PH Pulmonary Hypertension PH Pulmonary hypertension is an

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? m. PAP > 25 mm. Hg at rest m. PAP > 30 mm. Hg 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, >15 mm. Hg ▫ Group III - lung disease PCWP 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 P 2, TR, heptojugular reflux ▫ CXR, CT chest – enlarged PA’s ▫ EKG – V 1, 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 ▫ O 2 – 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 (Q 2 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 Fluid retention

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 ▫ 1980 s – 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 m. RAP (the most powerful hemodynamic predictor) and decreased cardiac index on RHC; and elevated BNP