Clinical predictors and prognostic implications of HFpEF following STEMI based on HFA-PEFF score: a multicenter cohort analysis
Highlight box
Key findings
• In patients with ST-segment elevation myocardial infarction (STEMI) who had preserved left ventricular ejection fraction (LVEF) after successful percutaneous coronary intervention (PCI), heart failure with preserved ejection fraction (HFpEF), defined by the Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final etiology (HFA-PEFF) score, was identified in a substantial proportion of patients and was associated with worse long-term clinical outcomes.
What is known and what is new?
• HFpEF is increasingly recognized after acute coronary syndromes, but its clinical relevance after STEMI has not been fully clarified, particularly among patients whose LVEF is preserved after revascularization.
• This study shows that the HFA-PEFF score can identify a clinically meaningful HFpEF phenotype after STEMI. Patients classified as having HFpEF had distinct clinical characteristics and a higher risk of adverse outcomes compared with those without HFpEF.
What is the implication, and what should change now?
• Systematic assessment for HFpEF using the HFA-PEFF score may help improve post-STEMI risk stratification in patients with preserved LVEF. Further prospective studies are needed to determine whether targeted follow-up and treatment strategies can improve outcomes in this population.
Introduction
ST-segment elevation myocardial infarction (STEMI) is a life-threatening manifestation of coronary artery disease (CAD) and remains a leading cause of morbidity and mortality worldwide (1,2). Advances in reperfusion therapy have markedly improved short-term survival (3). Nevertheless, long-term prognosis after STEMI remains a major clinical concern, primarily due to the subsequent development of heart failure (HF) (3,4), which is strongly associated with increased risks of death and recurrent hospitalization (5,6).
HF results from structural or functional myocardial impairment and is influenced by risk factors such as hypertension, diabetes, obesity, and CAD (7-9). CAD is the predominant cause of heart failure with reduced ejection fraction (HFrEF), typically through ischemic injury and adverse remodeling. In contrast, heart failure with preserved ejection fraction (HFpEF) is characterized by preserved systolic function with impaired diastolic relaxation and elevated filling pressures. Although HFpEF has traditionally been linked to chronic comorbidities, it may also occur in the setting of acute coronary syndromes, including STEMI (5).
HFpEF now accounts for approximately half of all HF cases and is especially common in older patients and those with multiple comorbidities (10,11). To enhance diagnostic accuracy, the Heart Failure Association Pre-test assessment, Echocardiography and natriuretic peptide, Functional testing, Final etiology (HFA-PEFF) score was introduced as a structured algorithm incorporating functional, morphological, and biomarker domains (12). Beyond diagnosis, the HFA-PEFF score has demonstrated prognostic utility, with higher scores associated with increased cardiovascular (CV) risk (13,14). However, data on its clinical application in patients with STEMI remain scarce. Therefore, in this study, we aimed to investigate the prevalence, clinical predictors, and prognostic implications of HFpEF following STEMI, using the HFA-PEFF score as a diagnostic and risk-stratification tool.
Importantly, most prior studies in STEMI populations have focused on patients with reduced LVEF, whereas risk stratification in patients with preserved LVEF remains poorly defined. In this context, HFpEF is frequently under-recognized despite its potential clinical impact. Furthermore, although the HFA-PEFF score has been validated in stable or ambulatory HFpEF populations, its prognostic utility in the post-acute myocardial infarction setting has not been well established. Therefore, this study aimed not only to assess the prevalence of HFpEF following STEMI but also to evaluate the prognostic significance of the HFA-PEFF score in patients with preserved LVEF using a multicenter cohort. We present this article in accordance with the STROBE reporting checklist (available at https://cdt.amegroups.com/article/view/10.21037/cdt-2026-1-0020/rc).
Methods
Study design and population
The Gyeongsang National University Hospital registry is a prospective, dual-center cohort study that consecutively enrolled patients hospitalized with acute or chronic coronary syndromes between January 2011 and December 2015. Patients were enrolled from two participating centers: Gyeongsang National University Changwon Hospital, Changwon, Republic of Korea, and Gyeongsang National University Hospital, Jinju, Republic of Korea. The registry collected comprehensive clinical data, laboratory measurements, and transthoracic echocardiographic parameters. Details of the study design have been reported previously (ClinicalTrials.gov identifier: NCT04650529) (15). For the present analysis, we included patients with STEMI who underwent percutaneous coronary intervention (PCI) during the index hospitalization. All enrolled patients achieved successful reperfusion within 24 hours of symptom onset and demonstrated a left ventricular ejection fraction (LVEF) ≥50% on follow-up echocardiography at 1 month. Patients without baseline or 1-month echocardiographic data, as well as those presenting with out-of-hospital cardiac arrest, were excluded (Figure 1).
Definition—HFA-PEFF score
The HFA-PEFF score was used to classify patients with preserved LVEF. This score comprises three domains—functional, morphological, and biomarker—each incorporating major and minor criteria (12). In this system, major criteria are assigned 2 points and minor criteria 1 point. The functional domain reflects diastolic performance, assessed by measures such as the E/e' ratio, tricuspid regurgitation velocity, and left atrial strain. The morphological domain captures structural abnormalities, including left atrial enlargement and left ventricular hypertrophy. The biomarker domain is based on circulating natriuretic peptide levels [brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide], interpreted according to sex-specific and rhythm-adjusted thresholds. The total score ranges from 0 to 6, with patients categorized as non-HFpEF (score 0–4) or HFpEF (score 5–6), consistent with the original HFA-PEFF diagnostic algorithm.
Data collection and outcomes
Clinical, laboratory, and echocardiographic data were prospectively collected. Patients were followed at 1, 6, and 12 months after the index procedure, and annually thereafter. The primary endpoint was the composite of CV death or hospitalization for HF; secondary endpoints were CV death and hospitalization for HF. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study protocol was approved by the Institutional Review Board of Gyeongsang National University Changwon Hospital (No. 2025-09-014). Gyeongsang National University Hospital was also informed of and agreed to participate in the study. Owing to the retrospective nature of this registry analysis, the requirement for written informed consent was waived.
Statistical analysis
Statistical analyses were performed using SPSS version 26.0 (IBM Corp., Armonk, NY, USA), R programming version 3.1.0 (The R Foundation for Statistical Computing, Vienna, Austria, http://www.R-project.org). Categorical variables were compared using the chi-square test or Fisher’s exact test, as appropriate. Continuous variables were analyzed with the independent t-test or Mann-Whitney U test, depending on data distribution. Survival curves were generated using the Kaplan-Meier method and compared with the log-rank test. Multivariable Cox proportional hazards regression analysis was performed to identify independent predictors of the primary outcome, adjusting for potential confounders including age, sex, and comorbidities. Variables were selected based on clinical relevance and prior literature, along with variables showing P<0.10 in univariable analysis. The proportional hazards assumption was tested and confirmed. To delineate the trend of primary outcome in relation to HFA-PEFF score, a restricted cubic spline modeling approach with three knots was utilized.
To identify clinical predictors of HFpEF at 1-month follow-up, univariate logistic regression was first performed using baseline demographic, clinical, and treatment variables. Variables with P<0.05 in univariate analysis were entered into a multivariable logistic regression model, which was constructed using backward stepwise selection. Only variables that remained statistically significant (P<0.05) were retained in the final model. Model diagnostics were performed to assess multicollinearity and overall goodness-of-fit.
Results
Study flow
Figure 1 summarizes the study flow. Among 7,703 patients enrolled in the registry, 421 had evaluable data for HF hospitalization. Of these, 280 patients demonstrated an LVEF ≥50% at 1 month and were included in the final analysis. Based on the HFA-PEFF score, 192 patients were classified as non-HFpEF and 88 as HFpEF.
Baseline characteristics
The mean age of the overall cohort was 64 years, 72.1% were male, 41.1% had hypertension, and 21.4% had diabetes. Compared with the non-HFpEF group, patients with HFpEF were significantly older (P<0.001), more frequently female (P<0.001), less likely to be current smokers (P=0.004), and more likely to have a history of ischemic heart disease (P=0.046) (Table 1).
Table 1
| Variable | Non-HFpEF (n=192) | HFpEF (n=88) | P value |
|---|---|---|---|
| Age, years | 60.76±12.01 | 70.45±11.40 | <0.001 |
| Female | 31 (16.1) | 41 (46.6) | <0.001 |
| Risk factor, n (%) | |||
| Hypertension | 74 (38.5) | 41 (46.6) | 0.25 |
| Diabetes | 36 (18.8) | 24 (27.3) | 0.14 |
| Obesity (BMI ≥25 kg/m2) | 67 (34.9) | 22 (25.0) | 0.13 |
| Current smoker | 98 (51.0) | 28 (31.8) | 0.004 |
| Previous history | |||
| Ischemic heart disease | 19 (9.9) | 17 (19.3) | 0.046 |
| Chronic kidney disease | 22 (11.5) | 12 (13.6) | 0.75 |
| Stroke | 8 (4.2) | 3 (3.4) | >0.99 |
| Killip class | 0.42 | ||
| I | 169 (88.0) | 78 (88.6) | |
| II | 12 (6.2) | 4 (4.5) | |
| III | 9 (4.7) | 3 (3.4) | |
| IV | 2 (1.0) | 3 (3.4) | |
| Procedural characteristics | |||
| Culprit vessel | 0.81 | ||
| Left main coronary artery | 5 (2.6) | 6 (6.8) | |
| Left anterior descending artery | 103 (53.6) | 42 (47.7) | |
| Left circumflex artery | 65 (33.9) | 33 (37.5) | |
| Right coronary artery | 21 (10.9) | 11 (12.5) | |
| Multivessel disease | 100 (52.1) | 45 (51.1) | 0.33 |
| Door to balloon time (min) | 58.67±89.45 | 74.30±186.86 | 0.46 |
| Symptom to balloon time (min) | 338.64±487.15 | 268.98±249.04 | 0.12 |
| Concomitant medications | |||
| Angiotensin blockade | 161 (83.9) | 77 (87.5) | 0.54 |
| Beta blocker | 174 (90.6) | 75 (85.2) | 0.26 |
| Statin | 187 (97.4) | 87 (98.9) | 0.73 |
Values are mean ± standard deviation or n (%). BMI, body mass index; HFpEF, heart failure with preserved ejection fraction.
Echocardiographic parameters also differed significantly between groups. The HFpEF group demonstrated a higher left ventricular mass index (P<0.001), left atrial volume index (P<0.001), septal E/e' ratio (P<0.001), and tricuspid regurgitation peak velocity (P<0.001) compared with the non-HFpEF group. In addition, plasma BNP levels were markedly higher in the HFpEF group (P=0.01) (Table 2).
Table 2
| Variable | Non-HFpEF (n=192) | HFpEF (n=88) | P value |
|---|---|---|---|
| IVSd (mm) | 9.1±1.2 | 9.6±1.4 | 0.008 |
| LVPwd (mm) | 9.1±1.2 | 9.6±1.5 | 0.006 |
| LVEDD (mm) | 50.6±5.2 | 50.1±5.6 | 0.42 |
| LVESD (mm) | 36.9±21.3 | 35.3±5.3 | 0.33 |
| LVMI (g/m2) | 95.8±20.4 | 109.1±24.1 | <0.001 |
| RWT | 0.36±0.06 | 0.39±0.08 | 0.008 |
| LAVI (mL/m2) | 27.4±7.7 | 38.8±8.8 | <0.001 |
| Septal e' (cm/s) | 6.1±1.9 | 4.6±1.5 | <0.001 |
| Septal E/e' | 10.2±3.1 | 13.9±4.7 | <0.001 |
| Average E/e' | 9.3±3.2 | 12.7±4.3 | <0.001 |
| TR peak velocity (m/s) | 2.2±0.3 | 2.5±0.3 | <0.001 |
| Ejection fraction (%) | 55.4±5.57 | 55.4±5.4 | 0.95 |
| PEFF_score | <0.001 | ||
| 0 | 17 (8.9) | ||
| 1 | 14 (7.3) | ||
| 2 | 50 (26.0) | ||
| 3 | 45 (23.4) | ||
| 4 | 66 (34.4) | ||
| 5 | 44 (50.0) | ||
| 6 | 44 (50.0) | ||
| PEFF_f | <0.001 | ||
| 0 | 50 (26.0) | 0 | |
| 1 | 28 (14.6) | 4 (4.5) | |
| 2 | 105 (54.7) | 84 (95.5) | |
| PEFF_b | <0.001 | ||
| 0 | 65 (33.9) | 0 | |
| 1 | 41 (21.4) | 11 (12.5) | |
| 2 | 80 (41.7) | 77 (87.5) | |
| PEFF_m | <0.001 | ||
| 0 | 115 (59.9) | 0 | |
| 1 | 50 (26.0) | 29 (33.0) | |
| 2 | 12 (6.2) | 59 (67.0) | |
| BNP, pg/mL | 27.0 (14.0–61.3) | 82.0 (41.5–228.5) | 0.01 |
Values are mean ± standard deviation, median (interquartile range) or n (%). BNP, B-type natriuretic peptide; e', early diastolic mitral annular velocity; E/e', ratio of early transmitral flow velocity to e'; HFpEF, heart failure with preserved ejection fraction; IVSd, interventricular septal thickness at end-diastole; LAVI, left atrial volume index; LVEDD, left ventricular end-diastolic diameter; LVESD, left ventricular end-systolic diameter; LVMI, left ventricular mass index; LVPWd, left ventricular posterior wall thickness at end-diastole; PEFF, Pre-test assessment; RWT, relative wall thickness; TR, tricuspid regurgitation.
Predictors of HFpEF
Twelve baseline variables were assessed as potential determinants of HFpEF. In multivariable logistic regression analysis, age ≥65 years [adjusted odds ratio (aOR) 2.22], female sex (aOR 5.53), and history of ischemic heart disease (aOR 3.05) emerged as independent predictors of HFpEF (Table 3).
Table 3
| Multivariable logistic regression | OR | P |
|---|---|---|
| Old age (≥65 years) | 2.22 | 0.01 |
| Female | 5.53 | <0.001 |
| Current smoker | 0.85 | 0.63 |
| Ischemic heart disease | 3.05 | 0.01 |
| Chronic kidney disease | 0.74 | 0.52 |
| Stroke | 0.56 | 0.46 |
| Atrial fibrillation on admission | 3.49 | 0.34 |
| Killip class | 0.83 | 0.36 |
| Multivessel disease | 0.90 | 0.74 |
| Angiotensin blockade | 1.58 | 0.30 |
| Beta_blocker | 0.55 | 0.21 |
| Statin | 1.42 | 0.80 |
OR, odds ratio.
Clinical outcomes
During a median follow-up of 908 days (interquartile range, 562–1,132 days), 2 patients (0.7%) died from CV causes and 29 (10.4%) were hospitalized for HF. CV deaths occurred exclusively in the HFpEF group (n=2). The incidence of HF hospitalization was significantly higher in the HFpEF group than in the non-HFpEF group (17.0% vs. 7.3%, P=0.04). Kaplan-Meier analysis demonstrated that patients with HFpEF had a significantly worse prognosis, with a higher cumulative incidence of the primary outcome at 3 years compared with those without HFpEF (18.2% vs. 8.1%, log-rank P=0.02) (Figure 2). In the multivariable Cox proportional hazards model adjusted for age, sex, smoking status, chronic kidney disease, and multivessel disease, HFpEF was independently associated with an increased risk of the composite outcome [hazard ratio (HR) 2.45; 95% confidence interval (CI): 1.10–5.44; P=0.03] (Table 4). Restricted cubic spline analysis further demonstrated a linear association between increasing HFA-PEFF score and higher risk of the primary outcome (Figure 3). To assess the incremental prognostic value of HFpEF, time-dependent ROC curve analysis was performed. Model 1 included age, sex, smoking status, chronic kidney disease, multivessel disease, and HFpEF, whereas Model 2 excluded HFpEF. The c-statistics were 0.702 (95% CI: 0.656–0.749) and 0.680 (95% CI: 0.625–0.735), respectively, with no significant difference between the models (P=0.34) (Figure S1).
Table 4
| Clinical outcomes | Total (n=280) | Non-HFpEF (n=192) | HFpEF (n=88) | HR (95% CI) | P value | |
|---|---|---|---|---|---|---|
| Unadjusted | Adjusted | |||||
| CV death | 2 (0.7) | 0 | 2 (2.3) | – | – | – |
| CV death/HF hospitalization composite | 29 (10.4) | 14 (7.3) | 15 (17.0) | 2.61 (1.26–5.41) | 2.45 (1.10–5.44) | 0.01/0.03* |
Values are n (%). *, adjusted for old age, female sex, current smoker, chronic kidney disease, and multivessel disease. CI, confidence interval; CV, cardiovascular; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HR, hazard ratio.
Discussion
In this study of patients with STEMI and preserved LVEF, approximately 30% met the criteria for HFpEF as defined by the HFA-PEFF score. These patients had significantly worse clinical outcomes than those without HFpEF, underscoring the prognostic importance of this phenotype in the post-STEMI setting. Independent predictors of HFpEF were female sex, advanced age, and a history of ischemic heart disease. In addition, restricted cubic spline analysis demonstrated a linear relationship between higher HFA-PEFF scores and increased event rates, reinforcing the value of this scoring system for risk stratification in this population. To our knowledge, this is one of the first studies to specifically evaluate the prognostic implications of the HFA-PEFF score in STEMI patients with preserved LVEF using a standardized post-acute echocardiographic assessment.
Mechanisms of HFpEF after STEMI
Traditionally, prognostic assessment after STEMI has focused on reduced LVEF (16). Recent studies have reported the incidence and clinical impact of HFrEF following acute coronary syndromes, highlighting the spectrum of post-ACS HF. In this context, our findings suggest that HFpEF may also be relevant in patients with preserved LVEF (17). Our findings emphasize that HFpEF, even in the context of preserved systolic function, carries a substantial prognostic burden and warrants equal clinical attention. The adverse outcomes observed in HFpEF following STEMI may be explained by several mechanisms. Ischemic injury can impair diastolic relaxation, elevate left atrial pressures, and promote atrial remodeling, all of which are characteristic features of HFpEF (9,18). The clustering of risk factors such as advanced age, female sex, and prior ischemic heart disease may further heighten susceptibility to recurrent congestion and hospitalization (19). In our cohort, higher BNP levels, enlarged left atrial volume index, and elevated E/e’ among HFpEF patients suggest persistent hemodynamic congestion, predisposing to adverse events. Moreover, microvascular dysfunction and systemic inflammation—key elements in the pathophysiology of HFpEF—may be exacerbated by ischemic injury (9,20). Finally, concentric remodeling and hypertrophy, reflected by an increased LV mass index, may contribute to maladaptive structural changes and worsening diastolic burden (21).
Clinical utility of the HFA-PEFF score in STEMI
Our findings extend the clinical applicability of the HFA-PEFF score to patients with acute coronary syndromes. Previous studies have validated its diagnostic and prognostic roles in general HFpEF cohorts, with higher scores consistently associated with adverse outcomes (22). In the present study, we demonstrate that the HFA-PEFF score can also identify HFpEF in STEMI patients and provide incremental prognostic information, with a clear dose-response relationship between higher scores and increased event risk. This suggests that the HFA-PEFF score may serve as a simple and practical tool for early risk stratification, guiding closer follow-up and individualized management in STEMI patients with preserved EF.
Integrating diastolic dysfunction into post-STEMI risk stratification
These results align with prior evidence indicating that HFpEF after myocardial infarction is not uncommon and confers a prognosis comparable to HFrEF (23). Whereas earlier studies primarily emphasized systolic dysfunction, our data highlight the prognostic relevance of diastolic dysfunction and the HFpEF phenotype. Furthermore, a recent meta-analysis confirmed that higher HFA-PEFF scores are associated with increased risk of all-cause mortality (HR 1.39) across diverse populations (24). Collectively, these findings support incorporating HFA-PEFF scoring into post-STEMI care as part of a more comprehensive risk assessment strategy.
Limitations
This study has several limitations. First, it was a retrospective analysis of a single cohort, and residual confounding cannot be excluded despite adjustment for multiple clinical variables. Important factors such as infarct size, extent of CAD, prior revascularization history, medication adherence, and socioeconomic variables were not fully captured and may have influenced the observed associations. Second, patients with events within the first month after STEMI were excluded because the HFA-PEFF score was assessed at the 1-month follow-up. This may have introduced selection bias by excluding patients with more severe early presentations and could limit generalizability to the broader STEMI population. However, this approach allowed for a more reliable assessment of HFpEF by minimizing the influence of acute-phase hemodynamic instability and transient diastolic dysfunction. Third, the number of CV deaths was relatively small, which may have reduced statistical power for detecting differences in mortality. Fourth, HFpEF was defined using the HFA-PEFF score at a single time point, without accounting for longitudinal changes in diastolic function or structural remodeling.
Conclusions
In this study of patients with STEMI and preserved LVEF, a substantial proportion met the criteria for HFpEF as defined by the HFA-PEFF score. These patients had significantly higher risks of CV death and HF hospitalization compared with those without HFpEF. Moreover, a linear relationship between increasing HFA-PEFF scores and adverse outcomes was observed. These findings underscore the prognostic utility of the HFA-PEFF score as a simple and practical tool for early risk stratification, supporting its integration into routine post-STEMI care.
Acknowledgments
None.
Footnote
Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2026-1-0020/rc
Data Sharing Statement: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2026-1-0020/dss
Peer Review File: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2026-1-0020/prf
Funding: This work was supported by
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-2026-1-0020/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study protocol was approved by the Institutional Review Board of Gyeongsang National University Changwon Hospital (No. 2025-09-014). Gyeongsang National University Hospital was also informed of and agreed to participate in the study. Owing to the retrospective nature of this registry analysis, the requirement for written informed consent was waived.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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