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ARTICLE

The Progression of Fenfluramine-Associated Valvular Heart Disease Assessed by Echocardiography

Steven T. Mast, MD; James G. Jollis, MD; Thomas Ryan, MD; Kevin J. Anstrom, MS; and Jack L. Crary, MD

20 February 2001 | Volume 134 Issue 4 | Pages 261-266

Background: An association between the dietary suppressants fenfluramine and dexfenfluramine and valvular heart disease was first described in patients from North Dakota and Minnesota in 1997. Limited data are available on the natural history of this valvulopathy after discontinuation of drug therapy.

Objective: To follow the progression of fenfluramine-associated valvular heart disease after discontinuation of therapy by using serial echocardiography.

Design: Retrospective cohort study.

Setting: Regional medical center in Fargo, North Dakota.

Patients: 50 patients with previous exposure to fenfluramines who had at least mild mitral regurgitation or aortic regurgitation after exposure to fenfluramines on serial echocardiography between December 1994 and February 1999 (96% were female, mean body mass index was 36.6 kg/m², and mean duration of drug exposure was 447 days).

Measurements: Serial echocardiograms were reviewed by two echocardiographers who were blinded to the order of image acquisition. The severity of valvular regurgitation and presence or absence of valve leaflet restriction were assessed.

Results: As described in the initial report, significant valvular disease on initial postexposure echocardiography was common in this cohort; 38 patients (76%) had at least mild mitral regurgitation and 43 patients (86%) had at least mild aortic regurgitation. On serial echocardiograms obtained an average of 356 days apart, mitral regurgitation improved by at least one grade in 17 patients (P = 0.001) and aortic regurgitation improved by at least one grade in 19 patients (P = 0.004). Nineteen and 22 patients, respectively, experienced no change in severity of mitral and aortic regurgitation. Two patients in each group experienced worsening of regurgitation by at least one grade. Results were similar for tricuspid (P = 0.002) and pulmonic (P = 0.012) regurgitation.

Conclusion: On serial echocardiography, fenfluramine-associated valvular regurgitation improved or remained stable in most patients after therapy ended. Worsening of valvular regurgitation was uncommon. The potential for stabilization or regression of valvular regurgitation should be taken into account when counseling patients and considering the need for and timing of valve surgery.

Author and Article Information

From Duke University Medical Center, Durham, North Carolina; and MeritCare Medical Center, Fargo, North Dakota.

Acknowledgments:The authors thank Liz Whirley and Karen Berger for invaluable assistance with this project.

Grant Support:By research grant HL03995-01 from the National Heart, Lung, and Blood Institute, Bethesda, Maryland.

Requests for Single Reprints:James G. Jollis, MD, Duke Clinical Research Institute, PO Box 17969, Durham, NC 27715.

Current Author Addresses:Drs. Mast, Jollis, and Ryan and Mr. Anstrom: Duke Clinical Research Institute, Durham, NC 27715.

Dr. Crary: MeritCare Medical Center, 737 Broadway, Fargo ND 58123.

Author Contributions:Conception and design: S.T. Mast, J.G. Jollis, T. Ryan, J.L. Crary.

Analysis and interpretation of the data: S.T. Mast, J.G. Jollis, T. Ryan, J.L. Crary.

Drafting of the article: S.T. Mast, J.G. Jollis, K.J. Anstrom, J.L. Crary.

Critical revision of the article for important intellectual content: S.T. Mast, J.G. Jollis, T. Ryan, K.J. Anstrom, J.L. Crary.

Final approval of the article: S.T. Mast, J.G. Jollis, T. Ryan, K.J. Anstrom, J.L. Crary.

Provision of study materials or patients: J.L. Crary.

Statistical expertise: J.G. Jollis, K.A. Anstrom.

Obtaining of funding: J.G. Jollis.

Administrative, technical, or logistic support: J.G. Jollis, T. Ryan.

Collection and assembly of data: S.T. Mast.

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