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

JACC Clin Electrophysiol. 2024 Jul;10(7 Pt 1):1455-1464. doi: 10.1016/j.jacep.2024.03.019. Epub 2024 May 22.

Abstract

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.

Keywords: LBBB; LBBBICMP; LV remodeling; cardiac resynchronization therapy; dilated cardiomyopathy; genetic background; super responder.

MeSH terms

  • Adult
  • Aged
  • Bundle-Branch Block / genetics
  • Bundle-Branch Block / physiopathology
  • Bundle-Branch Block / therapy
  • Cardiac Resynchronization Therapy*
  • Cardiomyopathy, Dilated* / genetics
  • Cardiomyopathy, Dilated* / physiopathology
  • Cardiomyopathy, Dilated* / therapy
  • Female
  • Heart Failure / genetics
  • Heart Failure / physiopathology
  • Heart Failure / therapy
  • Humans
  • Male
  • Middle Aged
  • Retrospective Studies
  • Treatment Outcome
  • Ventricular Dysfunction, Left / genetics
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Dysfunction, Left / therapy
  • Ventricular Remodeling* / genetics
  • Ventricular Remodeling* / physiology