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Pulmonary Hypertension

Pakinam Mekki


  • Symptoms: exertional dyspnea, presyncope, fatigue, exertional chest pain, edema; syncope is a very concerning symptom

  • Physical exam: JVD, widely split S2, holosystolic tricuspid regurgitation murmur, pulmonary diastolic murmur (Graham Steel), hepatomegaly, ascites, edema

  • Main chief complaint for admission: volume overload secondary to RV failure and/or hypoxia

  • WHO Groups and Causes: 

    • Group 1: Pulmonary arterial hypertension (PAH): obliteration of blood vessels in the lung 

      • Idiopathic, heritable 

      • Drugs/toxins (methamphetamine) 

      • Associated with CTD, HIV, portal HTN, congenital heart disease, schistosomiasis 

      • Pulmonary veno-occlusive disease (PVOD), pulmonary capillary hemangiomatosis 

    • Group 2: Left heart disease: back pressure and passive congestion 

      • HFrEF, HFpEF, valvular disease, LA stiffness 
    • Group 3: Chronic lung disease: chronic hypoxemia, chronic pulmonary vasoconstriction 

      • COPD, ILD, OSA, chronic high-altitude, developmental lung disorders 
    • Group 4: Chronic thromboembolic pulmonary hypertension (CTEPH) 

    • Group 5: Multifactorial

      • Hematologic disorders, chronic hemolytic anemia, sarcoidosis, pulmonary Langerhans cell histiocytosis, fibrosing mediastinitis, metabolic disorders 


  • Labs: BNP, CMP, HIV, rheumatologic serologies (ANA w/reflex ENA, RF/CCP, ANCA, Scl-70, Ro/La), blood gas (↑ A-a gradient, ↓ PaO2, ↓ PCO2; rule out hypercapnia from alveolar hypoventilation)

  • EKG: right atrial enlargement (peaked P waves), RBBB, RV hypertrophy

  • PFT: rule out obstructive and restrictive disease; PAH usually has mild restriction with mild DLCO impairment

  • Sleep studies: evaluation for chronic hypoxemia from OSA; if low suspicion for OSA/CSA, can start with overnight oximetry

  • 6-min walk test: important for prognostication, baseline exertional capacity, and to evaluate treatment response

  • Imaging

    • TTE with bubble: RVSP >35-40 is concerning for PH. TTE can show evidence of RV dilation and dysfunction (TAPSE <1.6cm), RRA dilation, septal flattening, pericardial effusion. It should evaluate for classification by quantifying L heart disease and shunt.
    • CT angiogram: evaluates for acute and chronic thrombi using contrast media; consider V/Q scan in setting of AKI and advanced CKD (discuss risk and benefits)
    • V/Q scan: better performance in evaluating small chronic embolism in contrast to CTA
    • High res CT: evaluates parenchymal lung disease, dilation of the pulmonary artery, RV size


  • May be suspected from clinical presentation and indirect surrogate markers of elevated PAP

  • A right heart catheterization is the gold standard for PH diagnosis and will differentiate between precapillary and postcapillary PH

    • Nitric oxide challenge during RHC assesses for drug response
    • Fluid challenge with 500ml LR during RHC assesses left heart compliance
Definitions Characteristics Causes
Pre-capillary PH

mPAP > 20 mmHg

PAWP ≤ 15 mmHg

PVR ≥ 3 WU

Groups 1, 3, 4, 5
Post-capillary PH

mPAP > 20 mmHg

PAWP > 15 mmHg

PVR < 3 WU

Group 2

Combined pre- and post-

capillary PH

mPAP > 20 mmHg

PAWP > 15 mmHg

PVR ≥ 3 WU

Group 2, 5


  • immunizations: yearly influenza, COVID, pneumococcal

  • Counsel to strongly avoid pregnancy

  • Identify decompensation triggers: progression of underlying disease, medication/dietary nonadherence, infection, arrhythmia, myocardial infarction/RV ischemia, shunting via PFO, pulmonary embolism

  • Treatment: aimed at preventing right heart failure, increasing vasoactive molecules (preventing further remodeling), symptom relief/quality of life, functional class (NYHA class)

    • Oxygenation goal >90%
    • Diuresis: do not be aggressive, these pts are preload dependent
  • Consult pulmonary hypertension if considering starting or changing PH medications.


  • Anticoagulation: For pts with confirmed CTEPH. Should be worked up for hypercoagulability including antiphospholipid syndrome. Pulmonary endarterectomy may be considered.

  • Oral CCB: used in pts who had a positive vasoreactive challenge on RHC

  • PAH-specific vasoactive medications (in order of escalation)

    • NOenhancers
      • PDE5-inhibitors: sildenafil, tadalafil
      • Soluble guanylate cyclase stimulant: riociguat
    • Endothelin receptor antagonists (ERAs): Bosentan, macitenatan, ambrisentan o - Prostacyclin analogs
      • Prostacyclin analogs increase cAMP-mediated pulmonary vasodilation
      • Side effects include jaw pain, flushing, arthralgias, and diarrhea
      • IV formulations are administered through a continuous pump. Never stop IV prostacyclins since even brief pauses can cause rebound vasoconstriction and death.
        • Epoprostenol: IV (Veletri) or inhaled (Flolan); half-life 4 minutes
        • Treprostinil: IV/subcutaneous/inhaled/PO; half-life 4 hours
        • Iloprost: inhaled, half-life minutes
        • Selexipag (Uptravi): PO, half-life hours
      • BMPR2-targeted therapies (eg, sotatercept) are under investigation for PAH
  • Balloon atrial septostomy: creation of a R->L shunt to offload the RV which reduces SpO2 but overall improved peripheral tissues DO2. Palliative procedure or bridge.

  • VA ECMO can be used as bridge to medical therapy or for lung transplant.

  • Lung transplantation can be considered for pts who are candidates and failing maximal medical therapy

  • Treatment escalation is based on a pt’s NYHA functional classification

    • Class I: no treatment or monotherapy
    • Class II: monotherapy or combination oral therapy
    • Class III: combination oral therapy or prostacyclin
    • Class IV: prostacyclin ± oral therapy

Poor prognostic factors

  • NYHA Functional Class III and IV

  • 6-minute walk test less than 300 meters

  • The present of AKI and/or hyponatremia

  • Low SBP (SBP < 90) when connective tissue disease or liver disease is the etiology

  • Poor hemodynamics on RHC (right atrial pressure > 20 mmHg; cardiac index less than 2)

  • TTE findings: tricuspid annular plane systolic excursion (TAPSE, marker of global RV function) < 1.8, the presence of a pericardial effusion, and severe RV dysfunction