BACKGROUND: A pathogenic variant in the gene encoding phospholamban (PLN), a protein regulating calcium homeostasis of cardiomyocytes, causes PLN cardiomyopathy. It is characterized by a high arrhythmic burden and can progress into severe cardiomyopathy. Risk assessment guides ICD therapy and benefits from personalization. It is unknown whether sex-specific differences in PLN cardiomyopathy exist.
OBJECTIVE: Improving accuracy of PLN cardiomyopathy diagnosis and risk assessment by investigating sex-specific aspects.
METHODS: We analyzed a multicenter cohort of 933 patients with the PLN p.(Arg14del) pathogenic variant following up on a recently developed PLN risk model. Sex-specific differences in incidence of risk model components were investigated: low voltage ECG, premature ventricular contractions (PVC), negative T waves, and left ventricular ejection fraction (LVEF).
RESULTS: Our cohort contained 412 males and 521 females. Sustained ventricular arrhythmias (VA) occurred in 77 (18.7%) males and 61 (11.7%) females (p = 0.004). Of 933 cohort members, 287 (31%) had ≥1 low voltage ECG during follow-up; 180 (63%) females and 107 (37%) males (p = 0.006). Female sex, age, age at clinical presentation, and proband status predicted low voltage ECG during follow-up (AUC: 0.78). Sustained VA-free survival was lowest in males with low voltage ECG (p < 0.001).
CONCLUSION: Low voltage ECGs predict sustained VA and are a component of the PLN risk model. Low voltage ECGs are more common 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.