Refinements to European Strategy Can Improve PAH-CHD Stratification

Researchers of a new study published in the American Journal of Cardiology say certain tweaks to a European risk stratification strategy can make the tool more reliable in risk stratification of patients with pulmonary arterial hypertension related to congenital heart disease (PAH-CHD).¹

The 2015 European Society of Cardiology (ESC)/European Respiratory Society risk stratification strategy, created from various studies, categorizes patient risk of 1-year mortality based on various factors, including World Health Organization functional class, N-terminal pro-brain natriuretic peptide (NT-proBNP), exercise capacity, and right atria area (RAA).

The updated mortality estimates using this stratification approach were more congruous with guideline-provided estimates. | Image Credit: © Halfpoint - stock.adobe.com

The strategy, which focuses on a “flexible approach,” was validated in a retrospective analysis of 3 patient registries accounting for over 3100 patients with the disease, showing clear differences in 5-year survival or transplantation-free survival based on the risk stratification.² However, the validation of the tool has been limited to certain patients with the disease, explained the researchers of the new study.¹

“The accuracy of the ESC risk assessment strategy has only been validated for incident and treatment-naïve patients at baseline (i.e., time of PAH diagnosis) and within 1 year–reflecting only initial treatment responses,” wrote the researchers. “Our study population included both incident (newly diagnosed) and prevalent PAH-CHD patients. As such, our instrument may better reflect a real-world setting and may be applied at any time during the disease course. Our instrument performs as well at predicting short-term prognosis in prevalent patients, who may achieve a low-risk profile later on in the disease course (after 1 year) and who may differ substantially from incident patients.”

The study included 220 patients over a 15-year period, stratifying them based on a median of 4 variables at baseline and a median of 3 variables at follow-up over 18 months following the initial visit.

When using the current PAH guidelines risk assessment strategy, survival did not vary significantly across the 76% of patients considered intermediate risk, 18% considered low risk, and 6% considered high risk. This finding, noted the researchers, is likely due to the uneven distribution of risk groups.

The group noted that the 1-year mortality rates for intermediate-risk patients (6%) and for high-risk patients (7%) were lower than expected. Mortality rates at 1 year for low-risk patients was 0%. Expected 1-year mortality rates according to the guidelines are under 5% for low-risk patients, between 5% and 10% for intermediate-risk patients, and over 10% for high-risk patients.³

When patients were reclassified based on the adjusted thresholds of NT-proBNP and 6-minute walk distance and the inclusion of tricuspid annular plane systolic excursion (TAPSE) rather than RAA, classification of patients improved significantly.

Overall, the refined guidelines reclassified 29% of patients. There were 35 patients who were classified as lower risk, 6 from high to intermediate risk, and 29 from intermediate to low risk. Meanwhile, 29 patients were reclassified as higher risk, 15 from low to intermediate and 14 from intermediate to high.

One-year mortality remained 0% and 6% for low-risk and intermediate-risk patients, respectively, and increased to 18% for high-risk patients. The updated mortality estimates were more congruous with guideline-provided estimates, explained the researchers.

“Our findings support the use of TAPSE as prognostic marker in PAH-CHD, which is in line with previous studies showing TAPSE as a strong predictor of mortality in PAH-CHD,” noted the researchers. “The use of RAA may pose a difficult marker in the PAH-CHD population, as many patients already have abnormal atrial anatomy and right atrial enlargement due to volume overload by an atrial septal defect instead of being a distinct marker of PAH disease severity.”

Based on the proposed refined strategy, the low threshold for TAPSE was defined as more than 20 mm, intermediate was defined as 16 to 20 mm, and high was defined as less than 16 mm.

References

1. van Dissel AC, D’Alto M, Farro A, et al. Improved risk prediction using a refined European guidelines instrument in pulmonary arterial hypertension related to congenital heart disease. Am J Cardiol. 2024;233:28-34. doi:10.1016/j.amjcard.2024.08.027
2. Galiè N, Channick RN, Frantz RP, et al. Risk stratification and medical therapy of pulmonary arterial hypertension. Eur Respir J. 2019;53(1):1801889. doi:10.1183/13993003.01889-2018
3. Hoeper MM, Kramer T, Pan Z, et al. Mortality in pulmonary arterial hypertension: prediction by the 2015 European pulmonary hypertension guidelines risk stratification model. Eur Respir J. 2017;50(2):1700740. doi:10.1183/13993003.00740-2017