Valvular heart disease in patients with Parkinson’s disease treated with pergolide. Course following treatment modifications

Abstract

Compared to controls, aortic regurgitation (OR: 3.1; 95% IC: 1.1-8.8) and mitral regurgitation (OR: 10.7; 95% IC: 2.1-53) were more frequent in PD patients (tricuspid: NS). The number of affected valves (n=2.4+/-0.7) and the sum of regurgitation grades (n=2.8+/-1.09) were higher (p=0.008 and p=0.006, respectively) in the pergolide group. Severity of regurgitation was not correlated with pergolide cumulative dose. A restrictive pattern of valvular regurgitation, suggestive of the role of pergolide, was observed in 12/30 (40%) patients including two with heart failure. Pergolide was discontinued in 10 patients with valvular heart disease, resulting in a lower regurgitation grade (p=0.01) at the second transthoracic echocardiography and the two patients with heart failure returned to nearly normal clinical examination. This study supports the high frequency of restrictive valve regurgitation in PD patients treated with pergolide and reveals that a significant improvement is usual when the treatment is converted to non-ergot dopamine agonists.

A long-term echocardiographic study of the course of valvular dysfunctions following discontinuation of ergot-derived dopamine agonists in patients with Parkinson's disease

“…In our patients at the follow-up assessment a statistically significant improvement of all echocardiographic parameters analyzed has been found, except for AR and PAP. The results of our study are in agreement with those by Dupuy et al [6] who first examined the course of EDA-related valvular damage in a group of 10 PD patients in which pergolide had been suspended for a median period of 13 months, reporting in 60% of them a significant improvement of the mitral valve regurgitation grading and of the sum of regurgitations grading, as well as of number of affected valves. Our findings on valvular regurgitation differ from those published by Rasmussen et al [7], who didn't find any significant change in AR, MR and TR one year after EDA discontinuation, whereas a worsening of these parameters was observed in patients who continued taking the EDA.…”

“…In the few followup studies [6][7][8][9], aimed at the assessment of the clinical outcome of VHD, an echocardiographic examination made on average 3 months to about 22 months after EDA withdrawal showed a trend toward a partial regression of VHD, but a complete resolution of the valvular functional and/or morphological damage has not been found. These results are in line with those previously reported with anorectic drugs, such as fenfluramine and dexfenfluramine [14], which share the same mitogenic effect on cardiac valvular fibroblasts and smooth muscle cells, believed to be mediated by stimulation of the 5HT2B receptors family, even though other factors might be involved [15].…”

“…An aspect that remains poorly investigated is the extent of reversibility of the valvular dysfunction after drug discontinuation. To date, only a few studies [6][7][8][9] have been formally conducted to assess this issue, reporting both a stability or a partial regression of valvular abnormalities. Furthermore, there are no data about the long term outcome of these valvulopathies, raising the doubt that the above reported findings could be due to a too short drug-free period of follow-up.…”

Dose Dependency and Reversibility of Serotonin-Induced Valvular Heart Disease in Rats

“…Drug dose was not the primary endpoint and was retrospectively acquired that led to inevitable bias [28]. Only a few reports describe the natural evolution of (dex)fenfluramine-and pergolide-induced valvulopathy in a limited number of patients [12][13][14]29]. These studies suggested that VHD was unlikely to progress if the causal drug was removed, and even regression of AR was described in some patients after removal.…”

“…Beside dose dependency, reversibility is also topic of interest. Few studies show spontaneous regression of VHD after cessation of the causal drug, but not in all patients [12][13][14].…”