Pulmonary Hypertension¶

Pakinam Mekki

Background¶

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

Evaluation¶

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

Diagnosis¶

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

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

Management¶

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.

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