The link between acute haemodynamic adrenergic beta-blockade and long-term effects in patients with heart failure: A study on diastolic function, heart rate and myocardial metabolism following intravenous metoprolol

The present study was performed to find possible mechanismslinking the early effects of beta-blockade with the observedlong-term effects in patients with heart failure. In 57 patients with heart failure, 13±3.1 mg of metoprololwas given intravenously. The patients were investigated by invasivehaemodynamics (n = 34), including collection of myocardial metabolicdata during atrial pacing stress (n = 16), by radionuclide angiographyduring physiological atrial pacing (n = 13), and by a bedsideevaluation (n = 10). Diastolic function, measured by early peak filling rate, followedchanges in heart rate, but was similar when heart rate was heldconstant by atrial pacing before and after beta-blockade. Followingbeta-blockade and slower heart rates, diastolic filling volumeswere redistributed to late diastole. Metoprolol induced a paralleldecrease in coronary sinus flow and myocardial oxygen consumption.Myocardial oxygen consumption following beta-blockade decreasedboth during spontaneous rhythm (25±15 to 16±8.8ml. min^–1; P = 0.006), and during atrial pacing stress(30±13 to 23±11 ml.min^–1; P = 0.004). Cardiacindex decreased owing to reduction of heart rate (2.3±1.0to 1.9±0.64 l.min^–1.m²; P = 0.0003), while leftventricular filling pressure was unchanged. Ejection fractionand ventricular volumes were unaltered following atrial pacingor beta-blockade. There was a reflex increase in noradenalineconcentration after beta-blockade injection (0.96±0.66to 1.20±0.91 nmol.l^–1; P = 0.002), whereas myocardialnoradrenaline overflow was unchanged. There was a trend towardsan increase in myocardial lactate consumption after beta-blockadeadministration during atrial pacing stress. It is suggested that the surprisingly good tolerability seenafter acute administration of beta-blockers to patients withsevere heart failure may be explained by prolongation of thediastolic filling phase, which outweighs the negative ino tropiceffects. The reduced myocardial metabolic demand may allow thefailing myocardium to recover and explain the excellent long-termeffect on heart function following beta-blockade treatment.