ObjectiveWe tested the hypothesis that direct intramyocardial injection of bone marrow
mononuclear cells in patients with non-ischemic dilated cardiomyopathy can improve
left ventricular function and physical capacity.MethodsThirty non-ischemic dilated cardiomyopathy patients with left ventricular ejection
fraction <35% were randomized at a 1:2 ratio into two groups, control and
treated. The bone marrow mononuclear cells group received 1.06±108 bone marrow
mononuclear cells through mini-thoracotomy. There was no intervention in the
control group. Assessment was carried out through clinical evaluations as well as
a 6-min walk test, nuclear magnectic resonance imaging and echocardiogram.ResultsThe bone marrow mononuclear cells group showed a trend toward left ventricular
ejection fraction improvement, with magnectic resonance imaging - at 3 months,
showing an increase from 27.80±6.86% to 30.13±9.06% (P=0.08) and
returning to baseline at 9 months (28.78%, P=0.77). Magnectic
resonance imaging showed no changes in left ventricular ejection fraction during
follow-up of the control group (28.00±4.32%, 27.42±7.41%, and 29.57±4.50%).
Echocardiogram showed left ventricular ejection fraction improved in the bone
marrow mononuclear cells group at 3 months, 25.09±3.98 to 30.94±9.16
(P=0.01), and one year, 30.07±7.25%
(P=0.001). The control group showed no change (26.1±4.4 vs
26.5±4.7 and 30.2±7.39%, P=0.25 and 0.10, respectively). Bone
marrow mononuclear cells group showed improvement in New York Heart Association
functional class, from 3.40±0.50 to 2.41±0.79 (P=0.002); patients
in the control group showed no change (3.37±0.51 to 2.71±0.95;
P=0.17). Six-minute walk test improved in the bone marrow
mononuclear cells group (348.00±93.51m at baseline to 370.41±91.56m at 12 months,
P=0.66) and there was a non-significant decline in the control
group (361.25±90.78m to 330.00±123.42m after 12 months, P=0.66).
Group comparisons were non-significant.ConclusionThe trend of intragroup functional and subjective improvement was not confirmed
when compared to the control group. Direct intramyocardial application of bone
marrow mononuclear cells in non-ischemic dilated cardiomyopathy was not associated
with significant changes in left ventricular function. Differences observed within
the bone marrow mononuclear cells group could be due to placebo effect or low
statistical power.
Bone marrow mononuclear cells (BMMC) effects have been investigated in small series of nonischemic dilated cardiomyopathy (NIDC). Left ventricular myocardial contractility improvements occur, but doubt remains about their mechanism of action. We compared contractility changes in areas treated (free wall) and nontreated (septal wall) with BMMC, in selected patients who have showed significant ventricular improvement after free wall-only intramyocardial stem cells injection. From 15 patients with functional class III/IV (NYHA) and LVEF inferior to 35%, who received 9.6 ± 2.6 × 10(7) BMMC divided into 10 points over the left ventricular free wall, 7 (46.7%) showed LVEF relative improvement greater than 15%. Those patients were selected for further contractility study. BMMC were collected from iliac bone and isolated with Ficoll-Hypaque. Magnetic resonance imaging was used to measure the systolic thickening of the septal (nontreated) and free wall (treated) before injection and 3 months postoperatively. Mean systolic septal wall thickening increased from 0.46 to 1.23 mm (an absolute 0.77 ± 1.3 mm and relative 167.4% increase) and in the free wall from 1.13 to 1.87 mm (an absolute 0.74 ± 1.5 mm and relative increase of 65.5%). There was no difference in the rate of absolute or relative systolic thickening between the two walls (p = 0.866 and 1.0, respectively), when cells were injected only in the left ventricular free wall. BMMC transplantation in nonischemic dilated cardiomyopathy can improve ventricular function by an overall effect, even in areas that are not directly injected. This finding favors the existence of a diffuse mechanism of action, rather than a local effect, and should be reminded when the pathophysiology of stem cells is considered.
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