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This is a clinician-written, evidence-based summary aligned to the USMLE Step 2 CK Content Outline. It is intended for medical students preparing for USMLE Step 2 CK. Management reflects current ACC/AHA, USPSTF, and APA guidelines. Always cross-reference with UpToDate, institutional protocols, and clinical judgment.
The Bottom Line
- Defined as mean PAP >20 mmHg on right heart catheterization (2022 update from prior >25 threshold)
- WHO Group 1 (PAH): idiopathic, heritable, drug-induced, CTD-associated (scleroderma), HIV, portal HTN. Treated with PAH-specific vasodilators
- WHO Group 2 (left heart disease): most common overall. Treat the underlying LV dysfunction — PAH drugs are CONTRAINDICATED
- WHO Group 3 (lung disease/hypoxia): COPD, ILD. Treat underlying disease + supplemental O2
- WHO Group 4 (CTEPH): chronic thromboembolic PH — potentially curable with pulmonary thromboendarterectomy (PTE)
- Right heart catheterization is required to confirm diagnosis and classify (pre-capillary vs post-capillary based on PCWP)
Overview
Pulmonary hypertension (PH) is elevated pulmonary arterial pressure from diverse causes classified into 5 WHO groups. The critical distinction is pre-capillary (PCWP <=15, Groups 1/3/4/5 — elevated PVR) vs post-capillary (PCWP >15, Group 2 — passive backpressure from left heart disease). Group 1 PAH is treated with targeted vasodilator therapy. Group 2 is the most common form overall and is managed by treating the underlying left heart disease — PAH-specific drugs can cause pulmonary edema. Group 4 (CTEPH) is the only potentially curable form through surgery.
Epidemiology
Group 2 (left heart disease) is by far the most common cause of PH. Idiopathic PAH (Group 1) is rare (~5-15 per million), more common in women (3:1), median age ~45 at diagnosis. Scleroderma-associated PAH is the most common CTD cause. CTEPH affects ~3-4% of patients after acute PE. Without treatment, median survival of idiopathic PAH was historically 2-3 years; modern therapy has improved this substantially.
Clinical Features
Symptoms
Progressive exertional dyspnea (most common presenting symptom)
Fatigue, exercise intolerance
Exertional syncope or presyncope (inability to increase CO, fixed RV output)
Exertional chest pain (RV ischemia from increased wall stress)
Lower extremity edema, abdominal distension (right heart failure)
Signs
Loud P2 (pulmonic component of S2) — most consistent finding
Right ventricular heave (parasternal lift)
Elevated JVP with prominent "a" wave (RV non-compliance) or "v" wave (TR)
Tricuspid regurgitation murmur (holosystolic at LLSB, increases with inspiration — Carvallo sign)
Hepatomegaly, ascites, peripheral edema (right HF)
Cyanosis and clubbing (Eisenmenger syndrome — congenital shunt reversal)
Investigations
First-line
EchocardiogramScreening: estimated RVSP >35 mmHg suggests PH. RV dilation/dysfunction, RA enlargement, TR jet velocity, D-shaped septum (RV pressure overload), pericardial effusion (poor prognostic sign)
ECGRVH (right axis deviation, tall R in V1, RV strain pattern), RAE (P pulmonale), RBBB
CXREnlarged pulmonary arteries (main PA >29 mm), pruning of peripheral vessels, RV enlargement
PFTs + DLCOTo assess for underlying lung disease (Group 3). Isolated reduced DLCO without obstruction/restriction raises suspicion for PAH or CTEPH
Second-line
V/Q scanScreen for CTEPH (Group 4). Mismatched perfusion defects. V/Q is preferred over CTA for CTEPH screening (higher sensitivity for chronic subsegmental disease)
CT chestParenchymal lung disease (Group 3), enlarged PA, mosaic perfusion (CTEPH)
Autoimmune panelANA, anti-Scl-70, anti-centromere (scleroderma), anti-dsDNA (SLE), RF (RA)
HIV, LFTs, TFTsRule out associated conditions
Specialist
Right heart catheterizationREQUIRED for definitive diagnosis. Confirms: mPAP >20 mmHg. Pre-capillary (PCWP <=15, PVR >=3 WU) vs post-capillary (PCWP >15). Vasoreactivity testing with inhaled NO or IV epoprostenol for Group 1 PAH: positive response (mPAP drop >=10 to <=40 with maintained/improved CO) → trial of CCB (nifedipine/diltiazem). Only ~10% of PAH patients are vasoreactive
1
General measures (all PH)
- Supplemental O2 to maintain SpO2 >=90%
- Diuretics for RV volume overload (loop diuretics, use cautiously — RV is preload-dependent)
- Avoid excessive physical exertion; supervised exercise rehabilitation is beneficial
- Avoid pregnancy (extremely high maternal mortality in PAH ~30-50%)
- Anticoagulation: considered in idiopathic PAH (controversial); mandatory in CTEPH
- Flu and pneumococcal vaccination
2
Group 1 PAH — targeted therapy
- Vasoreactive (~10%): oral CCB (nifedipine, diltiazem — NOT verapamil due to negative inotropy)
- Non-vasoreactive (majority): combination therapy based on risk stratification
- PDE5 inhibitors: sildenafil 20 mg TID, tadalafil 40 mg daily
- Endothelin receptor antagonists (ERA): ambrisentan, bosentan, macitentan. Bosentan requires monthly LFTs (hepatotoxicity). All ERAs are teratogenic
- Prostacyclin pathway: epoprostenol IV (most potent, continuous infusion, half-life ~5 min), treprostinil (SC/IV/inhaled), iloprost (inhaled), selexipag (oral IP receptor agonist)
- sGC stimulator: riociguat (also for CTEPH). CANNOT be combined with PDE5i
- Initial combination therapy (ERA + PDE5i) is now recommended for most intermediate-high risk patients upfront (AMBITION trial)
3
Group 2 (left heart disease)
- Treat underlying: HFrEF GDMT, valvular surgery, AF management
- PAH-specific vasodilators are CONTRAINDICATED (can cause pulmonary edema by increasing flow across diseased left heart)
4
Group 3 (lung disease)
- Optimize underlying lung disease: bronchodilators (COPD), antifibrotics (IPF), supplemental O2
- Inhaled treprostinil approved for PH-ILD (INCREASE trial)
- Other PAH drugs generally not used (limited evidence, potential harm)
5
Group 4 (CTEPH)
- Lifelong anticoagulation
- Pulmonary thromboendarterectomy (PTE): potentially curative surgical option — assess operability at experienced center
- Balloon pulmonary angioplasty (BPA): for inoperable CTEPH
- Riociguat: for inoperable/persistent CTEPH post-PTE (CHEST-1 trial)
6
Advanced / refractory
- Atrial septostomy: palliative bridge — creates R-to-L shunt to decompress RV (at cost of hypoxemia)
- Lung transplant (bilateral) or heart-lung transplant: for refractory Group 1 PAH
Complications
- Right heart failure: Progressive RV dilation and dysfunction — leading cause of death in PAH
- Syncope/SCD: From inability to augment CO or from arrhythmia
- Hemoptysis: Bronchial artery hypertrophy + rupture
- Pericardial effusion: From elevated RA pressure — poor prognostic sign
- Pregnancy: Extremely high maternal mortality (~30-50%) in PAH
USMLE Step 2 CK Exam Tips
- 1Right heart catheterization is required to confirm PH and classify it. Echo only estimates — it is not diagnostic
- 2Group 2 (left heart disease) is the MOST COMMON cause of PH. PAH-specific drugs are CONTRAINDICATED in Group 2
- 3Loud P2 + exertional dyspnea + RV signs = PH. Check echo first, then catheterize
- 4CTEPH (Group 4): suspect in any patient with PH + history of PE. V/Q scan is the screening test (not CTA). Potentially curable with PTE
- 5Vasoreactivity testing: only done in Group 1 PAH. Positive = trial of CCB. Only ~10% respond
- 6Pregnancy is essentially contraindicated in PAH (~30-50% maternal mortality) — always counsel
- 7Eisenmenger syndrome (L-to-R shunt reversal from long-standing PH): cyanosis, clubbing, polycythemia. Do NOT close the shunt (RV cannot tolerate the afterload)
- 8Scleroderma is the most common CTD associated with PAH — screen with annual echo + DLCO
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