Impact of DCM-Causing Genetic Background on Long-Term Response to Cardiac Resynchronization Therapy
Matteo Dal Ferro1, Alessia Paldino1, Caterina Gregorio2
1Cardiovascular Department, Azienda Sanitaria Universitaria Giuliano Isontina (ASUGI), University of Trieste, Trieste, Italy. Member of the European Reference Network for rare, low-prevalence, or complex diseases of the Heart (ERN GUARD-Heart).
Insights
Genetic testing in dilated cardiomyopathy (DCM) patients undergoing cardiac resynchronization therapy (CRT) helps predict treatment response. Patients without a genetic cause (idDCM) showed better long-term outcomes and remodeling compared to those with a genetic background (GEN+DCM).
Area of Science:
- Cardiology
- Genetics
- Heart Failure Research
Background:
- Cardiac resynchronization therapy (CRT) benefits patients with nonischemic dilated cardiomyopathy (DCM), severe left ventricular (LV) dysfunction, and complete left bundle branch block.
- Response to CRT is highly variable, and the influence of genetic factors on outcomes remains underexplored.
- Identifying predictors of CRT response is crucial for optimizing patient selection and management.
Purpose of the Study:
- To investigate differences in LV remodeling and CRT outcome prediction based on the presence or absence of a DCM-causing genetic background.
- To stratify patients undergoing CRT based on genetic testing results.
- To assess the impact of genetic background on long-term response to CRT.
Main Methods:
- Retrospective analysis of 74 DCM patients who underwent CRT and genetic testing.
- Patients were classified as genetically determined disease (GEN+DCM) or idiopathic DCM (idDCM).
- Primary outcomes: long-term LV remodeling and super response to CRT; Secondary outcome: heart failure-related death/transplant/LV assist device.
Main Results:
- GEN+DCM and idDCM groups were similar at baseline, except for longer QRS duration in idDCM.
- The idDCM group showed significantly higher long-term LV reverse remodeling and super response rates (27% vs 5%, P=0.025).
- The GEN+DCM group experienced a higher incidence of heart failure-related death/transplant/LV assist device (53% vs 24%, P=0.028).
Conclusions:
- Genotyping provides valuable risk stratification for DCM patients undergoing CRT.
- Genetic background significantly influences long-term LV remodeling and clinical outcomes after CRT.
- Differentiating between genetically determined and idiopathic DCM can refine prognostication in CRT candidates.
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.
