Giuseppe Rosano

Background: The VICTOR trial did not meet its primary composite endpoint of cardiovascular death or first hospitalization for heart failure (HF) but demonstrated a nominally significant reduction in the prespecified and powered endpoint of cardiovascular death with vericiguat in patients with HF and reduced ejection fraction (HFrEF). Bayesian and actuarial methods offer complementary frameworks to quantify the probability and lifetime implications of this mortality benefit. Methods: This post hoc analysis of the VICTOR trial applied Bayesian and actuarial analyses. Bayesian analysis estimated the probability that vericiguat reduces mortality, integrating trial data with prior evidence. Actuarial analysis used restricted mean survival time (RMST) to quantify event-free survival at 1 and 2 years, and age-based Cox proportional hazards modelling to project lifetime survival gains across ages 45–80. Results: Bayesian analyses showed a consistently high probability of mortality benefit with vericiguat, regardless of whether sceptical or optimistic prior evidence was weighted. For cardiovascular mortality, the sceptical prior yielded a 98.4% posterior probability of any benefit, a 77.6% probability of at least a 10% relative reduction, and a 20.4% probability of at least a 20% reduction. The VICTORIA-based optimistic prior yielded 99.1%, 60.7%, and 2.2%, respectively. Similar results were observed for all-cause mortality. Actuarial analyses demonstrated greater event-free survival with vericiguat over 1 and 2 years. Lifetime projections suggested that vericiguat may extend overall survival across a broad age range, with the largest gains observed of ∼1.6 to 1.9 years for those aged 55 to 60 at randomization. Conclusion: In this post hoc analysis, Bayesian and actuarial methods provided hypothesis-generating evidence of a cardiovascular mortality benefit with vericiguat in HFrEF, an endpoint for which the trial was prospectively powered, that warrants prospective confirmation.

Background and Aims: It is uncertain whether the effect of vericiguat varies across levels of background guideline-directed medical therapy (GDMT) in heart failure with reduced ejection fraction (HFrEF). Methods: We conducted an exploratory analysis of VICTOR, which enrolled 6105 ambulatory patients with HFrEF without recent worsening. GDMT exposure was classified as basic adherence (on vs off), indication-corrected adherence (accounting for eligibility and contraindications), and dose-corrected adherence (≥50% target dose). A GDMT intensity score was computed from class-specific dose levels. The primary endpoint was the composite of cardiovascular death or first HF hospitalization. Stratified Cox proportional hazards regression models estimated adjusted hazard ratios for vericiguat versus placebo within GDMT strata, with a treatment-by-GDMT interaction test. Results: Baseline contemporary GDMT use was high (any ARNI/ACE/ARB 93.9%, ARNI 56%, SGLT2i 59%, MRA 78%, beta-blocker 94%). Basic adherence: adjusted HRs for the primary endpoint were similar whether or not patients were on ACEi/ARB, ARNI, any RAS inhibitor, beta-blocker, or SGLT2i. Dose-corrected adherence: adjusted HRs favoured vericiguat in ARNI target-dose users (0.73; 0.57–0.93) and in any RAS target-dose users (0.77; 0.64–0.93), with lower risk on vericiguat in patients not meeting MRA target dose (0.67; 0.48–0.95); interaction P-values were nominally significant. The GDMT intensity score showed no significant interaction with treatment. Patterns for cardiovascular death and all-cause death paralleled the primary endpoint. Conclusion: In ambulatory patients with HFrEF receiving contemporary GDMT, we did not find convincing evidence that the neutral effect of vericiguat on cardiovascular death or first HF hospitalization was modified by GDMT class, dose attainment, or overall intensity, in a cohort with very high background GDMT use and limited power for interaction testing. These exploratory, hypothesis-generating findings do not establish independent efficacy or pathway additivity for vericiguat and should not be used to guide clinical recommendations regarding GDMT sequencing. Clinical Trial Registration: NCT05093933

Myocarditis is an important and frequently underrecognized cause of atrioventricular conduction disease and ventricular arrhythmias and may also be associated with atrial arrhythmias and sinus node dysfunction. Arrhythmic risk evolves over time as a result of the interplay between myocardial inflammation, fibrosis, and genetic predisposition. Despite its clinical relevance, guidance for the diagnosis, treatment, and follow-up of arrhythmias in myocarditis has remained limited. This consensus statement provides a structured framework for the management of arrhythmias in myocarditis and inflammatory cardiomyopathy (Infl-CMP), integrating disease phase and genetic background into clinical decision-making. It offers practical guidance across the disease spectrum, including diagnostic evaluation, therapeutic strategies, and longitudinal follow-up. The document was jointly developed by the European Heart Rhythm Association of the European Society of Cardiology (ESC) in collaboration with the Heart Failure Association of the ESC, the ESC Working Group on Myocardial & Pericardial Diseases, and the European Association of Preventive Cardiology of the ESC, together with the Heart Rhythm Society, the Asia Pacific Heart Rhythm Society, and the Latin American Heart Rhythm Society. Consensus advice is organized using a phase-aware framework distinguishing hot, hot-to-cold, and cold phases, with clinical consensus statements graded according to opinion-, observational-, or randomized trial-based evidence and supported by formal author voting. Arrhythmia management is stratified by disease phase. During active inflammation, antiarrhythmic therapy is combined with aetiology-targeted treatment or immunosuppression when indicated. In later stages, substrate-based strategies include pharmacological therapy, device implantation, or ablation. Emphasis is placed on hot-to-cold transition as an arrhythmogenic window and on risk stratification.

Myocarditis is an important and frequently underrecognized cause of atrioventricular conduction disease and ventricular arrhythmias and may also be associated with atrial arrhythmias and sinus node dysfunction. Arrhythmic risk evolves over time as a result of the interplay between myocardial inflammation, fibrosis, and genetic predisposition. Despite its clinical relevance, guidance for the diagnosis, treatment, and follow-up of arrhythmias in myocarditis has remained limited. This consensus statement provides a structured framework for the management of arrhythmias in myocarditis and inflammatory cardiomyopathy (Infl-CMP), integrating disease phase and genetic background into clinical decision-making. It offers practical guidance across the disease spectrum, including diagnostic evaluation, therapeutic strategies, and longitudinal follow-up. The document was jointly developed by the European Heart Rhythm Association of the European Society of Cardiology (ESC) in collaboration with the Heart Failure Association of the ESC, the ESC Working Group on Myocardial & Pericardial Diseases, and the European Association of Preventive Cardiology of the ESC, together with the Heart Rhythm Society, the Asia Pacific Heart Rhythm Society, and the Latin American Heart Rhythm Society. Consensus advice is organized using a phase-aware framework distinguishing hot, hot-to-cold, and cold phases, with clinical consensus statements graded according to opinion-, observational-, or randomized trial-based evidence and supported by formal author voting. Arrhythmia management is stratified by disease phase. During active inflammation, antiarrhythmic therapy is combined with aetiology-targeted treatment or immunosuppression when indicated. In later stages, substrate-based strategies include pharmacological therapy, device implantation, or ablation. Emphasis is placed on hot-to-cold transition as an arrhythmogenic window and on risk stratification.

Patients with cancer usually report limitations of their functional capacity, which may range from subclinical impairment of cardiopulmonary exercise reserve to poor quality of life with physical, cognitive, or psychosocial consequences. Exercise training is a potent multi-targeted approach to control pre-existing and new risk factors. Preliminary evidence shows that it is associated with a lower risk of cancer therapy-related cardiotoxicity and increased self-reported well-being in patients with cancer. Current evidence demonstrates that supervised exercise therapy, including high-intensity interval training, is safe and well-tolerated and reduces risk in subjects with cancer in the pre-, active-, and post-treatment settings. The present consensus document will discuss the role of exercise training in cardio-oncology, focusing on patients with cardiovascular diseases induced by cancer treatment and on those who received cardiotoxic therapies.

Acute heart failure (AHF) is a systemic condition characterised by multiorgan involvement that varies from subclinical to overt organ failure. The liver is particularly vulnerable due to its dual blood supply and sensitivity to haemodynamic and inflammatory disturbances. Abnormal liver function tests are highly prevalent in patients with AHF, reflecting major mechanisms: passive hepatic venous congestion from elevated central venous pressure, hepatocellular ischaemia from low cardiac output, systemic inflammation and poor metabolic status associated with cachexia. In patients with AHF, liver function tests at admission, during hospitalisation and at discharge are independently associated with rehospitalisation, cardiovascular and all-cause mortality. Persistent abnormalities after hospitalisation often reflect incomplete decongestion or irreversible structural liver changes. Therapeutic strategies focus on decongestion, optimisation of cardiac output and medication adjustments to avoid hepatotoxicity. Despite significant advances in understanding cardio-hepatic interactions, major gaps remain, including the lack of standardised definitions, limited mechanistic studies and the underrepresentation of patients with heart failure with preserved ejection fraction in contemporary research. Future research should explore targeted therapies to improve cardiohepatic interactions and patient outcomes.

Acute heart failure with preserved ejection fraction (acute heart failure–heart failure with preserved ejection fraction) is increasingly prevalent, resulting from the interaction between a dysfunctional ventricle, the patient’s comorbidity burden and acute triggers. Patients are typically older, commonly female and have cardiometabolic, renal, arrhythmic, ischaemic and inflammatory comorbidities that produce vulnerability to decompensation. Acute episodes manifest with pulmonary and/or systemic congestion, from abrupt rises in left-sided filling pressures due to cardiac and arterial stiffness driven by neurohormonal activation and inflammation. Congestion and elevated blood pressure are common, but clinical presentation is more heterogeneous, reflecting the haemodynamic abnormalities, severity of triggers and comorbidity load. Diagnosis relies on integrating clinical context, echocardiography, adjusted thresholds of natriuretic peptides, and invasive and/or stress haemodynamics when diagnosis is uncertain. Management requires individualised decongestion, alongside treatment of precipitants. Early initiation of disease-modifying therapies after haemodynamic stability, including sodium–glucose cotransporter 2 inhibitors, mineralocorticoid receptor antagonists and glucagon-like peptide-1 receptor agonists, improves outcomes. Acute heart failure–heart failure with preserved ejection fraction follows a relapsing–remitting trajectory, underscoring the importance of comorbidity management, structured follow-up and preventive strategies.

Heart failure (HF) continues to challenge clinicians worldwide, not only because of its high morbidity and mortality but also due to the persistent difficulty in translating therapeutic advances into routine care. Despite the availability of effective treatments, data show striking gaps in the optimal use of guideline-directed medical therapy. Among the four pillars of guideline-directed medical therapy, mineralocorticoid receptor antagonists (MRAs) remain the least prescribed. This underuse is concerning considering the evidence demonstrating consistent benefits of MRAs across different HF phenotypes. In this review, we revisit the role of MRAs across the spectrum of HF. We summarise the supporting evidence, discuss their mechanisms of action and provide practical guidance on patient eligibility and initiation strategies. In addition, we address common barriers that often limit their use. By combining mechanistic insights, trial evidence and pragmatic recommendations, this review aims to facilitate broader and earlier use of MRAs, thereby helping to close a major gap in the implementation of evidence-based HF care.

Heart failure (HF) remains a major cause of morbidity, mortality and costs for the healthcare systems worldwide, despite advances in diagnostic and therapeutic strategies. The enhancement of preventive measures is now a priority, but effective prevention requires a multidisciplinary strategy addressing a broad spectrum of comorbidities and risk factors. It must also consider the changes in the prevailing phenotype of the patients with HF with a lower impact of coronary artery disease and the increasing role of renal and metabolic conditions leading mostly to HF with preserved ejection fraction. Prevention of HF must take into consideration arterial hypertension, chronic kidney disease, diabetes mellitus, sedentary lifestyle, obesity, dyslipidemia, female-specific risk factors, as well as adverse effects of chemotherapy and radiotherapy. Other key factors include infections and the protective role of vaccination, and environmental and socio-economic determinants of health. In 2022, a position paper of the Heart Failure Association and the European Association of Preventive Cardiology of the ESC was published as a complete overview on this topic and as a compendium to the 2021 ESC Guidelines on HF. However, since then, significant evidence has emerged regarding the potential to prevent HF, particularly in the context of metabolic disorders, diabetes and kidney diseases. This scientific statement aims to provide an updated perspective, highlighting the importance of a holistic and tailored approach to managing the multifaceted contributors to this syndrome.