Citation: Supplement to Journal of the American College of Cardiology February 2000, Vol. 35, Issue 2, Suppl. A, page 523

Steven T. Mast, James G. Jollis, Thomas Ryan, Carolyn K. Landolfo, Jack L. Crary

Background: An association between the dietary suppressant fenfluramines and valvular heart disease was first described among a cohort of patients from North Dakota and Minnesota in 1997. The natural history of this valvulopathy remains unknown.

Methods: We compared serial echocardiograms among 18 patients in the original report, and 32 additional patients presenting to MeritCare Medical Center in Fargo, ND who met FDA criteria for fenfluramine-associated valvulopathy to determine disease progression after stopping the medication. The mean duration of drug exposure was 13 months. Echo-Doppler studies were reviewed by two cardiologists blinded to the order of acquisition to assess the severity of valvular regurgitation and leaflet thickening or restriction.

Results: As described in the initial report, moderate to severe valvular disease was relatively common among this cohort (n = 50) on initial post-exposure echo [mitral regurgitation (MR)-mild 8 pts (16%), moderate 9 (18%), severe 12 (24%); aortic regurgitation (AR)-mild 9 (18%), moderate 13 (26%), severe 11 (22%)]. The change in severity of regurgitation on follow-up echos performed a mean of 12 months following the initial post-exposure echo is displayed below:

% Patients MR AR

Improving >1 grade 34% 38%

Without change 58% 54%

Worsening >1 grade 8% 8%

For the majority of patients, the degree of valve regurgitation was unchanged. Among patients whose regurgitation changed, more were likely to show improvement of at least one grade (P < 0.05), including two patients whose severe regurgitation at baseline was considered mild on follow-up. Conversely, further deterioration was uncommon, which may be partly attributable to the substantial number of patients who were initially graded as severe. Conclusion: This is the first description of the natural history of fenfluramine-associated valvular disease. The regression of valvular regurgitation occurring in some patients should be taken into account when considering the timing of valve surgery.