PHPulmonary 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.

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•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?

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

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•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

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•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

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•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%

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•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

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•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?

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•Treatment – Medications▫Prostanoids – epoprostenol, treprostinil,

and iloprost▫ERA’s (endothelin receptor antagonists) –

bosentan and ambrisentan▫Phosphodiesterase-5 (PDE-5) inhibitors -

sildenafil

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•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)

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•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

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•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

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•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

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•Treatment by Classification▫I – monitor▫II – oral sildenafil (Revatio)▫III – oral sildenafil or bosentan (Tracleer)

and inhaled or intravenous prostanoids ▫IV – intravenous prostanoids

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•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

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•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

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•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

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•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