doi: 10.2169/internalmedicine.1381-22
Intern Med Advance Publication
http://internmed.jp【 CASE REPORT 】

Multimodal Imaging of Constrictive Pericarditis Induced byLong-term Pergolide Treatment for Parkinson’s Disease
Hiroyuki Aoyagi 1, Shingo Tsujinaga 1,2, Yuki Takahashi 1, Seiichiro Naito 1, Takuma Sato 1,Takuya Otsuka 3, Yoji Tamaki 1, Ko Motoi 1, Suguru Ishizaka 1, Yasuyuki Chiba 1,Kiwamu Kamiya 1, Hiroyuki Iwano 1,4, Toshiyuki Nagai 1, Satoru Wakasa 5 and Toshihisa Anzai 1

Abstract:
We herein report the first case of constrictive pericarditis (CP) induced by long-term pergolide treatment
for Parkinson’s disease that was assessed using multimodal imaging in a 72-year-old patient with leg edema
and dyspnea. The patient was correctly diagnosed with CP using multimodal imaging and successfully treatedwith pericardiectomy. The treatment history of Parkinson’s disease and pathological findings of the removed
pericardium suggested that long-term pergolide was the cause of CP. Properly recognizing pergolide as thecause of CP and accurately diagnosing CP using multimodal imaging may contribute to the early detection
and treatment of pergolide-induced CP.
Key words: Constrictive pericarditis, Multimodal imaging, Parkinson’s disease, Pergolide(Intern Med Advance Publication)(DOI: 10.2169/internalmedicine.1381-22)

oxygen saturation was 96% in room air. Paradoxical pulse,
jugular venous distention, Kussmaul’s sign, and leg edema
were observed, while pericardial rub was not.
Laboratory tests revealed increased levels of serum Nterminal pro-B-type natriuretic peptide (3,426 pg/mL), creatinine (2.04 mg/dL), aspartate aminotransferase (36 U/L),
and alkaline phosphatase (371 U/L). The results of screening
blood tests for viral, bacterial, or fungal infections, including
tuberculosis; connective tissue diseases; and malignant tumors were negative.
Chest radiography revealed mild cardiomegaly (cardiothoracic ratio, 53%) and bilateral pleural effusion with no pericardial calcification. Electrocardiography revealed sinus
rhythm and low voltage with no significant ST-segmentchanges. Echocardiography demonstrated a normal left ventricular (LV) end-diastolic dimension (46 mm), LV ejection
fraction (70%), and no LV hypertrophy. No significant valvular disease was present, although thickening of all valve
leaflets was observed. Pericardial thickening, septal bounce

Introduction
Case Report

A 72-year-old man with a history of Parkinson’s disease
was admitted to our department with diuretic-resistant(azosemide 40 mg/day) leg edema and dyspnea lasting for 2months. Parkinson’s disease had been diagnosed 40 years
previously, and he had been treated with anti-parkinsonian
agents, such as pergolide mesylate (500 μg/day), levodopa(300 mg/day), benserazide hydrochloride (75 mg/day), andselegiline hydrochloride (7.5 mg/day), for approximately 20years. He had no history of chest radiation or open-heart
surgery.
A physical examination on admission revealed that hewas 164 cm tall and weighed 77 kg. His body mass index
was 28.6 kg/m2. He was apyrexial. His pulse rate was 85/
min, blood pressure was 111/68 mmHg, and transcutaneous
１

Department of Cardiovascular Medicine, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Japan, ２ Department ofCardiology, Hokkaido Ohno Memorial Hospital, Japan, ３ Department of Surgical Pathology, Hokkaido University Hospital, Japan, ４ Departmentof Cardiovascular Medicine, Teine Keijinkai Hospital, Japan and ５ Department of Cardiovascular and Thoracic Surgery, Faculty of Medicine andGraduate School of Medicine, Hokkaido University, Japan
Received: November 30, 2022; Accepted: February 12, 2023; Advance Publication by J-STAGE: March 31, 2023
Correspondence to Dr. Shingo Tsujinaga, shingo-t.0207@hotmail.co.jp

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DOI: 10.2169/internalmedicine.1381-22

Figure 1. (A, B) Apical four-chamber echocardiographic view demonstrating the leftward ventricular septal shift during inspiration (yellow arrows). (C) Pulsed-wave Doppler recording at the level ofthe open mitral leaflet tips in the apical view showing an inspiratory decrease and expiratory increasein early mitral inflow velocity. Exp: expiration, Insp: inspiration

Figure 2. (A) CT scan of the heart demonstrating the significantly thickened pericardium (5 mm)(yellow arrows) with no pericardial calcification. (B) FDG positron emission tomography revealing noabnormal FDG uptake in the pericardium (yellow arrows).

with the inspiratory motion of interventricular septum(Fig. 1A, B, Supplementary Video 1), respiration-relatedchanges in mitral E velocity (47%) (Fig. 1C), higher mitralthan lateral annular e’ velocities (septal e’ 13.5 cm/s vs. lateral e’ 10.5 cm/s), and dilation of the inferior vena cava (26mm) were observed. These echocardiographic findings wereconsidered suggestive of constrictive pericarditis (CP).
Computed tomography (CT) of the heart revealed a significantly thickened pericardium (5 mm) with no pericardial

calcification (Fig. 2A). 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) showed no abnormal FDG
uptake in the pericardium (Fig. 2B). Cardiac magnetic resonance (CMR) imaging also indicated a thickened pericardium (Fig. 3A, Supplementary Video 2), and twodimensional CMR tissue tracking demonstrated reduced
peak strain values at the LV basal anterolateral and inferior
walls, indicating pericardial adhesions (Fig. 3B).
The patient underwent cardiac catheterization. Coronary2

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Figure 3. (A) CMR imaging demonstrating the thickened pericardium (yellow arrows). (B) Twodimensional CMR tissue tracking revealed the reduction in the peak strain values at the LV basal
anterolateral (purple line) and inferior (light blue line) walls.

Figure 4. (A) Simultaneous pressure tracing of the left (red line) and right (yellow line) ventricles
demonstrating elevated and similar end-diastolic pressures and dip-and-plateau patterns. (B) Discordant changes in the left (red line) and right (yellow line) ventricular systolic pressure during respiration. LV: left ventricle, RV: right ventricle, Exp: expiration, Insp: inspiration

angiography revealed no stenotic lesions. Right atrium (RA)pressure tracing revealed an elevated mean RA pressure (23mmHg) with a prominent Y descent. The pulmonary arterypressure was 38/25 mmHg, and the mean pulmonary capillary wedge pressure (28 mmHg) was elevated, reflecting
strong congestion. Simultaneous pressure tracing of the left
and right ventricles revealed elevated, similar end-diastolicpressures and dip-and-plateau patterns (Fig. 4A), as well as
ventricular interdependence (Fig. 4B). The systolic area index, which is the ratio of the right ventricular to the LV systolic pressure-time area on inspiration versus expiration, was
1.3 (>1.1). Based on these findings and the course of treatment for Parkinson’s disease, the patient was diagnosed withCP induced by long-term pergolide treatment.
Pergolide was discontinued, and the patient was administered intravenous diuretics; however, his symptoms demonstrated little improvement. Consequently, he became a candidate for surgery, and pericardiectomy was performed. Thepericardium was removed almost completely. The histopa-

thological findings of the removed pericardium revealed nomalignancy, infection, or tuberculous granuloma. However,thickened fibrotic pericardial tissue and focal inflammation(Fig. 5A, B and C) were found, which was consistent withCP induced by long-term pergolide treatment causing fibrosis reaction.
Postoperatively, the patient’s hemodynamics improved
substantially. The mean RA pressure decreased (5 mmHg)
with no prominent Y descent. The pulmonary artery pressure(28/8 mmHg) and mean pulmonary capillary wedge pressure(8 mmHg) decreased. Simultaneous pressure tracing of theleft and right ventricles revealed no dip-and-plateau patternor ventricular interdependence. The systolic area index decreased to 1.0. Serum levels of N-terminal pro-B-type natriuretic peptide (484 pg/mL) and creatinine (1.48 mg/dL) improved. He now has no leg edema or dyspnea with only alow dose of diuretics (furosemide 20 mg/day) administeredin the 1.5 years after surgery. Control of Parkinson’s diseasehas been achieved by increasing the dose of selegiline hy3

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DOI: 10.2169/internalmedicine.1381-22Figure 5. Histopathological specimens of the removed pericardium revealing thickened fibrotic
pericardial tissue (A: pathological macro finding, B: Hematoxylin and Eosin staining, ×400, C: Elastica-Masson stain, ×100).

drochloride (from 7.5 to 10 mg/day).

by long-term pergolide treatment for Parkinson’s disease,
there have been no previous reports of a multimodality
evaluation, so this fact was a new finding.
CP often mimics other forms of heart failure and requires
a specialized work-up; therefore, the diagnosis may be difficult. Meticulous echocardiography allows for the initial detection of dissociation of the intrathoracic and intracardiac
pressures and enhanced ventricular interaction, changes thatare suggestive of CP. Cardiac CT facilitates the assessmentof pericardial thickening and calcification, although neither
finding is necessary for a diagnosis. CMR tissue tracking offers additional information, including allowing the identification of pericardial-myocardial adhesions. Cross-sectional imaging and hemodynamic catheterization are necessary toconfirm the CP diagnosis.
There are various subtypes of CP. Although rare, there arecases of effusive CP and mixed CP being complicated bymyocardial disease, requiring special anti-inflammatory therapy or disease-specific treatment. CMR and PET are usefulin differentiating such cases. The use of multimodal imaging
has helped to differentiate the subtypes of CP, identify patients who would benefit from medical therapy, and guidepre-operative planning. Thus, the diagnosis of CP requires
multimodal imaging (5), as in the present case. It is important to make accurate diagnoses and treatment plans using
all imaging modalities available. Complete surgical pericardiectomy remains the only definitive treatment for CP.
This case demonstrates the importance of performing
multimodal imaging of CP induced by long-term pergolide
treatment for Parkinson’s disease. Both the recognition ofDiscussion
We herein report the first case of CP induced by longterm pergolide treatment for Parkinson’s disease, which wasassessed using multimodal imaging.
CP is a chronic inflammatory process often characterized
by chronic scarring, fibrosis, and calcification of the pericardium associated with diastolic dysfunction, eventually leading to heart failure. The most frequent causes of CP are idiopathy, post cardiac surgery and previous radiation therapy
to the mediastinum in the Western world (1). Although rare,
an association between an ergoline-based dopamine receptor
agonist, such as pergolide, and CP has been recognized (2, 3). Pergolide may induce fibrotic changes in thelung, pleura, retroperitoneum, and cardiac valve leaflets,
which are potentially mediated by the 5-HT2B agonist activity on the serotonergic receptors (4). In the present case,thickening of all of the valve leaflets and pericardium wereobserved. Although the mechanism underlying CP induced
by long-term pergolide with the absence of significant extracardiac lesions remains unclear, pergolide is associatedwith idiosyncratic fibrotic reactions that may lead to CP, asindicated by the pathological findings of the pericardium inthis case.
The findings obtained in our imaging study were notmarkedly different from those of previous studies on idiopathic CP, postoperative CP, and radiation-induced CP. Although no characteristic findings were found for CP induced4Intern Med Advance Publication

DOI: 10.2169/internalmedicine.1381-22

diectomy. Circulation 100: 1380-1386, 1999.
2. Balachandran KP, Stewart D, Berg GA, Oldroyd KG. Chronic
pericardial constriction linked to the antiparkinsonian dopamineagonist pergolide. Postgrad Med J 78: 49-50, 2002.
3. Townsend M, Maclver DH. Constrictive pericarditis and pleuropulmonary fibrosis secondary to cabergoline treatment for Parkinson’sdisease. Heart 90: e47, 2004.
4. Antonini A, Poewe W. Fibrotic heart-valve reactions to dopamineagonist treatment in Parkinson’s disease. Lancet Neurol 6: 826829, 2007.
5. Welch TD. Constrictive pericarditis: diagnosis, management andclinical outcomes. Heart 104: 725-731, 2018.

pergolide-caused CP and its accurate diagnosis using multimodal imaging will contribute to the early detection andtreatment of CP induced by pergolide.
The authors state that they have no Conflict of Interest (COI).
Funding/Grants
None.

References

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