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Clinicopathologic Correlation of a Calcium Channel Responsive Patient with Idiopathic Pulmonary Arterial Hypertension (IPAH

R. K. Cooke

A. G. Duarte

M. A. Eltorky

N. Boroumand

D. F. Cowan

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Conference: 2008 International PHA Conference and Scientific Sessions

Release Date: 06.20.2008

Presentation Type: Abstracts

Cooke R.K., Duarte A.G., Eltorky M.A., Boroumand N., Cowan D.F.

University of Texas Medical Branch - Galveston, TX, USA 

BACKGROUND: Idiopathic pulmonary arterial hypertension is a progressive, irreversible condition characterized by pulmonary vascular resistance and right ventricular failure. Management of IPAH involves right heart catheterization and vasoreactivity testing to identify patients with improvements in hemodynamics. While only 5-15 % of patients respond to acute vasodilator testing, this subset of patients may be treated with calcium channel blockers, which have been reported to portend an improved prognosis. We describe the clinical and pathologic findings of a patient with IPAH initially responsive to calcium channel blockers and treated with combination therapy for 12 years.

METHODS:  Retrospective case report correlating 15 years of clinical history with postmortem anatomic and pathologic findings.

RESULTS: This patient developed progressive dyspnea and fatigue at age 47 and was diagnosed with IPAH by right heart catheterization. Vasoreactive testing performed using nitric oxide (20 ppm) followed by nifedipine revealed a 25% decrease in mean pulmonary artery pressure from 65 to 50 mm Hg and improvement in cardiac output from 2.8 to 3.8 L/min.  For 5 ½ years, symptoms and exercise tolerance remained stable. Decreased functional class led to the addition of bosentan followed by sildenafil. When right heart catheterization revealed worsening hemodynamics, inhaled iloprost was added. After 8 months of iloprost, her clinical state had not improved and intravenous treprostinil was initiated with remarkable improvement in symptoms and functional class. Twelve years after initial diagnosis, she developed a viral pericarditis requiring drainage, mechanical ventilation and inotrope support. After 10 days of treatment, care was withdrawn and the patient died.  A postmortem examination of the heart and lungs was performed. 

Autopsy revealed cardiomegaly, with dilatation and hypertrophy of the right ventricle.  The trabeculae carni of the right heart were markedly thickened, while the left ventricular wall was normal in thickness.  The main pulmonary trunk exhibited aneurysmal dilatation, measuring 15 cm in greatest circumference, with eight intimal tears of varying thickness and degrees of healing.  The largest intimal disruption began adjacent to the pulmonic valve and measured more than 9 cm in greatest dimension.  The pulmonary arteries exhibited widespread atheromatous plaques.

Sections of left and right ventricles and each lobe of the lungs were obtained for microscopic examination. The left ventricle was histologically normal, while the right was markedly hypertrophied.  Myocyte nuclei within the right heart were enlarged.  The pulmonary trunk was thickened and multiple acute intimal tears were observed. Medial disruption with associated hemorrhage and localized medial dissection were also detected in some of the intimal tears.  Movat pentachrome staining demonstrated cellular proliferation of the intima and marked thickening of the media of pulmonary arterioles, occurring in a background of pulmonary congestion.  Concentric laminar intimal fibrosis and arteriolar muscularization of pulmonary arterioles was noted, with near complete luminal obstruction.  Fibrinoid necrosis and arteritis were identified in pulmonary arterioles, with a marked inflammatory infiltrate permeating the media.  Pulmonary arterial plexiform lesions were also observed.

COMMENTS AND CONCLUSIONS: Intimal injury and repair of the large and medium sized pulmonary arteries was observed in a patient living with IPAH.  Intimal tears of the main pulmonary trunk have not been previously reported in patients surviving with PAH.