Pathologic fibrosis and connective tissue matrix in left ventricular hypertrophy due to chronic arterial hypertension in humans.

OBJECTIVE: To investigate pathologic fibrosis and connective tissue matrix in left ventricular hypertrophy due to chronic arterial hypertension in humans. DESIGN AND METHODS: Seventeen human hearts were studied. Group 1 consisted of control hearts (four hearts, weighing 280 +/- 40 g each), from subjects who had had no evidence of heart disease and for whom the diagnoses of death were noncardiac. Groups 2 (five hearts, weighing 440 +/- 50 g each), 3 (five hearts, weighing 560 +/- 50 g each), and 4 (three hearts, weighing 680 +/- 60 g each) consisted of hearts from subjects who had had a history of systemic hypertension. All hearts had no valvular deformities and no evidence of ischemic disease at the postmortem examination. A cell-maceration method was employed to evaluate the myocardial connective matrix after removal of the nonfibrous elements of myocardial tissue, leaving behind a noncollapsed matrix, thus allowing a better three-dimensional view. Myocardial tissue was also processed for conventional light microscopic and morphometric studies.
RESULTS: The minor transverse diameter of myocytes from hearts in groups 1-4 hearts were 13.7 +/- 7.8, 23.7 +/- 3.4, 26.6 +/- 3.7, and 32.8 +/- 5.8 microm, respectively. The volume fraction of fibrosis of the controls was 6.5%, whereas the volume fractions in hypertensive hearts increased progressively according to heart weight: 15.4, 22.9, and 31.1% for hearts in groups 2, 3, and 4, respectively. The most striking feature was the diffuse marked increase in amount of pericellular collagen weave fibers (endomysial matrix), parallel to the increase of heart weight. The hypertrophied myocytes were encased in a dense weave of collagen fibrils continuous with those of adjacent myocytes. The muscle fibers in hypertrophied hearts were markedly larger than normal, although this was extremely variable from an area to another. Besides, a diffuse increase in the number of thick collagen fibers constituting broad bands and sheets of collagen surrounding disorganized muscle bundles (perimysial matrix) was observed. Scattered dense scar-like foci, apparently replacing areas of myocyte loss, could be seen, mainly on the periphery of muscle bundles. This latter finding was more commonly observed among hypertrophied hearts from group 3 and, mainly, among hypertrophied hearts of group 4. Importantly, a progressive disarray of the connective tissue skeleton of the myocardium could be seen in parallel to the progressive increase of cardiac hypertrophy.
CONCLUSIONS: The progressive accumulation of interstitial collagen fibers in left ventricular hypertrophy, in parallel to an increase in heart weight, can be expected to contribute to a spectrum of ventricular dysfunction involving either the diastolic or systolic phase of the cardiac cycle, or both, that is associated with the greater than normal arrhythmogenic risk for a hypertensive heart. Moreover, the methodology used is useful for studying the spatial organization of the collagen fibrils of the myocardium under normal and pathologic conditions.