open access

Vol 25, No 4 (2018)
Original articles — Clinical cardiology
Submitted: 2018-06-23
Accepted: 2018-08-08
Published online: 2018-09-12
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Effects of trans-endocardial delivery of bone marrow-derived CD133+ cells on angina and quality of life in patients with refractory angina: A sub-analysis of the REGENT-VSEL trial

Tomasz Jadczyk1, Joanna Ciosek1, Aleksandra Michalewska-Wludarczyk1, Wojciech Szot23, Zofia Parma1, Beata Ochala1, Miroslaw Markiewicz4, Wojciech Rychlik5, Magdalena Kostkiewicz6, Katarzyna Gruszczynska7, Anna Blach1, Monika Dzierzak-Mietla4, Lukasz Rzeszutko8, Lukasz Partyka910, Wojciech Zasada89, Grzegorz Smolka1, Tomasz Pawlowski1, Marek Jedrzejek1, Zdenek Starek1112, Krzysztof Plens9, Andrzej Ochala1, Michal Tendera1, Wojciech Wojakowski1
DOI: 10.5603/CJ.2018.0082
·
Pubmed: 30211929
·
Cardiol J 2018;25(4):521-529.
Affiliations
  1. Division of Cardiology and Structural Heart Diseases, Medical University of Silesia, Katowice, Poland
  2. Hygiene and Dietary Department, Jagiellonian University, Collegium Medicum, Krakow, Poland
  3. Department of Nuclear Medicine, Hospital John Paul II, Krakow, Poland
  4. Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia, Katowice, Poland
  5. Department of Anaesthesiology and Intensive Care with Cardiac Monitoring, Upper Silesian Medical Centre, Katowice, Poland
  6. Department of Cardiovascular Diseases, Jagiellonian University, Hospital John Paul II, Krakow, Poland
  7. Division of Diagnostic Imaging, Medical University of Silesia, Katowice, Poland
  8. 2nd Department of Cardiology and Cardiovascular Interventions, University Hospital, Krakow, Poland
  9. Krakow Cardiovascular Research Institute, Krakow, Poland
  10. Department of Angiology, University Hospital, Krakow, Poland
  11. International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic
  12. Masaryk University, Faculty of Medicine, Brno, Czech Republic

open access

Vol 25, No 4 (2018)
Original articles — Clinical cardiology
Submitted: 2018-06-23
Accepted: 2018-08-08
Published online: 2018-09-12

Abstract

Background: The REGENT-VSEL trial demonstrated a neutral effect of transendocardial injection of autologous bone marrow (BM)-derived CD133+ in regard to myocardial ischemia. The current sub-analysis of the REGENT VSEL trial aims to assess the effect stem cell therapy has on quality of life (QoL) in patients with refractory angina.
Methods: Thirty-one patients (63.0 ± 6.4 years, 70% male) with recurrent CCS II–IV angina, despite optimal medical therapy, enrolled in the REGENT-VSEL single center, randomized, double-blinded, and placebo-controlled trial. Of the 31 patients, 16 individuals were randomly assigned to the active stem cell group and 15 individuals were randomly assigned to the placebo group on a 1:1 basis. The inducibility of ischemia, (≥ one myocardial segment) was confirmed for each patient using Tc-99m SPECT. QoL was measured using the Seattle Angina Questionnaire. Each patient completed the questionnaire prior to treatment and at the time of their outpatient follow-up visits at 1, 4, 6, and 12 months after cell/placebo treatment.
Results: The main finding of the REGENT-VSEL trial sub-analysis was that transendocardial injection of autologous BM-derived CD133+ stem cells in patients with chronic refractory angina did not show significant improvement in QoL in comparison to the control group. Moreover, there was no significant difference between cell therapy and placebo in a number of patients showing improvement of at least 1 Canadian Cardiovascular Society class during the follow-up period.
Conclusions: Intra-myocardial delivery of autologous CD133+ stem cells is safe and feasible but does not show a significant improvement in the QoL or angina pectoris symptoms in patients with chronic myocardial ischemia.

Abstract

Background: The REGENT-VSEL trial demonstrated a neutral effect of transendocardial injection of autologous bone marrow (BM)-derived CD133+ in regard to myocardial ischemia. The current sub-analysis of the REGENT VSEL trial aims to assess the effect stem cell therapy has on quality of life (QoL) in patients with refractory angina.
Methods: Thirty-one patients (63.0 ± 6.4 years, 70% male) with recurrent CCS II–IV angina, despite optimal medical therapy, enrolled in the REGENT-VSEL single center, randomized, double-blinded, and placebo-controlled trial. Of the 31 patients, 16 individuals were randomly assigned to the active stem cell group and 15 individuals were randomly assigned to the placebo group on a 1:1 basis. The inducibility of ischemia, (≥ one myocardial segment) was confirmed for each patient using Tc-99m SPECT. QoL was measured using the Seattle Angina Questionnaire. Each patient completed the questionnaire prior to treatment and at the time of their outpatient follow-up visits at 1, 4, 6, and 12 months after cell/placebo treatment.
Results: The main finding of the REGENT-VSEL trial sub-analysis was that transendocardial injection of autologous BM-derived CD133+ stem cells in patients with chronic refractory angina did not show significant improvement in QoL in comparison to the control group. Moreover, there was no significant difference between cell therapy and placebo in a number of patients showing improvement of at least 1 Canadian Cardiovascular Society class during the follow-up period.
Conclusions: Intra-myocardial delivery of autologous CD133+ stem cells is safe and feasible but does not show a significant improvement in the QoL or angina pectoris symptoms in patients with chronic myocardial ischemia.

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Keywords

quality of life; refractory angina; bone marrow; cell therapy; CD133 cells

About this article
Title

Effects of trans-endocardial delivery of bone marrow-derived CD133+ cells on angina and quality of life in patients with refractory angina: A sub-analysis of the REGENT-VSEL trial

Journal

Cardiology Journal

Issue

Vol 25, No 4 (2018)

Pages

521-529

Published online

2018-09-12

Page views

1941

Article views/downloads

1256

DOI

10.5603/CJ.2018.0082

Pubmed

30211929

Bibliographic record

Cardiol J 2018;25(4):521-529.

Keywords

quality of life
refractory angina
bone marrow
cell therapy
CD133 cells

Authors

Tomasz Jadczyk
Joanna Ciosek
Aleksandra Michalewska-Wludarczyk
Wojciech Szot
Zofia Parma
Beata Ochala
Miroslaw Markiewicz
Wojciech Rychlik
Magdalena Kostkiewicz
Katarzyna Gruszczynska
Anna Blach
Monika Dzierzak-Mietla
Lukasz Rzeszutko
Lukasz Partyka
Wojciech Zasada
Grzegorz Smolka
Tomasz Pawlowski
Marek Jedrzejek
Zdenek Starek
Krzysztof Plens
Andrzej Ochala
Michal Tendera
Wojciech Wojakowski

References (29)
  1. O'Flaherty M, Huffman MD, Capewell S. Declining trends in acute myocardial infarction attack and mortality rates, celebrating progress and ensuring future success. Heart. 2015; 101(17): 1353–1354.
  2. Smolina K, Wright FL, Rayner M, et al. Determinants of the decline in mortality from acute myocardial infarction in England between 2002 and 2010: linked national database study. BMJ. 2012; 344: d8059.
  3. Ford ES, Ajani UA, Croft JB, et al. Explaining the decrease in U.S. deaths from coronary disease, 1980-2000. N Engl J Med. 2007; 356(23): 2388–2398.
  4. Mannheimer C, Camici P, Chester MR, et al. The problem of chronic refractory angina; report from the ESC Joint Study Group on the Treatment of Refractory Angina. Eur Heart J. 2002; 23(5): 355–370.
  5. Montalescot G, Sechtem U, Achenbach S, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013; 34(38): 2949–3003.
  6. Mukherjee D, Comella K, Bhatt DL, et al. Clinical outcome of a cohort of patients eligible for therapeutic angiogenesis or transmyocardial revascularization. Am Heart J. 2001; 142(1): 72–74.
  7. Andréll P, Ekre O, Grip L, et al. Fatality, morbidity and quality of life in patients with refractory angina pectoris. Int J Cardiol. 2011; 147(3): 377–382.
  8. Rodrigo SF, Mann I, van Ramshorst J, et al. Reduction of healthcare utilization after bone marrow cell therapy for refractory angina pectoris. Int J Cardiol. 2016; 202: 571–572.
  9. Losordo DW, Henry TD, Davidson C, et al. Intramyocardial, Autologous CD34+ Cell Therapy for Refractory Angina. Circ Res. 2011; 109(4): 428–436.
  10. Tse HF, Thambar S, Kwong YL, et al. Prospective randomized trial of direct endomyocardial implantation of bone marrow cells for treatment of severe coronary artery diseases (PROTECT-CAD trial). Eur Heart J. 2007; 28(24): 2998–3005.
  11. van Ramshorst J, Bax JJ, Beeres SL, et al. Intramyocardial bone marrow cell injection for chronic myocardial ischemia: a randomized controlled trial. JAMA. 2009; 301(19): 1997–2004.
  12. Jimenez-Quevedo P, Gonzalez-Ferrer JJ, Sabate M, et al. Selected CD133⁺ progenitor cells to promote angiogenesis in patients with refractory angina: final results of the PROGENITOR randomized trial. Circ Res. 2014; 115(11): 950–960.
  13. Wojakowski W, Jadczyk T, Michalewska-Włudarczyk A, et al. Effects of Transendocardial Delivery of Bone Marrow-Derived CD133 Cells on Left Ventricle Perfusion and Function in Patients With Refractory Angina: Final Results of Randomized, Double-Blinded, Placebo-Controlled REGENT-VSEL Trial. Circ Res. 2017; 120(4): 670–680.
  14. Spertus J, Winder J, Dewhurst T, et al. Development and evaluation of the Seattle Angina questionnaire: A new functional status measure for coronary artery disease. J Am Coll Cardiol. 1995; 25(2): 333–341.
  15. Rodrigo SF, Mann I, van Ramshorst J, et al. Safety and efficacy of percutaneous intramyocardial bone marrow cell injection for chronic myocardial ischemia: Long-term results. J Interv Cardiol. 2017; 30(5): 440–447.
  16. Povsic T, Henry T, Traverse J, et al. The RENEW Trial. Efficacy and Safety of Intramyocardial Autologous CD34(+) Cell Administration in Patients With Refractory Angina. JACC: Cardiovascular Interventions. 2016; 9(15): 1576–1585.
  17. Mann I, Rodrigo SF, van Ramshorst J, et al. Repeated Intramyocardial Bone Marrow Cell Injection in Previously Responding Patients With Refractory Angina Again Improves Myocardial Perfusion, Anginal Complaints, and Quality of Life. Circ Cardiovasc Interv. 2015; 8(8).
  18. Rodrigo SF, van Ramshorst J, Beeres SL, et al. Intramyocardial injection of bone marrow mononuclear cells in chronic myocardial ischemia patients after previous placebo injection improves myocardial perfusion and anginal symptoms: an intra-patient comparison. Am Heart J. 2012; 164(5): 771–778.
  19. Beeres SL, Bax JJ, Dibbets-Schneider P, et al. Sustained effect of autologous bone marrow mononuclear cell injection in patients with refractory angina pectoris and chronic myocardial ischemia: twelve-month follow-up results. Am Heart J. 2006; 152(4): 684.e11–684.e16.
  20. Mathiasen AB, Haack-Sørensen M, Jørgensen E, et al. Autotransplantation of mesenchymal stromal cells from bone-marrow to heart in patients with severe stable coronary artery disease and refractory angina--final 3-year follow-up. Int J Cardiol. 2013; 170(2): 246–251.
  21. Lasala GP, Silva JA, Kusnick BA, et al. Combination stem cell therapy for the treatment of medically refractory coronary ischemia: a Phase I study. Cardiovasc Revasc Med. 2011; 12(1): 29–34.
  22. Noiseux N, Mansour S, Weisel R, et al. The IMPACT-CABG trial: A multicenter, randomized clinical trial of CD133 stem cell therapy during coronary artery bypass grafting for ischemic cardiomyopathy. J Thorac Cardiovasc Surg. 2016; 152(6): 1582–1588.e2.
  23. Nasseri BA, Ebell W, Dandel M, et al. Autologous CD133+ bone marrow cells and bypass grafting for regeneration of ischaemic myocardium: the Cardio133 trial. Eur Heart J. 2014; 35(19): 1263–1274.
  24. Stamm C, Kleine HD, Choi YH, et al. Intramyocardial delivery of CD133+ bone marrow cells and coronary artery bypass grafting for chronic ischemic heart disease: safety and efficacy studies. J Thorac Cardiovasc Surg. 2007; 133(3): 717–725.
  25. Kurbonov U, Dustov A, Barotov A, et al. Intracoronary Infusion of Autologous CD133(+) Cells in Myocardial Infarction and Tracing by Tc99m MIBI Scintigraphy of the Heart Areas Involved in Cell Homing. Stem Cells Int. 2013; 2013: 582527.
  26. Bartunek J, Vanderheyden M, Vandekerckhove B, et al. Intracoronary injection of CD133-positive enriched bone marrow progenitor cells promotes cardiac recovery after recent myocardial infarction: feasibility and safety. Circulation. 2005; 112(9 Suppl): I178–I183.
  27. Mansour S, Roy DC, Bouchard V, et al. One-Year Safety Analysis of the COMPARE-AMI Trial: Comparison of Intracoronary Injection of CD133 Bone Marrow Stem Cells to Placebo in Patients after Acute Myocardial Infarction and Left Ventricular Dysfunction. Bone Marrow Res. 2011; 2011: 385124.
  28. Traverse JH, Henry TD, Pepine CJ, et al. Effect of the use and timing of bone marrow mononuclear cell delivery on left ventricular function after acute myocardial infarction: the TIME randomized trial. JAMA. 2012; 308(22): 2380–2389.
  29. Rodrigo SF, van Ramshorst J, Mann I, et al. Predictors of response to intramyocardial bone marrow cell treatment in patients with refractory angina and chronic myocardial ischemia. Int J Cardiol. 2014; 175(3): 539–544.

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