Complex relationship between iron status and outcomes of STEMI: hypothesis-generating study

AIMS: Iron deficiency (ID) is common amongst patients with ST-elevation myocardial infarction (STEMI). Its impact on outcomes remains contested. Previous studies reported favourable or adverse impacts depending on outcome measures, sampling timepoints, ID definition and follow-up duration. This study systematically characterises the prognostic impact of iron status on short-term, mid-term and long-term outcomes, and evaluates the effect of sampling timepoint and ID definition on these prognostic relationships. METHODS & RESULTS: We performed an observational cohort study in patients with acute STEMI (n = 167) and no prior heart failure (HF). Iron markers were sampled at presentation, and successive timepoints thereafter. Cardiac Magnetic Resonance was performed at 2 days and 6 months. Major adverse cardiovascular events (MACE), consisting of new-onset HF, recurrent MI or cardiac death were recorded over 4.5 years. Mechanisms were evaluated in a preclinical model of MI.ID was common at presentation, affecting between 44.9% and 67%, depending on ID definition. Tsat <20%, serum iron<13μM, or European Society of Cardiology's definition, but not ferritin<100μg/L, independently predicted lower risk of MACE. Lower Tsat at presentation predicted attenuated infarct and non-infarct T1, and smaller left ventricular volumes at 2 days. This prognostic effect was weakened by delayed sampling. Lower Tsat and serum iron in the post-acute timepoints, but not at presentation, predicted lower myocardial salvage at 6 months. In mice, MI triggered an acute myocardial labile iron storm and early LV remodelling, progressing to HF. Baseline ID and acute iron chelation averted these effects. CONCLUSIONS: This study gives rise to the hypothesis that ID at presentation with STEMI improves long-term outcomes by attenuating myocardial injury. It reconciles previous conflicting reports by revealing the confounding effects of delayed sampling, and non-interchangeability of different ID definitions. It suggests iron chelation in the acute stage, followed by post-acute iron repletion might improve long-term outcomes.