Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: The FOCUS-CCTRN trial

Emerson C. Perin, James T. Willerson, Carl J. Pepine, Timothy D. Henry, Stephen G. Ellis, David X M Zhao, Guilherme V. Silva, Dejian Lai, James D. Thomas, Marvin W. Kronenberg, A. Daniel Martin, R. David Anderson, Jay H. Traverse, Marc S. Penn, Saif Anwaruddin, Antonis K. Hatzopoulos, Adrian P. Gee, Doris A. Taylor, Christopher R. Cogle, Deirdre SmithLynette Westbrook, James Chen, Eileen Handberg, Rachel E. Olson, Carrie Geither, Sherry Bowman, Judy Francescon, Sarah Baraniuk, Linda B. Piller, Lara M. Simpson, Catalin Loghin, David Aguilar, Sara Richman, Claudia Zierold, Judy Bettencourt, Shelly L. Sayre, Rachel W. Vojvodic, Sonia I. Skarlatos, David J. Gordon, Ray F. Ebert, Minjung Kwak, Lemuel A. Moyé, Robert D. Simari

Research output: Contribution to journalArticle

304 Citations (Scopus)

Abstract

Context: Previous studies using autologous bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy have demonstrated safety and suggested efficacy. Objective: To determine if administration of BMCs through transendocardial injections improves myocardial perfusion, reduces left ventricular end-systolic volume (LVESV), or enhances maximal oxygen consumption in patients with coronary artery disease or LV dysfunction, and limiting heart failure or angina. Design, Setting, and Patients: Aphase 2 randomized double-blind, placebo-controlled trial of symptomatic patients (New York Heart Association classification II-III or Canadian Cardiovascular Society classification II-IV) with a left ventricular ejection fraction of 45% or less, a perfusion defect by single-photon emission tomography (SPECT), and coronary artery diseasenotam enable to revascularization who were receiving maximal medical therapy at 5 National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) sites between April 29, 2009, and April 18, 2011. Intervention: Bone marrow aspiration (isolation of BMCs using a standardized automated system performed locally) and transendocardial injection of 100 million BMCs or placebo (ratio of 2 for BMC group to 1 for placebo group). Main Outcome Measures: Co-primary end points assessed at 6 months: changes in LVESV assessed by echocardiography, maximal oxygen consumption, and reversibility on SPECT. Phenotypic and functional analyses of the cell product were performed by the CCTRN biorepository core laboratory. Results: Of 153 patients who provided consent, a total of 92 (82 men; average age: 63 years) were randomized (n=61 in BMC group and n=31 in placebo group). Changes in LVESV index (-0.9 mL/m2 [95% CI, -6.1 to 4.3]; P=.73), maximal oxygen consumption (1.0 [95% CI, -0.42 to 2.34]; P=.17), and reversible defect (-1.2 [95% CI, -12.50 to 10.12]; P=.84) were not statistically significant. There were no differences found in any of the secondary outcomes, including percent myocardial defect, total defect size, fixed defect size, regional wall motion, and clinical improvement. Conclusion: Among patients with chronic ischemic heart failure, transendocardial injection of autologous BMCs compared with placebo did not improve LVESV, maximal oxygen consumption, or reversibility on SPECT. Trial Registration: clinicaltrials.gov Identifier: NCT00824005.

Original languageEnglish (US)
Pages (from-to)1717-1726
Number of pages10
JournalJAMA - Journal of the American Medical Association
Volume307
Issue number16
DOIs
StatePublished - Apr 25 2012

Fingerprint

Cell- and Tissue-Based Therapy
Left Ventricular Function
Bone Marrow Cells
Heart Failure
Perfusion
Stroke Volume
Oxygen Consumption
Placebos
Research
Single-Photon Emission-Computed Tomography
Injections
National Heart, Lung, and Blood Institute (U.S.)
Cardiomyopathies
Photons
Echocardiography
Coronary Artery Disease
Coronary Vessels
Bone Marrow
Tomography
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure : The FOCUS-CCTRN trial. / Perin, Emerson C.; Willerson, James T.; Pepine, Carl J.; Henry, Timothy D.; Ellis, Stephen G.; Zhao, David X M; Silva, Guilherme V.; Lai, Dejian; Thomas, James D.; Kronenberg, Marvin W.; Martin, A. Daniel; Anderson, R. David; Traverse, Jay H.; Penn, Marc S.; Anwaruddin, Saif; Hatzopoulos, Antonis K.; Gee, Adrian P.; Taylor, Doris A.; Cogle, Christopher R.; Smith, Deirdre; Westbrook, Lynette; Chen, James; Handberg, Eileen; Olson, Rachel E.; Geither, Carrie; Bowman, Sherry; Francescon, Judy; Baraniuk, Sarah; Piller, Linda B.; Simpson, Lara M.; Loghin, Catalin; Aguilar, David; Richman, Sara; Zierold, Claudia; Bettencourt, Judy; Sayre, Shelly L.; Vojvodic, Rachel W.; Skarlatos, Sonia I.; Gordon, David J.; Ebert, Ray F.; Kwak, Minjung; Moyé, Lemuel A.; Simari, Robert D.

In: JAMA - Journal of the American Medical Association, Vol. 307, No. 16, 25.04.2012, p. 1717-1726.

Research output: Contribution to journalArticle

Perin, EC, Willerson, JT, Pepine, CJ, Henry, TD, Ellis, SG, Zhao, DXM, Silva, GV, Lai, D, Thomas, JD, Kronenberg, MW, Martin, AD, Anderson, RD, Traverse, JH, Penn, MS, Anwaruddin, S, Hatzopoulos, AK, Gee, AP, Taylor, DA, Cogle, CR, Smith, D, Westbrook, L, Chen, J, Handberg, E, Olson, RE, Geither, C, Bowman, S, Francescon, J, Baraniuk, S, Piller, LB, Simpson, LM, Loghin, C, Aguilar, D, Richman, S, Zierold, C, Bettencourt, J, Sayre, SL, Vojvodic, RW, Skarlatos, SI, Gordon, DJ, Ebert, RF, Kwak, M, Moyé, LA & Simari, RD 2012, 'Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: The FOCUS-CCTRN trial', JAMA - Journal of the American Medical Association, vol. 307, no. 16, pp. 1717-1726. https://doi.org/10.1001/jama.2012.418
Perin, Emerson C. ; Willerson, James T. ; Pepine, Carl J. ; Henry, Timothy D. ; Ellis, Stephen G. ; Zhao, David X M ; Silva, Guilherme V. ; Lai, Dejian ; Thomas, James D. ; Kronenberg, Marvin W. ; Martin, A. Daniel ; Anderson, R. David ; Traverse, Jay H. ; Penn, Marc S. ; Anwaruddin, Saif ; Hatzopoulos, Antonis K. ; Gee, Adrian P. ; Taylor, Doris A. ; Cogle, Christopher R. ; Smith, Deirdre ; Westbrook, Lynette ; Chen, James ; Handberg, Eileen ; Olson, Rachel E. ; Geither, Carrie ; Bowman, Sherry ; Francescon, Judy ; Baraniuk, Sarah ; Piller, Linda B. ; Simpson, Lara M. ; Loghin, Catalin ; Aguilar, David ; Richman, Sara ; Zierold, Claudia ; Bettencourt, Judy ; Sayre, Shelly L. ; Vojvodic, Rachel W. ; Skarlatos, Sonia I. ; Gordon, David J. ; Ebert, Ray F. ; Kwak, Minjung ; Moyé, Lemuel A. ; Simari, Robert D. / Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure : The FOCUS-CCTRN trial. In: JAMA - Journal of the American Medical Association. 2012 ; Vol. 307, No. 16. pp. 1717-1726.
@article{d3c114264e7248c7956bde2df72fc789,
title = "Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure: The FOCUS-CCTRN trial",
abstract = "Context: Previous studies using autologous bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy have demonstrated safety and suggested efficacy. Objective: To determine if administration of BMCs through transendocardial injections improves myocardial perfusion, reduces left ventricular end-systolic volume (LVESV), or enhances maximal oxygen consumption in patients with coronary artery disease or LV dysfunction, and limiting heart failure or angina. Design, Setting, and Patients: Aphase 2 randomized double-blind, placebo-controlled trial of symptomatic patients (New York Heart Association classification II-III or Canadian Cardiovascular Society classification II-IV) with a left ventricular ejection fraction of 45{\%} or less, a perfusion defect by single-photon emission tomography (SPECT), and coronary artery diseasenotam enable to revascularization who were receiving maximal medical therapy at 5 National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) sites between April 29, 2009, and April 18, 2011. Intervention: Bone marrow aspiration (isolation of BMCs using a standardized automated system performed locally) and transendocardial injection of 100 million BMCs or placebo (ratio of 2 for BMC group to 1 for placebo group). Main Outcome Measures: Co-primary end points assessed at 6 months: changes in LVESV assessed by echocardiography, maximal oxygen consumption, and reversibility on SPECT. Phenotypic and functional analyses of the cell product were performed by the CCTRN biorepository core laboratory. Results: Of 153 patients who provided consent, a total of 92 (82 men; average age: 63 years) were randomized (n=61 in BMC group and n=31 in placebo group). Changes in LVESV index (-0.9 mL/m2 [95{\%} CI, -6.1 to 4.3]; P=.73), maximal oxygen consumption (1.0 [95{\%} CI, -0.42 to 2.34]; P=.17), and reversible defect (-1.2 [95{\%} CI, -12.50 to 10.12]; P=.84) were not statistically significant. There were no differences found in any of the secondary outcomes, including percent myocardial defect, total defect size, fixed defect size, regional wall motion, and clinical improvement. Conclusion: Among patients with chronic ischemic heart failure, transendocardial injection of autologous BMCs compared with placebo did not improve LVESV, maximal oxygen consumption, or reversibility on SPECT. Trial Registration: clinicaltrials.gov Identifier: NCT00824005.",
author = "Perin, {Emerson C.} and Willerson, {James T.} and Pepine, {Carl J.} and Henry, {Timothy D.} and Ellis, {Stephen G.} and Zhao, {David X M} and Silva, {Guilherme V.} and Dejian Lai and Thomas, {James D.} and Kronenberg, {Marvin W.} and Martin, {A. Daniel} and Anderson, {R. David} and Traverse, {Jay H.} and Penn, {Marc S.} and Saif Anwaruddin and Hatzopoulos, {Antonis K.} and Gee, {Adrian P.} and Taylor, {Doris A.} and Cogle, {Christopher R.} and Deirdre Smith and Lynette Westbrook and James Chen and Eileen Handberg and Olson, {Rachel E.} and Carrie Geither and Sherry Bowman and Judy Francescon and Sarah Baraniuk and Piller, {Linda B.} and Simpson, {Lara M.} and Catalin Loghin and David Aguilar and Sara Richman and Claudia Zierold and Judy Bettencourt and Sayre, {Shelly L.} and Vojvodic, {Rachel W.} and Skarlatos, {Sonia I.} and Gordon, {David J.} and Ebert, {Ray F.} and Minjung Kwak and Moy{\'e}, {Lemuel A.} and Simari, {Robert D.}",
year = "2012",
month = "4",
day = "25",
doi = "10.1001/jama.2012.418",
language = "English (US)",
volume = "307",
pages = "1717--1726",
journal = "JAMA - Journal of the American Medical Association",
issn = "0002-9955",
publisher = "American Medical Association",
number = "16",

}

TY - JOUR

T1 - Effect of transendocardial delivery of autologous bone marrow mononuclear cells on functional capacity, left ventricular function, and perfusion in chronic heart failure

T2 - The FOCUS-CCTRN trial

AU - Perin, Emerson C.

AU - Willerson, James T.

AU - Pepine, Carl J.

AU - Henry, Timothy D.

AU - Ellis, Stephen G.

AU - Zhao, David X M

AU - Silva, Guilherme V.

AU - Lai, Dejian

AU - Thomas, James D.

AU - Kronenberg, Marvin W.

AU - Martin, A. Daniel

AU - Anderson, R. David

AU - Traverse, Jay H.

AU - Penn, Marc S.

AU - Anwaruddin, Saif

AU - Hatzopoulos, Antonis K.

AU - Gee, Adrian P.

AU - Taylor, Doris A.

AU - Cogle, Christopher R.

AU - Smith, Deirdre

AU - Westbrook, Lynette

AU - Chen, James

AU - Handberg, Eileen

AU - Olson, Rachel E.

AU - Geither, Carrie

AU - Bowman, Sherry

AU - Francescon, Judy

AU - Baraniuk, Sarah

AU - Piller, Linda B.

AU - Simpson, Lara M.

AU - Loghin, Catalin

AU - Aguilar, David

AU - Richman, Sara

AU - Zierold, Claudia

AU - Bettencourt, Judy

AU - Sayre, Shelly L.

AU - Vojvodic, Rachel W.

AU - Skarlatos, Sonia I.

AU - Gordon, David J.

AU - Ebert, Ray F.

AU - Kwak, Minjung

AU - Moyé, Lemuel A.

AU - Simari, Robert D.

PY - 2012/4/25

Y1 - 2012/4/25

N2 - Context: Previous studies using autologous bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy have demonstrated safety and suggested efficacy. Objective: To determine if administration of BMCs through transendocardial injections improves myocardial perfusion, reduces left ventricular end-systolic volume (LVESV), or enhances maximal oxygen consumption in patients with coronary artery disease or LV dysfunction, and limiting heart failure or angina. Design, Setting, and Patients: Aphase 2 randomized double-blind, placebo-controlled trial of symptomatic patients (New York Heart Association classification II-III or Canadian Cardiovascular Society classification II-IV) with a left ventricular ejection fraction of 45% or less, a perfusion defect by single-photon emission tomography (SPECT), and coronary artery diseasenotam enable to revascularization who were receiving maximal medical therapy at 5 National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) sites between April 29, 2009, and April 18, 2011. Intervention: Bone marrow aspiration (isolation of BMCs using a standardized automated system performed locally) and transendocardial injection of 100 million BMCs or placebo (ratio of 2 for BMC group to 1 for placebo group). Main Outcome Measures: Co-primary end points assessed at 6 months: changes in LVESV assessed by echocardiography, maximal oxygen consumption, and reversibility on SPECT. Phenotypic and functional analyses of the cell product were performed by the CCTRN biorepository core laboratory. Results: Of 153 patients who provided consent, a total of 92 (82 men; average age: 63 years) were randomized (n=61 in BMC group and n=31 in placebo group). Changes in LVESV index (-0.9 mL/m2 [95% CI, -6.1 to 4.3]; P=.73), maximal oxygen consumption (1.0 [95% CI, -0.42 to 2.34]; P=.17), and reversible defect (-1.2 [95% CI, -12.50 to 10.12]; P=.84) were not statistically significant. There were no differences found in any of the secondary outcomes, including percent myocardial defect, total defect size, fixed defect size, regional wall motion, and clinical improvement. Conclusion: Among patients with chronic ischemic heart failure, transendocardial injection of autologous BMCs compared with placebo did not improve LVESV, maximal oxygen consumption, or reversibility on SPECT. Trial Registration: clinicaltrials.gov Identifier: NCT00824005.

AB - Context: Previous studies using autologous bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy have demonstrated safety and suggested efficacy. Objective: To determine if administration of BMCs through transendocardial injections improves myocardial perfusion, reduces left ventricular end-systolic volume (LVESV), or enhances maximal oxygen consumption in patients with coronary artery disease or LV dysfunction, and limiting heart failure or angina. Design, Setting, and Patients: Aphase 2 randomized double-blind, placebo-controlled trial of symptomatic patients (New York Heart Association classification II-III or Canadian Cardiovascular Society classification II-IV) with a left ventricular ejection fraction of 45% or less, a perfusion defect by single-photon emission tomography (SPECT), and coronary artery diseasenotam enable to revascularization who were receiving maximal medical therapy at 5 National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network (CCTRN) sites between April 29, 2009, and April 18, 2011. Intervention: Bone marrow aspiration (isolation of BMCs using a standardized automated system performed locally) and transendocardial injection of 100 million BMCs or placebo (ratio of 2 for BMC group to 1 for placebo group). Main Outcome Measures: Co-primary end points assessed at 6 months: changes in LVESV assessed by echocardiography, maximal oxygen consumption, and reversibility on SPECT. Phenotypic and functional analyses of the cell product were performed by the CCTRN biorepository core laboratory. Results: Of 153 patients who provided consent, a total of 92 (82 men; average age: 63 years) were randomized (n=61 in BMC group and n=31 in placebo group). Changes in LVESV index (-0.9 mL/m2 [95% CI, -6.1 to 4.3]; P=.73), maximal oxygen consumption (1.0 [95% CI, -0.42 to 2.34]; P=.17), and reversible defect (-1.2 [95% CI, -12.50 to 10.12]; P=.84) were not statistically significant. There were no differences found in any of the secondary outcomes, including percent myocardial defect, total defect size, fixed defect size, regional wall motion, and clinical improvement. Conclusion: Among patients with chronic ischemic heart failure, transendocardial injection of autologous BMCs compared with placebo did not improve LVESV, maximal oxygen consumption, or reversibility on SPECT. Trial Registration: clinicaltrials.gov Identifier: NCT00824005.

UR - http://www.scopus.com/inward/record.url?scp=84860200127&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84860200127&partnerID=8YFLogxK

U2 - 10.1001/jama.2012.418

DO - 10.1001/jama.2012.418

M3 - Article

C2 - 22447880

AN - SCOPUS:84860200127

VL - 307

SP - 1717

EP - 1726

JO - JAMA - Journal of the American Medical Association

JF - JAMA - Journal of the American Medical Association

SN - 0002-9955

IS - 16

ER -