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To test the hypothesis that impaired cardiac performance in some patients with pressureoverload hypertrophy is due to inappropriately high wall stress, rather than depressed contractility, the importance of hemodynamic and geometric factors was assessed in 14 patients with isolated aortic stenosis and various degrees of left ventricular failure (ejection fraction range 0.19-0.85). There was poor correlation between either aortic valve area, peak left ventricular systolic pressure, or left ventricular mass, and measures of ventricular function. In contrast, there were close correlations between circumferential wall stress and both ejection fraction (r= 0.96) and velocity of fiber shortening (r = 0.91) in patients with aortic stenosis. Forcevelocity- shortening relationships in six normal control subjects fell on the same regression line as that defined by the patients with aortic stenosis, while force-velocity-shortening relationships of patients with primary myocardial failure clearly differed. A major determinant of wall stress was the ratio of left ventricular wall thickness to cavity radius (h/R). Patients with h/R ratios > 0.36 had higher values for ejection fraction (0.61 ± 0.06 vs 0.36 i 0.07, p>0.05), Vcf (0.79 ± 0.10 vs 0.39 ± 0.04 sec ', p>0.05) and stroke work index (71 ± 10 vs 45 9 g-m/m2, p>0.005) than those with lower ratios.The results indicate that left ventricular wall thickness and geometry are closely correlated with ventricular performance in patients with pressure-overload hypertrophy due to aortic stenosis. Poor cardiac performance in some such patients may be due to inadequate hypertrophy (or inappropriate geometry) rather than to depression of myocardial contractility.