Pulmonary Hypertension

Definition

Pulmonary hypertension (PH) is a haemodynamic state defined by a mean pulmonary artery pressure (mPAP) >20 mmHg at rest on right heart catheterisation — the 2022 ESC/ERS threshold, lowered from ≥25 mmHg. PH is not a single disease but a haemodynamic consequence of diverse aetiologies spanning pulmonary vascular disease (Group 1/PAH), left heart disease (Group 2), lung disease (Group 3), thromboembolic obstruction (Group 4), and unclear/multifactorial mechanisms (Group 5).

Key Concepts

Epidemiology

• Global PH prevalence: ~1% of global population; left heart disease (Group 2) is the leading cause worldwide; COPD is the second most common cause. (sources/PHT-ESC-2022 — very high)
• PAH (Group 1): Incidence ~6 cases/million adults; prevalence 48–55 cases/million adults. IPAH accounts for 50–60% of PAH; historically female-predominant but increasingly diagnosed in older patients with equal sex distribution. (sources/PHT-ESC-2022)
• CTEPH (Group 4): Incidence 2–6 cases/million adults; cumulative incidence post-acute PE: 0.6% (all PE patients), 3.2% (survivors). (sources/PHT-ESC-2022)
• PH-LHD (Group 2): Post-capillary PH affects ≥50% of symptomatic HFpEF patients; PH present in 60–70% of severe mitral valve disease; up to 50% of symptomatic aortic stenosis. (sources/PHT-ESC-2022)

Pathophysiology

• Pulmonary vascular resistance (PVR): The key haemodynamic driver in pre-capillary PH. Elevated PVR reflects pulmonary vascular remodelling (smooth muscle proliferation, endothelial dysfunction, in situ thrombosis, adventitial fibrosis) — not reversible by vasodilators alone in established disease. (sources/PHT-ESC-2022)
• Right ventricular adaptation: RV adapts initially to elevated afterload (concentric hypertrophy, maintained contractility). Failure occurs when RV cannot maintain coupling with pulmonary vasculature — RV-PA uncoupling → dilatation, tricuspid regurgitation, systemic venous congestion. RV failure is the proximate cause of death in PAH.
• Vasoconstriction vs remodelling: In early PAH, vasoconstriction is reversible (acute vasoreactivity testing determines eligibility for CCBs); in established PAH, fixed structural remodelling dominates and vasoreactivity is absent in >90% of patients. (sources/PHT-ESC-2022)
• Post-capillary mechanisms (Group 2): Elevated PAWP from left heart disease raises pulmonary venous pressure passively → PH. In some patients, compensatory pulmonary vasoconstriction develops → combined pre- and post-capillary PH (CpcPH) with elevated PVR — this subset may benefit from PAH-targeted therapy at specialised centres. (sources/PHT-ESC-2022)

Diagnosis

• Right heart catheterisation (RHC): Gold standard — mandatory for PH confirmation and before initiating PAH-targeted therapy. Measures mPAP, PAWP, PVR, CO, and SvO₂. (sources/PHT-ESC-2022)
• Echocardiography: First-line non-invasive investigation; assigns PH probability by TRV (>2.8 m/s = high probability) plus additional echo signs (dilated RV, septal flattening, dilated pulmonary artery, reduced TAPSE). Cannot confirm PH diagnosis — RHC required. (sources/PHT-ESC-2022)

Key Treatment Targets

• Low-risk status (by 3-strata model): WHO-FC I/II, 6MWD >440 m, NT-proBNP in normal range, RAP <8 mmHg, CI ≥2.5 L/min/m², SVI ≥38 mL/m², mVO₂ >65% — the primary treatment goal. (sources/PHT-ESC-2022)
• Initial combination therapy ERA + PDE5i: Class I/B for most low-to-intermediate-risk PAH (AMBITION trial: ambrisentan + tadalafil; 2022 adds macitentan + tadalafil as Class I). (sources/PHT-ESC-2022)

PH and Right Ventricular Failure

• Chronic pressure afterload from PH is the prototype of RV failure via progressive RV remodeling; see concepts/Right-Ventricular-Failure for full pathophysiology
• Treatment contraindications by PH group: Pulmonary vasodilators (PDE5i, ERAs) are Class I in Group 1 PAH but Class III (harmful) in isolated post-capillary PH (Group 2, HFpEF-associated); SIOVAC trial — sildenafil worsened outcomes in persistent PH after left-sided valvular disease correction; 77% of US centres continue to use PAH-approved therapies in non-Group 1 PH despite evidence of harm (sources/rvfailure-nejm-2023, rating: very high)
• In LHD-associated PH: reduction of LA pressure via GDMT optimisation is the correct afterload-reduction strategy, not pulmonary vasodilators (sources/rvfailure-nejm-2023, rating: very high)
• Sotatercept: Activin ligand trap; FDA-approved for PAH; improves RV–PA coupling (PA pressures, compliance, Ees/Ea) in STELLAR trial; emerging evidence of direct RV cardioprotection via TGF-β/activin pathway; long-term RV effects unclear (sources/rv-failure-aha-2026, rating: very high)

Contradictions / Open Questions

• New mPAP threshold (>20 mmHg) without drug evidence: All approved PAH drugs studied only in mPAP ≥25 mmHg + PVR >3 WU. Patients newly diagnosed under the lower threshold represent an evidence-free zone for treatment decisions. (sources/PHT-ESC-2022)
• PDE5i in HFpEF + post-capillary PH: Class III (not recommended): Despite biological rationale, PDE5i in isolated post-capillary PH (HFpEF-associated) shows no benefit and possible harm. This distinguishes Group 1 from Group 2 PH mechanistically and therapeutically. (sources/PHT-ESC-2022)

Connections

• Related to concepts/Pulmonary-Hypertension-Classification
• Related to concepts/PAH-Risk-Stratification
• Related to concepts/Right-Heart-Catheterization
• Related to concepts/Balloon-Pulmonary-Angioplasty
• Related to concepts/Right-Ventricular-Failure
• Related to concepts/RV-PA-Coupling
• Related to entities/CTEPH

Sources

• sources/PHT-ESC-2022
• sources/rvfailure-nejm-2023 (very high)