Myocardial performance improvement after iron replacement in heart failure patients: The IRON-PATH II echo-substudy

Iron deficiency (ID) is a prevalent comorbidity in heart failure (HF) patients associated with poor prognosis and impaired physical capacity. Functional limitations linked to ID may be related to cardiac function abnormalities, which could be reversible with iron repletion. Some echocardiographic parameters, such as global longitudinal strain (GLS), myocardial work (MW), and its derivatives constructive work (CW), wasted work (WW), and work efficiency (WE), may provide additive value in advanced cardiac performance assessment. The IRON-PATH II was a multicenter, prospective and observational study designed to describe pathophysiological pathways associated to ID. The echo-substudy included 100 HF patients undergoing a specific pilot echocardiographic evaluation. Patients had left ventricular ejection fraction (LVEF) ≤50%, were in stable clinical condition, on standard HF medication, and with hemoglobin ≥11 g/dL. The final cohort included 98 patients. The ID group showed worse cardiac function, with lower GLS (–8.5±9% vs –10±10%), WE (74±10% vs 80±10%), and MW (665[453-1013] vs 947[542-1199] mmHg%), as well as higher WW (290[228-384] vs 212[138-305] mmHg%) and lower RV free wall strain (–13[-20-(–11)] % vs –17[-23-(–14)] %). Following iron repletion, ID patients demonstrated improved LV (GLS, MW, WE, and WW) and RV performance (RV free wall strain), aligning with non-ID patients (all p-values >0.05 compared to the non-ID group). In conclusion, among HF patients with reduced LVEF, ID was associated with worse myocardial performance in both the LV and RV, with these alterations being reversible after intravenous iron repletion.