Short‐Term Changes in Left and Right Ventricular Cardiac Magnetic Resonance Feature Tracking Strain Following Ferric Carboxymaltose in Patients With Heart Failure: A Substudy of the Myocardial‐IRON Trial

Abstract

Background The mechanisms explaining the clinical benefits of ferric carboximaltose (FCM) in patients with heart failure, reduced or intermediate left ventricular ejection fraction, and iron deficiency remain not fully clarified. The Myocardial‐IRON trial showed short‐term cardiac magnetic resonance (CMR) changes suggesting myocardial iron repletion following administration of FCM but failed to find a significant increase in left ventricular ejection fraction in the whole sample. Conversely, the strain assessment could evaluate more specifically subtle changes in contractility. In this subanalysis, we aimed to evaluate the effect of FCM on the short‐term left and right ventricular CMR feature tracking derived strain. Methods and Results This is a post hoc subanalysis of the double‐blind, placebo‐controlled, randomized clinical trial that enrolled 53 ambulatory patients with heart failure and left ventricular ejection fraction <50%, and iron deficiency [Myocardial‐IRON trial (NCT03398681)]. Three‐dimensional left and 2‐dimensional right ventricular CMR tracking strain (longitudinal, circumferential, and radial) changes were evaluated before, 7 and 30 days after randomization using linear mixed‐effect analysis. The median (interquartile range) age of the sample was 73 years (65–78), and 40 (75.5%) were men. At baseline, there were no significant differences in CMR feature tracking strain parameters across both treatment arms. At 7 days, the only global 3‐dimensional left ventricular circumferential strain was significantly higher in the FCM treatment‐arm (difference: −1.6%, P =0.001). At 30 days, and compared with placebo, global 3‐dimensional left ventricular strain parameters significantly improved in those allocated to FCM treatment‐arm [longitudinal (difference: −2.3%, P <0.001), circumferential (difference: −2.5%, P <0.001), and radial (difference: 4.2%, P =0.002)]. Likewise, significant improvements in global right ventricular strain parameters were found in the active arm at 30 days (longitudinal [difference: −3.3%, P =0.010], circumferential [difference: −4.5%, P <0.001], and radial [difference: 4.5%, P =0.027]). Conclusions In patients with stable heart failure, left ventricular ejection fraction <50%, and iron deficiency, treatment with FCM was associated with short‐term improvements in left and right ventricular function assessed by CMR feature tracking derived strain parameters. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03398681.

High salt intake damages myocardial viability and induces cardiac remodeling via chronic inflammation in the elderly

“…An important finding of this study was the correlation between salt intake and myocardial strain rates. The myocardial strain rate has been demonstrated to be a direct and sensitive evaluation index for myocardial viability and early changes in cardiac function ( 10 – 13 ). In this study, we found significant differences in global SRe, SRa, and SRs between individuals with higher salt intake and those with lower salt intake.…”

“…The strain rate (SR) is a sensitive and direct index of myocardial viability and changes in cardiac function ( 10 – 13 ). SR quantifies the velocity of myocardial contraction and correlates with cardiomyocyte hypertrophy and fibrosis ( 14 , 15 ).…”

Intravenous iron in heart failure with reduced ejection fraction: just about right

“…17 In addition, all global 2D strain parameters of the right ventricle, assessed with CMR, were improved 30 days after FCM therapy. 11 The analysis by Martens et al provides evidence for more sustained favourable changes in RV function, 3 months after FCM therapy, with preliminary findings of reverse remodelling as evident from reduced RV end-systolic and end-diastolic areas. The remodelling findings, however, will need additional confirmation.…”

“…In a recently reported sub-study of the Myocardial-IRON trial, which evaluated whether ferric carboxymaltose (FCM) repletes myocardial iron better than placebo in patients with HF and LVEF <50%, analysis of ventricular mechanics with cardiac magnetic resonance (CMR) demonstrated improvement of global three-dimensional left ventricular (LV) strain parameters 30 days after FCM administration. 11 Of note, the main Myocardial-IRON trial reported CMR findings consistent with myocardial iron repletion with FCM, but the improvement in LVEF was not significantly better in the FCM arm versus placebo, suggesting that LVEF alone may not be sensitive enough to detect beneficial metabolic effects of iron supplementation on myocardial function. 12 There are even more limited data on the effect of iron supplementation therapy on right ventricular (RV) function and 13 published in this issue of the Journal is an important addition to the literature.…”

“…In a post‐hoc analysis of the Myocardial‐IRON trial, there were early (7 days) and sustained (30 days) improvements in RV ejection fraction with FCM therapy, 17 with a mean improvement of 8.1% at 30 days 17 . In addition, all global 2D strain parameters of the right ventricle, assessed with CMR, were improved 30 days after FCM therapy 11 . The analysis by Martens et al .…”