Pulmonary Hypertension RYAN O’GOWAN, MBA, PA-C FAPACVS FCCM Disclosures I have no financial relationships with any drug or device manufacturers to disclose. Objectives At the conclusion of this lecture the participant should be able to: Define Pulmonary Arterial Hypertension (PAH) and discuss its clinical relevance, including various modes of evaluation and diagnosis. Discuss and define the various subgroups of PAH according to the World Health Organization (WHO) classification. Discuss available treatment strategies and their mechanisms for selected WHO subgroups. Definition Pulmonary Arterial Hypertension: “is a syndrome resulting from restricted flow through the pulmonary arterial circulation resulting in increased pulmonary vascular resistance and ultimately in right heart failure. ” ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension Clinical Diagnosis Clinical Definition of pulmonary hypertension: Mean PA pressure>25 mm Hg PCWP <15mm Hg Cardiac output may be normal or reduced Galie N, et al. Eur Heart J. 2009;30(20):2493-2537. Normal Pulmonary Physiology Pathophysiology Pathophysiology Causes of Pulmonary Hypertension ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension Diseases Associated with Pulmonary Hypertension ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension Presentation Shortness of breath with exertion Dry cough Lower extremity edema Weakness & malaise No Physical Exam findings other than those associated with Right Heart failure can reliably diagnose pulmonary hypertension American Thoracic Society source document on Pulmonary Hypertension Epidemiology of Pulmonary Hypertension Average age at presentation- 36 years Prevalence women>men by 2:1 Three year survival after diagnosis ~50% Incidence: 10-15 people per million of population Number of U.S. patients: 10,000-20,000. Patients who survive go on to be candidates for total lung transplant. American Thoracic Society source document on Pulmonary Hypertension Evaluation and Diagnosis •S W A N - G A N Z C A T H E T E R I Z A T I O N •S E L E C T I V E R I G H T H E A R T CATHETERIZATION •E C H O C A R D I O G R A P H Y •C T S C A N N I N G F O R P U L M O N A R Y E M B O L I Swan Ganz Catheterization Clinical Procedures in Anesthesia and Intensive Care, p 416. JB Lippincott, 1994 Selective Right Heart Catheterization Uses the Swan to gather: right atrial pressure (RAP) right ventricular pressure (RVP) pulmonary arterial pressure (PAP) pulmonary capillary wedge pressure (PCWP) systemic arterial pressure (BP) and heart rate cardiac output (CO) pulmonary arterial vasoreactivity pulmonary arterial (PA) ("mixed venous") saturation superior vena cava (SVC) saturation inferior vena cava (IVC) saturation right atrial (RA) saturation right ventricular (RV) saturation Echocardiography Rev Esp Cardiol. 2010;63:583-96 - Vol. 63 Num.05 CT Chest- PE Protocol WHO Classification •C L A S S I IDIOPATHIC PAH (IPAH) •C L A S S I I PAH WITH LEFT HEART DISEASE •C L A S S I I I PAH SECONDARY TO HYPOXIA •C L A S S I V CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION (CTEPH) •C L A S S V MISCELLANEOUS Class I Pulmonary Hypertension Idiopathic (IPAH) Heritable (HPAH) Bone morphogenetic protein receptor type 2 (BMPR2) Activin receptor-like kinase 1 gene (ALK1), endoglin Drug- and toxin-induced Cocaine,Amphetamines Fenfluramine (Taken off the market) Associated with (APAH): Connective tissue diseases (SLE) Human immunodeficiency virus (HIV) infection Portal hypertension Congenital heart disease (CHD) Schistosomiasis Chronic hemolytic anemia Persistent pulmonary hypertension of the newborn (PPHN) J Am Coll Cardiol. 2009;54:S43–54. Class II Pulmonary Hypertension PAH with Left Heart Disease: Mitral Valve Disease (Stenosis/Regurgitation) Aortic Valve Disease (Stenosis/Regurgitation) Systolic Dysfunction Diastolic Dysfunction J Am Coll Cardiol. 2009;54:S43–54. Class III Pulmonary Hypertension PAH secondary to hypoxia: COPD Interstitial Lung Disease (ILD) Pulmonary Diseases with Mixed Restrictive and Obstructive Patterns Obstructive Sleep Apnea (OSA) Alveolar Hypoventilation Disorders Chronic Exposure to High Altitudes J Am Coll Cardiol. 2009;54:S43–54. Class IV Pulmonary Hypertension Chronic thromboembolic pulmonary hypertension (CTEPH) Patients may have presentations consistent with hypercoagulable states. Common heritable sources of thrombosis include: Factor V Leiden Prothrombin G 20101A Mutation Proteins C & S Deficiency Lupus Procoagulant J Am Coll Cardiol. 2009;54:S43–54. Class V Pulmonary Hypertension Miscellaneous Hematological disorders: myeloproliferative disorders, splenectomy Systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders Others: tumor obstruction, fibrosing mediastinitis, chronic renal failure on dialysis J Am Coll Cardiol. 2009;54:S43–54. Treatment Strategies GROUPS 1-5 PHARMACOLOGIC THERAPIES PULMONARY ENDARTERECTOMY FOR GROUP 4 Updated Evidence-Based Treatment Algorithm in Pulmonary Arterial Hypertension J Am Coll Cardiol. 2009;54(1s1):S78-S84. . Copyright © The American College of Cardiology. All rights reserved. Used with permission. Initial Pharmacologic Treatment Mainstay of treatment: Group 1-4 Calcium Channel Blockers with Vasoreactivity Treatment (Class B- for responders) Amlodipine Diltiazem Nifedipine Pharmacologic Treatment Group 2 Pulmonary Hypertension Ambrisentan Bosentan Sildenafil Pharmacologic Treatment Group 3 Pulmonary Hypertension Ambrisentan Bosentan Epoprostenol IV Iloprost Inhaled Sildenafil Group 4 Pulmonary Hypertension Epoprostenol IV (Class A) Iloprost Inhaled (Class B) Pulmonary Thromboendarterectomy (Performed in selected referral centers-UC-San Diego*) TPA for active clot from “fresh” PE Endovascular Treatment CTE Pulmonary Endarterectomy Endovascular Treatment CTE Thank you for your time.