Committee on Social Security CV Disability Criteria Disability in Patients with Pulmonary Hypertension R Ronald ld J. J Oudiz, O di MD representing ep ese t g Pulmonary u o a y Hypertension ype te s o Association ssoc at o

PAH Classification: 2010 „ „ „

„

IPAH HPAH Associated with: C Connective i Tissue Ti Disease Di HIV Drugs and Toxins Portal Hypertension Congenital Heart Disease Chronic Hemolytic Anemia Schistosomiasis Associated with venous or capillary involvement (PVOD, PCH)

PH – Not PAH „

„

Pulmonary venous hypertension systolic y or diastolic dysfunction, y , or valvular disease PH associated with hypoxemia/parenchymal yp /p y lung disease COPD, ILD, sleep disordered breathing, alveolar l l hypoventilation h til ti disorders, di d altitude

„

Ch i thromboembolic Chronic th b b li PH

„

Miscellaneous (unclear, multifactorial mechanisms)

Pulmonary Hypertension: Diagnostic classification (Dana Point, CA 2008) 1. Pulmonary arterial hypertension (PAH) 1.1. Idiopathic PAH (IPAH) 1.2. Heritable 1.2.1. BMPR2 1.2.2. ALK1,, endoglin e dog (with ( or o without ou hereditary hemorrhagic telangiectasia) 1.2.3. Unknown 1.3. Drug- and toxin-induced 1.4. Associated with 1.4.1. Connective tissue diseases 1.4.2. HIV infection 1.4.3. Portal hypertension 1 4 4 Congenital heart diseases 1.4.4. 1.4.5. Schistosomiasis 1.4.6. Chronic hemolytic anemia 1.5 Persistent pulmonary hypertension of the newborn 2. Pulmonary hypertension owing to left heart disease 2.1. Systolic dysfunction 2.2. Diastolic dysfunction 2.3. Valvular disease

3. PH due to Lung Diseases and/or Hypoxemia 3.1. Chronic obstructive pulmonary disease 3.2. Interstitial lung disease 3.3. Other pulmonary diseases with mixed t i ti and d obstructive b t ti pattern tt restrictive 3.4. Sleep-disordered breathing 3.5. Alveolar hypoventilation disorders p to high g altitude 3.6. Chronic exposure 3.7. Developmental abnormalities 4. Chronic thromboembolic pulmonary hypertension (CTEPH) 5.

Pulmonary hypertension with unclear multifactorial mechanisms 5.1. Hematologic disorders: myeloproliferative disorders splenectomy disorders, 5.2. Systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis: lymphangioleiomyomatosis, neurofibromatosis, vasculitis 5.3. Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders 5.4. Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis

Pathophysiology: Disease Progression

Pre-symptomatic/ Compensated

CO

Symptomatic/ Decompensating

Declining/ Decompensated

Symptom Threshold

PAP PVR

Right Ventricular Dysfunction y

Time

Symptoms „ „

„ „ „ „

Fatigue Shortness of breath Chest pain Dizziness Palpitations p Syncope/fainting

„ „

„ „ „ „

Edema/swelling Increased abdominal girth Hemoptysis Jaundice Abdominal p pain Hoarseness

Prognosis g of IPAH Advanced lung cancer 6 months th

WHO Class Cl IV IPAH Advanced colorectal cancer Advanced breast cancer

2.6 years

WHO Class III IPAH

4.9 years

WHO Class I - II IPAH Ischemic cardiomyopathy 0

D'Alonzo, Barst et al. Ann Intern Med 1991 Kato et al. Cancer 2001 Felker et al. N Engl J Med 2000

1

2

3 4 5 Survival (years)

6

7

Survival in PAH 1.0 Congenital heart disease

0.9 0.8 0.7

Portopulmonary

0.6 6 Percent 0 survival 0.5

IPAH

0.4 0.3

Connective tissue disease

0.2

HIV

0.1 0

0

1

2

3 Y Years

McLaughlin VV et al. CHEST 2004

4

5

Pulmonary Hypertension (PH) : common in Left-Sided Heart Disease (LHD)

• Up to 65% of patients with LHD have PH • PH is a predictor of mortality in LHD, such as: ¾ p post myocardial y infarction ¾ idiopathic dilated cardiomyopathy ¾ post cardiac transplantation

Johnson LW, et al. Pulmonary hypertension in isolated aortic stenosis. Hemodynamic correlations and follow-up. J Thorac Cardiovasc Surg 1988;95:603-607. Faggiano P, et al. Pulmonary artery hypertension in adult patients with symptomatic valvular aortic stenosis. Am J Cardiol 2000;85:204-8.

After M.I., mortality increases as PAP rises

Moller JE, et al. Prognostic importance of secondary pulmonary hypertension after acute myocardial infarction. Am J Cardiol 2005;96:199-203.

Diagnostic Tests „ „ „ „

ECG CXR Echocardiogram Ventilation perfusion lung scan – Pulmonary angiogram

„ „

„

Chest CT scan Pulmonary function testing, oximetry [ l [sleep study] t d ]

„

„

RIGHT HEART CATHETERIZATON S l i l testing Serological t ti – HIV – Connective tissue diseases

„

Liver function and hepatitis profile

Diagnostic Tests „ „ „ „

ECG CXR Echocardiogram Ventilation perfusion lung scan – Pulmonary angiogram

„ „

„

Chest CT scan Pulmonary function testing, oximetry [ l [sleep study] t d ]

„

„

RIGHT HEART CATHETERIZATON S l i l testing Serological t ti – HIV – Connective tissue diseases

„

Liver function and hepatitis profile

Echocardiography in PH ● Usually y first to “detect” the p presence of PH ● Useful for excluding CHD, evaluating left-sided function and anatomy y ● Several echo parameters are prognostic

-

RV function (TEI index, TAPSE), effusion

● Simple calculation for estimating RV (and thus PA systolic) pressure): RVP-RAP = 4V2

-

RAP is estimated; V is the TR velocity in m/sec

Echocardiography in PH Problems

● 15% of p patients will not display p y TR jets j

-

Saline contrast can enhance TR jet

● Not all congenital g heart lesions will be obvious ● Poor method to measure LH filling pressure or cardiac output (CO) ● Small errors in TR velocity y ((TRV)) measurements can significantly alter results ● TRV can underestimate RVSP or overestimate RVSP Stephen B, et al. Chest. 1999;116:73-77.

Diagnostic Tests „ „ „ „

ECG CXR Echocardiogram Ventilation perfusion lung scan – Pulmonary angiogram

„ „

„

Chest CT scan Pulmonary function testing, oximetry [ l [sleep study] t d ]

„

„

RIGHT HEART CATHETERIZATON S l i l testing Serological t ti – HIV – Connective tissue diseases

„

Liver function and hepatitis profile All are essential tests for PH patients

PH Diagnostic Algorithm History, Symptoms, Signs Suggestive of PH

Consider Common Causes of PH

Lung Diseases and/or Hypoxia yp

Left Heart Disease

No

Adapted from Galie N, et al. Eur Heart J 2009

PAH Diagnostic Algorithm mPAP ≥25 mmHg PCWP ≤15 mmHg H

P f Perform RHC

Increased PVR

No

Yes

Search for other causes Specific diagnostic tests for PAH causes

Adapted from Galie N, et al. Eur Heart J 2009

Once a diagnosis of PH is made a functional made, evaluation is essential „

NYHA/WHO class

Assessment of PH Severity: WHO Functional Classification (NYHA Modification for PH) WHO Class

Description

I

No limitation of usual activities

II

Mild limitation of usual activities No discomfort at rest

III

Normal physical activity causes increased dyspnea, fatigue, chest pain, or presyncope Marked limitation of physical activity No discomfort at rest

IV

Less than ordinary activity causes increased dyspnea, fatigue, chest pain, or presyncope P ti t unable Patient bl to t perform f any physical h i l activity ti it att restt and d may have signs of right ventricular failure Dyspnea and/or fatigue and/or syncope/near-syncope may be present at rest, and symptoms are increased by almost any physical activity

Rich S. WHO 1998

Once a diagnosis of PH is made, a functional evaluation is essential „ „

NYHA/WHO class E Exercise i testing t ti – 6MW distance – Cardiopulmonary exercise testing (CPET) Both are safe, both are prognostic, both correlate with functional class and with QoL

Goals of PAH Treatment • Improve Overall Quality of Life • Improve Survival

PAH Approved Therapy: 2010 „

„

„

Prostacyclin li analogues l Flolan™ Flolan ™ - IV (epoprostenol) Remodulin™ Remodulin ™ – IV, IV subcutaneous (treprostinil) Tyvaso™ Tyvaso ™ – inhaled (treprostinil) Ventavis™ Ventavis ™ – inhaled (iloprost) Endothelin receptor antagonists Tracleer™ Tracleer ™ - oral ( bosentan) Letairis™ Letairis ™ - oral (ambrisentan) Phosphodiesterase 5 inhibitors Revatio™ Revatio ™ - oral ( sildenafil) Adcirca™ Adcirca ™ - oral (tadalafil)

Choice of Initial PAH Therapy „

Dependent on many factors – Disease severity – Approval status – Route of administration – SideSide-effect profile – Patient preference – Physician experience, literature, clinical judgment

Barst RJ, et al. J ACC 2009

Administration of Chronic IV E Epoprostenol t l (Flolan™) (Fl l ™) Rapidly (t1/2 = 3 min) hydrolyzed in circulation to 6-keto-PGF1α No oral preparation Must be given via continuous intravenous infusion to achieve sustained pharmacologic effect

• Catheter maintenance • Pump setup/maintenance

Daily prostanoid preparation

IV Epoprostenol: T l Tolerability bilit and d Safety S f t „Jaw

pain

„Infection,

„Headache „Diarrhea,

Sepsis

„Thromboemboli

Nausea

„Systemic

events

hypotension

„Rash

„Increased

„Leg

„Coronary

steal

„Impotence p

„Rebound

PH ((interrupt p infusion))

„Weight

„Thrombocytopenia

and foot pain loss

ascites

Side Effects „

„

„

„

PDE 5 inhibitors: headache, nosebleeds, nasal congestion, conjunctival injection, lightheadedness ETRA-, edema, nasal congestion, headache, acute hepatotoxicity Inhaled prostacyclin analogues: cough, nausea, headache, flushing, lightheadedness, time consuming Intravenous/subcutaneous prostacyclin analogues: l nausea, vomiting, iti diarrhea, di h anorexia, weight loss, flushing and rash, faintness, time consuming, leg pain, infection, sepsis, thromboembolic events, e.g. stroke, pulmonary emboli

Evaluation of Response p to Therapy „

„

„ „ „

Physical exam – JVD, murmurs, edema, ascites, liver enlargement, hypotension (systolic BP380 m