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Published in: Current Heart Failure Reports 5/2020

01-10-2020 | Heart Failure | Nonpharmacologic Therapy: Surgery, Ventricular Assist Devices, Biventricular Pacing, and Exercise (A Hasan, Section Editor)

Stem Cell Therapy for Chronic and Advanced Heart Failure

Authors: Gregor Poglajen, Sabina Frljak, Gregor Zemljič, Andraž Cerar, Renata Okrajšek, Miran Šebeštjen, Bojan Vrtovec

Published in: Current Heart Failure Reports | Issue 5/2020

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Abstract

Purpose of Review

The purpose of this review is to discuss recent advances in the field of cell therapy in patients with heart failure with reduced ejection fraction (HFrEF) of ischemic (iCMP) and nonischemic (dCMP) etiology, heart failure with preserved ejection fraction (HFpEF), and in advanced heart failure patients undergoing mechanical circulatory support (LVAD).

Recent Findings

In HFrEF patients (iCMP and dCMP cohorts), autologous and/or allogeneic cell therapy was shown to improve myocardial performance, patients’ functional capacity, and neurohumoral activation. In HFpEF patient population, the concept of cell therapy in novel and remains largely unexplored. However, initial data are very encouraging and suggest at least a similar benefit in improvements of myocardial performance (also diastolic function of the left ventricle), exercise capacity, and neurohumoral activation. Recently, cell therapy was explored in the sickest population of advanced heart failure patients undergoing LVAD support also showing a potential benefit in promoting myocardial reverse remodeling and recovery.

Summary

In the past decade, several cell therapy-based clinical trials showed promising results in various chronic and advanced heart failure patient cohorts. Future cell treatment strategies should aim for more personalized therapeutic approaches by defining optimal stem cell type or their combination, dose, and delivery method for an individual patient adjusted for patient’s age and stage/duration of heart failure.
Literature
2.
go back to reference Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016;18(8):891–975. https://doi.org/10.1002/ejhf.592.CrossRefPubMed Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the task force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016;18(8):891–975. https://​doi.​org/​10.​1002/​ejhf.​592.CrossRefPubMed
4.
14.
go back to reference Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Hölschermann, et al. Improved clinical outcome after intracoronary administration of bone-marrowderived progenitor cells in acutemyocardial infarction: final 1-year results of the REPAIR-AMI trial. Eur Heart J. 2006;27(23):2775–83. https://doi.org/10.1093/eurheartj/ehl388.CrossRefPubMed Schachinger V, Erbs S, Elsasser A, Haberbosch W, Hambrecht R, Hölschermann, et al. Improved clinical outcome after intracoronary administration of bone-marrowderived progenitor cells in acutemyocardial infarction: final 1-year results of the REPAIR-AMI trial. Eur Heart J. 2006;27(23):2775–83. https://​doi.​org/​10.​1093/​eurheartj/​ehl388.CrossRefPubMed
16.
go back to reference Assmus B, Fischer-Rasokat U, Honold J, Seeger FH, Fichtlscherer S, Tonn T, et al. Transcoronary transplantation of functionally competent BMCs is associated with a decrease in natriuretic peptide serum levels and improved survival of patients with chronic postinfarction heart failure: results of the TOPCARE-CHD registry. Circ Res. 2007;100(8):1234–41. https://doi.org/10.1161/01.RES.0000264508.47717.6b.CrossRefPubMed Assmus B, Fischer-Rasokat U, Honold J, Seeger FH, Fichtlscherer S, Tonn T, et al. Transcoronary transplantation of functionally competent BMCs is associated with a decrease in natriuretic peptide serum levels and improved survival of patients with chronic postinfarction heart failure: results of the TOPCARE-CHD registry. Circ Res. 2007;100(8):1234–41. https://​doi.​org/​10.​1161/​01.​RES.​0000264508.​47717.​6b.CrossRefPubMed
21.
23.
go back to reference Tendera M, Wojakowski W, Ruzyllo W, Chojnowska L, Kepka C, Tracz W, et al. Intracoronary infusion of bone marrow-derived selected CD34(+)CXCR4(+) cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre myocardial regeneration by intracoronary infusion of selected population of stem cells in acute myocardial infarction (REGENT) trial. Eur Heart J. 2009;30(11):1313–21. https://doi.org/10.1093/eurheartj/ehp073.CrossRefPubMed Tendera M, Wojakowski W, Ruzyllo W, Chojnowska L, Kepka C, Tracz W, et al. Intracoronary infusion of bone marrow-derived selected CD34(+)CXCR4(+) cells and non-selected mononuclear cells in patients with acute STEMI and reduced left ventricular ejection fraction: results of randomized, multicentre myocardial regeneration by intracoronary infusion of selected population of stem cells in acute myocardial infarction (REGENT) trial. Eur Heart J. 2009;30(11):1313–21. https://​doi.​org/​10.​1093/​eurheartj/​ehp073.CrossRefPubMed
29.
go back to reference • Theiss HD, David R, Engelmann MG, Barth A, Schotten K, Naebauer M, et al. Circulation of CD34+ progenitor cell populations in patients with idiopathic dilated and ischaemic cardiomyopathy (DCM and ICM). European Heart Journal. 2007;28:1258–64. https://doi.org/10.1093/eurheartj/ehm011This study outline the correlation with stem cell reserve and heart failure type and stage.CrossRefPubMed • Theiss HD, David R, Engelmann MG, Barth A, Schotten K, Naebauer M, et al. Circulation of CD34+ progenitor cell populations in patients with idiopathic dilated and ischaemic cardiomyopathy (DCM and ICM). European Heart Journal. 2007;28:1258–64. https://​doi.​org/​10.​1093/​eurheartj/​ehm011This study outline the correlation with stem cell reserve and heart failure type and stage.CrossRefPubMed
32.
go back to reference Fischer-Rasokat U, Assmus B, Seeger FH, Honold J, Leistner D, Fichtlscherer S, et al. A pilot trial to assess potential effects of selective intracoronary bone marrow-derived progenitor cell infusion in patients with nonischemic dilated cardiomyopathy: final 1-year results of the transplantation of progenitor cells and functional regeneration enhancement pilot trial in patients with nonischemic dilated cardiomyopathy. Circ Heart Fail. 2009;2:417–23. https://doi.org/10.1161/CIRCHEARTFAILURE.109.855023.CrossRefPubMed Fischer-Rasokat U, Assmus B, Seeger FH, Honold J, Leistner D, Fichtlscherer S, et al. A pilot trial to assess potential effects of selective intracoronary bone marrow-derived progenitor cell infusion in patients with nonischemic dilated cardiomyopathy: final 1-year results of the transplantation of progenitor cells and functional regeneration enhancement pilot trial in patients with nonischemic dilated cardiomyopathy. Circ Heart Fail. 2009;2:417–23. https://​doi.​org/​10.​1161/​CIRCHEARTFAILURE​.​109.​855023.CrossRefPubMed
33.
37.
go back to reference • Vrtovec B, Poglajen G, Lezaic L, Sever M, Domanovic D, Cernelc P, et al. Effects of intracoronary CD34+ stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up. Circ Res. 2013;112(1):165–73. https://doi.org/10.1161/CIRCRESAHA.112.276519Study to present the longest follow-up data of cell therapy in non-ischemic cardiomyopathy and suggests potential survival benefit of cell therapy in this patient cohort.CrossRefPubMed • Vrtovec B, Poglajen G, Lezaic L, Sever M, Domanovic D, Cernelc P, et al. Effects of intracoronary CD34+ stem cell transplantation in nonischemic dilated cardiomyopathy patients: 5-year follow-up. Circ Res. 2013;112(1):165–73. https://​doi.​org/​10.​1161/​CIRCRESAHA.​112.​276519Study to present the longest follow-up data of cell therapy in non-ischemic cardiomyopathy and suggests potential survival benefit of cell therapy in this patient cohort.CrossRefPubMed
38.
go back to reference • Vrtovec B, Poglajen G, Lezaic L, Sever M, Socan A, Domanovic D, et al. Comparison of transendocardial and intracoronary CD34+ cell transplantation in patients with nonischemic dilated cardiomyopathy. Circulation. 2013;128(11 Suppl 1):S42–9. https://doi.org/10.1161/CIRCULATIONAHA.112.000230This study presents one of the strongest clinical data to support transendocardial cell delivery over intracoronary cell injections.CrossRefPubMed • Vrtovec B, Poglajen G, Lezaic L, Sever M, Socan A, Domanovic D, et al. Comparison of transendocardial and intracoronary CD34+ cell transplantation in patients with nonischemic dilated cardiomyopathy. Circulation. 2013;128(11 Suppl 1):S42–9. https://​doi.​org/​10.​1161/​CIRCULATIONAHA.​112.​000230This study presents one of the strongest clinical data to support transendocardial cell delivery over intracoronary cell injections.CrossRefPubMed
40.
go back to reference • Hare JM, DL DF, Rieger AC, Florea V, Landin AM, El-Khorazaty J, et al. Randomized comparison of allogeneic versus autologous mesenchymal stem cells for nonischemic dilated cardiomyopathy: POSEIDON-DCM Trial. J Am Coll Cardiol. 2017;69(5):526–37. https://doi.org/10.1016/j.jacc.2016.11.009First study to compare autologous to allogeneic cell therapy in non-ischemic cardiomyopathy patients.CrossRefPubMed • Hare JM, DL DF, Rieger AC, Florea V, Landin AM, El-Khorazaty J, et al. Randomized comparison of allogeneic versus autologous mesenchymal stem cells for nonischemic dilated cardiomyopathy: POSEIDON-DCM Trial. J Am Coll Cardiol. 2017;69(5):526–37. https://​doi.​org/​10.​1016/​j.​jacc.​2016.​11.​009First study to compare autologous to allogeneic cell therapy in non-ischemic cardiomyopathy patients.CrossRefPubMed
43.
go back to reference Mohammed SF, Hussain S, Mirzoyev SA, Edwards WD, Maleszewski JJ, Redfield MM. Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction. Circulation. 2015;131:550–9.CrossRefPubMed Mohammed SF, Hussain S, Mirzoyev SA, Edwards WD, Maleszewski JJ, Redfield MM. Coronary microvascular rarefaction and myocardial fibrosis in heart failure with preserved ejection fraction. Circulation. 2015;131:550–9.CrossRefPubMed
48.
52.
go back to reference •• Yau TM, Pagani FD, Mancini DM, Chang HL, Lala A, Woo YJ, et al. Intramyocardial injection of mesenchymal precursor cells and successful temporary weaning from left ventricular assist device support in patients with advanced heart failure: a randomized clinical trial. JAMA. 2019;321(12):1176–86. https://doi.org/10.1001/jama.2019.2341The largest clinical trial of cell therapy in LVAD-supported patients.CrossRefPubMedPubMedCentral •• Yau TM, Pagani FD, Mancini DM, Chang HL, Lala A, Woo YJ, et al. Intramyocardial injection of mesenchymal precursor cells and successful temporary weaning from left ventricular assist device support in patients with advanced heart failure: a randomized clinical trial. JAMA. 2019;321(12):1176–86. https://​doi.​org/​10.​1001/​jama.​2019.​2341The largest clinical trial of cell therapy in LVAD-supported patients.CrossRefPubMedPubMedCentral
53.
go back to reference Zheng Y, Sampaio LC, Li K, Silva GV, Cabreira-Hansen M, Vela D, et al. Safety and feasibility of mapping and stem cell delivery in the presence of an implanted left ventricular assist device: a preclinical investigation in sheep. Tex Heart Inst J. 2013;40:229–34.PubMedPubMedCentral Zheng Y, Sampaio LC, Li K, Silva GV, Cabreira-Hansen M, Vela D, et al. Safety and feasibility of mapping and stem cell delivery in the presence of an implanted left ventricular assist device: a preclinical investigation in sheep. Tex Heart Inst J. 2013;40:229–34.PubMedPubMedCentral
Metadata
Title
Stem Cell Therapy for Chronic and Advanced Heart Failure
Authors
Gregor Poglajen
Sabina Frljak
Gregor Zemljič
Andraž Cerar
Renata Okrajšek
Miran Šebeštjen
Bojan Vrtovec
Publication date
01-10-2020
Publisher
Springer US
Published in
Current Heart Failure Reports / Issue 5/2020
Print ISSN: 1546-9530
Electronic ISSN: 1546-9549
DOI
https://doi.org/10.1007/s11897-020-00477-9

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