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
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.
1---2name: managing-pulmonary-hypertension3description: Structures PH evaluation with right heart catheterization interpretation and treatment classification. Use when evaluating pulmonary hypertension, interpreting RHC data, or classifying PH by WHO group.4---56# Managing Pulmonary Hypertension78Structures PH evaluation with right heart catheterization interpretation and treatment classification.910## Why This Skill Exists1112Pulmonary 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.1314Delay 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.1516---1718## Checkpoint A: Pre-Draft Intake (Mandatory)19201. What are the presenting symptoms — dyspnea (NYHA/WHO FC), exertional syncope, chest pain, edema? (default: "Symptoms not documented")212. What is the echocardiographic estimated RVSP? (default: "Echo not available")223. Has right heart catheterization been performed? What are the hemodynamics? (default: "RHC not yet performed")234. What is the suspected WHO Group? (default: "Group not yet classified")245. Has a ventilation-perfusion (V/Q) scan been performed? (default: "V/Q not obtained")256. What are the pulmonary function tests and CT chest results? (default: "PFTs and CT not provided")267. Are connective tissue disease serologies available (ANA, anti-SCL-70, anti-centromere)? (default: "Serologies not obtained")278. Is the patient on any PH-specific therapy currently? (default: "No current PH therapy")2829### Documents to Request3031- Echocardiogram with RV assessment (RVSP, TAPSE, RV size)32- Right heart catheterization hemodynamic data33- V/Q scan (to exclude CTEPH)34- Pulmonary function tests with DLCO35- CT chest (high-resolution for parenchymal disease)36- CT pulmonary angiography (if CTEPH suspected)37- Autoimmune serologies (ANA, ENA panel, anti-SCL-70, anti-centromere)38- HIV, hepatitis B/C serologies39- Liver function tests and liver ultrasound (portopulmonary evaluation)40- 6-minute walk distance41- BNP/NT-proBNP42- Sleep study (if OSA/hypoventilation suspected)43- Thyroid function tests4445---4647## Step 1: Hemodynamic Classification by RHC4849**2022 ESC/ERS Hemodynamic Definitions:**5051| Type | mPAP | PCWP | PVR | Definition |52|------|------|------|-----|-----------|53| Pre-capillary PH | > 20 mmHg | ≤ 15 mmHg | > 2 WU | WHO Groups 1, 3, 4, 5 |54| Isolated post-capillary PH (IpcPH) | > 20 mmHg | > 15 mmHg | ≤ 2 WU | WHO Group 2 |55| Combined pre- and post-capillary PH (CpcPH) | > 20 mmHg | > 15 mmHg | > 2 WU | WHO Group 2 with pre-capillary component |5657**Key Hemodynamic Measurements to Document:**58- mPAP, PCWP (or LVEDP if PCWP unreliable)59- PVR = (mPAP − PCWP) / CO (in Wood units)60- Cardiac output (thermodilution and/or Fick)61- Cardiac index62- Mixed venous O₂ saturation (SvO₂) — < 60% indicates severely reduced CO63- Transpulmonary gradient (TPG) = mPAP − PCWP (> 12 mmHg suggests pre-capillary component)64- Diastolic pressure gradient (DPG) = diastolic PAP − PCWP (> 7 mmHg suggests pre-capillary component)6566---6768## Step 2: WHO Group Classification6970**WHO Group Classification and Common Etiologies:**7172| Group | Category | Common Causes |73|-------|----------|--------------|74| 1 | Pulmonary arterial hypertension (PAH) | Idiopathic, heritable, CTD-associated (scleroderma), drug-induced, HIV, portal HTN, CHD |75| 2 | PH due to left heart disease | HFrEF, HFpEF, valvular disease |76| 3 | PH due to lung disease/hypoxia | COPD, ILD, OSA, chronic altitude |77| 4 | Chronic thromboembolic PH (CTEPH) | Unresolved PE; operable vs. inoperable |78| 5 | Multifactorial/unclear mechanisms | Sarcoidosis, myeloproliferative, renal failure, thyroid disease |7980**Diagnostic Algorithm (Sequential Exclusion):**811. Echo: estimate RVSP, assess LV function and valve disease → if left heart disease likely → Group 2822. PFTs + CT chest: if significant lung disease (FEV1 < 60% or extensive ILD) → Group 3833. V/Q scan: mismatched perfusion defects → CTEPH workup (Group 4)844. If Groups 2–4 excluded → evaluate for Group 1 (PAH) or Group 5855. Confirm with RHC (mandatory before initiating PAH-specific therapy)8687---8889## Step 3: Risk Stratification for PAH (Group 1)9091**ESC/ERS Risk Assessment (low, intermediate, high mortality risk):**9293| Parameter | Low Risk (< 5%) | Intermediate (5–20%) | High Risk (> 20%) |94|-----------|-----------------|---------------------|-------------------|95| WHO FC | I–II | III | IV |96| 6MWD | > 440 m | 165–440 m | < 165 m |97| BNP (pg/mL) | < 50 | 50–800 | > 800 |98| NT-proBNP (pg/mL) | < 300 | 300–1400 | > 1400 |99| RA pressure (mmHg) | < 8 | 8–14 | > 14 |100| Cardiac index (L/min/m²) | ≥ 2.5 | 2.0–2.4 | < 2.0 |101| SvO₂ (%) | > 65 | 60–65 | < 60 |102103**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.104105---106107## Step 4: Treatment by WHO Group108109**Group 1 (PAH) — Targeted Therapy:**110111| Risk Level | Initial Therapy |112|-----------|----------------|113| Low/intermediate risk | Oral combination: PDE5i (sildenafil/tadalafil) OR sGC stimulator (riociguat) + ERA (ambrisentan/macitentan/bosentan) |114| High risk | IV/SC prostacyclin (epoprostenol, treprostinil) + oral combination ERA + PDE5i |115| Inadequate response | Escalate to triple therapy; add IV prostacyclin; consider transplant referral |116117**Vasoreactivity Testing (for IPAH only):**118- Inhaled NO, IV epoprostenol, or IV adenosine during RHC119- Positive response: mPAP decrease ≥ 10 mmHg to ≤ 40 mmHg with maintained/improved CO120- Positive responders (~10–15% of IPAH): trial of high-dose CCB (nifedipine, diltiazem, amlodipine)121122**Group 2 (Left Heart Disease):** Treat underlying HF/valve disease. PAH-targeted therapies are NOT indicated (harmful in Group 2).123124**Group 3 (Lung Disease):** Treat underlying lung disease. Inhaled treprostinil approved for PH-ILD. Avoid vasodilators that worsen V/Q mismatch.125126**Group 4 (CTEPH):**127- Pulmonary endarterectomy (PEA): surgical cure for operable CTEPH → refer to expert center128- Balloon pulmonary angioplasty (BPA): for inoperable or residual PH post-PEA129- Riociguat: approved for inoperable CTEPH or persistent PH post-PEA130- Lifelong anticoagulation (warfarin; DOACs under study)131132---133134## Step 5: Monitoring and Follow-Up135136**Follow-Up Assessment Schedule:**137138| Timepoint | Actions |139|-----------|---------|140| 3–4 months after treatment initiation | WHO FC, 6MWD, BNP/NT-proBNP, echo; reassess risk |141| Every 6–12 months (stable) | WHO FC, 6MWD, BNP, echo; annual RHC if clinical concern |142| Clinical deterioration | Urgent reassessment with RHC; therapy escalation |143144**Treatment Goals:**145- Achieve and maintain low-risk profile (WHO FC I–II, 6MWD > 440 m, BNP < 50)146- If not at low risk at 3–6 months → escalate therapy147- Refer for lung transplant evaluation if high risk persists despite maximal therapy148149---150151## Checkpoint B: Post-Draft Alignment (Mandatory)1521531. Is the hemodynamic classification (pre-capillary, post-capillary, combined) correct per RHC data?1542. Is the WHO Group assignment supported by the diagnostic workup?1553. Is risk stratification documented for PAH patients using ESC/ERS criteria?1564. Is the treatment plan group-specific (not applying PAH therapy to Group 2)?1575. Are follow-up intervals and treatment escalation criteria defined?158159---160161## Quality Audit162163- [ ] RHC hemodynamics documented: mPAP, PCWP, PVR, CO/CI, SvO₂164- [ ] Hemodynamic classification stated (pre-capillary, IpcPH, CpcPH)165- [ ] WHO Group assigned with diagnostic evidence166- [ ] V/Q scan performed to exclude CTEPH (or absence justified)167- [ ] PFTs and CT chest reviewed for Group 3 exclusion168- [ ] Autoimmune serologies obtained for CTD-PAH screening169- [ ] 6MWD performed as baseline functional assessment170- [ ] BNP/NT-proBNP documented171- [ ] Risk stratification completed (ESC/ERS or REVEAL)172- [ ] Vasoreactivity testing performed for IPAH candidates173- [ ] Treatment matched to WHO Group174- [ ] Combination therapy initiated for Group 1 per risk level175- [ ] Transplant referral considered for high-risk patients176- [ ] Follow-up schedule with reassessment milestones documented177178---179180## Guidelines1811821. RHC is mandatory before initiating PAH-specific therapy — echocardiographic estimates of RVSP are insufficient for diagnosis and treatment decisions.1832. 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.1843. V/Q scan must be performed in every PH workup to exclude CTEPH — CT angiography alone has insufficient sensitivity for chronic thromboembolic disease.1854. For newly diagnosed PAH at low-to-intermediate risk, upfront oral combination therapy (ERA + PDE5i) is now standard of care (AMBITION trial).1865. Epoprostenol (IV prostacyclin) remains the only therapy with proven mortality benefit in PAH — it is first-line for WHO FC IV / high-risk patients.1876. 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).1887. CTEPH is the only potentially curable form of PH — all CTEPH patients must be evaluated at a PEA-experienced center before being deemed "inoperable."1898. Patients on ERAs (bosentan, macitentan, ambrisentan) require monthly LFTs (bosentan) and monitoring for fluid retention and anemia — pregnancy is absolutely contraindicated.