Beneficial Effects of Heart Rate Reduction on Cardiac Mechanics and Energetics in Patients With Left Ventricular Dysfunction

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Abstract
It has been shown recently that the force-frequency relationship is blunted in experimental heart failure models. Furthermore, tachycardia is thought to have adverse effects on the diseased heart for several reasons, one of which is an increase in myocardial oxygen consumption. Inversely, the oxygen-saving effects of bradycardia may be beneficial for the treatment of heart failure. The aim of this study was to elucidate how heart rate (HR) modulates cardiac mechanics and energetics in patients with left ventricular (LV) dysfunction. LV pressure-volume data and myocardial oxygen consumption (MVO2) was assessed using conductance and coronary sinus thermodilution catheters in 14 patients with moderate LV dysfunction (mean ejection fraction 34%) under 3 conditions: (a) basal, (b) HR increased by 20% using atrial pacing, and (c) HR decreased by 16% using a specific bradycardic agent, zatebradine (7.5 mg po). Atrial pacing decreased external work (EW) (from 0.39 to 0.31 J beat-1 m-2, p2 per beat with a marginal increase in LV contractility index (Ees) (from 2.34 to 2.76 mmHg m-1 m-2, p=0.08), resulting in a decrease in mechanical efficiency (EW/MVO2) (from 25.9 to 22.1%, pes (from 2.34 to 2.24 mmHg ml-1 m-2, NS), but increased EW (from 0.39 to 0.42 J beat-1 m -2, p2 per beat, resulting in improved mechanical efficiency (from 25.9 to 29.7%, pJpn Circ J 1999; 63: 957 - 964)