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Effect of Iron Isomaltoside on Skeletal Muscle Energetics in Patients With Chronic Heart Failure and Iron Deficiency.
- Source :
-
Circulation [Circulation] 2019 May 21; Vol. 139 (21), pp. 2386-2398. - Publication Year :
- 2019
-
Abstract
- Background: Iron repletion augments exercise capacity in chronic heart failure (HF), but there is a lack of mechanistic data explaining how iron could augment exercise performance despite minimal changes in hemoglobin (Hb). Besides Hb, iron is an obligate component of mitochondrial enzymes that generate cellular energy in the form of adenosine triphosphate and phosphocreatine (PCr). Dynamic phosphorus magnetic resonance spectroscopy is a noninvasive tool that quantifies in vivo muscle energetics by measuring the kinetics of PCr recovery after exertion. We tested the hypothesis that intravenous iron repletion in chronic HF enhances skeletal muscle energetics as reflected by shorter PCr recovery half-times (PCr t <subscript>1/2</subscript> ) on phosphorus magnetic resonance spectroscopy.<br />Methods: We enrolled 40 patients (50% anemic) with chronic HF, New York Heart Association class ≥II, left ventricular ejection fraction ≤45%, and iron deficiency (ferritin<100 μg/L or 100-300 μg/L with transferrin saturation <20%). Subjects underwent stratified (anemic versus nonanemic) randomization (1:1) to a single, double-blinded, total dose infusion of iron isomaltoside or saline placebo with end points reassessed early at 2 weeks posttreatment to minimize confounding from exercise adaptation. The primary end point was PCr t <subscript>1/2</subscript> at 2 weeks. Secondary end points included ADP recovery half-time (ADP t <subscript>1/2;</subscript> energetic marker), iron status, symptoms, Hb, exercise capacity, and safety.<br />Results: In the total population, treatment groups were similar at baseline. At 2 weeks, iron isomaltoside improved PCr t <subscript>1/2</subscript> (adjusted difference, -6.8 s; 95% CI, 11.5 to -2.1; P=0.006), ADP t <subscript>1/2</subscript> (-5.3 s; 95% CI, -9.7 to -0.9; P=0.02), ferritin (304 ng/mL; 95% CI, 217-391; P<0.0001), transferrin saturation (6.8%; 95% CI, 2.7-10.8; P=0.002), New York Heart Association class (-0.23; 95% CI, -0.46 to -0.01; P=0.04), resting respiratory rate (-0.7 breaths/min; 95% CI, -1.2 to -0.2; P=0.009), and postexercise Borg dyspnea score (-2.0; 95% CI, -3.7 to -0.3; P=0.04), but not Hb (2.4 g/L; 95% CI, -3.5 to 8.4; P=0.41). Adverse events were similar between groups. In subgroup analyses, iron isomaltoside improved PCr t <subscript>1/2</subscript> in anemic (-8.4 s; 95% CI, -16.7 to -0.2; P=0.04) and nonanemic (-5.2 s; 95% CI, -10.6 to 0.2; P=0.06) cohorts.<br />Conclusions: In patients with chronic HF and iron deficiency, a total repletion dose of iron isomaltoside given at a single sitting is well tolerated and associated with faster skeletal muscle PCr t <subscript>1/2</subscript> at 2 weeks, implying better mitochondrial function. Augmented skeletal muscle energetics might therefore be an important mechanism via which iron repletion confers benefits in chronic HF despite minimal Hb changes.<br />Clinical Trial Registration: URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-005592-13/GB . Unique identifier: EudraCT 2012-005592-13.
- Subjects :
- Aged
Aged, 80 and over
Anemia, Iron-Deficiency blood
Anemia, Iron-Deficiency diagnosis
Biomarkers blood
Disaccharides adverse effects
Double-Blind Method
Female
Ferric Compounds adverse effects
Heart Failure diagnosis
Heart Failure physiopathology
Hematinics adverse effects
Humans
Iron blood
London
Magnetic Resonance Spectroscopy
Male
Middle Aged
Muscle, Skeletal metabolism
Muscle, Skeletal physiopathology
Phosphocreatine metabolism
Recovery of Function
Time Factors
Treatment Outcome
Anemia, Iron-Deficiency drug therapy
Disaccharides therapeutic use
Energy Metabolism drug effects
Exercise Tolerance drug effects
Ferric Compounds therapeutic use
Heart Failure drug therapy
Hematinics therapeutic use
Iron Deficiencies
Muscle, Skeletal drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1524-4539
- Volume :
- 139
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Circulation
- Publication Type :
- Academic Journal
- Accession number :
- 30776909
- Full Text :
- https://doi.org/10.1161/CIRCULATIONAHA.118.038516