Regression of Cardiac Valvulopathy Related to Ergot-Derived Dopamine Agonists

Abstract

SUMMARY Aims:In a previous echocardiographic prevalence study we reported a significant increase in the frequency of heart valve regurgitation in patients with Parkinson's disease taking the ergot-derived dopamine agonists pergolide and cabergoline versus controls. We followed-up our original cohort of patients to ascertain whether valvulopathy regressed after discontinuation of treatment and/or its incidence increased over time. Methods: Prospective follow-up of 101 patients treated with ergot-derived dopamine agonists included in the prevalence study: 53 given pergolide and 48 cabergoline (64% male; 66.4 ± 8.7 years of age, 11.5 ± 5.9 years of disease, 21.8 ± 5.9 months of followup); 55 stopped treatment while 46 continued. The main outcomes measures, were: echocardiographic quantification of regurgitant valve disease, abnormal leaflet, or cusp thickening and measurement of mitral valve tenting area. Results: Valve abnormalities regressed in about one third of patients with significant multivalvular and in about half of the patients with monovalvular regurgitation who withdrew; no progression was observed in remaining patients. Patients continuing ergot-derived dopamine agonists showed progression of cardiac valvulopathy: seven new cases with three to four regurgitation grade of any valve occurred during follow-up; this regarded also patients who had been on pergolide for many years. Conclusion: Owing to the persistence of risk of heart valve damage over time and the lack of its mid-term reversibility in many patients, we believe that pergolide and cabergoline should be prescribed only when therapeutic alternatives with a better risk/benefit ratio are unavailable and the patient has access to echocardiography.

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

“…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. Zanettini et al observed a significant decrease of composite regurgitation score, but not of the single valve regurgitation score, in a cohort of 21 PD patients with moderate to severe (grade 3 to 4) regurgitation 22 months on average after the cessation of cabergoline and pergolide [8], whereas in our patients the improvement of the sum of regurgitations was associated to an amelioration of MR and TR. In our patients only AR showed an evolution apparently independent from the withdrawal of EDA, even though the aortic-valve was functionally less affected than the mitral and tricuspid valves.…”

“…Indeed, one of the limitations of these studies is the relatively short follow-up after EDA suspension, which could have caused an underestimation of the extent of regression of VHD. Our study, although conducted on a small number of PD patients, is the first to investigate the outcome of VHD associated to EDA with a follow-up duration on average more than double as compared to the longest so far reported [8]. On the other hand, a long follow-up could have some limitations.…”

“…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.…”

Evaluation of the valvular and biventricular functions in Parkinson patients using ergotamine-derived dopamine agonist: an observational study

“…We also used a composite scoring system derived from the sum of mitral, aortic, and tricuspid scores (value range of the composite score: 0 to 12; higher scores indicate more severe disease) as used in previous studies (14). Abnormal leaflet or cusp thickening was accepted to be present when the thickness was >5 mm.…”