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PREDICTORS OF DEATH AND STROKE IN PATIENTS WITH PAROXYSMAL ATRIAL FIBRILLATION: Results FROM THE CANADIAN REGISTRY OF ATRIAL FIBRILLATION
Abstracts
249 LOW-VOLTAGE AREA BUT NOT THE FRACTIONATION SURFACE AREA PREDICTS RECURRENCES AFTER STEPWISE ABLATION OF PERSISTENT ATRIAL FIBRILLATION A Enriquez, F Sadiq Ali, K Michael, C Simpson, H Abdollah, M Jansen, A Baranchuk, D Redfearn Kingston, Ontario BACKGROUND:
Catheter ablation is a highly effective therapy for the long-term management of paroxysmal atrial fibrillation (AF), but the results in persistent AF are more limited. Predictors of success after ablation in this group of patients, especially if long-standing, are not well defined. AIM: The purpose of this study was to determine the association between complex atrial fractionated electrograms (CFAE) surface area or low-voltage area with long-term outcomes after catheter ablation for long-standing persistent AF. METHODS: We included 68 patients with persistent AF 12 months undergoing de novo catheter ablation using a stepwise approach. Bipolar electrogram fractionation and voltage were registered during AF. Regions with a mean cycle length (mCL) between 50-120 ms were considered CFAE and a peak-to-peak bipolar voltage less than 0.1 mV was defined as abnormal. RESULTS: The mean age of the patients was 64 9 years, with 76% being male, duration of AF 86 94 months, LA volume 132 36 ml. Conversion to sinus rhythm or organization into atrial tachycardia with ablation was achieved in 69% of patients during ablation. CFAE involved 48 17% of the LA area and low-voltage was recorded from 11 11%. After a follow-up of 23 14 months 51% of patients were free of arrhythmia recurrences. In patients that recurred the area of low-voltage was greater than in those who remained free of arrhythmias (8 vs 15%, p 0.03). No differences were observed regarding the CFAE surface area. CONCLUSION: In conclusion, among patients with longstanding persistent AF a larger low-voltage area is associated with increased recurrence of arrhythmia during follow-up.
250 HIGH RATES OF CONCOMITANT ANTIPLATELET USE IN PATIENTS WITH ATRIAL FIBRILLATION TREATED WITH ORAL ANTICOAGULATION: INSIGHTS FROM THE STROKE PREVENTION AND RHYTHM INTERVENTIONS IN ATRIAL FIBRILLATION (SPRINT-AF) REGISTRY M Gupta, N Singh, S Verma, JL Cox, P Dorian, C Fournier, DJ Gladstone, E Lockwood, G Mancini, C Saldanha, A Shuaib, M Kajil, M Tsigoulis, AC Ha Toronto, Ontario
Among patients with atrial fibrillation (AF) treated with oral anticoagulation (OAC) for stroke prevention, concomitant use of antiplatelet (AP) agents increases bleeding risk. Also, when compared to OAC alone, additional AP use confers uncertain benefits in terms of reduction of ischemic
BACKGROUND:
S183
vascular events. Since little is known regarding the factors which influence the use of OAC+AP vs. OAC alone in current clinical practice, we sought to identify them in a contemporary, national, observational registry. METHODS: From December 2012 to July 2013, a crosssectional analysis of 850 consecutive AF patients was performed. They were enrolled from 101 practices in 7 Canadian provinces. Demographics of patients treated with OAC+AP (primarily aspirin) vs. OAC alone were identified. Multivariable logistic regression was performed to identify factors associated with OAC+AP vs. OAC use. RESULTS: Seven hundred and five (87%) patients were treated with OAC, amongst whom 135 (19%) were treated with OAC+AP and 570 (81%) were treated with OAC alone. Amongst patients treated with OAC+AP, 58 (43%) did not have a known history of coronary artery disease (CAD) (defined as presence of stable CAD, acute coronary syndrome, percutaneous coronary intervention (PCI), or coronary artery bypass surgery) or peripheral arterial disease (PAD). In the OAC+AP group, 38 (28%) patients had PCI and 51 (38%) patients had diabetes. Patients treated with OAC+AP vs. OAC alone did not significantly differ in age: 77.5 (71.4, 82.3) vs. 76.9 (69.0, 83.0) years (median, IQR). On univariable analysis, male sex, dyslipidemia, PAD, non-CNS systemic embolism, and CAD were associated with OAC+AP use (vs. OAC alone). On multivariable analysis, CAD (OR 4.20, 95% CI 2.83 to 6.24, p<0.01) and male sex (OR 1.60, 95% CI 1.01 to 2.61, p¼0.047) were associated with OAC+AP use. CONCLUSION: In this contemporary registry of AF patients treated with OAC for stroke prevention, we found that 1 in 5 patients was treated with OAC+AP. Although a history of CAD was associated with OAC+AP use, a substantial proportion of patients in this subgroup did not have compelling indications for being treated with AP agents (e.g. history of PCI). Since OAC+AP use increases bleeding risk without discernible benefits in stroke or myocardial infarction reduction, the relatively high rate of AP co-prescription in OACtreated AF patients represents a potential practice gap. Efforts are needed to address this practice pattern to minimize the over-prescription of AP agents in this patient population. Bayer Inc.
251 PREDICTORS OF DEATH AND STROKE IN PATIENTS WITH PAROXYSMAL ATRIAL FIBRILLATION: RESULTS FROM THE CANADIAN REGISTRY OF ATRIAL FIBRILLATION A Ahmadi, A Parsa, J Swampillai, S Connolly, P Dorian, M Green, K Humphries, G Klein, H Qian, M Talajic, C Kerr Vancouver, British Columbia INTRODUCTION:
Atrial Fibrillation is the most commonly encountered sustained arrhythmia. Following initial diagnosis, AF can be associated with poor outcomes such as death and stroke. A paucity of data exists regarding risk factors associated
S184
with occurrence of poor outcomes in setting of AF, highlighting the need for comprehensive long-term follow up studies. METHODS: The Canadian Registry of Atrial Fibrillation (CARAF) enrolled patients from 7 centres in Canada at the time of first electrocardiographic diagnosis of AF. Comprehensive clinical and echocardiographic data were collected and patients were followed annually, documenting clinical outcomes, recurrence of PAF, and progression to CAF. Univariate and multivariable Cox proportionate hazards analyses were performed to model the association between baseline clinical, electrocardiographic, and echocardiographic variables and outcomes of stroke and death in patients with AF. RESULTS: A total of 897 patients with non-surgical paroxysmal AF (PAF) were included in the analysis. The medial follow-up time was 8.89 years (interquartile range of 5 to 9.12 years). A total of 268 deaths and 84 strokes occurred during the follow-up period. Univariate analyses identified 13 risk factors that were independently associated with risk of death and 9 risk factors that were independently associated with risk of stroke. Of these risk factors, history of cardiomyopathy, presence of congestive heart failure (CHF), severe mitral regurgitation (MR) and older age had the highest hazard ratios (HR) for occurrence of death (HR ¼2.74, 2.61, 2.11 and 2.10, respectively (p<0.001)). The factors were also statistically associated with death in multivariate analysis. Presence of moderate to severe mitral stenosis (MS), cardiomyopathy, increase in left ventricular (LV) posterior wall dimension, CHF and age were highly associated with occurrence of stroke (HR¼ 3.99, 3.23, 2.51, 1.94 and 1.73, respectively (p<0.03)). In multivariable analysis, MS, age, And LV posterior wall dimension were associated with stroke. CONCLUSION: In patients with diagnosis of PAF, there are various clinical and echocardiographic risk factors that are independently associated with higher risk of poor outcomes such as death and stroke.
Canadian Cardiovascular Society (CCS) Oral CARDIAC STEM CELLS Sunday, October 26, 2014 252 ISOLATION AND RECOVERY OF HUMAN CARDIAC STEM CELLS FROM CRYOPRESERVED CARDIAC TISSUE R Jackson, B Ye, V Chan, M Boodhwani, RA Davies, H Haddad, DR Davis Ottawa, Ontario BACKGROUND:
The value of preserving high quality biospecimens for fundamental research is significant as linking cellular and molecular changes to clinical and epidemiological data has fueled many recent advances in medicine. Unfortunately, storage of traditional biospecimens is limited to fixed (dead) samples or isolated genetic material. Therefore, we
Canadian Journal of Cardiology Volume 30 2014
evaluated the effect of immediate or delayed cryopreservation of routine myocardial biopsies on cardiac and induced pluripotent stem cell culture outcomes. MATERIAL AND METHODS: Human atrial and ventricular biopsies were obtained from patients undergoing clinicallyindicated procedures for cardiac stem cell (CSC) culture from fresh tissue (fresh CSCs), immediately cryopreserved tissue (early cryopreserved CSCs) or tissue cryopreserved after suspension in cardioplegia (St. Thomas solution) for 12 hours (delayed cryopreserved CSCs). Both cryopreserved tissue sources were stored for at least one month before starting cell culture. When compared to fresh tissue sources, early or delayed cryopreservation of tissue did not alter CSC culture yields (4.51.5 or 2.90.4 vs. 3.50.9 105cells/mg of plated tissue, respectively; p¼0.5) or in vitro proliferation (population doubling time: 19.52.04 or 18.83.2 vs. 18.52.4 hours; p¼0.8). The phenotype of early and late cryopreserved CSCs did not differ from CSCs sourced from fresh tissue sources in the proportion of cardiac (c-Kit+ 1.60.3 and 1.80.2 vs. 1.60.6%, respectively; p¼0.7), endothelial (CD31+ 0.50.2 and 0.40.1 vs. 0.50.1%, respectively; p¼0.8) and mesenchymal (CD90+ 337 and 277 vs. 267%, respectively; p¼0.6) progenitor sub-populations. Cryopreservation did not alter the cytokine content (HGF, VEGF, IGF-1, SDF-1 or IL-6) of CSC conditioned media or the ability of this media to promote angiogenesis and recruit resident stem cells. Early or late cryopreservation had negligible effects the ability of CSCs to adopt a cardiac fate (alpha smooth muscle actin, cardiac troponin and von Willebrand Factor) in conditions known to favor cardiogenesis. Transplantation of both fresh and cryopreserved CSCs into a mouse model 1 week after myocardial infarction improved echocardiographic left ventricular ejection fraction and myocardial scarring to a similar extent with equivalent effects on CSC engraftment and the generation of new cardiomyocytes. Finally, cryopreservation did not influence the ability of CSCs to undergo genetic reprogramming into inducible pluripotent stem cells. CONCLUSION: Cryopreservation and recovery of minced atrial or ventricular myocardial biopsies does not influence the cellular yield, phenotype, proliferative capacity of human CSCs. This innovation provides simple low cost means of storing cardiac samples for post-ischemic cardiac repair or inducible pluripotent stem cells based disease modeling. CIHR, HSF
253 IGF-1 ENGINEERED HUMAN CARDIAC STEM CELLS PROMOTE REPAIR OF ISCHEMIC MYOCARDIUM BY IMPROVING TRANSPLANT CELL SURVIVAL AND REDUCING MYOCARDIAL APOPTOSIS R Jackson, EL Tilokee, N Latham, B Ye, M Boodhwani, V Chan, M Ruel, EJ Suuronen, DJ Stewart, DR Davis Ottawa, Ontario
249 LOW-VOLTAGE AREA BUT NOT THE FRACTIONATION SURFACE AREA PREDICTS RECURRENCES AFTER STEPWISE ABLATION OF PERSISTENT ATRIAL FIBRILLATION A Enriquez, F Sadiq Ali, K Michael, C Simpson, H Abdollah, M Jansen, A Baranchuk, D Redfearn Kingston, Ontario BACKGROUND:
Catheter ablation is a highly effective therapy for the long-term management of paroxysmal atrial fibrillation (AF), but the results in persistent AF are more limited. Predictors of success after ablation in this group of patients, especially if long-standing, are not well defined. AIM: The purpose of this study was to determine the association between complex atrial fractionated electrograms (CFAE) surface area or low-voltage area with long-term outcomes after catheter ablation for long-standing persistent AF. METHODS: We included 68 patients with persistent AF 12 months undergoing de novo catheter ablation using a stepwise approach. Bipolar electrogram fractionation and voltage were registered during AF. Regions with a mean cycle length (mCL) between 50-120 ms were considered CFAE and a peak-to-peak bipolar voltage less than 0.1 mV was defined as abnormal. RESULTS: The mean age of the patients was 64 9 years, with 76% being male, duration of AF 86 94 months, LA volume 132 36 ml. Conversion to sinus rhythm or organization into atrial tachycardia with ablation was achieved in 69% of patients during ablation. CFAE involved 48 17% of the LA area and low-voltage was recorded from 11 11%. After a follow-up of 23 14 months 51% of patients were free of arrhythmia recurrences. In patients that recurred the area of low-voltage was greater than in those who remained free of arrhythmias (8 vs 15%, p 0.03). No differences were observed regarding the CFAE surface area. CONCLUSION: In conclusion, among patients with longstanding persistent AF a larger low-voltage area is associated with increased recurrence of arrhythmia during follow-up.
250 HIGH RATES OF CONCOMITANT ANTIPLATELET USE IN PATIENTS WITH ATRIAL FIBRILLATION TREATED WITH ORAL ANTICOAGULATION: INSIGHTS FROM THE STROKE PREVENTION AND RHYTHM INTERVENTIONS IN ATRIAL FIBRILLATION (SPRINT-AF) REGISTRY M Gupta, N Singh, S Verma, JL Cox, P Dorian, C Fournier, DJ Gladstone, E Lockwood, G Mancini, C Saldanha, A Shuaib, M Kajil, M Tsigoulis, AC Ha Toronto, Ontario
Among patients with atrial fibrillation (AF) treated with oral anticoagulation (OAC) for stroke prevention, concomitant use of antiplatelet (AP) agents increases bleeding risk. Also, when compared to OAC alone, additional AP use confers uncertain benefits in terms of reduction of ischemic
BACKGROUND:
S183
vascular events. Since little is known regarding the factors which influence the use of OAC+AP vs. OAC alone in current clinical practice, we sought to identify them in a contemporary, national, observational registry. METHODS: From December 2012 to July 2013, a crosssectional analysis of 850 consecutive AF patients was performed. They were enrolled from 101 practices in 7 Canadian provinces. Demographics of patients treated with OAC+AP (primarily aspirin) vs. OAC alone were identified. Multivariable logistic regression was performed to identify factors associated with OAC+AP vs. OAC use. RESULTS: Seven hundred and five (87%) patients were treated with OAC, amongst whom 135 (19%) were treated with OAC+AP and 570 (81%) were treated with OAC alone. Amongst patients treated with OAC+AP, 58 (43%) did not have a known history of coronary artery disease (CAD) (defined as presence of stable CAD, acute coronary syndrome, percutaneous coronary intervention (PCI), or coronary artery bypass surgery) or peripheral arterial disease (PAD). In the OAC+AP group, 38 (28%) patients had PCI and 51 (38%) patients had diabetes. Patients treated with OAC+AP vs. OAC alone did not significantly differ in age: 77.5 (71.4, 82.3) vs. 76.9 (69.0, 83.0) years (median, IQR). On univariable analysis, male sex, dyslipidemia, PAD, non-CNS systemic embolism, and CAD were associated with OAC+AP use (vs. OAC alone). On multivariable analysis, CAD (OR 4.20, 95% CI 2.83 to 6.24, p<0.01) and male sex (OR 1.60, 95% CI 1.01 to 2.61, p¼0.047) were associated with OAC+AP use. CONCLUSION: In this contemporary registry of AF patients treated with OAC for stroke prevention, we found that 1 in 5 patients was treated with OAC+AP. Although a history of CAD was associated with OAC+AP use, a substantial proportion of patients in this subgroup did not have compelling indications for being treated with AP agents (e.g. history of PCI). Since OAC+AP use increases bleeding risk without discernible benefits in stroke or myocardial infarction reduction, the relatively high rate of AP co-prescription in OACtreated AF patients represents a potential practice gap. Efforts are needed to address this practice pattern to minimize the over-prescription of AP agents in this patient population. Bayer Inc.
251 PREDICTORS OF DEATH AND STROKE IN PATIENTS WITH PAROXYSMAL ATRIAL FIBRILLATION: RESULTS FROM THE CANADIAN REGISTRY OF ATRIAL FIBRILLATION A Ahmadi, A Parsa, J Swampillai, S Connolly, P Dorian, M Green, K Humphries, G Klein, H Qian, M Talajic, C Kerr Vancouver, British Columbia INTRODUCTION:
Atrial Fibrillation is the most commonly encountered sustained arrhythmia. Following initial diagnosis, AF can be associated with poor outcomes such as death and stroke. A paucity of data exists regarding risk factors associated
S184
with occurrence of poor outcomes in setting of AF, highlighting the need for comprehensive long-term follow up studies. METHODS: The Canadian Registry of Atrial Fibrillation (CARAF) enrolled patients from 7 centres in Canada at the time of first electrocardiographic diagnosis of AF. Comprehensive clinical and echocardiographic data were collected and patients were followed annually, documenting clinical outcomes, recurrence of PAF, and progression to CAF. Univariate and multivariable Cox proportionate hazards analyses were performed to model the association between baseline clinical, electrocardiographic, and echocardiographic variables and outcomes of stroke and death in patients with AF. RESULTS: A total of 897 patients with non-surgical paroxysmal AF (PAF) were included in the analysis. The medial follow-up time was 8.89 years (interquartile range of 5 to 9.12 years). A total of 268 deaths and 84 strokes occurred during the follow-up period. Univariate analyses identified 13 risk factors that were independently associated with risk of death and 9 risk factors that were independently associated with risk of stroke. Of these risk factors, history of cardiomyopathy, presence of congestive heart failure (CHF), severe mitral regurgitation (MR) and older age had the highest hazard ratios (HR) for occurrence of death (HR ¼2.74, 2.61, 2.11 and 2.10, respectively (p<0.001)). The factors were also statistically associated with death in multivariate analysis. Presence of moderate to severe mitral stenosis (MS), cardiomyopathy, increase in left ventricular (LV) posterior wall dimension, CHF and age were highly associated with occurrence of stroke (HR¼ 3.99, 3.23, 2.51, 1.94 and 1.73, respectively (p<0.03)). In multivariable analysis, MS, age, And LV posterior wall dimension were associated with stroke. CONCLUSION: In patients with diagnosis of PAF, there are various clinical and echocardiographic risk factors that are independently associated with higher risk of poor outcomes such as death and stroke.
Canadian Cardiovascular Society (CCS) Oral CARDIAC STEM CELLS Sunday, October 26, 2014 252 ISOLATION AND RECOVERY OF HUMAN CARDIAC STEM CELLS FROM CRYOPRESERVED CARDIAC TISSUE R Jackson, B Ye, V Chan, M Boodhwani, RA Davies, H Haddad, DR Davis Ottawa, Ontario BACKGROUND:
The value of preserving high quality biospecimens for fundamental research is significant as linking cellular and molecular changes to clinical and epidemiological data has fueled many recent advances in medicine. Unfortunately, storage of traditional biospecimens is limited to fixed (dead) samples or isolated genetic material. Therefore, we
Canadian Journal of Cardiology Volume 30 2014
evaluated the effect of immediate or delayed cryopreservation of routine myocardial biopsies on cardiac and induced pluripotent stem cell culture outcomes. MATERIAL AND METHODS: Human atrial and ventricular biopsies were obtained from patients undergoing clinicallyindicated procedures for cardiac stem cell (CSC) culture from fresh tissue (fresh CSCs), immediately cryopreserved tissue (early cryopreserved CSCs) or tissue cryopreserved after suspension in cardioplegia (St. Thomas solution) for 12 hours (delayed cryopreserved CSCs). Both cryopreserved tissue sources were stored for at least one month before starting cell culture. When compared to fresh tissue sources, early or delayed cryopreservation of tissue did not alter CSC culture yields (4.51.5 or 2.90.4 vs. 3.50.9 105cells/mg of plated tissue, respectively; p¼0.5) or in vitro proliferation (population doubling time: 19.52.04 or 18.83.2 vs. 18.52.4 hours; p¼0.8). The phenotype of early and late cryopreserved CSCs did not differ from CSCs sourced from fresh tissue sources in the proportion of cardiac (c-Kit+ 1.60.3 and 1.80.2 vs. 1.60.6%, respectively; p¼0.7), endothelial (CD31+ 0.50.2 and 0.40.1 vs. 0.50.1%, respectively; p¼0.8) and mesenchymal (CD90+ 337 and 277 vs. 267%, respectively; p¼0.6) progenitor sub-populations. Cryopreservation did not alter the cytokine content (HGF, VEGF, IGF-1, SDF-1 or IL-6) of CSC conditioned media or the ability of this media to promote angiogenesis and recruit resident stem cells. Early or late cryopreservation had negligible effects the ability of CSCs to adopt a cardiac fate (alpha smooth muscle actin, cardiac troponin and von Willebrand Factor) in conditions known to favor cardiogenesis. Transplantation of both fresh and cryopreserved CSCs into a mouse model 1 week after myocardial infarction improved echocardiographic left ventricular ejection fraction and myocardial scarring to a similar extent with equivalent effects on CSC engraftment and the generation of new cardiomyocytes. Finally, cryopreservation did not influence the ability of CSCs to undergo genetic reprogramming into inducible pluripotent stem cells. CONCLUSION: Cryopreservation and recovery of minced atrial or ventricular myocardial biopsies does not influence the cellular yield, phenotype, proliferative capacity of human CSCs. This innovation provides simple low cost means of storing cardiac samples for post-ischemic cardiac repair or inducible pluripotent stem cells based disease modeling. CIHR, HSF
253 IGF-1 ENGINEERED HUMAN CARDIAC STEM CELLS PROMOTE REPAIR OF ISCHEMIC MYOCARDIUM BY IMPROVING TRANSPLANT CELL SURVIVAL AND REDUCING MYOCARDIAL APOPTOSIS R Jackson, EL Tilokee, N Latham, B Ye, M Boodhwani, V Chan, M Ruel, EJ Suuronen, DJ Stewart, DR Davis Ottawa, Ontario