G-CSF for Extensive STEMI
Felice Achilli, Gianluca Pontone, Beatrice Bassetti, Lidia Squadroni, Jeness Campodonico, Elena Corrada, Camilla Facchini, Luca Mircoli, Giovanni Esposito, Daniele Scarpa, Stefano Pidello, Stefano Righetti, Filiberto Di Gennaro, Marco Guglielmo, Giuseppe Muscogiuri, Andrea Baggiano, Alberto Limido, Laura Lenatti, Giuseppe Di Tano, Cristina Malafronte, Federica Soffici, Martina Ceseri, Stefano Maggiolini, Gualtiero I Colombo, Giulio Pompilio, STEM-AMI OUTCOME CMR Sub-Study Investigators, Felice Achilli, Gianluca Pontone, Beatrice Bassetti, Lidia Squadroni, Jeness Campodonico, Elena Corrada, Camilla Facchini, Luca Mircoli, Giovanni Esposito, Daniele Scarpa, Stefano Pidello, Stefano Righetti, Filiberto Di Gennaro, Marco Guglielmo, Giuseppe Muscogiuri, Andrea Baggiano, Alberto Limido, Laura Lenatti, Giuseppe Di Tano, Cristina Malafronte, Federica Soffici, Martina Ceseri, Stefano Maggiolini, Gualtiero I Colombo, Giulio Pompilio, STEM-AMI OUTCOME CMR Sub-Study Investigators
Abstract
Rationale: In the exploratory Phase II STEM-AMI (Stem Cells Mobilization in Acute Myocardial Infarction) trial, we reported that early administration of G-CSF (granulocyte colony-stimulating factor), in patients with anterior ST-segment-elevation myocardial infarction and left ventricular (LV) dysfunction after successful percutaneous coronary intervention, had the potential to significantly attenuate LV adverse remodeling in the long-term.
Objective: The STEM-AMI OUTCOME CMR (Stem Cells Mobilization in Acute Myocardial Infarction Outcome Cardiac Magnetic Resonance) Substudy was adequately powered to evaluate, in a population showing LV ejection fraction ≤45% after percutaneous coronary intervention for extensive ST-segment-elevation myocardial infarction, the effects of early administration of G-CSF in terms of LV remodeling and function, infarct size assessed by late gadolinium enhancement, and myocardial strain.
Methods and results: Within the Italian, multicenter, prospective, randomized, Phase III STEM-AMI OUTCOME trial, 161 ST-segment-elevation myocardial infarction patients were enrolled in the CMR Substudy and assigned to standard of care (SOC) plus G-CSF or SOC alone. In 119 patients (61 G-CSF and 58 SOC, respectively), CMR was available at baseline and 6-month follow-up. Paired imaging data were independently analyzed by 2 blinded experts in a core CMR lab. The 2 groups were similar for clinical characteristics, cardiovascular risk factors, and pharmacological treatment, except for a trend towards a larger infarct size and longer symptom-to-balloon time in G-CSF patients. ANCOVA showed that the improvement of LV ejection fraction from baseline to 6 months was 5.1% higher in G-CSF patients versus SOC (P=0.01); concurrently, there was a significant between-group difference of 6.7 mL/m2 in the change of indexed LV end-systolic volume in favor of G-CSF group (P=0.02). Indexed late gadolinium enhancement significantly decreased in G-CSF group only (P=0.04). Moreover, over time improvement of global longitudinal strain was 2.4% higher in G-CSF patients versus SOC (P=0.04). Global circumferential strain significantly improved in G-CSF group only (P=0.006).
Conclusions: Early administration of G-CSF exerted a beneficial effect on top of SOC in patients with LV dysfunction after extensive ST-segment-elevation myocardial infarction in terms of global systolic function, adverse remodeling, scar size, and myocardial strain.
Clinical trial registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01969890.
Keywords: granulocyte colony-stimulating factor; left ventricular remodeling; myocardial infarction; percutaneous coronary intervention; standard of care.
Source: PubMed