In the 1990s several studies reported the association between appetite suppressant medications and valvular heart disease, particularly aortic and mitral regurgitation. These medications included fenfluramine and its D-isomer dexfenfluramine used alone or in combination with phentermine. Although they were withdrawn from the market, patients with valvular involvement may be encountered and some may require surgical attention. In most cases, the severity of valvular regurgitation is mild to moderate. Some studies have suggested the improvement of valvular disease after discontinuation of the medication. Occasionally, however, patients develop significant valvular regurgitation requiring surgical correction. In addition to valvular heart disease, pulmonary hypertension is a common finding in these patients. Serotonin-induced pulmonary vasoconstriction is believed to play a major role in the genesis of this condition. Ergotamine therapy is another medication that may induce valvular heart disease. The rare cases of ergot alkaloid–induced valvular diseases involve the aortic and/or mitral position.

In most patients, echocardiography shows a type IIIa valvular dysfunction with leaflet thickening and retraction and with chordae thickening and shortening in both the mitral and the tricuspid positions. Most patients present with valvular regurgitation combined with varying degrees of stenosis.

The pathological findings are similar to those observed in carcinoid heart disease, with thickening of the valvular leaflets as well as the subvalvular apparatus. The architecture of the leaflets is intact, and histological examination shows proliferative myofibroblasts and a significant increase in the extracellular matrix.

In patients with severe symptomatic valvular disease, surgical therapy remains the only reliable option. In the aortic position, valve replacement is mandatory. In the mitral and tricuspid positions, a valve reconstruction could be considered in favorable cases using leaflet patch extension and remodeling annuloplasty. It should be noted that surgical experience is extremely limited in this setting with no long-term data currently available.