Pulmonary Hypertension PH Pulmonary Hypertension

PH Pulmonary hypertension is an abnormal elevation of the pulmonary artery pressure (PAP) and the pulmonary vascular resistance (PVR) resulting in right ventricular (RV) failure and premature death.

PH PH used to be recognized as a disease with a grim prognosis. Over the last decade, new medications have been developed to treat PH. These medications have improved both the quantity and quality of life for patients with PH. Since we can now treat PH, we need to be more aware of pursuing it as a diagnosis.

PH What is PH? What are the most common symptoms? mPAP > 25 mmHg at rest mPAP > 30 mmHg with activity What are the most common symptoms? Worsening SOB Chest pain Fatigue Palpitations Lower extremity edema Syncope

PH WHO classification Group I- PAH Group II- PVH, PH secondary to LV failure Group III- PH associated with lung disease or hypoxia Group IV- PH secondary to chronic thromboembolic disease Group V- miscellaneous - HIV infection, drug exposure

PH Group I - PAH Replaces primary pulmonary hypertension No known underlying risk factors Usually seen in women of childbearing age Rare - 2 to 3 per million per year Genetic predisposition

PH Facts: Group II – PVH – most common, PCWP >15 mmHg Group III - lung disease COPD – mild PH seen in up to 50% of pts OSA – usually associated with mild PH OHS – more commonly seen with cor pulmonale Group IV - chronic PTED – up to 4%

PH Pathophysiology Pulmonary endothelial cell dysfunction or injury causing vascular changes Intimal proliferation Hypertrophy Proliferation of smooth muscle cells Vasoconstriction In situ thrombosis

PH Making the diagnosis High index of suspicion PE – early, Nl; increased P2, TR, heptojugular reflux CXR, CT chest – enlarged PA’s EKG – V1, tall R wave and short S wave (RV hypertrophy); II, p-pulmonale (RAE) Transthoracic ECHO – evaluate LV function, estimate RVSP and PAP’S Right heart catheterization – measure PAP’s and PCWP

PH Further Evaluation Lab – ANA, RF, HIV, CBC, LFT’s, TFT’s PFT’s – OLD or ILD; decrease in DLCO Overnight oximetry – desaturation is seen in 70% of pts PSG V/Q scan, CT chest, pulmonary angiography

PH Treatment – General measures O2 – keep sats > 90% Avoid vasoconstricting decongestants, B blockers, stimulants and anorexigens Do low level aerobic exercise Follow a low sodium (<2400 mg) diet Avoid pregnancy Anticoagulation Diuretics Digoxin?

PH Treatment – Medications Prostanoids – epoprostenol, treprostinil, and iloprost ERA’s (endothelin receptor antagonists) – bosentan and ambrisentan Phosphodiesterase-5 (PDE-5) inhibitors - sildenafil

PH Prostanoids – prostacyclin analogues Prostacyclin is a potent vasodilator and antiplatelet agent Deficient in pts with PH Improve symptoms Improve hemodynamics Overdosage causes hypotension and hyperdynamic state with high-output cardiac failure

PH Prostanoids cont. Epoprostenol – only drug with proven survival benefit; 6 minute half-life Must be kept cold during storage and administration Continuous IV infusion thru tunneled catheter Treprostinil – not shown to improve survival; 3 hour half life Continuous SQ infusion Iloprost – inhaled route of administration; 6-9 times a day (Q2 hours while awake)

PH ERA’s – improve sx and functional class; antagonizes vasoconstriction and smooth muscle proliferation Bosentan (Tracleer) – oral, BID LFT’s Anemia Fluid retention HA’s Ambrisentan (Letairis) – oral, QD

PH PDE-5’s – improve sx and functional class; augments vasodilatory effects of nitric oxide Sildenafil (Revatio) – oral, TID HA’s Flu-like sx Flushing Epistaxis

PH NYHA classification of functional status of pts with PH I – no limitations in nl physical activity II – mild limitation, no sx at rest, worsening sx with exertion III – marked limitation, no sx at rest, worsening sx with light activity IV – sx at rest, unable to do any activity, signs of RV failure at rest

PH Treatment by Classification I – monitor II – oral sildenafil (Revatio) III – oral sildenafil or bosentan (Tracleer) and inhaled or intravenous prostanoids IV – intravenous prostanoids

PH Goals of Treatment Improvement to class I or II Improvement in the 6 MWDT to 380 m or better Max SBP with exercise of 120 mm Hg or greater Decrease in BNP to < 180 pg/ml

PH Other treatments Surgery Atrial septostomy – decrease right-sided pressures, may worsen hypoxia Lung transplant – curative, post op median survival 5 years Pulmonary thromboendarterectomy – curative for PH from chronic PTED, tx of choice in appropriate candidates

PH Upcoming therapies Treprostinil – infusion and inhaled available now, working on oral formulation Sitaxsentan – approved in Europe, application is pending with FDA Tadalafil (Cialis) – longer half-life and greater selectivity and potency than sildenafil; in trials now

PH Prognosis 1980s – grim, medial survival of 2.8 years from time of diagnosis in untreated pts Current – newer medications have greatly improved the outlook for pts with PH Poor prognostic indicators – low 6 MWDT; pericardial effusion, RV dysfunction, and RAE on ECHO; increased mRAP (the most powerful hemodynamic predictor) and decreased cardiac index on RHC; and elevated BNP