Hypertrophic Cardiomyopathy and Risk of Out-of-Hospital Cardiac Arrest.

Importance: Hypertrophic cardiomyopathy (HCM) is associated with an elevated risk of sudden cardiac death, often preceded by an out-of-hospital cardiac arrest (OHCA). However, population-based estimates of OHCA risk in patients with HCM are limited. Objective: To estimate the risk of OHCA in patients with HCM and identify characteristics associated with OHCA. Design, Setting, and Participants: This cohort study used multiple Danish registers during an observation period ranging from June 1, 2001, to December 31, 2022, and included a nested case-control study. All Danish residents aged 18 to 85 years during the study period constituted the source population. Patients with HCM were identified using codes from the International Statistical Classification of Diseases, Tenth Revision. The cohort included patients with a first-time HCM diagnosis and exposure-matched controls. In the nested case-control study, patients with HCM who experienced OHCA were risk-set matched with controls with HCM and no OHCA at the index time. Analyses were performed between September 1 and November 30, 2025. Exposure: First-time diagnosis of HCM. Main Outcomes and Measures: Time to OHCA from exposure or the matching date was the primary outcome. Risk estimates were determined using the Aalen-Johansen estimator. Association between covariates and OHCA was determined by conditional logistic regression. Results: The cohort included a total of 29 240 individuals: 5901 patients with HCM (median age, 65 [IQR, 54-75] years; 3277 male [55.5%]) and 23 339 matched controls (median age, 65 [IQR, 55-75] years; 12 982 male [55.6%]). In the group aged 61 to 85 years, the 10-year risk of OHCA was 4.3% (95% CI, 3.4%-5.1%) in patients and 3.3% (95% CI, 3.0%-3.7%) in controls. In the group aged 18 to 60 years, the 10-year risk was 2.8% (95% CI, 1.9%-3.7%) in patients and 1.5% (95% CI, 1.2%-1.8%) in controls. The nested case-control study included 250 cases with HCM and OHCA (167 male [66.8%]; median age, 68 [IQR, 59-76] years) and 1000 controls with HCM and no OHCA (668 male [66.8%]; median age, 68 [IQR, 59-76] years). Heart failure, both recent and longer term, was associated with an increased rate of OHCA (hazard ratio, 3.63 [95% CI, 1.55-8.50] and 2.82 [95% CI, 1.88-4.22], respectively). Conclusions and Relevance: The findings of this cohort study suggest that HCM was associated with an increased risk of OHCA in people aged 18 to 85 years. The rate of OHCA was associated with heart failure, underscoring the need for improved risk stratification to optimize primary prevention.