Worse CTD-PAH Prognosis Seen With Higher HFA-PEFF Score

All-cause mortality and clinical worsening events are more likely to occur among patients who have connective tissue disease–associated pulmonary arterial hypertension (CTD-PAH) and a Heart Failure Association–preserved ejection fraction (HFA-PEFF) algorithm score of 5 or higher, according to a new study published in BMC Cardiovascular Disorders.¹

The study authors explain that patients who have CTD-PAH and left heart dysfunction have greater risk of a worse overall prognosis and that the HFA-PEFF algorithm is a reliable tool for diagnosing heart failure with preserved ejection fraction (HFpEF) and disease outcomes in this population.^2,3 There are 4 steps to this algorithm, they add:

1. Pretest assessment
2. HFA-PEFF score calculation
3. Functional testing for intermediate scores
4. Investigation of specific etiologies

Patients included in this single-center retrospective study were equally divided into 2 groups: HFA-PEFF score below 5 (n = 74), indicating low and intermediate probability of HFpEF, and 5 or higher (n = 73), indicating high probability of HFpEF. The primary end point of interest was all-cause mortality, and the secondary end point of interest was clinical worsening events. Most of this population was female (95.25%), 39 years or older (P = .153), and taking a glucocorticoid (89.1%) or on combination therapy (70.75%).

Adult patients were included in this analysis if their condition was diagnosed by right heart catheterization (RHC) between June 2016 and January 2024, they had an ultrasound-guided cardiogram within 1 month of the RHC, they were followed for at least 3 months, and they fit the criteria for PAH: mean pulmonary arterial pressure (mPAP) above 20 mm Hg, pulmonary arterial wedge pressure of 15 mm Hg or below, and pulmonary vascular resistance (PVR) above 2 WU. The follow-up was every 3 months.

Patient Results

Overall, several important clinical measures were worse among the patients with a HFA-PEFF score of 5 or higher vs below 5. They had a shorter time from diagnosis of CTD (0.90 vs 31.50 months; P = .046), shorter 6-minute walking distance (6MWD) results (386 vs 465 m; P < .001), and higher serum NT-proBNP level (2094 vs 202 pg/mL, P < .001), and more patients with World Health Organization functional class (WHO FC) III-IV disease (68.1% vs 28.4%; P < .001).

“These findings highlight the importance of using the HFA-PEFF score for risk stratification and prognosis in CTD-PAH patients, allowing for more targeted management and improved outcomes,” the study authors explain. | Image Credit: © Dzianis Vasilyeu-stock.adobe.com

These patients also had higher baseline mPAP (48 vs 37 mm Hg; P < .001), PVR (9.66 vs 5.43 mm Hg; P < .001), mean right atrial pressure (6 vs 4 mm Hg; P = .022), and mean right ventricular (RV) pressure (27 vs 22; P < .001); lower cardiac index (2.54 vs 3.10; P < .001); larger RV end-diastolic volume index (115.0 vs 89.3 mL/m²; P = .025), RV end-systolic volume index (75.1 vs 54.3; P < .001), and RV mass index (16.1 vs 10.4; P < .001); smaller tricuspid annular plane systolic excursion (TAPSE; 15.3 vs 17.3 mm; P = .001); and lower TAPSE/pulmonary artery systolic pressure (0.19 vs 0.29; P < .001), RV fractional area change (28.2% vs 32.9%; P < .001), and RV ejection fraction (27.0% vs 39.3%).

Further, measures of left heart function were inferior in those with HFA-PEFF score of 5 or higher: left ventricular (LV) end diastolic volume index (54.7 vs 68.9 mL/m²; P = .001), LV end systolic volume index (22.5 vs 29.3 mL/m²; P < .001), and LV mass index (38.2 vs 43.4 g/m²; P = .014).

Univariable and multivariable Cox regression analyses demonstrated connections between HFA-PEFF score of 5 or higher and all-cause mortality (HR, 5.865; 95% CI, 1.678-20.500; P = .006) and clinical worsening events (HR, 2.670; 95% CI, 1.166-6.117; P = .020). At follow-up, these patients were also more likely to have higher serum NT-proBNP, shorter 6MWD, and more cases of WHO FC III-IV disease.

Concluding Thoughts

Of their findings, the study authors explained that these data demonstrate more severe PAH among patients diagnosed with CTD-PAH and that there is an independent association between a baseline HFA-PEFF score of 5 or higher and increased risk of all-cause mortality and clinical worsening events. They also write that their results echo previous research on the coexistence of PAH and left heart dysfunction,^4,5 as well as higher RV and atrial pressures.

“The primary contributors to HFpEF in this population appear to be RV enlargement and myocardial edema or fibrosis,” they write. “These findings highlight the importance of using the HFA-PEFF score for risk stratification and prognosis in CTD-PAH patients, allowing for more targeted management and improved outcomes.”

References

1. Dai J, Ma L, Zhang Y, et al. The prognostic value of HFA-PEFF score in connective tissue disease-associated PAH: evidence from a cohort study. BMC Cardiovasc Disord. 2025;25(1):258. doi:10.1186/s12872-025-04691-y

2. Egashira K, Sueta D,Komorita T, et al. HFA-PEFF scores: prognostic value in heart failure with preserved left ventricular ejection fraction. Korean J Intern Med. 2021;37(1):96-108. doi:10.3904/kjim.2021.272

3. Pieske B, Tschöpe C, de Boer RA, et al. How to diagnose heart failure with preserved ejection fraction: the HFA-PEFF diagnostic algorithm: a consensus recommendation from the Heart Failure Association (HFA) of the European Society of Cardiology (ESC). Eur J Heart Fail. 2020;22(3):391-412. doi:10.1002/ejhf.1741

4. Lui JK, Cozzolino M, Winburn M, et al. Role of left ventricular dysfunction in systemic sclerosis-related pulmonary hypertension. Chest. 2024;165(6):1505-1517. doi:10.1016/j.chest.2023.12.018.

5. Mclaughlin VV, Vachiery JL, Oudiz RJ, et al. Patients with pulmonary arterial hypertension with and without cardiovascular risk factors: results from the AMBITION trial. J Heart Lung Transplant. 2019;38(12):1286-1295. doi:10.1016/j.healun.2019.09.010