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Keywords: Phospholamban; Eplerenone; Fibrosis; Cardiomyopathy; Heart failure; Randomized clinical trial EN Phospholamban Eplerenone Fibrosis Cardiomyopathy Heart failure Randomized clinical trial 4284 4287 4 10/25/23 20231021 NES 231021 Introduction Phospholamban ( I PLN i ; p.Arg14del) cardiomyopathy is an inherited disease caused by the pathogenic p.Arg14del variant in the I PLN i gene. The phospholamban p.(Arg14del) pathogenic variant leads to cardiomyopathy with heart failure and is unresponsive to standard heart failure therapy. Future research into I PLN i p.Arg14del cardiomyopathy disease progression or modification - and more broadly, research into asymptomatic carriers of pathogenic variations associated with genetic cardiomyopathies - may be better designed using the knowledge obtained in this study. Phospholamban R14del mutation in patients diagnosed with dilated cardiomyopathy or arrhythmogenic right ventricular cardiomyopathy: evidence supporting the concept of arrhythmogenic cardiomyopathy. [Extracted from the article]

Background: In the failing heart, energy metabolism is shifted towards increased ketone body oxidation. Nevertheless, the association of beta-hydroxybutyrate (β- OHB) with development of heart failure (HF) remains unclear. We investigated the association between plasma β-OHB and the risk of HF in a prospective populationbased cohort. Design: Plasma β-OHB concentrations were measured in 6134 participants of the PREVEND study. Risk of incident HF with reduced (HFrEF) or preserved (HFpEF) ejection fraction was estimated using multivariable-adjusted Cox regression models. Results: During median follow-up for 8.2 years, 227 subjects were diagnosed with HF (137 with HFrEF; 90 with HFpEF). Cox regression analyses revealed a significant association of higher β-OHB concentrations with incident HF (HR per 1 standard deviation increase, 1.40 (95% CI: 1.21-1.63; P < .001), which was largely attributable to HFrEF. In women, the hazard ratio (HR) for HFrEF per 1 standard deviation increase in β-OHB was 1.73 (95% confidence interval (CI): 1.17-2.56, P = .005) in age, BMI, type 2 diabetes, hypertension, myocardial infarction, smoking, alcohol consumption, total cholesterol, HDL-C, triglycerides, glucose, eGFR and UAE adjusted analysis. In men, in the same fully adjusted analysis, the HR was 1.14 (CI: 0.86-1.53, P = .36) (P < .01 for sex interaction). In N-terminal pro-brain natriuretic peptide (NT-proBNP)-stratified analysis, the age-adjusted association with HF was significant in women with higher NT-proBNP levels (P = .008). Conclusions: This prospective study suggests that high plasma concentrations of β-OHB are associated with an increased risk of HFrEF, particularly in women. The mechanisms responsible for the sex differences of this association warrant further study. [ABSTRACT FROM AUTHOR]

Background: Epicardial adipose tissue (EAT) has been implicated in the pathophysiology of heart failure (HF) with left ventricular ejection fraction (LVEF) >40%, but whether this is due to a regional or global effect of EAT remains unclear., Hypothesis: Regional EAT is associated with alterations in local cardiac structure and function., Methods: Patients with HF and LVEF >40% were studied. Cardiac Magnetic Resonance imaging was used to localize EAT surrounding the right ventricle (RV) and LV separately, using anterior- and posterior interventricular grooves as boundaries. Atrial- and ventricular EAT were differentiated using the mitral-valve position. All EAT depots were related to the adjacent myocardial structure., Results: 102 consecutive HF patients were enrolled. The majority of EAT was present around the RV (42% of total EAT, p < .001). RV-EAT showed a strong association with increased RV mass (β = 0.60, p < .001) and remained associated with RV mass after adjusting for total EAT, sex, N-terminal prohormone of brain natriuretic peptide (NT-proBNP), renal function and blood glucose. LV-EAT showed a similar association with LV mass in univariable analysis, albeit less pronounced (β = 0.24, p = .02). Atrial EAT was increased in patients with atrial fibrillation compared to those without atrial fibrillation (30 vs. 26 ml/m 2 , p = .04), whereas ventricular EAT was similar (74 vs. 75 ml/m 2 , p = .9)., Conclusions: Regional EAT is strongly associated with local cardiac structure and function in HF patients with LVEF >40%. These data support the hypothesis that regional EAT is involved in the pathophysiology of HF with LVEF >40%., (© 2021 The Authors. Clinical Cardiology published by Wiley Periodicals LLC.)