Elsevier

Journal of Cardiac Failure

Volume 17, Issue 11, November 2011, Pages 899-906
Journal of Cardiac Failure

Clinical Investigation
Iron Deficiency Predicts Impaired Exercise Capacity in Patients With Systolic Chronic Heart Failure

https://doi.org/10.1016/j.cardfail.2011.08.003Get rights and content

Abstract

Background

Iron is an indispensable element of hemoglobin, myoglobin, and cytochromes, and, beyond erythropoiesis, is involved in oxidative metabolism and cellular energetics. Hence, iron deficiency (ID) is anticipated to limit exercise capacity. We investigated whether ID predicted exercise intolerance in patients with systolic chronic heart failure (CHF).

Methods and Results

We prospectively studied 443 patients with stable systolic CHF (age 54 ± 10 years, males 90%, ejection fraction 26 ± 7%, New York Heart Association Class I/II/III/IV 49/188/180/26). ID was defined as: serum ferritin <100 μg/L or serum ferritin 100–300 μg/L with serum transferrin saturation <20%. Exercise capacity was expressed as peak oxygen consumption (VO2) and ventilatory response to exercise (VE-VCO2 slope). ID was present in 35 ± 4% (±95% confidence interval) of patients with systolic CHF. Those with ID had reduced peak VO2 and increased VE-VCO2 slope as compared to subjects without ID (peak VO2: 13.3 ± 4.0 versus 15.3 ± 4.5 mL•min•kg, VE-VCO2 slope: 50.9 ± 15.8 versus 43.1 ± 11.1, respectively, both P < .001, P < .05). In multivariable models, the presence of ID was associated with reduced peak VO2 (β = −0.14, P < .01 P < .05) and higher VE-VCO2 slope (β = 0.14, P < .01 P < .05), adjusted for demographics and clinical variables. Analogous associations were found between serum ferritin, and both peak VO2 and VE-VCO2 slope (P < .05).

Conclusions

ID independently predicts exercise intolerance in patients with systolic CHF, but the strength of these associations is relatively weak. Whether iron supplementation would improve exercise capacity in iron-deficient subjects requires further studies.

Section snippets

Study Population

The recruitment phase of the study was conducted among patients with systolic CHF attending outpatient clinics or admitted electively in 2 tertiary referral cardiology centers (Wroclaw and Zabrze, Poland). The criteria for study inclusion were: 1) a documented history of CHF (established diagnosis of CHF) of a ≥6-month duration; 2) left ventricular ejection fraction (LVEF) ≤45% as assessed by echocardiography (performed at the time of screening using a Simpson’s planimetric method to determine

Results

Table 1 displays the baseline clinical characteristics of the entire cohort of 443 patients with stable systolic CHF. One hundred twenty-four (28%) patients were examined in Wroclaw, and 319 (72%) in Zabrze. ID was found in 155 (35 ± 4%, ± 95% confidence intervals) patients with systolic CHF (48 [39 ± 9%] and 107 [34 ± 5%] subjects in Wroclaw and Zabrze, respectively, P > .2). Clinical characteristics of patients with versus without ID are presented in Table 1.

Discussion

The main novel finding of our study is that in patients with systolic CHF the presence of ID as well as reduced serum ferritin is associated with impaired exercise tolerance, independently of the other parameters traditionally linked with poor exercise capacity.

In recent decades, ID has been noticed as the major nutritional deficiency with unfavorable effects recorded on the population level.8, 13 In the context of the greater prevalence of ID without anemia that ID with overt anemia, the

Conclusions

In patients with systolic CHF, ID independently relates to exercise intolerance expressed as reduced peak oxygen uptake and augmented ventilatory response to exercise, but the strength of these associations is relatively weak. Whether iron supplementation would improve exercise capacity in iron-deficient subjects requires further studies.

Disclosures

None.

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    This research was financially supported by the Ministry of Science and Higher Education (Poland) grant no. 4022/B/T02/2008/34. A.W. received a fee from Vifor Pharma. G.F. received grants from Vifor Pharma. S.D.A. received consulting fees from Amgen Inc, Fresenius Kabi, Professional Dietetics, Vifor Pharma, and honoraria from Amgen Inc, Fresenius Kabi, Vifor Pharma. P.P. received consulting fees from Vifor Pharma and Amgen Inc., honoraria from Vifor Pharma, and travel/accommodation expensed covered by Vifor Pharma and Amgen Inc.

    All the other authors report no conflict of interest related to the content of this manuscript.

    See page 905 for disclosure information.

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