Advanced Pulmonary Arteriopathy in a Patient With Exercise-Induced Pulmonary Arterial Hypertensio

Abstract

INTRODUCTION: Exercise-induced pulmonary arterial hypertension (EiPAH) has been previously described as elevation in mean pulmonary arterial pressure of more than or equal to 30 mmHg on exercise as measured during right heart catheterization. This definition of pulmonary hypertension on exercise is no longer supported in recent guidelines. The clinical and pathologic significance of EiPAH has been poorly elucidated, to date. Pathologic material in these patients is rarely available. Here, we describe a case of exercise-induced pulmonary hypertension with advanced pulmonary arteriopathy on lung biopsy. CASE PRESENTATION: The patient is a 56 year-old male who presented with chronic dyspnea on exertion. Seven years prior, he was diagnosed with Type I sarcoidosis. Because of marked exertional dyspnea, he underwent Level III cardiopulmonary exercise testing. The patient was found to have a pulmonary vascular limit to exercise. Resting right heart catheterization showed a normal mean pulmonary arterial pressure, which increased to 43mmHg during exercise. Despite empiric trials of tadalafil, ambrisentan, and inhaled treprostinil, the patient remained symptom limited. Repeat pulmonary function testing demonstrated a markedly reduced diffusing capacity but only mild obstruction. Chest CT scan showed mild ground glass opacities bilaterally. Possible diagnoses of pulmonary veno-occlusive disease or interstitial lung disease were entertained. Video assisted thoracoscopic lung biopsy was performed. The lung biopsy revealed Grade 3 pulmonary arteriopathy, evidence of microthrombi, scattered non-caseating granulomas consistent with sarcoid, and mild airway inflammation. DISCUSSION: Pulmonary arterial hypertension is a panvasculopathy mainly affecting small pulmonary arteries. It is characterized by a variety of arterial abnormalities, including intimal hyperplasia, medial hypertrophy, adventitial proliferation, thrombosis in situ, varying degrees of inflammation, and plexiform arteriopathy. The pathologic features of pulmonary hypertension are the same regardless of the etiology. Other characteristics include constrictive and complex arterial lesions involving to varying degrees the pre- and intra-acinar pulmonary arteries. Medial smooth muscle cell hypertrophy is a characteristic pathological feature of pulmonary hypertension that involves muscularized arteries (ranging between 70 and 500 @m in diameter), and precapillary vessels (below 70 @m in diameter). Although it is difficult to relate the morphologic identification of medial remodeling to severity of pulmonary arterial hypertension and the pulmonary artery pressures, these pathologic features, particularly medial thickening, is important in the pathogenesis of this disease. This patient had pulmonary plexogenic arteriopathy which was described in the histopathologic sections as recanalized pulmonary arteries. In the revised pathologic classification of vasculopathies of pulmonary hypertension, pulmonary arteriopathy Grades 2 and 3 correspond to pulmonary arteriopathy with medial hypertrophy and concentric laminar intimal thickening.4 CONCLUSIONS: This case demonstrates the marked pulmonary vascular remodeling seen in a patient with EiPAH, suggesting that this physiologic abnormality may, in fact, be quite significant.