Hypertrophic cardiomyopathy (HC) is associated with an increased risk of sudden cardiac
death or death from heart failure. Little is known of the pathologic substrate for
risk of premature death in this disease. We therefore set out to correlate the pathologic
findings with the mode of death and risk profile in 75 patients with HC. Hearts with
HC were obtained after death or transplantation. The clinical details were correlated
with the macroscopic findings and the percent fibrosis, disarray, and small-vessel
disease across 19 sections of each heart. Thirty-nine patients died suddenly, 28 had
end-stage heart failure, and 8 died of other causes. Myocyte disarray correlated positively
with evidence of ischemia (r = 0.5, p <0.0001), and was greater in patients who died
before age 21 years (mean disarray 33% vs 18%, p <0.0001) and in those with an abnormal
vascular response to exercise (mean disarray and 30% vs 19%, p = 0.04). Myocardial
fibrosis was greater in patients who died in heart failure (mean percent fibrosis
was 2.8% versus 0.9%, p = 0.003), and in patients with nonsustained ventricular tachycardia
or a high risk fractionation study (4.9% vs 2.7%, p = 0.04, and 6.84% vs 2.8%, p =
0.03, respectively). In conclusion, young patients who die with HC have greater disarray
than their older counterparts. In contrast, myocardial fibrosis is the substrate for
premature deaths from heart failure and is associated with an increased risk of a
primary ventricular arrhythmia.