title: Serial echocardiographic and clinical evaluation of valvular regurgitation before, during, and after treatment with fenfluramine or dexfenfluramine and mazindol or phentermine.
abstract: 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 echocardiograms before treatment with appetite suppressants to determine the incidence of new cases and to evaluate the clinical implication of the echocardiographic findings.
  
  
  METHODS
  We studied 69 men [Mean+/-Standard Deviation (S) age 49+/-8] and 17 women (mean+/-S age 50+/-7) who had 233 echocardiograms before, during, and after a weight-loss program that used predominantly fenfluramine (or dexfenfluramine) with mazindol (or phentermine). Mean drug exposure was 17 months. Blinded echocardiographic readings were performed to identify and grade aortic regurgitation (AR) or mitral regurgitation (MR).
  
  
  RESULTS
  Seven of 86 patients (8%) had pre-existing regurgitation with five (6%) meeting our case definition. Thirteen (16.5%) of initially normal patients 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 could be auscultated. There was significantly greater risk for developing valvulopathy for those who took medications longer than 6 months (p = 0.03), and no new cases were observed in patients exposed for less than 8 months. No increased risk associated with age, presence of hypertension, or exposure to fenfluramine-phentermine combination was demonstrated. Although there was a higher incidence of new regurgitation in women (31% vs. 13% for men), this was not statistically significant (p = 0.093).
  
  
  CONCLUSIONS
  Some patients who had normal echocardiograms at baseline developed cardiac valvular regurgitation after exposure to fenfluramine or dexfenfluramine with mazindol or phentermine. The development of valvulopathy was significantly correlated with duration of exposure. The clinical implications of echocardiographically demonstrated regurgitation are uncertain, since there were only two audible murmurs and no other clinically relevant signs or symptoms among the patients.
authors.affiliation: Pennington Biomedical Research Center, Baton Rouge, LA 70808-4124, USA. RYANDH@MHS.PBRC.EDU
authors.forename: D H
authors.initials: DH
authors.lastname: Ryan
authors.forename: G A
authors.initials: GA
authors.lastname: Bray
authors.forename: F
authors.initials: F
authors.lastname: Helmcke
authors.forename: G
authors.initials: G
authors.lastname: Sander
authors.forename: J
authors.initials: J
authors.lastname: Volaufova
authors.forename: F
authors.initials: F
authors.lastname: Greenway
authors.forename: P
authors.initials: P
authors.lastname: Subramaniam
authors.forename: D L
authors.initials: DL
authors.lastname: Glancy
mesh_terms: D001022:Aortic Valve Insufficiency / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000453:epidemiology; D001067:Appetite Depressants / Q000009:adverse effects* / Q000627:therapeutic use; D015992:Body Mass Index; D003376:Counseling; D020372:Dexfenfluramine / Q000009:adverse effects / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004452:Echocardiography; D005260:Female; D005277:Fenfluramine / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D008297:Male; D008454:Mazindol / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D008944:Mitral Valve Insufficiency / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000453:epidemiology; D009765:Obesity / Q000188:drug therapy*; D015588:Observer Variation; D010645:Phentermine / Q000009:adverse effects / Q000627:therapeutic use; D015995:Prevalence; D015431:Weight Loss
chemical_list: D001067:Appetite Depressants; D005277:Fenfluramine; D010645:Phentermine; D008454:Mazindol; D020372:Dexfenfluramine