Pergolide is a dopamine receptor agonist that is used in the treatment of Parkinson's disease and restless legs syndrome. This drug, an ergotamine derivative, has been associated with retroperitoneal, pleural, and pericardial fibrosis similar to that caused by other drugs in this class (such as methysergide and ergotamine). More recently, restrictive valvular heart disease has been reported in patients taking pergolide, but the incidence was only one in 20,000 patients. Van Camp and colleagues sought to establish the frequency, severity, and reversibility of pergolide-associated restrictive valvular heart disease and to examine the possibility of dose dependency.
The researchers invited patients with Parkinson's disease who were attending outpatient neurology clinics at four Dutch hospitals to participate in the study. Persons with a history of coronary or valvular heart disease were excluded from the study. Patients also were excluded if they had been receiving ergot-derived medications, anorectic drugs, or Chinese herbs. All study participants were examined by transthoracic echocardiography with special attention to the cardiac valves. The same technician using the same equipment performed the echocardiography. Interpretations were made by an independent sonographer who was masked to the patient's treatment.
A total of 78 patients who had been treated with pergolide were enrolled in the study, along with 18 persons who had never been treated with an ergot-derived dopamine agonist. On average, the patients receiving pergolide were a little younger than those in the control group (mean ages, 70.9 and 72.8 years, respectively). One half of the patients in the control group were women, but only 33 of the 78 patients receiving pergolide were women. Evidence of restrictive valvular heart disease was not found in any of the 18 control patients. Twenty-six patients in the pergolide group had evidence of restrictive valvular heart disease, with the mitral valve being the most commonly affected (26 percent of patients), followed by the aortic valve (9 percent) and the tricuspid valve (8 percent). Clinically significant disease was present in 15 patients (19 percent) receiving pergolide but in none of the patients in the control group. Restrictive valvular disease was more common in patients taking high-dose pergolide versus low-dose pergolide (42 and 29 percent, respectively), and a significant correlation was demonstrated between the cumulative doses of pergolide and the tenting areas of the mitral valves. Pergolide therapy was discontinued in six patients; two showed significant regression of mitral valve disease within six months. Mean systolic pulmonary artery pressures also were increased significantly in patients receiving pergolide. These pressures remained elevated after exclusion of patients with relevant mitral valve disease.
The authors conclude that restrictive valvular cardiac disease is common in patients receiving pergolide for Parkinson's disease. They believe the underlying pathology to be fibrotic changes in leaflets and subvalvular apparatus of valves that causes stiffening of the valves and distortion of their normal functioning. In older patients with Parkinson's disease, changes in the tricuspid valve may be most diagnostic, because the aortic and mitral valves may show age-related changes. Pergolide also may cause pulmonary hypertension as it interacts with the serotonin 5-HT receptor implicated in the induction of heart disease by appetite-suppressing drugs.