Cardiomyopathy in First-Degree Relatives of Patients Presenting With Acute Myocarditis: Prevalence and Prognostic Significance

BACKGROUND: Acute myocarditis has been genetically linked to dilated cardiomyopathy (DCM), but the clinical significance remains uncertain. We investigated the prevalence and long-term prognosis of DCM and heart failure (HF) among unselected patients hospitalized with acute myocarditis and their first-degree relatives compared with an age- and sex-matched cohort. METHODS: This was an observational study utilizing the Danish nationwide registries, where all patients with a first-time myocarditis diagnosis from 1995 to 2018 were identified and matched (on birth year and sex) with 10 controls from the general population. RESULTS: Totally 3176 patients with acute myocarditis and 31 760 controls were included (median age, 49.8 [Q1–Q3, 32.5–70.2] years; 35.6% female). At baseline, patients with myocarditis had a higher prevalence of DCM (7 [0.2%] versus 8 [0.0%]) and HF (336 [10.6%] versus 695 [2.2%]) than controls; P <0.0001 for both. Patients with myocarditis more often had siblings with DCM (12 [0.4%] versus 17 [0.05%]) or HF (36 [1.1%] versus 89 [0.3%]); P <0.0001, odds ratios 7.09 (3.38–14.85) and 2.92 (1.25–6.80), respectively, whereas parental DCM and HF did not differ among patients with myocarditis and controls. Patients with myocarditis had greater 20-year incidence of DCM, HF, and all-cause mortality (0.5% [0.3%–0.9%], 15% [13%–17%], and 47% [44%–50%]) compared with controls (0.06% [0.03%–0.11%], 6.8% [6.4%–7.3%], and 34% [33%–35%]; P <0.0001). Having a first-degree relative with DCM or HF was associated with increased long-term mortality among the patients with myocarditis (hazard ratio, 1.40 [1.11–1.77]) but not among the controls (hazard ratio, 0.90 [0.81–1.01]; P difference =0.0008). CONCLUSIONS: Acute myocarditis aggregates with DCM within families, where it carries a worsened prognosis. A differential association between parents and siblings (with sibling preponderance) could suggest that additional environmental factors are important for myocarditis development even in predisposed individuals.