ESC Risk Stratification Cutoff Points for Pulmonary Hypertension Severity
The ESC/ERS guidelines stratify pulmonary arterial hypertension severity into three risk categories based on estimated 1-year mortality: low risk (<5% mortality), intermediate risk (5-10% mortality), and high risk (>10% mortality), using specific cutoff values across multiple clinical, functional, biochemical, imaging, and hemodynamic parameters. 1
Risk Category Definitions and Mortality Estimates
The three-tiered risk stratification system provides prognostic estimates that directly guide treatment decisions 1:
- Low risk: Estimated 1-year mortality <5%, typically WHO functional class I-II, no progression of symptoms, no syncope, and preserved right ventricular function 1
- Intermediate risk: Estimated 1-year mortality 5-10%, typically WHO functional class III with moderately impaired exercise capacity and signs of RV dysfunction but not RV failure 1
- High risk: Estimated 1-year mortality >10%, typically WHO functional class III-IV with progressive disease, severe RV dysfunction or RV failure with secondary organ dysfunction 1
Specific Cutoff Values by Parameter Category
Clinical Assessment
- WHO Functional Class: Low risk = I-II; Intermediate risk = III; High risk = IV 1
- Syncope: Low risk = absent; Intermediate risk = occasional syncope during brisk/heavy exercise or occasional orthostatic syncope; High risk = repeated syncope with minimal activity 1
- Right heart failure signs: Low risk = absent; Intermediate risk = absent; High risk = present 1
- Symptom progression: Low risk = none; Intermediate risk = slow; High risk = rapid 1
Exercise Capacity
- 6-Minute Walk Distance (6MWD): Low risk = >440 m; Intermediate risk = 165-440 m; High risk = <165 m 1, 2
- Peak VO2 on CPET: Low risk = >15 ml/min/kg (>65% predicted); Intermediate risk = 11-15 ml/min/kg (35-65% predicted); High risk = <11 ml/min/kg (<35% predicted) 1
- VE/VCO2 slope: Low risk = <36; Intermediate risk = 36-44.9; High risk = ≥45 1
Biochemical Markers
- BNP levels: Low risk = <50 ng/L; Intermediate risk = 50-300 ng/L; High risk = >300 ng/L 1
- NT-proBNP levels: Low risk = <300 ng/L; Intermediate risk = 300-1400 ng/L; High risk = >1400 ng/L 1, 2
Imaging Parameters (Echocardiography/CMR)
- Right atrial area: Low risk = <18 cm²; Intermediate risk = 18-26 cm²; High risk = >26 cm² 1
- Pericardial effusion: Low risk = absent; Intermediate risk = absent or minimal; High risk = present 1
Hemodynamic Parameters
- Cardiac Index (CI): Low risk = ≥2.5 L/min/m²; Intermediate risk = 2.0-2.4 L/min/m²; High risk = <2.0 L/min/m² 1, 3
- Right Atrial Pressure (RAP): Low risk = <8 mmHg; Intermediate risk = 8-14 mmHg; High risk = >14 mmHg 1, 3
- Mixed Venous Oxygen Saturation (SvO2): Low risk = >65%; Intermediate risk = 60-65%; High risk = <60% 1
Application in Clinical Practice
Multiparametric Assessment Requirement
No single variable provides sufficient prognostic information; comprehensive assessment using multiple parameters is mandatory. 1 The basic evaluation should include functional class determination, at least one exercise capacity measurement (6MWD or CPET), and RV function assessment (BNP/NT-proBNP or echocardiography) 1.
Assessment Frequency
Regular follow-up assessments every 3-6 months are required in stable patients, with reassessment 3-6 months after treatment changes 1, 2.
Treatment Goals Based on Risk Status
Achievement and maintenance of low-risk status is the primary treatment goal, as this correlates with good exercise capacity, quality of life, RV function, and low mortality risk. 1, 2 Intermediate-risk status should be considered an inadequate treatment response warranting treatment escalation in most patients 1.
Critical Caveats and Limitations
Population-Specific Validation
Most cutoff values were validated primarily in idiopathic PAH populations and may not apply equally to other PAH forms (e.g., connective tissue disease-associated PAH) 1. CTD-PAH patients demonstrate higher baseline risk profiles, with 67-70% at intermediate or high risk despite background therapy 2.
Variable Discordance
Variables may fall into different risk categories for the same patient; the overall assessment pattern should guide therapeutic decisions rather than any single parameter 1. When ≥2 variables are measured, each is assigned a score of 1-3 (corresponding to low/intermediate/high risk), and the average score determines overall risk category 4.
Expert Opinion Basis
Many proposed cutoff values are based on expert opinion rather than prospective validation, requiring careful application to individual patients 1. The REVEAL 2.0 calculator demonstrates superior discrimination (c-statistic 0.73-0.76) compared to ESC/ERS-based strategies (c-statistic 0.62-0.64) in some validation studies 5.
Influence of Therapy
Approved therapies and their effects on measured variables must be considered when evaluating risk 1.
Age and Comorbidity Adjustments
Lower 6MWD values may be acceptable in elderly patients or those with comorbidities, while values >440 m may be insufficient in younger, otherwise healthy patients 1. The presence of heart or lung disease increases mortality risk even with mildly abnormal hemodynamics 6.