Morphologic evidence for "small vessel disease" in patients with hypertrophic cardiomyopathy.

Many patients with hypertrophic cardiomyopathy (HCM) have signs and symptoms or metabolic and hemodynamic evidence of myocardial ischemia and dysfunction in the absence of extramural coronary atherosclerosis. To investigate the possibility that a form of "small vessel disease" could account for these findings, a histologic analysis of left ventricular myocardium obtained at necropsy was carried out in 48 patients with hypertophic cardiomyopathy and in 68 controls with either normal hearts or acquired heart disease. In HCM, abnormal intramural coronary arteries (IMCA) were characterized by thickening of the vessel wall and an apparent decrease in luminal size (external arterial diameter less than 1500 micron; average 300 micron). The wall thickening was due to proliferation of medial and/or intimal components, particularly smooth muscle cells and collagen. Of the 48 patients with HCM,40 (83%) had abnormal IMCAs located in the ventricular septum (33 patients), anterior left ventricular free wall (20 patients) or posterior free wall (nine patients); an average of 3.0 +/- 0.7 IMCA were identified per tissue section. Altered IMCAs were also significantly more common in tissue sections having considerable myocardial fibrosis (31 out of 42, 74%) than in those with no or mild fibrosis (31 or 102, 30%; p less than 0.001). Abnormal IMCA wera also identified in 3 out of 8 infants who died of HCM before 1 year of age. In contrast, only rare altered IMCA were identified in six (9%) of the 69 control patients, and those arteries showed only mild thickening of the wall and minimal luminal narrowing (abnormal IMCA per section: 0.1 +/- 0.05: p less than 0.001). Moreover, of those patients who did show abnormal IMCA, such vessels were about twenty times more frequent in patients with HCM (0.9 +/- 0.2/cm2 myocardium) than in controls (0.04 +/- 0.02/cm2 myocardium). Hence, abnormal IMCA with markedly thickened walls and narrowed lumens are present in increased numbers in most patients with HCM at necropsy, and may represent a congenital component of the underlying cardiomyopathic process. Although the clinical significance of "small vessel coronary artery disease" in HCM is unclear, the occurrence of structurally altered IMCA within or adjacent to areas of substantial myocardial fibrosis suggests a causal role for these arteries in producing ischemia.