The remodeling paradox in ischemic HFrEF: dissociation between left ventricular cavity reduction and functional recovery according to ischemic phenotype

Background Current guidelines emphasize reverse remodeling as a therapeutic goal in Heart Failure with reduced Ejection Fraction (HFrEF). However, the influence of the specific non-coronary vs ischemic clinical history (ST-elevation Myocardial Infarction (STEMI) vs. Non-ST-elevation Myocardial Infarction (STEMI) vs. Chronic Ischemia) on long-term myocardial recovery in HFrEF remains poorly defined. Methods Retrospective study following 357 HFrEF patients (Left Ventricle Ejection Fraction (LVEF) <40%) over a 60-month period, categorized into four groups: Non-ischemic (G1), Chronic Ischemic (G2), nSTEMI (G3), and STEMI (G4). Serial echocardiography assessed LVEF, ventricular diameters, and diastolic function (lateral E/e'). Statistical differences in final and absolute changes among the four phenotypes were assessed using One-way ANOVA followed by Bonferroni post-hoc test for multiple comparisons. Results Left Ventricle Ejection Fraction: At 5-year follow-up, LVEF recovery was significantly asymmetrical (p=0.030). Non-ischemic G1 achieved the highest functional improvement (+14.3%), whereas STEMI (G4) and nSTEMI (G3) patients showed the most blunted responses (+4.2% and +4.9%, respectively). Left Ventricle (LV) End-Diastolic Diameter: Paradoxically, the STEMI group exhibited the most pronounced reduction in LV end-diastolic diameter (-7.31 mm vs. -4.42 mm in non-ischemic G1, p=0.001), suggesting a pattern of structural remodeling without functional recovery. Right Ventricular Function and Diastolic Function: Furthermore, STEMI was the only group where right ventricular function (TAPSE) failed to improve (-0.2 mm vs. +2.2 mm in non-coronary G1, p=0.001) and diastolic filling pressures significantly worsened (lateral E/e' +5.6% vs. -11.6% in G1, p=0.013). Conclusions Long-term ventricular recovery in HFrEF is highly phenotype-dependent. Post-STEMI patients exhibit a "Remodeling Paradox," where significant reduction in ventricular size does not translate into functional LVEF recovery, likely due to fixed myocardial fibrosis with persistent microvascular dysfunction, reduced contractile miocardiocitic reserve due to ischemic cell apoptosis and reduced exposure time to prognosis modifying pharmacotherapy through reduced survival. Inversely the greatest reduction in Left Ventricle telediastolic diameter was observed in this particular STEMI subgroup reflecting the positive effects coronary revascularization and optimal prognostic pharmacotherapy can have on cardiac ventricular remodeling. The increased lateral E/E’ ratio observed in group 3 and 4 acute ischemic cardiomyopathies (diastolic dysfunction) could be related to impaired aerobic pathaways with reduced Adenosine Triphosphate (ATP) regeneration and deficient myosin and actinine interaction at the myocardiocite level; reflecting the myocardium’s reduced capillarity and increased need of non oxygen related pathaways to create and destroy actin-myosine cross-bridges.