Usefulness of Granulocyte Colony-Stimulating Factor in Patients With a Large Anterior Wall Acute Myocardial Infarction to Prevent Left Ventricular Remodeling (The Rigenera Study)

doi:10.1016/j.amjcard.2007.03.036

The American Journal of Cardiology

Volume 100, Issue 3, 1 August 2007, Pages 397-403

https://doi.org/10.1016/j.amjcard.2007.03.036 Get rights and content

Intracoronary injection of bone marrow stem cells seems to improve left ventricular (LV) function after acute myocardial infarction (AMI). Granulocyte colony-stimulating factor (G-CSF) could improve myocardial function and perfusion noninvasively through mobilization of stem cells into peripheral blood, although previous clinical trials have produced controversial results. Forty-one patients with large anterior wall AMI at high risk of unfavorable remodeling were randomized 1:2 to G-CSF (10 μg/kg/day for 5 days) or to conventional therapy. All patients underwent successful primary or rescue percutaneous coronary intervention. LV function was assessed by echocardiography before G-CSF administration, ≥5 days after AMI, and at follow-up. Only patients with a LV ejection fraction <50% at baseline were enrolled in the study. After a median follow-up of 5 months (range 4 to 6) patients treated with G-CSF exhibited improvement in LV ejection fraction, from 40 ± 6% to 45 ± 6% (p = 0.068) in the absence of LV dilation (LV end-diastolic volume from 147 ± 33 to 144 ± 46 ml at follow-up, p = 0.77). In contrast, patients treated conventionally exhibited significant LV dilation (LV end-diastolic volume from 141 ± 35 to 168 ± 41 ml, p = 0.002) in the absence of change in LV ejection fraction (from 38 ± 6% to 38 ± 8%, p = 0.95). However, when comparing patients treated with G-CSF with controls, variations in these parameters were significantly different at 2-way analysis of variance (p = 0.04 for LV end-diastolic volume, p = 0.02 for LV ejection fraction). In conclusion, G-CSF prevents unfavorable LV remodeling and improves LV function in patients with large anterior wall AMI and decreased LV ejection fraction after successful percutaneous coronary intervention.

Section snippets

Patients and protocol

The present study assessed the potential efficacy of G-CSF administration on cardiac function in patients with a first large anterior AMI and a LV ejection fraction <50% despite successful percutaneous revascularization of the infarct-related artery. Exclusion criteria were cardiogenic shock, uncontrolled myocardial ischemia or arrhythmias, malignancies, severe infections, hematologic diseases, splenomegaly on abdominal echocardiography, and age >80 years.

From June 2003 to May 2006, 72 patients

Clinical and laboratory findings

All patients underwent successful percutaneous coronary intervention of the infarct-related artery and 11 (26.8%) of a noninfarct–related artery (4 in the G-CSF group, 28.5%, and 7 in the control group, 25.9%). However, complete revascularization was achieved in all patients (Table 1). All patients at discharge and then at follow-up were on standard therapy consisting of aspirin, clopidogrel, carvedilol, ramipril, and atorvastatin. No patient exhibited major adverse cardiac events or severe

Discussion

In our study, G-CSF was associated with a significant improvement in LV function similar to that observed after intracoronary injection of stem cells in patients with AMI and, more interestingly, a lack of LV dilation compared with patients treated conventionally, in whom, in contrast, we found no improvement in LV ejection fraction and a significant dilation of LV volumes in addition to currently recommended medical therapy. With regard to the a lack of an improvement in LV function in

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Moreover, this spontaneous mobilization of CD34+ cells significantly correlated to endogenous G-CSF levels in the peripheral blood [52]. Taken together, these two studies supported the concept that pharmacological administration of G-CSF might be a suitable non-invasive method for the regeneration of myocardial tissue and recovery of contractile function after AMI, thus creating a rationale for the subsequent RIGENERA study [53]. A subcutaneous administration of G-CSF is an attractive therapeutic option since it does not require repeated coronary catheterizations and ex vivo cell purification and expansion.
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: This study was supported by a grant from the Fondazione Cassa di Risparmio di Roma, Rome, Italy, to UNICATT Cord Blood Bank of the Catholic University of the Sacred Heart of Rome and by Fondazione Internazionale Ricerche Per il Cuore, ONLUS, Rome, Italy. Lenograstim (Myelostim 34) was supplied by Italfarmaco S.p.A., Milan, Italy,which had no role in the collection, analysis, and interpretation of the data.

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Coronary artery diseaseUsefulness of Granulocyte Colony-Stimulating Factor in Patients With a Large Anterior Wall Acute Myocardial Infarction to Prevent Left Ventricular Remodeling (The Rigenera Study)

Section snippets

Patients and protocol

Clinical and laboratory findings

Discussion

Int J Cardiol

Am Heart J

J Am Coll Cardiol

Am Heart J

J Am Coll Cardiol

Clinical applications of stem cells for the heart

Circ Res

Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease

Circ Res

Mobilized bone marrow cells repair the infarcted heart, improving function and survival

Proc Natl Acad Sci USA

Mobilization of bone marrow-derived stem cells after myocardial infarction and left ventricular function

Eur Heart J

Safety of granulocyte-colony-stimulating factor in acute myocardial infarction (the Rigenera study)

Heart

Use of granulocyte-colony stimulating factor during acute myocardial infarction to enhance bone marrow stem cell mobilization in humans: clinical and angiographic safety profile

Eur Heart J

Coronary artery disease
Usefulness of Granulocyte Colony-Stimulating Factor in Patients With a Large Anterior Wall Acute Myocardial Infarction to Prevent Left Ventricular Remodeling (The Rigenera Study)