Introduction: Cardiomyopathies are a clinically and genetically heterogeneous group of diseases, that are associated with significant morbidity and mortality. The aim of the present study is to clarify the molecular-genetic characteristics of cardiomyopathies in patients in Bulgaria. Material and methods: In the present study, targeted analysis of an expanded panel of 242 genes, associated with cardiomyopathy, and an additional panel of 20 genes, associated with hereditary amyloidosis, was performed in a total of 20 Bulgarian patients, diagnosed with cardiomyopathy, as follows: 12 patients with hypertrophic cardiomyopathy (HCM), including 1 pediatric patient, 6 patients with dilated cardiomyopathy (DCM), of whom 2 pediatric patients, and 2 patients with restrictive cardiomyopathy (RCM). Family segregation analyses were performed by direct Sanger sequencing. Results: Genetic findings were present in 90% of the patients. Pathogenic/likely pathogenic variants were found in 12 of the patients (60%), while genetic findings related to the clinical symptoms were not detected in the RCM patients (10%). Approximately 1/3 of the patients had a family history of sudden cardiac death or cardiomyopathy. Pathogenic/likely pathogenic variants were found in 55% of HCM patients with no family history, in ~67% of HCM patients with family history or with sporadic DCM, and in 100% of DCM patients with a positive family history. A respectively 2,5 and 4-fold higher frequency of truncating variants was found in the study group compared to the reports of around 10% in the literature, both in patients with HCM, and in patients with DCM. Pathogenic/likely pathogenic variants in the MYBPC3 gene (71%) were found with the highest frequency in HCM, while DCM is characterized by a diverse genetic profile, and genetic findings in the NDUFB11 and TAZ genes were associated with severe clinical presentation in pediatric patients in the first postnatal days. Results of segregation analyses were reported in 6 of the affected families. Conclusion: The data from the present study supports the importance of conducted genetic testing and medical-genetic counseling in patients and affected families with cardiomyopathy in Bulgaria

This case report concerns a 48-year-old man with a history of ischemic stroke at the age of 41 who reported cardiac hypertrophy, registered in his twenties when explained by increased physical activity. Family history was positive for a mother with permanent atrial fibrillation from her mid-thirties. At the age of 44, he had a first episode of persistent atrial fibrillation, accompanied by left atrial thrombosis while on a direct oral anticoagulant. He presented at our clinic at the age of 45 with another episode of persistent atrial fibrillation and decompensated heart failure. Echocardiography revealed a dilated left atrium, reduced left ventricular ejection fraction, and an asymmetric left ventricular hypertrophy. Cardiac magnetic resonance was positive for a cardiomyopathy with diffuse fibrosis, while slow-flow phenomenon was present on coronary angiography. Genetic testing by whole-exome sequencing revealed three variants in the patient, c.309C > A, p.His103Gln in the ACTC1 gene, c.116T > G, p.Leu39Ter in the PLN gene, and c.5827C > T, p.His1943Tyr in the SCN5A gene, the first two associated with hypertrophic cardiomyopathy and the latter possibly with familial atrial fibrillation. This case illustrates the need for advanced diagnostics in unexplained left ventricular hypertrophy, as hypertrophic cardiomyopathy is often overlooked, leading to potentially debilitating health consequences.