Ergotamine-Associated Valvulopathy with Recurrent Chylous Pleural Effusion

Abstract

We report a rare case of ergotamine-associated mitral stenosis in a 55-year-old woman who presented with recurrent chylous pleural effusion. Echocardiographic, gross, and microscopic features of the mitral valve were consistent with chronic ergotamine-induced valvulopathy. We conclude that medication-induced valvulopathy should be included in the differential diagnosis of valvular heart disease. In addition, cardiac function should be monitored before and during long-term therapy with ergotamine or ergotamine-derived dopamine agonists.

A patient with ergotamine-associated mitral stenosis presented with a chylous pleural effusion. Our search of the medical literature found no other reports of ergotamine-associated development of chylothorax.

Case Report

A 55-year-old woman with a 34-year history of recurrent migraines treated with high-dose ergotamine suppositories was referred for surgical treatment of a 3rd recurrence of chylous effusion due to recurrent, right-sided chylothorax. She had developed edema one month before her evaluation at our institution. A holosystolic murmur was noted preoperatively, but electrocardiographic findings were normal.

Over the course of the following 3 weeks, her treatment included video-guided thoracoscopic drainage of the pleural effusion, wedge resection of the lower lobe of the right lung, ligation of collateral lymphatic vessels, and talc pleurodesis. Pleural fluid analysis confirmed the chylous effusion. Thoracoscopy and bronchoscopy showed no evidence of malignancy, endobronchial lesion, or any localized cause of the chylous leak. On the 2nd postoperative day, dyspnea and tachycardia developed.

Physical examination showed a heart rate of 145 beats/min and a blood pressure of 110/60 mmHg. The patient was in respiratory distress. Jugular venous pressure was elevated to 15 cm of water, and pressure readings showed prominent V waves. The carotid upstroke was brisk. Cardiac examination showed sternal lift and apical thrill. Auscultation revealed a soft S₁, an increased pulmonary component of S₂, a grade 4/6 holosystolic murmur that was loudest at the apex and radiated to the axilla, and a grade 2/6 apical diastolic rumble. Bilateral crackles were noted at mid-lung.

A complete blood count revealed normocytic anemia (11.2 g/dL), and the results of an electrolyte panel (including creatinine) were within normal limits. A chest radiograph revealed a large, right-sided pleural effusion (Fig. 1). Electrocardiography showed sinus tachycardia (heart rate, 145 beats/min) and left atrial enlargement. Transesophageal echocardiography showed moderately severe mitral regurgitation (grade 3/4) (Figs. 2 and 3) and mitral stenosis, an elevated mean gradient secondary to the mitral stenosis, and increased flow secondary to the mitral regurgitation. The total mitral valve area was 1.2 cm². The valve itself was sclerotic, as evidenced by an immobile posterior leaflet, a thickened anterior leaflet, and limited leaflet excursion. Analysis of the patient's moderate tricuspid regurgitation (peak velocity, 4.3 m/s) showed severe pulmonary hypertension (pulmonary artery pressure, 84 mmHg). The left ventricular ejection fraction was 0.75.

Fig. 1 Chest radiograph shows a large, right-sided pleural effusion and a chest tube (arrow) in situ. The cephalization of the vasculature suggests pulmonary venous hypertension.

Fig. 2 Transesophageal echocardiogram (diastolic frame) shows marked thickening of the anterior and posterior mitral valve leaflets (arrows). Poor mobility is suggested by the doming during diastole and the associated large left atrium.

LA = left atrium; LV = left ventricle; RV = right ventricle

Fig. 3 Transesophageal color-flow Doppler echocardiograms show A) turbulence of flow during left ventricular filling in diastole and B) the associated mitral regurgitation jet in systole.

LA = left atrium; LV = left ventricle; RV = right ventricle

Ultimately, mitral valve replacement was performed with a 27-mm St. Jude mechanical prosthesis (St. Jude Medical, Inc.; St. Paul, Minn). Gross examination of the excised valve showed diffuse leaflet thickening and commissural fusion, extensive chordal involvement with thickening, and shortening and fusion of chordae without calcification, vegetation, or perforation (Fig. 4). Microscopic evaluation revealed encasement in a collagenous matrix (Fig. 5). These findings were consistent with chronic, ergotamine-induced valvulopathy. The patient was advised to discontinue all ergot therapy.

Fig. 4 Photograph of the excised mitral valve shows the marked, noncalcified, irregular leaflet thickening, chordal thickening, chordal shortening, and commissural fusion that led to stenosis and regurgitation.

Fig. 5 Photomicrograph of a mitral leaflet shows a prominent fibrous pad (arrow) (H & E, orig. ×25).

Gross inspection of the tricuspid valve did not reveal a specific underlying disease process. Echocardiographic data obtained during the following 10 years indicated only stable moderate regurgitation, without evidence of stenosis.

Clinical follow-up showed significant improvement in the patient's pulmonary hypertension. The most recent echocardiogram, performed 10 years and 1 month postoperatively, revealed a pulmonary systolic pressure of 36 mmHg.

Discussion

This case has 2 interesting and unusual features: 1) valvulopathy as a rare sequela of ergotamine use, and 2) chylothorax as a sequela of severe valvular heart disease. Ergotamine-associated valvulopathy has been identified previously,¹ but the concurrent development of chylothorax during ergotamine administration has not, to the best of our knowledge, been documented.

The mechanism behind the development of chylothorax secondary to ergotamine use is uncertain. Atraumatic chylothorax in relation to underlying valvular disease was first described by Brenner and colleagues in 1978.² In the current patient, ergotamine-induced pericarditis may have incited development of the chylothorax.

Previously, Benard and associates³ documented not only ergotamine-induced fibrosis of cardiac valves but inflammation and consequent scarring of the pericardial serosal layer. Other case studies⁴ have depicted the onset of pericarditis 2 years after the initiation of ergoline-based medications. If constrictive pericarditis is the responsible entity, chylothorax develops due to increased pressure in the lymphatic system, secondary to elevated subclavian pressure.⁵ Although evidence of pericardial inflammation was not noted during mitral valve surgery in our patient, we cannot eliminate resolved pericarditis from the differential diagnosis.

Another possible cause of chylothorax in our patient was elevated right-sided cardiac pressure. Brenner and colleagues² showed a correlation between right-sided heart failure secondary to valvular disease and the resultant development of chylothorax. Our patient presented with pulmonary artery pressures of >80 mmHg. Two months after the surgical placement of a mechanical mitral valve, her pulmonary artery pressure dropped to 54 mmHg, with no recurrence of chylothorax. The postulate for the pathophysiologic mechanism is similar to that for constrictive pericarditis: elevated pressure in the subclavian vein raises pressure in the lymphatic system.

Chylothorax and ergotamine-associated valvular disease are both rare entities. Nevertheless, chylothorax development secondary to ergotamine use should be considered in patients who present with both valvulopathy and a history of taking ergotamine-derived medications. Moreover, cardiac function should be monitored before and during long-term therapy with ergotamine or ergotamine-derived dopamine agonists.