Managing Pulmonary Hypertension

Documents to Request

• Echocardiogram with RV assessment (RVSP, TAPSE, RV size)
• Right heart catheterization hemodynamic data
• V/Q scan (to exclude CTEPH)
• Pulmonary function tests with DLCO
• CT chest (high-resolution for parenchymal disease)
• CT pulmonary angiography (if CTEPH suspected)
• Autoimmune serologies (ANA, ENA panel, anti-SCL-70, anti-centromere)
• HIV, hepatitis B/C serologies
• Liver function tests and liver ultrasound (portopulmonary evaluation)
• 6-minute walk distance
• BNP/NT-proBNP
• Sleep study (if OSA/hypoventilation suspected)
• Thyroid function tests

Step 1: Hemodynamic Classification by RHC

2022 ESC/ERS Hemodynamic Definitions:

Key Hemodynamic Measurements to Document:

• mPAP, PCWP (or LVEDP if PCWP unreliable)
• PVR = (mPAP − PCWP) / CO (in Wood units)
• Cardiac output (thermodilution and/or Fick)
• Cardiac index
• Mixed venous O₂ saturation (SvO₂) — < 60% indicates severely reduced CO
• Transpulmonary gradient (TPG) = mPAP − PCWP (> 12 mmHg suggests pre-capillary component)
• Diastolic pressure gradient (DPG) = diastolic PAP − PCWP (> 7 mmHg suggests pre-capillary component)

Step 2: WHO Group Classification

WHO Group Classification and Common Etiologies:

Diagnostic Algorithm (Sequential Exclusion):

1. Echo: estimate RVSP, assess LV function and valve disease → if left heart disease likely → Group 2
2. PFTs + CT chest: if significant lung disease (FEV1 < 60% or extensive ILD) → Group 3
3. V/Q scan: mismatched perfusion defects → CTEPH workup (Group 4)
4. If Groups 2–4 excluded → evaluate for Group 1 (PAH) or Group 5
5. Confirm with RHC (mandatory before initiating PAH-specific therapy)

Step 3: Risk Stratification for PAH (Group 1)

ESC/ERS Risk Assessment (low, intermediate, high mortality risk):

REVEAL 2.0 Risk Score: Validated in PAH; incorporates age, etiology, NYHA FC, vitals, 6MWD, BNP, renal function, eGFR, PVR, HR — categorizes into 1-year mortality risk zones.

Step 4: Treatment by WHO Group

Group 1 (PAH) — Targeted Therapy:

Vasoreactivity Testing (for IPAH only):

• Inhaled NO, IV epoprostenol, or IV adenosine during RHC
• Positive response: mPAP decrease ≥ 10 mmHg to ≤ 40 mmHg with maintained/improved CO
• Positive responders (~10–15% of IPAH): trial of high-dose CCB (nifedipine, diltiazem, amlodipine)

Group 2 (Left Heart Disease): Treat underlying HF/valve disease. PAH-targeted therapies are NOT indicated (harmful in Group 2).

Group 3 (Lung Disease): Treat underlying lung disease. Inhaled treprostinil approved for PH-ILD. Avoid vasodilators that worsen V/Q mismatch.

Group 4 (CTEPH):

• Pulmonary endarterectomy (PEA): surgical cure for operable CTEPH → refer to expert center
• Balloon pulmonary angioplasty (BPA): for inoperable or residual PH post-PEA
• Riociguat: approved for inoperable CTEPH or persistent PH post-PEA
• Lifelong anticoagulation (warfarin; DOACs under study)

Step 5: Monitoring and Follow-Up

Follow-Up Assessment Schedule:

Treatment Goals:

• Achieve and maintain low-risk profile (WHO FC I–II, 6MWD > 440 m, BNP < 50)
• If not at low risk at 3–6 months → escalate therapy
• Refer for lung transplant evaluation if high risk persists despite maximal therapy

Checkpoint B: Post-Draft Alignment (Mandatory)

1. Is the hemodynamic classification (pre-capillary, post-capillary, combined) correct per RHC data?
2. Is the WHO Group assignment supported by the diagnostic workup?
3. Is risk stratification documented for PAH patients using ESC/ERS criteria?
4. Is the treatment plan group-specific (not applying PAH therapy to Group 2)?
5. Are follow-up intervals and treatment escalation criteria defined?

Quality Audit

• RHC hemodynamics documented: mPAP, PCWP, PVR, CO/CI, SvO₂
• Hemodynamic classification stated (pre-capillary, IpcPH, CpcPH)
• WHO Group assigned with diagnostic evidence
• V/Q scan performed to exclude CTEPH (or absence justified)
• PFTs and CT chest reviewed for Group 3 exclusion
• Autoimmune serologies obtained for CTD-PAH screening
• 6MWD performed as baseline functional assessment
• BNP/NT-proBNP documented
• Risk stratification completed (ESC/ERS or REVEAL)
• Vasoreactivity testing performed for IPAH candidates
• Treatment matched to WHO Group
• Combination therapy initiated for Group 1 per risk level
• Transplant referral considered for high-risk patients
• Follow-up schedule with reassessment milestones documented

Guidelines

1. RHC is mandatory before initiating PAH-specific therapy — echocardiographic estimates of RVSP are insufficient for diagnosis and treatment decisions.
2. NEVER start PAH-targeted therapy (PDE5i, ERA, prostacyclin) for Group 2 PH — these agents can cause pulmonary edema by increasing blood flow to a failing left heart.
3. V/Q scan must be performed in every PH workup to exclude CTEPH — CT angiography alone has insufficient sensitivity for chronic thromboembolic disease.
4. For newly diagnosed PAH at low-to-intermediate risk, upfront oral combination therapy (ERA + PDE5i) is now standard of care (AMBITION trial).
5. Epoprostenol (IV prostacyclin) remains the only therapy with proven mortality benefit in PAH — it is first-line for WHO FC IV / high-risk patients.
6. Vasoreactivity testing is only valid in idiopathic PAH — do not test or treat with CCBs in other PAH subtypes (CTD-PAH, HIV-PAH, porto-PH).
7. CTEPH is the only potentially curable form of PH — all CTEPH patients must be evaluated at a PEA-experienced center before being deemed "inoperable."
8. Patients on ERAs (bosentan, macitentan, ambrisentan) require monthly LFTs (bosentan) and monitoring for fluid retention and anemia — pregnancy is absolutely contraindicated.