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COLLAGEN-CCN1 MATRIX FOR THE TREATMENT OF MYOCARDIAL INFARCTION
Abstracts
with men. Despite this, baseline IL-6 geometric means before both mental and physical stress were twice as high in women 50 years of age compared to age-matched men (3.8 vs. 1.8 pg/ mL, p¼0.001, across both conditions), while they were similar in women and men age >50 years (2.3 vs. 2.2 pg/mL, p¼0.83). After mental stress, IL-6 concentrations increased in both women and men in a similar fashion and remained twice as high in women 50 years than men at both 60 min (5.4 vs. 2.6 pg/ mL, p¼0.002) and 90 min (5.9 vs. 3.4 pg/mL, p¼0.01). No significant difference was found between women and men >50 years of age at any time point after mental stress. Results were similar for physical stress. After accounting for SDS, IL-6 concentrations in young women remained higher after both mental and physical stress. Baseline IL-6 concentrations were not significantly related to inducible ischemia. CONCLUSION: After MI, young women aged 50 years or younger, compared with age-matched men, have remarkably higher concentrations of inflammatory markers at baseline and after both mental and physical stress, with a similar inflammatory response to both stressors. Sustained concentrations of inflammation in young women, not their response to stress, may contribute to their adverse outcomes post-MI.
536 COLLAGEN-CCN1 MATRIX FOR THE TREATMENT OF MYOCARDIAL INFARCTION B McNeill, B Vulsevic, N Blackburn, M Ruel, EJ Suuronen Ottawa, Ontario BACKGROUND:
Cardiac remodeling and subsequent heart failure remain critical issues following myocardial infarction (MI). CCN1 is a pro-angiogenic matricellular protein that has been shown to induce fibroblast senescence and restrict fibrosis during wound healing. Herein, we test the hypothesis that injection of a collagen matrix containing CCN1 will attenuate adverse cardiac remodeling and improve function in a mouse MI model. METHODS/RESULTS: One week after LAD ligation, mice were randomized to receive intramyocardial injections of PBS, CCN1 (in PBS), matrix, or CCN1-matrix, administered under echocardiographic guidance. Function was evaluated up to 4 weeks post-MI by echocardiography. At 1-wk post-treatment, significant improvements in LVEF were observed for both the CCN1 (48.13.3%) and CCN1-matrix (41.93.5%) treated groups compared to PBS (34.62.8%; p<0.03). By 4 weeks, LVEF was superior in CCN1-matrix treated hearts (49.72.1%) compared to PBS (28.92.9%), CCN1 (38.02.6%) and matrix (38.71.6%) groups (p<0.01). In vitro evaluation revealed a protective effect of the CCN1-matrix on cultures of neonatal cardiomyocytes as there was a 39.3% increase in cell survival under stress conditions compared to matrix-cultured cardiomyocytes (p¼0.03). The in vitro culture of fibroblasts on the CCN1matrix resulted in a 2.30.7 and 1.60.2 fold reduction in proliferation compared to fibroblasts cultured on tissue
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culture polystyrene (TCPS; p¼0.008) and matrix (p¼0.04), respectively. Furthermore, the collagenase activity of CCN1matrix cultured fibroblasts was reduced compared to both TCPS- and matrix-cultured fibroblasts. Circulating angiogenic cells (CACs) responded to CCN1-matrix treatment with a 2.20.2 fold increase in proliferation and a 1.80.2 fold increase in migration towards VEGF compared to matrix (p¼0.001) cultured CACs. In an angiogenic assay, CCN1matrix cultured CACs demonstrated a 4.11.6 fold increase in cell incorporation into capillary-like structures (p¼0.03) and a 5.10.6 fold increase in overall tubule network formation (p¼0.007), compared to matrix-cultured CACs. CONCLUSION: Here, we demonstrate a novel approach to treat MI using a CCN1-containing collagen biomaterial. The functional benefits achieved with CCN1 treatment persisted for the 4 weeks only when it was delivered with the matrix. These data suggest that CCN1-matrix improves cardiac function in the MI heart by reducing fibrosis and promoting neovascularization and cardiomyocyte survival. HSF
537 DURATION OF DUAL ANTIPLATELET THERAPY AND ASSOCIATED OUTCOMES FOLLOWING PERCUTANEOUS CORONARY INTERVENTION FOR ACUTE MYOCARDIAL INFARCTION: CONTEMPORARY PRACTICE INSIGHTS FROM THE CANADIAN OBSERVATIONAL ANTIPLATELET STUDY (COAPT) JJ Russo, SG Goodman, A Bagai, J Dery, MK Tan, HN Fisher, X Zhang, YE Zhu, RC Welsh, A Della Siega, BY Wong, M Henderson, S Lutchmedial, SR Mehta, AT Yan Toronto, Ontario BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) has not been well established. Furthermore, DAPT is often discontinued prior to the guideline recommended duration of 12 months. Using contemporary data, we examined practice patterns, patient characteristics, and clinical outcomes following PCI for myocardial infarction (MI) in relation to DAPT duration. METHODS: The Canadian Observational Antiplatelet Study (COAPT) was a prospective, multicenter, cohort study examining ADP receptor antagonist use following PCI for acute MI. In the current analysis, we compared practice patterns, patient characteristics, and clinical outcomes in relation to pre-specified DAPT duration intervals (<6 weeks, 6 weeks to <6 months, 6 to <12 months, and 12 months or more). Ischemic and safety outcomes included death, MI, stent thrombosis, and bleeding. RESULTS: From 2179 patients enrolled between December 2011 to May 2013, 2034 were discharged on DAPT following PCI for MI and followed for 15 months (26 hospitals; median age 60 years; 21% female; 62% STEMI). At discharge, clopidogrel was used in 72% of patients, ticagrelor in 17%, and prasugrel in 11%. DAPT duration was <6 weeks in 5.2% of
with men. Despite this, baseline IL-6 geometric means before both mental and physical stress were twice as high in women 50 years of age compared to age-matched men (3.8 vs. 1.8 pg/ mL, p¼0.001, across both conditions), while they were similar in women and men age >50 years (2.3 vs. 2.2 pg/mL, p¼0.83). After mental stress, IL-6 concentrations increased in both women and men in a similar fashion and remained twice as high in women 50 years than men at both 60 min (5.4 vs. 2.6 pg/ mL, p¼0.002) and 90 min (5.9 vs. 3.4 pg/mL, p¼0.01). No significant difference was found between women and men >50 years of age at any time point after mental stress. Results were similar for physical stress. After accounting for SDS, IL-6 concentrations in young women remained higher after both mental and physical stress. Baseline IL-6 concentrations were not significantly related to inducible ischemia. CONCLUSION: After MI, young women aged 50 years or younger, compared with age-matched men, have remarkably higher concentrations of inflammatory markers at baseline and after both mental and physical stress, with a similar inflammatory response to both stressors. Sustained concentrations of inflammation in young women, not their response to stress, may contribute to their adverse outcomes post-MI.
536 COLLAGEN-CCN1 MATRIX FOR THE TREATMENT OF MYOCARDIAL INFARCTION B McNeill, B Vulsevic, N Blackburn, M Ruel, EJ Suuronen Ottawa, Ontario BACKGROUND:
Cardiac remodeling and subsequent heart failure remain critical issues following myocardial infarction (MI). CCN1 is a pro-angiogenic matricellular protein that has been shown to induce fibroblast senescence and restrict fibrosis during wound healing. Herein, we test the hypothesis that injection of a collagen matrix containing CCN1 will attenuate adverse cardiac remodeling and improve function in a mouse MI model. METHODS/RESULTS: One week after LAD ligation, mice were randomized to receive intramyocardial injections of PBS, CCN1 (in PBS), matrix, or CCN1-matrix, administered under echocardiographic guidance. Function was evaluated up to 4 weeks post-MI by echocardiography. At 1-wk post-treatment, significant improvements in LVEF were observed for both the CCN1 (48.13.3%) and CCN1-matrix (41.93.5%) treated groups compared to PBS (34.62.8%; p<0.03). By 4 weeks, LVEF was superior in CCN1-matrix treated hearts (49.72.1%) compared to PBS (28.92.9%), CCN1 (38.02.6%) and matrix (38.71.6%) groups (p<0.01). In vitro evaluation revealed a protective effect of the CCN1-matrix on cultures of neonatal cardiomyocytes as there was a 39.3% increase in cell survival under stress conditions compared to matrix-cultured cardiomyocytes (p¼0.03). The in vitro culture of fibroblasts on the CCN1matrix resulted in a 2.30.7 and 1.60.2 fold reduction in proliferation compared to fibroblasts cultured on tissue
S283
culture polystyrene (TCPS; p¼0.008) and matrix (p¼0.04), respectively. Furthermore, the collagenase activity of CCN1matrix cultured fibroblasts was reduced compared to both TCPS- and matrix-cultured fibroblasts. Circulating angiogenic cells (CACs) responded to CCN1-matrix treatment with a 2.20.2 fold increase in proliferation and a 1.80.2 fold increase in migration towards VEGF compared to matrix (p¼0.001) cultured CACs. In an angiogenic assay, CCN1matrix cultured CACs demonstrated a 4.11.6 fold increase in cell incorporation into capillary-like structures (p¼0.03) and a 5.10.6 fold increase in overall tubule network formation (p¼0.007), compared to matrix-cultured CACs. CONCLUSION: Here, we demonstrate a novel approach to treat MI using a CCN1-containing collagen biomaterial. The functional benefits achieved with CCN1 treatment persisted for the 4 weeks only when it was delivered with the matrix. These data suggest that CCN1-matrix improves cardiac function in the MI heart by reducing fibrosis and promoting neovascularization and cardiomyocyte survival. HSF
537 DURATION OF DUAL ANTIPLATELET THERAPY AND ASSOCIATED OUTCOMES FOLLOWING PERCUTANEOUS CORONARY INTERVENTION FOR ACUTE MYOCARDIAL INFARCTION: CONTEMPORARY PRACTICE INSIGHTS FROM THE CANADIAN OBSERVATIONAL ANTIPLATELET STUDY (COAPT) JJ Russo, SG Goodman, A Bagai, J Dery, MK Tan, HN Fisher, X Zhang, YE Zhu, RC Welsh, A Della Siega, BY Wong, M Henderson, S Lutchmedial, SR Mehta, AT Yan Toronto, Ontario BACKGROUND: The optimal duration of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) has not been well established. Furthermore, DAPT is often discontinued prior to the guideline recommended duration of 12 months. Using contemporary data, we examined practice patterns, patient characteristics, and clinical outcomes following PCI for myocardial infarction (MI) in relation to DAPT duration. METHODS: The Canadian Observational Antiplatelet Study (COAPT) was a prospective, multicenter, cohort study examining ADP receptor antagonist use following PCI for acute MI. In the current analysis, we compared practice patterns, patient characteristics, and clinical outcomes in relation to pre-specified DAPT duration intervals (<6 weeks, 6 weeks to <6 months, 6 to <12 months, and 12 months or more). Ischemic and safety outcomes included death, MI, stent thrombosis, and bleeding. RESULTS: From 2179 patients enrolled between December 2011 to May 2013, 2034 were discharged on DAPT following PCI for MI and followed for 15 months (26 hospitals; median age 60 years; 21% female; 62% STEMI). At discharge, clopidogrel was used in 72% of patients, ticagrelor in 17%, and prasugrel in 11%. DAPT duration was <6 weeks in 5.2% of