF) or reduced ejection fraction (EF < 50%; LF/REF) and were then stratified according to an MPG < or ≥ 40 mmHg. Patients with SVI >35 mL/m 2 (normal flow; NF) served as controls., Results: 597 patients with LF/NEF, 264 patients with LF/REF and 975 patients with NF were identified. Among all groups those patients with a low MPG were characterized by higher cardiovascular risk. In patients with LF/REF, functional improvement post-TAVI was less pronounced in low-MPG patients. One-year survival was significantly worse in LF AS patients with a low vs. high MPG (LF/NEF 16.5% vs. 10.5%, p = 0.022; LF/REF 25.4% vs. 8.0%, p = 0.002), whereas no differences were found in NF patients (8.7% vs. 10.0%, p = 0.550). In both LF AS groups, a low pre-procedural MPG emerged as an independent predictor of mortality., Conclusions: In patients with LF AS, an MPG cut-off of 40 mmHg defines two patient populations with fundamental differences in outcomes after TAVI. Patients with LF AS and a high MPG have the same favorable prognosis as patients with NF AS., (© 2021 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals LLC.)

Inflammation is a hallmark of the period after a myocardial infarction (MI) that is either promoted or resolved by distinct subtypes of circulating inflammatory cells. The three main monocyte subpopulations play different roles inflammation. This study examined whether the type of MI (type 1 or type 2) or the extent of myocardial injury is associated with differences in monocyte subpopulations. For this purpose, peripheral whole blood from patients with a suspected MI was used for flow cytometric measurements of the monocyte subpopulations, and myocardial injury was classified by cardiac troponin levels in serum. In patients with acute coronary syndrome ( n = 82, 62.2% male) similar proportions of the monocyte subsets were associated with the two types of MI, whereas total monocyte counts were increased in patients with substantial myocardial injury vs. those with minor injury ( p = 0.045). This was accompanied by a higher proportion of intermediate ( p = 0.045) and classical monocytes ( p = 0.059); no difference was found for non-classical monocytes ( p = 0.772). In patients with chronic coronary syndrome ( n = 144, 66.5% male), an independent association with myocardial injury was also observed for classical monocytes ( p = 0.01) and intermediate monocytes ( p = 0.08). In conclusion, changes in monocyte subpopulation counts, particularly for classical and intermediate monocytes, were related to the extent of myocardial injury in acute and stable coronary artery disease but not to the type of MI., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Askari, Lipps, Voss, Staubach, Grün, Klingenberg, von Jeinsen, Wolter, Kriechbaum, Dörr, Nef, Liebetrau, Hamm and Keller.)

Background: Complete revascularization in ST elevation myocardial infarction (STEMI) patients with multivessel disease has resulted in reduction in composite clinical endpoints in medium sized trials. Only one trial showed an effect on hard clinical endpoints, but the revascularization procedure was guided by angiographic evaluation of stenosis severity. Consequently, it is not clear how Fractional Flow Reserve (FFR)-guided percutaneous coronary intervention (PCI) affects hard clinical endpoints in STEMI., Methods and Results: The Ffr-gUidance for compLete non-cuLprit REVASCularization (FULL REVASC) - is a pragmatic, multicenter, international, registry-based randomized clinical trial designed to evaluate whether a strategy of FFR-guided complete revascularization of non-culprit lesions, reduces the combined primary endpoint of total mortality, non-fatal MI and unplanned revascularization. 1,545 patients were randomized to receive FFR-guided PCI during the index hospitalization or initial conservative management of non-culprit lesions. We found that in angiographically severe non-culprit lesions of 90-99% severity, 1 in 5 of these lesions were re-classified as non-flow limiting by FFR. Considering lesions of intermediate severity (70%-89%), half were re-classified as non-flow limiting by FFR. The study is event driven for an estimated follow-up of at least 2.75 years to detect a 9.9%/year>7.425%/year difference (HR = 0.74 at 80% power (α = .05)) for the combined primary endpoint., Conclusion: This large randomized clinical trial is designed and powered to evaluate the effect of complete revascularization with FFR-guided PCI during index hospitalization on total mortality, non-fatal MI and unplanned revascularization following primary PCI in STEMI patients with multivessel disease. Enrollment completed in September 2019 and follow-up is ongoing., (Copyright © 2021. Published by Elsevier Inc.)

Abstract: Statin therapy after transcatheter aortic valve replacement (TAVI) is associated with better short-term and long-term outcomes. It is of interest to identify specific patient populations that may profit from statin therapy. In this retrospective, observational analysis of 2862 patients with symptomatic aortic stenosis after successful transfemoral TAVI, survival during a three-year observation period was characterized by Kaplan-Meier analyses according to statin therapy. Hazard ratios and potential interactions for specific subgroups of patients were determined by Cox regression analyses. At hospital discharge 1761 patients were on low-intensity or moderate-intensity statins, 246 patients were on high-intensity statins, and 855 patients did not take statins. Statin therapy adherence during the first 3 months post-TAVI was 91%. Mortality rates were 18.5%, 12.9%, and 6.9% for patients with no statin, low-intensity or moderate-intensity statins, and high-intensity statins (P < 0.001). Any statin therapy proved to be effective in patients in different classes of age, risk, and manifest cardiovascular disease and was independent of background medication. Statins were of particular benefit in high-risk patients with coronary artery disease [hazard ratio (HR) = 0.57], ejection fraction <40% (HR = 0.64), or low-flow low-gradient aortic stenosis (HR = 0.58) and showed additional benefit even in patients taking renin-angiotensin system blockers (HR = 0.74). Statins also reduced mortality in patients with malignant disease (HR = 0.47). Our analysis confirmed the beneficial effect of statins on survival after TAVI and documented this phenomenon in key patient subsets. The protective effect of statins in our study is consistent with the cardioprotective mechanisms but must be explained by other, yet undetermined pleiotropic effects of statins., Competing Interests: M. Renker: speaker fees from St. Jude Medical/Abbott. C. Liebetrau: speaker fees from Abbott. Y.-H. Choi: proctor/speaker/scientific advisor fees from Getinge, Jotec/CryoLife, Cytosorbents. C. W. Hamm: advisory board Medtronic. W.-K. Kim: proctor/speaker fees from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, Meril Liefe Sciences, Shockwave Medical. The remaining authors report no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To assess the Usefulness of oral anticoagulation therapy (OAT) in patients with coronary artery aneurysm (CAA)., Background: Data on the most adequate antithrombotic CAA management is lacking., Methods: Patients 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., Results: One 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)., Conclusion: OAT decreases the composite endpoint of UA, myocardial infarction, and aneurysm thrombosis in patients with CAA, despite a non-significant higher risk of bleeding., (© 2020 Wiley Periodicals LLC.)

Purpose: The aim of the study was to investigate the potential of electrocardiogram (ECG)-gated computed tomography pulmonary angiography (CTPA) as a predictor of disease severity in patients with chronic thromboembolic pulmonary hypertension (CTEPH)., Method: Forty-five CTEPH patients with a mean age of 63.8 years±12.7 y (±standard deviation) who had undergone ECG-gated CTPA and right heart catheterization (RHC) were included in the study. Right ventricular to left ventricular volume ratio (RVV/LVV), diameter ratio on 4-chamber view (RVD4CH/LVD4CH), pulmonary trunk (PT) diameter, PT to aortic diameter ratio (PT/A), and septal angle were correlated to mean pulmonary artery pressure (mPAP). Moreover, RVV/LVV and RVD4CH/LVD4CH were adjusted to pulmonary diameter index (PADi) and PT/A index. Areas under the curve (AUC) for predicting mPAP above 40 mmHg, 35 mmHg, and 30 mmHg were calculated., Results: RVD4CH/LVD4CH revealed the strongest correlation to mPAP before (r = 0.6507) and after (r = 0.7650; p < 0.0001) PT/A adjustment. The AUCs for predicting pH with mPAP over 40 mmHg and 30 mmHg were 0.9229 and 0.864, respectively. A cutoff value of 1.298 enabled prediction of pH with mPAP over 40 mmHg with a sensitivity, specificity, positive predictive, and negative predictive value of 80.00 %, 95.83 %, 88.46 %, and 94.12 %, respectively. Intra- and interobserver variability were excellent for all parameters., Conclusion: Combining different and easily evaluable ECG-gated CTPA parameters enables excellent prediction of pulmonary hemodynamics in CTEPH patients. Ventricular diameter ratio on 4-chamber view adjusted by the PT/A ratio yielded the best correlation to mPAP., Competing Interests: CBW has received speaker fees and/or consultant honoraria from Actelion, AOP Orphan Pharmaceuticals AG, Bayer AG, BTG, MSD, and Pfizer. SG has received speaker fees from Actelion, Bayer, GSK, MSD and Pfizer. The other authors declare that they have no competing interests., (© 2021 Published by Elsevier Ltd.)

Background: The plasma volume status (PVS) is considered a marker of non-overt cardiac congestion and is of prognostic value. Patients with low-flow, low-gradient (LFLG) aortic stenosis (AS) suffer from impaired left ventricular function and show signs of heart failure (HF). We hypothesized that PVS might predict post-interventional rehospitalization and cardiovascular mortality in high-risk patients undergoing transcatheter aortic valve implantation (TAVI)., Methods: In this retrospective, observational analysis, PVS before transfemoral TAVI was calculated by a formula taking into account hematocrit and weight. The predictive performance of PVS was compared with that of prior cardiac decompensation (PCD)., Results: In the entire cohort of n=2,458 patients, PVS >-4% (high plasma volume) identified patients (n=1,013) with a higher post-interventional 1-year mortality rate than patients (n=1,445) with a PVS ≤-4% (low plasma volume). However, PVS lost prognostic independence when adjusted for anemia, whereas PCD did not. A high PVS and PCD were not correlated, and both parameters similarly revealed a low sensitivity and specificity but a high negative predictive value (NPV) for future HF events. PVS was not different between control patients (n=1,512) and those with intermediate (paradoxical LFLG-AS, n=327) or high risk scores (LFLG-AS, n=239). The accuracy of high PVS in predicting adverse events in these subpopulations was the same as in the study population overall. Kaplan-Maier analyses demonstrated similar prognostic impacts for PVS and PCD., Conclusions: PVS and PCD represent two independent parameters of volume overload with unfavorable prognostic significance. Pre-interventional PVS does not appear to be suitable for predicting clinical outcomes in high-risk patients undergoing TAVI., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/cdt-21-286). MR receives speaker fees from Abbott. CL receives lecture, consulting fees and/or support for attending meetings and/or travel from Abbott, Astra Zeneca, Bayer, Berlin Chemie, Boehringer lngelheim, Daiichi-Sankyo, Pfizer-Bristol-Myers Squibb, Thermo Fisher, Xenios AG. Yeong-Hoon Choi receives proctor/speaker/scientific advisor fees from Getinge, Jotec/CryoLife, Cytosorbents. CWH is on advisory board of Medtronic. WKK receives proctor/advisory board/speaker fees from Abbott, Boston Scientific, Edwards Lifesciences, Medtronic, Meril Life Sciences, Shockwave Medical. The other authors have no conflicts of interest to declare., (2021 Cardiovascular Diagnosis and Therapy. All rights reserved.)

Importance: It is unclear whether ticagrelor or prasugrel hydrochloride is superior for patients with acute coronary syndrome (ACS) treated with percutaneous coronary intervention (PCI)., Objective: To assess the safety and efficacy of ticagrelor vs prasugrel for patients with ACS treated with PCI., Design, Setting, and Participants: A prespecified analysis was performed of a postrandomization subgroup of 3377 patients who presented with ACS and were treated with PCI in the investigator-initiated, multicenter, phase 4, open-label Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 5 randomized clinical trial, conducted from September 1, 2013, to February 28, 2018. Statistical analysis was performed from September 1, 2020, to January 30, 2021. Analysis was performed according to the intention-to-treat principle., Interventions: Patients were randomly assigned to a ticagrelor-based or prasugrel-based strategy. This analysis focuses on the subgroup of patients who underwent PCI that was formed after randomization., Main Outcomes and Measures: The primary end point was a composite consisting of all-cause death, myocardial infarction, or stroke at 12 months. The safety end point was Bleeding Academic Research Consortium (BARC) type 3 to 5 bleeding., Results: The ticagrelor group comprised 1676 patients (1323 men [78.9%]; mean [SD] age, 64.4 [12.0] years), and the prasugrel group comprised 1701 patients (1341 men [78.8%]; mean [SD] age, 64.7 [12.0] years). The primary end point occurred for 162 patients (9.8%) in the ticagrelor group and 120 patients (7.1%) in the prasugrel group (hazard ratio [HR], 1.41; 95% CI, 1.11-1.78; P = .005). Myocardial infarction occurred in 88 patients (5.3%) in the ticagrelor group compared with 55 patients (3.8%) in the prasugrel group (HR, 1.67; 95% CI, 1.19-2.34; P = .003). The safety end point, BARC type 3 to 5 bleeding, occurred in 84 of 1672 patients (5.3%) in the ticagrelor group and 78 of 1680 patients (4.9%) in the prasugrel group (HR; 1.10; 95% CI, 0.81-1.50; P = .54)., Conclusions and Relevance: Among patients presenting with ACS who were treated with PCI, the incidence of the primary composite end point occurred less frequently for patients who received prasugrel compared with those who received ticagrelor. The incidence of bleeding events was comparable between the 2 groups. These results suggest that, for patients presenting with ACS who undergo PCI, a prasugrel-based strategy is superior to a ticagrelor-based strategy. However, because these observations are based on a postrandomization subgroup, these findings should be regarded as hypothesis generating and dedicated randomized clinical trials may be warranted to confirm these findings., Trial Registration: ClinicalTrials.gov Identifier: NCT01944800.

Background: Treatment of acute myocardial infarction (AMI) patients with prior stroke is a common clinical dilemma. Currently, the application of optimal medical therapy (OMT) and its impact on clinical outcomes are not clear in this patient population., Methods: We retrieved 765 AMI patients with prior stroke who underwent percutaneous coronary intervention (PCI) during the index hospitalization from the international multicenter BleeMACS registry. All of the subjects were divided into two groups based on the prescription they were given prior to discharge. Baseline characteristics and procedural variables were compared between the OMT and non-OMT groups. Mortality, re-AMI, major adverse cardiovascular events (MACE), and bleeding were followed-up for 1 year., Results: Approximately 5% of all patients presenting with AMI were admitted to the hospital for ischemic stroke. Although the prescription rate of each OMT medication was reasonably high (73.3%-97.3%), 47.7% lacked at least one OMT medication. Patients receiving OMT showed a significantly decreased occurrence of mortality (4.5% vs 15.1%, p  < 0.001), re-AMI (4.2% vs 9.3%, p  = 0.004), and the composite endpoint of death/re-AMI (8.6% vs 20.5%, p  < 0.001) compared to those without OMT. No significant difference was observed between the groups regarding bleeding. After adjusting for confounding factors, OMT was the independent protective factor of 1-year mortality, while age was the independent risk factors., Conclusions: OMT at discharge was associated with a significantly lower 1-year mortality of patients with AMI and prior stroke in clinical practice. However, OMT was provided to just half of the eligible patients, leaving room for substantial improvement., Clinical Trial Registration: NCT02466854., Competing Interests: Conflict of interest statement: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2021.)

[Figure: see text].

Introduction: Refractory angina (RA) is considered the end-stage of coronary artery disease, and often has no interventional treatment options. Coronary sinus Reducer (CSR) is a recent addition to the therapeutic arsenal, but its efficacy has only been evaluated on small populations. The RESOURCE registry provides further insights into this therapy., Methods: The RESOURCE is an observational, retrospective registry that includes 658 patients with RA from 20 centers in Europe, United Kingdom and Israel. Prespecified endpoints were the amelioration of anginal symptoms evaluated with the Canadian Cardiovascular Society (CCS) score, the rates of procedural success and complications, and MACEs as composite of all-cause mortality, acute coronary syndromes, and stroke., Results: At a median follow-up of 502 days (IQR 225-1091) after CSR implantation, 39.7% of patients improved by ≥2 CCS classes (primary endpoint), and 76% by ≥1 class. Procedural success was achieved in 96.7% of attempts, with 3% of procedures aborted mostly for unsuitable coronary sinus anatomy. Any complication occurred in 5.7% of procedures, but never required bailout surgery nor resulted in intra- or periprocedural death or myocardial infarction. One patient developed periprocedural stroke after inadvertent carotid artery puncture. At the last available follow-up, overall mortality and MACE were 10.4% and 14.6% respectively. At one, three and five years, mortality rate at Kaplan-Meier analysis was 4%, 13.7%, and 23.4% respectively., Conclusions: CSR implantation is safe and reduces angina in patients with refractory angina., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Recent guidelines recommend a risk-adjusted, non-invasive work-up in patients presenting with chest discomfort to exclude coronary artery disease (CAD). However, a risk-adjusted diagnostic approach remains challenging in clinical practice. An acoustic detection device for analyzing micro-bruits induced by stenosis-generated turbulence in the coronary circulation has shown potential for ruling out CAD in patients with low-to-intermediate likelihood. We examined the diagnostic value of this acoustic detection system in a high-prevalence cohort. In total, 226 patients scheduled for clinically indicated invasive coronary angiography (ICA) were prospectively enrolled at two centers and examined using a portable, acoustic detection system. The acoustic analysis was performed in double-blinded fashion prior to quantitative ICA and following percutaneous coronary intervention (PCI). An acoustic detection result (CAD score) was obtained in 94% of all patients. The mean baseline CAD score was 41.2 ± 11.9 in patients with obstructive CAD and 33.8 ± 13.4 in patients without obstructive CAD (p < 0.001). ROC analysis revealed an AUC of 0.661 (95% CI 0.584-0.737). Sensitivity was 97.6% (95% confidence interval (CI) 91.5-99.7%), specificity was 14.5% (CI 9.0-21.7%), negative predictive value was 90.5% (CI 69.6-98.8%), and positive predictive value was 41.7% (CI 34.6-49.0%). Following PCI, the mean CAD score decreased from 40.5 ± 11.2 to 38.3 ± 13.7 (p = 0.039). Using an acoustic detection device identified individuals with CAD in a high-prevalence cohort with high sensitivity but relatively low specificity. The negative predictive value was within the predicted range and may be of value for a fast rule-out of obstructive CAD even in a high-prevalence population.

Aim: This study assessed the utility of osteopontin (OPN) and galectin-3 (Gal-3) as biomarkers of maladaptive right ventricular remodeling in pulmonary hypertension (PH). Materials & methods: We examined plasma levels of OPN and Gal-3 in patients with PH (n = 62), dilated cardiomyopathy (n = 34), left ventricular hypertrophy (LVH; n = 47), and controls without right ventricle (RV) or LV abnormalities (n = 38). Results: OPN and Gal-3 levels were higher in PH, dilated cardiomyopathy and LVH than in the controls. OPN concentrations in PH patients with maladaptive RV were significantly higher than in those with adaptive RV. Gal-3 did not differentiate between adaptive and maladaptive RV remodeling in PH. OPN and Gal-3 levels did not correlate with parameters of LV remodeling. Conclusion: OPN is a potential biomarker of RV maladaptation.

Background: The use of Renin-Angiotensin system inhibitors (RASi) in patients with coronavirus disease 2019 (COVID-19) has been questioned because both share a target receptor site., Methods: HOPE-COVID-19 (NCT04334291) is an international investigator-initiated registry. Patients are eligible when discharged after an in-hospital stay with COVID-19, dead or alive. Here, we analyze the impact of previous and continued in-hospital treatment with RASi in all-cause mortality and the development of in-stay complications., Results: We included 6503 patients, over 18 years, from Spain and Italy with data on their RASi status. Of those, 36.8% were receiving any RASi before admission. RASi patients were older, more frequently male, with more comorbidities and frailer. Their probability of death and ICU admission was higher. However, after adjustment, these differences disappeared. Regarding RASi in-hospital use, those who continued the treatment were younger, with balanced comorbidities but with less severe COVID19. Raw mortality and secondary events were less frequent in RASi. After adjustment, patients receiving RASi still presented significantly better outcomes, with less mortality, ICU admissions, respiratory insufficiency, need for mechanical ventilation or prone, sepsis, SIRS and renal failure (p<0.05 for all). However, we did not find differences regarding the hospital use of RASi and the development of heart failure., Conclusion: RASi historic use, at admission, is not related to an adjusted worse prognosis in hospitalized COVID-19 patients, although it points out a high-risk population. In this setting, the in-hospital prescription of RASi is associated with improved survival and fewer short-term complications., Competing Interests: Conflict of interest None declared., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Patients with symptomatic aortic stenosis (AS) can have concomitant systolic heart failure (HF) that persists even after correction of afterload by transcatheter aortic valve implantation (TAVI). These patients qualify as potential candidates for prophylactic therapy with an implantable cardioverter defibrillator (ICD). We compared survival between patients with or without an ICD after successful TAVI. This retrospective study analyzed Kaplan-Meier survival data during a follow-up period of three years in two populations: (a) patients with a left ventricular ejection fraction (LVEF) ≤ 35% before TAVI (overall population); (b) patients with additionally documented LVEF ≤ 35% 3 months after TAVI (persistent LV dysfunction subpopulation). In the overall population, 53 patients with and 193 patients without an ICD had similar baseline characteristics and procedural success rates, and HF medication at discharge was comparable. Three-year mortality rates were 26.4% for patients with an ICD and 24.4% for patients without an ICD ( p = 0.758). Cardiovascular death rates were similar between groups ( p = 0.914), and deaths were most often attributed to worsening of HF. Survival rates in patients with persistent LV dysfunction with an ICD ( n = 24) or without an ICD ( n = 59) were similar between groups ( p = 0.872), with cardiovascular deaths mostly qualified as worsening HF and none as sudden cardiac death. Patients of the overall study population with biventricular pacing devices showed only a tendency to have better outcomes ( p = 0.298). ICD therapy in elderly patients with AS and LV dysfunction undergoing TAVI did not demonstrate a survival benefit during a 3-year follow-up period.

Background: Transcatheter aortic valve implantation (TAVI) is the standard treatment option for patients with severe aortic stenosis (AS) at intermediate or high surgical risk. Preexisting right bundle branch block (RBBB) is a strong predictor of new pacemaker implantation (PPM) after TAVI, and previous data indicate a worse short- and long-term outcome of patients. The aim of this study was to investigate whether preexisting RBBB has an effect on the short- and mid-term outcome of patients undergoing TAVI in a German high-volume TAVI center., Methods: For the present retrospective analysis, a total of 1,891 patients with native severe AS with successful TAVI without preexisting PPM were included. The primary endpoint was all-cause mortality after 30 days and 12 months. Baseline RBBB was present in 190 (10.1%) of cases., Results: Patients with preexisting RBBB had a considerably higher rate of new PPM after TAVI compared with patients without RBBB (87/190 [45.8%] vs. 219/1,701 [12.9%]; p<0.001). RBBB had no impact on all-cause mortality at 30 days (2.1% vs. 2.7%; p = 0.625) and at 12 months (14.4% vs. 13.6%; p = 0.765). Further stratification according to the presence of new PPM showed a difference in mid-term survival rates between the four groups, with the worst outcome for patients without RBBB and new PPM (log rank p = 0.024). However, no difference in mid-term cardiovascular survival was found., Conclusion: Preexisting RBBB is a common finding in patients with severe AS undergoing TAVI and is associated with considerably higher PPM rates but not with worse short- and mid-term outcome., Competing Interests: MR received speaker fees from Abbott, CWH contributes to the advisory board of Medtronic, and WK received proctor/speaker honoraria from Abbott, Boston Scientific, Edwards Lifesciences, and Medtronic (other authors have nothing to disclose). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objectives: No standard therapy, including anticoagulation regimens, is currently recommended for coronavirus disease 2019. Aim of this study was to evaluate the efficacy of anticoagulation in coronavirus disease 2019 hospitalized patients and its impact on survival., Design: Multicenter international prospective registry (Health Outcome Predictive Evaluation for Corona Virus Disease 2019)., Setting: Hospitalized patients with coronavirus disease 2019., Patients: Five thousand eight hundred thirty-eight consecutive coronavirus disease 2019 patients., Interventions: Anticoagulation therapy, including prophylactic and therapeutic regimens, was obtained for each patient., Measurements and Main Results: Five thousand four hundred eighty patients (94%) did not receive any anticoagulation before hospitalization. Two-thousand six-hundred one patients (44%) during hospitalization received anticoagulation therapy and it was not associated with better survival rate (81% vs 81%; p = 0.94) but with higher risk of bleeding (2.7% vs 1.8%; p = 0.03). Among patients admitted with respiratory failure (49%, n = 2,859, including 391 and 583 patients requiring invasive and noninvasive ventilation, respectively), anticoagulation started during hospitalization was associated with lower mortality rates (32% vs 42%; p < 0.01) and nonsignificant higher risk of bleeding (3.4% vs 2.7%; p = 0.3). Anticoagulation therapy was associated with lower mortality rates in patients treated with invasive ventilation (53% vs 64%; p = 0.05) without increased rates of bleeding (9% vs 8%; p = 0.88) but not in those with noninvasive ventilation (35% vs 38%; p = 0.40). At multivariate Cox' analysis mortality relative risk with anticoagulation was 0.58 (95% CI, 0.49-0.67) in patients admitted with respiratory failure, 0.50 (95% CI, 0.49-0.67) in those requiring invasive ventilation, 0.72 (95% CI, 0.51-1.01) in noninvasive ventilation., Conclusions: Anticoagulation therapy in general population with coronavirus disease 2019 was not associated with better survival rates but with higher bleeding risk. Better results were observed in patients admitted with respiratory failure and requiring invasive ventilation., Competing Interests: Drs. Romero and García Aguado received support for article research from the National Institutes of Health. Dr. Moreno Munguia received support for article research from Instituto de Investigación Sanitaria del Hospital Clínico San Carlos. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2021 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: The most common method of percutaneous closure in transfemoral transcatheter aortic valve implantation (TAVI) employs two obtusely oriented ProGlide devices. The aim of this study was to assess the feasibility and safety of using a single ProGlide system for primary access site closure in comparison with the double ProGlide approach in an all-comers TAVI population., Methods: Between March 2016 and December 2018, a total of 1105 patients underwent transfemoral TAVI for severe aortic stenosis at our center. Application of two ProGlide systems was standard until April 2017 (n = 432), whereas thereafter a single ProGlide system was used (n = 663). A 1:1 propensity score matching was performed to adjust for baseline differences between the two groups, resulting in 327 matched cases. Primary outcomes of interest were main access site-related vascular complications., Results: The mean number of ProGlide devices used per patient was 1.03 (SD 0.2) in the single-ProGlide group versus 2.01 (SD 0.14) in the double-ProGlide group. An additional vascular closure device was required to obtain full hemostasis in 23.2% versus 9.5% of patients (p < 0.001) in the two groups, respectively. Technical success of ProGlide usage was similar (94.3% versus 92.1%, p = 0.163). In the matched cohorts, the rates of main access site-related major vascular complications were similar (4.0% vs. 6.4%, p = 0.217)., Conclusion: The single-ProGlide technique is feasible, with rates of technical success similar to those of the double-ProGlide technique. Use of this method did not lead to more frequent access site-related complications but was more cost effective than the double-ProGlide approach., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Development of acute kidney injury (AKI) in invasively managed patients with acute coronary syndrome (ACS) is associated with a markedly increased mortality risk. Different definitions of AKI are in use, leading to varying prevalence and outcome measurements. The aim of the present study is to analyze an ACS population undergoing coronary angiography for differences in AKI prevalence and outcome using four established AKI definitions., Methods: 944 patients (30% female) were enrolled in a prospective registry between 2003 and 2005 with 6-month all-cause mortality as outcome measure. Four established AKI definitions were used: an increase in serum creatinine (sCR) ≥ 1.5 fold, ≥ 0.3 mg/dl, and ≥ 0.5 mg/dl and a decrease in eGFR > 25% from baseline (AKIN 1, AKIN 2, CIN, and RIFLE definition groups, respectively)., Results: AKI rates varied widely between the different groups. Using the CIN definition, AKI frequency was lowest (4.4%), whereas it was highest if the RIFLE definition was applied (13.2%). AKIN 2 displayed a twofold higher AKI prevalence compared with AKIN 1 (10.2% vs. 5.3% (p < 0.001)). AKI was a strong risk factor for mid-term mortality, with distinctive variability between the definitions. The lowest mortality risk was found in the RIFLE group (HR 6.0; 95% CI 3.7-10.0; p < 0.001), whereas CIN revealed the highest risk (HR 16.7; 95% CI 9.9-28.1; p < 0.001)., Conclusion: Prevalence and outcome in ACS patients varied considerably depending on the AKI definition applied. To define patients with highest renal function-associated mortality risk, use of the CIN definition seems to have the highest prognostic relevance.

The aim of our study was to analyse the protein expression of cartilage intermediate layer protein (CILP)1 in a mouse model of right ventricular (RV) pressure overload and to evaluate CILP1 as a biomarker of cardiac remodelling and maladaptive RV function in patients with pulmonary hypertension (PH).Pulmonary artery banding was performed in 14 mice; another nine mice underwent sham surgery. CILP1 protein expression was analysed in all hearts using Western blotting and immunostaining. CILP1 serum concentrations were measured in 161 patients (97 with adaptive and maladaptive RV pressure overload caused by PH; 25 with left ventricular (LV) hypertrophy; 20 with dilative cardiomyopathy (DCM); 19 controls without LV or RV abnormalities)In mice, the amount of RV CILP1 was markedly higher after banding than after sham. Control patients had lower CILP1 serum levels than all other groups (p<0.001). CILP1 concentrations were higher in PH patients with maladaptive RV function than those with adaptive RV function (p<0.001), LV pressure overload (p<0.001) and DCM (p=0.003). CILP1 showed good predictive power for maladaptive RV in receiver operating characteristic analysis (area under the curve (AUC) 0.79). There was no significant difference between the AUCs of CILP1 and N-terminal pro-brain natriuretic peptide (NT-proBNP) (AUC 0.82). High CILP1 (cut-off value for maladaptive RV of ≥4373 pg·mL -1 ) was associated with lower tricuspid annular plane excursion/pulmonary artery systolic pressure ratios (p<0.001) and higher NT-proBNP levels (p<0.001).CILP1 is a novel biomarker of RV and LV pathological remodelling that is associated with RV maladaptation and ventriculoarterial uncoupling in patients with PH., Competing Interests: Conflict of interest: S. Keranov reports grants from German Research Foundation (Project B07, Collaborative Research Center 1213-Pulmonary Hypertension and Cor Pulmonale), during the conduct of the study. Conflict of interest: O. Dörr reports grants from German Research Foundation (Project B07, Collaborative Research Center 1213-Pulmonary Hypertension and Cor Pulmonale), during the conduct of the study. Conflict of interest: L. Jafari has nothing to disclose. Conflict of interest: C. Troidl has nothing to disclose. Conflict of interest: C. Liebetrau reports grants from German Research Foundation (Project B07, Collaborative Research Center 1213-Pulmonary Hypertension and Cor Pulmonale), during the conduct of the study. Conflict of interest: S. Kriechbaum reports grants from German Research Foundation (Project B07, Collaborative Research Center 1213-Pulmonary Hypertension and Cor Pulmonale), during the conduct of the study. Conflict of interest: T. Keller has nothing to disclose. Conflict of interest: S. Voss has nothing to disclose. Conflict of interest: T. Bauer has nothing to disclose. Conflict of interest: J. Lorenz has nothing to disclose. Conflict of interest: M.J. Richter has nothing to disclose. Conflict of interest: K. Tello has nothing to disclose. Conflict of interest: H. Gall has nothing to disclose. Conflict of interest: H.A. Ghofrani has nothing to disclose. Conflict of interest: E. Mayer has nothing to disclose. Conflict of interest: C.B. Wiedenroth has nothing to disclose. Conflict of interest: S. Guth has nothing to disclose. Conflict of interest: H. Lörchner has nothing to disclose. Conflict of interest: J. Pöling has nothing to disclose. Conflict of interest: P. Chelladurai has nothing to disclose. Conflict of interest: S.S. Pullamsetti has nothing to disclose. Conflict of interest: T. Braun has nothing to disclose. Conflict of interest: W. Seeger has nothing to disclose. Conflict of interest: C.W. Hamm reports grants from German Research Foundation (Project B07, Collaborative Research Center 1213-Pulmonary Hypertension and Cor Pulmonale), during the conduct of the study. Conflict of interest: H. Nef reports grants from German Research Foundation (Project B07, Collaborative Research Center 1213-Pulmonary Hypertension and Cor Pulmonale), during the conduct of the study., (Copyright ©ERS 2021.)

Aims: Both surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) are established options to treat aortic valve stenosis. We present the outcome of the complete cohort of all patients undergoing SAVR or TAVI in Germany during the calendar year 2019., Methods and Results: Data concerning all isolated aortic valve procedures performed in Germany in 2019 were retrieved from the mandatory nationwide quality control program: 22,973 transvascular (TV)-TAVI procedures, 7905 isolated SAVR (iSAVR), and 1413 transapical (TA)-TAVI. Data was complete in 99.9% (n = 32,156). In-hospital mortality after TV-TAVI (2.3%) was significantly lower when compared with iSAVR (2.8%, p = 0.007) or TA-TAVI (6.3%; p < 0.001). Expected mortality was calculated with a new version of the German Aortic valve score (AKL Score) based on the data of either catheter-based (AKL-CATH) or surgical (AKL-CHIR) aortic valve replacements in Germany in 2018. TV-TAVI and iSAVR both showed lower observed mortality in 2019 than expected based on their respective performance in 2018, yielding an observed/expected (O/E) mortality ratio < 1. This was particularly apparent for patients at low risk. After exclusion of emergency procedures, in-hospital mortality after TV-TAVI (2.1%) and after iSAVR (2.1%) was identical, even though patients undergoing TV-TAVI showed a considerably higher perioperative risk profile., Conclusion: After excluding emergency procedures, in-hospital mortality of TV-TAVI and iSAVR in 2019 in Germany was identical. In 2019, TV-TAVI and iSAVR both show lower matched mortality ratios compared with 2018, which suggests technical improvements of both therapies.

Background: the coronavirus disease 2019 (COVID-19) is characterized by poor outcomes and mortality, particularly in older patients., Methods: post hoc analysis of the international, multicentre, 'real-world' HOPE COVID-19 registry. All patients aged ≥65 years hospitalised for COVID-19 were selected. Epidemiological, clinical, analytical and outcome data were obtained. A comparative study between two age subgroups, 65-74 and ≥75 years, was performed. The primary endpoint was all cause in-hospital mortality., Results: about, 1,520 patients aged ≥65 years (60.3% male, median age of 76 [IQR 71-83] years) were included. Comorbidities such as hypertension (69.2%), dyslipidaemia (48.6%), cardiovascular diseases (any chronic heart disease in 38.4% and cerebrovascular disease in 12.5%), and chronic lung disease (25.3%) were prevalent, and 49.6% were on ACEI/ARBs. Patients aged 75 years and older suffered more in-hospital complications (respiratory failure, heart failure, renal failure, sepsis) and a significantly higher mortality (18.4 vs. 48.2%, P < 0.001), but fewer admissions to intensive care units (11.2 vs. 4.8%). In the overall cohort, multivariable analysis demonstrated age ≥75 (OR 3.54), chronic kidney disease (OR 3.36), dementia (OR 8.06), peripheral oxygen saturation at admission <92% (OR 5.85), severe lymphopenia (<500/mm3) (OR 3.36) and qSOFA (Quick Sequential Organ Failure Assessment Score) >1 (OR 8.31) to be independent predictors of mortality., Conclusion: patients aged ≥65 years hospitalised for COVID-19 had high rates of in-hospital complications and mortality, especially among patients 75 years or older. Age ≥75 years, dementia, peripheral oxygen saturation <92%, severe lymphopenia and qSOFA scale >1 were independent predictors of mortality in this population., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Chronic thromboembolic pulmonary hypertension constitutes a significant late sequela of pulmonary embolism. It is defined by precapillary pulmonary hypertension with mismatched perfusion defects and pulmonary arterial lesions after at least 3 months of effective anticoagulation. Symptomatic patients who do not have pulmonary hypertension yet fulfill all other criteria are diagnosed with chronic thromboembolic disease. The treatment of chronic thromboembolic pulmonary hypertension is based on 3 pillars: pulmonary endarterectomy, pulmonary arterial hypertension-targeted medication, and balloon pulmonary angioplasty. Surgical pulmonary endarterectomy is the standard of care and can be performed in 2/3 of all patients. Targeted medication with or without balloon pulmonary angioplasty is reserved for inoperable patients or those with residual pulmonary hypertension after surgical treatment. Despite the lack of profound evidence, the treatment of chronic thromboembolic disease is similar to that of patients with pulmonary hypertension: pulmonary endarterectomy is offered to operable individuals, whereas balloon pulmonary angioplasty is considered in inoperable patients. Since therapeutic strategies are complex, and diagnostic and therapeutic procedures-demanding, treatment in a specialized, experienced center is mandatory.

Background: Event adjudication by a clinical event committee (CEC) provides a standardized, independent outcome assessment. However, the added value of CEC to investigators reporting remains debated. GLASSY (GLOBAL LEADERS Adjudication Sub-Study) implemented, in a subset of the open-label, investigator-reported (IR) GLOBAL LEADERS trial, an independent adjudication process of reported and unreported potential outcome events (triggers). We describe metrics of GLASSY feasibility and efficiency, diagnostic accuracy of IR events, and their concordance with corresponding CEC-adjudicated events., Methods: We report the proportion of myocardial infarction, bleeding, stroke, and stent thrombosis triggers with sufficient evidence for assessment (feasibility) that were adjudicated as outcome events (efficiency), stratified by source (IR or non-IR). Using CEC-adjudicated events as criterion standard, we describe sensitivity, specificity, positive and negative predictive value, and global diagnostic accuracy of IR events. Using Gwet AC coefficient, we examine the concordance between IR- and corresponding CEC-adjudicated triggers. There was sufficient evidence for assessment for 2592 (98.3%) of 2636 triggers., Results: Overall, the adjudicated end point-to-trigger ratio was high and similar between IR- (88%) and non-IR-reported (87%) triggers. The global diagnostic accuracy and concordance between IR-reported and CEC-adjudicated outcome events was 0.70 (95% CI, 0.65-0.74) and 0.54 (95% CI, 0.45-0.62), respectively, for myocardial infarction; 0.77 (95% CI, 0.75-0.79) and 0.71 (95% CI, 0.68-0.74) for bleeding; 0.70 (95% CI, 0.62-0.79) and 0.59 (95% CI, 0.43-0.74) for stroke; 0.59 (95% CI, 0.52-0.66) and 0.39 (95% CI, 0.25-0.53) for stent thrombosis. For IR bleedings, the concordance with the CEC on type of events was generally weak., Conclusions: Implementing CEC adjudication in a pragmatic open-label trial with IR events is feasible and efficient. Our findings of modest global diagnostic accuracy for IR events and generally weak concordance between investigators and CEC support the role for CEC adjudication in such settings. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03231059.

Aims: During the COVID-19 pandemic, hospital admissions for cardiac care have declined. However, effects on mortality are unclear. Thus, we sought to evaluate the impact of the lockdown period in central Germany on overall and cardiovascular deaths. Simultaneously we looked at catheterization activities in the same region., Methods and Results: Data from 22 of 24 public health-authorities in central Germany were aggregated during the pandemic related lockdown period and compared to the same time period in 2019. Information on the total number of deaths and causes of death, including cardiovascular mortality, were collected. Additionally, we compared rates of hospitalization (n = 5178) for chronic coronary syndrome (CCS), acute coronary syndrome (ACS), and out of hospital cardiac arrest (OHCA) in 26 hospitals in this area. Data on 5,984 deaths occurring between March 23, 2020 and April 26, 2020 were evaluated. In comparison to the reference non-pandemic period in 2019 (deaths: n = 5832), there was a non-significant increase in all-cause mortality of 2.6% [incidence rate ratio (IRR) 1.03, 95% confidence interval (CI) 0.99-1.06; p = 0.16]. Cardiovascular and cardiac mortality increased significantly by 7.6% (IRR 1.08, 95%-CI 1.01-1.14; p = 0.02) and by 11.8% (IRR 1.12, 95%-CI 1.05-1.19; p < 0.001), respectively. During the same period, our data revealed a drop in cardiac catherization procedures., Conclusion: During the COVID-19-related lockdown a significant increase in cardiovascular mortality was observed in central Germany, whereas catherization activities were reduced. The mechanisms underlying both of these observations should be investigated further in order to better understand the effects of a pandemic-related lockdown and social-distancing restrictions on cardiovascular care and mortality.

Background: The accuracy of current prediction tools for ischaemic and bleeding events after an acute coronary syndrome (ACS) remains insufficient for individualised patient management strategies. We developed a machine learning-based risk stratification model to predict all-cause death, recurrent acute myocardial infarction, and major bleeding after ACS., Methods: Different machine learning models for the prediction of 1-year post-discharge all-cause death, myocardial infarction, and major bleeding (defined as Bleeding Academic Research Consortium type 3 or 5) were trained on a cohort of 19 826 adult patients with ACS (split into a training cohort [80%] and internal validation cohort [20%]) from the BleeMACS and RENAMI registries, which included patients across several continents. 25 clinical features routinely assessed at discharge were used to inform the models. The best-performing model for each study outcome (the PRAISE score) was tested in an external validation cohort of 3444 patients with ACS pooled from a randomised controlled trial and three prospective registries. Model performance was assessed according to a range of learning metrics including area under the receiver operating characteristic curve (AUC)., Findings: The PRAISE score showed an AUC of 0·82 (95% CI 0·78-0·85) in the internal validation cohort and 0·92 (0·90-0·93) in the external validation cohort for 1-year all-cause death; an AUC of 0·74 (0·70-0·78) in the internal validation cohort and 0·81 (0·76-0·85) in the external validation cohort for 1-year myocardial infarction; and an AUC of 0·70 (0·66-0·75) in the internal validation cohort and 0·86 (0·82-0·89) in the external validation cohort for 1-year major bleeding., Interpretation: A machine learning-based approach for the identification of predictors of events after an ACS is feasible and effective. The PRAISE score showed accurate discriminative capabilities for the prediction of all-cause death, myocardial infarction, and major bleeding, and might be useful to guide clinical decision making., Funding: None., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Objectives: The aim of this study was to evaluate very long-term results after unrestricted everolimus-eluting bioresorbable scaffolds (BRS) implantation., Background: Previous randomized studies mainly included selected patients differing from those seen during daily routine and long-term data from all-comers registries are sparse., Methods: Consecutive patients undergoing BRS implantation were included in this observational, single center study. Clinical follow-up was conducted up to 5 years. Endpoint of interest was the composite of target lesion failure (TLF), including target-vessel myocardial infarction and target lesion revascularization and cardiac death. Furthermore, ARC-defined scaffold thrombosis (ScT) were assessed., Results: A total of 176 patients with a median age of 64 (55 - 72) years were analyzed, of which 59.6% presented an acute coronary syndrome. A total of 183 mainly complex lesions (55.8%) were treated. At 5 years, the rate for TLF was 21.6%. Definite or probable ScT rate was 4.1%. The rate of ScT within the first year was 2.8% and afterwards 1.2%. Notably, no ScT was seen later than 2 years., Conclusions: Although this real-world registry displays high rates of clinical events during long-term follow-up, no ScT was seen after 2 years., (© 2020 The Authors. Catheterization and Cardiovascular Interventions published by Wiley Periodicals, Inc.)

Objectives: Aortic valve calcification (AVC) determined by computed tomography has emerged as a complementary measure of aortic stenosis (AS) severity and as a predictor of adverse events. Thus, AVC can guide further treatment decisions in patients with low-gradient AS (LG-AS). We compared the symptomatic and prognostic outcome of patients with low vs. high AVC after transcatheter aortic valve implantation (TAVI)., Methods: Patients with an aortic valve area index ≤ 0.6 cm 2 /m 2 and a mean pressure gradient (MPG) < 40 mmHg were classified as low-flow, low-gradient AS (LFLG-AS; stroke volume index [SVI] ≤ 35 ml/m 2 , left ventricular ejection fraction [LVEF] < 50%, n = 173), paradoxical LFLG-AS (pLFLG-AS, SVI ≤ 35 ml/m 2 , LVEF ≥ 50%, n = 233), or normal-flow, low-gradient AS (NFLG-AS, SVI > 35 ml/m 2 , LVEF ≥ 50%, n = 244); patients with MPG ≥ 40 mmHg (n = 1142) served as controls. Patients were further categorized according to published AVC thresholds., Results: Demographic characteristics and cardiovascular risk were not different between patients with high vs. low AVC in any of the subgroups. Patients with low AVC had a lower MPG. Symptom improvement at 30 days was observed in the majority of patients but was less pronounced in LFLG-AS patients with low vs. those with high AVC. Kaplan-Meier 1-year survival curves were identical between patients with low and high AVC in all three LG-AS groups., Conclusions: The severity of LG-AS based on AVC has no impact on 1-year prognosis once TAVI has been performed., Key Points: • Aortic valve calcification (AVC) determined by computed tomography has emerged as a complementary measure of aortic stenosis (AS) severity and is of prognostic value in selected patients. • Patients with inconsistent echocardiographic measures can be classified as having severe or nonsevere AS by the computed tomography-derived AVC score. • The prognostic value of AVC in patients with low-gradient AS is abrogated after correction of afterload by TAVI.

Background: Primary coronary slow-flow phenomenon (CSFP) is defined as delayed opacification of contrast media in at least 1 coronary vessel in the absence of obstructive epicardial coronary artery disease (CAD) during coronary angiography. Epicardial fat tissue (EFT) surrounding coronary vessels provides paracrine effects. Released cytokines diffusing in the vessel wall may induce local inflammatory reactions that potentially result in endothelial dysfunction. The latter is thought to be the underlying cause of primary CSFP. However, to date, there are no data describing an association between EFT and CSFP. Therefore, the aim of the present study was to compare EFT thickness, clinical parameters, and outcomes in patients with and without CSFP., Methods: Coronary angiograms with primary CSFP obtained during a 10-year period were included in the analysis. EFT was measured in the 2-dimensional echocardiographic records. Clinical and diagnostic data were compared with non-CSFP patients who were matched for age, sex, and body mass index. Long-term follow-up was conducted by telephone interview., Results: A total of 48 CSFP patients (90% male; mean age, 64 ± 11.4 years) were identified, resulting in a prevalence of 0.13%. CSFP was observed in 87.5% in the left anterior descending artery, 50% in the right coronary artery, and 20.8% in the circumflex artery. Almost half of all patients showed CSFP in >1 vessel. There were no differences in baseline characteristics between CSFP patients and matched controls except for smoking history (31% vs 13%; P=.03). Median EFT thickness was significantly different between patients with and without CSFP (4.9 mm [interquartile range, 4.0-6.1 mm] vs 3.9 mm [interquartile range, 3.1-4.9 mm], respectively; P<.01). No differences in outcomes were observed., Conclusion: EFT is thicker in CSFP patients than in matched controls, but this appears to have no impact on long-term outcomes. Further studies are needed to elucidate the role of EFT in CSFP.