ACE Inhibitors for Chronic Mitral Regurgitation
October 1, 1998 3 minutes read
ACE Inhibitors for Chronic Mitral Regurgitation
ABSTRACT & COMMENTARY
Synopsis: In asymptomatic patients with chronic severe MR due to mitral valve prolapse, six months of ACE inhibitor therapy lead to modest but significant reductions in LV volumes and mass.
Source: Tischler MD, et al. Am J Cardiol 1998;82:242-245.
Although vasodilator therapy has been used in chronic aortic regurgitation with some demonstrated benefit, there are a paucity of data on chronic mitral regurgitation (MR). Thus, Tischler and associates studied 12 asymptomatic patients with chronic severe MR due to mitral valve prolapse. All had normal left ventricular function and had not been treated with vasodilators. Enalapril was titrated to a target dose of 10 mg bid. Patients were studied by upright bicycle exercise before and two weeks and six months on enalapril with echocardiograms done supine before and immediately after maximum exercise. Enalapril had no effect on exercise duration, nor on heart rate, blood pressure or plasma catecholamine levels at rest, or exercise. Left ventricular volumes (end-diastolic, end-systolic, and stroke) and mass were significantly reduced at rest and after exercise. Left ventricular ejection fraction increased at rest, but not after exercise. Although MR was still graded by color flow Doppler as severe, the regurgitant volume and fraction were significantly reduced at rest and exercise. One patient did not complete the study due to clinical deterioration leading to valve surgery. Two additional patients developed symptoms requiring surgery at 6 and 12 months. Another patient suddenly died two months after the study drug was discontinued due to ruptured chordae tendineae. Tischler et al conclude that in asymptomatic patients with chronic severe MR due to mitral valve prolapse, six months of ACE inhibitor therapy lead to modest but significant reductions in LV volumes and mass. Despite these favorable changes, exercise tolerance was not increased, three patients developed symptoms requiring surgery, and one died suddenly within one year of the study.
COMMENT BY MICHAEL H. CRAWFORD, MD
Acute hemodynamic studies in MR patients with dihydroperidine calcium blockers, hydralazine, ACE inhibitors, and nitrates have shown conflicting results. Prior studies have evaluated heterogeneous groups of patients with mostly rheumatic MR. Some investigators have suggested that rheumatic MR does not respond as well to vasodilators because the relatively fixed orifice does not change with reductions in left ventricular volume, leading to reduced forward output, hypotension, and eventual left ventricular dilation. On the other hand, the regurgitant orifice may decrease dynamically with changes in volume in mitral valve prolapse patients. Thus, Tischler et al studied mitral valve prolapse patients, evaluating relatively acute and longer term responses.
The results confirmed the hypothesis that the regurgitant orifice could be reduced with vasodilator therapy and potentially beneficial changes in left ventricular volume, mass, and regurgitant fraction could be demonstrated. However, the clinical results were disappointing; exercise tolerance was unchanged, and one-third of the patients did poorly. Based on my experience, this is not unexpected since all the patients had severe MR. Even though they were asymptomatic and had normal ejection fractions, we would refer such patients for surgery. Our experience mirrors theirs; most such patients require surgery within two years.
Vasodilator therapy is probably best used in patients with moderate MR to delay the onset of symptoms and need for surgery. In this regard, the favorable hemodynamic results of this study are encouraging. Also, the fact that ACE inhibitors provided this benefit chronically seems to answer the controversy surrounding these agents as opposed to other vasodilators. ACE inhibitors have less adverse effects and are preferred by patients, but, until now, the most consistent beneficial data were with dihydroperidine calcium blockers and hydralazine.
Until more definitive data are obtained, I would suggest seriously considering surgery in patients with severe MR-especially if it is rheumatic in origin-even if the patient is asymptomatic. For those with moderate MR and no symptoms or left ventricular dysfunction, a trial of ACE inhibitors seems warranted.
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