Noninvasive Imaging Estimation of Myocardial Iron Repletion Following Administration of Intravenous Iron: The Myocardial-IRON Trial

Julio Núñez, Gema Miñana, Ingrid Cardells, Patricia Palau, Pau Llàcer, Lorenzo Fácila, Luis Almenar, Maria P López-Lereu, Jose V Monmeneu, Martina Amiguet, Jessika González, Alicia Serrano, Vicente Montagud, Raquel López-Vilella, Ernesto Valero, Sergio García-Blas, Vicent Bodí, Rafael de la Espriella-Juan, Josep Lupón, Jorge Navarro, José Luis Górriz, Juan Sanchis, Francisco J Chorro, Josep Comín-Colet, Antoni Bayés-Genís, Myocardial‐IRON Investigators* †, Meritxell Soler, Amparo Villaescusa, Jose Civera, Anna Mollar, Maria Del Carmen Moreno, Veronica Vidal, Julio Núñez, Gema Miñana, Ingrid Cardells, Patricia Palau, Pau Llàcer, Lorenzo Fácila, Luis Almenar, Maria P López-Lereu, Jose V Monmeneu, Martina Amiguet, Jessika González, Alicia Serrano, Vicente Montagud, Raquel López-Vilella, Ernesto Valero, Sergio García-Blas, Vicent Bodí, Rafael de la Espriella-Juan, Josep Lupón, Jorge Navarro, José Luis Górriz, Juan Sanchis, Francisco J Chorro, Josep Comín-Colet, Antoni Bayés-Genís, Myocardial‐IRON Investigators* †, Meritxell Soler, Amparo Villaescusa, Jose Civera, Anna Mollar, Maria Del Carmen Moreno, Veronica Vidal

Abstract

Background Intravenous ferric carboxymaltose (FCM) improves symptoms, functional capacity, and quality of life in heart failure and iron deficiency. The mechanisms underlying these effects are not fully understood. The aim of this study was to examine changes in myocardial iron content after FCM administration in patients with heart failure and iron deficiency using cardiac magnetic resonance. Methods and Results Fifty-three stable heart failure and iron deficiency patients were randomly assigned 1:1 to receive intravenous FCM or placebo in a multicenter, double-blind study. T2* and T1 mapping cardiac magnetic resonance sequences, noninvasive surrogates of intramyocardial iron, were evaluated before and 7 and 30 days after randomization using linear mixed regression analysis. Results are presented as least-square means with 95% CI. The primary end point was the change in T2* and T1 mapping at 7 and 30 days. Median age was 73 (65-78) years, with N-terminal pro-B-type natriuretic peptide, ferritin, and transferrin saturation medians of 1690 pg/mL (1010-2828), 63 ng/mL (22-114), and 15.7% (11.0-19.2), respectively. Baseline T2* and T1 mapping values did not significantly differ across treatment arms. On day 7, both T2* and T1 mapping (ms) were significantly lower in the FCM arm (36.6 [34.6-38.7] versus 40 [38-42.1], P=0.025; 1061 [1051-1072] versus 1085 [1074-1095], P=0.001, respectively). A similar reduction was found at 30 days for T2* (36.3 [34.1-38.5] versus 41.1 [38.9-43.4], P=0.003), but not for T1 mapping (1075 [1065-1085] versus 1079 [1069-1089], P=0.577). Conclusions In patients with heart failure and iron deficiency, FCM administration was associated with changes in the T2* and T1 mapping cardiac magnetic resonance sequences, indicative of myocardial iron repletion. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT03398681.

Keywords: cardiac magnetic resonance; ferric carboxymaltose; heart failure; iron deficiency; myocardial iron.

Figures

Figure 1
Figure 1
Flow chart. FCM indicates ferric carboxymaltose; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide.
Figure 2
Figure 2
T2* and T1 mapping after administration of FCM. A, Seven‐day comparison of LSM (95% CIs) between FCM and placebo. B, Thirty‐day comparison of LSM (95% CIs) between FCM and placebo. FCM indicates ferric carboxymaltose; LSM, least‐square means from a linear mixed regression analysis.
Figure 3
Figure 3
Association of posttreatment changes in myocardial iron content (T2* and T1 mapping) with concomitant changes in systemic iron status in the active arm. A, Changes in CMR sequences and changes in ferritin; B, A, Changes in CMR sequences and changes in TSAT. Values are the least‐square means (95% CIs) from each linear regression analysis (OLS). TSAT indicates transferrin saturation.
Figure 4
Figure 4
Association of posttreatment changes in myocardial iron content (T2* and T1 mapping) with concomitant changes in surrogate markers of disease severity in the active‐arm. A, Changes in CMR sequences and changes in LVEF; B, Changes in CMR sequences and changes in KCCQ; C, Changes in CMR sequences and changes in 6MWT; D, Changes in CMR sequences and changes in NYHA class; E, Changes in CMR sequences and changes in NT‐proBNP. Values are the least‐square means (95% CIs) from each linear regression analysis (OLS). 6MWT indicates distance walked in 6 minutes; CMR, cardiac magnetic resonance; KCCQ, Kansas City Cardiomyopathy Questionnaire; LVEF, left ventricular ejection fraction; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; NYHA, New York Heart Association.

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