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.

Keywords: CMR feature tracking; ferric carboxymaltose; heart failure; iron deficiency; ventricular strain.

Figure 1. Left ventricular (LV) and right ventricular (RV) cardiac magnetic resonance feature tracking in the short‐axis (A), and 2‐chamber (B), 3‐chamber (C), and 4‐chamber (D) cine images at end‐diastole.

The red and green curves delineate the endocardial and epicardial contours in LV, respectively; the yellow and cyan curves delineate the endocardial and epicardial contours in the RV, respectively. The blue and magenta points represent the superior and inferior RV insertion points on short‐axis cines (A). The blue (LV) and orange (RV) lines are used to define the base and apex of the mitral annulus plane and the apical plane (B through D). Representation of LV global longitudinal strain, global circumferential strain, and global radial strain curves using 3D cardiac magnetic resonance feature tracking (E through G). Representation of RV global longitudinal strain, global circumferential strain, and global radial strain curves using 2D cardiac magnetic resonance feature tracking (H through J).

Figure 2. Differences in left vetricular (LV) strain on cardiac magnetic resonance feature tracking at 7 and 30 days following the administration of ferric carboxymaltose in patients included in the Myocardial‐IRON trial.

Values are presented as the least square means from each linear mixed model. All models were adjusted by the participant center (as a cluster variable), the interaction term treatment visit (7 and 30 days), age, sex, and the baseline (pretreatment) value of the regressed outcome. (A) LV 3D‐GLS. (B) LV 3D‐GCS. (C) LV 3D‐GRS. 3D‐GCS indicates 3‐dimensional global circumferential strain; 3D‐GLS, 3‐dimensional global longitudinal strain; and 3D‐GRS, 3‐dimensional global radial strain.

Figure 3. Differences in right ventricular (RV) strain on cardiac magnetic resonance feature tracking at 7 and 30 days following the administration of ferric carboxymaltose in patients included in the Myocardial‐IRON trial.

Values are presented as the least square means from each linear mixed effects model. All models were adjusted by the participant center (as a cluster variable), the interaction term treatment*visit (7 and 30 days), age, sex, and the baseline (pretreatment) value of the regressed outcome. (A) RV 2D‐GLS. (B) RV 2D‐GCS. (C) RV 2D‐GRS. 2D‐GCS indicates 2‐dimensional global circumferential strain; 2D‐GLS, 2‐dimensional global longitudinal strain; and 2D‐GRS, 2‐dimensional global radial strain.

Figure 4. Association of left ventricular 3D‐global radial strain with changes in myocardial iron content (T2*).

Values are the least‐square means (95% CIs) from each linear regression analysis. LV 3D‐GRS indicates left ventricular 3‐dimensional global radial strain.

Figure 5. Overview for the short‐term improvements in left and right ventricular function, assessed by cardiac magnetic resonance feature tracking derived strain parameters, on patients with stable heart failure and iron deficiency after treatment with ferric carboxymaltose.

CMR indicates cardiac magnetic resonance; CS, circumferential strain; FCM, ferric carboxymaltose; LS, longitudinal strain; LV, left ventricular; RS, radial strain; RV, right ventricular; and SSFP, steady‐state free precession.