Heart failure in patients with preserved left ventricular systolic function: do digitalis glycosides have a role?

It is being increasingly appreciated that a substantial number of patients with congestive heart failure (CHF) have relatively preserved systolic function. Although these individuals appear to have a somewhat better prognosis than those with low ejection fractions, they experience significant symptoms and frequently require hospitalization. In these patients, CHF is often attributed to left ventricular diastolic dysfunction, but this represents a potentially misleading over-simplification. In contrast to CHF associated with left ventricular systolic dysfunction, little is known about how to treat patients with preserved systolic function. Perhaps the major point of consensus has been that the use of digitalis glycosides is inappropriate in this group. Unexpectedly, however, in the recently completed Digitalis Investigators Group trial, a subgroup of nearly 1,000 patients with radionuclide ejection fractions > or = 45% experienced a similar reduction in heart failure endpoints with digoxin therapy as patients with 25% to 44% ejection fractions. The purpose of this article is to review the diverse causes of CHF with preserved systolic function and to examine the potential mechanisms by which digoxin may be producing beneficial effect in this setting.