Improvement in supine bicycle exercise performance in refractory congestive heart failure after isosorbide dinitrate: Radionuclide and hemodynamic evaluation of acute effects

Abstract

The acute effects of oral isosorbide dinitrate on exercise performance in congestive heart failure were evaluated in 11 patients. All patients underwent rest and supine bicycle exercise equilibrium radionuclide ventriculography and hemodynamic measurements before and after oral administration of isosorbide dinitrate, 40 mg four times a day for 24 hours. Ninety minutes after the last dose, isosorbide dinitrate increased the duration of exercise (+ 28 percent, probability [p] < 0.01) and the total work performed (+ 32 percent, p < 0.01); with this drug, significantly (p < 0.05) fewer patients terminated exercise because of dyspnea. At rest, the left ventricular ejection fraction increased after administration of isosorbide dinitrate (+ 14 percent of value before administration, p < 0.02); there were decreases in mean pulmonary arterial pressure (− 23 percent, p < 0.02), mean arterial pressure (− 8 percent, p < 0.05), systemic vascular resistance (− 18 percent, p < 0.005) and pulmonary vascular resistance (− 46 percent, p < 0.001). During comparable levels of exercise, isosorbide dinitrate decreased pulmonary capillary wedge pressure (− 19 percent, p < 0.001), mean pulmonary arterial pressure (− 23 percent, p < 0.001), mean arterial pressure (− 7 percent, p < 0.001), heart rate (− 5 percent, p < 0.01), systemic vascular resistance (− 20 percent, p < 0.01) and pulmonary vascular resistance (− 37 percent, p < 0.01), and increased cardiac index (+ 15 percent, p < 0.02), stroke volume index (+ 19 percent, p < 0.01) and stroke work index (+ 16 percent, p < 0.05). Ejection fraction did not change significantly (+ 7 percent, difference not significant [NS]). During maximal exercise, isosorbide dinitrate produced decreases in pulmonary capillary wedge pressure (− 15 percent, p = 0.05), mean pulmonary arterial pressure (− 15 percent, p < 0.01), systemic vascular resistance (− 23 percent, p < 0.05) and pulmonary vascular resistance (− 30 percent, p < 0.01) and increases in cardiac index (+ 30 percent, p < 0.001), stroke volume index (+ 31 percent, p < 0.001) and stroke work index (+ 40 percent, p < 0.001). Ejection fraction did not change significantly (+ 9 percent, p = NS). Ten minutes after exercise, isosorbide dinitrate produced decreases in pulmonary capillary wedge pressure (− 34 percent, p < 0.02), mean pulmonary arterial pressure (− 23 percent, p < 0.02), mean arterial pressure (− 10 percent, p < 0.01) and systemic vascular resistance (− 24 percent, p < 0.001) and increases in stroke volume index (+ 18 percent, p < 0.05) and ejection fraction (+ 12 percent, p < 0.05). It is concluded that oral isosorbide dinitrate, by causing reductions in preload and afterload, produces significant beneficial acute effects on left ventricular performance during exercise in patients with refractory chronic congestive heart failure.