ENERGETIC CONSEQUENCES OF SUBSTANCES CURRENTLY USED OR RECOMMENDED FOR LONG-TERM TREATMENT OF CHRONIC HEART-FAILURE

Abstract

Vasodilators have been shown to improve hemodynamics of the failing heart as a short-term effect, and to decrease mortality as a long-term result. We, therefore, studied the effects of vasodilators and inotropic agents on myocardial mechanics and energetics in patients with congestive heart failure New York Heart Association (NYHA) classes II-III. In these patients, who underwent routine heart catheterization, myocardial oxygen consumption was measured using the argon method, and LV pressure and geometry were obtained from LV angiography using a Millar microtipped catheter. All data were analyzed for one single heart beat. The best correlation was found between MVO2/beat and the systolic stress-time integral which considers LV pressure, LV wall thickness, and LV geometry. The relation between MVO2/beat and peak systolic wall stress was less relevant. No correlation was found between MVO2/beat and pressure-volume work, dP/dt(max), and mean velocity of circumferential fiber shortening. The intravenous application of nitroprusside and the ACE-inhibitor benazepril decreased both the systolic stress-time integral and the myocardial oxygen consumption in proportion to each other, indicating unchanged economy of myocardial contraction. In contrast, beta1-agonists and phosphodiesterase inhibitors increased myocardial oxygen consumption independently of changes in the stress-time integral. In conclusion, vasodilators decrease LV pressure and chamber size and thereby proportionally reduce MVO2/beat. The reduction of energy needed for myocardial contraction may partially explain the long-term effects of the ACE-inhibitors and combinations of vasodilators. Pure inotropic substances, especially beta-1-agonists, increase myocardial oxygen consumption with only minor changes of systolic stress-time integral. The effect of phosphodiesterase inhibitors on MVO2/beat depends on the balance between the energy-consuming positive inotropic effect and the energy-saving effect of vasodilation. The lack of MVO2 reduction in patients with phosphodiesterase inhibitors or beta-1-agonists may partially explain why mortality is not decreased in long-term treatment.