Correspondence

Endocardial Fibrosis Associated with Fenfluramine–Phentermine

N Engl J Med 1998; 338:1316-1317April 30, 1998

Article

To the Editor:

It has been previously reported that valvular heart disease may be associated with the use of anorectic drugs.1 We report a case of restrictive cardiomyopathy due to endocardial fibrosis after short-term use of fenfluramine–phentermine.

A 35-year-old woman was hospitalized for congestive heart failure. Five months earlier she had begun taking 10 mg of fenfluramine three times a day and 15 mg of phentermine once a day, prescribed at her request because of obesity (height, 1.77 m; weight, 94.5 kg; body-mass index [calculated as the weight in kilograms divided by the square of the height in meters], 30.3). After three months she had lost 7 kg (15 lb) but discontinued the anorectic drugs, reporting fatigue, cough, chest discomfort, and exertional dyspnea. Pulmonary rales were present, a course of antibiotics was given without producing relief, and she was referred for further evaluation. One year earlier a series of common upper respiratory tract infections culminated during her 39th week of pregnancy in an episode of bronchopneumonia and pleurisy, which resolved. Her peripartum course was otherwise uncomplicated, and her medical and family histories were unremarkable.

Physical examination showed a generally normal appearance without rash, pallor, or fever. The blood pressure was 104/78 mm Hg, the respiratory rate was 18, and the pulse was regular at 108 per minute. The chest was clear except for decreased right basilar sounds. There was no cardiac murmur, gallop, or friction rub, but mild hepatomegaly and peripheral edema were present, with jugular venous distention but no Kussmaul's sign. The results of laboratory tests and electrocardiography were unremarkable, and a chest X-ray film showed a small right pleural effusion. Echocardiography revealed a normal left ventricle and aortic valve, mild mitral and tricuspid regurgitation, right atrial enlargement, and inferior vena caval engorgement but no pericardial effusion or thickening. Cardiac catheterization disclosed normal pulmonary-artery pressures (36/19 mm Hg; mean, 25), elevated ventricular end-diastolic pressures (right, 14 mm Hg; left, 24 mm Hg), a dip-and-plateau right-ventricular-pressure wave form, and a mean right atrial pressure of 15 mm Hg, all consistent with the presence of restrictive cardiomyopathy. The findings on coronary and left ventricular angiography were normal (ejection fraction, 0.60). A right ventricular endomyocardial biopsy was performed,2 revealing thickened endocardium with extensive fibrosis and collagen but no inflammation (Figure 1AFigure 1Photomicrographs of a Right Ventricular Endomyocardial-Biopsy Specimen. and Figure 1B).

These endocardial findings strongly resemble the valvular lesions reported with the use of fenfluramine–phentermine.1 Endocardial and valvular fibrosis associated with anorectic drugs is strikingly similar to the plaque material found in patients with the carcinoid syndrome 3 and those exposed to methysergide,4,5 and it may arise from common mechanisms. Surveillance of patients at risk should be heightened, and further clinical investigation should be conducted to determine possible risk factors and pathophysiology.

Robert E. Fowles, M.D.
Tom V. Cloward, M.D.
Robert L. Yowell, M.D., Ph.D.
LDS Hospital, Salt Lake City, UT 84143

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   Markus Flesch, Erland Erdmann. (2006) The problem of polypharmacy in heart failure. Current Cardiology Reports 8:3, 217-225
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   Lisa L Ioannides-Demos, Joseph Proietto, Andrew M Tonkin, John J McNeil. (2006) Safety of Drug Therapies Used for Weight Loss and Treatment of Obesity. Drug Safety 29:4, 277-302
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   Paul C. McDonald, Janet E. Wilson, Min Gao, Shannon McNeill, John J. Spinelli, O.Dale Williams, Salima Harji, Jennifer Kenyon, Bruce M. McManus. (2002) Quantitative analysis of human heart valves. Cardiovascular Pathology 11:5, 251-262
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   Craig H Steffee, Harsharan K Singh, W.Randolph Chitwood. (1999) Histologic Changes in Three Explanted Native Cardiac Valves Following Use of Fenfluramines. Cardiovascular Pathology 8:5, 245-253
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   &NA;. (1998) Fenfluramine/phentermine. Reactions Weekly &NA;:700, 8
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