1. Pulmonary HypertensionPH
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? 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

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

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