Effect of maintenance digoxin therapy on aerobic performance and exercise left ventricular function in mild to moderate heart failure due to coronary artery disease: A randomized, placebo-controlled, crossover trial

Despite 200 years of use, the ability of digitalis glycosides to improve exercise capacity in patients with congestive heart failure remains controversial, partly because of imprecise end points and suboptimal study design. Therefore, this question was examined in 10 ambulatory patients (8 men and 2 women) aged 46 to 70 years (mean 57.8) in sinus rhythm with mild to moderate chronic stable congestive heart failure due to coronary artery disease and systolic left ventricular dysfunction (ejection fraction 32 ± 12). All underwent maximal treadmill exercise with respiratory gas analysis and upright cycle ergometry with gated radionuclide angiography after 4 weeks of digoxin or placebo therapy, administered in a randomized double-blind crossover protocol. Neither treadmill exercise duration (7.7 ± 2.3 versus 7.3 ± 2.7 min) nor peak oxygen consumption (18.7 ± 3.7 versus 18.4 ± 5.4 ml/kg per min) differed between digoxin and placebo regimens. However, the change in peak oxygen consumption induced by digoxin was inversely related to the peak oxygen consumption during placebo therapy (r = −0.64, p < 0.05). At maximal treadmill effort, heart rate (138 ± 16 versus 141 ± 21 beats/min), oxygen pulse (10.3 ± 2.1 versus 9.9 ± 2.2 ml/beat), ventilation (40.3 ± 10.6 versus 42.0 ± 10.8 liters/min) and ventilatory equivalent (29.4 ± 4.8 versus 31.5 ± 6.8) did not differ between digoxin and placebo treatment, although systolic blood pressure was higher during digoxin therapy (163.0 ± 23.1 versus 153.2 ± 25.3 mm Hg, p < 0.05). Left ventricular ejection fraction at rest (32 ± 12 versus 29 ± 12) and maximal cycle work load achieved (75 ± 32 versus 75 ± 28 W) were not affected by glycoside treatment, but ejection fraction and systolic blood pressure at maximal effort were both higher during digoxin than during placebo therapy (32 ± 8 versus 27 ± 9, p < 0.05. and 177 ± 25 versus 165 ± 21 mm Hg, p < 0.05, respectively). The change in peak treadmill oxygen consumption and the change in peak ergometric left ventricular ejection fraction induced by digoxin were not related (r = −.035, p = NS). Therefore, in ambulatory patients with coronary artery disease and chronic, predominantly mild to moderate heart failure, systolic left ventricular dysfunction and sinus rhythm, maintenance digoxin treatment did not elicit an increase in aerobic capacity despite improvement in left ventricular performance during exercise. Nevertheless, the inverse relation between the peak oxygen consumption du