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What is wrong with positive inotropic drugs? Lessons from basic science and clinical trials

B Swynghedauw* and D Charlemagne

U127-INSERM, Hôpital Lariboisière, Paris, France

* Correspondence: B. Swynghedauw, U127-INSERM, Hôpital Lariboisière, 41 Bd de la Chapelle, 75475, Paris Cedex 10, France.

Abstract

Chronic mechanical overload modifies myocardial performance to adapt muscle economy to new environmental conditions. Improved thermodynamic status is achieved by reexpression of the foetal programme, which slows the maximum shortening velocity and impairs the adrenergic system. This is followed by the most characteristic structural change in chronic mechanical overload - the development of a permanent negative inotropic state. Consequently, the prescription of inotropic drugs in chronic heart failure (CHF) goes against the physiological processes of adaptation. The situation in clinical practice is confused by the fact that several inotropic drugs have additional vasodilatory effects. However, large clinical trials have shown that, except for digitalis, inotropes have an overall deleterious effect on long-term survival in CHF. The Digitalis Investigation Group (DIG) trial concluded that digoxin has no influence on all-cause or cardiovascular mortality, but that it reduces risk of hospitalization for CHF. It is proposed that the beneficial effects of digitalis are due to its sympatholytic effects. Given that several other classes of drugs have clearly been shown to reduce mortality, there is decreasing support for long-term use of digoxin in CHF. This class of drugs should now be considered most suitable for short-term use in acute episodes of decompensated heart failure.

Key Words: Cardiac hypertrophy • digitalis • heart failure • inotropic drugs • phosphodiesterase inhibitors

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