Iron deficiency in patients with heart failure with preserved ejection fraction and its association with reduced exercise capacity, muscle strength and quality of life
- 275 Downloads
The prevalence of iron deficiency (ID) in outpatients with heart failure with preserved ejection fraction (HFpEF) and its relation to exercise capacity and quality of life (QoL) is unknown.
190 symptomatic outpatients with HFpEF (LVEF 58 ± 7%; age 71 ± 9 years; NYHA 2.4 ± 0.5; BMI 31 ± 6 kg/m2) were enrolled as part of SICA-HF in Germany, England and Slovenia. ID was defined as ferritin < 100 or 100–299 µg/L with transferrin saturation (TSAT) < 20%. Anemia was defined as Hb < 13 g/dL in men, < 12 g/dL in women. Low ferritin-ID was defined as ferritin < 100 µg/L. Patients were divided into 3 groups according to E/e′ at echocardiography: E/e′ ≤ 8; E/e′ 9–14; E/e′ ≥ 15. All patients underwent echocardiography, cardiopulmonary exercise test (CPX), 6-min walk test (6-MWT), and QoL assessment using the EQ5D questionnaire.
Overall, 111 patients (58.4%) showed ID with 89 having low ferritin-ID (46.84%). 78 (41.1%) patients had isolated ID without anemia and 54 patients showed anemia (28.4%). ID was more prevalent in patients with more severe diastolic dysfunction: E/e′ ≤ 8: 44.8% vs. E/e′: 9–14: 53.2% vs. E/e′ ≥ 15: 86.5% (p = 0.0004). Patients with ID performed worse during the 6MWT (420 ± 137 vs. 344 ± 124 m; p = 0.008) and had worse exercise time in CPX (645 ± 168 vs. 538 ± 178 s, p = 0.03). Patients with low ferritin-ID had lower QoL compared to those without ID (p = 0.03).
ID is a frequent co-morbidity in HFpEF and is associated with reduced exercise capacity and QoL. Its prevalence increases with increasing severity of diastolic dysfunction.
KeywordsHeart failure with preserved ejection fraction Iron deficiency Exercise capacity Quality of life
Analysis of variance
Body mass index
Cardiopulmonary exercise test
Dual energy X-ray absorptiometry
Heart failure with preserved ejection fraction
Heart failure with reduced ejection fraction
Left atrial volume index
6-min walk test
New York Heart Association
Quality of life
Studies investigating co-morbidities aggravating heart failure
The study was funded by the European Commission’s 7th Framework program (FP7/2007–2013) under grant agreement number 241558 (clinical.trial.gov).
Compliance with ethical standards
Conflict of interest
SvH is consulting and has received honoraria for speaking from Solartium Dietetics, Professional Dietetics, Vifor, Novartis, Respicardia, Sorin, and Pfizer. SDA is consulting, has received honoraria for speaking and/or attended advisory boards for Amgen Inc, Professional Dietetics, Psioxus Therapeutics, GTx, Helsinn, GSK, Sanofi, Regeneron, Novartis, Takeda, Servier, Chugai and Vifor. All other authors report no conflict of interest.
- 7.Pellicori P, Kallvikbacka-Bennett A, Khaleva O, Carubelli V, Costanzo P, Castiello T, Wong K, Zhang J, Cleland JG, Clark AL (2014) Global longitudinal strain in patients with suspected heart failure and a normal ejection fraction: does it improve diagnosis and risk stratification? Int J Cardiovasc Imaging 30:69–79CrossRefGoogle Scholar
- 10.Anker SD, Comin Colet J, Filippatos G, Willenheimer R, Dickstein K, Drexler H, Lüscher TF, Bart B, Banasiak W, Niegowska J, Kirwan BA, Mori C, von Eisenhart Rothe B, Pocock SJ, Poole-Wilson PA, Ponikowski P (2009) FAIR-HF Trial Investigators. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 361:2436–2448CrossRefGoogle Scholar
- 14.Fairbanks V, Beutler E (2001) Iron deficiency. In: Beutler E (ed) Williams hematology, 6th edn. McGraw-Hill, New York, pp 295–304 (447–70).Google Scholar
- 20.Lewis GD, Malhotra R, Hernandez AF, McNulty SE, Smith A, Felker GM, Tang WHW, LaRue SJ, Redfield MM, Semigran MJ, Givertz MM, Van Buren P, Whellan D, Anstrom KJ, Shah MR, Desvigne-Nickens P, Butler J, Braunwald E (2017) Effect of Oral Iron Repletion on Exercise Capacity in Patients With Heart Failure With Reduced Ejection Fraction and Iron Deficiency: the IRONOUT HF randomized clinical trial. JAMA 19:1958–1966CrossRefGoogle Scholar
- 21.Ponikowski P, van Veldhuisen DJ, Comin-Colet J, Ertl G, Komajda M, Mareev V, McDonagh Th, Parkhomenko A, Tavazzi L, Levesque V, Mori C, Roubert B, Filippatos G, Ruschitzka F, Anker SD (2015). on behalf of for the CONFIRM-HF Investigators. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients with symptomatic heart failure and iron deficiency. Eur Heart J 36:657–668CrossRefGoogle Scholar
- 25.Jankowska EA, Rozentryt P, Witkowska A, Nowak J, Hartmann O, Ponikowska B, Borodulin-Nadzieja L, Banasiak W, Polonski L, Filippatos G, McMurray JJ, Anker SD, Ponikowski P (2010) Iron deficiency: an ominous sign in patients with systolic chronic heart failure. Eur Heart J 31:1872–1880CrossRefGoogle Scholar
- 26.von Haehling S, Lainscak M, Doehner W, Ponikowski P, Rosano G, Jordan J, Rozentryt P, Rauchhaus M, Karpov R, Tkachuk V, Parfyonova Y, Zaritskey AY, Shlyakhto EV, Cleland JG, Anker SD (2010) Diabetes mellitus, cachexia and obesity in heart failure: rationale and design of the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF). J Cachexia Sarcopenia Muscle 1:187–194CrossRefGoogle Scholar
- 27.Paulus WJ, Tschöpe C, Sanderson JE, Rusconi C, Flachskampf FA, Rademakers FE, Marino P, Smiseth OA, De Keulenaer G, Leite-Moreira AF, Borbély A, Edes I, Handoko ML, Heymans S, Pezzali N, Pieske B, Dickstein K, Fraser AG, Brutsaert DL (2007) How to diagnose diastolic heart failure: a consensus statement on the diagnosis of heart failure with normal left ventricular ejection fraction by the Heart Failure and Echocardiography Associations of the European Society of Cardiology. Eur Heart J 28:2539–2550CrossRefGoogle Scholar
- 29.Bruce RA, Blackmon JR, Jones JW, Strait G (1963) Exercise testing in adult normal subjects and cardiac patients. Pediatrics 32:742–756Google Scholar
- 30.Naughton J, Sevellus G, Balke B (1963) Physiologic responses of normal and pathologic subjects to a modified work capacity test. J Sports Med 31:201Google Scholar
- 36.Phan TT, Abozguia K, Nallur Shivu G, Mahadevan G, Ahmed I, Williams L, Dwivedi G, Patel K, Steendijk P, Ashrafian H, Henning A, Frenneaux M (2009) Heart failure with preserved ejection fraction is characterized by dynamic impairment of active relaxation and contraction of the left ventricle on exercise and associated with myocardial energy deficiency. J Am Coll Cardiol 54:402–409CrossRefGoogle Scholar
- 37.Anker SD, Colet JC, Filippatos G et al (2009) Rationale and design of Ferinject assessment in patients with IRon deficiency and chronic Heart Failure (FAIR-HF) study: a randomized, placebo-controlled study of intravenous iron supplementation in patients with and without anaemia. Eur J Heart Fail 11:1084–1091CrossRefGoogle Scholar