managing-pulmonary-hypertension

# Managing Pulmonary Hypertension

Structures PH evaluation with right heart catheterization interpretation and treatment classification.

## Why This Skill Exists

Pulmonary hypertension (PH) is defined hemodynamically as a mean pulmonary artery pressure (mPAP) > 20 mmHg at rest by right heart catheterization. The 2022 ESC/ERS Guidelines for Pulmonary Hypertension redefined the hemodynamic threshold (from > 25 to > 20 mmHg) and updated the PVR cutoff for pre-capillary PH. Accurate WHO Group classification (I–V) is essential because treatment is group-specific — PAH-targeted therapies (Group 1) are harmful if given to patients with Group 2 (left heart disease) PH.

Delay in PH diagnosis averages 2–3 years from symptom onset. The diagnostic workup requires systematic exclusion of secondary causes before initiating PAH-specific therapy. Misclassification and inappropriate treatment carry significant morbidity.

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## Checkpoint A: Pre-Draft Intake (Mandatory)

1. What are the presenting symptoms — dyspnea (NYHA/WHO FC), exertional syncope, chest pain, edema? (default: "Symptoms not documented")
2. What is the echocardiographic estimated RVSP? (default: "Echo not available")
3. Has right heart catheterization been performed? What are the hemodynamics? (default: "RHC not yet performed")
4. What is the suspected WHO Group? (default: "Group not yet classified")
5. Has a ventilation-perfusion (V/Q) scan been performed? (default: "V/Q not obtained")
6. What are the pulmonary function tests and CT chest results? (default: "PFTs and CT not provided")
7. Are connective tissue disease serologies available (ANA, anti-SCL-70, anti-centromere)? (default: "Serologies not obtained")
8. Is the patient on any PH-specific therapy currently? (default: "No current PH therapy")

### 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

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## Step 1: Hemodynamic Classification by RHC

**2022 ESC/ERS Hemodynamic Definitions:**

| Type | mPAP | PCWP | PVR | Definition |
|------|------|------|-----|-----------|
| Pre-capillary PH | > 20 mmHg | ≤ 15 mmHg | > 2 WU | WHO Groups 1, 3, 4, 5 |
| Isolated post-capillary PH (IpcPH) | > 20 mmHg | > 15 mmHg | ≤ 2 WU | WHO Group 2 |
| Combined pre- and post-capillary PH (CpcPH) | > 20 mmHg | > 15 mmHg | > 2 WU | WHO Group 2 with pre-capillary component |

**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)

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## Step 2: WHO Group Classification

**WHO Group Classification and Common Etiologies:**

| Group | Category | Common Causes |
|-------|----------|--------------|
| 1 | Pulmonary arterial hypertension (PAH) | Idiopathic, heritable, CTD-associated (scleroderma), drug-induced, HIV, portal HTN, CHD |
| 2 | PH due to left heart disease | HFrEF, HFpEF, valvular disease |
| 3 | PH due to lung disease/hypoxia | COPD, ILD, OSA, chronic altitude |
| 4 | Chronic thromboembolic PH (CTEPH) | Unresolved PE; operable vs. inoperable |
| 5 | Multifactorial/unclear mechanisms | Sarcoidosis, myeloproliferative, renal failure, thyroid disease |

**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)

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## Step 3: Risk Stratification for PAH (Group 1)

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

| Parameter | Low Risk (< 5%) | Intermediate (5–20%) | High Risk (> 20%) |
|-----------|-----------------|---------------------|-------------------|
| WHO FC | I–II | III | IV |
| 6MWD | > 440 m | 165–440 m | < 165 m |
| BNP (pg/mL) | < 50 | 50–800 | > 800 |
| NT-proBNP (pg/mL) | < 300 | 300–1400 | > 1400 |
| RA pressure (mmHg) | < 8 | 8–14 | > 14 |
| Cardiac index (L/min/m²) | ≥ 2.5 | 2.0–2.4 | < 2.0 |
| SvO₂ (%) | > 65 | 60–65 | < 60 |

**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.

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## Step 4: Treatment by WHO Group

**Group 1 (PAH) — Targeted Therapy:**

| Risk Level | Initial Therapy |
|-----------|----------------|
| Low/intermediate risk | Oral combination: PDE5i (sildenafil/tadalafil) OR sGC stimulator (riociguat) + ERA (ambrisentan/macitentan/bosentan) |
| High risk | IV/SC prostacyclin (epoprostenol, treprostinil) + oral combination ERA + PDE5i |
| Inadequate response | Escalate to triple therapy; add IV prostacyclin; consider transplant referral |

**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)

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## Step 5: Monitoring and Follow-Up

**Follow-Up Assessment Schedule:**

| Timepoint | Actions |
|-----------|---------|
| 3–4 months after treatment initiation | WHO FC, 6MWD, BNP/NT-proBNP, echo; reassess risk |
| Every 6–12 months (stable) | WHO FC, 6MWD, BNP, echo; annual RHC if clinical concern |
| Clinical deterioration | Urgent reassessment with RHC; therapy escalation |

**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

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## 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?

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## 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

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## 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.