Correspondence

Valvular Heart Disease Associated with Dexfenfluramine

N Engl J Med 1997; 337:636August 28, 1997

Article

To the Editor:

The appetite-suppressant drugs fenfluramine, dexfenfluramine (the purified d isomer of fenfluramine), and phentermine have each been associated with an increased risk of pulmonary hypertension when used alone.1-3 In this issue of the Journal, an unusual form of valvular heart disease is reported to be associated with use of the combination drug fenfluramine–phentermine,4 but whether valvular disease is also associated with use of the single agent dexfenfluramine is unknown. We wish to report a case of unusual valvular heart disease involving primarily the mitral valve in a young woman taking dexfenfluramine.

A 32-year-old woman was referred for evaluation of a heart murmur and the recent onset of dyspnea on exertion. She had no history of cardiac disease. Her only medication was dexfenfluramine (15 mg twice a day for the previous 10 months), and she had not taken antidepressant agents or ergotamine preparations. The physical examination was notable for the absence of jugular venous distention, the presence of clear lungs, a soft S₃ gallop, a grade 2/4 holosystolic murmur at the apex with radiation into the axilla, and a grade 1–2/4 decrescendo diastolic murmur at the base. The echocardiogram revealed unusual thickening of the mitral-valve leaflets and chordae tendineae with leaflet retraction (Figure 1AFigure 1Echocardiographic Studies in a Patient Taking Dexfenfluramine.), which resulted in malcoaptation of the valve (Figure 1A, arrow). There was severe central mitral regurgitation (Figure 1B), which extended back into the pulmonary vein. The estimated pulmonary arterial pressure was 60 mm Hg. Mild-to-moderate aortic and tricuspid regurgitation was also present. Dexfenfluramine was discontinued, and the patient was given long-acting nifedipine. Her symptoms improved, and the estimated pulmonary arterial pressure returned to a normal level, but she still had severe mitral regurgitation on follow-up echocardiography.

These mitral-valve changes are reminiscent of the right-sided valvular disease seen in association with the carcinoid syndrome and are similar to the changes described by Connolly et al.4 in patients treated with fenfluramine–phentermine. Although we do not have histologic information about this patient's mitral valve, she was a previously healthy young woman in whom symptomatic multivalvular disease developed during treatment with dexfenfluramine. The unusual valvular changes seen on the echocardiogram are not characteristic of congenital or rheumatic heart disease. Although prospective studies are needed to validate an association between valvular heart disease and the use of dexfenfluramine, a heightened clinical awareness of this problem seems prudent on the basis of the growing concern about such an association.

Lauralyn B. Cannistra, M.D.
Steven M. Davis, M.D.
Anne G. Bauman, M.D.
Brown University School of Medicine, Providence, RI 02912

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