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PA mean pressure >25 mmHg at rest

Pathobiology (NEJM 2004;35:1655)

•  Smooth muscle & endothelial cell proliferation; mutations in bone morphogenic protein receptor 2 (BMPR2) in ~50% familial & ~26% sporadic cases of IPAH (NEJM 2001;345:319)

•  Imbalance between vasoconstrictors and vasodilators

↑ vasoconstrictors: thromboxane A2 (TXA2), serotonin (5-HT), endothelin-1 (ET-1)

↓ vasodilators: prostacyclin (PGI2), nitric oxide (NO), vasoactive peptide (VIP)

•  In situ thrombosis: ↑ TXA2, 5-HT, PAI-1; ↓ PGI2, NO, VIP, tissue plasminogen activator

Clinical manifestations

•  Dyspnea, exertional syncope (hypoxia, ↓ CO), exertional chest pain (RV ischemia)

•  Symptoms of R-sided CHF (eg, peripheral edema, RUQ fullness, abdominal distention)

•  WHO class: I=asx w/ ordinary activity; II=sx w/ ord. activ.; III=sx w/ min activ.; IV=sx at rest

Physical exam

•  PHT: prominent P2, R-sided S4, RV heave, PA tap & flow murmur, PR (Graham Steell), TR

•  ± RV failure: ↑ JVP, hepatomegaly, peripheral edema

Diagnostic studies & workup (Circ 2009;119:2250)

•  IPAH yearly incidence 1–2 per million, ∴ r/o 2° causes

•  CXR and high-resolution chest CT: dilatation & pruning of pulmonary arteries, enlargement of RA and RV; r/o parenchymal lung disease

•  ECG: RAD, RBBB, RAE (“P pulmonale”), RVH (Se 55%, Sp 70%)

•  PFTs: ↓ DLco, mild restrictive pattern; r/o obstructive and restrictive lung disease

•  ABG & polysomnography: ↓ PaO2 and SaO2 (esp. w/ exertion), ↓ PaCO2, ↑ A-a gradient; r/o hypoventilation and OSA

•  TTE: ↑ RVSP (but over or under by ≥10 mmHg in 1/2 of PHT Pts; Chest 2011;139:988), flattened (“D”) septum, TR, PR; r/o LV dysfxn, MV disease and congenital heart disease

•  RHC: ↑ RA, RV, & PA pressures, nl PCWP (unless due to L-sided heart disease), ↑ transpulm gradient (PAP-PCWP >12–15, but can be nl if due to LV or valvular dis.), ↑ PVR, ↓ CO; r/o ↑ L-sided pressures shunt

•  CTA (large/med vessel), V/Q scan (small vessel to r/o CTEPH), ± pulmonary angiogram: r/o PE and chronic thromboembolic disease

•  Vasculitis labs: ANA (~40%  in PAH), RF, anti-Scl-70, anticentromere, ESR

•  LFTs & HIV: r/o portopulmonary and HIV-associated PAH

•  6-min walk test (6MWT) or cardiopulmonary exercise testing to establish fxnl capacity

Treatment (NEJM 2004;351:1425; JIM 2005;258:199; Circ 2009;119:2250)

•  Principles

   1) prevent and reverse vasoactive substance imbalance and vascular remodeling

   2) prevent RV failure: ↓ wall stress (↓ PVR, PAP, RV diam); ensure adeq. systemic DBP

•  Supportive

Oxygen: maintain SaO2 >90–92% (reduces vasoconstriction)

Diuretics: ↓ RV wall stress and relieve RHF sx; gentle b/c RV is preload dependent

Digoxin: control AF, ? counteract neg. inotropic effects CCB

Dobutamine and inhaled NO for decompensated PHT

Anticoagulation: ↓ VTE risk of RHF; ? prevention of in situ microthrombi; ? mort. benefit even if in NSR (Circ 1984;70:580; Chest 2006;130:545)

•  Vasodilators (right heart catheterization prior to initiation) acute vasoreactivity test: use inhaled NO, adenosine or prostacyclin to identify Pts likely to have a long-term response to oral CCB (vasoreactive response defined as ↓ PAP ≥10 mmHg to a level <40 mmHg with ↑ or stable CO); ~10% Pts are acute responders; no response → still candidates for other vasodilators (NEJM2004;351:1425)

•  Treat underlying causes of 2° PHT; can use vasodilators, although little evidence

•  Refractory PHT:

balloon atrial septostomy: R→L shunt causes ↑ CO, ↓ SaO2, net ↑ tissue O2 delivery

lung transplant (single or bilateral); heart-lung needed if Eisenmenger physiology

Figure 2-5 Treatment of PAH (modified from JACC 2009;54:S78)

Management of ICU patient

•  Avoid overly aggressive volume resuscitation

•  Caution with vasodilators if any L-sided dysfunction

•  May benefit from inotropes/chronotropes

•  Consider fibrinolysis if acute, refractory decompensation (eg, TPA 100 mg over 2 h)


•  Median survival after dx ~2.8 y; PAH (all etiologies): 2-y 66%, 5-y 48% (Chest 2004;126:78-S)

•  Poor prognostic factors: clinical evidence of RV failure, rapidly progressive sx, WHO (modified NYHA) class IV, 6MWT <300 m, peak VO2 <10.4 mL/kg/min, ↑ RA or RV or RV dysfxn, RA >20 or CI <2.0, ↑ BNP (Chest 2006;129:1313)

•  Lung transplant: 1-y survival 66–75%; 5-y survival 45–55% (Chest 2004;126:63-S)