Canadian Pediatric Cardiology Association (CPCA) CPCA275 poster: Pediatric and Congenital Tuesday, October 26, 2010

Canadian Pediatric Cardiology Association (CPCA) CPCA275 poster: Pediatric and Congenital Tuesday, October 26, 2010

Abstracts Canadian Pediatric Cardiology Association (CPCA) CPCA275 Poster PEDIATRIC AND CONGENITAL Tuesday, October 26, 2010 this study was to evalu...

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Abstracts

Canadian Pediatric Cardiology Association (CPCA) CPCA275 Poster PEDIATRIC AND CONGENITAL Tuesday, October 26, 2010

this study was to evaluate the long-term clinical and functional evolution of ischemic sequelae in patients with ALCAPA. Surviving patients with surgically corrected ALCAPA normalised SF at 1 year, normalised ST segment at 10 years but mitral regurgitation persisted in all patients at the last follow-up. The treadmill of all patients was normal and the long-term functional status was excellent.

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N Dahdah, A Fournier, C Houde Montréal, Québec BACKGROUND: The long term sequelae of Kawasaki disease (KD) are typically based on the coronary complications. Attempts to detect peripheral endothelial dysfunction remain controversial. Other reports suggesting an increase of the intima media thickness in the carotid arteries also tried to mimic atherosclerotic pathophysiology concepts. Instead of extrapolating from the atherosclerosis hypothesis, we based our hypothesis on the fact that KD causes a generalized vasculitis, with documented aneurisms in the femoral, iliac, renal, axillary and brachial arteries. The aim of this work was to study the aortic biophysical properties (ABP) following KD attempting to study the integrative systemic arterial vasculature. CONCLUSION: Our study identified significant alteration of multiple ABP parameters in a cohort of KD patients with coronary artery sequelae. The findings reflect increased strain, stiffness and vascular impedance. This implies that despite an apparent resolution of the systemic vaculitis, the acute impact of the disease persists years after contracting KD. Unlike the intima media thickness of the carotid arteries and the brachial flow mediated response studies this non-invasive assessment of the systemic vasculature biophysical properties represents the integrated and complex function of the systemic arterial tree. Future directions towards arterial multilevel and multilayer scarring, renal vascular interaction, and vascular autonomous dysregulation need to be studies thoroughly. Reseau Mère Enfant de la Francophonie

A McNeal-Davidson, N Dahdah, A Fournier, R Scuccimarri, AB Dancea, C Houde, M Bellavance Montréal, Québec The prevalence of coronary artery (CA) involvement in untreated cases of Kawasaki disease (KD) is approximately 15-25%, which decreases to less than 5% when IVIG is administered within 10 days of onset of fever. The rate of CA aneurysm regression has been shown to be mostly related to their initial size, giant aneurysms = 8mm (GA) rarely regress and exhibit the highest risk of subsequent stenosis. We therefore sought to determine the outcomes related to GA in the province of Québec, as there is little population-based long-term data available for the Canadian population. KD-related GA occurred in nearly 2% of patients of this retrospective analysis. It seems to affect Québec residents proportionally to its ethnic make-up, without specific predilection to Asians. The current management of GA is based on institutional preferences due to the absence of evidence-based recommendations. These initial Québec-based observations warrant a larger national collaborative study. Partially funded by Fondation En Coeur, Fondation des enfants cardiaques du Québec

THE BIOPHYSICAL PROPERTIES OF THE AORTA ARE ALTERED FOLLOWING KAWASAKI DISEASE WITH SEVERE CORONARY ARTERY LESIONS

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ECHO-DOPPLER ASSESSMENT OF THE BIOPHYSICAL PROPERTIES OF THE AORTA IN CHILDREN WITH CHRONIC KIDNEY DISEASE M Alghamdi, AM De Souza, TM Potts, C White, JE Potts, GG Sandor Vancouver, British Columbia BACKGROUND: To study the biophysical properties of the thoracic aorta in children with chronic kidney disease (CKD) using a non-invasive Echo-Doppler technique. CONCLUSION: The increased Zi and Zc in pediatric CKD patients indicate intravascular changes resulting in a higher pulsatile ejection load for the left ventricle. The increased arterial stiffness indexes may be secondary to increased blood pressure. However, the normal PWV suggests that central arterial changes have not occurred yet. Further studies may elucidate the factors responsible for these vascular changes and methods of prevention of permanent vascular disease reported in the late stages of CKD.

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CLINICAL AND FUNCTIONAL EVOLUTION OF ISCHEMIC SEQUELAE IN PATIENTS WITH ABNORMAL LEFT CORONARY ARTERY ORIGINATING FROM THE PULMONARY ARTERY (ALCAPA) M Desjardins, M Bourdages, P Chetaille, F Dallaire, G Delisle, C Houde, J Perron, J Côté Québec, Québec ALCAPA is a rare congenital malformation usually with dramatic manifestations if unrecognised and untreated surgically. In the early post-operative period, ischemic sequelae including left ventricular dysfunction, mitral regurgitation and fibroelastosis persist despite a good repair. The purpose of

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THE FATE AND CURRENT MANAGEMENT OF GIANT CORONARY ARTERY ANEURYSMS SECONDARY TO KAWASAKI DISEASE IN THE PROVINCE OF QUEBEC

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ASSOCIATION BETWEEN SLEEP AND CARDIOVASCULAR RISK FACTORS IN ADOLESCENTS C Manlhiot, M Shalabi, SW Dobbin, D Gisbon, N Chahal, H Wong, K Stearne, O Makerewich, A Fisher, J Davies, BW McCrindle Toronto, Ontario Emerging data in adult patients have shown that there is an association between lower quantity and quality of sleep and increased cardiovascular risk. A similar association in adolescents has not yet been reported. In adolescents, sleep duration and disturbances are associated with increased cardiovascular risk and adipostiy in cross-sectional assessment. The underlying mechanisms and causality of the associations necessitate further study.

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INCREMENTAL UTILITY OF USING WAIST CIRCUMFERENCE IN ADDITION TO BODY MASS INDEX WHEN EVALUATING THE ASSOCIATION BETWEEN ADIPOSITY AND CARDIOVASCULAR RISK IN ADOLESCENTS M Khoury, C Manlhiot, SW Dobbin, D Gisbon, N Chahal, H Wong, K Stearne, O Makerewich, A Fisher, J Shaw, BW McCrindle Toronto, Ontario Previous studies have shown a clear link between increased adiposity and cardiovascular risk in children and adolescents. Although body mass index (BMI) is used in most studies, controversy remains as to what populationbased measures of adiposity best correlate with cardiovascular risk. We sought to investigate whether adding the measurement of waist circumference to BMI improves specification of the association between adiposity and cardiovascular risk. The addition of waist circumference to BMI assessment in adolescents improves stratification of cardiovascular risk and should be a component of evaluations and counseling.

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Abstracts

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C Drolet, S Yoo, A Redington, L Grosse-Wortmann Toronto, Ontario BACKGROUND: Chronic pulmonary regurgitation (PR) after Tetralogy of Fallot (TOF) repair is associated with cardiomegaly and adverse outcomes. In clinical practice the left pulmonary artery (LPA) contributes more than the right (RPA) to total pulmonary regurgitation. Multiple mechanisms are speculated to influence the degree of differential PR but evidence-based data is lacking. We aimed to identify factors that determine the differences in magnitude of flow reversal from the LPA and RPA, using magnetic resonance imaging (MRI). CONCLUSION: Sternotomy for Tetralogy of Fallot repair and chronic RV dilatation lead to an altered configuration of the ribs and sternum as well as to a changed mediastinal geometry with increased cardiac angle. These changes result in decreased left lung volume, and presumably, increased vascular resistance. This does not affect systolic flow, but leads to increased diastolic flow reversal in the LPA and consequently increases the regurgitant fraction and volume. Increased PR leads to worsening right ventricular dilatation, contributing to further deterioration and imbalance of pulmonary perfusion.

L Tan, M Belanger, C Wittnich Toronto, Ontario Approximately, 5% of newborn infants need ventilator stimulation after birth, 20% of which require more extensive ventilator support. Typically, inspired air is composed of 21% O2, however using O2 levels of 100% during newborn resuscitation is routine practice. Exposing newborns to 100% O2, introduces a condition known as hyperoxia. A recent clinical study demonstrated gender-specific differences in the beneficial effects produced by avoiding hyperoxia. It is known that hyperoxia in newborn males results in hemodynamic impairment. However, these changes have yet to be established in females. Therefore, we investigated gender-specific hemodynamic differences in a newborn’s response to hyperoxia. This study demonstrates that sex-related differences exist even in the newborn’s hemodynamic responses to hyperoxia. Specifically, newborn females, when compared to males, showed an exaggerated hemodynamic response with earlier and greater reductions in SBP, DBP, MAP, and greater increases in heart rate. These observations suggest there is a sex-related difference in hemodynamic response to hyperoxia, which must be taken into account in newborn resuscitation strategies. Heart and Stroke Foundation

DETERMINANTS OF PULMONARY REGURGITATION AFTER TETRALOGY OF FALLOT REPAIR

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NEW AUDITORY TRAINING PROGRAM RAPIDLY TEACHES STUDENTS TO DISTINGUISH INNOCENT AND PATHOLOGICAL MURMURS WITH 90% ACCURACY J Finley, P Nicol, R Caissie, A Newman, B Hoyt, D MacAulay Halifax, Nova Scotia BACKGROUND: Recognition of normal and abnormal heart sounds and murmurs is of key importance in detecting heart disease in children and adults as well as avoiding unnecessary investigations and anxiety. Many reports have shown that heart auscultation is poorly performed by physicians and physicians in training. Current teaching methods are often archaic, lack clear objectives and not informed by modern neuropsychological understanding of sound recognition. Repetition is crucial to auditory recognition but many teaching programs emphasize a variety of murmurs and sounds rather than repetition of a few common examples, normal and abnormal. New approaches for teaching auscultation are needed. CONCLUSION: This new auditory training program rapidly teaches students to distinguish innocent and pathological murmurs with 90% accuracy. Medical education is not necessary for success with the program. Reinforcement teaching will likely be important. Results to be updated to meeting date.

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ECHO DOPPLER ASSESSMENT OF VASCULAR FUNCTION IN POST-OPERATIVE CONGENITAL HEART DISEASE Y Mivelaz, MT Potts, AM De Souza, JE Potts, GG Sandor Vancouver, British Columbia BACKGROUND: Most children with congenital heart disease (CHD) now survive until adulthood with a good quality of life. In some forms of CHD the aorta may be large and abnormal which has implications for future cardiovascular risk. Therefore, we sought to assess the biophysical properties of the aorta of children with 3 types of CHD: tetralogy of Fallot (TOF); coarctation of the aorta (COA); and transposition of great arteries (TGA). CONCLUSION: Children with certain forms of CHD have impaired biophysical properties of the aorta, with increased PWV, impedance and stiffness. This predisposes them to early-onset cardiovascular events such as elevated blood pressure and ischemic events. Further studies are needed to determine if improvements in surgical techniques and post-surgical therapy can modify the biophysical properties of the aorta. Fondazione Ettore e Valeria Rossi

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NEWBORN FEMALE HEMODYNAMIC DISADVANTAGE IN RESPONSE TO HYPEROXIA

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SERUM ALBUMIN LEVEL Z-SCORE IS ASSOCIATED WITH CORONARY ARTERY ABNORMALITIES IN PATIENTS WITH ACUTE KAWASAKI DISEASE AA Abadilla, A Waheeb, C Manlhiot, N Chahal, RS Yeung, BW McCrindle Toronto, Ontario Absolute serum albumin level is one of the few universally recognized risk factors for coronary artery abnormalities after Kawasaki disease (KD). There is a high correlation between serum albumin level and age at diagnosis, but there is a paucity of information on normal values in healthy children. Current risk stratification for patients with KD is based on absolute blood albumin level; based on this study it is possible that risk stratification be improved by using albumin z-score rather than absolute values. This would be contingent on obtaining age-appropriate normal values for blood albumin level in this population.

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OUTCOMES OF OBSTRUCTIVE PEDIATRIC PRIMARY CARDIAC TUMOURS: A 20-YEAR SINGLE CENTRE REVIEW M Mendelson, N Ahmad, C Manlhiot, BW McCrindle, E Jaeggi, L Nield Toronto, Ontario BACKGROUND: Primary cardiac tumours in the pediatric age group are rare and often benign; however, intervention is sometimes necessary for those causing hemodynamically significant obstruction. Observation is recommended for obstructive cardiac tumours without clinical instability and with the potential for regression. As the sensitivity of both fetal and postnatal echocardiography has improved, tumours have been identified more frequently and with various degrees of subclinical obstruction. The safety and long-term outcomes from the contemporary conservative management for asymptomatic obstructive tumours has not been well evaluated. CONCLUSION: Our data suggest that children with intracardiac tumours with echocardiographic features of obstruction but without clinical symptoms can be safely observed. However, close follow-up is indicated as 2 out of 9 patients managed conservatively in our study had issues related to their aortic valve after regression of the left ventricular outflow tract tumours. We did not observe a rising trend in the detection of cardiac tumours or subclinical obstruction during our study period.

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GENETIC DISSECTION OF PATENT DUCTUS ARTERIOSUS AND COARCTATION OF THE AORTA: ANALYSIS OF A RECESSIVE FAMILY SHOWS A DIGENIC MODEL OF INHERITANCE N Tremblay, M Brousseau, K Riopel, G Andelfinger Montréal, Québec BACKGROUND: Persistant ductus arteriosus (PDA) and coarctation of the aorta (CoA) are two frequent forms of congenital heart disease which sometimes co-occur. A genetic basis for these diseases has been suspected based on several reports of familial recurrence. We recently enrolled an extended family with PDA and CoA. The presence of five inbreeding loops with 5 affecteds in consanguineous marriages strongly suggested autosomal recessive inheritance. CONCLUSION: We report the first recessive family with PDA/CoA which is amenable to genetic mapping. Our results show significant linkage of PDA/CoA to chromosome 9 and 16. To our knowledge, this is the first digenic model of inheritance for a congenital heart disease. Since homozygosity at a single locus is insufficient for the development of disease, epistasis at two loci is required for full disease penetrance.

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UNDER-DOSING OF CALCIUM CHANNEL BLOCKERS IN OBESE CHILDREN WITH RENAL DISEASES F Jamali, S Hanafy, M Pinsk Edmonton, Alberta BACKGROUND: Pediatric patients with renal disease have an increased propensity to hypertension. Calcium channel blockers (CCBs) and angiotensin interruption agents (ANGI, angiotensin converting enzyme inhibitors or angiotensin II receptor blockers) are the most commonly prescribed drugs to treat hypertension in children with renal disease. Dosage recommendations for these agents are the same for obese and non-obese children. Obesity has been found to be associated with increased concentration of inflammatory mediators. We studied the effect of obesity on the pharmacodynamic response to CCBs, ANGI or combination of the two in pediatric patients. CONCLUSION: Reduce response to calcium channel blockers observed in obesity is similar to those reported for rheumatoid arthritis and Crohn’s disease. Current dosing recommendations of CCBs need to be reconsidered in obese children with renal diseases. CIHR, CFI

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ACTIVE HEALTHY LIFESTYLES FOR YOUNG CHILDREN: PROMOTING “HOW” NOT “WHAT” PE Longmuir, BW McCrindle Toronto, Ontario BACKGROUND: Efforts to encourage healthy eating and physical activity have intensified as the epidemic of childhood obesity has moved into the mainstream media. Despite a decade of interventions, the proportion of overweight, obesity, and diabetes among youth continues to increase. A survey of child health policy makers indicates that research clearly documents the problem, but that data demonstrating the effectiveness of community-based interventions are lacking. The goal of this project was to design the ideal community for enabling young children, up to 8 years of age, to adopt a healthy lifestyle of nutritious food and daily physical activity. CONCLUSION: Parents and caregivers of young children seek policy changes, implementation strategies and community-based opportunities to achieve healthy, active lifestyles for their children. Educational campaigns focused on “what” should be done lead more often to guilt and frustration, than desired behaviour change. The use of a grounded-theory influenced approach produced a health promotion campaign that differed significantly from traditional strategies. Ministry of Health Promotion Healthy Communities Fund

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IMPROVEMENTS IN THE SCREENING OF CONGENITAL HEART DISEASES: A 28-YEAR RETROSPECTIVE STUDY Y Mivelaz, KI Lim, WJ Duncan, F Tessier, BG Sinclair, DF Farquharson, AJ Barlow, C Mayer, AM Skoll, JE Potts, GG Sandor Vancouver, British Columbia BACKGROUND: Congenital heart disease (CHD) is the most common congenital anomaly (approximately 800/100,000 pregnancies). Progress in the resolution of the echocardiography machines and in the training and experience of cardiologists, radiologists and perinatologists who perform primary and secondary ultrasound screening has allowed for improvement in the detection of CHD. The purpose of this study was to assess the change in the detection rate of duct-dependent and/or complex CHD in British Columbia. CONCLUSION: Prenatal detection of CHD increased about 50-fold during the past 28 years, reflecting major improvements in technology, knowledge, experience and training of primary and secondary ultrasound screening centres. The CONO group showed the greatest rate of diagnostic improvement. This is probably the result of the more common use of outflow tracts and 3-vessel views as part of the screening protocols. Continuous training, additional cardiac views and new modalities such as 3D ultrasound should be explored in order to achieve improved screening of CHD. Fondazione Ettore e Valeria Rossi

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OUTCOMES OF CHILDREN AND ADULTS WITH CONGENITAL HEART DISEASE WHO WERE PREVIOUSLY LOST TO FOLLOW-UP AS Mackie, KN Rankin Edmonton, Alberta BACKGROUND: Published guidelines recommend cardiology follow-up of patients with moderate or complex congenital heart disease (CHD) throughout life. However, loss to follow-up is a problem among both children and adults with CHD. Failure to receive continuity of care predisposes patients to delayed recognition of new or evolving cardiac problems, which in turn may complicate subsequent patient management and predispose to life-threatening complications. Our objective was to describe morbidity and cardiac findings at the time of the return cardiology clinic appointment among children and adults who were previously lost to follow-up. CONCLUSION: Greater than one third of individuals with moderate or complex CHD that had been lost to follow-up for > 3 years had hemodynamically significant cardiac problems at the time they were first seen following this lapse in care. The proportion of controls having residual hemodynamic problems was similar to cases, and reflects the high burden of late cardiac morbidity experienced by this patient population. Increased efforts are required to prevent children and adults with moderate or complex CHD from becoming lost to cardiology follow-up.

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THE QUEBEC KAWASAKI DISEASE REGISTRY (QKDR) FROM THE FIRST KNOWN CASE UNTIL 2008 N Dahdah, A Fournier, R Scuccimarri, C Houde, M Bellavance Montréal, Québec BACKGROUND: The first case report of Kawasaki disease (KD) from the province of Québec occurred in 1979. Many genetically determined illnesses exhibit higher incidence among Québecers compared to other Canadian communities, and KD seems to follow the pattern. It is estimated that around 2600 French settlers among the initial 8500 newcomers are the founding generation of the vast majority (6 Million) of the current Québec dwellers. We sought to study the epidemiology of KD in Québec since the 1970’s until 2008. This collaborative retrospective study was set forth by the QKDR. CONCLUSION: Although the mix of the current Québec population is not particularly high in Asians the incidence of KD rates among the highest in North America. It approaches that of Toronto Metropolitan area where the Asian community is particularly high and at risk. Population

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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

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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.

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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

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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.

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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.

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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.

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