Relation of Indirect Vasodilator Use to Prognosis in Patients with Chronic Severe Mitral Regurgitation

Abstract

Objectives: The relation of indirect vasodilator use to cardiac events (CE) is undefined for chronic severe nonischemic mitral regurgitation (MR). The aim of this study was to resolve this knowledge deficiency. Methods: Data from 52 consecutive patients in our prospective natural history study with isolated chronic severe nonischemic MR were assessed post hoc over 19 years to examine the relation of indirect vasodilator use to subsequent CE (death or indications for valve surgery). At entry, no patient had surgical indications, 14% had hypertension (HTN) and 7 chronically received vasodilators (5 angiotensin-converting enzyme inhibitor, 1 receptor blocker and 1 α-adrenergic blocker). CE differences were assessed by log-rank comparison of Kaplan-Meier curves. Results: During follow-up, CE included sudden death (1 patient), heart failure (7 patients), atrial fibrillation (6 patients), left ventricular (LV) systolic dimension >4.5 cm (12 patients), LV ejection fraction (EF) <60% (7 patients), right ventricular EF <35% (2 patients) and combination CE (7 patients). Overall, vasodilator use did not predict CE (not significant). However, patients without HTN had higher CE rates with vasodilators than without (p = 0.007), while those with HTN and vasodilators had lower CE rates than those without vasodilators (p = 0.04). Conclusion: Vasodilator use appears to confer no survival benefit in patients with chronic severe MR. The small number of patients with HTN precludes conclusions about modulation of vasodilator effect by HTN. Randomized trials are needed to conclusively evaluate this association.

A Vasodilator Is a Vasodilator Is a Vasodilator?

“…This uncertainty is reinforced by the observations of Supino et al [1], which are consistent with previous experiences with vasodilators in VHD. Prior experience in HF, especially in the V-HeFT trials, suggests that AB may be less effective in certain populations, just as was observed by Supino et al [1] in VHD.…”

“…In fact, current guidelines for HF management recommend the routine use of nitrates, hydralazine and AB in the therapeutic regimen for appropriate patients with HF. It should be noted that other direct vasodilators, like minoxidil, and other indirect vasodilators, like prazosin, were not shown to be clinically effective in HF, analogous to the observations of Supino et al [1]. …”

“…In the above context, the observations of Supino et al [1] may not be so surprising. Historically, direct-acting vasodilators, specifically nitrates and hydralazine, were among the first shown to produce a hemodynamic improvement and eventually clinical benefits in patients with HF.…”

“…The report by Supino et al [1] provides needed information about the potential role of vasodilators in one type of valvular heart disease (VHD), mitral regurgitation (MR). The primary finding that vasodilators, mainly by angiotensin blockade (AB) with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, were of no overall survival benefit in patients with MR may come as a surprise, considering the generally favorable perceptions of vasodilators, in particular AB in heart failure (HF), a major complication of MR.…”

“…This may be due in part to the fact that large clinical trials of vasodilators in nonvalvular cardiovascular disease have tended to exclude patients with primary VHD on the assumption that their treatment would ultimately be surgical, thereby compromising interpretation of the trial outcomes. Obviously aware of the differences among vasodilators and the general acceptance of the consistently beneficial effects of these agents, Supino et al [1] have wisely used the term ‘indirect vasodilators' in describing their experience, which involved almost entirely the use of AB.…”