Role of dyssynchrony in short-term left ventricular systolic function after iron repletion in patients with heart failure

The mechanisms underlying the clinical benefit of intravenous iron in patients with heart failure (HF), left ventricular ejection fraction (LVEF) < 50%, and iron deficiency (ID) remain incompletely defined. Clinical evidence suggests that iron repletion may improve ventricular synchrony and augment the response to cardiac resynchronization therapy (CRT). The longitudinal systolic dyssynchrony index (L-SDI), derived from cardiac magnetic resonance feature tracking (CMR-FT), provides a non-invasive measure of mechanical dyssynchrony. This subanalysis of the Myocardial-IRON trial evaluated the short-term effects of ferric carboxymaltose (FCM) on L-SDI and explored its relationship with global left ventricular longitudinal strain (GLS). In this post hoc analysis of the randomized, double-blind, placebo-controlled Myocardial-IRON trial (NCT03398681), 51 of 53 ambulatory patients (96.2%) with stable HF, LVEF < 50%, and ID underwent CMR-FT at baseline, and at 7-day, and 30-days post-FCM. Linear mixed-effects models assessed the effect of FCM versus placebo on L-SDI, including subgroup analyses by baseline QRS duration, and evaluated associations between changes in L-SDI and changes in GLS, T2*, and T1-mapping. Data are presented as mean ± SD or median (IQR), as appropriate. The participants have a mean age of 70.4 ± 9.6 years, with a median CMR-derived LVEF of 38.5% (IQR 33–45); the mean global longitudinal strain is −7.5 ± 3.6%. FCM leads to a greater reduction in L-SDI over time versus placebo (omnibus p = 0.015), with significance at 30 days (Δ=–3.8; 95% CI –6.9 to –0.7; p = 0.011). The benefit is most pronounced in patients with baseline electrical dyssynchrony (interaction p < 0.001). Improvements in L-SDI are strongly associated with GLS gains (p < 0.001) and myocardial iron uptake [T2*changes (p = 0.045) and T1-mapping changes (p = 0.011)]. In HF with LVEF < 50% and ID, FCM improves short-term LV mechanical synchrony, particularly in those with electrical dyssynchrony, and this is linked to enhanced systolic function and greater myocardial iron repletion. Canto, Miñana, Cardells et al. assess left ventricular systolic dyssynchrony by cardiac magnetic resonance feature tracking following treatment with ferric carboxymaltose in people with chronic heart failure, iron deficiency, and a left ventricular ejection fraction <50%. A significant short-term improvement is seen. Iron deficiency is common in patients with heart failure and makes their condition worse. Although giving iron through an intravenous infusion is known to improve how patients feel and function, we do not fully understand how it benefits the heart itself. In this study, we used a type of heart imaging, cardiac magnetic resonance scans, to determine whether iron treatment improves heart pump coordination and synchronization. We found that patients who received an iron infusion showed clearer improvement in how well their heart muscle worked within 30 days compared with those who received a placebo. The benefit was especially noticeable in patients who already had abnormal heart electrical patterns. These findings suggest that iron treatment helps the heart muscle contract more uniformly, making the heart pump more efficiently and helping to explain why this therapy improves the health of people with heart failure.