Does transendocardial injection of mesenchymal stem cells improve myocardial function locally or globally?

An analysis from the percutaneous stem cell injection delivery effects on neomyogenesis (POSEIDON) randomized trial

Viky Y. Suncion, Eduard Ghersin, Joel Fishman, Juan Pablo Zambrano, Vasileios Karantalis, Nicole Mandel, Katarina H. Nelson, Gary Gerstenblith, Darcy L. Difede Velazquez, Elayne Breton, Kranthi Sitammagari, Ivonne H Schulman, Sabrina N. Taldone, Adam R. Williams, Cristina Sanina, Peter V. Johnston, Jeffrey Brinker, Peter Altman, Muzammil Mushtaq, Barry Trachtenberg & 8 others Adam M. Mendizabal, Melissa Tracy, Jose Da Silva, Ian K. McNiece, Alberto C. Lardo, Richard T. George, Joshua Hare, Alan W. Heldman

Research output: Contribution to journalArticle

61 Citations (Scopus)

Abstract

Rationale: Transendocardial stem cell injection (TESI) with mesenchymal stem cells improves remodeling in chronic ischemic cardiomyopathy, but the effect of the injection site remains unknown. Objective: To address whether TESI exerts its effects at the site of injection only or also in remote areas, we hypothesized that segmental myocardial scar and segmental ejection fraction improve to a greater extent in injected than in noninjected segments. Methods and results: Biplane ventriculographic and endocardial tracings were recorded. TESI was guided to 10 sites in infarct-border zones. Sites were mapped according to the 17-myocardial segment model. As a result, 510 segments were analyzed in 30 patients before and 13 months after TESI. Segmental early enhancement defect (a measure of scar size) was reduced by TESI in both injected (-43.7±4.4%; n=95; P<0.01) and noninjected segments (-25.1±7.8%; n=148; P<0.001; between-group comparison P<0.05). Conversely, segmental ejection fraction (a measure of contractile performance) improved in injected scar segments (19.9±3.3-26.3±3.5%; P=0.003) but not in noninjected scar segments (21.3±2.6-23.5±3.2%; P=0.20; between-group comparison P<0.05). Furthermore, segmental ejection fraction in injected scar segments improved to a greater degree in patients with baseline segmental ejection fraction <20% (12.1±1.2-19.9±2.7%; n=18; P=0.003), versus <20% (31.7±3.4-35.5±3.3%; n=12; P=0.33, between-group comparison P<0.0001). Conclusions: These findings illustrate a dichotomy in regional responses to TESI. Although scar size reduction was evident in all scar segments, scar size reduction and ventricular functional responses preferentially occurred at the sites of TESI versus non-TESI sites. Furthermore, improvement was greatest when segmental left ventricular dysfunction was severe.

Original languageEnglish
Pages (from-to)1292-1301
Number of pages10
JournalCirculation Research
Volume114
Issue number8
DOIs
StatePublished - Jan 1 2014

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Mesenchymal Stromal Cells
Stem Cells
Cicatrix
Injections
Left Ventricular Dysfunction
Cardiomyopathies

Keywords

  • cells
  • magnetic resonance imaging
  • myocardial infarction
  • tomography

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Does transendocardial injection of mesenchymal stem cells improve myocardial function locally or globally? An analysis from the percutaneous stem cell injection delivery effects on neomyogenesis (POSEIDON) randomized trial. / Suncion, Viky Y.; Ghersin, Eduard; Fishman, Joel; Zambrano, Juan Pablo; Karantalis, Vasileios; Mandel, Nicole; Nelson, Katarina H.; Gerstenblith, Gary; Difede Velazquez, Darcy L.; Breton, Elayne; Sitammagari, Kranthi; Schulman, Ivonne H; Taldone, Sabrina N.; Williams, Adam R.; Sanina, Cristina; Johnston, Peter V.; Brinker, Jeffrey; Altman, Peter; Mushtaq, Muzammil; Trachtenberg, Barry; Mendizabal, Adam M.; Tracy, Melissa; Da Silva, Jose; McNiece, Ian K.; Lardo, Alberto C.; George, Richard T.; Hare, Joshua; Heldman, Alan W.

In: Circulation Research, Vol. 114, No. 8, 01.01.2014, p. 1292-1301.

Research output: Contribution to journalArticle

Suncion, VY, Ghersin, E, Fishman, J, Zambrano, JP, Karantalis, V, Mandel, N, Nelson, KH, Gerstenblith, G, Difede Velazquez, DL, Breton, E, Sitammagari, K, Schulman, IH, Taldone, SN, Williams, AR, Sanina, C, Johnston, PV, Brinker, J, Altman, P, Mushtaq, M, Trachtenberg, B, Mendizabal, AM, Tracy, M, Da Silva, J, McNiece, IK, Lardo, AC, George, RT, Hare, J & Heldman, AW 2014, 'Does transendocardial injection of mesenchymal stem cells improve myocardial function locally or globally? An analysis from the percutaneous stem cell injection delivery effects on neomyogenesis (POSEIDON) randomized trial', Circulation Research, vol. 114, no. 8, pp. 1292-1301. https://doi.org/10.1161/CIRCRESAHA.114.302854
Suncion, Viky Y. ; Ghersin, Eduard ; Fishman, Joel ; Zambrano, Juan Pablo ; Karantalis, Vasileios ; Mandel, Nicole ; Nelson, Katarina H. ; Gerstenblith, Gary ; Difede Velazquez, Darcy L. ; Breton, Elayne ; Sitammagari, Kranthi ; Schulman, Ivonne H ; Taldone, Sabrina N. ; Williams, Adam R. ; Sanina, Cristina ; Johnston, Peter V. ; Brinker, Jeffrey ; Altman, Peter ; Mushtaq, Muzammil ; Trachtenberg, Barry ; Mendizabal, Adam M. ; Tracy, Melissa ; Da Silva, Jose ; McNiece, Ian K. ; Lardo, Alberto C. ; George, Richard T. ; Hare, Joshua ; Heldman, Alan W. / Does transendocardial injection of mesenchymal stem cells improve myocardial function locally or globally? An analysis from the percutaneous stem cell injection delivery effects on neomyogenesis (POSEIDON) randomized trial. In: Circulation Research. 2014 ; Vol. 114, No. 8. pp. 1292-1301.
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abstract = "Rationale: Transendocardial stem cell injection (TESI) with mesenchymal stem cells improves remodeling in chronic ischemic cardiomyopathy, but the effect of the injection site remains unknown. Objective: To address whether TESI exerts its effects at the site of injection only or also in remote areas, we hypothesized that segmental myocardial scar and segmental ejection fraction improve to a greater extent in injected than in noninjected segments. Methods and results: Biplane ventriculographic and endocardial tracings were recorded. TESI was guided to 10 sites in infarct-border zones. Sites were mapped according to the 17-myocardial segment model. As a result, 510 segments were analyzed in 30 patients before and 13 months after TESI. Segmental early enhancement defect (a measure of scar size) was reduced by TESI in both injected (-43.7±4.4{\%}; n=95; P<0.01) and noninjected segments (-25.1±7.8{\%}; n=148; P<0.001; between-group comparison P<0.05). Conversely, segmental ejection fraction (a measure of contractile performance) improved in injected scar segments (19.9±3.3-26.3±3.5{\%}; P=0.003) but not in noninjected scar segments (21.3±2.6-23.5±3.2{\%}; P=0.20; between-group comparison P<0.05). Furthermore, segmental ejection fraction in injected scar segments improved to a greater degree in patients with baseline segmental ejection fraction <20{\%} (12.1±1.2-19.9±2.7{\%}; n=18; P=0.003), versus <20{\%} (31.7±3.4-35.5±3.3{\%}; n=12; P=0.33, between-group comparison P<0.0001). Conclusions: These findings illustrate a dichotomy in regional responses to TESI. Although scar size reduction was evident in all scar segments, scar size reduction and ventricular functional responses preferentially occurred at the sites of TESI versus non-TESI sites. Furthermore, improvement was greatest when segmental left ventricular dysfunction was severe.",
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TY - JOUR

T1 - Does transendocardial injection of mesenchymal stem cells improve myocardial function locally or globally?

T2 - An analysis from the percutaneous stem cell injection delivery effects on neomyogenesis (POSEIDON) randomized trial

AU - Suncion, Viky Y.

AU - Ghersin, Eduard

AU - Fishman, Joel

AU - Zambrano, Juan Pablo

AU - Karantalis, Vasileios

AU - Mandel, Nicole

AU - Nelson, Katarina H.

AU - Gerstenblith, Gary

AU - Difede Velazquez, Darcy L.

AU - Breton, Elayne

AU - Sitammagari, Kranthi

AU - Schulman, Ivonne H

AU - Taldone, Sabrina N.

AU - Williams, Adam R.

AU - Sanina, Cristina

AU - Johnston, Peter V.

AU - Brinker, Jeffrey

AU - Altman, Peter

AU - Mushtaq, Muzammil

AU - Trachtenberg, Barry

AU - Mendizabal, Adam M.

AU - Tracy, Melissa

AU - Da Silva, Jose

AU - McNiece, Ian K.

AU - Lardo, Alberto C.

AU - George, Richard T.

AU - Hare, Joshua

AU - Heldman, Alan W.

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Rationale: Transendocardial stem cell injection (TESI) with mesenchymal stem cells improves remodeling in chronic ischemic cardiomyopathy, but the effect of the injection site remains unknown. Objective: To address whether TESI exerts its effects at the site of injection only or also in remote areas, we hypothesized that segmental myocardial scar and segmental ejection fraction improve to a greater extent in injected than in noninjected segments. Methods and results: Biplane ventriculographic and endocardial tracings were recorded. TESI was guided to 10 sites in infarct-border zones. Sites were mapped according to the 17-myocardial segment model. As a result, 510 segments were analyzed in 30 patients before and 13 months after TESI. Segmental early enhancement defect (a measure of scar size) was reduced by TESI in both injected (-43.7±4.4%; n=95; P<0.01) and noninjected segments (-25.1±7.8%; n=148; P<0.001; between-group comparison P<0.05). Conversely, segmental ejection fraction (a measure of contractile performance) improved in injected scar segments (19.9±3.3-26.3±3.5%; P=0.003) but not in noninjected scar segments (21.3±2.6-23.5±3.2%; P=0.20; between-group comparison P<0.05). Furthermore, segmental ejection fraction in injected scar segments improved to a greater degree in patients with baseline segmental ejection fraction <20% (12.1±1.2-19.9±2.7%; n=18; P=0.003), versus <20% (31.7±3.4-35.5±3.3%; n=12; P=0.33, between-group comparison P<0.0001). Conclusions: These findings illustrate a dichotomy in regional responses to TESI. Although scar size reduction was evident in all scar segments, scar size reduction and ventricular functional responses preferentially occurred at the sites of TESI versus non-TESI sites. Furthermore, improvement was greatest when segmental left ventricular dysfunction was severe.

AB - Rationale: Transendocardial stem cell injection (TESI) with mesenchymal stem cells improves remodeling in chronic ischemic cardiomyopathy, but the effect of the injection site remains unknown. Objective: To address whether TESI exerts its effects at the site of injection only or also in remote areas, we hypothesized that segmental myocardial scar and segmental ejection fraction improve to a greater extent in injected than in noninjected segments. Methods and results: Biplane ventriculographic and endocardial tracings were recorded. TESI was guided to 10 sites in infarct-border zones. Sites were mapped according to the 17-myocardial segment model. As a result, 510 segments were analyzed in 30 patients before and 13 months after TESI. Segmental early enhancement defect (a measure of scar size) was reduced by TESI in both injected (-43.7±4.4%; n=95; P<0.01) and noninjected segments (-25.1±7.8%; n=148; P<0.001; between-group comparison P<0.05). Conversely, segmental ejection fraction (a measure of contractile performance) improved in injected scar segments (19.9±3.3-26.3±3.5%; P=0.003) but not in noninjected scar segments (21.3±2.6-23.5±3.2%; P=0.20; between-group comparison P<0.05). Furthermore, segmental ejection fraction in injected scar segments improved to a greater degree in patients with baseline segmental ejection fraction <20% (12.1±1.2-19.9±2.7%; n=18; P=0.003), versus <20% (31.7±3.4-35.5±3.3%; n=12; P=0.33, between-group comparison P<0.0001). Conclusions: These findings illustrate a dichotomy in regional responses to TESI. Although scar size reduction was evident in all scar segments, scar size reduction and ventricular functional responses preferentially occurred at the sites of TESI versus non-TESI sites. Furthermore, improvement was greatest when segmental left ventricular dysfunction was severe.

KW - cells

KW - magnetic resonance imaging

KW - myocardial infarction

KW - tomography

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