Aortic and Mitral Fenfluramine-phentermine Valvulopathy in 64 Patients Treated with Anorectic Agents

Context: Few published studies of the pathology of fenfluramine-phentermine (fen-phen) valvulopathy, described by Connolly and colleagues in 1997, have appeared.

Objectives: To define temporal changes in the morphology of the stuck-on plaques and to determine whether the plaques progress or regress after cessation of fen-phen.

Methods: The available clinical information and pathology material from 35 aortic valves (AVs) and 43 mitral valves (MVs) from 64 patients were reviewed.

Results: The valves fell into 3 groups: 17 AVs and 28 MVs had fen-phen lesions only, 2 AVs and 7 MVs had fen-phen changes associated with other valve diseases, and 16 AVs and 8 MVs had no fen-phen changes. Fenfluramine-phentermine-attributable dysfunction was regurgitation in all instances. Typical plaques showed proliferation of myofibroblastic cells with myxoid stroma. Small vascular channels and slight lymphocytic accumulations were often present. Deeper parts of some plaques had dense fibroelastic tissue underlying typical plaque.

Conclusions: Considerable individual variation in the time course of anorectic agent use and the severity of fen-phen valvulopathy was observed. Possible plaque regression could not be assessed from this study. The observations suggest that in some patients fen-phen-induced plaques may continue to have surface proliferation despite drug withdrawal.