Factors determining the physical performance of patientswith heart failure and anemia

Authors: Kupryashov A.A., Rivnyak M.I., Koloskova N.N., Glushko L.A., Mironenko V.A., Bockeria L.A.

Company: Bakoulev National Medical Research Center for Cardiovascular Surgery, Ministry of Health of the Russian Federation, Rublevskoe shosse, 135, Moscow, 121552, Russian Federation

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Type:  Original articles


DOI: https://doi.org/10.24022/1997-3187-2019-13-4-349-362

For citation: Kupryashov A.A., Rivnyak M.I., Koloskova N.N., Glushko L.A., Mironenko V.A., Bockeria L.A. Factors determining the physical performance of patients with heart failure and anemia. Creative Cardiology. 2019; 13 (4): 349–62 (in Russ.). DOI: 10.24022/1997-3187-2019-13-4-349-362

Received / Accepted:  03.12.2019/11.12.2019

Keywords: heart failure ferropenia anemia exercise capacity

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Abstract

Objective. To study is the prognoses of tolerance to exercise capacity depending on impaired hemodynamics and severity of anemia.

Material and methods. The prospective observational cohort study included 79 patients with chronic heart failure. The dependent variables were the functional physical performance class, assessed in a 6-minute walk test and based on the determination of peak oxygen consumption using a cardiorespiratory test. Indicators of morphofunctional state of the left ventricle, hematological parameters and characteristics of iron metabolism (iron, transferrin, ferritin) were considered as independent variables.

Results. When assessing physical performance on the basis of a 6-minute walk test, it was shown that higher peak oxygen consumption (с=0,767), higher concentrations of iron (с=0,524) and transferrin (с=0,368) provided a higher load tolerance, while the anaerobic threshold (с=–0,066) and hematocrit (с=–0,024) affected it negatively. When assessing physical performance on the basis of the cardiorespiratory test, it was revealed that higher oxygen consumption at rest (с=0,288) and anaerobic threshold (с=0,608), as well as hematocrit (с=0,266), suggest a greater tolerance to physical activity, while VE/VO2 (с=–0,326), VE/VCO2 (с=–0,199), end-diastolic volume (EDV) of left ventricular (LV) (с=–0,218), serum iron (с=–0,061) had negative prognostic value. It was shown that, depending on EDV LV, hematocrit, serum iron and transferrin concentrations, patients with heart failure can be combined into three clusters: with minimal laboratory and hemodynamic disorders, mainly with hemodynamic disorders and mainly with iron deficiency.

Conclusion. The level of transferrin less than 200 mg/dl in patients with heart failure associated with anemia should suggest the elimination of disorders of iron metabolism, and LV EDV more than 300 ml indicates a predominant contribution of hemodilution to a decrease in hemoglobin concentration.

References

  1. Adams K.F., Patterson J.H., Oren R.M., Mehra M.R., O'Connor C.M., Pin~a I.L. et al. Prospective assessment of the occurrence of anemia in patients with heart failure: results from the Study of Anemia in a Heart Failure Population (STAMINAHFP) Registry. Am. Heart J. 2009; 157 (5): 926–32. DOI: 10.1016/j.ahj.2009.01.012
  2. Androne A.S., Katz S.D., Lund L., LaManca J., Hudaihed A., Hryniewicz K. et al. Hemodilution is common in patients with advanced heart failure. Circulation. 2003; 107 (2): 226–9. DOI: 10.1161/01.cir.0000052623.16194.80
  3. Hung M., Ortmann E., Besser M., Martin-Cabrera P., Richards T., Ghosh M. et al. A prospective observational cohort study to identify the causes of anaemia and association with outcome in cardiac surgical patients. Heart. 2015; 101 (2): 107–12. DOI: 10.1136/heartjnl-2014-305856
  4. Sanders J., Jackie A.C., Farrar D., Braithwaite S., Sandhu U. et al. Pre-operative anaemia is associated with total morbidity burden on days 3 and 5 after cardiac surgery: a cohort study. Perioper. Med. (Lond). 2017; 6: 1. DOI: 10.1186/s13741-017-0057-4
  5. Okonko D.O., Mandal A.K., Missouris C.G., Poole-Wilson P.A. Disordered iron homeostasis in chronic heart failure: prevalence, predictors, and relation to anemia, exercise capacity, and survival. J. Am. Coll. Cardiol. 2011; 58: 1241–51. DOI: 10.1016/j.jacc.2011.04.040
  6. Opasich C., Cazzola M., Scelsi L., De Feo S., Bosimini E., Lagioia R. et al. Blunted erythropoietin production and defective iron supply for erythropoiesis as major causes of anaemia in patients with chronic heart failure. Eur. Heart J. 2005; 26: 2232–7. DOI: 10.1093/eurheartj/ehi388
  7. Trey J.E., Kushner I. The acute phase response and the hematopoietic system: the role of cytokines. Crit. Rev. Oncol. Hematol. 1995; 21: 1–18. DOI: 10.1016/1040-8428(94)00141-3
  8. Virani S.A., Khosla A., Levin A. Chronic kidney disease, heart failure and anemia. Can. J. Cardiol. 2008; 24 (Suppl. B): 22B–24B. DOI: 10.1016/s0828-282x(08)71026-2
  9. Go A.S., Yang J., Ackerson L.M., Lepper K., Robbins S., Massie B.M. et al. Hemoglobin level, chronic kidney disease, and the risks of death and hospitalization in adults with chronic heart failure: the Anemia in Chronic Heart Failure: Outcomes and Resource Utilization (ANCHOR) Study. Circulation. 2006; 113: 2713–23. DOI: 10.1161/CIRCULATIONAHA.105.577577
  10. Wali R.K., Henrich W.L. Chronic kidney disease: a risk factor for cardiovascular disease. Cardiol. Clin. 2005; 23: 343–62. DOI: 10.1016/j.ccl.2005.03.007
  11. Al-Ahmad A., Rand W.M., Manjunath G., Konstam M.A., Salem D.N., Levey A.S. et al. Reduced kidney function and anemia as risk factors for mortality in patients with left ventricular dysfunction. J. Am. Coll. Cardiol. 2001; 39: 955–62. DOI: 10.1016/s0735-1097(01)01470-x
  12. Witte K.K., Desilva R., Chattopadhyay S., Ghosh J., Cleland J.G., Clark A.L. Are hematinic deficiencies the cause of anemia in chronic heart failure? Am. Heart J. 2004; 147 (5): 924–30. DOI: 10.1016/j.ahj.2003.11.007
  13. Berry C., Poppe K.K., Gamble G.D., Earle N.J., Ezekowitz J.A., Squire I.B. et al. Prognostic significance of anaemia in patients with heart failure with preserved and reduced ejection fraction: results from the MAGGIC individual patient data meta-analysis. QJM. 2016; 109 (6): 377–82. DOI: 10.1093/qjmed/hcv087
  14. Jankowska E.A., Rozentryt P., Witkowska A., Nowak J., Hartmann O., Ponikowska B. et al. Iron deficiency predicts impaired exercise capacity in patients with systolic chronic heart failure. J. Card. Fail. 2011; 17 (11): 899–906. DOI: 10.1016/j.cardfail.2011.08.003
  15. Guyatt G.H., Sullivan M.J., Thompson P.J., Ernest L.F., Stewart O.P., Taylor D.W. et al. The 6-minute walk: a new measure of exercise capacity in patients with chronic heart failure. Can. Med. Assoc. J. 1985; 132 (8): 919–23. PMCID: PMC1345899
  16. Weber K.T., Janicki J.S. Cardiopulmonary exercise testing for evaluation of chronic cardiac failure. Am. J. Cardiol. 1985; 55: 22A–31A. DOI: 10.1016/0002-9149(85)90792-1
  17. Kupryashov A.A., Rivnyak M.I., Koloskova N.N., Glushko L.A., Plyushch M.G., Mironenko V.A., Bockeria L.A. Association of preload with hemoglobin level in patients with heart failure. Clinical Physiology of Circulation. 2018; 15 (3): 178–89 (in Russ.). DOI: 10.24022/1814-6910-2018-15-3-178-189
  18. Zahidova K. Indexes of the erythropoietin level in the blood plasma of chronic heart failure patients with anemia. J. Basic. Clin. Physiol. Pharmacol. 2018; 29 (1): 11–7. DOI: 10.1515/jbcpp-2016-0102
  19. Garimella P.S., Katz R., Patel K.V., Kritchevsky S.B., Parikh C.R., Ix J.H. et al. Association of serum erythropoietin with cardiovascular events, kidney function decline, and mortality: the Health Aging and Body Composition Study. Circ. Heart Fail. 2016; 9 (1): e002124. DOI: 10.1161/CIRCHEARTFAILURE.115.002124
  20. Hentze M.W., Muckenthaler M.U., Galy B., Camaschella C. Two to tango: regulation of mammalian iron metabolism. Cell. 2010; 142 (1): 24–38. DOI: 10.1016/j.cell.2010.06.028
  21. Dai L., Mick S.L., McCrae K.R., Houghtaling P.L., Sabik J.F. 3rd., Blackstone E.H. et al. Preoperative anemia in cardiac operation: does hemoglobin tell the whole story? Ann. Thorac. Surg. 2018; 105 (1): 100–7. DOI: 10.1016/j.athoracsur.2017.06.074
  22. Tkaczyszyn M., Drozd M., We,grzynowska- Teodorczyk K., Flinta I., Kobak K., Banasiak W. et al. Depleted iron stores are associated with inspiratory muscle weakness independently of skeletal muscle mass in men with systolic chronic heart failure. J. Cachex. Sarcop. Musc. 2018; 9 (3): 547–56. DOI: 10.1002/jcsm.12282
  23. Hoes M.F., Grote Beverborg N., Kijlstra J.D., Kuipers J., Swinkels D.W., Giepmans B.N. et al. Iron deficiency impairs contractility of human cardiomyocytes through decreased mitochondrial function. Eur. J. Heart Fail. 2018; 20 (5): 910–9. DOI: 10.1002/ejhf.1154
  24. Abramov D., Cohen R.S., Katz S.D., Mancini D., Maurer M.S. Comparison of blood volume characteristics in anemic patients with low versus preserved left ventricular ejection fractions. Am. J. Cardiol. 2008; 102 (8): 1069–72. DOI: 10.1016/j.amjcard.2008.05.058
  25. Otto J.M., Plumb J.O.M., Clissold E., Kumar S.B., Wakeham D.J., Schmidt W. et al. Hemoglobin concentration, total hemoglobin mass and plasma volume in patients: implications for anemia. Haematologica. 2017; 102 (9): 1477–85. DOI: 10.3324/haematol.2017.169680
  26. Miller W.L., Mullan B.P. Peripheral venous hemoglobin and red blood cell mass mismatch in volume overload systolic heart failure: implications for patient management. J. Cardiovasc. Transl. Res. 2015; 8 (7): 404–10. DOI: 10.1007/s12265-015-9650-4
  27. Otto J.M., Plumb J.O.M., Wakeham D., Clissold E., Loughney L., Schmidt W. et al. Total haemoglobin mass, but not haemoglobin concentration, is associated with preoperative cardiopulmonary exercise testing-derived oxygen-consumption variables. Br. J. Anaesth. 2017; 118 (5): 747–54. DOI: 10.1093/bja/aew445
  28. Shander A., Javidroozi M., Ozawa S., Hare G.M. What is really dangerous: anaemia or transfusion? Br. J. Anaesth. 2011; 107 (1): i41–59. DOI: 10.1093/bja/aer350
  29. Korolnek T., Hamza I. Like iron in the blood of the people: the requirement for heme trafficking in iron metabolism. Front Pharmacol. 2014; 5: 126. DOI: 10.3389/fphar.2014.00126
  30. Paul B.T., Manz D.H., Torti F.M., Torti S.V. Mitochondria and iron: current questions. Exp. Rev. Hematol. 2017; 10: 65–79. DOI: 10.1080/17474086.2016.1268047
  31. Semenza G.L., Koury S.T., Nejfelt M.K., Gearhart J.D., Antonarakis S.E. Cell-type-specific and hypoxia-inducible expression of the human erythropoietin gene in transgenic mice. Proc. Natl. Acad. Sci. USA. 1991; 88: 8725–9. DOI: 10.1073/pnas.88.19.8725
  32. Mole D.R. Iron homeostasis and its interaction with prolyl hydroxylases. Antioxid. Redox Signal. 2010; 12: 445–58. DOI: 10.1089/ars.2009.2790
  33. Simpson R.J. Effect of hypoxic exposure on iron absorption in heterozygous hypotransferrinaemic mice. Ann. Hematol. 1992; 65: 260–4. DOI: 10.1007/bf01836070
  34. Peyssonnaux C., Zinkernagel A.S., Schuepbach R.A., Rankin E., Vaulont S., Haase V.H. et al. Regulation of iron homeostasis by the hypoxia-inducible transcription factors (HIFs). J. Clin. Invest. 2007; 117: 1926–32. DOI: 10.1172/JCI31370
  35. Hirota K. An intimate crosstalk between iron homeostasis and oxygen metabolism regulated by the hypoxia-inducible factors (HIFs). Free Radic. Biol. Med. 2019; 133: 118–29. DOI: 10.1016/j.freeradbiomed.2018.07.018
  36. Sanchez M., Galy B., Muckenthaler M.U., Hentze M.W. Iron-regulatory proteins limit hypoxia-inducible factor-2[alpha] expression in iron deficiency. Nat. Struct. Mol. Biol. 2007; 14: 420–6. DOI: 10.1038/nsmb1222
  37. Salahudeen A.A., Bruick R.K. Maintaining mammalian iron and oxygen homeostasis: sensors, regulation, and cross-talk. Ann. N.Y Acad. Sci. 2009; 1177: 30–8. DOI: 10.1111/j.1749-6632.2009.05038.x
  38. Mastrogiannaki M., Matak P., Keith B., Simon M.C., Vaulont S., Peyssonnaux C. HIF- 2alpha, but not HIF-1alpha, promotes iron absorption in mice. J. Clin. Invest. 2009; 119: 1159–66. DOI: 10.1172/JCI38499
  39. Shah Y.M., Matsubara T., Ito S., Yim S.H., Gonzalez F.J. Intestinal hypoxia-inducible transcription factors are essential for iron absorption following iron deficiency. Cell Metab. 2009; 9: 152–64. DOI: 10.1016/j.cmet.2008.12.012

About Authors

  • Aleksey A. Kupryashov, Dr. Med. Sc., Head of Department; ORCID
  • Marina I. Rivnyak, Cardiologist
  • Nadezhda N. Koloskova, Cand. Med. Sc., Head of Department
  • Lyudmila A. Glushko, Cand. Med. Sc., Head of Group; ORCID
  • Vladimir A. Mironenko, Dr. Med. Sc., Head of Department; ORCID
  • Leo A. Bockeria, Dr. Med. Sc., Professor, Academician of RAS and RAMS, President; ORCID

Chief Editor

Leo A. Bockeria, MD, PhD, DSc, Professor, Academician of Russian Academy of Sciences, President of Bakoulev National Medical Research Center for Cardiovascular Surgery