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Infusion of bone marrow cells several weeks after heart attack does not appear to improve ventricular function

Date:
November 16, 2011
Source:
JAMA and Archives Journals
Summary:
Intracoronary infusion of bone marrow mononuclear cells 2-3 weeks following a heart attack among patients with left ventricular dysfunction and who had a procedure such as balloon angioplasty or stent placement performed did not result in overall improvement in ventricular function after 6 months, according to a new study.

Intracoronary infusion of bone marrow mononuclear cells 2-3 weeks following a heart attack among patients with left ventricular dysfunction and who had a procedure such as balloon angioplasty or stent placement performed did not result in overall improvement in ventricular function after 6 months, according to a study appearing in the November 16 issue of JAMA. The study is being released early online to coincide with its presentation at the American Heart Association Scientific Sessions.

"Several randomized trials have demonstrated that administration of autologous [derived from the same individual] bone marrow mononuclear cells (BMCs) following acute myocardial infarction [MI; heart attack] may result in improvement in left ventricular ejection fraction [LVEF; a measure of how well the left ventricle of the heart pumps with each contraction] or regional LV function, and may be associated with decreased clinical adverse events. However, the majority of trials have administered BMCs within the first week following primary percutaneous coronary intervention [PCI; procedures such as balloon angioplasty or stent placement used to open narrowed coronary arteries]," according to background information in the article. The authors add that because a substantial number of patients do not receive cell delivery within one week because of factors that may include medical issues, the effectiveness of autologous BMC delivery 2 to 3 weeks after a heart attack warrants investigation.

Jay H. Traverse, M.D., of the Minneapolis Heart Institute Foundation at Abbott Northwestern Hospital, Minneapolis, and colleagues conducted a randomized, placebo-controlled trial designed to investigate the use and therapeutic efficacy of intracoronary autologous BMC delivery 2 to 3 weeks following heart attack. The trial (LateTIME) of the National Heart, Lung, and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network included 87 patients (average age, 57 years; 83 percent men) with significant LV dysfunction following successful primary PCI between July 2008 and February 2011. Patients received either intracoronary infusion of autologous BMCs or placebo.

The researchers found that the changes from baseline to 6 months for various measures of LV function were not statistically significant between the BMC group and placebo group: for LVEF (48.7 percent to 49.2 percent vs. 45.3 percent to 48.8 percent , respectively; the change in wall motion (the movement of the wall of the heart during contraction) in the infarct zone (the region of the heart that has been infarcted [or killed off from the blockage, usually becomes scar tissue]) (6.2 to 6.5 mm vs. 4.9 to 5.9 mm, respectively; and the change in wall motion in the border zone (the region of the heart adjacent to the infarct zone) (16.0 to 16.6 mm vs. 16.1 to 19.3 mm, respectively).

"No significant change in LV volumes [the volumes of the left ventricle or cavity size when it is completely filled with blood] and infarct volumes [the volume of heart muscle that has been infarcted] was observed; both groups decreased by a similar amount at 6 months vs. baseline," the authors write.

"Patients recruited to the LateTIME trial constituted a high-risk cohort with depressed LV function that persisted several weeks following successful revascularization with stenting. Although retrospective analyses suggest that these patients may derive the most benefit from cell therapy in this setting, no improvement in LV function was noted, even in the subgroup with the most depressed LVEF."

The researchers add that it is likely that the timing of cell delivery post-MI may have a major influence on treatment effect and, ultimately, may have contributed to their negative findings.

Editorial: Bone Marrow Therapy for Myocardial Infarction

Joshua M. Hare, M.D., of the University of Miami, writes in an accompanying editorial that the LateTIME trial offers important take-home messages.

"To the extent that intracoronary infusions of BMCs prove to offer clinical benefit for patients with heart disease, there is most likely a therapeutic window of opportunity that does not exceed 2 to 3 weeks following ischemic injury. For later time points, trials should use intramyocardial delivery systems that have documented efficacy in early studies. Ongoing research is essential to obtain cell preparations that are more effective, but also efficient to produce. Important ongoing clinical investigations such as the TIME and BAMI trials will add additional essential information and help define the possibility of using BMCs to treat disorders of cardiac injury, and numerous ongoing trials are testing other cell sources. Although the results of this well-conducted trial may be disappointing or viewed by some as a setback, it should be remembered that definitive negative trials in a new area help to focus the design of future investigations, thereby ultimately advancing the field."


Story Source:

The above story is based on materials provided by JAMA and Archives Journals. Note: Materials may be edited for content and length.


Journal References:

  1. J. H. Traverse, T. D. Henry, S. G. Ellis, C. J. Pepine, J. T. Willerson, D. X. M. Zhao, J. R. Forder, B. J. Byrne, A. K. Hatzopoulos, M. S. Penn, E. C. Perin, K. W. Baran, J. Chambers, C. Lambert, G. Raveendran, D. I. Simon, D. E. Vaughan, L. M. Simpson, A. P. Gee, D. A. Taylor, C. R. Cogle, J. D. Thomas, G. V. Silva, B. C. Jorgenson, R. E. Olson, S. Bowman, J. Francescon, C. Geither, E. Handberg, D. X. Smith, S. Baraniuk, L. B. Piller, C. Loghin, D. Aguilar, S. Richman, C. Zierold, J. Bettencourt, S. L. Sayre, R. W. Vojvodic, S. I. Skarlatos, D. J. Gordon, R. F. Ebert, M. Kwak, L. A. Moye, R. D. Simari. Effect of Intracoronary Delivery of Autologous Bone Marrow Mononuclear Cells 2 to 3 Weeks Following Acute Myocardial Infarction on Left Ventricular Function: The LateTIME Randomized Trial. JAMA: The Journal of the American Medical Association, 2011; 306 (19): 2110 DOI: 10.1001/jama.2011.1670
  2. J. M. Hare. Bone Marrow Therapy for Myocardial Infarction. JAMA: The Journal of the American Medical Association, 2011; 306 (19): 2156 DOI: 10.1001/jama.2011.1686

Cite This Page:

JAMA and Archives Journals. "Infusion of bone marrow cells several weeks after heart attack does not appear to improve ventricular function." ScienceDaily. ScienceDaily, 16 November 2011. <www.sciencedaily.com/releases/2011/11/111116051723.htm>.
JAMA and Archives Journals. (2011, November 16). Infusion of bone marrow cells several weeks after heart attack does not appear to improve ventricular function. ScienceDaily. Retrieved October 1, 2014 from www.sciencedaily.com/releases/2011/11/111116051723.htm
JAMA and Archives Journals. "Infusion of bone marrow cells several weeks after heart attack does not appear to improve ventricular function." ScienceDaily. www.sciencedaily.com/releases/2011/11/111116051723.htm (accessed October 1, 2014).

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Delayed Stem Cell Therapy Following Heart Attack Is Safe but Not Effective

Nov. 16, 2011 Stem cells obtained from bone marrow, known as BMCs, can be safely injected into people two to three weeks following a heart attack, reports a new clinical trial. However, while safe, the BMCs did ... read more

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