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ARTICLES: Mitsutoshi Yamamoto, Tadahisa Uesugi, and Takeo Nakayama Dopamine agonists and cardiac valvulopathy in Parkinson disease: A case–control study Neurology 2006; 67: 1225-1229 [Abstract] [Full text] [PDF]

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Dopamine agonists and cardiac valvulopathy in Parkinson disease: A case–control study

Mehmet G. Senol, MD, R. Erdem Togrol, MD   (21 March 2007)

Reply from authors

Mitsutoshi Yamamoto, Tadahisa Uesugi; Department of Cardiology, Kagawa Prefectural Central Hospital , Takeo Nakayama Kyoto University, Graduate School of Public Health   (21 March 2007)

Dopamine agonists and cardiac valvulopathy in Parkinson disease: A case–control study 21 March 2007
Mehmet G. Senol, MD, GMMA Haydarpasa Education Hospital Istanbul, Turkey, R. Erdem Togrol, MD Send Correspondence to journal: Re: Dopamine agonists and cardiac valvulopathy in Parkinson disease: A case–control study mgsenol{at}yahoo.com Mehmet G. Senol, MD, et al.	We read the article by Yamamoto et al who address the issue of the management of PD.[1] The large number of subjects and the conclusions are impressive. We have a few concerns with the design of the study. The number of subjects was not equal or similar among the treatment groups (cabergoline-16, pramipexole-16, pergolide-66, past-treated-27). In addition, the female/male ratio in the cabergoline and control groups was high in comparison to the other groups and the illness duration of the patients who received pramipexole was not significantly different from the control group, while it was longer for the other groups. The duration of illness is significantly higher in the pergolide and cabergoline treated groups than the control group and the other two treatment groups. The patients in these have had the disease for a significantly longer time than the patients in the other two treatment groups. The Hoehn and Yahr Score(HYS) is high in the pergolide(2.6) and cabergoline-treated(2.63) groups compared to the control group, while it is similar to the control group in the other treatment groups and the duration of illness is lower in the pramipexole group than the other groups. The cumulative dose is low for the pramipexole group, although the daily dose is in the therapeutic range. This is because the duration of treatment is longer in the other groups. In the study by Murakami et al [2], the low dose of pergolide is reported to be 1.5mg. In the present study, the reported mean pergolide dose is 1.4mg. The 85 patients in the control group were not treated for an average of five years, while the HYS is relatively high(>2). We would like clarification about the follow-up in this study. In reviewing the authors' references, we note that the study by Van Camp et al is a study solely on pergolide [3], and the study by Horvath et al [4] reports complications with the use of pergolide and cabergoline together. There is no study on the monotherapy with cabergoline or pramipexole in their references 8-11 or 13. The cited study by Dhawan et al [5] reports results on patients with previous histories of congestive heart disease and hypertension and they did trans-thoracic echocardiography only on patients with complaints. Since this study is not prospective, there is no information of the baseline ECG, telecardiography, and trans-thoracic echocardiography of the subjects. There is no information whether the patients had previous cardiac disease. Similar and more carefully designed studies are needed to address these concerns. References 1. Yamamoto M, Uesugi T, Nakayama T. Dopamine agonists and cardiac valvulopathy in Parkinson disease: A case–control study. Neurology 2006; 67: 1225–1229. 2. Murakami M, Mikami T, Kitaguchi M, et al. Effects of low-dose pergolide therapy on cardiac valves in patients with Parkinson's disease [in Japanese]. J Cardiol 2005;46:221–227. 3. Van Camp G, Flamez A, Cosyns B, Goldstein J, Perdaens C, Schoors D. Heart valvular disease in patients with Parkinson's disease treated with high-dose pergolide. Neurology 2003;61:859-861. 4. Horvath J, Fross RD, Kleiner-Fisman G, et al. Severe multivalvular heart disease: a new complication of the ergot derivative dopamine agonists. Move Disord 2004;19:656–662. 5. Dhawan V, Medcalf P, Stegie F, et al. Retrospective evaluation of cardio-pulmonary fibrotic side effects in symptomatic patients from a group of 234 Parkinson's disease patients treated with cabergoline. J Neural Transm 2005;112:661–668. Disclosure: The authors report no conflicts of interest.
Reply from authors 21 March 2007
Mitsutoshi Yamamoto, Kagawa Prefectural Central Hospital 5-4-16 Bancho, Takamatsu 760-8557, Japan, Tadahisa Uesugi; Department of Cardiology, Kagawa Prefectural Central Hospital , Takeo Nakayama Kyoto University, Graduate School of Public Health Send Correspondence to journal: Re: Reply from authors dryama{at}mail.netwave.or.jp Mitsutoshi Yamamoto, et al.	We thank Senol and Togrol for their comments. However, we disagree with them about the results of the multiple logistic analysis of our study. This analysis clearly showed that the male and female ratio and duration of illness are not risk factors. The Framingham Heart Study demonstrated that frequencies of valvular regurgitations increase with aging. [6] Although the age of our controls was higher than the those of dopamine agonist-treated group, the difference in age distribution is controlled for the present analysis. It is very difficult to follow de novo patients without treatment over a long term as correspondence. The control group consisted of patients with de novo, treatment with standard levodopa, anti-cholinergics and amantadine as described in the text. In this study, almost all patients were treated with single dopamine agonist and standard Levodopa. Regarding heart disease in patients, one patient has a sick sinus syndrome and cardiac pacemaker implantation in her heart. This is a case-control study regarding a relatively low dose of dopamine agonist. However difficult, all neurologists would benefit from the results of prospective study. Reference 6. Singh JP, Evans JC, Levy D et al. Prevalence and clinical determinations of mitral, tricuspid, and aortic regurgitation (The Framingham Hear study). Am J Cardiol 1999;83:897-902. Disclosure: The authors report no conflicts of interest.