Correspondence

Regression of Multivalvular Regurgitation after the Cessation of Fenfluramine and Phentermine Treatment

N Engl J Med 1998; 339:771September 10, 1998

Article

To the Editor:

Treatment with the appetite-suppressant drugs fenfluramine and dexfenfluramine, alone or in combination with phentermine, has been associated with cardiac-valve abnormalities.1-3 Five echocardiologic surveys reviewed by the Food and Drug Administration suggested that the prevalence of cardiac-valve abnormalities is 30 to 38 percent among patients who have taken these drugs2 and led to the withdrawal of fenfluramine and dexfenfluramine from the U.S. market on September 15, 1997. Whether these lesions resolve, progress, or remain unchanged after discontinuation of the drugs is not yet known. We report the possibility of regression of multivalvular regurgitation associated with fenfluramine and phentermine in a patient who was followed for two years after she stopped taking the drugs.

A 44-year-old woman with morbid obesity was hospitalized in July 1996 for atypical chest pain. Myocardial infarction was ruled out, and an echocardiogram revealed normal chamber sizes and mildly reduced global systolic function. However, moderate-to-moderately-severe aortic regurgitation, mild mitral regurgitation, and moderate tricuspid regurgitation were present. The estimated pulmonary-artery pressure was mildly elevated (38 mm Hg). The patient had no history of cardiac disease. Her only medications were 60 mg of fenfluramine and 30 mg of phentermine daily, which she had taken for the previous 50 weeks, during which time she had lost 40 kg (87 lb). These drugs were discontinued, and the patient began taking 10 mg of lisinopril daily and 25 mg of metoprolol twice daily for borderline hypertension. In December 1997, an echocardiogram showed improved left ventricular function and a decrease in all regurgitant lesions, with no clinically significant change in the estimated pulmonary-artery pressure. In May 1998, physical examination revealed a weight of 198 kg (436 lb), blood pressure of 130/90 mm Hg, and a 1–2/6 systolic ejection murmur along the left sternal border. An echocardiogram obtained in June 1998 (two years after the initial study) demonstrated only trace aortic and tricuspid regurgitation without mitral regurgitation.

In this case, serial echocardiographic studies over a two-year period document regression of multivalvular regurgitation first discovered while the patient was taking fenfluramine and phentermine. Although this patient was treated with lisinopril, the marked degree of improvement in all the regurgitant lesions is unlikely to be attributable to this medical intervention alone.4 Follow-up studies involving larger numbers of affected patients are clearly needed to document the natural history of these lesions. This case report suggests, however, that mild-to-moderate valvular involvement associated with fenfluramine and phentermine may be at least partially reversible on discontinuation of these drugs.

Lauralyn B. Cannistra, M.D.
Anthony J. Cannistra, M.D.
Brown University School of Medicine, Providence, RI 02912

4 References

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   Connolly HM, Crary JL, McGoon MD, et al. Valvular heart disease associated with fenfluramine-phentermine. N Engl J Med 1997;337:581-588[Erratum, N Engl J Med 1997;337:1783.]
   Full Text | Web of Science | Medline

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   Cannistra LB, Davis SM, Bauman AG. Valvular heart disease associated with dexfenfluramine. N Engl J Med 1997;337:636-636
   Full Text | Web of Science | Medline

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   Cardiac valvulopathy associated with exposure to fenfluramine or dexfenfluramine: US. Department of Health and Human Services interim public health recommendations. MMWR Morb Mortal Wkly Rep 1997;46:1061-1066
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   Levine HJ, Gaasch WH. Vasoactive drugs in chronic regurgitant lesions of the mitral and aortic valves. J Am Coll Cardiol 1996;28:1083-1091
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Citing Articles (16)

Citing Articles

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   S. Droogmans, D. Kerkhove, B. Cosyns, G. Van Camp. (2009) Role of echocardiography in toxic heart valvulopathy. European Journal of Echocardiography 10:4, 467-476
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   Benoit Drolet, Chantale Simard, Paul Poirier. (2007) Impact of Weight-Loss Medications on the Cardiovascular System. American Journal of Cardiovascular Drugs 7:4, 273-288
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   Zara Cooper, Cesar E. Escareno, David B. Lautz. 2006. Management of Perioperative Cardiac Risk in the Bariatric Patient. , 365-380.
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   2006. Fenfluramines. , 1333-1344.
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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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   Andrei Barasch, Monika M. Safford. (2002) Diet medications and valvular hearl disease: the current evidence. Special Care in Dentistry 22:3, 108-114
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   Chari Y. Teramae, Heidi M. CONNOLLY, Martha Grogan, Fletcher A. Miller. (2000) Diet Drug-Related Cardiac Valve Disease: The Mayo Clinic Echocardiographic Laboratory Experience. Mayo Clinic Proceedings 75:5, 456-461
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   C Y Teramae, H M Connolly, M Grogan, F A Miller. (2000) Diet drug-related cardiac valve disease: the Mayo Clinic echocardiographic laboratory experience.. Mayo Clinic Proceedings 75:5, 456-461
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   Donald D. Hensrud. (2000) PHARMACOTHERAPY FOR OBESITY. Medical Clinics of North America 84:2, 463-476
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    Neil J Weissman, John F Tighe, John S Gottdiener, John T Gwynne. (1999) Prevalence of valvular-regurgitation associated with dexfenfluramine three to five months after discontinuation of treatment. Journal of the American College of Cardiology 34:7, 2088-2095
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    Richard W. Asinger. (1999) The Fen-Phen Controversy: Is Regression Another Piece of the Puzzle?. Mayo Clinic Proceedings 74:12, 1302-1304
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    D D Hensrud, H M Connolly, M Grogan, F A Miller, K R Bailey, M D Jensen. (1999) Echocardiographic improvement over time after cessation of use of fenfluramine and phentermine.. Mayo Clinic Proceedings 74:12, 1191-1197
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    Ananth Prasad, Mandeep Mehra, Myung Park, Robert Scott, Patricia A Uber, P.Michael McFadden. (1999) Cardiac allograft valvulopathy: a case of donor-anorexigen-induced valvular disease. The Annals of Thoracic Surgery 68:5, 1840-1841
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    (1999) Appetite-Suppressant Drugs and Valvular Heart Disease. New England Journal of Medicine 340:6, 476-480
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    I Mclean Baird. (1998) Risks of heart-valve abnormalities with appetite suppressants. The Lancet 352:9138, 1403-1404
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    &NA;. (1998) Fenfluramine/phentermine. Reactions Weekly &NA;:719, 7
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