Identifying Predictors for Heart Failure Outcomes in Phospholamban p.(Arg14del)-Positive Individuals

Abstract

BACKGROUND: Phospholamban (PLN) p.(Arg14del)-positive individuals are at high risk of developing PLN p.(Arg14del)-related cardiomyopathy, which can lead to progressive heart failure that is poorly amenable to standard heart failure treatment. Genetic therapies for patients with hereditary cardiomyopathy are rapidly advancing, but identifying patients who will benefit from and rely on these therapies is challenging because of reduced penetrance and highly variable expression. OBJECTIVES: The aim of this study is to identify clinical predictors of heart failure outcomes in PLN p.(Arg14del)-positive individuals. METHODS: Data were collected of 904 PLN p.(Arg14del)-positive individuals from the PLN/ACM Registry. The primary endpoint of the study was a composite endpoint of heart failure outcomes, defined as heart failure hospitalization, left ventricular or biventricular assist device implantation, heart transplantation, or heart failure-related death. Predictors of heart failure outcomes were identified using Least Absolute Shrinkage and Selection Operator Cox regression analyses with different penalization parameters. RESULTS: During a median follow-up of 5.4 years (Q1-Q3: 2.3-9.7 years), 116 study participants (13%) reached the primary endpoint (heart failure hospitalization [75%], heart transplantation [10.3%], left ventricular or biventricular assist device implantation [9.5%], and heart failure-related death [5.2%]). The predictors that remained significant across all analyses were left ventricular ejection fraction, low-voltage electrocardiogram, and NYHA functional class ?II, measured at first evaluation. CONCLUSIONS: This study identified predictors for heart failure outcomes in PLN p.(Arg14del)-positive individuals that can improve risk prediction. Identifying those at risk for heart failure outcomes is of great importance given the rapid advancements in genetic therapies that may offer potential treatments for hereditary cardiomyopathy.