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

Abstract

Background 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). Methods 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. Results 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 (Delta=-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)]. Conclusions 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.