CABG Plus Stem Cells Equals Improved LV Function in MI Patients with Heart Failure

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Findings from a small randomized trial show that isolated coronary artery bypass graft (CABG) surgery combined with autologous bone marrow stem cells improves left ventricular (LV) function and exercise tolerance compared with CABG alone in patients with previous myocardial infarction (MI) and chronic heart failure. The study appears in the June 14, 2011, issue of the Journal of the American College of Cardiology.

Researchers led by Shengshou Hu, MD, PhD, of Fuwai Hospital (Beijing, China), randomized 59 patients with triple-vessel disease, previous MI (at least 3 months prior), and chronic heart failure at their institution to undergo isolated CABG with bone marrow stem cell therapy (n = 31) or placebo (n = 28). Stem cells were harvested on the day of the CABG procedure from each patient, with an average number of 13.17 ± 10.66 x 107 cells. Solution containing placebo or stem cells was injected into the bypass graft during the procedure in the hopes of enabling cell delivery into the myocardium. The aorta was declamped 5 minutes after cell injection.

Baseline characteristics were well balanced between the 2 groups, with an average New York Heart Association class of 2 and an LVEF of 23 ± 0.6%.

After 6 months, patients receiving bone marrow stem cells achieved greater improvements in median LVEF (primary endpoint), LV end systolic volume index, and wall motion index score (table 1).

Table 1. Six-Month Outcomes


Stem Cell Group
(n = 31)

Placebo Group
(n = 28)

P Value

Change in LVEF




Change in LVESVI, mL/m2




Change in Wall Motion Index Score




Abbreviation: LVESVI, left ventricular end systolic volume index.

Patients in the stem cell group performed better than those in the placebo group at 6 months on the 6-minute walking test (500 m vs. 470 m; P = 0.009), with a greater increase from baseline (45 m after stem cells vs. 10 m after placebo; P = 0.042). In addition, serum B-type natriuretic peptide levels showed more improvement from baseline in stem cell patients compared with placebo patients (476 fmol/L vs. 34 fmol/L; P = 0.034).

There were no deaths or MIs in either group during follow-up, and no arrhythmias occurred in the postoperative period. Three patients in each group experienced heart failure.

According to the authors, “these results indicate that [bone marrow stem cells] can improve heart function in patients with [previous] MI complicated by chronic heart failure in the short term and might have a positive impact on long-term prognosis.” The benefits may be achieved through the cells’ potential for inducing angiogenesis and myocardial regeneration, they say.

Stem cell therapy is usually delivered via intramyocardial injection, Dr. Hu and colleagues note, but the technique has sometimes resulted in low cell survival and uneven distribution. By delivering the bone marrow stem cells via a bypass graft into an arrested heart, the researchers hoped to overcome these hurdles and increase the number of cells migrating to the myocardium and decrease the cells washed out of the heart.

Based on the results, the researchers called for larger randomized trials “to assess the effects of [stem cells] on the long-term prognosis of patients using more clinically meaningful outcomes.”

How Long Will the Benefits Last?

“This study further validates the concept that macrorevascularization with coronary artery bypass surgery and microrevascularization with cell therapy have a synergistic benefit to patients over bypass surgery alone,” Amit N. Patel, MD, MS, of the University of Utah (Salt Lake City, UT), wrote in an e-mail communication with TCTMD. “The question is, how long will this benefit last? And will re-dosing of cells via catheter technique be required in the long term?”

He noted that while administering stem cells via the bypass graft is not a new application, it is a practical one. “[But] when the heart is restarted, is there significant washout as has been demonstrated with other intracoronary techniques where most cells end up in the lung, liver, and/or spleen?” Dr. Patel added.

Warren Sherman, MD, of Columbia University Medical Center (New York, NY), indicated that although the results are positive, important questions remain. In a telephone interview with TCTMD, he noted that the protocol called for a 3-mL injection into the saphenous vein graft to reach the target coronary artery.

Devil in the Details

“Three milliliters in some of these vein grafts is barely enough to fill the graft, so these cells might have hung out in the graft until the aorta was declamped, at which point they wash right through,” he said. “If you just inject [that amount] of any fluid into a venous graft at a proximal anastomosis, it’s just going to stay in the graft and not even reach the distal circulation. Now, they might have followed that with a volume that would have gotten the cells into the area where they’re believed to do some good. I can’t tell. There’s a level of detail that’s missing.”

Dr. Sherman reported that administering cell therapy via the bypass graft is atypical compared with where the field is generally heading. “Every other study that has attempted to compare an intravascular infusion of cells like this with an intramyocardial application of cells has shown greater cell retention with the latter technique compared with the former,” he said, noting that nevertheless, in terms of providing enough evidence to lead to a larger, randomized trial, “this may be enough to go on.”

The key, he added, is teasing out exactly where the benefits came from. “The problem with adjunctive cell therapy is telling what’s biologic to the cell and what’s [from the reperfusion procedure],” Dr. Sherman said. “It plagues every study that tries to combine these therapies.”


Hu S, Liu S, Zheng Z, et al. Isolated coronary artery bypass graft combined with bone marrow mononuclear cells delivered through a graft vessel for patients with previous myocardial infarction and chronic heart failure: A single-center, randomized, double-blind, placebo-controlled clinical trial. J Am Coll Cardiol. 2011;57:2409-2415.



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  • The study was supported by the Key Project in the National Science and Technology Pillar Program, the Key Project of Beijing Municipal Science and Technology Commission, and the Basic Scientific Research Fund of the National Public Scientific Institute.
  • Drs. Hu, Patel, and Sherman report no relevant conflicts of interest.