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Global PAH Registries

Risk assessments are based on registries

Multiple registries from across the globe track thousands of patients with pulmonary arterial hypertension (PAH). Because of the depth and breadth of information collected in worldwide PAH registries, registry data are the foundation of today’s treatment guidelines.1,2 The data are consistent: Patients who achieve low-risk status within their first year after diagnosis were shown to have a better likelihood of survival. Formal risk calculation methods based on these registry data can help you predict your patients’ chance of survival at 5 years.3-8

What are the benefits of using registry data?

Patient registries contain a wealth of real-world information and allow for discoveries of patterns outside the strict confines of RCTs. Robust registries focus on a specified population of patients, for example, patients with PAH, while collecting prespecified data from multiple institutions. Registries collect data on thousands of patients over time—far longer than RCTs—thus following large numbers of patients throughout their PAH journey.9

Generalized limitations of registry data

PAH risk assessment methods are based on large patient registry data sets. To use these registries thoughtfully, limitations of registry data should be acknowledged.

A few limitations to consider when reviewing registry data analysis include7,8,10:

  • Limited generalization, depending on the patient population and the size of the registry
  • Dependent on data collected, not the data that may be needed for a study
  • Historical data, some of which may be bypassed for updated knowledge and therapies
  • Potential need for prospective, external validation

US REVEAL Registry

The US-based REVEAL Registry supports the prognostic utility of risk stratification.6-8 REVEAL 2.0 and REVEAL Lite 2 risk calculators can be used to calculate your patients’ risk status.6-8 REVEAL-ECHO calculations include updates that emphasize the importance of Echo measurements for an accurate prognosis and critical risk assessment results.10

REVEAL 2.07
REVEAL Lite 28
REVEAL-ECHO10

Overview

US multicenter, retrospective refinements of study (2006-2013); N=2529

US multicenter, retrospective echocardiographic data (2006-2013); N=2400

Variables

13 variables*:

  • WHO Group 1 subgroup
  • Age/sex
  • Renal insufficiency
  • NYHA/WHO FC
  • SBP
  • HR
  • 6MWD
  • BNP/NT-proBNP
  • Pericardial effusion
  • DLCO
  • mRAP
  • PVR
  • All-cause hospitalizations ≤6 months

6 noninvasive variables:

  • Renal insufficiency
  • NYHA/WHO FC
  • SBP
  • HR
  • 6MWD
  • BP/NT-proBNP

4 echocardiographic parameters:

  • RV chamber enlargement
  • RV reduced systolic function
  • Tricuspid regurgitation severity
  • Pericardial effusion
  • PAH etiology subgroup

Risk calculation

Weighted scores assigned to each value based on the variable’s contribution to risk

Risk stratification:

  • Low-risk score (≤6)
  • Intermediate-risk score (7-8)
  • High-risk score (≥9)

Weighted scores assigned to each value based on the variable’s contribution to risk

Risk stratification:

  • Low-risk score (≤5)
  • Intermediate-risk score (6-7)
  • High-risk score (≥8)

Weighted scores assigned to each value based on the variable’s contribution to risk

Risk stratification:

  • Low-risk score (0-1)
  • Intermediate-risk score (2-3)
  • High-risk score (4-10)

Suggested use2,8,10

Baseline risk assessment

Annual risk assessment

Follow-up risk assessment

Follow-up risk assessment

Potential complementary use with other risk tools

REVEAL 2.07

Overview

US multicenter, retrospective refinements of study (2006-2013); N=2529

Variables

13 variables*:

  • WHO Group 1 subgroup
  • Age/Sex
  • Renal insufficiency
  • NYHA/WHO FC
  • SBP
  • HR
  • 6MWD
  • BNP/NT-proBNP
  • Pericardial effusion
  • DLCO
  • mRAP
  • PVR
  • All-cause hospitalizations ≤6 months

Risk calculation

Weighted scores assigned to each value based on the variable’s contribution to risk

Risk stratification:

  • Low-risk score (≤6)
  • Intermediate-risk score (7-8)
  • High-risk score (≥9)

Suggested use

Baseline risk assessment

Annual risk assessment

Follow-up risk assessment

REVEAL Lite 28

Overview

Variables

6 noninvasive variables:

  • Renal insufficiency
  • NYHA/WHO FC
  • SBP
  • HR
  • 6MWD
  • BP/NT-proBNP

Risk calculation

Weighted scores assigned to each value based on the variable’s contribution to risk

Risk stratification:

  • Low-risk score (≤5)
  • Intermediate-risk score (6-7)
  • High-risk score (≥8)

Suggested use

Follow-up risk assessment

REVEAL-ECHO10

Overview

US multicenter, retrospective echocardiographic data (2006-2013); N=2400

Variables

4 echocardiographic parameters:

  • RV chamber enlargement
  • RV reduced systolic function
  • Tricuspid regurgitation severity
  • Pericardial effusion
  • PAH etiology subgroup

Risk calculation

Weighted scores assigned to each value based on the variable’s contribution to risk

Risk stratification:

  • Low-risk score (0-1)
  • Intermediate-risk score (2-3)
  • High-risk score (4-10)

Suggested use

Potential complementary use with other risk tools

*At least 7 variables are needed for an accurate calculation.2REVEAL Lite 2 is most accurate when all 6 variables are measured; good discrimination between risk groups is seen when missing 1 variable. At least 2 of the 3 most prognostic variables (BNP/NT-proBNP, 6MWD, and FC) should be included in calculations.8Further validation and modeling are needed to establish the clinical utility of the REVEAL-ECHO risk score.10

European registries

European registries involving more than 3000 patients also support the prognostic utility of risk stratification.3-5 Online calculators developed from these registries, ESC/ERS Treatment Guidelines, COMPERA 2.0: 4-Risk Strata, and French Noninvasive Criteria, can be used to calculate your patient’s risk status.

COMPERA4
COMPERA 2.01,11

Overview

European prospective observational study (2009-2016); N=1588

European prospective observational study (2009-2020); N=1655

Variables

6 variables:

  • WHO FC
  • 6MWD
  • RAP
  • CI
  • NT-proBNP or BNP
  • SvO2

3 variables:

  • WHO FC
  • 6MWD
  • NT-proBNP or BNP

Risk calculation

Assigned risk-category grades to each variable based on ESC/ERS Treatment Guidelines (1=low, 2=intermediate, 3=high)

Risk category obtained by dividing sum of all grades by number of available variables and rounding to nearest integer

Assigned risk-category grades to each variable with cutoffs modified from REVEAL and ESC/ERS Treatment Guidelines to include 4 strata (1=low, 2=intermediate-low, 3=intermediate-high, 4=high)

Risk category obtained by dividing sum of all grades by number of available variables and rounding to next integer

Suggested use

Baseline risk assessment

Follow-up risk assessment

Follow-up risk assessment

COMPERA4

Overview

European prospective observational study (2009-2016); N=1588

Variables

6 variables:

  • WHO FC
  • 6MWD
  • RAP
  • CI
  • NT-proBNP or BNP
  • SvO2

Risk calculation

Assigned risk-category grades to each variable based on ESC/ERS Treatment Guidelines (1=low, 2=intermediate, 3=high)

Risk category obtained by dividing the sum of all grades by the number of available variables and rounding to the nearest integer

Suggested use

Baseline risk assessment

Follow-up risk assessment

COMPERA 2.01,11

Overview

European prospective observational study (2009-2020); N=1655

Variables

3 variables:

  • WHO FC
  • 6MWD
  • NT-proBNP or BNP

Risk calculation

Assigned risk-category grades to each variable with cutoffs modified from REVEAL and ESC/ERS Treatment Guidelines to include 4 strata (1=low, 2=intermediate-low, 3=intermediate-high, 4=high)

Risk category obtained by dividing sum of all grades by number of available variables and rounding to next integer

Suggested use

Follow-up risk assessment

French PAH Registry3
SPAHR5

Overview

French retrospective analysis (2006-2016); N=1017

Swedish observational study (2008-2016); N=530

Variables

4 variables:

  • WHO/NYHA FC
  • 6MWD
  • RAP
  • CI*

8 variables:

  • WHO FC
  • 6MWD
  • RAP
  • CI
  • NT-proBNP
  • SvO2
  • Pericardial effusion
  • RA area

Risk calculation

Invasive: 4 variables above were used to classify patients by number of low-risk criteria present

Noninvasive: 3 variables (WHO/NYHA FC, 6MWD, and BNP/NT-proBNP) were used to classify patients by number of low-risk criteria present

Assigned risk-category grades to each variable based on ESC/ERS Treatment Guidelines (1=low, 2=intermediate, 3=high)

Risk category obtained by dividing sum of all grades by number of available variables and rounding to nearest integer

Suggested use

Follow-up risk assessment

Baseline risk assessment

Follow-up risk assessment

French PAH Registry3

Overview

French retrospective analysis (2006-2016); N=1017

Variables

4 variables:

  • WHO/NYHA FC
  • 6MWD
  • RAP
  • CI*

Risk calculation

Invasive: 4 variables above were used to classify patients by number of low-risk criteria present

Noninvasive: 3 variables (WHO/NYHA FC, 6MWD, and BNP/NT-proBNP) were used to classify patients by number of low-risk criteria present

Suggested use

Follow-up risk assessment

SPAHR5

Overview

Swedish observational study (2008-2016); N=530

Variables

8 variables:

  • WHO FC
  • 6MWD
  • RAP
  • CI
  • NT-proBNP
  • SvO₂
  • Pericardial effusion
  • RA area

Risk calculation

Assigned risk-category grades to each variable based on ESC/ERS Treatment Guidelines (1=low, 2=intermediate, 3=high)

Risk category obtained by dividing sum of all grades by number of available variables and rounding to nearest integer

Suggested use

Baseline risk assessment

Follow-up risk assessment

*NT-proBNP or BP and SvO2 were included as an exploratory analysis when data were available.3

Use risk calculators to inform treatment plans

Risk Calculators
6MWD=6-minute walk distance; BNP=B-type natriuretic peptide; CI=cardiac index; COMPERA=Comparative, Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension; DLCO=diffusing capacity for carbon monoxide; Echo=echocardiography; ERS=European Respiratory Society; ESC=European Society of Cardiology; FC=functional class; HR=heart rate; mRAP=mean right atrial pressure; NT-proBNP=N-terminal pro–B-type natriuretic peptide​; NYHA=New York Heart Association; PVR=pulmonary vascular resistance; RA=right atrium/right atrial; RAP=right atrial pressure; RCT=randomized controlled trial; REVEAL=Registry to EValuate Early And Long-term pulmonary arterial hypertension disease management; SPAHR=Swedish Pulmonary Arterial Hypertension Registry; SvO2=mixed venous oxygen saturation; WHO=World Health Organization.
References: 1. Humbert M, et al. Eur Heart J. 2022;43(38):3618‐3731. 2. Dardi F, et al. Eur Respir J. 2024;64(4):2401323. 3. Boucly A, et al. Eur Respir J. 2017;50(2):1700889. 4. Hoeper MM, et al. Eur Respir J. 2017;50(2):1700740. 5. Kylhammar D, et al. Eur Heart J. 2018;39(47):4175-4181. 6. Benza RL, et al. Circulation. 2010;122(2):164-172. 7. Benza RL, et al. Chest. 2019;156(2):323-337. 8. Benza RL, et al. Chest. 2021;159(1):337-346. 9. Pop B, et al. Med Pharm Rep. 2019;92(1):7-14. 10. El-Kersh K, et al. Chest. 2023;163(5):1232-1244. 11. Hoeper M, et al. Eur Respir J. 2022;60:2102311.
Various calculators on the PAH Risk Score Calculator app