Hypertrophic cardiomyopathy histopathology

Editors-In-Chief: C. Michael Gibson, M.S., M.D. [mailto:mgibson@perfuse.org]

Overview
On histopathologic examination, hypertrophic cardiomyopathy is characterized by both myocardial disarray and by periarteriolar fibrosis. Myocardial disarray can be associated with aberrant impulse conduction and arrhythmias, and periarteriolar fibrosis can be associated with myocardial ischemia.

Myocardial Disarray
In HCM, the normal alignment of muscle cells is disrupted (there is a swirling pattern to the arrangement of the muscle cells), a phenomenon known as myocardial disarray. HCM is believed to be due to a mutation in one of many genes that results in a mutated myosin heavy chain, one of the components of the myocyte (the muscle cell of the heart). Histopathologically, the cardiac sarcomere is abnormal resulting in hypertrophy of the left ventricle in the absence of other disorders that could produce the condition such as hypertension, amyloid or aortic stenosis. The presence of myocardial disarray may be associated with abnormalities of electrical conduction in the heart (including electrical reentry loops) which thereby contributes to an increased risk of sudden cardiac death.

Periarteriolar Fibrosis
Compared to normal arterioles on the left, the arterioles from a patient with hyertension (middle) show moderate periarteriolar thickening and fibrosis. Shown on the right is a patient with HCM in which there is even more signficant periarteriolar thickening and fibrosis. This thickening of the wall of the intramyocardial arterioles leads to an increased wall/lumen ratio, subendocardial ischemia and impaired coronary flow reserve. Patients who subsequently died in one series had abnormal coronary flow reserve on PET scanning at baseline indicating that ischemia may play a role, at least in part, in subsequent mortality.

Microscopic Pathological Findings
Histopathologically, small vessels have hypertrophy of the tunica media. Combined with increased wall tension, decreased vasodilator reserve and inadequate capillary density, there is a mismatch between blood supply and demand. Over time, it is thought that there is repeated ischemia followed by fibrosis and eventually, dilation and systolic dysfunction (“burned out hypertrophy”).