Download PAH

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?
 mPAP > 25 mmHg at rest
 mPAP > 30 mmHg with activity
 What are the most common symptoms?
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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
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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
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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
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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
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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
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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