Felice Achilli1, Gianluca Pontone2,3, Beatrice Bassetti4, Lidia Squadroni5, Jeness Campodonico6, Elena Corrada7, Camilla Facchini8, Luca Mircoli9, Giovanni Esposito10, Daniele Scarpa11, Stefano Pidello12, Stefano Righetti1, Filiberto Di Gennaro13, Marco Guglielmo2, Giuseppe Muscogiuri2, Andrea Baggiano2, Alberto Limido14, Laura Lenatti15, Giuseppe Di Tano16, Cristina Malafronte1, Federica Soffici1, Martina Ceseri17, Stefano Maggiolini18, Gualtiero I Colombo19, Giulio Pompilio4. 1. From the Departments of Cardiology (F.A., S.R., C.M., F.S.), ASST-Monza, San Gerardo Hospital, Monza, Italy. 2. Cardiovascular Imaging (G. Pontone, M.G., G.M., A.B.), Centro Cardiologico Monzino IRCCS, Milano, Italy. 3. Dipartimento di Scienze Cliniche e di Comunità, Università degli Studi di Milano, Italy (G.P.). 4. Vascular Biology and Regenerative Medicine Unit (B.B., G. Pompilio), Centro Cardiologico Monzino IRCCS, Milano, Italy. 5. Department of Cardiology, San Carlo Borromeo Hospital, Milano, Italy (L.S.). 6. Intensive Cardiac Care Unit (J.C.), Centro Cardiologico Monzino IRCCS, Milano, Italy. 7. Cardiovascular Department, Humanitas Clinical and Research Center IRCCS, Rozzano, Italy (E.C.). 8. Cardiology, Bassini Hospital, Cinisello Balsamo, Italy (C.F.). 9. Cardiology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy (L.M.). 10. Division of Cardiology, Department of Advanced Biomedical Sciences, University of Naples Federico II, Napoli, Italy (G.E.). 11. Cardiology, Department of Cardiac, Thoracic and Vascular Sciences, University of Padova, Italy (D.S.). 12. Cardiology, Città della Salute e della Scienza University Hospital of Torino, Italy (S.P.). 13. Radiology (F.D.G.), ASST-Monza, San Gerardo Hospital, Monza, Italy. 14. Coronary Intensive Care Unit, ASST-Settelaghi, Ospedale di Circolo-Fondazione Macchi, Varese, Italy (A.L.). 15. Cardiology, Alessandro Manzoni Hospital, Lecco, Italy (L.L.). 16. Cardiology, ASST of Cremona, Italy (G.D.T.). 17. ANMCO Research Center, Heart Care Foundation, Firenze, Italy (M.C.). 18. Cardiology, San Leopoldo Mandic Hospital, Merate, Italy (S.M.). 19. Immunology and Functional Genomics Unit (G.I.C.), Centro Cardiologico Monzino IRCCS, Milano, Italy.
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 tostandard 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.
RCT Entities:
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 infarctionpatients 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-CSFpatients. ANCOVA showed that the improvement of LV ejection fraction from baseline to 6 months was 5.1% higher in G-CSFpatients 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-CSFpatients 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.
Entities:
Keywords:
granulocyte colony-stimulating factor; left ventricular remodeling; myocardial infarction; percutaneous coronary intervention; standard of care
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