Serial echocardiographic and clinical evaluation of valvular regurgitationbefore, during, and after treatment with fenfluramine or dexfenfluramine and mazindol or phentermine

Objective: The prevalence of cardiac valvular regurgitation demonstrated by echocardiography in patients who took appetite-suppressant medication for weight loss has been assessed at 5%-30%. We studied 86 patients who had ech ocardiograms before treatment with appetite suppressants to determine the i ncidence of new cases and to evaluate the clinical implication of the echoc ardiographic findings. Research Methods and Procedures: We studied 69 men [Mean +/- Standard Devia tion (S) age 49 +/- 8] and 17 women (mean +/- S age 50 +/- 7) who had 233 e chocardiograms before, during, and after a weight-loss program that used pr edominantly fenfluramine (or dexfenfluramine) with mazindol (or phentermine ). Mean drug exposure was 17 months. Blinded echocardiographic readings wer e performed to identify and grade aortic regurgitation (AR) or mitral regur gitation (MR). Results: Seven of 86 patients (8%) had pre-existing regurgitation with five (6%) meeting our case definition. Thirteen (16.5%) of initially normal pat ients developed valvular regurgitation and were new cases. Of the new cases , 12 were grade I/IV AR and one was both grade II/III MR and II/IV AR. All 13 patients were asymptomatic, and only two aortic insufficiency murmurs co uld be auscultated. There was significantly greater risk for developing val vulopathy for those who took medications longer than 6 months (p = 0.03), a nd no new cases were observed in patients exposed for less than 8 months. N o increased risk associated with age, presence of hypertension, or exposure to fenfluramine-phentermine combination was demonstrated. Although there w as a higher incidence of new regurgitation in women (31% vs. 13% for men), this was not statistically significant (p = 0.093). Discussion: Some patients who had normal echocardiograms at baseline develo ped cardiac valvular regurgitation after exposure to fenfluramine or dexfen fluramine with mazindol or phentermine. The development of valvulopathy was significantly correlated with duration of exposure. The clinical implicati ons of echocardiographically demonstrated regurgitation are uncertain, sinc e there were only two audible murmurs and no other clinically relevant sign s or symptoms among the patients.