1. RYAN O’GOWAN, MBA, PA-C FAPACVS FCCM Pulmonary Hypertension

2. Disclosures I have no financial relationships with any drug or device manufacturers to disclose.

3. 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.

4. 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

5. 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.

6. Normal Pulmonary Physiology

7. Pathophysiology

9. Causes of Pulmonary Hypertension ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension

10. Diseases Associated with Pulmonary Hypertension ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension

11. 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

12. 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

13. SWAN-GANZ CATHETERIZATION SELECTIVE RIGHT HEART CATHETERIZATION ECHOCARDIOGRAPHY CT SCANNING FOR PULMONARY EMBOLI Evaluation and Diagnosis

14. Swan Ganz Catheterization Clinical Procedures in Anesthesia and Intensive Care, p 416. JB Lippincott, 1994

15. 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

16. Echocardiography Rev Esp Cardiol. 2010;63:583-96 - Vol. 63 Num.05

17. CT Chest- PE Protocol

18. CLASS IIDIOPATHIC PAH (IPAH) CLASS IIPAH WITH LEFT HEART DISEASE CLASS IIIPAH SECONDARY TO HYPOXIA CLASS IV CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION (CTEPH) CLASS VMISCELLANEOUS WHO Classification

19. 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.

20. 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.

21. 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.

22. 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.

23. 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.

24. GROUPS 1-5 PHARMACOLOGIC THERAPIES PULMONARY ENDARTERECTOMY FOR GROUP 4 Treatment Strategies

25. Copyright © The American College of Cardiology. All rights reserved. Used with permission. Updated Evidence-Based Treatment Algorithm in Pulmonary Arterial Hypertension J Am Coll Cardiol. 2009;54(1s1):S78-S84..

26. Initial Pharmacologic Treatment Mainstay of treatment: Group 1-4  Calcium Channel Blockers with Vasoreactivity Treatment (Class B- for responders)  Amlodipine  Diltiazem  Nifedipine

27. Pharmacologic Treatment Group 2 Pulmonary Hypertension  Ambrisentan  Bosentan  Sildenafil

28. Pharmacologic Treatment Group 3 Pulmonary Hypertension  Ambrisentan  Bosentan  Epoprostenol IV  Iloprost Inhaled  Sildenafil

29. 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

30. Endovascular Treatment CTE

31. Pulmonary Endarterectomy

32. Endovascular Treatment CTE

33. Thank you for your time.