Left ventricular myocardial remodeling and contractile state in chronic aortic regurgitation

Background: In chronic aortic regurgitation, eccentric hypertrophy, with co mbined concentric hypertrophy of the left ventricle, is an important adapti ve response to volume overload, which in itself is a compensatory mechanism for permitting the ventricle to normalize its afterload and to maintain no rmal ejection performance (physiologic hypertrophy). However, progressive d ilatation of the left ventricle leads to depressed left ventricular (LV) co ntractility and myocardial structural changes, including cellular hypertrop hy and interstitial fibrosis (pathological hypertrophy). Hypothesis: The study was undertaken to determine the relationship between left ventricular myocardial structure and contractile function in 14 patien ts with chronic aortic regurgitation by cardiac catheterization and endomyo cardial biopsies. Methods: Myocardial cell diameter and percent interstitial fibrosis were ob tained from biopsy samples. Contractile function was evaluated from the rat io of end-systolic wall stress to end-systolic volume index (ESS/ESVI) and the ejection fraction-end-systolic stress (EF-ESS) relationship, which was obtained from 30 normal control subjects. Results: Myocardial cell diameter correlated significantly with the ESVI (r = 0.72, p<0.005), ejection fraction (r = -0.58, p < 0.05), and ESS/ESVI (r = -0.58, p < 0.05). The percent interstitial fibrosis also correlated inve rsely with ESS/ESVI (r = -0.71, p < 0.005). Compared with very few patients with an ESVI <70 ml/m(2), the majority of patients with ESVI greater than or equal to 70 ml/m(2) had a cell diameter of greater than or equal to 30 m u m and a percent interstitial fibrosis of greater than or equal to 10%. Th e nine patients who had depressed contractile function, as assessed from th e EF-ESS relationship, had a higher percent interstitial fibrosis (p < 0.05 ) than five patients showing a normal EF-ESS relationship, despite the fact that there was no significant difference in myocardial cell diameter betwe en them. Thus, advanced cellular hypertrophy and excessive interstitial fib rosis were significantly and independently associated with myocardial contr actile dysfunction and appeared to be responsible for ventricular remodelin g. Conclusion: Our findings suggest that in many patients with aortic regurgit ation, eccentric hypertrophy changes its nature from physiologic to nonphys iologic during the earlier stages in the course of the disease rather than during the stage described previously.