PH

1. PH Pulmonary Hypertension

2. 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.

3. 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.

4. PH • What is PH? • 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

5. 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

6. 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

7. 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%

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

9. 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

10. 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

11. 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?

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

13. 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

14. 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)

15. 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

16. 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

17. 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

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

19. 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

20. 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

21. 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

22. 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