Jefferson Heart Institute 925 Chestnut Street

Referring Physician Name of physician Office Address Pride Communication More referrals

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Reason for the visit (a.k.a., chief complaint)

Reason for the visit Pulmonary hypertension evaluation Elevated pulmonary artery pressure by echocardiogram Elevated pulmonary artery pressure by right heart catheterization

History of Present Illness W.H.O. Functional Class W.H.O. Group Drugs trialed and response to therapy Relevant family history Relevant testing

Symptoms of PH DyspneaFatigue SyncopeEdema DizzinessChest Pain Non-specific nature of complaint can lead to: Confusion with other conditions Delayed diagnosis Gaine et al. The Lancet, ; 719

W.H.O. Functional Classification Class I: Patients with PH but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain or near syncope. Class II: Patients with PH resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope. Class III: Patients with PH resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope. Class IV: Patients with PH with inability to carry out any physical activity without symptoms. These patients manifest signs of right heart failure. They are comfortable at rest. Dyspnea and/or fatigue may even be present at rest. Discomfort is increased by any physical activity. (Syncope)

W.H.O. Classification Pulmonary arterial hypertension (PAH) 1.1 Idiopathic 1.2 Heritable BMPR ALK1, endoglin (with or without hereditary hemorrhagic telangiectasia) Unknown 1.3 Drug- and toxin-induced 1.4 Associated with Connective tissue diseases HIV Portal hypertension Congenital Heart Diseases Schistosomiasis Chronic hemolytic anemia 1.4 Associated with significant venous or capillary involvement 1.5 Persistent pulmonary hypertension of the newborn 1’. Pulmonary veno-occlusive disease (PVOD) and/or pulmonary capillary hemangiomatosis (PCH)

2. Pulmonary hypertension owing to left heart disease 2.1 Systolic dysfunction 2.2 Diastolic dysfunction 2.3 Valvular disease 3. Pulmonary hypertension owing to lung diseases and/or hypoxemia 3.1 Chronic obstructive pulmonary disease 3.2 Interstitial lung disease 3.3 Other pulmonary diseases with mixed restrictive and obstructive pattern 3.4 Sleep disordered breathing 3.5 Alveolar hypoventilation disorders 3.6 Chronic exposure to high altitude 3.7 Developmental abnormalities 4. Chronic thromboembolic pulmonary hypertension (CTEPH) 5. Pulmonary hypertension with unclear multifactorial mechanisms 5.1 Hematologic disorders: myeloproliferative disorders, splenectomy 5.2 Systemic disorders: sarcoidosis, Langerhans cell histiocytosis: lymphangioleiomymatosis, 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 W.H.O. Classification

Past Medical History W.H.O. Group 1 Heritable Collagen vascular disease HIV Portal hypertension Anorexigenic agents Hemoglobinopathies

Past Medical History W.H.O. Group II Left heart disease W.H.O. Group III Lung diseases and/or hypoxemia W.H.O. Group IV Chronic thromboembolic PH W.H.O. Group V Unclear multifactorial mechanisms

Heritable pulmonary arterial hypertension Dresdale, 1953 reported family NIH Registry, 1987:6% with one or more affected family members Autosomal dominance Fetal wasting Genetic anticipation Incomplete penetrance

Idiopathic PAH - Epidemiology Female Young to middle age NIH Registry, 1991

Idiopathic PAH - Epidemiology

Shear stress from increased pulmonary blood flow Increased pulmonary artery pressures Majority of unrepaired truncus arteriosus develop PH Large VSD, 50% develop PH ASD, 10% develop PH Eisenmenger’s syndrome Medical or surgical therapy effective Congenital Heart Disease Epidemiology

Connective Tissue Diseases Epidemiology -Limited systemic sclerosis o SLE, MCTD, RA, Sjogren’s

HIV Epidemiology 0.5% prevalence– no decline since HAART Occurrence depends upon length of infection, not CD4 count or prior opportunistic infections

Portopulmonary Hypertension Epidemiology  2-6% prevalence in cirrhotics, higher in liver transplant candidates (8%)  Risk increases with duration of portal hypertension - High cardiac flow states and LV diastolic dysfunction complicate PH

Pulmonary Hemodynamic Scenarios in the Setting of Portal Hypertension TypeMPAPPAOPCOPVRTPG I. Hyperdynamic, high flow state↑n↑↓n II. Increased pulmonary venous vol.↑↑↑↓n III. Portopulmonary hypertension Pulmonary vascular obstruction; normal volume↑↓↑↑↑ Pulmonary vascular obstruction; ↑↑↑↑↑ excess volume M Krowka. Medscape Cardiology 2006

Associated Drugs and Toxins Epidemiology Definite: Appetite suppressant drugs (anorexigens) Fenfluramine and dexfenfluramine Aminorex Toxic Rapeseed Oil Likely: L-tryptophan Methamphetamine Cocaine

Hemoglobinopathies Epidemiology Sickle cell disease PH 10-30% Yearly echocardiogram 50% - 2 year mortality with PH Thromboembolic disease Restrictive pulmonary disease Left heart disease Homozygous beta-thalassemia Hereditary spherocytosis

Chronic ThromboEmbolic Pulmonary Hypertension (CTEPH) Cumulative Incidence Historically considered rare: % of acute, non-fatal pulmonary embolism: Fedullo PF et al. N Engl J Med months1.0% 12 months3.1% 24 months3.8% Pengo V, et al NEJM 2004

Past Surgical History Lung resection Thyroidectomy Splenectomy CABG Cardiac valve repair/replacement Repair of congenital heart defect

Family History Pulmonary hypertension CHF/sudden cardiac death at a young age Sarcoid Connective tissue disorders Clotting disorders – DVT, PE, CVA

Social History Tobacco ETOH Recreational Drugsmethamphetamines Cocaine IVDU Prescription diet pills Bush tea Pets (birds) Social Network – “Friends and Family”, not “Verizon”

Allergies /Adverse Reactions Beware of hypotensive response to vasodilators CCBs Nitrates Sildenafil

Medications Nitrates Calcium channel blockers Warfarin Beta blockers Oxygen Diuretics Digoxin

Medications ERAs (Bosentan) Hepatotoxins – monitor LFTs, Hgb Glyburide may increase risk of hepatoxicity Cyclosporine Ketoconazole Statins Warfarin (Ambrisentan*)

Medications PDE V Inhibitors Sildenafil (Revatio) Tadalafil (Adcirca)

Medications Prostacyclins Parenteral Route of administration Inhaled ng/kg/minute mcg/dose ml/24 hrs frequency

Inhaled Iloprost (Ventavis)

Review of Systems Neurologic:Headache, prior TIA/CVA, lightheadedness or syncope HEENT:Epistaxis, dry eyes, dry mouth, oral ulcers. CV:Anginal quality chest pain, orthopnea, PND, palpitations, peripheral edema Rheumatologic: Joint pain or swelling, Raynaud’s phenomenon GU/Gyn:Hematuria, Gravida : Para (spontaneous abortions) GI:Liver disease, dysphagia, heartburn, hematemesis, varices or hemorrhoids, ascites

Review of Systems Hematologic/Lymphatic:DVT, PE, CVA, TIA (hypercoaguable state) swollen lymph glands (Sjogren’s, sarcoid) Dermatologic: Rashes, skin lesions, painful ulcers on fingertips. Psychiatric:Confusion, memory loss, depression, anxiety HIV risk factors:Blood transfusions, known contacts, HIV serum test (date) Sleep:Snoring, witnessed apneas, restless sleeper, awakens unrefreshed, daytime hypersomnolence

Physical Examination Jugular venous distention at 45 o Widened split S2 Loud pulmonic valve closure (P 2 ) TR murmur Right ventricular heave, PA pulsation Enlarged, pulsatile liver – hepatojugular reflux Peripheral edema, ascites Skin/Mouth:Telangiectasias, spider hemangiomas *Infusion catheters and site problems

Barst, R. J. et al. J Am Coll Cardiol 2004 Guidelines for evaluating pulmonary hypertension

Laboratory evaluation LV RV LA RA IVS

Impression 1. (Suspected) Pulmonary (arterial) hypertension (with/without) right ventricular dysfunction due to __________: W.H.O. Functional Class Other conditions contributing to cardio-respiratory complaints

Recommendations and Plan Defend you reason for your assessment Defend your reason for testing ordered Defend your reason for medical therapy One paragraph per “Impression #” Write so that the referring doctor will understand Write so you may use this note as a reminder for what you wish to do at next visit. Jefferson Heart Institute – follow-up

Tools for Patients Cardiology nurses for RHC teaching PH literature tearouts Teaching aides – RHC booklets Parenteral infusion CDs Inhalation device models

Tools for Fellows/Faculty Pulmonary order sheets –Sleep lab –Pulmonary function lab PH Reading List

Projects ISWT - PAH –retrospective: ongoing –prospective: needs design – other groups, e.g. pre-op assessment – needs collaboration with Surgery CT evaluation of PAH and RVD in subjects with PH W.H.O. Group 1 – collaboration with Radiology: ongoing Echocardiographic evaluation of RV function in PH subsets – collaboration with cardiology, ongoing. PROSPECT Registry

Thank you!