Left ventricular myocardial remodeling and contractile state in chronic aortic regurgitation

Background: In chronic aortic regurgitation, eccentric hypertrophy, with combined concentric hypertrophy of the left ventricle, is an important adaptive response to volume overload, which in itself is a compensatory mechanism for permitting the ventricle to normalize its afterload and to maintain normal ejection performance (physiologic hypertrophy). However, progressive dilatation of the left ventricle leads to depressed left ventricular (LV) contractility and myocardial structural changes, including cellular hypertrophy and interstitial fibrosis (pathological hypertrophy). Hypothesis: The study was undertaken to determine the relationship between left ventricular myocardial structure and contractile function in 14 patients with chronic aortic regurgitation by cardiac catheterization and endomyocardial biopsies. Methods: Myocardial cell diameter and percent interstitial fibrosis were obtained from biopsy samples. Contractile function was evaluated from the ratio 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 inversely with ESS/ESVI (r = −0.71, p< 0.005). Compared with very few patients with an ESVI <70 ml/m2, the majority of patients with ESVI ≥ 70 ml/m2 had a cell diameter of ≥30 mm and a percent interstitial fibrosis of ≥l0%. The nine patients who had depressed contractile function, as assessed from the 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 between them. Thus, advanced cellular hypertrophy and excessive interstitial fibrosis were significantly and independently associated with myocardial contractile dysfunction and appeared to be responsible for ventricular remodeling. Conclusion: Our findings suggest that in many patients with aortic regurgitation, eccentric hypertrophy changes its nature from physiologic to nonphysiologic during the earlier stages in the course of the disease rather than during the stage described previously.