TY - JOUR
T1 - Identifying Predictors for Heart Failure Outcomes in Phospholamban p.(Arg14del)–Positive Individuals
AU - van der Heide, Myrthe Y. C.
AU - Verstraelen, Tom E.
AU - de Brouwer, Remco
AU - van Drie, Esmée
AU - Proost, Virginnio M.
AU - van Lint, Freyja H. M.
AU - Bosman, Laurens P.
AU - Houweling, Arjan C.
AU - Dickhoff, Cathelijne
AU - Germans, Tjeerd
AU - Schoonderwoerd, Bas A.
AU - Gimeno-Blanes, Juan R.
AU - Meems, Laura M. G.
AU - te Riele, Anneline S. J. M.
AU - van Spaendonck-Zwarts, Karin Y.
AU - Cox, Moniek G. P. J.
AU - Amin, Ahmad S.
AU - van Tintelen, J. Peter
AU - de Boer, Rudolf A.
AU - Zwinderman, Aeilko H.
AU - Wilde, Arthur A. M.
N1 - Publisher Copyright:
© 2025 The Authors
PY - 2025/10/1
Y1 - 2025/10/1
N2 - 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.
AB - 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.
KW - PLN p.(Arg14del) cardiomyopathy
KW - clinical risk predictors
KW - genetic therapy
KW - heart failure
KW - hereditary cardiomyopathy
KW - risk prediction
UR - https://www.scopus.com/pages/publications/105012599166
U2 - 10.1016/j.jchf.2025.102558
DO - 10.1016/j.jchf.2025.102558
M3 - Article
C2 - 40782726
SN - 2213-1779
VL - 13
JO - JACC: Heart Failure
JF - JACC: Heart Failure
IS - 10
M1 - 102558
ER -