Insights into the Epidemiology of Hypertrophic Cardiomyopathy in Forensic Autopsies: A Nationwide Portuguese Study

TRABAJO LIBRE SOMETIDO AL III CONGRESO INTERNACIONAL DE CIENCIAS FORENSES DE HONDURAS 8-10 DE OCTUBRE 2025, TEGUCIGALPA, HONDURAS

Abstract

Introduction: Hypertrophic cardiomyopathy (HCM) is the most common monogenic cardiac disorder, with an estimated prevalence of 1:500. Approximately half of the cases diagnosed in adolescents and adults are familial, caused by deleterious variants in genes encoding cardiac sarcomeric proteins, which are typically inherited in an autosomal dominant manner. The phenotypic expression of HCM is highly variable, ranging from asymptomatic individuals to patients with overt heart failure or sudden cardiac death. While the disease is expected to be equally prevalent based on its genetic inheritance, up to 70% of detected cases are males. This study aimed to determine the prevalence of HCM in forensic autopsies across Portugal.

Methods: We conducted a retrospective observational study of 31,325 forensic autopsies—including 22,854 males (72.9%) and 8,471 females (27.0%)—performed at the Portuguese National Institute of Legal Medicine and Forensic Sciences (INMLCF) between 2017 and 2022. Inclusion criteria followed the European Society of Cardiology (ESC) 2023 guidelines and the INMLCF morphological nomenclature for HCM, based on macroscopic identification and histological confirmation. Demographic, postmortem cardiac, and extracardiac data were collected for each case. Statistical analyses included prevalence estimates, χ² tests, Fisher’s exact tests, ANOVA, and odds ratios, with significance set at p<0.05.

Results: A total of 52 HCM cases were identified, corresponding to an overall prevalence of 0.16% (95% CI: 0.12–0.22%), which is consistent with epidemiological expectations. Regional prevalences differed significantly, being highest in the South (0.31%, p<0.001). The prevalence of HCM was significantly higher in males (0.20%; n = 46) than in females (0.07%; n = 6), with a significant difference between sexes (χ² = 5.88; p = 0.015; OR = 2.91 (95% CI: 1.24−6.80)). The mean age of HCM cases was 59.21 ± 15.74 years (range: 24–92).
Most deaths occurred at home (71.7%) and were attributed to natural causes (89.1%), primarily cardiovascular disease (78.2%). Besides the cardiomegaly, postmortem examination revealed myocardial fibrosis (in 69.2% of the cases), asymmetric septal hypertrophy, and myocyte disarray. Only 4.3% had a premortem diagnosis of HCM. The most frequent extracardiac finding was pulmonary edema (53.8%).

Conclusion: This study provides novel epidemiological data on HCM in the Portuguese population revealing a higher male-to-female ratio than typically reported and marked regional differences. Most cases remained undiagnosed during life, underscoring the need for earlier recognition to reduce morbidity and prevent sudden cardiac death. Forensic autopsies and postmortem genetic investigation can provide clinically relevant information, guiding timely genetic screening and counselling of the relatives.