Valvular heart disease in patients exposed to pergolide: insights from the clinical presentation.

PURPOSE: The aim of this study was to determine whether the presence of symptoms would aid in the detection of valvular heart disease (VHD) in those exposed to pergolide. METHODS: Utilizing a prospective, cross-sectional study design, patients with an exposure to pergolide were asked regarding the presence or absence of chest pain, shortness of breath or lower extremity edema through a questionnaire. Echocardiograms were obtained on the same day as the questionnaire and were blinded to all staff involved in the study. The sensitivity, specificity, positive and negative predictive value of the reported symptoms towards the outcome moderate or severe valvular regurgitation were obtained. Using the area under the receiver-operating characteristic curve, we also ascertained whether a relationship existed between symptoms, pergolide dose and presence of VHD. To understand the associations between symptoms and echocardiographic covariates, a logistic regression analysis was performed adjusted for age and gender. RESULTS: The sensitivity, specificity, positive and negative predictive value of symptom presentation and total dose was sufficiently low that it did not aid in the determination whether significant valvular regurgitation was present. Multivariable analysis noted a significant association with indexed left atrial volume (p = 0.011), estimated pulmonary artery pressure (p = 0.047) and shortness of breath. CONCLUSIONS: The presence or absence of symptoms does not help guide whether valvular regurgitation is present or absent in individuals exposed to pergolide. Therefore, echocardiography is needed to confirm or refute pergolide-associated VHD.

Clinical features in early Parkinson disease and survival.

OBJECTIVE: To examine the association between demographic and clinical features in early Parkinson disease (PD) and length of survival in a multiethnic population. DESIGN: Clinical features within 2 years of diagnosis were determined for an inception cohort established during 1994-1995. Vital status was determined through December 31, 2005. Predictor variables included age at diagnosis, sex, race/ethnicity, as well as clinical subtype (modified tremor dominant, postural instability gait difficulty), symmetry, cognitive impairment, depression, dysphagia, and hallucinations. Cox proportional hazards regression analysis was used to identify factors associated with shorter survival. SETTING: Kaiser Permanente Medical Care Program, northern California. PATIENTS: Five hundred seventy-three men and women with newly diagnosed PD. RESULTS: Three hundred fifty-two participants in the PD cohort (61.4%) had died in the follow-up period. Older age at diagnosis (hazard ratio [HR], 1.1; 95% confidence interval [CI], 1.09-1.12), modified postural instability gait difficulty subtype (HR, 1.8; 95% CI, 1.3-2.7), symmetry of motor signs (HR, 2.0; 95% CI, 1.1-3.7), mild (HR, 1.7; 95% CI, 1.3-2.2) and severe (HR, 2.7; 95% CI, 1.9-3.9) cognitive impairment, dysphagia (HR, 1.4; 95% CI, 1.1-1.9), and hallucinations (HR, 2.1; 95% CI, 1.3-3.2) were associated with increased all-cause mortality, after adjusting for age, sex, and race/ethnicity. None of the other factors altered mortality risk. In an empirical predictive analysis, most previous significant predictors remained associated with shorter survival. CONCLUSIONS: Both motor and nonmotor features in early PD predict increased mortality risk, particularly postural instability gait difficulty, cognitive impairment, and hallucinations. These predictors may be useful in clinical practice and when designing clinical trials.

Severe multivalvular heart disease: a new complication of the ergot derivative dopamine agonists.

We report on 4 new cases of valvular heart disease in Parkinson's disease patients treated with the ergot derivative dopamine agonists pergolide and cabergoline. Noninflammatory fibrotic degeneration of cardiac valves has been reported to occur in patients with carcinoid syndrome and to occasionally complicate therapies with the anti-migraine ergot alkaloid ergotamine and methysergide and with the appetite suppressants fenfluramine and dexfenfluramine. In these cases, the pathogenesis is suspected to involve serotonin-mediated abnormal fibrogenesis by means of the 5-HT2B receptors, which are expressed in the fibroblasts of heart valves. Based on strikingly similar echocardiographic and histopathological features, we strongly suspect that ergot-derived dopamine agonists may cause a valvular heart disease nearly identical to that seen in those conditions. These cases add to a rapidly growing and worrying list of similar published reports, suggesting that we may well be facing a novel, yet unrecognized, complication of this class of agents, which are widely used not only in Parkinson's disease but also in restless legs syndrome and various common endocrine dysfunctions. Therefore, until more is known about the true prevalence of this side effect, we propose that an assessment of cardiac function be performed before and in the course of a long-term therapy with ergot derivative dopamine agonists.

Incidence of Parkinson's disease: variation by age, gender, and race/ethnicity.

The goal of this study was to estimate the incidence of Parkinson's disease by age, gender, and ethnicity. Newly diagnosed Parkinson's disease cases in 1994-1995 were identified among members of the Kaiser Permanente Medical Care Program of Northern California, a large health maintenance organization. Each case met modified standardized criteria/Hughes diagnostic criteria as applied by a movement disorder specialist. Incidence rates per 100,000 person-years were calculated using the Kaiser Permanente membership information as the denominator and adjusted for age and/or gender using the direct method of standardization. A total of 588 newly diagnosed (incident) cases of Parkinson's disease were identified, which gave an overall annualized age- and gender-adjusted incidence rate of 13.4 per 100,000 (95% confidence interval (CI): 11.4, 15.5). The incidence rapidly increased over the age of 60 years, with only 4% of the cases being under the age of 50 years. The rate for men (19.0 per 100,000, 95% CI: 16.1, 21.8) was 91% higher than that for women (9.9 per 100,000, 95% CI: 7.6, 12.2). The age- and gender-adjusted rate per 100,000 was highest among Hispanics (16.6, 95% CI: 12.0, 21.3), followed by non-Hispanic Whites (13.6, 95% CI: 11.5, 15.7), Asians (11.3, 95% CI: 7.2, 15.3), and Blacks (10.2, 95% CI: 6.4, 14.0). These data suggest that the incidence of Parkinson's disease varies by race/ethnicity.