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Left ventricular end-systolic pressure-volume analysis was employed to assess the inotropic effect of the phosphodiesterase inhibitor enoximone (formerly MDL-17,043) in nine patients with severe heart failure (New York Heart Association class IV symptoms, mean ejection fraction = 0.22). Left ventricular pressure-volume loops were constructed using high fidelity left ventricular pressure measured with micromanometer-tipped catheters and simultaneous left ventricular volume obtained by gated blood pool imaging. Afterload was reduced with the vasodilator nitroprusside to generate the baseline left ventricular end-systolic pressure-volume relation, a relatively load-independent measure of contractile function.

Functional capacity assessed by maximum oxygen consumption (MV02) and percent age-sex adjusted MVO2achieved (% MVO2) predicts survival in heart failure (HF). To determine the exercise parameters which best predict survival, 66 patients with advanced HF (mean age 51±9.9 mean ± SD; 58% NYHA III, 18% NYHA IV; mean LVEF 0.22±0.07) underwent simultaneous cardiopulmonary exercise testing and first-pass rest/exercise radionuc1ide ventriculography during transplant (TX) evaluation. Mean MV02was 11.8±4.2 ml/kg/min, mean % MVO238±11.9%. During median followup 93 weeks, 16/66 patients (25%) died. Univariate predictors of survival included restRVEF > 0.35, exRVEF > 0.35, and % MVO2> 45% (all p<0.05). In a multivariate proportional hazards survival model, exRVEF > 0.35 (p<0.01) and % MV02> 45% (p=0.01) were selected as predictors. 28/66 patients (42%) reached the combined end-point of death or hospitalization for inotropic/mechanical bridging (IN) to cardiac TX. Univariate predictors of IN-free survival included restRVEF > 0.35 (p=0.01), exRVEF > 0.35 (p<0.01). NYHAC (p<0.05), mid % MV02> 45% (p=0.05). exRVEF > 0.35 (p=0.01) was the only predictor of IN-free survival selected in a multivariate proportional hazards model. MV02, CI rest/exercise, LVEF rest/exercise, exercise-related rise or fall> 0.05 in LVEF or RVEF were not predictive of survival or IN-free survival in any univariate or multivariate analysis.