Modern Management of Pulmonary Hypertension: Expert Guidance for Individualized Care in the Community Practice Setting

Transcription

1 Modern Management of Pulmonary Hypertension: Expert Guidance for Individualized Care in the Community Practice Setting Agenda 1. Welcome & introduction 2. Brief summary of best practices for optimal screening, diagnosis, and treatment of pulmonary hypertension (PH) 3. Interactive discussion of how to improve the care of patients with PH in the community setting: questions and challenging cases from participants

2 Presentation 1 Evidence-Based Strategies for Screening, Early Detection, and Diagnosis of Pulmonary Hypertension

3 Clinical Classification of Pulmonary Hypertension 1. Pulmonary Arterial Hypertension (PAH) Idiopathic PAH Heritable PAH BMPR2 ALK-1, ENG, SMAD9, CAV1, KCNK3 Unknown Drug- and toxin-induced Associated with: CTD HIV infection Portal hypertension Congenital heart disease Schistosomiasis 1. PVOD and/or PCH 1. Persistent PH of the Newborn 2. PH Due to Left Heart Disease Left ventricular systolic dysfunction Left ventricular diastolic dysfunction Valvular disease Congenital/acquired left heart inflow/outflow tract obstruction and congenital cardiomyopathies 3. PH Due to Lung Diseases and/or Hypoxia COPD Interstitial lung disease Other pulmonary diseases with mixed restrictive and obstructive pattern Sleep-disordered breathing Alveolar hypoventilation disorders Chronic exposure to high altitude Developmental lung diseases 4. Chronic Thromboembolic PH (CTEPH) 5. PH With Unclear Multifactorial Mechanisms Hematologic disorders Systemic disorders Metabolic disorders Others BMPR: bone morphogenic protein receptor type II; CAV1: caveolin-1; CTD: connective tissue disease; ENG: endoglin; PCH: pulmonary capillary hemangiomatosis; PH: pulmonary hypertension; PVOD: pulmonary veno-occlusive disease. Simonneau G et al. J Am Coll Cardiol. 2013;62:D34-D41.

4 PAH Classification: Baseline Characteristics From REVEAL Registry APAH: associated PAH; CHD: congenital heart disease; CVD: collagen vascular disease; FPAH: familial PAH; HT: hypertension; IPAH: idiopathic PAH; PPHN: pulmonary HT of the newborn; WHO: World Health Organization. Badesch DB et al. Chest. 2010;137:

5 Seven-Year Survival Estimates: REVEAL Registry Adapted from: Benza R et al. Chest. 2012,142:

6 PAH: Signs and Symptoms Symptoms Exertional dyspnea Lethargy and fatigue Exertional angina and/or syncope Palpitation/arrhythmias Physical Signs Distended jugular veins Right ventricular heave Loud pulmonary second sound (P 2 ) Right S 3, S 4, tricuspid regurgitation (late) Elevated jugular venous pressure (late) Peripheral edema and ascites (late) Nonspecific symptoms difficult to distinguish from other cardiopulmonary disorders Diagnosis of PAH is significantly delayed as it is not considered early in the differential diagnosis of disease; awareness of disease is needed S 3 : third heart sound; S 4 : fourth heart sound. McLaughlin VV et al. J Am Coll Cardiol. 2009;53:

7 Definition of PAH Hemodynamic Parameter Mean pulmonary arterial pressure (mpap) at rest Pulmonary capillary wedge pressure (PCWP) or left ventricular end-diastolic pressure (LVEDP) Pulmonary vascular resistance (PVR) Value >25 mmhg 15 mmhg >3 Wood units Hoeper MM et al. J Am Coll Cardiol. 2013;62:D42-D50.

8 WHO Functional Classification of PAH Functional Class Description I PH that causes no limitations on physical activities Routine physical activity does not cause increased dyspnea, chest pain, fatigue, or presyncope II PH that causes mild limitations on physical activities Patients are comfortable at rest but routine physical activity results in increased dyspnea, chest pain, fatigue, or syncope III PH that causes marked limitations on physical activities Patients are comfortable at rest, but less than routine physical activity results in dyspnea, chest pain, fatigue, or syncope IV PH that results in inability to perform any physical activities without symptoms Patients may have signs of right-heart failure Dyspnea with or without fatigue may be present at rest, and symptoms are increased by any physical activity Rich S, ed. Executive Summary from the World Symposium on Primary Pulmonary Hypertension, 1998; cosponsored by the World Health Organization. Evian, France.

9 Recommended Screening Approaches for Patients at Risk for PAH Condition Conferring PAH Risk BMPR2 mutation 1st degree relative of pt with BMPR2 mutation or within pedigree of 2 pts with PAH dx Systemic sclerosis a HIV infection Portal hypertension Prior appetite suppressant use (fenfluramine) Congenital heart disease with shunt Recent acute pulmonary embolism Sickle cell disease Screening Strategy Yearly echo; then RHC if echo shows high RVSP or right heart enlargement (RHE) Genetic counseling; recommendation for BMPR2 genotyping Yearly echo; then RHC if echo shows high RVSP or RHE Echo if signs or symptoms of PAH; then RHC if echo shows high RVSP or RHE Echo if OLT considered; then RHC if echo shows high RVSP or RHE Echo only if symptomatic Echo and RHC at time of diagnosis V/Q scintigraphy 3 mo after event if symptomatic; pulmonary angiogram if positive Yearly echo; then RHC if echo shows high RVSP or RHE a May change based on DETECT trial results. echo: echocardiogram; OLT: orthotopic liver transplantation; RHC: right heart catheterization; RVSP: right ventricular systolic pressure; V/Q: ventilation/perfusion. Adapted from: McLaughlin VV et al. J Am Coll Cardiol. 2009;53:

10 Screening Can Help in Diagnosing the Disease in an Early Stage 1,2 No Screening With Screening Without screening: the majority of patients were diagnosed in WHO-FC III or FC IV, and only 24% were in WHO-FC II FC: functional class. 1. Humbert M et al. Am J Respir Crit Care Med. 2006;173: Hachulla E et al. Arthritis Rheum. 2005;52:

11 Origin of Routine Practice and Detected Patients 1 French PAH Registry 2 n = 674 consecutive adult PAH Other PAH n = 600 Prevalent PAH-SSc n = 58 PAH-SSc n = 74 ItinérAIR-Sclérodermie 3,4 n = 599 consecutive adult SSc Prevalent PAH-SSc n = 29 Systematic detection program (cardiac echo Doppler) n = 570 RHC due to suspicion of PAH (VTR >3 m/s or VTR m/s with unexplained dyspnea) Adjudication panel review of case report forms Incident routine practice cohort n = 16 Incident detection cohort n = 16 SSc: systemic sclerosis; VTR: peak tricuspid regurgitant jet velocity. 1. Humbert M et al. Arthritis Rheum. 2011;63: Humbert M et al. Am J Respir Crit Care Med. 2006;173: Hachulla E et al. Arthritis Rheum. 2005;52: Hachulla E et al. Arthritis Rheum. 2009;60:

12 Clinical Characteristics at PAH-SSc Diagnosis: Routine Practice and Detection Patients Routine Practice a (n = 16) Detection a (n = 16) P Age, y 62.7 ± ± Female patients, n (%) 12 (75) 15 (94).33 Time since first non-rp symptom, y 12.5 ± ± dcssc patients, n (%) 2 (12.5) 8 (50).052 NYHA FC, n (%) I II III IV 0 (0) 2 (12.5) 11 (69) 3 (18.5) 1 (6) 7 (44) 8 (50) 0 (0).036 6MWD, m 249 ± ± a Except where otherwise stated, values are mean ± SD. 6MWD: 6-minute walk distance; dcssc: diffuse cutaneous SSc; NYHA: New York Heart Association; RP: Raynaud s phenomenon. Adapted from: Humbert M et al. Arthritis Rheum. 2011;63:

13 Hemodynamics at PAH-SSc Diagnosis: Routine Practice and Detection Patients Routine Practice a (n = 16) Detection a (n = 16) P RAP, mmhg 10 ± 5 6 ± mpap, mmhg 49 ± ± mpawp, mmhg 9 ± 4 10 ± 3.28 Cardiac output, L/min 3.59 ± ± 1.51 <.0001 Cardiac index, L/min/m ± ± PVR index, dynes. s. cm -5. m -2 1,500 ± ± 400 <.0001 a Values are mean ± SD. mpawp: mean pulmonary artery wedge pressure; RAP: right atrial pressure. Humbert M et al. Arthritis Rheum. 2011;63:

14 Prognosis of Routine Practice and Detection PAH-SSc Patients % 81% 73% P =.0037 HR = 4.15 (95% CI, ) 80 75% 64% Survival, % % 25% 17% Detection PAH-SSc Routine practice PAH-SSc Time of Follow-Up, years Adapted from: Humbert M et al. Arthritis Rheum. 2011;63:

15 Evaluation of Screening Tests in SSc Patients: DETECT DETECT will evaluate more than 10 screening tools and their combinations against the confirmatory gold standard diagnostic test for PAH right heart catheterization Coghlan JG et al. Ann Rheum Dis May 18. [Epub ahead of print]. doi: /annrheumdis

16 DETECT: The 8 Variables in the Final Screening Algorithm Variable a Non-PH PAH P b ROC AUC (95% CI) FVC % pred. / DLCO % pred. Current or past telangiectasias 1.8 ± ± 0.7 < ( ) < ( ) Serum ACA positive < ( ) Serum NT-proBNP, log 10 (pg/ml) 2.1 ± 0.5 (230.0 ± 538.6) 2.4 ± 0.5 (516.4 ± 805.0) < ( ) Serum urate, mg/100 ml Right axis deviation c on ECG 4.7 ± ± 1.5 < ( ) ( ) Right atrium area, cm ± ± 6.2 < ( ) TR velocity, m/s 2.4 ± ± 0.8 < ( ) a Data are mean ± standard deviation or %; b Wald 2 test; c QRS axis 90. ACA: anticentromere antibody; DLCO: diffusing capacity of lung for carbon monoxide; FVC: forced vital capacity; NTproBNP: N-terminal pro brain natriuretic peptide; pred.: predicted; ROC AUC: area under the receiver operating characteristic curve.; TR: tricuspid regurgitant jet. Coghlan JG et al. Ann Rheum Dis May 18. [Epub ahead of print]. doi: /annrheumdis

17 PAH-QuERI: Adherence to Guideline-Recommended Screening PAH Quality Enhancement Research Initiative (PAH-QuERI): database of 62 community and academic centers in the US; initiated in 2005 ACCP-Recommended Screening Strategy Patients Screened, % Complete blood cell count 90.6 Liver function testing D echocardiography 96.8 Connective tissue disease 49.9 HIV 28.9 Chest radiography 88.2 ECG 81.5 Pulmonary function tests 82.7 V/Q lung scanning MWD 78.9 Right heart catheterization 90.3 Recommended screening tools are underutilized Adapted from: McLaughlin VV et al. Chest. 2013;1438:

18 Diagnostic Algorithm for PAH Symptoms, signs, hx suggestive of PH Echocardiography compatible with PH? Yes Consider most common causes of PH (ie, LH disease, lung disease) No PH unlikely Yes Signs of severe PH/RV dysfunction No Treat underlying disease Dx of heart or lung disease confirmed? Yes Refer to PH expert center No CTEPH likely CT angiography, RHC + PA (PEA expert center) Hx, signs, risk factors, ECG, x-ray, PFT incl. DLCO, consider BGA, HR-CT V/Q scintigraphy Unmatched perfusion defects? Yes Consider other causes or recheck Consider other causes BGA: blood gas analysis; HR-CT: high-resolution computed tomography; LH: left heart; PA: pulmonary angiography; PEA: pulmonary endarterectomy; PFT: pulmonary function testing; RV: right ventricle. Adapted from Hoeper MM et al. J Am Coll Cardiol. 2013;62:D42-D50. No RHC mpap 25 mmhg, PAWP 15 mmhg, PVR >3 WU No Yes CTD, drugs/toxins, HIV, PVOD/PCH, CHD, portopulmonary, schistosomiasis, other (group 5?) PAH likely Specific diagnostic tests Idiopathic or heritable PAH Family hx, consider genetic tests

19 Differentiating CTEPH From PAH 1-3 CTEPH PAH Risk factors Diagnosis Treatment PE; infected surgical cardiac shunt or pacemaker; splenectomy; anti-phospholipid antibodies; high levels of factor VIII; abnormal fibrinolytic response Segmental perfusion defects on V/Q scan; confirmation with pulmonary angiography, CTA, or MRA; RHC; pulmonary flow murmur PEA for patients considered operable; riociguat for the treatment of patients with inoperable CTEPH or persistent/recurrent PH after PEA Genetic mutation; certain drugs/toxins; HIV; connective tissue disorders; congenital heart disease No segmental perfusion defects on V/Q scan; RHC; vasodilator trial Medical treatments targeting dysfunctional pathways in endothelial cells 1. Dartevelle P et al. Eur Respir J. 2004;23: Galiè N et al. Eur Heart J. 2009;30: Keogh AM et al. J Am Coll Cardiol. 2009;54:S67-S77.

20 Right Heart Catheterization Rigorous diagnosis of PAH requires RHC prior to initiation of therapy RHC remains the gold standard assessment of hemodynamics in PAH Measure Pressure PCWP RA PA RV Measure PVR PA: pulmonary arterial; RA: right atrial; RV: right ventricular. McLaughlin VV et al. J Am Coll Cardiol. 2009;53: Image courtesy of Curt Daniels, MD. Measure cardiac output

21 Distinguishing Heart Failure With Preserved Ejection Fraction From Pulmonary Hypertension PH-HFpEF may often be misclassified as WHO class I PAH Distinction is important as therapies for PAH can be detrimental in HFpEF Characteristic HFpEF PAH PH-HFpEF Age Older Younger Older Comorbidities Frequent Rare More frequent Right atrial enlargement Absent More frequent Less frequent Left atrial enlargement Frequent Absent Frequent Aortic systolic pressure Elevated Normal Elevated Mean RAP Normal Normal-high High Cardiac output Normal Low Normal PVR Normal Markedly elevated Moderately elevated HFpEF: heart failure with preserved ejection fraction; PH-HFpEF: pulmonary hypertension associated with HFpEF. Thenappan T et al. Circ Heart Fail. 2011;4:

22 Delay in Recognition of PAH: REVEAL Registry REVEAL registry: enrolled 2,967 adult patients with PAH from Mar 2006-Sep 2007 In 21.1% of patients, symptoms were experienced for >2 years before PAH was recognized Factors for Delayed PAH Recognition Odds Ratio PAH symptom onset before age History of obstructive airways disease 1.93 Sleep apnea MWD <250 m 1.91 RAP <10 mmhg 1.77 PVR <10 Wood units 1.28 Adapted from: Brown LM et al. Chest. 2011;140:19-26.

23 Summary Evaluate symptoms Exclude non-pah causes of PH Confirm diagnosis of PAH by RHC Classify the type of PAH

24 Presentation 2 Exploring Recent Advances in the Treatment of Pulmonary Hypertension

25 PAH Determinants of Risk Lower Risk Determinants of Risk Higher Risk No Clinical evidence of RV failure Gradual Progression of symptoms Rapid II/III WHO functional class IV >400 m 6MWD <300 m Peak VO 2 >10.4 ml/kg/min Minimal RV dysfunction RAP <10 mmhg; CI >2.5 L/min/m 2 Cardiopulmonary exercise test Echocardiography Hemodynamics Yes Peak VO 2 <10.4 ml/kg/min Pericardial effusion, significant RV enlargement/dysfunction; RA enlargement RAP >20 mmhg; CI <2.0 L/min/m 2 Minimally elevated BNP Significantly elevated BNP: brain natriuretic peptide; CI: cardiac index; peak VO 2 : average peak oxygen uptake during exercise. Adapted from: McLaughlin VV et al. J Am Coll Cardiol. 2009;53:

26 Currently Available Therapies to Treat PAH Therapeutic Class Prostacyclin analogs (prostanoids) Endothelin receptor antagonists Phosphodiesterase type 5 (PDE-5) inhibitors Stimulator of soluble guanylate cyclase Currently Approved Agents Epoprostenol (IV) Treprostinil (oral, IV, subcutaneous, and inhaled) Iloprost (IV and inhaled) Bosentan Ambrisentan Macitentan b Sildenafil Tadalafil Riociguat c a On December 20, 2013, the FDA approved oral treprostinil for treatment of patients with PAH. b On October 18, 2013, the FDA approved macitentan for the treatment of patients with PAH. c On October 8, 2013, the FDA approved riociguat for the treatment of patients with PAH and CTEPH. CTEPH: chronic thromboembolic pulmonary hypertension.

27 Published Clinical Trials of Combination Therapy in PAH Trial Agents Endpoint Effects BREATHE-2 1 (N = 33) STEP-I 2 (N = 67) COMBI 3 (N = 40) PACES-1 4 (N = 267) TRIUMPH-1 5 (N = 212) Epoprostenol IV + bosentan vs epoprostenol + PBO Bosentan + iloprost PI vs bosentan + PBO Bosentan + iloprost PI vs bosentan monotherapy Epoprostenol IV + sildenafil vs epoprostenol IV + PBO Sildenafil or bosentan + treprostinil PI vs sildenafil or bosentan + PBO TPR 6MWD 6MWD 6MWD 6MWD No significant difference Improvement of 6MWD (P <.051), FC (P =.0023), Borg dyspnea scale (P <.03), mpap (P <.001), PVR (P <.001) Futility analysis; premature discontinuation Improvement of TTCW (P =.012), 6MWD (P <.001), mpap (P <.0001) Increase in 6MWD (P <.005); no changes in TTCW, Borg dyspnea scale, FC PBO: placebo; PI: per inhalation; TPR: total pulmonary resistance; TTCW: time to clinical worsening. 1. Humbert M et al. Eur Respir J. 2004;24:353e McLaughlin VV et al. Am J Respir Crit Care Med. 2006;174:1257e Hoeper MM et al. Eur Respir J. 2006;28:691e Simonneau G et al. Ann Intern Med. 2008;149:521e McLaughlin VV et al. J Am Coll Cardiol. 2010;55:1915e1922.

28 ACCF/AHA Consensus PAH Treatment Algorithm Anticoagulant ± diuretics ± oxygen ± digoxin Acute vasoreactivity testing Positive Negative Oral CCB Lower risk Higher risk Sustained response No ERA or PDE-5 inhibitor (oral) Epoprostenol or treprostinil (IV) Iloprost (inhaled) Epoprostenol or treprostinil (IV) Iloprost (inhaled) ERA or PDE-5 inhibitor (oral) Treprostinil (SC, inhaled) Treprostinil (SC) Yes Reassess: consider combination therapy Continue CCB Investigational protocols Atrial septostomy Lung transplant CCB: calcium channel blocker; ERA: endothelin receptor antagonist; SC: subcutaneous. Figure from J Am Coll Cardiol, Vol 53, no. 17, McLaughlin VV et al., ACCF/AHA 2009 Expert Consensus Document on Pulmonary Hypertension, , 2009; used with permission from Elsevier.

29 Fifth WSPH PAH Treatment Algorithm Nonresponder to acute vasoreactivity test Recommendation Evidence WHO-FC II WHO-FC III WHO-FC IV Ambrisentan, bosentan, I A or B epoprostenol IV, iloprost Ambrisentan, bosentan, inhaled, macitentan, macitentan, riociguat, riociguat, sildenafil, sildenafil, tadalafil tadalafil, treprostinil SC, Epoprostenol IV inhaled IIa C Iloprost IV a, treprostinil IV Ambrisentan, bosentan, iloprost inhaled and IV a, macitentan, riociguat, sildenafil, tadalafil, treprostinil SC, IV, inhaled IIb B Beraprost a C Initial combination therapy Initial combination therapy Prostanoids Sequential combination tx (I-A) ERAs + + INADEQUATE CLINICAL RESPONSE PDE-5i or sgcs INADEQUATE CLINICAL RESPONSE ON MAX TX Referral for lung transplant (I-C) or BAS (IIa-C) a Iloprost IV and beraprost are not FDA approved. BAS: balloon atrial septostomy; sgcs: soluble guanylate cyclase stimulators. Adapted from: Galiè N et al. J Am Coll Cardiol. 2013;62:D60-D72. + Consider eligibility for lung transplant

30 Changes in PAH Trials Over Time Given the changes in PAH treatment, short-term assessment of 6MWD may not be the best PAH trial endpoint in Changes in PAH Tx and clinical trials 2014 Epoprostenol More tx options Epoprostenol Treprostinil Iloprost Bosentan Ambrisentan Sildenafil Tadalafil High mortality in first months 12 PAH expert centers FC III and IV No background tx Often incident pts US and EU only 6MWD at wk Changes in outcomes Expanded access to care Different trial participants Same trial endpoint? Some pts remain alive on tx for years 60+ US centers and widespread tx in community FC II-III Background tx common Often prevalent pts Global trial enrollment? 6MWD at wk Adapted from: McLaughlin VV. Chest. 2012;142:

31 Evolution From Exercise Capacity to Morbidity and Mortality RCTs MWD Trials Study 351 BREATHE-1 EARLY ARIES-1 ARIES-2 SUPER-1 Simonneau et al (2002) STEP PHIRST PACES AIR Morbidity and Mortality Trials SERAPHIN GRIPHON AMBITION N = 32 N = 213 N = 185 N = 202 N = 192 N = 277 N = 470 N = 67 N = 405 N = 267 N = 203 a N = 742 N = 1,150 N = 545 c Weeks a Estimated mean study drug exposure. b Estimated median study drug exposure. c Estimated target enrollment. RCT: randomized controlled trial. 1. Channick RN et al. Lancet. 2001;358: Rubin LJ et al. N Engl J Med. 2002;346: Galiè N et al. Lancet. 2008;371: Galiè N et al. Circulation. 2008;117: Galiè N et al. N Engl J Med. 2005;353: Simonneau G et al. Am J Respir Crit Care Med. 2002;165: McLaughlin VV et al. Am J Respir Crit Care Med. 2006;174: Galiè N et al. Circulation. 2009;119: Simonneau G et al. Ann Intern Med. 2008;149: Olschewski H et al. N Engl J Med. 2002;347: Pulido T et al. N Engl J Med. 2013;369: GRIPHON and AMBITION study designs available at: a b Investigational trials

32 Summary of Clinical Trials in PAH Trial Summary of Findings SERAPHIN 1 Macitentan (both 3-mg and 10-mg doses) significantly reduced risk of death due to PAH or hospitalization for PAH vs placebo Macitentan (10-mg dose only) significantly reduced no. of PAH-related hospitalizations and inpatient days/year vs placebo PATENT-1 2 Baseline functional and hemodynamic parameters were impaired in pretreated and tx-naïve pts enrolled in study; riociguat increased no. of pts reaching predetermined tx goals (6MWD, cardiac index, SvO 2, FC) PATENT-2 3 Long-term tx with riociguat: well tolerated and showed sustained, clinically relevant benefits in 6MWD and FC when used as a monotherapy or in combination with concomitant PAH therapies PATENT At 12 wks, addition of riociguat or placebo to sildenafil resulted in similar PLUS 4 changes in BP Combination of sildenafil + riociguat: associated with high rates of discontinuation due to hypotension in long-term extension phase; no evidence of favorable clinical effect observed ATS: American Thoracic Society; SvO 2 : mixed venous oxygen saturation. 1. Pulido T et al. N Engl J Med. 2013; 369: Ghofrani HA et al. N Engl J Med. 2013; 369: Rubin LJ et al. Chest. 2013;144(4_MeetingAbstracts):1024A. 4. Galiè N et al. Am J Respir Crit Care Med. 187;2013:A3530.

33 Longitudinal Evaluation of the PAH Patient Clinical course Stable No in symptoms and/or decompensation No evidence of RH failure WHO-FC I/II 6MWD >400 m RV size/function normal RAP normal; CI normal BNP near normal, stable, or decreasing Oral therapy FC: functional class; RH: right heart. Adapted from: McLaughlin VV et al. J Am Coll Cardiol. 2009;53: Unstable in symptoms and/or decompensation Signs of RH failure WHO-FC IV 6MWD <300 m RV enlargement/dysfunction RAP high; CI low BNP elevated or increasing IV prostacyclin and/or combination treatment Evaluation frequency Every 3-6 months Every 1-3 months FC assessment Every clinic visit Every clinic visit 6MWD Every clinic visit Every clinic visit Echocardiogram Every 12 months or center dependent Every 6-12 mo or center dependent BNP Center dependent Center dependent RHC Clinical deterioration and center dependent Every 6-12 months or clinical deterioration

34 Important Prognostic Variables French Registry 1 Functional class 6MWD RAP CI Age Gender Etiology REVEAL Registry 2 Functional class 6MWD PVR, RAP Vitals BNP Pericardial effusion DLCO Age Gender Etiology 1. Humbert M et al. Circulation. 2010;122: Benza RL et al. Circulation. 2010;122:

35 What Are the Goals of Therapy for PAH Today? 1) WHO-FC I or II symptoms 2) 6MWD > meters 3) Cardiac index 2.5 L/min/m 2 4) Normal or near normal RV function on imaging (echocardiography, MRI) 5) Normal or near normal BNP or N-terminal probnp 6) CPET peak VO 2 >15 ml/min/kg, EqCO 2 <45 L/min/L/min Patients who achieve these goals seem to have a better prognosis than those who do not A more aggressive approach to goal-oriented therapy may help improve survival further CPET: cardiopulmonary exercise testing; EqCO 2 : ventilatory equivalent for carbon dioxide. McLaughlin VV et al. J Am Coll Cardiol. 2013;62:D73-D81.

36 Relationship Between Local Care and PH Center: A Collaborative Approach Local care Local care Local care Local care PH center Local care Create new avenues of communication to Confirm diagnosis Initiate treatment Change or intensify therapy Manage side effects Provide acute hospital care Manage over long-term Enhance awareness of and access to clinical trials Access and timing of lung transplantation Involvement with treatment is commensurate with ability, resources, and distance from PAH center

37 Summary Determine disease severity Select appropriate treatment (based on risk) Follow up appropriately (based on risk) Escalate therapy/manage side effects (if needed) Long-term management of patient Collaborate with PH center

38 Presentation 3 Implementation of Best Practices in the Goal-Oriented Care of Patients With Pulmonary Hypertension: A Case-Based Discussion

39 D.F.: A 37-Year-Old, Previously Healthy Woman Personal Medical History Two children; delivered second child 14 months previously IBS: diet-controlled Limited exercise tolerance since delivery, attributed to weight gain Experienced dyspnea 5 months ago while playing with older child; syncope while walking up an incline Chief Complaints Currently has dyspnea with IFOS, walks slowly in store Exertional light-headedness; atypical chest pain; occasional palpitations LE edema Additional History Meds: None Allergies: Contrast Family history: Persistent PH in a paternal aunt, CAD, diabetes, HT Social history: Rare ETOH, o/w unremarkable IFOS: ifosfamide; LE: lower extremity.

40 D.F.: Physical Exam HR: 90 bpm, BP 130/68 mmhg, Wt 190 lb, Ht 5'4" JVP: 15 cm, reduced carotid upstrokes Clear lungs Palpable RV heave, RRR, normal S, loud P 2, III/VI, TR murmur 2+ LE edema bpm: beats per minute; HR: heart rate; JVP: jugular venous pressure; RRR: regular rate and rhythm.

41 D.F.: Abnormal ECG Normal sinus rhythm; incomplete right bundle branch block; prolonged QT

42 D.F.: Laboratory Results ANA-negative Echo: normal LV function, RAE, RVE, RVSP 60 mmhg, TEE no shunt V/Q scan: normal PFTs: normal volumes and flows, DLCO 81% 6MWD: 222 meters 99%-96% PFTs: pulmonary function tests; TEE: transesophageal echocardiogram.

43 D.F.: Right Heart Catheterization Results January 2007 Baseline Nitric Oxide 20 ppm RAP, mmhg PAP, mmhg 93/40 (mean=63) 93/46 (mean=64) LVEDP, mmhg 10 Oxygen saturation, % Pulmonary artery Femoral artery Cardiac output/cardiac index, L/min Fick / /1.52 PVR (Wood units) Fick

44 D.F.: Initial Management Admitted following catheterization IV diuresis IV epoprostenol initiation

45 D.F.: Return Visit 4 Months Later Patient Condition Significantly improved No limitations Functional Class I Medications Epoprostenol 30 ng/kg/min Warfarin Furosemide 20 mg KCl 10 meq once daily Physical Exam HR 80 bpm, BP 103/59 mmhg, Wt lb JVP 6 cm, carotid upstrokes normal Clear lungs Palpable RV heave, normal S, loud P2, II/VI TR murmur No LE edema 6MWD 486 meters: 99%-97% 222 meters: 99%-96% (January, 2007)

46 Questions and Cases: Interactive Discussion

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