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.

Checkpoint A: Pre-Draft Intake (Mandatory)

What are the presenting symptoms — dyspnea (NYHA/WHO FC), exertional syncope, chest pain, edema? (default: "Symptoms not documented")
What is the echocardiographic estimated RVSP? (default: "Echo not available")
Has right heart catheterization been performed? What are the hemodynamics? (default: "RHC not yet performed")
What is the suspected WHO Group? (default: "Group not yet classified")
Has a ventilation-perfusion (V/Q) scan been performed? (default: "V/Q not obtained")
What are the pulmonary function tests and CT chest results? (default: "PFTs and CT not provided")
Are connective tissue disease serologies available (ANA, anti-SCL-70, anti-centromere)? (default: "Serologies not obtained")
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

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)

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):

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

| 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.

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)

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

Checkpoint B: Post-Draft Alignment (Mandatory)

Is the hemodynamic classification (pre-capillary, post-capillary, combined) correct per RHC data?
Is the WHO Group assignment supported by the diagnostic workup?
Is risk stratification documented for PAH patients using ESC/ERS criteria?
Is the treatment plan group-specific (not applying PAH therapy to Group 2)?
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

RHC is mandatory before initiating PAH-specific therapy — echocardiographic estimates of RVSP are insufficient for diagnosis and treatment decisions.
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.
V/Q scan must be performed in every PH workup to exclude CTEPH — CT angiography alone has insufficient sensitivity for chronic thromboembolic disease.
For newly diagnosed PAH at low-to-intermediate risk, upfront oral combination therapy (ERA + PDE5i) is now standard of care (AMBITION trial).
Epoprostenol (IV prostacyclin) remains the only therapy with proven mortality benefit in PAH — it is first-line for WHO FC IV / high-risk patients.
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).
CTEPH is the only potentially curable form of PH — all CTEPH patients must be evaluated at a PEA-experienced center before being deemed "inoperable."
Patients on ERAs (bosentan, macitentan, ambrisentan) require monthly LFTs (bosentan) and monitoring for fluid retention and anemia — pregnancy is absolutely contraindicated.