| Summary: | Abstract Approximately 10–20% of all deaths occur unexpectedly and suddenly due to underlying cardiac disease, i.e. sudden cardiac death (SCD). Non-ischemic myocardial diseases cause one in every five SCD cases and most of these cases occur without prior diagnosis of cardiac disease. The aim of this thesis was to investigate the electrocardiographic characteristics and genetic background of non-ischemic myocardial diseases leading to SCD. The study population included a total of 5,869 SCD victims from Northern Finland and 10,864 Finnish subjects from general population. In the I study, we found that early repolarization (ER) in the inferolateral leads of 12-lead ECG was a more common finding among victims of non-ischemic SCD than in general population. In the II study, we investigated the genetic background of non-ischemic SCD victims with primary myocardial fibrosis (PMF) as the cause of death. Likely disease-causing variants existed in 10% of the study subjects. The variants were predominantly in myocardial structure protein-coding genes that are generally associated with hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy. In the III study we found that 10% of the SCD victims with presumably acquired hypertrophic cardiac disease carried likely disease-causing genetic variants in myocardial genes. This suggests that rare genetic variants may play a role in SCD among patients with either hypertension or obesity-related cardiac disease. In study IV, we investigated the ECG characteristics of various amounts of myocardial fibrosis in SCD victims. The results suggest that fibrotic accumulation in the myocardium manifests as QRS prolongation, QRS fragmentation, pathologic Q waves and T wave abnormalities. In conclusion, the results of this thesis introduce genetic vulnerability in the development of life-threatening non-specific non-ischemic myocardial diseases and highlight the priority of meticulous post-mortem investigations in the case of unexpected SCD. ...
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