Sex-specific aspects of phospholamban cardiomyopathy: The importance and prognostic value of low-voltage electrocardiograms

摘要

BACKGROUND A pathogenic variant in the gene encoding phospholamban (PLN), a protein that regulates calcium homeostasis of cardiomyocytes, causes PLN cardiomyopathy. It is characterized by a high arrhythmic burden and can progress to severe cardiomyopathy. Risk assessment guides implantable cardioverter-defibrillator therapy and benefits from personalization. Whether sex-specific differences in PLN cardiomyopathy exist is unknown.& nbsp;OBJECTIVE The purpose of this study was to improve the accuracy of PLN cardiomyopathy diagnosis and risk assessment by investigating sex-specific aspects.& nbsp;METHODS We analyzed a multicenter cohort of 933 patients (412 male, 521 female) with the PLN p.(Arg14del) pathogenic variant following up on a recently developed PLN risk model. Sex-specific differences in the incidence of risk model components were investigated: low-voltage electrocardiogram (ECG), premature ventricular contractions, negative T waves, and left ventricular ejection fraction. RESULTS Sustained ventricular arrhythmias (VAs) occurred in 77 males (18.7%) and 61 females (11.7%) (P = .004). Of the 933 cohort members, 287 (31%) had ?1 low-voltage ECG during follow-up (180 females [63%], 107 males [37%]; P = .006). Female sex, age, age at clinical presentation, and proband status predicted low-voltage ECG during follow-up (area under the curve: 0.78). Sustained VA-free survival was lowest in males with low-voltage ECG (P < .001).& nbsp;CONCLUSION Low-voltage ECGs predict sustained VA and are a component of the PLN risk model. Low-voltage ECGs are more com-mon in females, yet prognostic value is greater in males. Future studies should determine the impact of this difference on the risk prediction of PLN cardiomyopathy and possibly other cardiomyopathies.& nbsp; (C) 2021 Heart Rhythm Society