Experimental models to resemble pulmonary arterial hypertension
A 22-year-old female with positive antiphospholipid antibodies was referred for pulmonary hypertension (PH) evaluation. She had history of deep venous thrombosis associated with ankle fracture when she was a teenager. She was on chronic warfarin therapy with target INR of 2.5-4.0. Patient complaint of progressive worsening of shortness of breath over a year and worsening dyspnea on exertion. Ventilation perfusion scan done as part of PH work up revealed a high probability scan. This patient underwent right heart catheterization in July 2009 and her hemodynamics were as follows: RA mean 4 mm Hg, PA pressure 96/36 mm Hg (mean 57), PCW 17 mm Hg and step up consistent with left to right shunt. Subsequent cardiac magnetic resolution imaging done to evaluate her “step up” showed no atrial septal defect, ventricular septal defect or anomalous pulmonary venous return. She was started on sildenafil. The patient underwent pulmonary arteriography on August 2010 that revealed “pouch web in the LUL, narrowing of the left descending PA, vessel attenuation in LLL, with narrowing of the right intra-lobar artery. These results were suggestive of lining disease of the descending pulmonary artery, concerning for pulmonary artery sarcoma. She was diagnosed with chronic thromboembolic pulmonary hypertension (CTEPH). Due to the poor prognosis and short life expectancy of this potential diagnosis, she underwent bilateral pulmonary thromboendarterectomy (PTE) surgery in March 2011 with removal of multiple emboli. No evidence of tumor was noted. The patient experienced significant improvement in her symptoms including resolution of her shortness of breath. The post-operative hemodynamics were: PA 50/22 mm Hg (mean 34) and CVP 15 mm Hg. Although this patient had persistent post-thromboendarterectomy PH, the postoperative course was uncomplicated. The patient remained on warfarin with higher INR goals for positive antiphospholipid antibodies but also due to the presence of small distal clots that were noted during PTE.
Chronic thromboembolic disease is an under diagnosed and under treated disease. There are about 600,000 cases per year of acute pulmonary embolism (PE) in United States of America. Estimated incidence of chronic thromboembolic pulmonary hypertension after acute PE is about 0.5% to over 4%. Based on a registry (2007 to 2009) including 679 patients from 16 European countries and Canada, history of acute PE was reported in nearly 75% of cases. A multidisciplinary team evaluation to determine candidacy for endarterectomy is important. As a potentially reversible cause of pulmonary hypertension, the recommended treatment for CTEPH is PTE. Appropriate patients with proximal clot burden who undergo this surgery have a good prognosis. In experienced centers, the mortality from this surgery is less than 4% and most patient report improvement of symptoms, resolution of PH, and this surgery in many cases obviates the need for PH therapy. CTEPH should always be included in the differential in a patient undergoing PH evaluation.
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