title: Detailed examination of fenfluramine-phentermine users with valve abnormalities identified in Fargo, North Dakota.
abstract: Although several studies have reported on valve abnormalities among users of fenfluramine or dexfenfluramine, detailed information on these subjects has not been provided, limiting the ability to understand who may be at risk for valve abnormalities and to generate hypotheses about the etiology and pathogenesis of these abnormalities. This study was a detailed medical record review of 18 previously reported users of fenfluramine and phentermine, all with valve abnormalities on echocardiogram and 2 with surgical pathology. Both clinical characteristics and medication use were recorded by trained abstracters using a standardized data collection form. Two subjects (11%) had other possible etiologies of valve disease: a history of rheumatic fever and prescribed ergotamine. Three subjects (17%) had a history of migraine headaches and 4 (22%) had murmurs noted before using fenfluramine. Use of medications that may affect serotonin receptors was common: ergotamine (1 subject, 5%), selective serotonin reuptake inhibitors (6, 33%), sumatriptan (2, 11%), and mirtazapine (1, 5%). Prior medication and nonmedication allergies were recorded in 6 (33%) and 3 (17%) subjects, respectively. All subjects had symptoms possibly due to fenfluramine or phentermine side effects. This study raises the hypotheses that valvular heart disease among fenfluramine users may be less common than previously estimated, that serotonin excess may play a role in valve pathology, and that a patient's response to anorexigens and other medications may serve as a marker for increased risk. Further study is needed to test these hypotheses.
authors.affiliation: Department of Medicine, Hospital of the University of Pennsylvania, and Center for Clinical Epidemiology, and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia 19104, USA. skimmel@cceb.med.upenn.edu
authors.forename: S E
authors.initials: SE
authors.lastname: Kimmel
authors.forename: M G
authors.initials: MG
authors.lastname: Keane
authors.forename: J L
authors.initials: JL
authors.lastname: Crary
authors.forename: J
authors.initials: J
authors.lastname: Jones
authors.forename: J L
authors.initials: JL
authors.lastname: Kinman
authors.forename: J
authors.initials: J
authors.lastname: Beare
authors.forename: M
authors.initials: M
authors.lastname: Sammel
authors.forename: M S
authors.initials: MS
authors.lastname: Sutton
authors.forename: B L
authors.initials: BL
authors.lastname: Strom
mesh_terms: D000328:Adult; D001067:Appetite Depressants / Q000009:adverse effects*; D005260:Female; D005277:Fenfluramine / Q000009:adverse effects*; D006349:Heart Valve Diseases / Q000139:chemically induced / Q000209:etiology*; D006351:Heart Valves / Q000002:abnormalities* / Q000000981:diagnostic imaging / Q000601:surgery; D006801:Humans; D008875:Middle Aged; D009658:North Dakota; D010645:Phentermine / Q000009:adverse effects*; D012307:Risk Factors; D014463:Ultrasonography
chemical_list: D001067:Appetite Depressants; D005277:Fenfluramine; D010645:Phentermine