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 Malafronte & 5 others Federica Soffici, Martina Ceseri, Stefano Maggiolini, Gualtiero I Colombo, Giulio Pompilio

Research output: Contribution to journalArticle

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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Scanning Transmission Electron Microscopy
Granulocyte Colony-Stimulating Factor
Magnetic Resonance Spectroscopy
Standard of Care
Ventricular Remodeling
Gadolinium
Left Ventricular Dysfunction
Percutaneous Coronary Intervention
Stroke Volume
ST Elevation Myocardial Infarction
Left Ventricular Function
Cicatrix
Clinical Trials

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G-CSF for Extensive STEMI : Results from the STEM-AMI OUTCOME CMR Substudy. / Achilli, Felice; Pontone, Gianluca; Bassetti, Beatrice; Squadroni, Lidia; Campodonico, Jeness; Corrada, Elena; Facchini, Camilla; Mircoli, Luca; Esposito, Giovanni; Scarpa, Daniele; Pidello, Stefano; Righetti, Stefano; Di Gennaro, Filiberto; Guglielmo, Marco; Muscogiuri, Giuseppe; Baggiano, Andrea; Limido, Alberto; Lenatti, Laura; Di Tano, Giuseppe; Malafronte, Cristina; Soffici, Federica; Ceseri, Martina; Maggiolini, Stefano; Colombo, Gualtiero I; Pompilio, Giulio.

In: Circulation Research, 29.05.2019.

Research output: Contribution to journalArticle

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, Malafronte, C, Soffici, F, Ceseri, M, Maggiolini, S, Colombo, GI & 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
Achilli, Felice ; Pontone, Gianluca ; Bassetti, Beatrice ; Squadroni, Lidia ; Campodonico, Jeness ; Corrada, Elena ; Facchini, Camilla ; Mircoli, Luca ; Esposito, Giovanni ; Scarpa, Daniele ; Pidello, Stefano ; Righetti, Stefano ; Di Gennaro, Filiberto ; Guglielmo, Marco ; Muscogiuri, Giuseppe ; Baggiano, Andrea ; Limido, Alberto ; Lenatti, Laura ; Di Tano, Giuseppe ; Malafronte, Cristina ; Soffici, Federica ; Ceseri, Martina ; Maggiolini, Stefano ; Colombo, Gualtiero I ; Pompilio, Giulio. / G-CSF for Extensive STEMI : Results from the STEM-AMI OUTCOME CMR Substudy. In: Circulation Research. 2019.
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title = "G-CSF for Extensive STEMI: Results from the STEM-AMI OUTCOME CMR Substudy",
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.",
author = "Felice Achilli and Gianluca Pontone and Beatrice Bassetti and Lidia Squadroni and Jeness Campodonico and Elena Corrada and Camilla Facchini and Luca Mircoli and Giovanni Esposito and Daniele Scarpa and Stefano Pidello and Stefano Righetti and {Di Gennaro}, Filiberto and Marco Guglielmo and Giuseppe Muscogiuri and Andrea Baggiano and Alberto Limido and Laura Lenatti and {Di Tano}, Giuseppe and Cristina Malafronte and Federica Soffici and Martina Ceseri and Stefano Maggiolini and Colombo, {Gualtiero I} and Giulio Pompilio",
year = "2019",
month = "5",
day = "29",
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language = "English",
journal = "Circulation Research",
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TY - JOUR

T1 - G-CSF for Extensive STEMI

T2 - Results from the STEM-AMI OUTCOME CMR Substudy

AU - Achilli, Felice

AU - Pontone, Gianluca

AU - Bassetti, Beatrice

AU - Squadroni, Lidia

AU - Campodonico, Jeness

AU - Corrada, Elena

AU - Facchini, Camilla

AU - Mircoli, Luca

AU - Esposito, Giovanni

AU - Scarpa, Daniele

AU - Pidello, Stefano

AU - Righetti, Stefano

AU - Di Gennaro, Filiberto

AU - Guglielmo, Marco

AU - Muscogiuri, Giuseppe

AU - Baggiano, Andrea

AU - Limido, Alberto

AU - Lenatti, Laura

AU - Di Tano, Giuseppe

AU - Malafronte, Cristina

AU - Soffici, Federica

AU - Ceseri, Martina

AU - Maggiolini, Stefano

AU - Colombo, Gualtiero I

AU - Pompilio, Giulio

PY - 2019/5/29

Y1 - 2019/5/29

N2 - 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.

AB - 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.

U2 - 10.1161/CIRCRESAHA.118.314617

DO - 10.1161/CIRCRESAHA.118.314617

M3 - Article

JO - Circulation Research

JF - Circulation Research

SN - 0009-7330

ER -