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 Previous studies using autologous bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy have demonstrated safety and suggested efficacy.
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.
A phase 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 disease not amenable 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.
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).
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.
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/m(2) [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.
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.
clinicaltrials.gov Identifier: NCT00824005.
Article: Positron emission tomography detects tissue metabolic activity in myocardial segments with persistent thallium perfusion defects.[show abstract] [hide abstract]
ABSTRACT: Positron emission tomography with 13N-ammonia and 18F-2-deoxyglucose was used to assess myocardial perfusion and glucose utilization in 51 myocardial segments with a stress thallium defect in 12 patients. Myocardial infarction was defined by a concordant reduction in segmental perfusion and glucose utilization, and myocardial ischemia was identified by preservation of glucose utilization in segments with rest hypoperfusion. Of the 51 segments studied, 36 had a fixed thallium defect, 11 had a partially reversible defect and 4 had a completely reversible defect. Only 15 (42%) of the 36 segments with a fixed defect and 4 (36%) of the 11 segments with a partially reversible defect exhibited myocardial infarction on study with positron tomography. In contrast, residual myocardial glucose utilization was identified in the majority of segments with a fixed (58%) or a partially reversible (64%) thallium defect. All of the segments with a completely reversible defect appeared normal on positron tomography. Apparent improvement in the thallium defect on delayed images did not distinguish segments with ischemia from infarction. Thus, positron emission tomography reveals evidence of persistent tissue metabolism in the majority of segments with a fixed or partially resolving stress thallium defect, implying that markers of perfusion alone may underestimate the extent of viable tissue in hypoperfused myocardial segments.Journal of the American College of Cardiology 09/1987; 10(3):557-67. · 14.16 Impact Factor
Article: Improved exercise capacity and ischemia 6 and 12 months after transendocardial injection of autologous bone marrow mononuclear cells for ischemic cardiomyopathy.[show abstract] [hide abstract]
ABSTRACT: We recently reported the safety and feasibility of autologous bone marrow mononuclear cell (ABMMNC) injection into areas of ischemic myocardium in patients with end-stage ischemic cardiomyopathy. The present study evaluated the safety and efficacy of this therapy at 6- and 12-month follow-up. Twenty patients with 6- and 12-month follow-up (11 treated subjects; 9 controls) were enrolled in this prospective, nonrandomized, open-label study. Complete clinical and laboratory evaluations as well as exercise stress (ramp treadmill), 2-dimensional Doppler echocardiography, single-photon emission computed tomography (SPECT) perfusion scanning, and 24-hour Holter monitoring were performed at baseline and follow-up. Transendocardial delivery of ABMMNCs was performed with the aid of electromechanical mapping to identify viable myocardium. Each patient received 15 ABMMNC injections of 0.2 mL each. At 6 and 12 months, total reversible defect, as measured by SPECT perfusion scanning, was significantly reduced in the treatment group as compared with the control group. At 12 months, exercise capacity was significantly improved in the treatment group. This improvement correlated well with monocyte, B-cell, hematopoietic progenitor cell, and early hemapoietic progenitor cell phenotypes. The 6- and 12-month follow-up data in this study suggest that transendocardial injection of ABMMNCs in patients with end-stage ischemic heart disease may produce a durable therapeutic effect and improve myocardial perfusion and exercise capacity.Circulation 10/2004; 110(11 Suppl 1):II213-8. · 14.74 Impact Factor
Article: Intramyocardial injection of autologous bone marrow mononuclear cells in patients with chronic myocardial infarction and severe left ventricular dysfunction.[show abstract] [hide abstract]
ABSTRACT: The present study investigated the safety, feasibility, and potential efficacy of autologous bone marrow cell injection in patients with chronic myocardial infarction and severe left ventricular (LV) dysfunction. In 15 patients (63 +/- 9 years; 14 men) bone marrow was aspirated from the iliac crest. Using the NOGA system (Biosense-Webster, Waterloo, Belgium), 94 +/- 14 x 10(6) bone marrow-derived mononuclear cells were injected into the infarction border zone. Bone marrow cell injection was performed without periprocedural complications in all patients. At 2.5 months, 1 patient died from worsening heart failure. New York Heart Association class improved from 3.5 +/- 0.5 at baseline to 2.7 +/- 0.8 at 3 months (p <0.01) and 2.9 +/- 0.8 at 6 months (p <0.01 vs baseline). LV ejection fraction (technetium-99m tetrofosmin single-photon emission computed tomography) increased from 23 +/- 8% to 27 +/- 9% at 3 months (p = 0.02) and regional wall thickening improved from 12.8 +/- 5.9% to 15.3 +/- 7.2% at 3 months (p = 0.02). Injected myocardial segments displayed a significant improvement in regional wall thickening (6.6 +/- 6.3% vs 11.7 +/- 7.0% at 3 months, p <0.01) and perfusion score (3.5 +/- 0.7 vs 3.0 +/- 0.9 at 3 months, p = 0.02) and a trend toward an improved fluorine-18 fluorodeoxyglucose score (2.9 +/- 0.9 vs 2.6 +/- 1.0 at 3 months, p = 0.06). Regional wall thickening (16.5 +/- 8.9% vs 19.1 +/- 9.1% at 3 months, p = NS), perfusion score (1.8 +/- 0.4 vs 1.7 +/- 0.5 at 3 months, p = NS), and fluorodeoxyglucose score (1.7 +/- 0.4 vs 1.6 +/- 0.4 at 3 months, p = NS) did not improve in noninjected myocardial segments. In conclusion, bone marrow cell injection in patients with chronic myocardial infarction and severe LV dysfunction is safe and feasible and appears to be associated with a decrease in heart failure symptoms and an improved LV function.The American Journal of Cardiology 11/2007; 100(7):1094-8. · 3.37 Impact Factor