On these bases several studies have evaluated the effect of G-CSF on LV function in patients with myocardial result with mixed results [13]. In general, G-CSF was proven safe but the effect appeared modest. However, in patients with large myocardial infarction the effect was significant and clinically relevant approaching a 5% increase in LVEF. In particular in the Rigenera Trial conducted at the Catholic University of the Sacred Heart of Rome 41 patients with large anterior wall AMI at high risk of unfavorable remodeling were randomized 1:2 to Lenograstim (rhu G-CSF, Myelostim 34, Italfarmaco) (10 μg/kg/day for 5 days) or to conventional therapy. After a median follow-up of 5 months patients treated with Lenograstim exhibited improvement of 5% in LVEF, in the absence of LV dilation. In contrast, patients treated conventionally exhibited significant LV dilation in the absence of an improvement in LVEF [14]. In the present study, a subgroup of 8 patients randomized to Lenograstim received also the administration of a second-generation ultrasound contrast agent containing sulphur hexafluoride (SonoVue®, Bracco, Milan, Italy) administered intravenously (5 ml at 1 ml/min) for myocardial opacification to collect diagnostic images by Myocardial Contrast Echocardiography. Interestingly, a post hoc analysis, revealed that only patients receiving Sonovue® showed a significant benefit on LV function [unpublished data]. This could be due to an increased homing effect of mobilized bone marrow derived stem cells due to the myocardial destruction of contrast medium-microbubbles by 3.5 MHz ultrasounds produced by the Echo machine. As this regard, two basic studies demonstrated that the highly focused ultrasound-mediated stimulation of microbubbles increased the migration of stem cells across the myocardial endothelium into the post-ischemic myocardium in vivo [15-16]. Moreover, long term (10 years) follow up data of the RIGENERA trial have been recently collected, confirming the safety of the procedure and a significant improvement of the quality of life assessed by NYHA functional class, Seattle Heart Failure Model, Minnesota Living with Heart Failure Questionnaire (p<0.005) when compairing patients treated with G-CSF versus standard therapy. Data regarding efficacy, in terms of LVEF, end-diastolic volume and end-systolic volume are currently under analysis.