Key result
Post-transplant genetic testing in non-ischemic cardiomyopathy yields a molecular diagnosis in ~39% of recipients.
Why the study?
Genetic testing in heart transplant patients with prior non-ischemic cardiomyopathy is not routinely performed despite its increasing importance for diagnosis and family risk assessment.
Does genetic testing identify pathogenic variants in heart transplant recipients with prior non-ischemic cardiomyopathy?
Observational (n=31)
Does genetic testing identify pathogenic variants in heart transplant recipients with prior non-ischemic cardiomyopathy?
Retrospective genetic testing in heart transplant recipients with prior non-ischemic cardiomyopathy yields a molecular diagnosis in nearly 40% of cases, facilitating important cascade screening for at-risk relatives.
May facilitate cascade screening in non-ischemic cardiomyopathy transplant recipients; leaves open prospective validation before routine adoption.
BACKGROUND: The importance of genetic testing for cardiomyopathies has increased in the last decade. However, in heart transplant patients with former cardiomyopathy, genetic testing in retrospect is not routinely performed. We hypothesize that the yield of genetic testing in this population is considerable, and will have a major impact for both patients and relatives. METHODS: Patients that underwent heart transplantation (HTx) between 1995 and 2020 and were still in follow-up, were offered genetic testing if the primary etiology was non-ischemic cardiomyopathy. Next generation sequencing (NGS) of known cardiomyopathy genes was performed and variants were classified as variant of unknown significance (class 3), likely pathogenic (class 4) or pathogenic (class 5) variant. RESULTS: Of the 99 HTx patients in active follow-up, only 6 patients had a genetic diagnosis at the time of HTx. In this study, 31 selected patients with prior non-ischemic cardiomyopathy underwent genetic testing post HTx. 23/31 patients (74.2%) carried a variant that was classified as class 3 or higher. In 12/31 patients a class 4/5 variant (38.7%) was identified, and in 11/31 patients (35.5%) a class 3 variant. Class 5 Variants in TTN were the most prevalent (7/31), followed by class 5 variants in MYBPC3 (2/31). A positive family history was present in 21/31 (67.7%) and a second precipitating factor (e.g., alcohol abuse, pregnancy) was present in 17/31 patients (54.8%). Diagnostic yield of genetic testing was similar between patients with or without familial history and/or second hit. Through cascade screening 48 family members were screened for presence of a class 4/5 variant, of whom 19 (39.6%) were genotype positive, of whom 10 (52.6%) showed a cardiac phenotype. Appropriate follow-up was offered. CONCLUSIONS: Genetic testing for cardiomyopathy genes established a molecular diagnosis in 38.7% of patients post HTx. These results highlight the importance of genetic testing in this population as it is still often overlooked in patients that already underwent HTx in the past. Genetic testing is highly recommended, independent of family history or second precipitating factors, as it might identify relatives at risk.
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Boen et al. (2022) conducted an observational in Heart transplant recipients with prior non-ischemic cardiomyopathy (n=31). Genetic testing (Next generation sequencing) was evaluated on Identification of a likely pathogenic or pathogenic (class 4/5) variant. Retrospective genetic testing in heart transplant recipients with prior non-ischemic cardiomyopathy established a molecular diagnosis in 38.7% of patients.
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