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Novel coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state, characterized by abnormal coagulation parameters and by increased incidence of cardiovascular complications. With this study, we aimed to investigate the activation state and the expression of transmembrane proteins in platelets of hospitalized COVID-19 patients. We investigated transmembrane proteins expression with a customized mass cytometry panel of 21 antibodies. Platelets of 8 hospitalized COVID-19 patients not requiring intensive care support and without pre-existing conditions were compared to platelets of healthy controls (11 donors) with and without in vitro stimulation with thrombin receptor-activating peptide (TRAP). Mass cytometry of non-stimulated platelets detected an increased surface expression of activation markers P-Selectin (0.67 vs. 1.87 median signal intensity for controls vs. patients, p  = 0.0015) and LAMP-3 (CD63, 0.37 vs. 0.81, p  = 0.0004), the GPIIb/IIIa complex (4.58 vs. 5.03, p  < 0.0001) and other adhesion molecules involved in platelet activation and platelet–leukocyte interactions. Upon TRAP stimulation, mass cytometry detected a higher expression of P-selectin in COVID-19 samples compared to controls ( p  < 0.0001). However, we observed a significantly reduced capacity of COVID-19 platelets to increase the expression of activation markers LAMP-3 and P-Selectin upon stimulation with TRAP. We detected a hyperactivated phenotype in platelets during SARS-CoV-2 infection, consisting of highly expressed platelet activation markers, which might contribute to the hypercoagulopathy observed in COVID-19. In addition, several transmembrane proteins were more highly expressed compared to healthy controls. These findings support research projects investigating antithrombotic and antiplatelet treatment regimes in COVID-19 patients, and provide new insights on the phenotypical platelet expression during SARS-CoV-2 infection.

ObjectiveThe optimal treatment of patients with acute and severe decompensation of aortic stenosis is unclear due to recent advances in transcatheter interventions and supportive therapies. Our aim was to assess the early outcome of emergency transcatheter aortic valve implantation (eTAVI) versus emergency balloon aortic valvuloplasty (eBAV) followed by TAVI under elective circumstances.MethodsEmergency conditions were defined as: cardiogenic shock with requirement of catecholamine therapy, severe acute dyspnoea (NYHA IV), cardiac resuscitation or mechanic respiratory support. The data were collected according to the Valve Academic Research Consortium 2 (VARC-2) criteria.ResultsIn five German centres, 23 patients (logistic Euroscore 37.7%±18.1) underwent eTAVI and 118 patients underwent eBAV (logistic Euroscore 35.3%±20.8). In the eTAVI group, immediate procedural mortality was 8.7%, compared with 20.3% for the eBAV group (p=0.19). After 30 days, cardiovascular mortality for the eTAVI group was 23.8% and for the eBAV group 33.0% (p=0.40). Analyses adjusting for potential confounders did not provide evidence of a difference between groups. Of note, the elective TAVI performed after eBAV (n=32, logistic Euroscore 25.9%±13.9) displayed an immediate procedural mortality of 9.4% and a cardiovascular mortality after 30 days of 15.6%. Major vascular complications were significantly more likely to occur after eTAVI (p=0.01) as well as stroke (p=0.01).ConclusionIn this multicentre cohort, immediate procedural and 30-day mortality of eTAVI and eBAV were high, and mortality of secondary TAVI subsequent to eBAV was higher than expected. Randomised study data are required to define the role of emergency TAVI in tertiary care centres with current device generations.

Photon‑counting detector CT (PCD‑CT) enables ultra‑high resolution (UHR, 0.2 mm) and may improve visualization of coronary stents compared with standard‑resolution (SR, 0.4 mm). In this ex- vivo study, we utilized a phantom heart model to simulate physiological attenuation and imitated the most common coronary bifurcation stenting techniques by creating multiple stent layers and stent- crush situations (single layer, crushed, two‑ and three‑layer). We compared UHR and SR PCD‑CT using Bv72 and Bv56 kernels. Objective endpoints were in‑stent lumen visibility, signal-to-noise ratio, and percentage change in stent attenuation; subjective image quality was rated on a 5‑point Likert scale (1 = excellent to 5 = non‑diagnostic). Depending on distribution, two‑sided t‑tests (mean ± SD) or Mann–Whitney U tests (median[IQR]) were applied, p‑values were Bonferroni‑corrected for multiple comparisons. In the pooled Crush cohort, UHR Bv72 improved in‑stent lumen visibility when compared with both, SR Bv72 (single-layer: 68.08 ± 4.30% vs. 79.03 ± 3.79%; crushed: 63.62 ± 4.97% vs. 74.73 ± 2.51%) and SR Bv56 (single-layer: 63.63 ± 4.47% vs. 79.03 ± 3.79%; crushed: 62.18 ± 3.55% vs. 74.73 ± 2.51%), all p < 0.01. The effect was even more pronounced in small stents (single‑layer 65.45 ± 1.91% (SR) vs. 77.11 ± 2.55% (UHR) and crushed 60.67 ± 2.67% vs. 74.00 ± 2.67%), both p < 0.01. Regarding subjective image quality, UHR was associated with better sharpness and less blooming, e.g., UHR Bv72 vs. SR Bv56 (multilayer: sharpness 1[0] vs. 2[0], blooming 1[0] vs. 2[0]; crush: sharpness 1[0] vs. 2[0], blooming 1[0] vs. 2[1]; all p ≤ 0.01) and UHR Bv72 vs. SR Bv72 (multilayer: sharpness 1[0] vs. 1[1], blooming 1[0] vs. 1[1]; crush: sharpness 1[0] vs. 1[1]; all p ≤ 0.05). These findings indicate that UHR PCD‑CT with Bv72 might enable assessment of complex stents in a phantom setting; even though clinical studies are warranted.

Alternative splicing (AS) is an important aspect of gene regulation. Nevertheless, its role in molecular processes and pathobiology is far from understood. A roadblock is that tools for the functional analysis of AS-set events are lacking. To mitigate this, we developed NEASE, a tool integrating pathways with structural annotations of protein-protein interactions to functionally characterize AS events. We show in four application cases how NEASE can identify pathways contributing to tissue identity and cell type development, and how it highlights splicing-related biomarkers. With a unique view on AS, NEASE generates unique and meaningful biological insights complementary to classical pathways analysis.

Severe mitral regurgitation (MR) is one of the most common valvular heart diseases and is frequently associated with advanced left ventricular (LV) systolic dysfunction. Transcatheter edge-to-edge repair (TEER) offers effective symptom relief but may induce abrupt hemodynamic changes leading to afterload mismatch and acute LV failure. Levosimendan may help mitigate this complication by improving contractility, yet evidence supporting its use in this setting is scarce. Therefore, the aim of this study was to systematically evaluate the evidence on the effects of Levosimendan in patients with severe MR and LV dysfunction undergoing TEER. We performed a comprehensive search of PubMed, Embase, Scopus, and Google Scholar. Primary outcomes were postprocedural LV ejection fraction (LVEF) and systolic pulmonary artery pressure (sPAP). Secondary outcomes included procedural success, procedure duration, and in-hospital complications. Five studies comprising 315 patients (n = 141 Levosimendan, n = 174 controls) met the inclusion criteria. Pooled analysis showed no significant difference in postprocedural LVEF between Levosimendan-treated patients and controls (mean difference 0.45%, 95% CI [−1.46–2.35] p = 0.65) and no significant change from baseline. Similarly, postprocedural sPAP did not differ significantly. Procedural success was higher with Levosimendan, and procedure duration was shorter. These hypothesis-generating findings highlight the need for larger, prospective randomized trials to clarify the role of Levosimendan in this setting.

Out-of-hospital cardiac arrest (OHCA) is one of the leading causes of death worldwide, with acute coronary syndromes accounting for most of the cases. While the benefit of early revascularization has been clearly demonstrated in patients with ST-segment-elevation myocardial infarction (STEMI), diagnostic pathways remain unclear in the absence of STEMI. We aimed to characterize OHCA patients presenting to 2 tertiary cardiology centers and identify predicting factors associated with survival. We retrospectively analyzed 519 patients after OHCA from February 2003 to December 2017 at 2 centers in Munich, Germany. Patients undergoing immediate coronary angiography (CAG) were compared to those without. Multivariate regression analysis and inverse probability treatment weighting (IPTW) were performed to identify predictors for improved outcome in a matched population. Immediate CAG was performed in 385 (74.1%) patients after OHCA with presumed cardiac cause of arrest. As a result of multivariate analysis after propensity score matching, we found that immediate CAG, return of spontaneous circulation (ROSC) at admission, witnessed arrest and former smoking were associated with improved 30-days-survival [(OR, 0.46; 95% CI, 0.26-0.84), (OR, 0.21; 95% CI, 0.10-0.45), (OR, 0.50; 95% CI, 0.26-0.97), (OR, 0.43; 95% CI, 0.23-0.81)], and 1-year-survival [(OR, 0.39; 95% CI, 0.19-0.82), (OR, 0.29; 95% CI, 0.12-0.7), (OR, 0.43; 95% CI, 0.2-1.00), (OR, 0.3; 95% CI, 0.14-0.63)]. In our study, immediate CAG, ROSC at admission, witnessed arrest and former smoking were independent predictors of survival in cardiac arrest survivors. Improvement in prehospital management including bystander CPR and best practice post-resuscitation care with optimized triage of patients to an early invasive strategy may help ameliorate overall outcome of this critically-ill patient population.

Magmaris is a bioresorbable magnesium scaffold that has shown favorable safety and efficacy in the treatment of de-novo coronary lesions. To report 1-year outcomes after Magmaris implantation in patients with predominantly complex coronary lesions in the Resorbable Magnesium Scaffold registry (RMS) and to compare them with outcomes from patients with mainly non-complex lesions in the BIOSOLVE-IV registry. The RMS registry is an ongoing, prospective, national, multicenter registry conducted in Germany. Enrollment took place from November 2020 until May 2023 at Cardiovascular Center Oberallgaeu-Kempten, Bavaria, Germany. Follow-up was performed by phone 12 months after index procedure. We report 1-year outcomes of the first 100 consecutively enrolled patients and provide an unadjusted statistical comparison with 1-year outcomes from the BIOSOLVE-IV registry. RMS patients were older (64.9 ± 8.5 vs. 61.9 ± 10.5 years;  = 0.006) and had a significantly more complex lesion profile (  < 0.001), with higher rates of type B2/C lesions (74.0% vs. 15.1%) and moderate-to-severe calcification (24.0% vs. 7.5%), whereas lesion length was similar between the registries (  = 0.118). At 12 months, target-lesion failure did not differ significantly between RMS and BIOSOLVE-IV (  = 0.885), while scaffold thrombosis was numerically more frequent in RMS (2.0% vs. 0.8%;  = 0.384). Despite a more complex lesion profile in RMS, no statistically significant differences in 1-year clinical outcomes were observed between the two registries. This analysis is hypothesis-generating though not conclusive. Conclusive analysis can only be provided by a randomized controlled trial. RMS registry, NCT04679740.

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality worldwide. Non-coding RNAs have already been linked to CVD development and progression. While microRNAs (miRs) have been well studied in blood samples, there is little data on tissue-specific miRs in cardiovascular relevant tissues and their relation to cardiovascular risk factors. Tissue-specific miRs derived from Arteria mammaria interna (IMA) from 192 coronary artery disease (CAD) patients undergoing coronary artery bypass grafting (CABG) were analyzed. The aims of the study were 1) to establish a reference atlas which can be utilized for identification of novel diagnostic biomarkers and potential therapeutic targets, and 2) to relate these miRs to cardiovascular risk factors. Overall, 393 individual miRs showed sufficient expression levels and passed quality control for further analysis. We identified 17 miRs–miR-10b-3p, miR-10-5p, miR-17-3p, miR-21-5p, miR-151a-5p, miR-181a-5p, miR-185-5p, miR-194-5p, miR-199a-3p, miR-199b-3p, miR-212-3p, miR-363-3p, miR-548d-5p, miR-744-5p, miR-3117-3p, miR-5683 and miR-5701–significantly correlated with cardiovascular risk factors (correlation coefficient >0.2 in both directions, p-value (p < 0.006, false discovery rate (FDR) <0.05). Of particular interest, miR-5701 was positively correlated with hypertension, hypercholesterolemia, and diabetes. In addition, we found that miR-629-5p and miR-98-5p were significantly correlated with acute myocardial infarction. We provide a first atlas of miR profiles in IMA samples from CAD patients. In perspective, these miRs might play an important role in improved risk assessment, mechanistic disease understanding and local therapy of CAD.

BackgroundCardiogenic shock (CS) induced by severe aortic stenosis (AS) is a life-threatening condition with high mortality. Despite advancements in emergency interventions, the optimal treatment approach remains uncertain.AimThis study aimed to systematically review and analyse the existing evidence on outcomes of emergency transcatheter aortic valve implantation (eTAVI) and emergency balloon aortic valvuloplasty (eBAV) in CS patients.MethodsA systematic literature review and meta-analysis was performed. The primary endpoint was mortality at 30 days. Secondary endpoints were in-hospital mortality, 1-year mortality, bleeding, major vascular complications, myocardial infarction, stroke, incidence of pacemaker implantation, acute kidney injury and aortic regurgitation.ResultsSeventeen studies were included, totalling 2811 patients. The analysis revealed a 30-day mortality pooled estimated rate for eTAVI of 19% (CI 0.17 - 0.20) and for eBAV 39% (CI 0.32 - 0.46). In-hospital mortality pooled estimated rates were 11% for eTAVI (CI 0.06 - 0.18) and for eBAV 40% (CI 0.28 - 0.54). One-year mortality pooled estimated rates for eTAVI were 29% (CI 0.20 - 0.40) and for eBAV 67% (CI 0.58 - 0.74). Pooled estimated rates of any bleeding were 12% for eTAVI (CI 0.06 - 0.20) and 15% for eBAV (CI 0.10 - 0.21). The rate of major vascular complications for eTAVI was 8% (CI 0.07 - 0.10) and 3% for eBAV (CI 0.0 - 0.23).ConclusionsThis meta-analysis indicates that mortality in CS due to AS remains high despite emergency interventional treatment. These findings offer critical insights for clinical decision-making optimising patient care in this critically ill population.

BackgroundIn patients with acute myocardial infarction (MI) receiving percutaneous coronary intervention (PCI), the role of systemic therapeutic hypothermia remains controversial. We sought to investigate the role of systemic therapeutic hypothermia versus standard of care in patients with acute MI treated with PCI.MethodsThis is a study-level meta-analysis of randomized trials. The primary outcome was all-cause death. The main secondary outcome was infarct size. Other secondary outcomes were recurrent MI, ischemia-driven target vessel revascularization (TVR), major adverse cardiovascular events, and bleeding.ResultsA total of 1012 patients with acute MI receiving a PCI in nine trials (503 randomly assigned to hypothermia and 509 to control) were available for the quantitative synthesis. The weighted median follow-up was 30 days. As compared to controls, patients assigned to hypothermia had similar risk of all-cause death (risk ratio, [95% confidence intervals], 1.25 [0.80; 1.95], p = 0.32), with a trend toward higher risk of ischemia-driven TVR (3.55 [0.80; 15.87], p = 0.09) mostly due to acute or subacute stent thrombosis. Although in the overall cohort, infarct size was comparable between groups (standardized mean difference [95% Confidence intervals], 0.06 [− 0.92; 1.04], p = 0.92), patients effectively achieving the protocol-defined target temperature in the hypothermia group had smaller infarct size as compared to controls (p for interaction = 0.016). Treatment strategies did not differ with respect to the other outcomes.ConclusionsAs compared to standard of care, systemic therapeutic hypothermia in acute MI patients treated with PCI provided similar mortality with a signal toward more frequent repeat revascularization. Among patients assigned to hypothermia, those effectively achieving the protocol-defined target temperature displayed smaller infarct size.Trial RegistrationPROSPERO, CRD42019138754.