Impact of DCM-Causing Genetic Background on Long-Term Response to Cardiac Resynchronization Therapy.

Background: Patients with nonischemic dilated cardiomyopathy (DCM), severe left ventricular (LV) dysfunction, and complete left bundle branch block benefit from cardiac resynchronization therapy (CRT). However, a large heterogeneity of response to CRT is described. Several predictors of response to CRT have been identified, but the role of the underlying genetic background is still poorly explored.
Objectives: In the present study, the authors sought to define differences in LV remodeling and outcome prediction after CRT when stratifying patients according to the presence or absence of DCM-causing genetic background.
Methods: From our center, 74 patients with DCM subjected to CRT and available genetic testing were retrospectively enrolled. Carriers of causative monogenic variants in validated DCM-causing genes, and/or with documented family history of DCM, were classified as affected by genetically determined disease (GEN+DCM) (n = 25). Alternatively, by idiopathic dilated cardiomyopathy (idDCM) (n = 49). The primary outcome was long-term LV remodeling and prevalence of super response to CRT (evaluated at 24-48 months after CRT); the secondary outcome was heart failure-related death/heart transplant/LV assist device.
Results: GEN+DCM and idDCM patients were homogeneous at baseline with the exception of QRS duration, longer in idDCM. The median follow-up was 55 months. Long-term LV reverse remodeling and the prevalence of super response were significantly higher in the idDCM group (27% in idDCM vs 5% in GEN+DCM; P = 0.025). The heart failure-related death/heart transplant/LV assist device outcome occurred more frequently in patients with GEN+DCM (53% vs 24% in idDCM; P = 0.028).
Conclusions: Genotyping contributes to the risk stratification of patients with DCM undergoing CRT implantation in terms of LV remodeling and outcomes.
Competing Interests: Funding Support and Author Disclosures This study was supported by CRTrieste Foundation and Cassa di Risparmio di Gorizia Foundation to Dr Sinagra. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)