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Published in: Clinical Research in Cardiology 2/2019

01-02-2019 | Original Paper

Iron deficiency in patients with heart failure with preserved ejection fraction and its association with reduced exercise capacity, muscle strength and quality of life

Authors: Tarek Bekfani, Pierpaolo Pellicori, Daniel Morris, Nicole Ebner, Miroslava Valentova, Anja Sandek, Wolfram Doehner, John G. Cleland, Mitja Lainscak, P. Christian Schulze, Stefan D. Anker, Stephan von Haehling

Published in: Clinical Research in Cardiology | Issue 2/2019

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Abstract

Background

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.

Methods

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.

Results

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).

Conclusion

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.
Literature
1.
go back to reference Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM (2006) Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 355:251–259CrossRefPubMed Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM (2006) Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 355:251–259CrossRefPubMed
2.
go back to reference Haykowsky MJ, Brubaker PH, John JM, Stewart KP, Morgan TM, Kitzman DW (2011) Determinants of exercise intolerance in elderly heart failure patients with preserved ejection fraction. J Am Coll Cardiol 58:265–274CrossRefPubMedPubMedCentral Haykowsky MJ, Brubaker PH, John JM, Stewart KP, Morgan TM, Kitzman DW (2011) Determinants of exercise intolerance in elderly heart failure patients with preserved ejection fraction. J Am Coll Cardiol 58:265–274CrossRefPubMedPubMedCentral
3.
go back to reference Borlaug BA, Melenovsky V, Russell SD, Kessler K, Pacak K, Becker LC, Kass DA (2006) Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction. Circulation 114:2138–2147CrossRefPubMed Borlaug BA, Melenovsky V, Russell SD, Kessler K, Pacak K, Becker LC, Kass DA (2006) Impaired chronotropic and vasodilator reserves limit exercise capacity in patients with heart failure and a preserved ejection fraction. Circulation 114:2138–2147CrossRefPubMed
4.
go back to reference Borlaug BA, Olson TP, Lam CS, Flood KS, Lerman A, Johnson BD, Redfield MM (2010) Global cardiovascular reserve dysfunction in heart failure with preserved ejection fraction. J Am Coll Cardiol 56:845–854CrossRefPubMedPubMedCentral Borlaug BA, Olson TP, Lam CS, Flood KS, Lerman A, Johnson BD, Redfield MM (2010) Global cardiovascular reserve dysfunction in heart failure with preserved ejection fraction. J Am Coll Cardiol 56:845–854CrossRefPubMedPubMedCentral
5.
go back to reference Bhella PS, Prasad A, Heinicke K, Hastings JL, Arbab-Zadeh A, Adams-Huet B, Pacini EL, Shibata S, Palmer MD, Newcomer BR, Levine BD (2011) Abnormal haemodynamic response to exercise in heart failure with preserved ejection fraction. Eur J Heart Fail 13:1296–1304CrossRefPubMedPubMedCentral Bhella PS, Prasad A, Heinicke K, Hastings JL, Arbab-Zadeh A, Adams-Huet B, Pacini EL, Shibata S, Palmer MD, Newcomer BR, Levine BD (2011) Abnormal haemodynamic response to exercise in heart failure with preserved ejection fraction. Eur J Heart Fail 13:1296–1304CrossRefPubMedPubMedCentral
6.
go back to reference Maeder MT, Thompson BR, Brunner-La Rocca HP, Kaye DM (2010) Hemodynamic basis of exercise limitation in patients with heart failure and normal ejection fraction. J Am Coll Cardiol 56:855–863CrossRefPubMed Maeder MT, Thompson BR, Brunner-La Rocca HP, Kaye DM (2010) Hemodynamic basis of exercise limitation in patients with heart failure and normal ejection fraction. J Am Coll Cardiol 56:855–863CrossRefPubMed
7.
go back to reference 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 30:69–79CrossRefPubMed 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 30:69–79CrossRefPubMed
8.
go back to reference Kitzman DW, Higginbotham MB, Cobb FR, Sheikh KH, Sullivan MJ (1991) Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism. J Am Coll Cardiol 17:1065–1072CrossRefPubMed Kitzman DW, Higginbotham MB, Cobb FR, Sheikh KH, Sullivan MJ (1991) Exercise intolerance in patients with heart failure and preserved left ventricular systolic function: failure of the Frank-Starling mechanism. J Am Coll Cardiol 17:1065–1072CrossRefPubMed
9.
go back to reference von Haehling S, van Veldhuisen DJ, Roughton M, Babalis D, de Boer RA, Coats AJS, Manzano L, Flather M, Anker S (2011) D. Anaemia among patients with heart failure and preserved or reduced ejection fraction: results from the SENIORS study. Eur J Heart Fail 13:656–663CrossRef von Haehling S, van Veldhuisen DJ, Roughton M, Babalis D, de Boer RA, Coats AJS, Manzano L, Flather M, Anker S (2011) D. Anaemia among patients with heart failure and preserved or reduced ejection fraction: results from the SENIORS study. Eur J Heart Fail 13:656–663CrossRef
10.
go back to reference 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 361:2436–2448CrossRefPubMed 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 361:2436–2448CrossRefPubMed
11.
go back to reference Clark AL, Poole-Wilson PA, Coats AJ (1996) Exercise limitation in chronic heart failure: central role of the periphery. J Am Coll Cardiol 28:1092–1102CrossRefPubMed Clark AL, Poole-Wilson PA, Coats AJ (1996) Exercise limitation in chronic heart failure: central role of the periphery. J Am Coll Cardiol 28:1092–1102CrossRefPubMed
12.
go back to reference Massie BM, Conway M, Rajagopalan B, Yonge R, Frostick S, Ledingham J, Sleight P, Radda G (1988) Skeletal muscle metabolism during exercise under ischemic conditions in congestive heart failure: evidence for abnormalities unrelated to blood flow. Circulation 78:320–326CrossRefPubMed Massie BM, Conway M, Rajagopalan B, Yonge R, Frostick S, Ledingham J, Sleight P, Radda G (1988) Skeletal muscle metabolism during exercise under ischemic conditions in congestive heart failure: evidence for abnormalities unrelated to blood flow. Circulation 78:320–326CrossRefPubMed
13.
go back to reference Dunn LL, Rahmanto YS, Richardson DR (2007) Iron uptake and metabolism in the new millennium. Trends Cell Biol 17:93–100CrossRefPubMed Dunn LL, Rahmanto YS, Richardson DR (2007) Iron uptake and metabolism in the new millennium. Trends Cell Biol 17:93–100CrossRefPubMed
14.
go back to reference Fairbanks V, Beutler E (2001) Iron deficiency. In: Beutler E (ed) Williams hematology, 6th edn. McGraw-Hill, New York, pp 295–304 (447–70). Fairbanks V, Beutler E (2001) Iron deficiency. In: Beutler E (ed) Williams hematology, 6th edn. McGraw-Hill, New York, pp 295–304 (447–70).
17.
go back to reference Haas JD, Brownlie TIV (2001) Iron deficiency and reduced work capacity: a critical review of the research to determine a causal relationship. J Nutr 131(Suppl 2):676–688CrossRef Haas JD, Brownlie TIV (2001) Iron deficiency and reduced work capacity: a critical review of the research to determine a causal relationship. J Nutr 131(Suppl 2):676–688CrossRef
18.
go back to reference Konishi M, Ishida J, Springer J, von Haehling S, Akashi YJ, Shimokawa H, Anker SD (2016) Heart failure epidemiology and novel treatments in Japan: facts and numbers. ESC Heart Fail 3(3):145–151CrossRefPubMedPubMedCentral Konishi M, Ishida J, Springer J, von Haehling S, Akashi YJ, Shimokawa H, Anker SD (2016) Heart failure epidemiology and novel treatments in Japan: facts and numbers. ESC Heart Fail 3(3):145–151CrossRefPubMedPubMedCentral
19.
go back to reference Yeo TJ, Yeo PS, Hadi FA, Cushway T, Lee KY, Tai BC, Lam CS (2016) Rationale and design of a pilot randomized controlled trial to assess the role of intravenous ferric carboxymaltose in Asian patients with heart failure (PRACTICE-ASIA-HF). ESC Heart Fail 3(2):71–76CrossRefPubMed Yeo TJ, Yeo PS, Hadi FA, Cushway T, Lee KY, Tai BC, Lam CS (2016) Rationale and design of a pilot randomized controlled trial to assess the role of intravenous ferric carboxymaltose in Asian patients with heart failure (PRACTICE-ASIA-HF). ESC Heart Fail 3(2):71–76CrossRefPubMed
20.
go back to reference 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 19:1958–1966CrossRef 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 19:1958–1966CrossRef
21.
go back to reference 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 36:657–668CrossRefPubMed 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 36:657–668CrossRefPubMed
22.
go back to reference Klip IT, Comin-Colet J, Voors AA, Ponikowski P, Enjuanes C, Banasiak W, Lok DJ, Rosentryt P, Torrens A, Polonski L, van Veldhuisen DJ, van der Meer P, Jankowska EA (2013) Iron deficiency in chronic heart failure: an international pooled analysis. Am Heart J 165:575–582CrossRefPubMed Klip IT, Comin-Colet J, Voors AA, Ponikowski P, Enjuanes C, Banasiak W, Lok DJ, Rosentryt P, Torrens A, Polonski L, van Veldhuisen DJ, van der Meer P, Jankowska EA (2013) Iron deficiency in chronic heart failure: an international pooled analysis. Am Heart J 165:575–582CrossRefPubMed
23.
go back to reference Okonko DO, Mandal AKJ, Missouris CG, Poole-Wilson PA (2011) Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relations to anemia, exercise capacity, and survival. J Am Coll Cardiol 58:1241–1251CrossRefPubMed Okonko DO, Mandal AKJ, Missouris CG, Poole-Wilson PA (2011) Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relations to anemia, exercise capacity, and survival. J Am Coll Cardiol 58:1241–1251CrossRefPubMed
24.
go back to reference Kasner M, Aleksandrov AS, Westermann D, Lassner D, Gross M, von Haehling S, Anker SD, Schultheiss HP, Tschöpe C (2013) Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction. Int J Cardiol 168:4652–4657CrossRefPubMed Kasner M, Aleksandrov AS, Westermann D, Lassner D, Gross M, von Haehling S, Anker SD, Schultheiss HP, Tschöpe C (2013) Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction. Int J Cardiol 168:4652–4657CrossRefPubMed
25.
go back to reference 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 31:1872–1880CrossRefPubMed 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 31:1872–1880CrossRefPubMed
26.
go back to reference 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 1:187–194CrossRef 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 1:187–194CrossRef
27.
go back to reference 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 28:2539–2550CrossRefPubMed 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 28:2539–2550CrossRefPubMed
28.
go back to reference Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelisa A (2009) Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr 10:165–193CrossRefPubMed Nagueh SF, Appleton CP, Gillebert TC, Marino PN, Oh JK, Smiseth OA, Waggoner AD, Flachskampf FA, Pellikka PA, Evangelisa A (2009) Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr 10:165–193CrossRefPubMed
29.
go back to reference Bruce RA, Blackmon JR, Jones JW, Strait G (1963) Exercise testing in adult normal subjects and cardiac patients. Pediatrics 32:742–756 Bruce RA, Blackmon JR, Jones JW, Strait G (1963) Exercise testing in adult normal subjects and cardiac patients. Pediatrics 32:742–756
30.
go back to reference Naughton J, Sevellus G, Balke B (1963) Physiologic responses of normal and pathologic subjects to a modified work capacity test. J Sports Med 31:201 Naughton J, Sevellus G, Balke B (1963) Physiologic responses of normal and pathologic subjects to a modified work capacity test. J Sports Med 31:201
31.
go back to reference Krack A, Sharma R, Figulla HR, Anker SD (2005) The importance of the gastrointestinal system in the pathogenesis of heart failure. Eur Heart J 26:2368–2374CrossRefPubMed Krack A, Sharma R, Figulla HR, Anker SD (2005) The importance of the gastrointestinal system in the pathogenesis of heart failure. Eur Heart J 26:2368–2374CrossRefPubMed
32.
go back to reference Silverberg DS (2011) The role of erythropoiesis stimulating agents and intravenous (IV) iron in the cardio renal anemia syndrome. Heart Fail Rev 16:609–614CrossRefPubMed Silverberg DS (2011) The role of erythropoiesis stimulating agents and intravenous (IV) iron in the cardio renal anemia syndrome. Heart Fail Rev 16:609–614CrossRefPubMed
34.
go back to reference Sandek A, Bauditz J, Swidsinski A, Buhner S, Weber-Eibel J, von Haehling S, Schroedl W, Karhausen T, Doehner W, Rauchhaus M, Poole-Wilson P, Volk HD, Lochs H, Anker SD (2007) Altered intestinal function in patients with chronic heart failure. J Am Coll Cardiol 50:1561–1569CrossRefPubMed Sandek A, Bauditz J, Swidsinski A, Buhner S, Weber-Eibel J, von Haehling S, Schroedl W, Karhausen T, Doehner W, Rauchhaus M, Poole-Wilson P, Volk HD, Lochs H, Anker SD (2007) Altered intestinal function in patients with chronic heart failure. J Am Coll Cardiol 50:1561–1569CrossRefPubMed
35.
36.
go back to reference 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 54:402–409CrossRefPubMed 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 54:402–409CrossRefPubMed
37.
go back to reference 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 11:1084–1091CrossRefPubMedPubMedCentral 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 11:1084–1091CrossRefPubMedPubMedCentral
38.
go back to reference van Veldhuisen DJ, Anker SD, Ponikowski P, Macdougall IC (2011) Anemia and iron deficiency in heart failure: mechanisms and therapeutic approaches. Nat Rev Cardiol 8:485–493CrossRefPubMed van Veldhuisen DJ, Anker SD, Ponikowski P, Macdougall IC (2011) Anemia and iron deficiency in heart failure: mechanisms and therapeutic approaches. Nat Rev Cardiol 8:485–493CrossRefPubMed
Metadata
Title
Iron deficiency in patients with heart failure with preserved ejection fraction and its association with reduced exercise capacity, muscle strength and quality of life
Authors
Tarek Bekfani
Pierpaolo Pellicori
Daniel Morris
Nicole Ebner
Miroslava Valentova
Anja Sandek
Wolfram Doehner
John G. Cleland
Mitja Lainscak
P. Christian Schulze
Stefan D. Anker
Stephan von Haehling
Publication date
01-02-2019
Publisher
Springer Berlin Heidelberg
Published in
Clinical Research in Cardiology / Issue 2/2019
Print ISSN: 1861-0684
Electronic ISSN: 1861-0692
DOI
https://doi.org/10.1007/s00392-018-1344-x

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