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Cardiac surgery in a patient with retroperitoneal fibrosis and heart valvulopathy, both due to pergolide medication for Parkinson's disease
© Apostolakis et al; licensee BioMed Central Ltd. 2009
Received: 31 August 2009
Accepted: 13 November 2009
Published: 13 November 2009
Retroperitoneal fibrosis is best described as a chronic inflammatory process which may be idiopathic, but can rarely be brought about by medications, such as pergolide, used for treating Parkinson's disease. Pergolide can produce a fibrotic process in heart valves, resulting in valve insufficiency in up to 25% of cases. Herein we describe the case of a 68-year-old man who received pergolide for 2 years for Parkinson's disease. The patient developed retroperitoneal fibrosis resulting in renal failure from ureteral obstruction necessitating ureteral stenting, as well as significant aortic and mitral valve insufficiency. He successfully underwent surgery for combined aortic valve, mitral valve and ascending aorta replacement because of severe valve insufficiency and dilated (d = 5.8 cm) ascending aorta. Retroperitoneal fibrosis improved with pergolide cessation and corticosteroid treatment. This is the second case reported in the literature, of a patient who had double valve and ascending aorta replacement surgery because he suffered from this rare but serious adverse effect of dopamine agonists used for managing Parkinson's disease.
Retroperitoneal fibrosis (RPF) describes a chronic inflammatory process of the retroperitoneum, with eventual fibrosis and entrapment of the ureters and other retroperitoneal organs, which can produce obstructive uropathy and renal failure [1, 2]. Rarely, is RPF related to drugs overt autoimmune disease and chronic infection, such as tuberculosis [1, 3]. In fact, retroperitoneal or pleural fibrosis, the so called "serosal fibrosis" secondary to pergolide has been reported by many authors [4, 5]. Apart from the above mentioned serosal fibrosis, another consequence of ergot dopamine agonists, such as pergolide, is heart valve regurgitation. Van Camp G et al  reported the development of moderate-to-severe heart-valve regurgitation in 15 of 78 patients treated with pergolide for Parkinson's disease. The changes mediated by the 5-HT2B agonist are closely connected to the serotoninergic receptors expressed on cardiac valvular fibroblasts [6, 7]. In fact, pergolide and cabergoline have high "affinity" for the 5-HT2B serotonin receptors, which are expressed in heart valves and might mediate mitogenesis and, in turn, the proliferation of fibroblasts. The latter process causes fibrotic changes such as thickening, retraction, and stiffening of valves, which result in incomplete leaflet closure and clinically significant regurgitation . Fortunately, heart valve replacement will only be necessary in a few of these patients.
Pergolide, a drug used for treating Parkinson's disease, can cause retroperitoneal fibrosis, as well as a dose-dependent heart valve fibrotic process, leading to severe valve insufficiency after two to three years of treatment [5–7]. There are no large series or case reports of patients undergoing cardiac surgery for double valvulopathy due to pergolide. Zanettini et al  examined the risk of heart valve degeneration and severity of valve disease by comparing 64 patients taking pergolide with 49 patients taking cabergoline, 42 patients taking a non-ergot derivative, and 90 control patients, and showed that the frequency of clinically important regurgitation in any cardiac valve was significantly higher in patients taking pergolide (23.4%) or cabergoline (28.6%), compared to patients taking non-ergot dopamine agonists (0%) or controls (5.6%). New evidence from population studies comparing patients with Parkinson's disease and non-parkinsonian controls suggests that the risk of substantial valve regurgitation is 5-6 times higher in patients with Parkinson's disease treated with cabergoline, and documents the occurrence of cardiac valvulopathy in patients treated with pergolide at doses around 3 mg/day or more . A similar study from Japan  reported a significantly (p < 0·05) increased risk of echocardiographically significant valvular regurgitation in patients taking cabergoline but not in those receiving pergolide. The reasons for the observed lower incidence of valve regurgitation in the Japanese study in comparison to Europeans studies is unclear and may be related to the lower pergolide doses used in Asian patients. There are only a few reported cases of patients who had surgery for cardiac disease acquired due to medications given for treatment of Parkinson's disease: A) by Zanettini et al , a 69-year-old man taking pergolide underwent mitral-valve and aortic-valve replacement for severe mitral regurgitation and moderate aortic regurgitation. The surgeon described the mitral and aortic valve leaflets in this patient as diffusely thickened and retracted. B) By Camp G, et al , a 73-year old female taking pergolide presented with a new holosystolic murmur, and required aortic valve replacement. In conclusion, we suggest that every patient taking pergolide for Parkinson's disease should be subjected to ECHO examination every six months, for heart valve function assessment.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the journal Editor-in-Chief.
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