Bosentan in Pulmonary Arterial Hypertension PowerPoint Presentation

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74%

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis?

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis?

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis?

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines?

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure PTE Specimen

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure PTE Specimen Hemodynamics – NIH Registry 4 Frequency Right Atrial Pressure (mm Hg) 30 20 10 0 8 12 16 20 24 28 10 40 50 30 Frequency Pulmonary Vascular Resistance Index(L/Min/M2) 25 20 15 10 0 30 70 80 5 20 60 90

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure PTE Specimen Hemodynamics – NIH Registry 4 Frequency Right Atrial Pressure (mm Hg) 30 20 10 0 8 12 16 20 24 28 10 40 50 30 Frequency Pulmonary Vascular Resistance Index(L/Min/M2) 25 20 15 10 0 30 70 80 5 20 60 90 Hemodynamic Abnormalitiesand Prognosis D'Alonzo et al. Annals Int Med 1991;115:343-349 Mean PAP 0 10 20 30 40 50 Median survival (months) Mean RAP Mean CI < 55 mmHg 85 mmHg < 10 mmHg 20 mmHg  4 L/min/m2 < 2 L/min/m2

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure PTE Specimen Hemodynamics – NIH Registry 4 Frequency Right Atrial Pressure (mm Hg) 30 20 10 0 8 12 16 20 24 28 10 40 50 30 Frequency Pulmonary Vascular Resistance Index(L/Min/M2) 25 20 15 10 0 30 70 80 5 20 60 90 Hemodynamic Abnormalitiesand Prognosis D'Alonzo et al. Annals Int Med 1991;115:343-349 Mean PAP 0 10 20 30 40 50 Median survival (months) Mean RAP Mean CI < 55 mmHg 85 mmHg < 10 mmHg 20 mmHg  4 L/min/m2 < 2 L/min/m2 Acute Testing of Vasoreactivity Goal is to determine whether oral vasodilator therapy may be worthwhile as first-line approach Testing should be performed in experienced setting with short-acting agent (ie, NO, PGI2, Adenosine) Few patients who do not have PPH will respond

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure PTE Specimen Hemodynamics – NIH Registry 4 Frequency Right Atrial Pressure (mm Hg) 30 20 10 0 8 12 16 20 24 28 10 40 50 30 Frequency Pulmonary Vascular Resistance Index(L/Min/M2) 25 20 15 10 0 30 70 80 5 20 60 90 Hemodynamic Abnormalitiesand Prognosis D'Alonzo et al. Annals Int Med 1991;115:343-349 Mean PAP 0 10 20 30 40 50 Median survival (months) Mean RAP Mean CI < 55 mmHg 85 mmHg < 10 mmHg 20 mmHg  4 L/min/m2 < 2 L/min/m2 Acute Testing of Vasoreactivity Goal is to determine whether oral vasodilator therapy may be worthwhile as first-line approach Testing should be performed in experienced setting with short-acting agent (ie, NO, PGI2, Adenosine) Few patients who do not have PPH will respond Definition of “Responder” Reduction of Pam to < 40 mm Hg: With a >10% fall in Pam And a normal CO Without change in SAPm PVR should be < 6 units JACC 2004: Proceedings of the Third World Symposium Chest 2004: ACCP Evidence-Based Guidelines

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure PTE Specimen Hemodynamics – NIH Registry 4 Frequency Right Atrial Pressure (mm Hg) 30 20 10 0 8 12 16 20 24 28 10 40 50 30 Frequency Pulmonary Vascular Resistance Index(L/Min/M2) 25 20 15 10 0 30 70 80 5 20 60 90 Hemodynamic Abnormalitiesand Prognosis D'Alonzo et al. Annals Int Med 1991;115:343-349 Mean PAP 0 10 20 30 40 50 Median survival (months) Mean RAP Mean CI < 55 mmHg 85 mmHg < 10 mmHg 20 mmHg  4 L/min/m2 < 2 L/min/m2 Acute Testing of Vasoreactivity Goal is to determine whether oral vasodilator therapy may be worthwhile as first-line approach Testing should be performed in experienced setting with short-acting agent (ie, NO, PGI2, Adenosine) Few patients who do not have PPH will respond Definition of “Responder” Reduction of Pam to < 40 mm Hg: With a >10% fall in Pam And a normal CO Without change in SAPm PVR should be < 6 units JACC 2004: Proceedings of the Third World Symposium Chest 2004: ACCP Evidence-Based Guidelines CCB Response Rates in PAH Lee SH and Rubin LJ: J Intern Med 2005; 258: 199-215. Sitbon O et al: Circulation 2005; 111: 3105-3111.

Slide 35 -

Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure PTE Specimen Hemodynamics – NIH Registry 4 Frequency Right Atrial Pressure (mm Hg) 30 20 10 0 8 12 16 20 24 28 10 40 50 30 Frequency Pulmonary Vascular Resistance Index(L/Min/M2) 25 20 15 10 0 30 70 80 5 20 60 90 Hemodynamic Abnormalitiesand Prognosis D'Alonzo et al. Annals Int Med 1991;115:343-349 Mean PAP 0 10 20 30 40 50 Median survival (months) Mean RAP Mean CI < 55 mmHg 85 mmHg < 10 mmHg 20 mmHg  4 L/min/m2 < 2 L/min/m2 Acute Testing of Vasoreactivity Goal is to determine whether oral vasodilator therapy may be worthwhile as first-line approach Testing should be performed in experienced setting with short-acting agent (ie, NO, PGI2, Adenosine) Few patients who do not have PPH will respond Definition of “Responder” Reduction of Pam to < 40 mm Hg: With a >10% fall in Pam And a normal CO Without change in SAPm PVR should be < 6 units JACC 2004: Proceedings of the Third World Symposium Chest 2004: ACCP Evidence-Based Guidelines CCB Response Rates in PAH Lee SH and Rubin LJ: J Intern Med 2005; 258: 199-215. Sitbon O et al: Circulation 2005; 111: 3105-3111. ACCP PAH GuidelinesPredictors of Poor Survival Advanced Functional Class (A) Poor Exercise Endurance (6MWT) (A) Presence of a Pericardial Effusion (A) Elevated Mean Right Atrial Pressure (A) Reduced Cardiac Index (A) McLaughlin VV et al. CHEST, 2004

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure PTE Specimen Hemodynamics – NIH Registry 4 Frequency Right Atrial Pressure (mm Hg) 30 20 10 0 8 12 16 20 24 28 10 40 50 30 Frequency Pulmonary Vascular Resistance Index(L/Min/M2) 25 20 15 10 0 30 70 80 5 20 60 90 Hemodynamic Abnormalitiesand Prognosis D'Alonzo et al. Annals Int Med 1991;115:343-349 Mean PAP 0 10 20 30 40 50 Median survival (months) Mean RAP Mean CI < 55 mmHg 85 mmHg < 10 mmHg 20 mmHg  4 L/min/m2 < 2 L/min/m2 Acute Testing of Vasoreactivity Goal is to determine whether oral vasodilator therapy may be worthwhile as first-line approach Testing should be performed in experienced setting with short-acting agent (ie, NO, PGI2, Adenosine) Few patients who do not have PPH will respond Definition of “Responder” Reduction of Pam to < 40 mm Hg: With a >10% fall in Pam And a normal CO Without change in SAPm PVR should be < 6 units JACC 2004: Proceedings of the Third World Symposium Chest 2004: ACCP Evidence-Based Guidelines CCB Response Rates in PAH Lee SH and Rubin LJ: J Intern Med 2005; 258: 199-215. Sitbon O et al: Circulation 2005; 111: 3105-3111. ACCP PAH GuidelinesPredictors of Poor Survival Advanced Functional Class (A) Poor Exercise Endurance (6MWT) (A) Presence of a Pericardial Effusion (A) Elevated Mean Right Atrial Pressure (A) Reduced Cardiac Index (A) McLaughlin VV et al. CHEST, 2004 ACCP PAH GuidelinesPredictors of Poor Survival Elevated Mean Pulmonary Artery Pressure (B) Elevated Tei index (C) Low VO2 max, peak SBP, DBP on CPET (C) ECG findings of RAE, RVE (C) Elevated BNP (C) McLaughlin VV et al. CHEST, 2004

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure PTE Specimen Hemodynamics – NIH Registry 4 Frequency Right Atrial Pressure (mm Hg) 30 20 10 0 8 12 16 20 24 28 10 40 50 30 Frequency Pulmonary Vascular Resistance Index(L/Min/M2) 25 20 15 10 0 30 70 80 5 20 60 90 Hemodynamic Abnormalitiesand Prognosis D'Alonzo et al. Annals Int Med 1991;115:343-349 Mean PAP 0 10 20 30 40 50 Median survival (months) Mean RAP Mean CI < 55 mmHg 85 mmHg < 10 mmHg 20 mmHg  4 L/min/m2 < 2 L/min/m2 Acute Testing of Vasoreactivity Goal is to determine whether oral vasodilator therapy may be worthwhile as first-line approach Testing should be performed in experienced setting with short-acting agent (ie, NO, PGI2, Adenosine) Few patients who do not have PPH will respond Definition of “Responder” Reduction of Pam to < 40 mm Hg: With a >10% fall in Pam And a normal CO Without change in SAPm PVR should be < 6 units JACC 2004: Proceedings of the Third World Symposium Chest 2004: ACCP Evidence-Based Guidelines CCB Response Rates in PAH Lee SH and Rubin LJ: J Intern Med 2005; 258: 199-215. Sitbon O et al: Circulation 2005; 111: 3105-3111. ACCP PAH GuidelinesPredictors of Poor Survival Advanced Functional Class (A) Poor Exercise Endurance (6MWT) (A) Presence of a Pericardial Effusion (A) Elevated Mean Right Atrial Pressure (A) Reduced Cardiac Index (A) McLaughlin VV et al. CHEST, 2004 ACCP PAH GuidelinesPredictors of Poor Survival Elevated Mean Pulmonary Artery Pressure (B) Elevated Tei index (C) Low VO2 max, peak SBP, DBP on CPET (C) ECG findings of RAE, RVE (C) Elevated BNP (C) McLaughlin VV et al. CHEST, 2004 Historical Mortality inClass III / IV PPH Days Percent survival 0 0 300 600 900 1200 1500 20 40 60 80 100 Class II & IIIClass IV

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure PTE Specimen Hemodynamics – NIH Registry 4 Frequency Right Atrial Pressure (mm Hg) 30 20 10 0 8 12 16 20 24 28 10 40 50 30 Frequency Pulmonary Vascular Resistance Index(L/Min/M2) 25 20 15 10 0 30 70 80 5 20 60 90 Hemodynamic Abnormalitiesand Prognosis D'Alonzo et al. Annals Int Med 1991;115:343-349 Mean PAP 0 10 20 30 40 50 Median survival (months) Mean RAP Mean CI < 55 mmHg 85 mmHg < 10 mmHg 20 mmHg  4 L/min/m2 < 2 L/min/m2 Acute Testing of Vasoreactivity Goal is to determine whether oral vasodilator therapy may be worthwhile as first-line approach Testing should be performed in experienced setting with short-acting agent (ie, NO, PGI2, Adenosine) Few patients who do not have PPH will respond Definition of “Responder” Reduction of Pam to < 40 mm Hg: With a >10% fall in Pam And a normal CO Without change in SAPm PVR should be < 6 units JACC 2004: Proceedings of the Third World Symposium Chest 2004: ACCP Evidence-Based Guidelines CCB Response Rates in PAH Lee SH and Rubin LJ: J Intern Med 2005; 258: 199-215. Sitbon O et al: Circulation 2005; 111: 3105-3111. ACCP PAH GuidelinesPredictors of Poor Survival Advanced Functional Class (A) Poor Exercise Endurance (6MWT) (A) Presence of a Pericardial Effusion (A) Elevated Mean Right Atrial Pressure (A) Reduced Cardiac Index (A) McLaughlin VV et al. CHEST, 2004 ACCP PAH GuidelinesPredictors of Poor Survival Elevated Mean Pulmonary Artery Pressure (B) Elevated Tei index (C) Low VO2 max, peak SBP, DBP on CPET (C) ECG findings of RAE, RVE (C) Elevated BNP (C) McLaughlin VV et al. CHEST, 2004 Historical Mortality inClass III / IV PPH Days Percent survival 0 0 300 600 900 1200 1500 20 40 60 80 100 Class II & IIIClass IV Echo/Doppler endpoints Effusion score RA area RVET (Tei Index) RV EF (surrogate) Mitral valve early filling LV diastolic dimensions

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure PTE Specimen Hemodynamics – NIH Registry 4 Frequency Right Atrial Pressure (mm Hg) 30 20 10 0 8 12 16 20 24 28 10 40 50 30 Frequency Pulmonary Vascular Resistance Index(L/Min/M2) 25 20 15 10 0 30 70 80 5 20 60 90 Hemodynamic Abnormalitiesand Prognosis D'Alonzo et al. Annals Int Med 1991;115:343-349 Mean PAP 0 10 20 30 40 50 Median survival (months) Mean RAP Mean CI < 55 mmHg 85 mmHg < 10 mmHg 20 mmHg  4 L/min/m2 < 2 L/min/m2 Acute Testing of Vasoreactivity Goal is to determine whether oral vasodilator therapy may be worthwhile as first-line approach Testing should be performed in experienced setting with short-acting agent (ie, NO, PGI2, Adenosine) Few patients who do not have PPH will respond Definition of “Responder” Reduction of Pam to < 40 mm Hg: With a >10% fall in Pam And a normal CO Without change in SAPm PVR should be < 6 units JACC 2004: Proceedings of the Third World Symposium Chest 2004: ACCP Evidence-Based Guidelines CCB Response Rates in PAH Lee SH and Rubin LJ: J Intern Med 2005; 258: 199-215. Sitbon O et al: Circulation 2005; 111: 3105-3111. ACCP PAH GuidelinesPredictors of Poor Survival Advanced Functional Class (A) Poor Exercise Endurance (6MWT) (A) Presence of a Pericardial Effusion (A) Elevated Mean Right Atrial Pressure (A) Reduced Cardiac Index (A) McLaughlin VV et al. CHEST, 2004 ACCP PAH GuidelinesPredictors of Poor Survival Elevated Mean Pulmonary Artery Pressure (B) Elevated Tei index (C) Low VO2 max, peak SBP, DBP on CPET (C) ECG findings of RAE, RVE (C) Elevated BNP (C) McLaughlin VV et al. CHEST, 2004 Historical Mortality inClass III / IV PPH Days Percent survival 0 0 300 600 900 1200 1500 20 40 60 80 100 Class II & IIIClass IV Echo/Doppler endpoints Effusion score RA area RVET (Tei Index) RV EF (surrogate) Mitral valve early filling LV diastolic dimensions Survival correlates with BNP values in PPH Nagaya N et al. Circulation 2000;102:865-70. 100 80 0 Survival rate (%) 60 40 20 0 12 24 36 48 Time (months) 0 100 80 60 40 20 0 Baseline BNP Follow-up BNP 12 24 36 48 Time (months) BNP < 180 pg/ml BNP  180 pg/ml BNP < 150 pg/ml BNP  150 pg/ml

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure PTE Specimen Hemodynamics – NIH Registry 4 Frequency Right Atrial Pressure (mm Hg) 30 20 10 0 8 12 16 20 24 28 10 40 50 30 Frequency Pulmonary Vascular Resistance Index(L/Min/M2) 25 20 15 10 0 30 70 80 5 20 60 90 Hemodynamic Abnormalitiesand Prognosis D'Alonzo et al. Annals Int Med 1991;115:343-349 Mean PAP 0 10 20 30 40 50 Median survival (months) Mean RAP Mean CI < 55 mmHg 85 mmHg < 10 mmHg 20 mmHg  4 L/min/m2 < 2 L/min/m2 Acute Testing of Vasoreactivity Goal is to determine whether oral vasodilator therapy may be worthwhile as first-line approach Testing should be performed in experienced setting with short-acting agent (ie, NO, PGI2, Adenosine) Few patients who do not have PPH will respond Definition of “Responder” Reduction of Pam to < 40 mm Hg: With a >10% fall in Pam And a normal CO Without change in SAPm PVR should be < 6 units JACC 2004: Proceedings of the Third World Symposium Chest 2004: ACCP Evidence-Based Guidelines CCB Response Rates in PAH Lee SH and Rubin LJ: J Intern Med 2005; 258: 199-215. Sitbon O et al: Circulation 2005; 111: 3105-3111. ACCP PAH GuidelinesPredictors of Poor Survival Advanced Functional Class (A) Poor Exercise Endurance (6MWT) (A) Presence of a Pericardial Effusion (A) Elevated Mean Right Atrial Pressure (A) Reduced Cardiac Index (A) McLaughlin VV et al. CHEST, 2004 ACCP PAH GuidelinesPredictors of Poor Survival Elevated Mean Pulmonary Artery Pressure (B) Elevated Tei index (C) Low VO2 max, peak SBP, DBP on CPET (C) ECG findings of RAE, RVE (C) Elevated BNP (C) McLaughlin VV et al. CHEST, 2004 Historical Mortality inClass III / IV PPH Days Percent survival 0 0 300 600 900 1200 1500 20 40 60 80 100 Class II & IIIClass IV Echo/Doppler endpoints Effusion score RA area RVET (Tei Index) RV EF (surrogate) Mitral valve early filling LV diastolic dimensions Survival correlates with BNP values in PPH Nagaya N et al. Circulation 2000;102:865-70. 100 80 0 Survival rate (%) 60 40 20 0 12 24 36 48 Time (months) 0 100 80 60 40 20 0 Baseline BNP Follow-up BNP 12 24 36 48 Time (months) BNP < 180 pg/ml BNP  180 pg/ml BNP < 150 pg/ml BNP  150 pg/ml McLaughlin, Circulation 2002 NYHA Functional Class Remains an Important Determinant of Survival in PPH

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure PTE Specimen Hemodynamics – NIH Registry 4 Frequency Right Atrial Pressure (mm Hg) 30 20 10 0 8 12 16 20 24 28 10 40 50 30 Frequency Pulmonary Vascular Resistance Index(L/Min/M2) 25 20 15 10 0 30 70 80 5 20 60 90 Hemodynamic Abnormalitiesand Prognosis D'Alonzo et al. Annals Int Med 1991;115:343-349 Mean PAP 0 10 20 30 40 50 Median survival (months) Mean RAP Mean CI < 55 mmHg 85 mmHg < 10 mmHg 20 mmHg  4 L/min/m2 < 2 L/min/m2 Acute Testing of Vasoreactivity Goal is to determine whether oral vasodilator therapy may be worthwhile as first-line approach Testing should be performed in experienced setting with short-acting agent (ie, NO, PGI2, Adenosine) Few patients who do not have PPH will respond Definition of “Responder” Reduction of Pam to < 40 mm Hg: With a >10% fall in Pam And a normal CO Without change in SAPm PVR should be < 6 units JACC 2004: Proceedings of the Third World Symposium Chest 2004: ACCP Evidence-Based Guidelines CCB Response Rates in PAH Lee SH and Rubin LJ: J Intern Med 2005; 258: 199-215. Sitbon O et al: Circulation 2005; 111: 3105-3111. ACCP PAH GuidelinesPredictors of Poor Survival Advanced Functional Class (A) Poor Exercise Endurance (6MWT) (A) Presence of a Pericardial Effusion (A) Elevated Mean Right Atrial Pressure (A) Reduced Cardiac Index (A) McLaughlin VV et al. CHEST, 2004 ACCP PAH GuidelinesPredictors of Poor Survival Elevated Mean Pulmonary Artery Pressure (B) Elevated Tei index (C) Low VO2 max, peak SBP, DBP on CPET (C) ECG findings of RAE, RVE (C) Elevated BNP (C) McLaughlin VV et al. CHEST, 2004 Historical Mortality inClass III / IV PPH Days Percent survival 0 0 300 600 900 1200 1500 20 40 60 80 100 Class II & IIIClass IV Echo/Doppler endpoints Effusion score RA area RVET (Tei Index) RV EF (surrogate) Mitral valve early filling LV diastolic dimensions Survival correlates with BNP values in PPH Nagaya N et al. Circulation 2000;102:865-70. 100 80 0 Survival rate (%) 60 40 20 0 12 24 36 48 Time (months) 0 100 80 60 40 20 0 Baseline BNP Follow-up BNP 12 24 36 48 Time (months) BNP < 180 pg/ml BNP  180 pg/ml BNP < 150 pg/ml BNP  150 pg/ml McLaughlin, Circulation 2002 NYHA Functional Class Remains an Important Determinant of Survival in PPH Influence of 6 Minute Walk on Survival in PPH Sitbon et al, JACC 2002: 40: 780-788

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure PTE Specimen Hemodynamics – NIH Registry 4 Frequency Right Atrial Pressure (mm Hg) 30 20 10 0 8 12 16 20 24 28 10 40 50 30 Frequency Pulmonary Vascular Resistance Index(L/Min/M2) 25 20 15 10 0 30 70 80 5 20 60 90 Hemodynamic Abnormalitiesand Prognosis D'Alonzo et al. Annals Int Med 1991;115:343-349 Mean PAP 0 10 20 30 40 50 Median survival (months) Mean RAP Mean CI < 55 mmHg 85 mmHg < 10 mmHg 20 mmHg  4 L/min/m2 < 2 L/min/m2 Acute Testing of Vasoreactivity Goal is to determine whether oral vasodilator therapy may be worthwhile as first-line approach Testing should be performed in experienced setting with short-acting agent (ie, NO, PGI2, Adenosine) Few patients who do not have PPH will respond Definition of “Responder” Reduction of Pam to < 40 mm Hg: With a >10% fall in Pam And a normal CO Without change in SAPm PVR should be < 6 units JACC 2004: Proceedings of the Third World Symposium Chest 2004: ACCP Evidence-Based Guidelines CCB Response Rates in PAH Lee SH and Rubin LJ: J Intern Med 2005; 258: 199-215. Sitbon O et al: Circulation 2005; 111: 3105-3111. ACCP PAH GuidelinesPredictors of Poor Survival Advanced Functional Class (A) Poor Exercise Endurance (6MWT) (A) Presence of a Pericardial Effusion (A) Elevated Mean Right Atrial Pressure (A) Reduced Cardiac Index (A) McLaughlin VV et al. CHEST, 2004 ACCP PAH GuidelinesPredictors of Poor Survival Elevated Mean Pulmonary Artery Pressure (B) Elevated Tei index (C) Low VO2 max, peak SBP, DBP on CPET (C) ECG findings of RAE, RVE (C) Elevated BNP (C) McLaughlin VV et al. CHEST, 2004 Historical Mortality inClass III / IV PPH Days Percent survival 0 0 300 600 900 1200 1500 20 40 60 80 100 Class II & IIIClass IV Echo/Doppler endpoints Effusion score RA area RVET (Tei Index) RV EF (surrogate) Mitral valve early filling LV diastolic dimensions Survival correlates with BNP values in PPH Nagaya N et al. Circulation 2000;102:865-70. 100 80 0 Survival rate (%) 60 40 20 0 12 24 36 48 Time (months) 0 100 80 60 40 20 0 Baseline BNP Follow-up BNP 12 24 36 48 Time (months) BNP < 180 pg/ml BNP  180 pg/ml BNP < 150 pg/ml BNP  150 pg/ml McLaughlin, Circulation 2002 NYHA Functional Class Remains an Important Determinant of Survival in PPH Influence of 6 Minute Walk on Survival in PPH Sitbon et al, JACC 2002: 40: 780-788 Maximal oxygen consumption as a determinant of survival in PPH Wensel et al. Circulation 2002; 106:319-24 - Cumulative survival (%) 100 Time (years) 80 60 40 20 0 0 1 2 3 Peak VO2  10.4 ml/kg/min Peak VO2 > 10.4 ml/kg/min Peak VO2  10.4 ml/kg/min Peak VO2 > 10.4 ml/kg/min At risk Deaths 36 29 14 8 0 3 9 11 At risk Deaths 34 14 2 0 0 16 23 23

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure PTE Specimen Hemodynamics – NIH Registry 4 Frequency Right Atrial Pressure (mm Hg) 30 20 10 0 8 12 16 20 24 28 10 40 50 30 Frequency Pulmonary Vascular Resistance Index(L/Min/M2) 25 20 15 10 0 30 70 80 5 20 60 90 Hemodynamic Abnormalitiesand Prognosis D'Alonzo et al. Annals Int Med 1991;115:343-349 Mean PAP 0 10 20 30 40 50 Median survival (months) Mean RAP Mean CI < 55 mmHg 85 mmHg < 10 mmHg 20 mmHg  4 L/min/m2 < 2 L/min/m2 Acute Testing of Vasoreactivity Goal is to determine whether oral vasodilator therapy may be worthwhile as first-line approach Testing should be performed in experienced setting with short-acting agent (ie, NO, PGI2, Adenosine) Few patients who do not have PPH will respond Definition of “Responder” Reduction of Pam to < 40 mm Hg: With a >10% fall in Pam And a normal CO Without change in SAPm PVR should be < 6 units JACC 2004: Proceedings of the Third World Symposium Chest 2004: ACCP Evidence-Based Guidelines CCB Response Rates in PAH Lee SH and Rubin LJ: J Intern Med 2005; 258: 199-215. Sitbon O et al: Circulation 2005; 111: 3105-3111. ACCP PAH GuidelinesPredictors of Poor Survival Advanced Functional Class (A) Poor Exercise Endurance (6MWT) (A) Presence of a Pericardial Effusion (A) Elevated Mean Right Atrial Pressure (A) Reduced Cardiac Index (A) McLaughlin VV et al. CHEST, 2004 ACCP PAH GuidelinesPredictors of Poor Survival Elevated Mean Pulmonary Artery Pressure (B) Elevated Tei index (C) Low VO2 max, peak SBP, DBP on CPET (C) ECG findings of RAE, RVE (C) Elevated BNP (C) McLaughlin VV et al. CHEST, 2004 Historical Mortality inClass III / IV PPH Days Percent survival 0 0 300 600 900 1200 1500 20 40 60 80 100 Class II & IIIClass IV Echo/Doppler endpoints Effusion score RA area RVET (Tei Index) RV EF (surrogate) Mitral valve early filling LV diastolic dimensions Survival correlates with BNP values in PPH Nagaya N et al. Circulation 2000;102:865-70. 100 80 0 Survival rate (%) 60 40 20 0 12 24 36 48 Time (months) 0 100 80 60 40 20 0 Baseline BNP Follow-up BNP 12 24 36 48 Time (months) BNP < 180 pg/ml BNP  180 pg/ml BNP < 150 pg/ml BNP  150 pg/ml McLaughlin, Circulation 2002 NYHA Functional Class Remains an Important Determinant of Survival in PPH Influence of 6 Minute Walk on Survival in PPH Sitbon et al, JACC 2002: 40: 780-788 Maximal oxygen consumption as a determinant of survival in PPH Wensel et al. Circulation 2002; 106:319-24 - Cumulative survival (%) 100 Time (years) 80 60 40 20 0 0 1 2 3 Peak VO2  10.4 ml/kg/min Peak VO2 > 10.4 ml/kg/min Peak VO2  10.4 ml/kg/min Peak VO2 > 10.4 ml/kg/min At risk Deaths 36 29 14 8 0 3 9 11 At risk Deaths 34 14 2 0 0 16 23 23 Peak SBP as a predictor of survivalin PPH Wensel et al. Circulation 2002; 106:319-24. - Cumulative survival (%) 100 Time (years) 80 60 40 20 0 0 1 2 3 Peak SBP  120 mmHg Peak SBP > 120 mmHg Peak SBP  120 mmHg Peak SBP > 120 mmHg At risk Deaths 45 35 16 8 0 3 10 12 At risk Deaths 25 8 2 0 16 22

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Diagnostic Evaluation of Pulmonary Arterial Hypertension: ACCP Guidelines Lewis J. Rubin, MD, FCCP, FRCP University of California, San Diego Disclosures Investigator and Consultant Actelion, Pfizer, CoTherix, Myogen, Schering, United Therapeutics, Mondobiotech, Nitrox Members of the ACCP Guidelines Committee Lewis Rubin, MD, FCCP, Chair University of California, San Diego Steven H. Abman, MD University of Colorado Gregory S. Ahearn, MD Duke University Rino Aldrighetti, PHA Rep Pulmonary Hypertension Association Charles Atwood, MD, FCCP University of Pittsburgh David B. Badesch, MD, FCCP University of Colorado Robyn J. Barst, MD, FCCP Columbia University Richard N. Channick, MD, FCCP University of California, San Diego John Conte, MD, FCCP Johns Hopkins University Ramona L. Doyle, MD, FCCP Stanford University Terry A. Fortin, MD Duke University Joe G. N. Garcia, MD, FCCP Johns Hopkins University Joseph A. Govert, MD, FCCP Duke University David Gutterman, MD, FCCP Medical College of Wisconsin Sandra Zelman Lewis, PhD American College of Chest Physicians James E. Loyd, MD, FCCP Vanderbilt University Douglas C. McCrory, MD, MHS Duke University Michael D. McGoon, MD, FCCP Mayo Clinic Vallerie V. McLaughlin, MD, FCCP University of Michigan Kenneth Presberg, MD, FCCP Medical College of Wisconsin Stuart Rich, MD, FCCP, ACC Rep Rush Presbyterian St. Luke’s Hospital Gerald Simonneau, MD Hospital Antoine Beclere Virginia Steen, MD Georgetown University John Sundy, MD Duke University Fredrick M. Wigley, MD, ACR Rep Johns Hopkins University Organizational Endorsements American College of Chest Physicians American College of Cardiology American College of Rheumatology American Heart Association Pulmonary Hypertension Association Cardiac Catheterization RA mean 10 mm Hg RV 100/14 mm Hg PA 100/40 (mean 60) mm Hg PCW mean 12 mm Hg LV 110/0-10 mm Hg Ao 110/70 (mean 83) mm Hg Cardiac Output 3.0 L/min Room Air SaO2 82%; SvO2 50% PVR 20 Units No acute response to iNO Echocardiogram also demonstrated no intracardiac shunt After 1 month of continuous intravenous epoprostenol therapy Baseline HRCT Baseline PFTs (% Predicted) FVC 80% FEV1 80% TLC 76% DLCO 22% Arterial Blood Gases Room Air: pH 7.46 PCO2 32 PO2 51 100% O2: PO2 67 What Would YOU Do? Begin oral therapy (either sildenafil or bosentan), and warfarin Begin therapy with epoprostenol Begin therapy with inhaled iloprost Do something else What was Done She was started on continuous intravenous epoprostenol and initially improved, with less dyspnea. The dose of epoprostenol was gradually increased from 2-12 ng/kg/min She returned 1 month later with the complaint of increased dyspnea. SaO2 was 74% After 1 month of continuous intravenous epoprostenol therapy Before continuous intravenous epoprostenol therapy What Would YOU Do? Add oral therapy (either sildenafil or bosentan) Increase epoprostenol dose after diuresis Discontinue epoprostenol and switch to another therapy Refer for a thoracoscopic lung biopsy Do something else What was Done She was switched to inhaled prostanoid therapy She stabilized but remained hypoxemic and her activity tolerance was severely impaired She underwent lung transplantation 6 months later What’s the Diagnosis? Pulmonary Arterial HypertensionDiagnostic classificationJACC 2004 and Chest 2004 Suspected Pulmonary Hypertension Echocardiogram Chest X-Ray PFT’s Sleep Study Ventilation- Perfusion scan, angiography Autoantibody tests HIV test LFTs and clinical evidence of cirrhosis and portal htn Left heart disease Valvular/Congenital Heart Disease Emphysema Fibrosis Thoracic abnl Sleep disorder Chronic Thrombo- embolism Scleroderma SLE RA Vasculitis HIV infection Portopulmonary Hypertension Diagnosis of Pulmonary Hypertension Required When Clinically Indicated Echocardiographic Appearance of PAH Tricuspid Regurgitant Jet Velocity Measurements from the echocardiogram in pulmonary hypertension, including the peak velocity of the regurgitant jet of the tricuspid valve Arcasoy et al: AJRCCM 2003; 167: 735-740 Mukerjee et al: Rheumatology 2004; 43: 461-466 The Chest X-ray Normal Right Heart Enlargement HRCT: Ground Glass or Septal Lines? CT AngiogramMosaic Pattern Perfusion Lung Scan CT AngiogramCentral Thrombus Hypoperfusion Hypoperfusion Abrupt cut-off Filling defect Web Pulmonary Angiography PTE: The Procedure PTE Specimen Hemodynamics – NIH Registry 4 Frequency Right Atrial Pressure (mm Hg) 30 20 10 0 8 12 16 20 24 28 10 40 50 30 Frequency Pulmonary Vascular Resistance Index(L/Min/M2) 25 20 15 10 0 30 70 80 5 20 60 90 Hemodynamic Abnormalitiesand Prognosis D'Alonzo et al. Annals Int Med 1991;115:343-349 Mean PAP 0 10 20 30 40 50 Median survival (months) Mean RAP Mean CI < 55 mmHg 85 mmHg < 10 mmHg 20 mmHg  4 L/min/m2 < 2 L/min/m2 Acute Testing of Vasoreactivity Goal is to determine whether oral vasodilator therapy may be worthwhile as first-line approach Testing should be performed in experienced setting with short-acting agent (ie, NO, PGI2, Adenosine) Few patients who do not have PPH will respond Definition of “Responder” Reduction of Pam to < 40 mm Hg: With a >10% fall in Pam And a normal CO Without change in SAPm PVR should be < 6 units JACC 2004: Proceedings of the Third World Symposium Chest 2004: ACCP Evidence-Based Guidelines CCB Response Rates in PAH Lee SH and Rubin LJ: J Intern Med 2005; 258: 199-215. Sitbon O et al: Circulation 2005; 111: 3105-3111. ACCP PAH GuidelinesPredictors of Poor Survival Advanced Functional Class (A) Poor Exercise Endurance (6MWT) (A) Presence of a Pericardial Effusion (A) Elevated Mean Right Atrial Pressure (A) Reduced Cardiac Index (A) McLaughlin VV et al. CHEST, 2004 ACCP PAH GuidelinesPredictors of Poor Survival Elevated Mean Pulmonary Artery Pressure (B) Elevated Tei index (C) Low VO2 max, peak SBP, DBP on CPET (C) ECG findings of RAE, RVE (C) Elevated BNP (C) McLaughlin VV et al. CHEST, 2004 Historical Mortality inClass III / IV PPH Days Percent survival 0 0 300 600 900 1200 1500 20 40 60 80 100 Class II & IIIClass IV Echo/Doppler endpoints Effusion score RA area RVET (Tei Index) RV EF (surrogate) Mitral valve early filling LV diastolic dimensions Survival correlates with BNP values in PPH Nagaya N et al. Circulation 2000;102:865-70. 100 80 0 Survival rate (%) 60 40 20 0 12 24 36 48 Time (months) 0 100 80 60 40 20 0 Baseline BNP Follow-up BNP 12 24 36 48 Time (months) BNP < 180 pg/ml BNP  180 pg/ml BNP < 150 pg/ml BNP  150 pg/ml McLaughlin, Circulation 2002 NYHA Functional Class Remains an Important Determinant of Survival in PPH Influence of 6 Minute Walk on Survival in PPH Sitbon et al, JACC 2002: 40: 780-788 Maximal oxygen consumption as a determinant of survival in PPH Wensel et al. Circulation 2002; 106:319-24 - Cumulative survival (%) 100 Time (years) 80 60 40 20 0 0 1 2 3 Peak VO2  10.4 ml/kg/min Peak VO2 > 10.4 ml/kg/min Peak VO2  10.4 ml/kg/min Peak VO2 > 10.4 ml/kg/min At risk Deaths 36 29 14 8 0 3 9 11 At risk Deaths 34 14 2 0 0 16 23 23 Peak SBP as a predictor of survivalin PPH Wensel et al. Circulation 2002; 106:319-24. - Cumulative survival (%) 100 Time (years) 80 60 40 20 0 0 1 2 3 Peak SBP  120 mmHg Peak SBP > 120 mmHg Peak SBP  120 mmHg Peak SBP > 120 mmHg At risk Deaths 45 35 16 8 0 3 10 12 At risk Deaths 25 8 2 0 16 22 Summary Comprehensive initial evaluation should focus on: Establishing etiology Assessing severity Determining preferred approach to treatment