Multicenter Study on Fibrotic Valvular Heart Disease in Patients With Parkinson's Disease Treated With Dopamine Agonists
Multicenter Study on Fibrotic Valvular Heart Disease in Patients With Parkinson's Disease Treated With Dopamine Agonists
Fibrotic valvular heart diseases are known as rare complications of long-time therapy of
 Parkinson's disease with ergot-derivatives including some ergot-dopamine agonists. The aim of
 this study is to assess the incidence of valvular heart disease, which may be an ergot-drug
 agonists side-effect or an overall complication of all dopamine agonists. Incidence,
 prevalence and addiction of dose or intake duration are not known so far. The reversibility
 of the changes is unknown too. To answer these questions the present study is designed as a
 cross sectional study followed by a 2 year follow-up prospective cohort study.
Rare incidence of pleuropulmonary and retroperitoneal fibrosis are known complications during
 the long-time therapy of Parkinson's disease (PD) with ergot-drug derivatives including some
 ergot dopamine agonists. Particularly the appearance of fibrotic valvular heart disease of
 Parkinson patients under Pergolide therapy caused an intense discussion about the safety of
 dopamine agonists at all. Single case reports of similar heart valve changes under the
 therapy of Bromocriptin and probably Cabergoline pointed to an effect of the whole substance
 class of the ergot-dopamine agonists.

 Cross-Sectional Study (part I):

 Within this study an initial cross-sectional analysis of the prevalence of fibrotic heart
 valvular disease will be done. Patients with Parkinson's disease with different exposition
 status will be recruited. An transthoracal echocardiographic examination (TTE) of the heart
 will be performed.

 Exposition status:

 -  patients with ergot-derived dopamine agonists

 -  patients with non-ergot-derived dopamine agonists

 -  After the TTE-report the study population is divided in affected (= pathological
 TTE-report: fibrotic valvular heart diseases) and healthy persons (= non-pathological
 TTE-report: no fibrotic valvular heart diseases). The therapy with dopamine agonist will
 be stopped in patients with a pathological TTE-report. Instead these patients will be
 treated with an equivalent dose of L-Dopa with or without COMT-inhibitors. The existing
 therapy regime will remain in patients without pathological findings.

 Longitudinal Section (part II and III):

 The cross-sectional study (part I) is followed by a two year follow-up study.

 Cohort I:

 -  patients with pathological TTE-report: fibrotic valvular heart disease

 -  patients without pathological TTE-report: no fibrotic valvular heart disease

 Part II: Within cohort I the reversibility of fibrotic valvular heart disease will be
 analysed with regard to the previously taken cumulative dose of dopamine agonists.

 Part III: Within cohort II there will be a prospective analysis of the (cumulative) incidence
 of fibrotic valvular heart disease in PD patients with different exposition status. If
 fibrotic valvular heart disease occurs, a patient will be changed from cohort II to cohort I.

 Primary Outcome:

 Cross-sectional study (part I):

 -  What is the prevalence of fibrotic valvular heart disease in PD patients under therapy
 with ergot-derived dopamine agonists and non-ergot-derived dopamine agonists?

 -  Is there an influence to the cumulative dose of dopamine agonists?

 Longitudinal study (prospective cohort study):

 -  (Part II) Is fibrotic valvular heart disease under therapy of ergot-derived dopamine
 agonists and non-ergot-derived dopamine agonists reversible?

 -  (Part III) What is the (cumulative) incidence of fibrotic valvular heart disease under
 the therapy of ergot-derived dopamine agonists and non-ergot-derived dopamine agonists?
Inclusion Criteria:

 -  Age > 18 years

 -  Diagnosis of Morbus Parkinson

 -  Written informed consent

 Exclusion Criteria:

 -  Patients with a history of carcinoid syndrome

 -  Patients with a history of post-inflammatory (rheumatic), degenerative (calcified) or
 ischaemic coronary heart or valvular heart disease

 -  Previous medication with ergot-derived drugs (eg. Methysergide, Ergotamine) except
 dopamine receptor agonists or anorectic drugs (eg. Fenfluramine, Dexfenfluramine)