Hypertrophic cardiomyopathy: the interrelation of disarray, fibrosis, and small vessel disease

Objective-To make a quantitative assessment of the relation between disarra y, fibrosis, and small vessel disease in hypertrophic cardiomyopathy. Design-Detailed macroscopic and histological examination at 19 segments of the left and right ventricle and the left atrial free wall. Patients-72 patients with hypertrophic cardiomyopathy who had suffered sudd en death or progression to end stage cardiac failure (resulting in death or heart transplantation). Main outcome measures-The presence of scarring, atrial dilatation, and a mi tral valve impact lesion were noted, and heart weight, wall thickness, per cent disarray, per cent fibrosis, and per cent small vessel disease quantit ated for each heart. Results-Within an individual heart the magnitude of hypertrophy correlated with the severity of fibrosis (p = 0.006) and disarray (p = 0.0002). Overal l, however, total heart weight related weakly but significantly to fibrosis (r = 0.4, p = 0.0001) and small vessel disease (r = 0.3, p = 0.03), but no t to disarray. Disarray was greater in hearts with mild left ventricular hy pertrophy (maximum wall thickness < 20 mm) and preserved systolic function (60.9 (26)% v 43 (20.4)% respectively, p = 0.02) and hearts without a mitra l valve impact lesion (26.3% v 18.9%, p = 0.04), but was uninfluenced by se x. Fibrosis was influenced by sex (7% in male patients and 4% in female, p = 0.04), but not by the presence of an impact lesion. No relation was found between disarray, fibrosis, and small vessel disease. Conclusions-Myocyte disarray is probably a direct response to functional or structural abnormalities of the mutated sarcomeric protein, while fibrosis and small vessel disease are secondary phenomena unrelated to disarray, bu t modified by factors such as left ventricular mass, sex, and perhaps local autocrine factors.