Prognostic value of diastolic dysfunction markers for heart failure–related outcomes after ST-elevation myocardial infarction: development and external validation of ACEF-3
K O Kuku, K W L M Ricken, C Lenselink, H M Garcia-Garcia, P van der Harst, E Lipsic, A A Voors, J J WykrzykowskaAbstract
Background
Despite treatment advances, residual cardiovascular risk persists after ST-Elevation myocardial infarction (STEMI), with heart failure representing a major driver of adverse outcomes. The parsimonious ACEF (Age, Creatinine, Ejection Fraction) score is a widely used risk model that relies primarily on systolic function. Whether incorporating diastolic dysfunction into ACEF improves risk discrimination in a contemporary STEMI cohort remains uncertain.
Purpose
To develop and externally validate an enhanced ACEF score incorporating guideline-based echocardiographic markers of diastolic dysfunction (ACEF-3) for the prediction of heart failure–related outcomes after STEMI.
Methods
We studied patients with STEMI from the GIPS-III trial (2011–2013; derivation cohort) and the CardioLines Coronary Biobank (2015–2021; validation cohort). ACEF score was calculated as age divided by left ventricular ejection fraction plus one point for elevated creatinine. Diastolic burden was defined by echocardiographic markers (E/e ratio′ ≥14 and Left atrial Volume Index ≥34 mL/m²) yielding a 0–2 point scale that was incorporated into ACEF to derive ACEF-3. The primary outcome was time to a heart failure–related composite of cardiovascular death, new-onset heart failure, or heart failure hospitalization evaluated at three and five years post-STEMI. Associations were evaluated using Cox regression, discrimination using Harrell’s C-index and incremental discrimination using bootstrap estimation of ΔC.
Results
In the derivation cohort (n=380; mean age 59 ± 12 years; 25% female), ACEF was associated with the 3-year heart failure composite in multivariable analysis (HR 2.88 per point; 95% CI 1.28–6.49; p=0.011), with a C-index of 0.78 (95% CI 0.63–0.92). The incorporation of diastolic burden improved model discrimination (C-index 0.89; 95% CI 0.84–0.95). Similar improvement was observed at 5 years, with discrimination increasing from 0.77 (95% CI 0.63–0.91) for ACEF to 0.87 (95% CI 0.80–0.94) for ACEF-3. In the validation cohort (n=416; mean age 63 ± 12 years; 26% female), ACEF demonstrated good discrimination for the 3-year heart failure composite (C-index 0.735). ACEF-3 showed comparable performance (C-index 0.743; ΔC=0.008; 95% CI −0.054 to 0.080). At 5 years, ACEF achieved a C-index of 0.728, compared with 0.710 for ACEF-3 (ΔC=−0.018; 95% CI −0.073 to 0.045). Incremental discrimination was not statistically significant (p > 0.05).
Conclusion
In a contemporary cohort of STEMI patients undergoing primary PCI, adding diastolic dysfunction markers to ACEF improved prediction of heart-failure–related outcomes in the development cohort but did not consistently enhance discrimination in external validation. These findings suggest that ACEF already captures much of the prognostic signal conveyed by diastolic burden, and that the value of diastolic parameters for risk stratification may be phenotype-specific, warranting further investigation.ACEF-3 Model Discrimination