Identifying Predictors for Heart Failure Outcomes in Phospholamban p.(Arg14del)–Positive Individuals
Year: 2025
Type: article
Study design: Observational Study
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.
Source: JACC Heart Failure
Authors: Myrthe Y.C. van der Heide, Tom E. Verstraelen, Remco de Brouwer, Esmée van Drie, Virginnio M. Proost, Freyja H.M. van Lint, Laurens P. Bosman, Arjan C. Houweling, Cathelijne Dickhoff, Tjeerd Germans, Bas A. Schoonderwoerd, Juan R. Gimeno-Blanes, Laura M.G. Meems, Anneline S.J.M. te Riele, Karin Y. van Spaendonck-Zwarts, Moniek G.P.J. Cox, Ahmad S. Amin, J. Peter van Tintelen, Rudolf A. de Boer, Aeilko H. Zwinderman, Arthur A.M. Wilde
Institutions: Amsterdam University Medical Centers, University of Amsterdam, University Medical Center Groningen, University of Groningen, Utrecht University, University Medical Center Utrecht, ERN GUARD-Heart, Vrije Universiteit Amsterdam, Amsterdam UMC Location Vrije Universiteit Amsterdam, Dijklander Ziekenhuis, Noordwest Ziekenhuisgroep, Frisius MC, Hospital Universitario Virgen de la Arrixaca, Universidad de Murcia, Erasmus MC, Amsterdam UMC Location University of Amsterdam
Language: English
Subfield: Cardiology and Cardiovascular Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $5,000
OpenAlex ID: W4413094450