G-CSF for Extensive STEMI: Results from the STEM-AMI OUTCOME CMR Substudy

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 MalafronteFederica Soffici, Martina Ceseri, Stefano Maggiolini, Gualtiero I Colombo, Giulio Pompilio

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Abstract

RATIONALE: In the exploratory Phase II STEM-AMI trial, we reported that early administration of granulocyte colony stimulating factor (G-CSF), in patients with anterior STEMI and left ventricular (LV) dysfunction after successful percutaneous coronary intervention (PCI), had the potential to significantly attenuate LV adverse remodeling in the long-term.

OBJECTIVE: The STEM-AMI OUTCOME Cardiac Magnetic Resonance (CMR) Substudy was adequately powered to evaluate, in a population showing LV ejection fraction (LVEF){less than or equal to}45% after PCI for extensive STEMI, the effects of early administration of G-CSF in terms of LV remodeling and function, infarct size assessed by late gadolinium enhancement (LGE), and myocardial strain.

METHODS AND RESULTS: Within the Italian, multicenter, prospective, randomized, Phase III STEM-AMI OUTCOME trial (NCT01969890), 161 STEMI 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 two blinded experts in a core CMR lab. The two groups were similar for clinical characteristics, cardiovascular risk factors and pharmacologic treatment, except for a trend towards a larger infarct size and longer symptom-to-balloon time in G-CSF patients. Analysis of covariance showed that the improvement of LVEF from baseline to 6 months was 5.1% higher in G-CSF patients vs. 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 LGE 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 vs. 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 STEMI in terms of global systolic function, adverse remodeling, scar size, and myocardial strain.

CLINICAL TRIAL REGISTRATION: NCT01969890.

Original languageEnglish
JournalCirculation Research
DOIs
Publication statusE-pub ahead of print - May 29 2019

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Achilli, F., Pontone, G., Bassetti, B., Squadroni, L., Campodonico, J., Corrada, E., Facchini, C., Mircoli, L., Esposito, G., Scarpa, D., Pidello, S., Righetti, S., Di Gennaro, F., Guglielmo, M., Muscogiuri, G., Baggiano, A., Limido, A., Lenatti, L., Di Tano, G., ... Pompilio, G. (2019). G-CSF for Extensive STEMI: Results from the STEM-AMI OUTCOME CMR Substudy. Circulation Research. https://doi.org/10.1161/CIRCRESAHA.118.314617