Abstract 12547: Obesity as Risk Factor for Malignant Ventricular Arrhythmias in Phospholamban Cardiomyopathy

Abstract

Introduction: The pathogenic phospholamban (PLN) p.Arg14del mutation can cause severe arrhythmogenic cardiomyopathy. However, disease penetrance and clinical course are heterogenous and can differ largely between affected individuals. The impact of external factors - such as lifestyle - on the clinical course has not been studied yet. Hypothesis: We hypothesized that obese PLN mutation carriers have worse clinical outcomes, characterized by a higher burden of malignant ventricular arrhythmias (MVA). Methods: PLN p.Arg14del mutation carriers from the Dutch PLN registry with available follow-up (FU) data were included. MVA was defined as either sustained ventricular tachycardia, ventricular fibrillation, appropriate implantable cardioverter defibrillator intervention or (aborted) cardiac arrest. Patients were categorized into three groups based on their body mass index (BMI): normal weight (BMI 18.5 - 24.9 kg/m 2 ), overweight (25.0 - 29.9 kg/m 2 ) and obese (BMI > 30.0 kg/m 2 ). Mutation carriers with a BMI < 18.5 kg/m 2 or MVA at baseline were excluded. Results: A total of 179 PLN mutation carriers were included in this analysis: 105 (58.7%) normal weight, 59 (33.0%) overweight, 15 (8.4%) obese. The obese group had the highest percentage of MVA (26.7%), followed by the overweight (13.6%) and normal weight (4.8%) groups, as shown in the Kaplan-Meier curve (log-rank 0.016). Continuous BMI was significantly correlated with the incidence of MVA during FU: hazard ratio 1.15 [1.04 - 1.27; p=0.006] per 1-unit increase of BMI, adjusted for age, sex and comorbidities (hypertension, type 2 diabetes mellitus, dyslipidemia, coronary heart disease). Additionally, BMI value predicted MVA with an area under the curve of 0.73 [0.63 - 0.84; p=0.002]. Conclusions: In PLN p.Arg14del mutation carriers, high BMI values and obesity are associated with higher incidence of MVA. This suggests a potential role for lifestyle intervention in the management of this genetic cardiomyopathy.