Chronic Thromboembolic Pulmonary Hypertension

4. Chronic Thromboembolic Pulmonary Hypertension AM Report Lauren Galpin, MD MA

5. Definitions “Thromboembolic obstruction of the major pulmonary arteries due to unresolved pulmonary embolism [with pulmonary hypertension]” “intraluminal thrombus organization and fibrous stenosis or complete obliteration of pulmonary arteries… The consequence is an increased pulmonary vascular resistance resulting in pulmonary hypertension and progressive right heart failure.”

6. Epidemiology • True incidence unknown • 500-2500 pts per year, 0.1-0.5% acute PE survivors • 2 prospective follow up studies of patients with acute PE: • 44% had persistent pulmonary htn +/- RV dysfunction, 5.1% developed CTEPH • 3.1% had CTEPH at 1 year, 3.8% at 2 years • Up to 2/3 of patients with CTEPH have no history of acute PE

7. Epidemiology • Risk factors: • 223 patient study: • Previous PE history • large perfusion deficit • younger age • 78 patient study: • Age>70 • systolic pulmonary artery pressure >50mmHg at time of diagnosis • Echo at 6 weeks accurately distinguished complete resolution from persistent pulmonary htn.

8. Pathophysiology • Recurrent thromboembolism • In situ pulmonary artery thrombosis • From underlying arteriopathy? • Pulmonary vascular remodeling • Genetic susceptibility? • Inflammatory mechanism?

9. Pulmonary Vascular Remodeling Low correlation between degree of obstruction and degree of pulmonary hypertension Hemodynamic progression is seen in absence of recurrent events Histopathologic evidence

10. Pulmonary Vascular Remodeling • “Two compartment pulmonary vasculature bed” – Braunwald and Moser, 1971 • Non-obstructed arteries showed changes consistent with chronic pumonary hypertension • Arteries distal to occlusion were normal

11. Associated conditions/risks • 10-20% have anticardiolipin antibody • Elevated factor VIII • Chronic inflammatory disorders • Myeloproliferative disorders • Venticulo-atrial shunt • Splenectomy • Abnormal RBCs interaction with pulmonary arteries? • Abnormal RBCs act as prothrombotic? • Abnormal platelet activation?

12. Clinical Manifestations • May be asymptomatic months – years • Physical exam findings • Accentuated pulmonic component S2 • Bruits over anterior lung fields • Dyspnea/exercise intolerance, chest pain, presyncope, syncope  late

13. Diagnosis LE Doppler V/Q scan CT angiogram Right heart catheterization Angioscopy MRA with contrast

14. Differential Diagnosis • Of segmental perfusion deficits on V/Q scan • Pulmonary veno-occlusive disease • Pulmonary capillary hemangiomatosis • Fibrosingmediastinitis • Pulmonary vasculitis • Sarcomas of pulmonary arteries

15. Prognosis • Without treatment • Pulmonary Arterial Pressure >40mmHg: 30% 5y survival • PAP>50mmHg: 10% 5y survival • In another study, >30mmHg: 10% survival

16. Prognosis • With Pulmonary Endarterectomy (+lifelong anticoagulation and IVC filter) • 5-24% perioperative mortality overall, <5% at experienced centers • In experienced centers, well-selected patients • Near normalization of hemodynamics • Substantial improvement in clinical symptoms

18. “… there is no degree of embolic occlusion within the pulmonary vascular tree that is inaccessible and no degree of right ventricular impairment or any level of pulmonary vascular resistance that is inoperable.” -- Jamieson et al, UCSD

19. Other treatment options • Medicine • Epoprostenol – prostacyclin infusion • Sildenafil – phosphodiesterase-5 inhibitor • Bosentan – endothelin receptor antagonist • Balloon angioplasty • Has been done successfully • Still considered experimental • Lung transplant • For people with advanced small vessel disease without comorbidities that preclude surgery

20. Take Home Points Review of systems and careful physical exam are important! Chronic thromboembolic disease is uncommon, but not rare Chronic thromboembolism is a treatable cause of pulmonary hypertension V/Q scan still an important diagnostic tool “No 21 year-old should ever be short of breath.”