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      The effect of iron deficiency on cardiac resynchronization therapy: results from the RIDE‐CRT Study

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          Abstract

          Aims

          Cardiac resynchronization therapy (CRT) improves functional status, induces reverse left ventricular remodelling, and reduces hospitalization and mortality in patients with symptomatic heart failure, left ventricular systolic dysfunction, and QRS prolongation. However, the impact of iron deficiency on CRT response remains largely unclear. The purpose of the study was to assess the effect of functional and absolute iron deficiency on reverse cardiac remodelling, clinical response, and outcome after CRT implantation.

          Methods and results

          The relation of iron deficiency and cardiac resynchronization therapy response (RIDE‐CRT) study is a prospective observational study. We enrolled 77 consecutive CRT recipients (mean age 71.3 ± 10.2 years) with short‐term follow‐up of 3.3 ± 1.9 months and long‐term follow‐up of 13.0 ± 3.2 months. Primary endpoints were reverse cardiac remodelling on echocardiography and clinical CRT response, assessed by change in New York Heart Association classification. Echocardiographic CRT response was defined as relative improvement of left ventricular ejection fraction ≥ 20% or left ventricular global longitudinal strain ≥ 20%. Secondary endpoints were hospitalization for heart failure and all‐cause mortality (mean follow‐up of 29.0 ± 8.4 months). At multivariate analysis, iron deficiency was identified as independent predictor of echocardiographic (hazard ratio 4.97; 95% confidence interval 1.15–21.51; P = 0.03) and clinical non‐response to CRT (hazard ratio 4.79; 95% confidence interval 1.30–17.72, P = 0.02). We found a significant linear‐by‐linear association between CRT response and type of iron deficiency ( P = 0.004 for left ventricular ejection fraction improvement, P = 0.02 for left ventricular global longitudinal strain improvement, and P = 0.003 for New York Heart Association response). Iron deficiency was also significantly associated with an increase in all‐cause mortality ( P = 0.045) but not with heart failure hospitalization.

          Conclusions

          Iron deficiency is a negative predictor of effective CRT therapy as assessed by reverse cardiac remodelling and clinical response. Assessment of iron substitution might be a relevant treatment target to increase CRT response and outcome in chronic heart failure patients.

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          Most cited references31

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          Cardiac-resynchronization therapy for mild-to-moderate heart failure.

          Cardiac-resynchronization therapy (CRT) benefits patients with left ventricular systolic dysfunction and a wide QRS complex. Most of these patients are candidates for an implantable cardioverter-defibrillator (ICD). We evaluated whether adding CRT to an ICD and optimal medical therapy might reduce mortality and morbidity among such patients. We randomly assigned patients with New York Heart Association (NYHA) class II or III heart failure, a left ventricular ejection fraction of 30% or less, and an intrinsic QRS duration of 120 msec or more or a paced QRS duration of 200 msec or more to receive either an ICD alone or an ICD plus CRT. The primary outcome was death from any cause or hospitalization for heart failure. We followed 1798 patients for a mean of 40 months. The primary outcome occurred in 297 of 894 patients (33.2%) in the ICD-CRT group and 364 of 904 patients (40.3%) in the ICD group (hazard ratio in the ICD-CRT group, 0.75; 95% confidence interval [CI], 0.64 to 0.87; P<0.001). In the ICD-CRT group, 186 patients died, as compared with 236 in the ICD group (hazard ratio, 0.75; 95% CI, 0.62 to 0.91; P = 0.003), and 174 patients were hospitalized for heart failure, as compared with 236 in the ICD group (hazard ratio, 0.68; 95% CI, 0.56 to 0.83; P<0.001). However, at 30 days after device implantation, adverse events had occurred in 124 patients in the ICD-CRT group, as compared with 58 in the ICD group (P<0.001). Among patients with NYHA class II or III heart failure, a wide QRS complex, and left ventricular systolic dysfunction, the addition of CRT to an ICD reduced rates of death and hospitalization for heart failure. This improvement was accompanied by more adverse events. (Funded by the Canadian Institutes of Health Research and Medtronic of Canada; ClinicalTrials.gov number, NCT00251251.).
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            Nutritional anaemias. Report of a WHO scientific group.

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              Effect of intravenous iron sucrose on exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure and iron deficiency FERRIC-HF: a randomized, controlled, observer-blinded trial.

              We tested the hypothesis that intravenous iron improves exercise tolerance in anemic and nonanemic patients with symptomatic chronic heart failure (CHF) and iron deficiency. Anemia is common in heart failure. Iron metabolism is disturbed, and administration of iron might improve both symptoms and exercise tolerance. We randomized 35 patients with CHF (age 64 +/- 13 years, peak oxygen consumption [pVO2] 14.0 +/- 2.7 ml/kg/min) to 16 weeks of intravenous iron (200 mg weekly until ferritin >500 ng/ml, 200 mg monthly thereafter) or no treatment in a 2:1 ratio. Ferritin was required to be <100 ng/ml or ferritin 100 to 300 ng/ml with transferrin saturation <20%. Patients were stratified according to hemoglobin levels (<12.5 g/dl [anemic group] vs. 12.5 to 14.5 g/dl [nonanemic group]). The observer-blinded primary end point was the change in absolute pVO2. The difference (95% confidence interval [CI]) in the mean changes from baseline to end of study between the iron and control groups was 273 (151 to 396) ng/ml for ferritin (p < 0.0001), 0.1 (-0.8 to 0.9) g/dl for hemoglobin (p = 0.9), 96 (-12 to 205) ml/min for absolute pVO2 (p = 0.08), 2.2 (0.5 to 4.0) ml/kg/min for pVO2/kg (p = 0.01), 60 (-6 to 126) s for treadmill exercise duration (p = 0.08), -0.6 (-0.9 to -0.2) for New York Heart Association (NYHA) functional class (p = 0.007), and 1.7 (0.7 to 2.6) for patient global assessment (p = 0.002). In anemic patients (n = 18), the difference (95% CI) was 204 (31 to 378) ml/min for absolute pVO2 (p = 0.02), and 3.9 (1.1 to 6.8) ml/kg/min for pVO2/kg (p = 0.01). In nonanemic patients, NYHA functional class improved (p = 0.06). Adverse events were similar. Intravenous iron loading improved exercise capacity and symptoms in patients with CHF and evidence of abnormal iron metabolism. Benefits were more evident in anemic patients. (Effect of Intravenous Ferrous Sucrose on Exercise Capacity in Chronic Heart Failure; http://www.clinicaltrials.gov/ct/show/NCT00125996; NCT00125996).
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                Author and article information

                Contributors
                florian.blaschke@charite.de
                Journal
                ESC Heart Fail
                ESC Heart Fail
                10.1002/(ISSN)2055-5822
                EHF2
                ESC Heart Failure
                John Wiley and Sons Inc. (Hoboken )
                2055-5822
                18 March 2020
                June 2020
                : 7
                : 3 ( doiID: 10.1002/ehf2.v7.3 )
                : 1072-1084
                Affiliations
                [ 1 ] Department of Cardiology Charité—Universitaetsmedizin Berlin, Campus Virchow‐Klinikum Augustenburger Platz 1 Berlin 13353 Germany
                [ 2 ] BCRT—Center for Regenerative Therapies
                [ 3 ] Institute of Biometry and Clinical Epidemiology Charité—Universitätsmedizin Berlin, Campus Benjamin Franklin Hindenburgdamm 30 Berlin 12203 Germany
                [ 4 ] Berlin Institute of Health Charitéplatz 1 Berlin 10117 Germany
                [ 5 ] DZHK (German Centre for Cardiovascular Research), Partner Site Berlin Berlin Germany
                Author notes
                [*] [* ] Correspondence to: Dr Florian Blaschke, PD, Department of Cardiology, Charité—Universitaetsmedizin Berlin, Campus Virchow‐Klinikum, Augustenburger Platz 1, Berlin 13353, Germany. Tel: +49 30 450 653635; Fax: +49 30 450 7553635. Email: florian.blaschke@ 123456charite.de

                Article
                EHF212675 ESCHF-19-00321
                10.1002/ehf2.12675
                7261541
                c1488509-18b9-491f-be40-9dd03627de22
                © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 26 September 2019
                : 09 February 2020
                : 19 February 2020
                Page count
                Figures: 2, Tables: 4, Pages: 13, Words: 4738
                Funding
                Funded by: Medtronic Research Grant
                Categories
                Original Research Article
                Original Research Articles
                Custom metadata
                2.0
                June 2020
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.8.3 mode:remove_FC converted:31.05.2020

                iron deficiency,cardiac resynchronization therapy,heart failure

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