BACKGROUND:Postoperative atrial fibrillation (POAF) is considered a convergence of preexisting vulnerability and periprocedural stressors. Although clinical risk scores such as the CHA2DS2-VA score capture clinical risk factors, they do not account for biological processes. Neutrophil activation and the release of extracellular DNA, counterbalanced by endogenous deoxyribonuclease (DNase) activity, may represent a mechanistically relevant pathway in POAF development. OBJECTIVE:We investigated neutrophil markers and DNase activity as indicators of POAF. METHODS:503 patients undergoing major cardiovascular surgery were investigated. Double-stranded DNA (dsDNA), citrullinated histone H3, neutrophil elastase, myeloperoxidase, and DNase activity were measured before surgery. Associations with POAF were assessed using logistic regression adjusted for the CHA2DS2-VA score. Cardiovascular and all-cause mortality was evaluated using Cox regression. Incremental prognostic information was assessed by comparing nested regression models. RESULTS:POAF occurred in 42.1% of patients. Although baseline dsDNA levels did not differ between groups, multivariable analysis identified dsDNA as independently associated with POAF. DNase activity was independently associated with lower risk of POAF. The DNase factor, calculated as dsDNA divided by DNase activity, conferred an increased risk of POAF. Inclusion of the DNase factor significantly improved model fit beyond the CHA2DS2-VA score. During a median follow-up of 72 months, 109 patients (21.7%) died. dsDNA independently predicted mortality. Higher DNase activity was independently associated with lower mortality. CONCLUSION:Preoperative extracellular DNA burden and DNase activity associate with POAF and long-term mortality after major cardiovascular surgery. Impaired regulation of extracellular DNA reflects a vulnerability phenotype not captured by established clinical risk scores and provides incremental prognostic information.

Pediatric out-of-hospital cardiac arrest (OHCA) is rare and often triggered by respiratory arrest. Its management is more complex than in adults, with low survival rates. In addition, European epidemiologic data on pediatric OHCA are scarce. This study analyzed the respective key figures of a west-European metropolitan area over the course of several years. This retrospective study examined pediatric non-traumatic OHCA cases treated by the Emergency Medical Service (EMS) Vienna between 01/2019 and 12/2023, reporting on incidences, rates of return of spontaneous circulation (ROSC), survival to hospital discharge, and neurological outcomes. Logistic regression explored the relationship between outcomes and predictors, while Poisson regression was applied to analyze the pandemic lockdowns. During the observational period, the EMS Vienna assessed 19,067 patients (all age groups) without signs of circulation, and started cardiopulmonary resuscitation (CPR) in 110 patients <18 years (1.2/100,000 population per year, 1.4

Despite recent advances in cardiovascular pharmacotherapy, prevention and treatment of many cardiovascular diseases remain limited with a clear need for more effective and safer pharmacological strategies. Here, we summarize the most relevant advances in cardiovascular pharmacotherapy in 2025, including the approval of four new drugs (aficamten, etripamil, lerodalcibep, and plozasiran), the label expansions for five already approved drugs, and the results of major randomized clinical trials with already approved drugs, including those that met the prespecified primary endpoints (positive trials) representing new pharmacological options for cardiovascular diseases, those with neutral or negative results, which did not confirm the primary endpoints and the withdrawal from the US market of Andexanet-alfa for safety concerns. Finally, we present the most promising experimental cardiovascular drugs currently being investigated in ongoing Phase 2 and 3 clinical trials.

Background: Heart failure (HF) and chronic kidney disease (CKD) create a mutually reinforcing cycle, escalating disease development, and increasing morbidity and mortality rates. Both are common comorbidities promoting AF and contributing to heightened symptom burden and poorer outcomes in AF. Here our aim was to investigate the relationship of HF and CKD with cardiorenal outcomes in patients with atrial fibrillation (AF). Methods: Patients with AF, treated at a tertiary centre between January 2005 and July 2019, were included. The primary endpoint was a composite of cardiovascular (CV) death and hospitalization for HF (HHF). Secondary outcomes were the individual components of the primary endpoint, all-cause death, renal death, and dialysis. Results: We included a total of 7,412 patients (median age 70 years, 39.7% female) with AF and followed them over a median of 4.5 years. There was a significant stepwise increase in 5-year event rates for the composite of CV death/HHF (no CKD and no HF: 23%, HF: 61%, CKD: 63%, CKD and HF: 82%; P log-rank <0.001). Both CKD (adjusted hazard ratio [HR]: 1.87, 95% confidence interval [CI]: 1.55–2.25) and HF (adjusted HR: 2.57, 95% CI: 2.22–2.98) were significantly associated with CV death/HHF after multivariable adjustment. A similar association was observed for the individual components of the primary endpoint and renal death/dialysis. Conclusions: Both CKD and HF significantly increase the risk of CV death and HHF, as well as renal death/dialysis in patients with AF. Risk assessment should expand beyond stroke and bleeding to cardiorenal complications including HHF, CV, and renal death, as well as kidney failure.

Heart failure (HF) and atrial fibrillation (AF) are major global health challenges with rising prevalence and significant morbidity, mortality, and healthcare burden. Despite advances in HF management, AF remains a critical comorbidity that worsens outcomes and requires ad hoc treatment strategies, increasing the risk of non-adherence and side effects. While rhythm control strategies in AF have gained attention for their prognostic benefits in HF, the pharmacological treatment of HF in patients with AF, including the benefit of rhythm versus rate control, remains underexplored. The relationship between HF and AF lacks sufficient evidence and targeted research to assess the optimal treatment strategies. This narrative review critically examines current HF pharmacotherapy in the context of AF, focusing on the four cornerstone treatments and modifiers of prognosis for HF with reduced ejection fraction: beta-blockers, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers/sacubitril-valsartan, aldosterone antagonists, and sodium–glucose co-transporter 2 inhibitors. Although these therapies are well-established in HF patients, their efficacy in patients with concomitant AF requires further prospective investigation. The unique challenges posed by AF, including arrhythmia-induced remodelling and cardiomyopathy, necessitate a more individually tailored treatment. We also highlight critical knowledge gaps and the need for dedicated clinical trials specifically assessing HF therapies in AF subgroups, such as paroxysmal, long-standing persistent and permanent AF, and the benefit of heart rate and rhythm control strategies. The future of precision medicine in HF-AF management lies in bridging these evidence gaps through targeted research and interdisciplinary collaboration.

BACKGROUND:Biomarkers of inflammation are reliable predictors of adverse cardiovascular events in coronary artery disease. However, the association between systemic inflammation and percutaneous coronary intervention (PCI)-related adverse events remains widely unclear. OBJECTIVES:The objective of this study was to investigate the association of routinely assessed inflammatory biomarkers C-reactive protein, leukocytes, and neutrophil-to-lymphocyte ratio (NLR) with patient outcomes in an unselected patient cohort undergoing PCI. METHODS:A total of 7,412 patients (median age 64 years, 73.2% male) were enrolled in this single-center observational trial with a median follow-up time of 4.6 years. Target lesion revascularization (TLR) and acute stent thrombosis (ST) were defined as primary endpoints. Further endpoints included mortality, cardiovascular mortality, and 3-point major adverse cardiovascular events (MACE) (composite of cardiovascular mortality, myocardial infarction, and stroke). Cox proportional hazard regression was used for statistical analysis with a level of significance set at P < 0.01. RESULTS:In the total study cohort, patients experiencing subsequent TLR (n = 488, 6.6%) had more comorbidities and underwent more complex primary interventions. Interestingly, no relation was found between systemic inflammation and subsequent TLR (eg, adjusted HR for C-reactive protein: 0.93 [95% CI: 0.85-1.03], P = 0.150), 30-day TLR (0.89 [95% CI: 0.75-1.05], P = 0.177), or acute ST (1.06 [95% CI: 0.79-1.42], P = 0.708) in multivariable analysis, neither in elective nor in acute interventions. All investigated inflammatory biomarkers were, however, significantly associated with all-cause mortality, cardiovascular mortality, and 3-point MACE, even after comprehensive adjustment for clinical and interventional parameters. CONCLUSIONS:While our results emphasize the importance of systemic inflammatory activation for mortality and MACE, elevated baseline inflammatory parameters show no correlation with TLR or acute ST and, therefore, should not delay PCI in the era of second-generation drug-eluting stents.

Hyperbaric oxygen therapy (HBOT) after out-of-hospital cardiac arrest (OHCA) remained untested in humans despite promising preclinical evidence. We thus evaluated feasibility, safety, and early biological signals of HBOT across distinct clinical cohorts and exposure subgroups. This prospective single centre randomized controlled multi-cohort study enrolled (i) intensive care (ICU) patients as soon as possible after return of spontaneous circulation (ROSC) (maximum 24 hours), (ii) long-term OHCA survivors, and (iii) healthy volunteers. Within each cohort, participants were stratified into HBOT exposure groups (no, one, or five sessions). Assessments included serial laboratory biomarkers (endothelial, inflammatory, oxidative stress, neuronal, myocardial), vascular stiffness, neurocognitive testing, and psychological questionnaires. Changes from baseline were analysed using Wilcoxon and Kruskal–Wallis tests, alongside adjusted general linear models (GLM) with key clinical covariates. HBOT delivery was feasible and safe, with full follow-up achieved across all three cohorts. In ICU patients, inflammatory (TNF-α, CRP), oxidative stress (MPO, TBARS, ROMO-1), and endothelial dysfunction markers (ET-1, ADMA) improved over time, while neuronal injury (NSE) showed partial attenuation; signals were most evident in the 1x and 5x HBOT exposure groups. Among long-term survivors, global and domain-specific cognition, arterial stiffness (pulse wave velocity), and psychological measures improved, with effects primarily observed in HBOT groups. Volunteers exhibited stable cognition but reproducible PWV reductions in HBOT groups, indicating a vascular effect beyond the post-cardiac arrest context. In this feasibility study, HBOT was successfully implemented across ICU patients, survivors, and healthy volunteers, with dose-stratified exposure subgroups. Converging biological signals indicate the potential of HBOT towards an attenuation of systemic inflammation and oxidative stress, recovery of endothelial and vascular function, and mitigation of neuronal and myocardial injury. These early findings provide a rationale for further evaluations of HBOT as a pleiotropic intervention targeting the endothelium–inflammation–injury axis after cardiac arrest.

The use of drug-coated balloons (DCB) in percutaneous coronary interventions (PCI) is increasing due to potential benefits mainly by avoiding foreign material although a widespread application area beyond in-stent restenosis lacks robust clinical data to date. As such, we aimed to assess the safety and efficacy of DCBs in treating de novo lesions. For this analysis, we included all patients treated with DCB in a de novo lesions from 2010 to 2019 at our institution. We performed a 1:1 propensity score matching to pair each DCB intervention with a comparable DES intervention. Follow-up continued until 09/2022 to assess clinical outcomes. A total of 303 patients with de novo lesion were matched to 303 patients with comparable baseline characteristics. The median follow-up time was 5.7 years (IQR 2.7–9.3). There were no significant differences in cardiovascular (CV) mortality (HR 1.01 [95

In critically ill patients with atrial fibrillation (AF), standard treatment algorithms might not be applicable. Emergency departments (ED) play a crucial role in implementing individualized treatment approaches. The aim of this study was to assess the association of lactate and cardioversion success rates in AF patients presenting to an ED. This was a retrospective single-center study analyzing 3535 AF episodes between 2012 and 2022. The main outcome was cardioversion (CV) to sinus rhythm (SR) depending on serum lactate levels (mmol/L). Lactate levels were divided into quintiles (lac < 1.1, 1.1-1.3, 1.4-1.7, 1.8-2.3 and > 2.3 mmol/L). Overall CV success declined with rising lactate levels (SR: lac < 1.1 79% (n = 547), 1.1-1.3 76% (n = 579), 1.4-1.7 73% (n = 562), 1.8-2.3 66% (n = 447), > 2.3 mmol/L 61% (n = 393); p < 0.001). Electrical CV (eCV) was conducted in 1021 (SR 95%), medical CV (mCV) in 706 (SR: 72%), facilitated CV in 523 (SR: 88%) and spontaneous conversion was observed in 591 (46% of all patients without treatment) cases. ECV was effective independent of lactate levels (SR: lac < 1.1 96% (n = 225), 1.1-1.3 93% (n = 253), 1.4-1.7 97% (n = 228), 1.8-2.3 92% (n = 154), > 2.3 mmol/L 95% (n = 106); p = 0.716). However, for mCV, conversion success decreased with increasing lactate levels (SR: lac < 1.1 84% (n = 95), 1.1-1.3 80% (n = 109), 1.4-1.7 75% (n = 115), 1.8-2.3 67% (n = 93), > 2.3 mmol/L 59% (n = 97); p < 0.001). Overall cardioversion success was less likely with rising lactate levels; especially medical cardioversion success rates decreased. Therefore, AF in critically ill may benefit from either electrical cardioversion, treatment of the underlying condition, or primary rate control.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) can damage the endothelium and increase arterial stiffness, potentially leading to adverse cardiovascular events. In parallel, systemic inflammation in COVID-19 also impacts endothelial function. Angiotensin-converting enzyme 2 (ACE2) promotes vasodilation and anti-inflammatory effects, but also facilitates SARS-CoV-2 entry into human cells. Thus, concerns have been raised about the use of RAAS inhibitors (RAASi) in COVID-19 patients due to potential ACE2 upregulation. However, the clinical significance of increased plasma ACE2 (sACE2) in RAASi-treated COVID-19 patients remains unclear. Methods: This prospective, single-centre study evaluated RAASi, sACE2, and vascular function in acutely ill patients with COVID-19 in comparison with acutely ill patients without COVID-19. Adult emergency department patients with confirmed or suspected COVID-19 were enrolled and underwent pulse wave velocity, ankle brachial index, and sACE2 measurements. Results: In the 152 included patients (50% female, median age 62 years, 68% COVID-19 positive), the sACE2 values were slightly higher in the COVID-19 (0.485 [0.364-1.329]) than in the non-COVID-19 subgroup (0.458 [0.356-1.138]; p = 0.70). No significant differences in sACE2 were observed between patients with and without RAASi, regardless of COVID-19 status. Pulse wave velocity values differed significantly between groups (p = 0.015). Conclusions: In emergency department patients, sACE2 was upregulated in COVID-19 patients, probably due to oxidative stress and inflammation. RAASi did not increase sACE2, but may have protective effects against inflammation. Elevated sACE2 appeared to have a beneficial effect on arterial stiffness in all patients. These findings support continued RAASi therapy in COVID-19 patients to protect against chronic inflammation and apoptosis.

Antithrombotic therapy is essential after coronary artery bypass graft surgery to reduce ischaemic events and prevent graft occlusion. Although aspirin remains the most commonly used agent, in higher-risk patients, dual antiplatelet therapy or combining antiplatelet therapy with oral anticoagulation may be beneficial, but this increases bleeding risk. The choice of antithrombotic therapy should be tailored to each patient, based on their ischaemic and bleeding risks, and regularly reassessed. Here, the scientific evidence underlying the key aspects of the choice of antithrombotic therapy after coronary artery bypass grafting is reviewed. Consensus statements for best clinical practice are provided and areas requiring further research are highlighted.

BACKGROUND:Out-of-hospital cardiac arrest (OHCA) has low survival rates worldwide. For the diagnosis of acute coronary syndrome causing OHCA and the identification of patients eligible for immediate coronary angiography, the post-return of spontaneous circulation electrocardiogram (post-ROSC ECG) is crucial. However, it is still unclear whether post-ROSC ECG features also pose a sensible feature for outcome prediction. METHODS:This retrospective study analysed adult non-traumatic OHCA cases with post-ROSC ECGs admitted to one of the three participating centers in Vienna (Austria), Pavia (Italy) and Lugano (Switzerland) between 01/2015 and 12/2018, and reports ECG features, survival and neurological outcome (at hospital discharge and after one year). Univariable and multivariable logistic regression assessed associations between ECG features and neurological outcome. RESULTS:STEMI was diagnosed in 53.5% of post-ROSC ECGs. 68.1% of patients were discharged, with 59.5% having a favorable neurological outcome. One year later, 61.6% of non-STEMI patients had a favorable outcome compared to 54% of STEMI patients. Univariable analysis indicated that ST-elevations in II, III, and aVF, as well as a broader QRS complex significantly influenced neurological outcomes at one year. CONCLUSIONS:ECG after ROSC can identify patients at high risk of death after OHCA earlier than other prognostic methods, not only in terms of short-term mortality, but also in terms of neurological outcome one year after OHCA. Wider QRS complex and ST-elevations in II, III, or aVF were identified as specific prognosticators.

Despite substantial advances in cardiovascular pharmacotherapy and devices in recent years, prevention and treatment of many cardiovascular diseases (CVDs) remain limited, thus reflecting the need for more effective and safer pharmacological strategies. In this review, we summarize the most relevant studies in cardiovascular pharmacotherapy in 2024, including the approval of first-in-class drugs for the treatment of resistant hypertension and pulmonary arterial hypertension, label expansions for bempedoic acid and semaglutide, and the results of major randomized clinical trials (RCTs) that have met the pre-specified primary endpoints, thereby filling some gaps in knowledge and opening new perspectives in the management of CVD, and those RCTs whose results did not confirm the proposed research hypotheses. We also include a section on drug safety, where we describe the newest data on adverse reactions and drug-drug interactions that may complicate treatment and/or reduce drug adherence with the consequent decrease in drug effectiveness. Finally, we present the most important ongoing phase 2 and phase 3 clinical trials assessing the efficacy and safety of cardiovascular drugs for the prevention and treatment of CVD.

AIMS:Antiarrhythmic drugs are used during cardiopulmonary resuscitation (CPR) to improve the chances of return of spontaneous circulation (ROSC) in shockable rhythms. To date, their impact on clinical outcomes remains uncertain. This review aimed to provide an evaluation of respective up-to-date evidence. METHODS AND RESULTS:We searched Embase, MEDLINE®, and Cochrane Central Register of Controlled Trials. Data on study design, population characteristics, antiarrhythmic drugs used, and predefined outcomes were extracted. A meta-analysis was conducted in groups with at least three studies reporting the same outcome. Additionally, we performed subgroup analysis according to the study design. Initially, 5080 studies were identified, and 29 were included, with, in total, 60 205 patients. A statistically significant difference in achieving ROSC was found comparing (i) lidocaine and no lidocaine, favouring lidocaine [odds ratio (OR) = 1.61, 95% confidence interval (CI): 1.11-2.32, P = 0.01]; (ii) nifekalant and lidocaine, favouring nifekalant (OR = 4.18, 95% CI: 2.23-7.83, P < 0.00001); and (iii) esmolol and no esmolol, favouring esmolol (OR = 3.0, 95% CI: 1.40-6.40, P = 0.005). For the effect on survival to hospital discharge, a significant difference between lidocaine and no lidocaine, favouring lidocaine (OR = 1.66, 95% CI: 1.02-2.7, P = 0.04), was found. CONCLUSION:Evidence supporting the use of any antiarrhythmic drugs during CPR remains limited and is partly inconclusive. For the effect on survival to hospital discharge, a statistically significant difference was only found favouring the administration of lidocaine compared to no lidocaine. Further research with improved trial design and into novel drug options should be conducted.

Tachydysrhythmias are a challenging aspect of emergency medicine, with atrial fibrillation being the most common. Electrical cardioversion is recommended for hemodynamically unstable patients, while treatment varies according to the dysrhythmia subtype in others. Landiolol, a relatively new ultra-short-acting cardioselective beta-blocker, may be a promising option for prehospital use due to its advantageous pharmacological properties. This observational study included all cases of Landiolol bolus administration of the Emergency Medical Service (EMS) Vienna from 08/2023 until 06/2024. Data were extracted from EMS reports and hospital records. The primary endpoint was drug safety and adverse events. Secondary outcomes were the effect on hemodynamic and rate- and rhythm control. We analysed reports of 111 patients having received push-dose Landiolol (median 74 [interquartile ranges (IQR) 62–81] years; 57

BACKGROUND:Regional data and trends in survival from out-of-hospital cardiac arrest (OHCA) are vital to improve favourable outcomes. Since the last cardiopulmonary resuscitation (CPR) guideline update, comprehensive OHCA data of the metropolitan area of Vienna, Austria, have been scarce. METHODS:This retrospective study analysed adult non-traumatic OHCA cases in Vienna between January 2019 and December 2023. It assessed emergency medical service records and clinical patient data and reported incidences, return of spontaneous circulation (ROSC) rates, survival to hospital discharge and neurological outcome. Logistic regression assessed associations between outcomes and predictors, while Poisson regression examined incidence changes before, during and after COVID-19 lockdowns. RESULTS:During the observation period, the Emergency Medical Service Vienna started CPR in a total of 7433 patients (77.1/100 000 population per year). Sustained ROSC was observed in 24.8%, survival to hospital discharge in 9.3% and a Cerebral Performance Category (CPC) Score of 1 or 2 in 6.8%, similar to prior data. However, patients with witnessed cardiac arrest of suspected cardiac aetiology and an initial shockable rhythm had a substantially higher rate of survival to hospital discharge (39%), and CPC of 1 or 2 (29.6%). Similarly, patients with CPC 1 or 2 before CPR had better outcomes than the overall cohort. During COVID-19, there was a decline in all outcome parameters. CONCLUSIONS:Survival after OHCA in Vienna seems stable, but significant improvements in outcome parameters are seen in a 'high outcome potential cohort' over the last 15 years. This reaffirms the need to continue focusing on rapid initiation of bystander CPR and early defibrillation.

AIMS:Metabolic disorders are established risk factors for coronary artery disease (CAD) and major adverse cardiovascular events (MACEs). Although obesity is closely associated with metabolic disease, data on its role as a separate cardiovascular risk modifier in metabolically healthy (MH) individuals are limited, particularly in patients with CAD. Thus, this study aims to investigate risk profiles of metabolic phenotypes on outcomes in patients undergoing invasive coronary angiography. METHODS AND RESULTS:A total of 12 760 patients evaluated for chronic coronary syndrome (CCS) were distinguished into four metabolic phenotypes: MH/metabolically unhealthy (MU) non-obese/obese (MHN, MHO, MUN, and MUO). The association of metabolic phenotypes with outcome was assessed using Cox regression models, adjusted for age, sex, and renal dysfunction. Within the total study cohort (median age 68 years, 57.3% male), 56.5% presented MH (43.3% MHN; 13.1% MHO) and 43.5% MU (28.3% MUN; 15.2% MUO). Irrespective of CCS, metabolic phenotypes showed different risks for MACE, all-cause mortality, and revascularization. While metabolic disease emerged as a robust predictor of events, obesity alone did not [e.g. in patients with obstructive CCS: MHO vs. MHN: adj. hazard ratio (HR) 0.947, 95% confidence interval (CI) 0.728-1.231, P = 0.683; MUO vs. MUN: adj. HR 0.974 (95% CI 0.809-1.172), P = 0.780]. However, MH individuals experienced lower event rates with increasing body mass index (BMI). CONCLUSION:This study indicates metabolic health, rather than obesity, is a key predictor of adverse events in CCS prevention, revealing an obesity paradox in MH individuals. Thus, cardiovascular risk assessment should prioritize metabolic health over BMI. Integrating metabolic profiling into routine evaluations may help optimize prevention and personalized treatment strategies.