RESUMEN
Primary myocardial fibrosis (PMF), defined as myocardial fibrosis in the absence of identifiable causes, may represent a common alternative phenotype in various cardiomyopathies and contribute to sudden cardiac death (SCD). No previous definitions of histopathological characteristics exist for PMF. We aimed to evaluate whether common features of fibrosis could be identified. PMF cases (n = 28) were selected from the FinGesture cohort consisting of 5,869 SCD victims that underwent a medicolegal autopsy. Twelve trauma controls and 10 ischemic heart disease cases were selected as reference groups. Further 3 PMF cases and 5 ischemic heart disease cases from autopsies performed in the University of Copenhagen, Denmark, were selected for a validation substudy. Relative area of fibrosis, amount of diffuse and perivascular fibrosis, and location of fibrosis were assessed from left ventricle myocardial samples stained with Masson trichrome. Further evaluations were performed with alpha-smooth muscle actin (α-SMA), vimentin, and CD68 stainings. Mean relative area of fibrosis was 5.8 ± 10.7%, 1.0 ± 0.7%, and 7.0 ± 7.4% in PMF, trauma controls, and ischemic cases, respectively. Fibrosis in the PMF group was mostly located in other sites than the endocardium. Most cases with fibrosis had vimentin-positive but α-SMA-negative stromal cells within fibrotic areas. Histopathologically, PMF represents a heterogeneous entity with variable fibrotic lesions affecting the whole myocardium and a suggested significant role of fibroblasts. These findings may bring validation to PMF being a common manifestation of cardiomyopathies. Evidently, PMF stands out as a particular entity demanding special attention as a cause of SCD.
RESUMEN
OBJECTIVE: A major challenge in reducing the incidence of sudden cardiac death (SCD) is the identification of patients at risk. Myocardial fibrosis has a substantial association with SCD risk but is difficult to identify among general populations. Our aim was to find electrocardiographic (ECG) markers of myocardial fibrosis among SCD victims. METHODS: Study population was acquired from the Fingesture study, which has gathered data from 5869 consecutive autopsied SCD victims in Northern Finland between 1998 and 2017. The degree of fibrosis was determined in histological samples taken from the heart during autopsy and was categorised into four groups: (1) no fibrosis, (2) scattered mild fibrosis, (3) moderate patchy fibrosis and (4) substantial fibrosis. We were able to collect ECGs from 1100 SCD victims. RESULTS: The mean age of the study subjects was 66±13 years and 75% were male. QRS duration in ECG correlated with the degree of fibrosis (p<0.001, ß=0.153). Prevalence of fragmented QRS complex, pathological Q waves and T wave inversions correlated with increased degree of fibrosis (p<0.001 in each). Depolarisation abnormalities were observed both in ischaemic and non-ischaemic heart disease. Repolarisation abnormalities reached statistical significance only among ischaemic SCD victims. An abnormal ECG was observed in 75.3% of the subjects in group 1, 73.7% in group 2, 88.5% in group 3 and 91.7% in group 4 patients (p<0.001). CONCLUSIONS: Myocardial fibrosis was associated with QRS prolongation, deep Q waves, T wave inversions and QRS fragmentation. The results provide potentially useful non-invasive early recognition of patients with fibrotic cardiomyopathy and risk of SCD.