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.4tags:5 - management6 - cardiology7 - treatment8 - valuation9metadata:10 author: casemark11 practice_areas:12 - Cardiology13 - Interventional Cardiology14 - Electrophysiology15 document_types:16 - Management Report17 skill_modes:18 - Management19 - Coordination20---2122# Managing Pulmonary Hypertension2324Structures PH evaluation with right heart catheterization interpretation and treatment classification.2526## Why This Skill Exists2728Pulmonary 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.2930Delay 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.3132---3334## Checkpoint A: Pre-Draft Intake (Mandatory)35361. What are the presenting symptoms — dyspnea (NYHA/WHO FC), exertional syncope, chest pain, edema? (default: "Symptoms not documented")372. What is the echocardiographic estimated RVSP? (default: "Echo not available")383. Has right heart catheterization been performed? What are the hemodynamics? (default: "RHC not yet performed")394. What is the suspected WHO Group? (default: "Group not yet classified")405. Has a ventilation-perfusion (V/Q) scan been performed? (default: "V/Q not obtained")416. What are the pulmonary function tests and CT chest results? (default: "PFTs and CT not provided")427. Are connective tissue disease serologies available (ANA, anti-SCL-70, anti-centromere)? (default: "Serologies not obtained")438. Is the patient on any PH-specific therapy currently? (default: "No current PH therapy")4445### Documents to Request4647- Echocardiogram with RV assessment (RVSP, TAPSE, RV size)48- Right heart catheterization hemodynamic data49- V/Q scan (to exclude CTEPH)50- Pulmonary function tests with DLCO51- CT chest (high-resolution for parenchymal disease)52- CT pulmonary angiography (if CTEPH suspected)53- Autoimmune serologies (ANA, ENA panel, anti-SCL-70, anti-centromere)54- HIV, hepatitis B/C serologies55- Liver function tests and liver ultrasound (portopulmonary evaluation)56- 6-minute walk distance57- BNP/NT-proBNP58- Sleep study (if OSA/hypoventilation suspected)59- Thyroid function tests6061---6263## Step 1: Hemodynamic Classification by RHC6465**2022 ESC/ERS Hemodynamic Definitions:**6667| Type | mPAP | PCWP | PVR | Definition |68|------|------|------|-----|-----------|69| Pre-capillary PH | > 20 mmHg | ≤ 15 mmHg | > 2 WU | WHO Groups 1, 3, 4, 5 |70| Isolated post-capillary PH (IpcPH) | > 20 mmHg | > 15 mmHg | ≤ 2 WU | WHO Group 2 |71| Combined pre- and post-capillary PH (CpcPH) | > 20 mmHg | > 15 mmHg | > 2 WU | WHO Group 2 with pre-capillary component |7273**Key Hemodynamic Measurements to Document:**74- mPAP, PCWP (or LVEDP if PCWP unreliable)75- PVR = (mPAP − PCWP) / CO (in Wood units)76- Cardiac output (thermodilution and/or Fick)77- Cardiac index78- Mixed venous O₂ saturation (SvO₂) — < 60% indicates severely reduced CO79- Transpulmonary gradient (TPG) = mPAP − PCWP (> 12 mmHg suggests pre-capillary component)80- Diastolic pressure gradient (DPG) = diastolic PAP − PCWP (> 7 mmHg suggests pre-capillary component)8182---8384## Step 2: WHO Group Classification8586**WHO Group Classification and Common Etiologies:**8788| Group | Category | Common Causes |89|-------|----------|--------------|90| 1 | Pulmonary arterial hypertension (PAH) | Idiopathic, heritable, CTD-associated (scleroderma), drug-induced, HIV, portal HTN, CHD |91| 2 | PH due to left heart disease | HFrEF, HFpEF, valvular disease |92| 3 | PH due to lung disease/hypoxia | COPD, ILD, OSA, chronic altitude |93| 4 | Chronic thromboembolic PH (CTEPH) | Unresolved PE; operable vs. inoperable |94| 5 | Multifactorial/unclear mechanisms | Sarcoidosis, myeloproliferative, renal failure, thyroid disease |9596**Diagnostic Algorithm (Sequential Exclusion):**971. Echo: estimate RVSP, assess LV function and valve disease → if left heart disease likely → Group 2982. PFTs + CT chest: if significant lung disease (FEV1 < 60% or extensive ILD) → Group 3993. V/Q scan: mismatched perfusion defects → CTEPH workup (Group 4)1004. If Groups 2–4 excluded → evaluate for Group 1 (PAH) or Group 51015. Confirm with RHC (mandatory before initiating PAH-specific therapy)102103---104105## Step 3: Risk Stratification for PAH (Group 1)106107**ESC/ERS Risk Assessment (low, intermediate, high mortality risk):**108109| Parameter | Low Risk (< 5%) | Intermediate (5–20%) | High Risk (> 20%) |110|-----------|-----------------|---------------------|-------------------|111| WHO FC | I–II | III | IV |112| 6MWD | > 440 m | 165–440 m | < 165 m |113| BNP (pg/mL) | < 50 | 50–800 | > 800 |114| NT-proBNP (pg/mL) | < 300 | 300–1400 | > 1400 |115| RA pressure (mmHg) | < 8 | 8–14 | > 14 |116| Cardiac index (L/min/m²) | ≥ 2.5 | 2.0–2.4 | < 2.0 |117| SvO₂ (%) | > 65 | 60–65 | < 60 |118119**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.120121---122123## Step 4: Treatment by WHO Group124125**Group 1 (PAH) — Targeted Therapy:**126127| Risk Level | Initial Therapy |128|-----------|----------------|129| Low/intermediate risk | Oral combination: PDE5i (sildenafil/tadalafil) OR sGC stimulator (riociguat) + ERA (ambrisentan/macitentan/bosentan) |130| High risk | IV/SC prostacyclin (epoprostenol, treprostinil) + oral combination ERA + PDE5i |131| Inadequate response | Escalate to triple therapy; add IV prostacyclin; consider transplant referral |132133**Vasoreactivity Testing (for IPAH only):**134- Inhaled NO, IV epoprostenol, or IV adenosine during RHC135- Positive response: mPAP decrease ≥ 10 mmHg to ≤ 40 mmHg with maintained/improved CO136- Positive responders (~10–15% of IPAH): trial of high-dose CCB (nifedipine, diltiazem, amlodipine)137138**Group 2 (Left Heart Disease):** Treat underlying HF/valve disease. PAH-targeted therapies are NOT indicated (harmful in Group 2).139140**Group 3 (Lung Disease):** Treat underlying lung disease. Inhaled treprostinil approved for PH-ILD. Avoid vasodilators that worsen V/Q mismatch.141142**Group 4 (CTEPH):**143- Pulmonary endarterectomy (PEA): surgical cure for operable CTEPH → refer to expert center144- Balloon pulmonary angioplasty (BPA): for inoperable or residual PH post-PEA145- Riociguat: approved for inoperable CTEPH or persistent PH post-PEA146- Lifelong anticoagulation (warfarin; DOACs under study)147148---149150## Step 5: Monitoring and Follow-Up151152**Follow-Up Assessment Schedule:**153154| Timepoint | Actions |155|-----------|---------|156| 3–4 months after treatment initiation | WHO FC, 6MWD, BNP/NT-proBNP, echo; reassess risk |157| Every 6–12 months (stable) | WHO FC, 6MWD, BNP, echo; annual RHC if clinical concern |158| Clinical deterioration | Urgent reassessment with RHC; therapy escalation |159160**Treatment Goals:**161- Achieve and maintain low-risk profile (WHO FC I–II, 6MWD > 440 m, BNP < 50)162- If not at low risk at 3–6 months → escalate therapy163- Refer for lung transplant evaluation if high risk persists despite maximal therapy164165---166167## Checkpoint B: Post-Draft Alignment (Mandatory)1681691. Is the hemodynamic classification (pre-capillary, post-capillary, combined) correct per RHC data?1702. Is the WHO Group assignment supported by the diagnostic workup?1713. Is risk stratification documented for PAH patients using ESC/ERS criteria?1724. Is the treatment plan group-specific (not applying PAH therapy to Group 2)?1735. Are follow-up intervals and treatment escalation criteria defined?174175---176177## Quality Audit178179- [ ] RHC hemodynamics documented: mPAP, PCWP, PVR, CO/CI, SvO₂180- [ ] Hemodynamic classification stated (pre-capillary, IpcPH, CpcPH)181- [ ] WHO Group assigned with diagnostic evidence182- [ ] V/Q scan performed to exclude CTEPH (or absence justified)183- [ ] PFTs and CT chest reviewed for Group 3 exclusion184- [ ] Autoimmune serologies obtained for CTD-PAH screening185- [ ] 6MWD performed as baseline functional assessment186- [ ] BNP/NT-proBNP documented187- [ ] Risk stratification completed (ESC/ERS or REVEAL)188- [ ] Vasoreactivity testing performed for IPAH candidates189- [ ] Treatment matched to WHO Group190- [ ] Combination therapy initiated for Group 1 per risk level191- [ ] Transplant referral considered for high-risk patients192- [ ] Follow-up schedule with reassessment milestones documented193194---195196## Guidelines1971981. RHC is mandatory before initiating PAH-specific therapy — echocardiographic estimates of RVSP are insufficient for diagnosis and treatment decisions.1992. 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.2003. V/Q scan must be performed in every PH workup to exclude CTEPH — CT angiography alone has insufficient sensitivity for chronic thromboembolic disease.2014. For newly diagnosed PAH at low-to-intermediate risk, upfront oral combination therapy (ERA + PDE5i) is now standard of care (AMBITION trial).2025. Epoprostenol (IV prostacyclin) remains the only therapy with proven mortality benefit in PAH — it is first-line for WHO FC IV / high-risk patients.2036. 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).2047. CTEPH is the only potentially curable form of PH — all CTEPH patients must be evaluated at a PEA-experienced center before being deemed "inoperable."2058. Patients on ERAs (bosentan, macitentan, ambrisentan) require monthly LFTs (bosentan) and monitoring for fluid retention and anemia — pregnancy is absolutely contraindicated.