WHY DO PATIENTS WITH CONGESTIVE-HEART-FAILURE TOLERATE THE INITIATIONOF BETA-BLOCKER THERAPY

Background. Despite its negative inotropic effects, the initiation of beta-adrenergic blockade is tolerated by patients with congestive hear t failure (CHF). Accordingly, we examined the acute hemodynamic effect s of beta-adrenergic blockade on systolic and diastolic left ventricul ar (LV) function and ventriculo-arterial coupling. In addition, isolat ed myocardium from patients with CHF shows selective beta1-receptor do wnregulation, implying a greater role for the beta2-receptor in mainta ining in vivo LV contractility. As a secondary aim, we hypothesized th at nonselective beta-adrenergic blockade would have greater negative i notropic effect than beta1-blockade in patients with CHF. Methods and Results. Patients with clinical CHF (n=24) and control patients withou t CHF (n=24) were given either the nonselective beta-blocker propranol ol or the beta1-selective blocker metoprolol. LV pressure-volume relat ions were obtained before and after the administration of intravenous beta-blocker, and measures of LV systolic and diastolic function were examined. Patients with CHF had a deterioration in LV systolic functio n with a fall in LV systolic pressure (139+/-6 to 125+/-6 mm Hg), card iac index (2.56+/-0.11 to 2.20+/-0.11 mL . min-1 . m-2), dP/dt(max) (1 173+/-63 to 897+/-50 mmHg/s), and end-systolic elastance (0.88+/-0.10 to 0.64+/-0.10 mm Hg/mL), P<.05 for all. Although there was deteriorat ion of active LV relaxation (isovolumetric relaxation 63+/-2 to 73+/-3 milliseconds, peak filling rate 543+/-33 to 464+/-28 mL/s, P<.05 for both), there was no change in passive LV diastolic function (pulmonary capillary wedge, 24+/-2 to 24+/-1 mm Hg; chamber stiffness, 0.0154+/- 0.0005 to 0.0163+/-0.0005 mL-1, P=NS for both), and a decrease in afte rload (arterial elastance 3.85+/-0.31 to 3.38+/-0.24 mm Hg/mL, P<.05). Control patients had no change in these parameters other than a prolo ngation of isovolumetric relaxation (48+/-1 to 55+/-2 milliseconds, P< .05). The effects of propranolol (n = 12) versus metoprolol (n=12) on these parameters in patients with CHF were similar. Conclusions. These data do not support a greater in vivo physiological role of the myoca rdial beta2-receptor in CHF. The preservation of passive diastolic fun ction and ventriculo-arterial coupling provide possible explanations o f why beta-adrenergic blockade is tolerated patients with CHF.