- Email: [email protected]
Canadian Society for Atherosclerosis, Thrombosis and Vascular Biology (CSATVB) CSATVB240 Poster: CSATVB Poster Session III Tuesday, October 26, 2010
Abstracts specific genetic studies among French Canadians seem particularly interesting. Nonetheless, environmental factors and genetic mixing might have contributed to the current observations. The still evolving case definition of CA dilatation prohibits appropriate counts and represents a significant burden from an epidemiological standpoint, but not that of the definition of CA aneurysms. Fondation En Coeur, fondation des enfants cardiaques du Québec
756
GENOTYPE ANALYSIS IN PATIENTS WITH ABSENT PULMONARY VALVE SYNDROME R Rauch, M Hofbeck, A Koch, A Rauch London, Ontario Microdeletion 22q11.2 deletion is the second most frequent genetic anomaly associated to congenital heart disease. It was found in a variety of cardiovascular malformations including pulmonary atresia, interrupted aortic arch, common arterial trunk and tetralogy of Fallot (TOF). Absent pulmonary valve (APV) is a distinct variant of TOF characterized by absent or rudimentary pulmonary valve cusps and massive dilation of the pulmonary arteries. We investigated, if 22q11.2 predisposes to APV, or if a causative mutation in TBX1 reported recently in a patient with APV (Rauch et al., 2009) is common in these patients. In APV the 22q11.2 deletion does appear to be of a considerable relevance and should be excluded in every patient. We recommend testing for TBX1 in familial occurrence of nonsyndromic TOF and APV in whom 22q11.2 deletion was excluded.
757
RESTRICTIVE PHYSIOLOGY AFTER TETRALOGY OF FALLOT REPAIR: NEW INSIGHTS FROM MAGNETIC RESONANCE IMAGING L Grosse-Wortmann, W Lee, A Redington, S Yoo Toronto, Ontario WITHDRAWN
Canadian Society for Atherosclerosis, Thrombosis and Vascular Biology (CSATVB) CSATVB240 Poster CSATVB POSTER SESSION III Tuesday, October 26, 2010 760
DIFFERENTIAL RESPONSES OF EARLY AND LATE ENDOTHELIAL PROGENITOR CELLS TO SCD40L L Bou Khzam, A Hachem, D Yacoub, JF Théorêt, M Tabrizian, WM Mourad, Y Merhi Montréal, Québec BACKGROUND: Endothelial progenitor cells (EPCs) play an emergent role in vascular repair, cell therapy and regenerative medicine. The recruitment of EPCs to sites of vascular lesions is facilitated by platelets, while EPCs bind and inhibit platelet activation and aggregation and thrombus formation. We have found that EPCs express CD40 and platelets constitute the main source of its soluble ligand CD40L (sCD40L). We hypothesized that the CD40/CD40L axis may be an important regulator of EPC differentiation and function. This study aims to investigate the effects and the signalling mechanisms involved in the responses of early and late EPCs to sCD40L stimulation. CONCLUSION: Early and late EPCs express CD40, but respond differently to sCD40L to produce MMP-9 and MMP-2, respectively. Such difference may be related to different patterns of TRAF expressions between early and late EPCs, which may regulate their responses to sCD40L stimulation, and therefore their functions in thrombosis and hemostasis during vascular repair. CIHR
Can J Cardiol Vol 26 Suppl D October 2010
761
DELAYED IMMUNE MEDIATED THROMBOCYTOPENIA AFTER RE-EXPOSURE TO ABCIXIMAB THERAPY M Rasti, M Blostein Montréal, Québec BACKGROUND: Abciximab is a potent antiplatelet agent that is increasingly being used to prevent ischemic complications of percutaneous coronary revascularization. Abciximab binds to the platelet glycoprotein IIb/IIIa receptor and inhibits platelet aggregation. Thrombocytopenia including acute profound thrombocytopenia has been reported to occur with Abciximab and it is thought to be an immune mediated reaction. Literature review provides limited information as to the timeframe over which this adverse reaction can occur, and indicates that it generally occurs within the first 24 hours of infusion but there have been reports of delayed severe thrombocytopenia associated with abciximab therapy that occurred after days. CONCLUSION: Although most cases of Acute and Delayed-onset Abciximab-induced thrombocytopenia have been reported after the first exposure to this medication, reexposure to this medication may induce the same picture even if the platelet count has been stable during previous administrations. A patient should be monitored after each exposure to this medication even if it was well tolerated previously and the delay could exceed over a week or more. CBC monitoring up to 2 weeks in every patient who receive Abciximab is an easy and safe way to minimize the risk of profound thrombocytopenia and its life threatening consequences. It should be considered in every patient who is exposed or reexposed to Abciximab even if there is no history of thrombocytopenia in previous exposures.
762
THROMBOEMBOLIC COMPLICATIONS IN INFECTIVE ENDOCARDITIS IN PEDIATRIC PATIENTS: A SINGLECENTRE EXPERIENCE KE Thom, P Sivaprakasam, JL Russell, S Williams, U Allen, LR Brandao Toronto, Ontario BACKGROUND: Despite the advances in pediatric care, infective endocarditis (IE) continues to be a condition associated with high morbidity in children. Contributing factors for IE-related morbidity include thromboembolic complications (TEC), such as acute ischemic stroke (AIS) and arterial/venous thrombotic events. This pediatric case series will describe patients diagnosed with IE and their respective TEC rate, attempting to identify potential TEC risk factors. CONCLUSION: The high incidence of TEC in children with confirmed IE described in this case series is consistent with the range previously published, indicating that there may be several risk factors for this complication. To date, the most commonly identified risk factor for IE is CHD but interestingly, neither CHD nor vegetations were predictive of TEC in this patient group. There continues to be limited information available on the use of antiplatelet and/or anticoagulants in this population. Prospective studies are needed to evaluate further risk factors and management of patients with IE.
763
INVESTIGATING THE ROLE OF GLYCOGEN SYNTHASE KINASE (GSK)-3 IN DIABETIC ATHEROSCLEROSIS C McAlpine, A Bowes, M Khan, Y Shi, G Werstuck Hamilton, Ontario BACKGROUND: Individuals with diabetes have a two to four times increased risk of developing cardiovascular disease (CVD) compared to individuals without diabetes. We do not currently understand the molecular mechanisms by which diabetes promotes the accelerated development and/or progression of atherosclerosis, the underlying cause of CVD. Our lab reported the presence of increased levels of endoplasmic reticulum (ER) stress within artery wall prior to lesion development. We hypothesize that ER stress promotes the activation of pro-atherogenic pathways though the activation of glycogen synthase kinase (GSK)-3. The goal of this project is to determine the role of GSK3α/β in diabetic atherosclerosis.
141D
Abstracts CONCLUSION: The observations that, i) accelerated atherosclerosis is associated with modulations inGSK3 status and, ii) that dietary supplementation with the GSK-3 inhibitor, valproate, attenuates atherosclerosis support a role for GSK3 in the development and/or progression of atherosclerosis. NSERC
764
HDL FACILITATES THE MIGRATION OF DENDRITIC CELLS Y Zhang, B Trigatti Hamilton, Ontario Dendritic cells (DC’s), primary antigen-presenting cells involved in inflammation and immune responses, have been found in atherosclerotic lesion. Whereas the role of DC’s in atherogenesis is beginning to be recognized, the influence of HDL on the biological behavior of DC’s has scarcely been investigated. To explore potential mechanisms for the antiatherosclerotic function of HDL, we examined the effects of HDL on the migration of human DC’s derived from THP-1 cells. Taken together, these results suggest that HDL may directly and indirectly facilitate the migration of DC’s, pointing to potential mechanisms that may contribute to HDL dependent atherosclerotic plaque regression and/or protection against atherosclerosis development.
765
CARBON MONOXIDE (CO) LIBERATED FROM CO-RELEASING MOLECULE (CORM) OFFERS PROTECTION AGAINST LPS-INDUCED ACTIVATION/DYSFUNCTION OF VASCULAR ENDOTHELIAL CELLS WHILE SUPPRESSING ACTIVITY OF SOD-1/-2 ENZYMES S Mizuguchi, A Capretta, DD Fraser, G Cepinskas London, Ontario Pleiotropic effects of CO are largely predisposed by its preferential binding to transition metals. Despite its reputation as a toxic gas, at low concentrations CO exerts remarkable beneficial effects. Our previous studies employing experimental model of sepsis indicate that protective effects of CO are at least in part associated to the ability of CO to modulate production of ROS in both, neutrophilic leukocytes (PMN) and vascular endothelial cells (HUVEC). Therefore, transition metal-containing anti-oxidant enzymes superoxide dismutases, SODs [cytosolic (Cu/Zn-SOD; SOD-1), mitochondrial (Mn-SOD; SOD-2) and extracellular (Cu/Zn-EC-SOD; SOD-3)] may be the potential cellular targets for CO-dependent regulation of oxidative stress. The findings of the present study indicate for the first time that CORM-3derived CO directly inhibits SOD-1 (Cu/Zn-SOD) and SOD-2 (Mn-SOD) activity and modulates the levels of cell surface-bound SOD-3 in vascular endothelial cells. Intriguingly, it appears that acute oxidative stress incurred by CORM-3-derived CO may be a necessary step in order to suppress subsequent inflammatory response in endothelial cells exposed to sepsis-relevant stimulus. In addition, these findings suggest that the ability of CO to interfere with molecule (e.g. SOD-3) binding to the cell surface may represent a novel mechanism of CO-dependent modulation of inflammatory response(s). HSFO-NA6171 and LHRI-IRF-025-09
766
POSTURAL CHANGE AND CEREBROVASCULAR HEMODYNAMICS IN OLDER MEN AND WOMEN AD Robertson, JM Thibert, RL Hughson Waterloo, Ontario BACKGROUND: Moving from a supine to an upright posture introduces an orthostatic stress, to which the cerebrovascular system must react to maintain sufficient blood supply to the brain. Age-related changes to arterial structure and function might influence the ability of the cardiovascular system, including blood vessels within the brain, to respond appropriately. The objective of this study was to examine dynamic and steady-state cerebrovascular hemodynamics in the elderly between supine, seated and standing postures. The potential impact of central arterial stiffening and
142D
impaired cerebral vasomotor reserve on cerebrovascular hemodynamics was examined. CONCLUSION: This study has demonstrated that, in the elderly, the upright posture imposes an orthostatic stress that threatens adequate perfusion of the brain. Notably, the transition from a supine to a seated posture is more challenging than from seated to standing. Although arterial stiffening and a reduced cerebral vasomotor reserve to CO2 do not appear to impact a person’s ability to maintain blood flow to the brain in upright postures, individuals with increased arterial stiffening, possibly indicative of accelerated vascular aging, might be more susceptible to transient drops in ABP during postural transitions. Canadian Institutes of Health Research
767
CYSTATIN C IMPROVES RISK STRATIFICATION AND PREDICTS LONG-TERM MORTALITY AFTER CORONARY ANGIOGRAPHY SC Pun, J Frohlich, JS Hill Vancouver, British Columbia BACKGROUND: Serum biomarkers are useful tools for identifying patients at risk of cardiovascular events or death. Cystatin C, a cysteine proteinase inhibitor produced and secreted by all nucleated cells, is a promising biomarker for the prediction of all-cause and cardiovascular mortality. We evaluated the prognostic value of cystatin C as a predictor of all-cause and cardiovascular mortality in a retrospective cohort of patients with known or suspected coronary artery disease. In addition, we evaluated whether cystatin C improved risk stratification for death from cardiovascular causes beyond traditional risk factors and high-sensitivity CRP. CONCLUSIONS: The mechanism by which increased serum cystatin C levels are associated with increased cardiovascular disease is not known. It is a sensitive marker of renal function and may identify increased risk of mortality and cardiovascular disease by providing a more accurate approximation of kidney function. Alternately, levels may be partially determined by other factors such as inflammation. Elevated cystatin C levels in subclinical renal disease may be the result of vascular inflammation, sclerosis and endothelial dysfunction, pathologic processes paralleled in coronary arteries and atherosclerosis. In summary, cystatin C levels predicted allcause and cardiovascular mortality in an angiographic cohort with a high burden of coronary artery disease. Furthermore, cystatin C improved risk stratification of individuals beyond models with traditional risk factors and CRP.
768
THE RELATIONSHIP BETWEEN STREET CONNECTIVITY AND OBESITY IN FOUR ETHNIC GROUPS AC Yew, SA Lear Vancouver, British Columbia BACKGROUND: The neighbourhood in which one lives has been implicated as a potential factor in the rapidly rising rates of obesity. Features within the built environment, such as the walkability of an area, have been found to contribute to lower body mass index (BMI). Higher intersection densities indicate smaller block sizes, providing evidence of better connected streets and a more walkable neighbourhood. The purpose of this study was to examine the relationship between BMI and street connectivity, measured as the number of intersections found within 1km of a participant’s residence along the surrounding road networks. CONCLUSION: Having a higher number of intersections near the household predicted a lower BMI in adults within the study. Using a road network buffer rather than a circular buffer enabled walkable areas to be captured, rather than potentially including areas which are inaccessible because of natural features or dead end roads. Differences in the number of intersections found amongst ethnic groups warrants further investigation into the influence of urban and rural settings. This research provides insight into one environmental feature that is related to lower obesity in adults. As obesity is recognized as a growing public health concern, identifying factors within the built environment that promote a healthy BMI may be one way to combat the rise in obesity from a public health perspective.
Can J Cardiol Vol 26 Suppl D October 2010
Abstracts
769
TNFα REDUCES COCHLEAR BLOOD FLOW VIA ENHANCED MICROVASCULAR S1P SIGNALING D Lidington, EQ Scherer, J Yang, M Canis, K Ivanov, CD Diehl, PH Backx, GW Wier, K Reimann, S Strieth, P Wangemann, J Voigtlaender-Bolz, SS Bolz Toronto, Ontario BACKGROUND: Antagonizing tumour necrosis factor alpha (TNFα) significantly improves auditory function in patients suffering sudden hearing loss (SHL), indicating a link between inflammation and inner ear dysfunction. The objective of this investigation is to demonstrate that TNFα, via sphingosine-1-phosphate (S1P) signaling, has the potential to alter cochlear blood flow and thus, cause ischemic hearing loss. CONCLUSION: TNFα indeed reduces cochlear blood flow via the activation of vascular S1P signaling. This integrates hearing loss into the family of ischemic microvascular pathologies, with implications for risk stratification, diagnosis and treatment. HSFO, CIHR, CFI, ORF, NIH
Canadian Society of Cardiac Surgeons (CSCS) CSCS360 Poster CSCS POSTER SESSION III Tuesday, October 26, 2010 772
GIANT-CELL ARTERITIS OF THE THORACIC AORTA: A YET “UNTAMED” DISEASE? D Kalavrouziotis, F Dagenais Québec, Québec BACKGROUND: The management of giant-cell arteritis (GCA) of the thoracic aorta remains controversial. We report our institutional experience of this entity and perform a qualitative literature review. CONCLUSION: Mid-term outcomes of patients following thoracic aortic surgery with histologically-proven GCA are acceptable and appear to be no worse than patients without GCA. However, no consensus exists regarding optimal management and follow-up of patients with thoracic aortic GCA. Better assessment of disease activity may identify patients at risk of disease progression and allow tailoring of steroid therapy.
773
MYECTOMY SURGERY REDUCES LA SIZE AND PREVENTS POSTOPERATIVE ATRIAL ARRHYTHMIAS IN PATIENTS WITH HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY (HOCM) RL Zur, CB Overgaard, AC Ralph-Edwards Toronto, Ontario The traditional indications for myectomy surgery for Hypertrophic Obstructive Cardiomyopathy (HOCM) include the presence of significant resting or provokable LVOT obstruction and concomitant mitral regurgitation, along with symptoms refractory to medical therapy. Over the past few years, novel indications for myectomy surgery have emerged, including the performance of ‘prophylactic’ myectomy to prevent the progression of left atrial (LA) enlargement and subsequent atrial arrhythmias. The clinical outcomes of patients referred for this indication are not known. This is the first study to examine the outcomes of patients with HOCM who underwent myectomy to prevent LA enlargement and future atrial arrhythmias as their primary surgical indication. Although the relative numbers of patients who underwent surgery for this indication was small (6%), this group experienced a significant reduction in LA size and subsequent arrhythmias with no major adverse postoperative clinical events. Myectomy with selective use of the MAZE procedure may be an effective strategy to prevent future morbidity in patients with HOCM who are minimally symptomatic but at higher risk for future arrhythmic events based on morphologic parameters.
Can J Cardiol Vol 26 Suppl D October 2010
774
SUPPURATIVE MEDIASTINITIS AFTER OPEN HEART SURGERY, LENGTH OF PRE-OPERATIVE HOSPITALIZATION: IS THIS AN INDEPENDENT RISK FACTOR? RK Chaturvedi, A Alam, B DeVarennes, P Goldberg, SL Sang, G Samoukovic, K Lachapelle Montréal, Québec BACKGROUND: Traditional risk factor for post sternotomy mediastinitis are age, chronic obstructive pulmonary disease (COPD), diabetes, and morbid obesity. As elective procedures decrease and more hospitalized patients are waiting for urgent cardiac procedures, the preoperative length of hospital stay (LOS) before surgery is increased significantly due to waiting period. The objective of this retrospective review was to examine the effect of LOS as a pre-operative predictor of post-operative mediastinitis. CONCLUSION: Apart from traditional risk factors like age, diabetes, COPD, obesity, the LOS prior to cardiac surgery was found to be an independent predictor for the development of mediastinitis. Length of preoperative hospital stay represents a modifiable risk factor which may impact nutritional or immune status. Results may help physicians for preoperative decision making.
775
A SIMPLE NON-INVASIVE METHOD TO PREDICT MITRAL VALVE GEOMETRICAL ORIFICE AREA FOLLOWING AN EDGE TO EDGE REPAIR E Gaillard Montréal, Québec BACKGROUND: The edge to edge repair (EtER) technique consists of anchoring the free edge of the diseased leaflet of the mitral valve to the corresponding edge of the opposing leaflet. When the middle sections of the leaflets are sutured, a “double-orifice” mitral valve is artificially created. The main consequence of this technique is that mitral valve geometric orifice area (MGOA) is sensibly reduced and a functional mitral stenosis might be created. The purpose of this study was to determine mathematically the MGOA with a simple non-invasive formula following an EtER. CONCLUSION: This study allowed us to introduce and validate a simple and non-invasive mathematical model to predict the resulting mitral geometric orifice area following an edge to edge repair. We have shown that, even if the “double-orifice” edge to edge repair technique seems to be an effective method to correct mitral regurgitation, the significant reduction of mitral valve area and so the occurrence of a mitral stenosis can become a problem for the patient. Finally, this simple mathematical model could be helpful for clinicians to determine the mitral valve area reduction after “double-orifice” EtER.
776
LONG-TERM SURVIVAL FOLLOWING AORTIC VALVE REPLACEMENT IN PROSTHESIS-PATIENT MISMATCH (PPM) CATEGORIES IN AGE GROUPINGS AND LEFT VENTRICULAR FUNCTION CATEGORIES REGARDLESS OF LACK OF PPM AS INDEPENDENT PREDICTOR J Higgins, WE Jamieson, J Ye, G Fradet, E Germann Vancouver, British Columbia BACKGROUND: PPM has been reported by the authors regardless of effective orifice area indexes (EOAI) to not be predictive of early,late and overall mortality. (Annals Thorac Surg 2010). The authors have also reported that within basal mass index (BMI) categories, those with normal EOAI had better long-term survival than those with severe PPM. (Can J Cardiol 2009). It was suggested that BMI associated with survival after AVR and PPM modifies the effect. CONCLUSION: Even though EOAI has no predictive effect on survival, whether early, late or overall the Kaplan-Meier survival curves do differ by EOAI categories. The reasons are related to complexity of patient populations in three categories especially category of severe prosthesis-patient mismatch for=60years and ejection fraction=50%.
143D
756
GENOTYPE ANALYSIS IN PATIENTS WITH ABSENT PULMONARY VALVE SYNDROME R Rauch, M Hofbeck, A Koch, A Rauch London, Ontario Microdeletion 22q11.2 deletion is the second most frequent genetic anomaly associated to congenital heart disease. It was found in a variety of cardiovascular malformations including pulmonary atresia, interrupted aortic arch, common arterial trunk and tetralogy of Fallot (TOF). Absent pulmonary valve (APV) is a distinct variant of TOF characterized by absent or rudimentary pulmonary valve cusps and massive dilation of the pulmonary arteries. We investigated, if 22q11.2 predisposes to APV, or if a causative mutation in TBX1 reported recently in a patient with APV (Rauch et al., 2009) is common in these patients. In APV the 22q11.2 deletion does appear to be of a considerable relevance and should be excluded in every patient. We recommend testing for TBX1 in familial occurrence of nonsyndromic TOF and APV in whom 22q11.2 deletion was excluded.
757
RESTRICTIVE PHYSIOLOGY AFTER TETRALOGY OF FALLOT REPAIR: NEW INSIGHTS FROM MAGNETIC RESONANCE IMAGING L Grosse-Wortmann, W Lee, A Redington, S Yoo Toronto, Ontario WITHDRAWN
Canadian Society for Atherosclerosis, Thrombosis and Vascular Biology (CSATVB) CSATVB240 Poster CSATVB POSTER SESSION III Tuesday, October 26, 2010 760
DIFFERENTIAL RESPONSES OF EARLY AND LATE ENDOTHELIAL PROGENITOR CELLS TO SCD40L L Bou Khzam, A Hachem, D Yacoub, JF Théorêt, M Tabrizian, WM Mourad, Y Merhi Montréal, Québec BACKGROUND: Endothelial progenitor cells (EPCs) play an emergent role in vascular repair, cell therapy and regenerative medicine. The recruitment of EPCs to sites of vascular lesions is facilitated by platelets, while EPCs bind and inhibit platelet activation and aggregation and thrombus formation. We have found that EPCs express CD40 and platelets constitute the main source of its soluble ligand CD40L (sCD40L). We hypothesized that the CD40/CD40L axis may be an important regulator of EPC differentiation and function. This study aims to investigate the effects and the signalling mechanisms involved in the responses of early and late EPCs to sCD40L stimulation. CONCLUSION: Early and late EPCs express CD40, but respond differently to sCD40L to produce MMP-9 and MMP-2, respectively. Such difference may be related to different patterns of TRAF expressions between early and late EPCs, which may regulate their responses to sCD40L stimulation, and therefore their functions in thrombosis and hemostasis during vascular repair. CIHR
Can J Cardiol Vol 26 Suppl D October 2010
761
DELAYED IMMUNE MEDIATED THROMBOCYTOPENIA AFTER RE-EXPOSURE TO ABCIXIMAB THERAPY M Rasti, M Blostein Montréal, Québec BACKGROUND: Abciximab is a potent antiplatelet agent that is increasingly being used to prevent ischemic complications of percutaneous coronary revascularization. Abciximab binds to the platelet glycoprotein IIb/IIIa receptor and inhibits platelet aggregation. Thrombocytopenia including acute profound thrombocytopenia has been reported to occur with Abciximab and it is thought to be an immune mediated reaction. Literature review provides limited information as to the timeframe over which this adverse reaction can occur, and indicates that it generally occurs within the first 24 hours of infusion but there have been reports of delayed severe thrombocytopenia associated with abciximab therapy that occurred after days. CONCLUSION: Although most cases of Acute and Delayed-onset Abciximab-induced thrombocytopenia have been reported after the first exposure to this medication, reexposure to this medication may induce the same picture even if the platelet count has been stable during previous administrations. A patient should be monitored after each exposure to this medication even if it was well tolerated previously and the delay could exceed over a week or more. CBC monitoring up to 2 weeks in every patient who receive Abciximab is an easy and safe way to minimize the risk of profound thrombocytopenia and its life threatening consequences. It should be considered in every patient who is exposed or reexposed to Abciximab even if there is no history of thrombocytopenia in previous exposures.
762
THROMBOEMBOLIC COMPLICATIONS IN INFECTIVE ENDOCARDITIS IN PEDIATRIC PATIENTS: A SINGLECENTRE EXPERIENCE KE Thom, P Sivaprakasam, JL Russell, S Williams, U Allen, LR Brandao Toronto, Ontario BACKGROUND: Despite the advances in pediatric care, infective endocarditis (IE) continues to be a condition associated with high morbidity in children. Contributing factors for IE-related morbidity include thromboembolic complications (TEC), such as acute ischemic stroke (AIS) and arterial/venous thrombotic events. This pediatric case series will describe patients diagnosed with IE and their respective TEC rate, attempting to identify potential TEC risk factors. CONCLUSION: The high incidence of TEC in children with confirmed IE described in this case series is consistent with the range previously published, indicating that there may be several risk factors for this complication. To date, the most commonly identified risk factor for IE is CHD but interestingly, neither CHD nor vegetations were predictive of TEC in this patient group. There continues to be limited information available on the use of antiplatelet and/or anticoagulants in this population. Prospective studies are needed to evaluate further risk factors and management of patients with IE.
763
INVESTIGATING THE ROLE OF GLYCOGEN SYNTHASE KINASE (GSK)-3 IN DIABETIC ATHEROSCLEROSIS C McAlpine, A Bowes, M Khan, Y Shi, G Werstuck Hamilton, Ontario BACKGROUND: Individuals with diabetes have a two to four times increased risk of developing cardiovascular disease (CVD) compared to individuals without diabetes. We do not currently understand the molecular mechanisms by which diabetes promotes the accelerated development and/or progression of atherosclerosis, the underlying cause of CVD. Our lab reported the presence of increased levels of endoplasmic reticulum (ER) stress within artery wall prior to lesion development. We hypothesize that ER stress promotes the activation of pro-atherogenic pathways though the activation of glycogen synthase kinase (GSK)-3. The goal of this project is to determine the role of GSK3α/β in diabetic atherosclerosis.
141D
Abstracts CONCLUSION: The observations that, i) accelerated atherosclerosis is associated with modulations inGSK3 status and, ii) that dietary supplementation with the GSK-3 inhibitor, valproate, attenuates atherosclerosis support a role for GSK3 in the development and/or progression of atherosclerosis. NSERC
764
HDL FACILITATES THE MIGRATION OF DENDRITIC CELLS Y Zhang, B Trigatti Hamilton, Ontario Dendritic cells (DC’s), primary antigen-presenting cells involved in inflammation and immune responses, have been found in atherosclerotic lesion. Whereas the role of DC’s in atherogenesis is beginning to be recognized, the influence of HDL on the biological behavior of DC’s has scarcely been investigated. To explore potential mechanisms for the antiatherosclerotic function of HDL, we examined the effects of HDL on the migration of human DC’s derived from THP-1 cells. Taken together, these results suggest that HDL may directly and indirectly facilitate the migration of DC’s, pointing to potential mechanisms that may contribute to HDL dependent atherosclerotic plaque regression and/or protection against atherosclerosis development.
765
CARBON MONOXIDE (CO) LIBERATED FROM CO-RELEASING MOLECULE (CORM) OFFERS PROTECTION AGAINST LPS-INDUCED ACTIVATION/DYSFUNCTION OF VASCULAR ENDOTHELIAL CELLS WHILE SUPPRESSING ACTIVITY OF SOD-1/-2 ENZYMES S Mizuguchi, A Capretta, DD Fraser, G Cepinskas London, Ontario Pleiotropic effects of CO are largely predisposed by its preferential binding to transition metals. Despite its reputation as a toxic gas, at low concentrations CO exerts remarkable beneficial effects. Our previous studies employing experimental model of sepsis indicate that protective effects of CO are at least in part associated to the ability of CO to modulate production of ROS in both, neutrophilic leukocytes (PMN) and vascular endothelial cells (HUVEC). Therefore, transition metal-containing anti-oxidant enzymes superoxide dismutases, SODs [cytosolic (Cu/Zn-SOD; SOD-1), mitochondrial (Mn-SOD; SOD-2) and extracellular (Cu/Zn-EC-SOD; SOD-3)] may be the potential cellular targets for CO-dependent regulation of oxidative stress. The findings of the present study indicate for the first time that CORM-3derived CO directly inhibits SOD-1 (Cu/Zn-SOD) and SOD-2 (Mn-SOD) activity and modulates the levels of cell surface-bound SOD-3 in vascular endothelial cells. Intriguingly, it appears that acute oxidative stress incurred by CORM-3-derived CO may be a necessary step in order to suppress subsequent inflammatory response in endothelial cells exposed to sepsis-relevant stimulus. In addition, these findings suggest that the ability of CO to interfere with molecule (e.g. SOD-3) binding to the cell surface may represent a novel mechanism of CO-dependent modulation of inflammatory response(s). HSFO-NA6171 and LHRI-IRF-025-09
766
POSTURAL CHANGE AND CEREBROVASCULAR HEMODYNAMICS IN OLDER MEN AND WOMEN AD Robertson, JM Thibert, RL Hughson Waterloo, Ontario BACKGROUND: Moving from a supine to an upright posture introduces an orthostatic stress, to which the cerebrovascular system must react to maintain sufficient blood supply to the brain. Age-related changes to arterial structure and function might influence the ability of the cardiovascular system, including blood vessels within the brain, to respond appropriately. The objective of this study was to examine dynamic and steady-state cerebrovascular hemodynamics in the elderly between supine, seated and standing postures. The potential impact of central arterial stiffening and
142D
impaired cerebral vasomotor reserve on cerebrovascular hemodynamics was examined. CONCLUSION: This study has demonstrated that, in the elderly, the upright posture imposes an orthostatic stress that threatens adequate perfusion of the brain. Notably, the transition from a supine to a seated posture is more challenging than from seated to standing. Although arterial stiffening and a reduced cerebral vasomotor reserve to CO2 do not appear to impact a person’s ability to maintain blood flow to the brain in upright postures, individuals with increased arterial stiffening, possibly indicative of accelerated vascular aging, might be more susceptible to transient drops in ABP during postural transitions. Canadian Institutes of Health Research
767
CYSTATIN C IMPROVES RISK STRATIFICATION AND PREDICTS LONG-TERM MORTALITY AFTER CORONARY ANGIOGRAPHY SC Pun, J Frohlich, JS Hill Vancouver, British Columbia BACKGROUND: Serum biomarkers are useful tools for identifying patients at risk of cardiovascular events or death. Cystatin C, a cysteine proteinase inhibitor produced and secreted by all nucleated cells, is a promising biomarker for the prediction of all-cause and cardiovascular mortality. We evaluated the prognostic value of cystatin C as a predictor of all-cause and cardiovascular mortality in a retrospective cohort of patients with known or suspected coronary artery disease. In addition, we evaluated whether cystatin C improved risk stratification for death from cardiovascular causes beyond traditional risk factors and high-sensitivity CRP. CONCLUSIONS: The mechanism by which increased serum cystatin C levels are associated with increased cardiovascular disease is not known. It is a sensitive marker of renal function and may identify increased risk of mortality and cardiovascular disease by providing a more accurate approximation of kidney function. Alternately, levels may be partially determined by other factors such as inflammation. Elevated cystatin C levels in subclinical renal disease may be the result of vascular inflammation, sclerosis and endothelial dysfunction, pathologic processes paralleled in coronary arteries and atherosclerosis. In summary, cystatin C levels predicted allcause and cardiovascular mortality in an angiographic cohort with a high burden of coronary artery disease. Furthermore, cystatin C improved risk stratification of individuals beyond models with traditional risk factors and CRP.
768
THE RELATIONSHIP BETWEEN STREET CONNECTIVITY AND OBESITY IN FOUR ETHNIC GROUPS AC Yew, SA Lear Vancouver, British Columbia BACKGROUND: The neighbourhood in which one lives has been implicated as a potential factor in the rapidly rising rates of obesity. Features within the built environment, such as the walkability of an area, have been found to contribute to lower body mass index (BMI). Higher intersection densities indicate smaller block sizes, providing evidence of better connected streets and a more walkable neighbourhood. The purpose of this study was to examine the relationship between BMI and street connectivity, measured as the number of intersections found within 1km of a participant’s residence along the surrounding road networks. CONCLUSION: Having a higher number of intersections near the household predicted a lower BMI in adults within the study. Using a road network buffer rather than a circular buffer enabled walkable areas to be captured, rather than potentially including areas which are inaccessible because of natural features or dead end roads. Differences in the number of intersections found amongst ethnic groups warrants further investigation into the influence of urban and rural settings. This research provides insight into one environmental feature that is related to lower obesity in adults. As obesity is recognized as a growing public health concern, identifying factors within the built environment that promote a healthy BMI may be one way to combat the rise in obesity from a public health perspective.
Can J Cardiol Vol 26 Suppl D October 2010
Abstracts
769
TNFα REDUCES COCHLEAR BLOOD FLOW VIA ENHANCED MICROVASCULAR S1P SIGNALING D Lidington, EQ Scherer, J Yang, M Canis, K Ivanov, CD Diehl, PH Backx, GW Wier, K Reimann, S Strieth, P Wangemann, J Voigtlaender-Bolz, SS Bolz Toronto, Ontario BACKGROUND: Antagonizing tumour necrosis factor alpha (TNFα) significantly improves auditory function in patients suffering sudden hearing loss (SHL), indicating a link between inflammation and inner ear dysfunction. The objective of this investigation is to demonstrate that TNFα, via sphingosine-1-phosphate (S1P) signaling, has the potential to alter cochlear blood flow and thus, cause ischemic hearing loss. CONCLUSION: TNFα indeed reduces cochlear blood flow via the activation of vascular S1P signaling. This integrates hearing loss into the family of ischemic microvascular pathologies, with implications for risk stratification, diagnosis and treatment. HSFO, CIHR, CFI, ORF, NIH
Canadian Society of Cardiac Surgeons (CSCS) CSCS360 Poster CSCS POSTER SESSION III Tuesday, October 26, 2010 772
GIANT-CELL ARTERITIS OF THE THORACIC AORTA: A YET “UNTAMED” DISEASE? D Kalavrouziotis, F Dagenais Québec, Québec BACKGROUND: The management of giant-cell arteritis (GCA) of the thoracic aorta remains controversial. We report our institutional experience of this entity and perform a qualitative literature review. CONCLUSION: Mid-term outcomes of patients following thoracic aortic surgery with histologically-proven GCA are acceptable and appear to be no worse than patients without GCA. However, no consensus exists regarding optimal management and follow-up of patients with thoracic aortic GCA. Better assessment of disease activity may identify patients at risk of disease progression and allow tailoring of steroid therapy.
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MYECTOMY SURGERY REDUCES LA SIZE AND PREVENTS POSTOPERATIVE ATRIAL ARRHYTHMIAS IN PATIENTS WITH HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY (HOCM) RL Zur, CB Overgaard, AC Ralph-Edwards Toronto, Ontario The traditional indications for myectomy surgery for Hypertrophic Obstructive Cardiomyopathy (HOCM) include the presence of significant resting or provokable LVOT obstruction and concomitant mitral regurgitation, along with symptoms refractory to medical therapy. Over the past few years, novel indications for myectomy surgery have emerged, including the performance of ‘prophylactic’ myectomy to prevent the progression of left atrial (LA) enlargement and subsequent atrial arrhythmias. The clinical outcomes of patients referred for this indication are not known. This is the first study to examine the outcomes of patients with HOCM who underwent myectomy to prevent LA enlargement and future atrial arrhythmias as their primary surgical indication. Although the relative numbers of patients who underwent surgery for this indication was small (6%), this group experienced a significant reduction in LA size and subsequent arrhythmias with no major adverse postoperative clinical events. Myectomy with selective use of the MAZE procedure may be an effective strategy to prevent future morbidity in patients with HOCM who are minimally symptomatic but at higher risk for future arrhythmic events based on morphologic parameters.
Can J Cardiol Vol 26 Suppl D October 2010
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SUPPURATIVE MEDIASTINITIS AFTER OPEN HEART SURGERY, LENGTH OF PRE-OPERATIVE HOSPITALIZATION: IS THIS AN INDEPENDENT RISK FACTOR? RK Chaturvedi, A Alam, B DeVarennes, P Goldberg, SL Sang, G Samoukovic, K Lachapelle Montréal, Québec BACKGROUND: Traditional risk factor for post sternotomy mediastinitis are age, chronic obstructive pulmonary disease (COPD), diabetes, and morbid obesity. As elective procedures decrease and more hospitalized patients are waiting for urgent cardiac procedures, the preoperative length of hospital stay (LOS) before surgery is increased significantly due to waiting period. The objective of this retrospective review was to examine the effect of LOS as a pre-operative predictor of post-operative mediastinitis. CONCLUSION: Apart from traditional risk factors like age, diabetes, COPD, obesity, the LOS prior to cardiac surgery was found to be an independent predictor for the development of mediastinitis. Length of preoperative hospital stay represents a modifiable risk factor which may impact nutritional or immune status. Results may help physicians for preoperative decision making.
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A SIMPLE NON-INVASIVE METHOD TO PREDICT MITRAL VALVE GEOMETRICAL ORIFICE AREA FOLLOWING AN EDGE TO EDGE REPAIR E Gaillard Montréal, Québec BACKGROUND: The edge to edge repair (EtER) technique consists of anchoring the free edge of the diseased leaflet of the mitral valve to the corresponding edge of the opposing leaflet. When the middle sections of the leaflets are sutured, a “double-orifice” mitral valve is artificially created. The main consequence of this technique is that mitral valve geometric orifice area (MGOA) is sensibly reduced and a functional mitral stenosis might be created. The purpose of this study was to determine mathematically the MGOA with a simple non-invasive formula following an EtER. CONCLUSION: This study allowed us to introduce and validate a simple and non-invasive mathematical model to predict the resulting mitral geometric orifice area following an edge to edge repair. We have shown that, even if the “double-orifice” edge to edge repair technique seems to be an effective method to correct mitral regurgitation, the significant reduction of mitral valve area and so the occurrence of a mitral stenosis can become a problem for the patient. Finally, this simple mathematical model could be helpful for clinicians to determine the mitral valve area reduction after “double-orifice” EtER.
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LONG-TERM SURVIVAL FOLLOWING AORTIC VALVE REPLACEMENT IN PROSTHESIS-PATIENT MISMATCH (PPM) CATEGORIES IN AGE GROUPINGS AND LEFT VENTRICULAR FUNCTION CATEGORIES REGARDLESS OF LACK OF PPM AS INDEPENDENT PREDICTOR J Higgins, WE Jamieson, J Ye, G Fradet, E Germann Vancouver, British Columbia BACKGROUND: PPM has been reported by the authors regardless of effective orifice area indexes (EOAI) to not be predictive of early,late and overall mortality. (Annals Thorac Surg 2010). The authors have also reported that within basal mass index (BMI) categories, those with normal EOAI had better long-term survival than those with severe PPM. (Can J Cardiol 2009). It was suggested that BMI associated with survival after AVR and PPM modifies the effect. CONCLUSION: Even though EOAI has no predictive effect on survival, whether early, late or overall the Kaplan-Meier survival curves do differ by EOAI categories. The reasons are related to complexity of patient populations in three categories especially category of severe prosthesis-patient mismatch for=60years and ejection fraction=50%.
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