Clinical correlates of the myocardial force-frequency relationship in patients with end-stage heart failure

This study tested the hypothesis that in patients with suspected heart failure, peak oxygen consumption was the best predictor of heart muscle failure. Failing human myocardium is characterized by an abnormal force-frequency relationship, which has been previously shown to be altered in parallel with the severity of heart failure.

We examined whether seven different functional parameters of isolated electrically driven ventricular trabeculae carneae obtained from 34 explanted hearts of patients undergoing heart transplantation for end-stage heart failure correlated with any of 47 separate pretransplantation clinical parameters. The functional muscle parameters were active force at 0.33 Hz, time to 80% relaxation (RT 80%) of twitch force at 0.33 Hz, optimal frequency (OF), active force at 1.0 Hz (AF1), diastolic force at 1.0 Hz (DF1), active force at 2.0 Hz (AF2), and diastolic force at 2.0 Hz (DF2).

Before transplantation the mean left ventricular ejection fraction was 21% +/- 10%, and all patients were in New York Heart Association class III or IV. Mean peak whole body VO2 was 10.9 +/- 3.3 ml/min/kg and percent body mass/age/sex-adjusted maximum VO2 oxygen consumption was 34.7% +/- 10.4%. Univariate analysis of VO2 yielded the following significant correlations: active force at 33 Hz, RT80%, OF, AF1, DF1, AF2, DF2; whereas univariate analysis of percent body mass/age/sex-adjusted VO2 yielded the following significant correlations: RT80%, OF, DF1, AF2, DF2. Multivariate analysis showed that OF and DF1 were independent predictors of peak VO2.

In this study we show that peak oxygen uptake measured during cardiopulmonary exercise testing obtained before transplantation is correlated with the force-frequency behavior of isolated muscles at the time of transplantation. Peak VO2 seems to be a strong indicator of the severity of cardiac contractile dysfunction in patients with heart failure.