The heart-musc study: hereditary neuromuscular disorders in cardiac transplant recipients

The Heart-Musc Study is a combined retrospective and cross-sectional study on heart transplant (HTx) recipients. Our main hypothesis is that patients with a non-ischemic cause of cardiomyopathy (CMP) may have a genotype that can cause both cardiomyopathy and a neuromuscular disorder (NMD). In Norway, 1057 subjects have received an HTx since the first procedure performed in 1983. In this retrospective study based on medical records, we studied deceased adult HTx patients that received a transplant in the 20-year period between 2002 and 2022. During these years, genetic tests became more available than previously. We aimed to assess the prevalence of probable genetic cause of CMP with or without NMD. We have until now investigated the phenotypic CMP and NMD, i.e symptoms and findings prior to HTx, family history and genetic test results if reported. From 2002 to 2022, 597 adult subjects received an HTx. Among these, 163 were deceased. Sixty-nine (42%) of these deceased patients had a non-ischemic CMP, while ninety-four (58%) had an ischemic heart disease or other acquired causes of heart failure. The mean age at HTx in the non-ischemic group was 53 years versus 54 years in the other group, and the majority were men in both groups. Genetic testing had been performed in only fourteen (20%) of the 69 HTx recipients with non-ischemic CMP. Eight patients were found to have a pathogenic variant in a known CMP gene, and for six of these patients the mutations were in genes that may also give rise to a NMD phenotype. Biopsies and other supplementary tests indicated NMD in additional three patients. Twenty-one (30 %) of the patients in the non-ischemic group had a positive family history of cardiomyopathy, arrhythmia, or suspected sudden cardiac death but were not tested In addition, 26 /69 subjects (38 %) had a possible clinical NMD phenotype based on journal records. Genetic and clinical investigations of the living HTx cohort is needed, to get a true number of genetic CMP with or without NMD in HTx recipients. The Heart-Musc Study is a combined retrospective and cross-sectional study on heart transplant (HTx) recipients. Our main hypothesis is that patients with a non-ischemic cause of cardiomyopathy (CMP) may have a genotype that can cause both cardiomyopathy and a neuromuscular disorder (NMD). In Norway, 1057 subjects have received an HTx since the first procedure performed in 1983. In this retrospective study based on medical records, we studied deceased adult HTx patients that received a transplant in the 20-year period between 2002 and 2022. During these years, genetic tests became more available than previously. We aimed to assess the prevalence of probable genetic cause of CMP with or without NMD. We have until now investigated the phenotypic CMP and NMD, i.e symptoms and findings prior to HTx, family history and genetic test results if reported. From 2002 to 2022, 597 adult subjects received an HTx. Among these, 163 were deceased. Sixty-nine (42%) of these deceased patients had a non-ischemic CMP, while ninety-four (58%) had an ischemic heart disease or other acquired causes of heart failure. The mean age at HTx in the non-ischemic group was 53 years versus 54 years in the other group, and the majority were men in both groups. Genetic testing had been performed in only fourteen (20%) of the 69 HTx recipients with non-ischemic CMP. Eight patients were found to have a pathogenic variant in a known CMP gene, and for six of these patients the mutations were in genes that may also give rise to a NMD phenotype. Biopsies and other supplementary tests indicated NMD in additional three patients. Twenty-one (30 %) of the patients in the non-ischemic group had a positive family history of cardiomyopathy, arrhythmia, or suspected sudden cardiac death but were not tested In addition, 26 /69 subjects (38 %) had a possible clinical NMD phenotype based on journal records. Genetic and clinical investigations of the living HTx cohort is needed, to get a true number of genetic CMP with or without NMD in HTx recipients.