van Dissel AC, D’Alto M, Farro A, Mathijssen H, Post MC, Bassareo PP, van Dijk APJ, Mulder BJM, Bouma BJ.Am J Cardiol. 2024 Dec 15;233:28-34. doi: 10.1016/j.amjcard.2024.08.027. Epub 2024 Sep 2.PMID: 39233061
Take-home Points:
- The ESC risk stratification tool for PAH has been validated in general PAH cohorts, utilizing WHO functional class, 6MWD, RAA, pericardial effusion, CI, RA pressures and mixed venous sats as a prognostic tool by dividing patients into low-, intermediate- and high-risk categories
- This instrument was now evaluated in a PAH-CHD cohort and compared to a modified risk assessment tool taking the following parameters into account:
- WHO functional class
- 6MWD
- TAPSE
- NT pro-BNP
- Pericardial effusion
- The new modified tool improved the prognostication and resulted in statistically different survival curves, with greater discriminatory power between the low-, intermediate- and high-risk groups
- Further external validation of this new tool is needed
Commentary from Dr. Blanche Cupido (Cape Town, South Africa), chief section editor of ACHD Journal Watch
Introduction:
The European guidelines on the diagnosis and treatment of PAH which incorporates WHO functional class, exercise capacity (6-minute walk distance – 6MWD), NT pro BNP levels and imaging and hemodynamic criteria, is currently used for risk stratification. Though validated in mixed PAH-etiology cohorts, it has not been well validated in PAH associated with CHD (PAH-CHD).
Aim: To identify the combination of markers that best prognosticates in PAH-CHD
Study Design: Retrospective cohort study conducted at 5 PAH-CHD expert centers in the Netherlands. Included were 223 adult patients seen between April 2004 and April 2019, those with PAH due to mixed etiologies were excluded. ± 50% of patients had their PAH diagnosed on echocardiography only (no RHC available).
Patients were first categorized into low-, intermediate- and high-risk categories based on the European guideline risk assessment tool, then with the new proposed tool which also includes TAPSE, and no invasive hemodynamic parameters. (previously shown to be a good prognostic marker in patients with Eisenmenger syndrome) – Table 1 below.
Key Finding:
- Mortality: Within 5 years of follow-up, 24.7% had died (n=55) and 1.3% (n=3) had undergone lung transplantation. The cause of death was right heart failure in 53.6%, sudden cardiac death in 9.3% and respiratory failure in 9.3%.
- Applying the European general PAH-guideline instrument classified 18% as low risk, 76% as intermediate risk, and 6% as high risk. Survival did not differ significantly between the 3 groups using this instrument, p=0.010 (Figure A below) Results were similar even when Eisenmenger cohort was analyzed separately. ROC AUC was 0.648
- Applying the new proposed tool: 6MWD and NT-proBNP thresholds were revised (see table 1) and TAPSE included instead of RA area. The prediction of survival was improved using this revised risk assessment tool (Figure B below) – ROC 0.701 was superior to the guideline-directed tool. Furthermore, the follow-up data showed greater discrimination between the 3 groups with 1 year mortality being 2%, 5%, and 15% respectively, p=0.001. This held true even when Eisenmenger patients were analyzed separately.
The revised tool reclassified 29% (n=64) of patients.
Discussion:
The ESC/European Respiratory Society guidelines risk stratification tool is based on variables and thresholds derived from multiple studies across various PAH subgroups. The validity for PAH-CHD is limited. PAH-CHD differs from other PAH etiologies in terms of cardiac anatomy, pathophysiology, clinical outcome, younger age of onset and less comorbidities, resulting in a 1- year mortality much lower than that of other PAH cohorts (5% vs 10.7%).
The inclusion of TAPSE is in line with previous studies showing its prognostic value. RA area pose a problem in CHD as most may already have abnormal RA anatomy due to anatomical defects.
Given that this cohort starts from 2004,before the accepted guideline directed PAH therapies, this cohort likely over-represents high risk patients.
Strengths:
- Unlike the ESC guideline risk stratification tool that was only validated in incident and treatment-naïve patients, this current cohort included incident and prevalent patients with PAH, thus better reflecting real-life cohorts.
- Analysis was performed separately too for Eisenmenger patients, to reduce confounding due to heterogeneity.
Limitations:
- Observational, retrospective
- Incomplete hemodynamic parameters – (only 47% have invasive RHC measurements), therefore the importance of invasive measures not considered in the new proposed tool. Only 12.6% had hemodynamic data on follow-up
- Study was done before the recent 2022 guidelines were published with some adaptations to the risk assessment tool (small changes though).
- Potential selection bias – there was a loss in patient numbers from baseline to follow-up (223 vs 178 patients)
- Small sample size, so subgroup analysis could only be performed for Eisenmenger and not other etiologies.
- External validation of this new tool is required.
Conclusion:
The external validity of the general ESC risk assessment tool for PAH has limited discriminatory value in PAH-CHD. The new refined risk stratification tool is proposed but requires external validation.
