Cardiologist Institut universitaire de cardiologie et pneumologie de Québec - Université Laval Québec, Quebec, Canada
Background: The genetic bases of major non-ischemic cardiomyopathies (hypertrophic, dilated, arrhythmogenic, and restrictive) have been well described, and substantial progress has been made since the 2011 HRS/EHRA expert consensus. A new EHRA/HRS statement published in 2022 outlines updated recommendations for genetic testing indications, highlighting its diagnostic, prognostic, and therapeutic implications. In some cases, a genetic diagnosis enables targeted therapies and facilitates familial screening to identify at-risk relatives for appropriate follow-up.
METHODS AND RESULTS: We retrospectively included all heart transplant recipients at the Quebec Heart and Lung Institute from 2014 to 2024. The final clinical diagnosis was obtained from the Vision C software. Histopathology results of the explanted hearts were reviewed to confirm or refine the diagnosis. For patients without ischemic or congenital cardiomyopathy, the appropriateness of genetic testing was assessed according to the 2022 EHRA/HRS guidelines. Genetic test results were classified as pathogenic variants (PV), variants of uncertain significance (VUS), or benign variants (BV) based on ACMG recommendations.
Between 2014 and 2024, 162 patients underwent heart transplantation. The overall mortality rate was 19.8%. Histopathological data were available for 159 patients (98.1%). Ischemic cardiomyopathy accounted for 37.7% of cases (n=61), and congenital heart disease for 7.4% (n=12). Among non-ischemic cases, 38 patients (23.4%) had dilated cardiomyopathy (DCM), and 17 (10.5%) had hypertrophic cardiomyopathy (HCM). In total, 53 patients (32.7%) underwent genetic testing. Of the 17 HCM patients, 15 (88.2%) were tested, yielding 6 PVs, 4 VUS, and 5 BVs. Among 38 DCM patients, 2 were non-genetic (severe valvular disease), and 19 (50%) underwent testing, with 13 PVs, 3 VUS, and 3 BVs identified.
Conclusion: As heart transplantation is reserved for end-stage cardiomyopathies, most recipients have severe disease. Regardless of the time elapsed since transplantation, clinicians involved in the care of heart transplant recipients should undertake a thorough review of each patient’s medical history to clarify the underlying etiology of cardiomyopathy and assess the appropriateness of genetic testing to enhance familial screening efforts.
