PAH Risk Stratification
Definition
PAH risk stratification is the systematic, multiparameter assessment of prognosis and treatment-response in pulmonary arterial hypertension, used to guide initial therapy selection and escalation decisions. The 2022 ESC/ERS guidelines use a 3-strata model at diagnosis (low/intermediate/high risk) and a 4-strata model at follow-up (low/intermediate-low/intermediate-high/high risk), with achieving and maintaining low-risk status as the primary treatment target.
Key Concepts
Risk Strata and Parameters
- 3-strata model at diagnosis and initial treatment planning: Low / Intermediate / High. (sources/PHT-ESC-2022, rating: very high)
- 4-strata model at follow-up: Low / Intermediate-Low / Intermediate-High / High. Sub-stratification within the intermediate range was added in 2022 to better guide escalation decisions. (sources/PHT-ESC-2022, rating: very high)
- Core risk parameters (at each assessment):
- WHO functional class (WHO-FC I/II = low; III = intermediate; IV = high)
- 6-minute walking distance (6MWD: >440 m = low; 165–440 m = intermediate; <165 m = high)
- NT-proBNP/BNP (NT-proBNP <300 ng/L = low; 300–1100 = intermediate; >1100 = high)
- Echocardiographic findings (RAP, RV/RA size and function, pericardial effusion)
- RHC haemodynamics (RAP, CI, SVI, mixed venous O₂ saturation)
- (sources/PHT-ESC-2022, rating: very high)
Low-Risk Target Haemodynamics
- RAP <8 mmHg
- Cardiac Index (CI) ≥2.5 L/min/m²
- Stroke Volume Index (SVI) ≥38 mL/m²
- Mixed venous O₂ saturation >65%
- (sources/PHT-ESC-2022, rating: very high)
Treatment Algorithm Based on Risk
- Low-to-intermediate risk at diagnosis: Initial combination ERA + PDE5i — Class I/B (ambrisentan + tadalafil or macitentan + tadalafil). (sources/PHT-ESC-2022, rating: very high)
- Intermediate risk with severe haemodynamic impairment (RAP ≥20 mmHg, CI <2.0 L/min/m², SVI <31 mL/m², and/or PVR ≥12 WU): Initial triple therapy including i.v./s.c. prostacyclin may be considered. (sources/PHT-ESC-2022, rating: very high)
- High risk at diagnosis: Initial triple therapy including parenteral prostacyclin; early lung transplantation evaluation. (sources/PHT-ESC-2022, rating: very high)
- Escalation trigger: If intermediate-high or high risk at reassessment (3–6 months) → add parenteral prostacyclin or escalate to lung transplantation. (sources/PHT-ESC-2022, rating: very high)
- Follow-up reassessment: Every 3–6 months — repeat WHO-FC, 6MWD, NT-proBNP, echocardiography; RHC as clinically indicated. (sources/PHT-ESC-2022, rating: very high)
Vasoreactivity Testing
- Acute vasoreactivity testing: Recommended in IPAH, HPAH, DPAH (Class I). Positive response: mPAP reduction ≥10 mmHg to reach absolute mPAP ≤40 mmHg with unchanged or increased CO. (sources/PHT-ESC-2022, rating: very high)
- <10% of IPAH/HPAH/DPAH patients are vasoreactive; non-responders should NOT receive CCBs. (sources/PHT-ESC-2022, rating: very high)
- Positive responders treated with high-dose CCBs (nifedipine, diltiazem, amlodipine, felodipine); complete reassessment including RHC at 3–6 months. (sources/PHT-ESC-2022, rating: very high)
Contradictions / Open Questions
- 4-strata follow-up model not prospectively validated: The intermediate-low/intermediate-high sub-stratification is clinically pragmatic but based on expert consensus rather than prospective validation of hard outcome differences between these two sub-groups. (sources/PHT-ESC-2022, rating: very high)
- Low-risk threshold achievability varies by PAH subtype: SSc-PAH and PAH associated with liver disease consistently have worse haemodynamic profiles and lower rates of reaching low-risk status than IPAH; the same treat-to-target approach may not be equally effective or realistic across all PAH subtypes. (sources/PHT-ESC-2022, rating: very high)
Connections
- Related to entities/Pulmonary-Hypertension
- Related to entities/CTEPH
- Related to sources/PHT-ESC-2022