- Email: [email protected]
COMPUTATIONAL FLUID DYNAMICS MODELS OF HEALTHY AND FAILING FONTAN CIRCULATIONS
Abstracts RESULTS:
There were 48 males (82.8%) with a median age at surgery of 11.3 years (0.04 - 17.9). Indications for surgery were stenosis in 32 (55.2%), regurgitation in 13 (22.4%) and mixed aortic valve disease in 13 (22.4%) patients. Survival at 10 and 25 years was 96.2% and 93.9%, respectively. There was one (1.7%) hospital death and two (3.4%) late deaths. Freedom from pulmonary autograftrelated reintervention (the aortic root prosthesis) was 93.9% and 69.7% at 10 and 25 years, respectively. Eleven patients underwent reoperations on the autograft at a median followup of 16.1 years. Aortic valve-sparing surgery was performed in 6 patients and a Bentall procedure in 4 patients (3 mechanical, 1 homograft). Over the study period, twice as many patients (34.5%) required pulmonary homograftrelated (right ventricular outflow tract) reintervention (10 transcatheter, 10 surgical conduit replacement). Freedom from homograft-related reintervention was 73% and 50.4% at 10 and 25 years, respectively. CONCLUSION: The Ross procedure is associated with excellent long term survival. Late reintervention for the homograft was more common than for the pulmonary autograft in our cohort.
578 INFLAMMATORY AND HEMOSTATIC RESPONSE TO CARDIAC SURGERY WITH CARDIOPULMONARY BYPASS IN CHILDREN: IMPACT OF INTRAOPERATIVE MANAGEMENT
S307
cytokines (EST: -0.016 (-0.023; -0.009) nat.log pg/ml IL-10 per mg/kg of steroids, p<0.001). Elevation of plateletderived microparticles was highest in patients with low sensitivity to heparin (EST: +1.6 (+0.5; +2.6) nat.log x10E6 microparticle/ml per 100U/kg predicted heparin requirement, p¼0.004) and in those receiving a greater volume of allogeneic platelet transfusions (EST: +0.19 (+0.12; +0.25) nat.log x10E6 microparticle/ml per 10 ml/kg, p¼0.004). Markers of thrombin generation were highest for patients receiving more allogeneic blood product transfusions, patients with low heparin sensitivity and those with lower antifactor Xa activity measured at the end of CPB. Finally, a network analysis recapitulating the associations between the various physiological markers outlined a strong association between the different markers of inflammation and thrombin generation, with multiple cross-associations. The link between inflammation and thrombin generation was primarily potentiated by the association of IL-6 and IL-8 with prothrombin fragment 1.2. Anticoagulation activity, as measured by anti-factor Xa activity, was a critical suppressor of the cross-talk between inflammation and thrombosis (Figure). CONCLUSION: CPB in children is associated with severe hemodilution, release of inflammatory cytokines, leukocyte and platelet activation and thrombin generation. Modifiable risk factors associated with the magnitude of these changes might be targets for the development of future protective strategies in this vulnerable population.
C Manlhiot, CE Gruenwald, HM Holtby, ML Rand, L Stenyk, K Westcott, AK Chan, GS Van Arsdell, CA Caldarone, SM Schwartz, V Sivarajan, BW McCrindle Toronto, Ontario BACKGROUND:
Cardiac surgery with cardiopulmonary bypass (CPB) is associated with a severe and potentially damaging physiological reaction primarily affecting inflammation and hemostasis. The extent of this physiological reaction and associated factors have not been determined in children with heart disease undergoing cardiac operations. METHODS: A total of 248 pediatric patients undergoing cardiac surgery were included in an observational study. RESULTS: CPB initiation was associated with severe hemodilution in all patients, with decreases of 39%, 56% and 45% in hemoglobin, platelet count and antithrombin, respectively. It was most severe in the youngest patients and those undergoing more complex operations. Inflammatory cytokines were universally affected by CPB, as were levels of leukocytes-derived and platelet-derived microparticles. CPB was associated with a significant increase in prothrombin fragment 1.2, thrombin-antithrombin complex and Ddimer levels in the blood. Release of inflammatory cytokines was highest for patients with low sensitivity to heparin (EST: +0.50 (+0.15; +0.86) nat.log pg/ml IL-10 and EST: +0.39 (+0.12; +0.67) nat.log pg/ml IL-6 per 100U/kg predicted heparin requirement, p¼0.006). Patients receiving steroids preoperatively experienced smaller increases in inflammatory
Canadian Institutes of Health Research
579 COMPUTATIONAL FLUID DYNAMICS MODELS OF HEALTHY AND FAILING FONTAN CIRCULATIONS MG Doyle, F Alvarado, W Zhang, O Honjo, H Ide, RD Weisel, LW Tse, CH Amon Toronto, Ontario
S308 BACKGROUND:
Failing Fontan circulation is a clinical diagnosis and can be characterized by elevated Fontan pressures and reduced cardiac output. For many of these patients, heart transplant is the only viable treatment option, and there are currently no minimally invasive medical devices available to bridge these patients to transplant. The goal of our study is to design, build, and test such a device. As a first step in the design process, we have developed representative computational models of blood flow in the total cavopulmonary connection (TCPC) in both healthy and failing Fontan cases, which are described in this abstract. METHODS: Measurements made from angiograms of paediatric Fontan patients were used to develop an average three-dimensional computational model of the TCPC. Computational fluid dynamics simulations were performed in ANSYS Fluent (ANSYS, Inc., Canonsburg, PA, USA) for both healthy and failing Fontan circulations. Representative boundary conditions were defined for our model at the superior vena cava and extracardiac conduit (inlets) and the left and right pulmonary arteries (outlets) based on data from our patient cohort. At the inlets, we specified flow rates based on cardiac outputs of 1.8 L/min for the healthy case and 0.94 L/min for the failing case and a 65%/35% flow split between the extracardiac conduit and the superior vena cava. At the outlets, we specified pressures of 11 mm Hg for the healthy case and 18 mm Hg for the failing case. RESULTS: Results for healthy and failing Fontan circulations are presented in Figure 1 as streamlines of the blood flow through the TCPC. As expected, the velocities were higher in the healthy case than in the failing case, and the pressures (not shown) were lower in the healthy case than in the failing case. CONCLUSION: We have successfully developed a computational model to predict the blood flow in the TCPC for both healthy and failing Fontan circulations. Our calculated pressures and flow rates were consistent with expected values and fit within relevant physiological ranges. These models are a first step in the design process to develop a medical device for short-term minimally-invasive treatment for failing Fontan circulation as a bridge to heart transplant.
Canadian Journal of Cardiology Volume 31 2015
580 ADULTS WITH REPAIRED COARCTATION: REFINING THE NEED FOR MRI IMAGING V Pinphanichakarn, T Sehgal, S Islam, J Windram, AS Mackie, IF Vonder Muhll Edmonton, Alberta BACKGROUND:
Guidelines for the management of adult congenital heart disease recommend evaluation of patients with repaired coarctation (rCoA) by MRI or CT at least once in adulthood and repeated at intervals of 5 years or less. The incidence of pathology identified by this approach is uncertain. In an era of rationalization of healthcare costs, it is desirable to identify a low-risk subset of patients that may not require advanced tomographic imaging. Our objective was to determine the yield of MRI in detecting recoarctation or aneurysm in rCoA. We hypothesized that clinical assessment could identify patients at high risk for recoarctation or aneurysm, and conversely that prediction rules could be developed to identify those at low risk of complications. METHOD: We performed a retrospective study in adults post surgical repair of aortic coarctation who had undergone MRI imaging. Recoarctation was defined as a ratio of the minimal aortic diameter/aortic diameter at the diaphragm of <0.6. Aneurysm was defined as a ratio of the widest diameter of the proximal descending aorta/ aortic diameter at the diaphragm of >1.5. An optimal repair was defined as no imaging evidence of recoarctation or aneurysm. RESULTS: 74 consecutive patients with rCoA underwent MRI, mean age 32 years (range 18-69), 60% male. Recoarctation or aneurysm was identified in 17 patients (23%). Clinical predictors of recoarctation or aneurysm were upper-lower blood pressure gradient (ULG)>20 mmHg (OR 9.5, 95% CI 2.1- 43.7, p¼0.004) and a history of reintervention after coarctation repair (OR 4.7, 1.4- 15.6, p¼0.01). A prediction rule combining clinical factors (repair before age 5 without need for reintervention, no Dacron patch, no ULG and no hypertension) had a positive predictive value of 95% (95% CI 77%100%) for identifying patients with an optimal repair. In our cohort, 22 patients satisfied the prediction rule, representing 30% of the sample. CONCLUSION: Routine MRI imaging after repair of aortic coarctation is of moderate yield with 23% of patients having recoarctation or aneurysm. The strongest predictors of these complications are ULG>20 mmHg and a history of reintervention. Imaging should routinely be performed in such patients. Our clinical risk predictor (repair before age 5 without need for intervention, absence of Dacron patch, absence of ULG and absence of hypertension) has excellent predictive value for identifying an optimal repair. This tool has the potential to identify a subset of patients who are at low risk of complications and may not require imaging.
There were 48 males (82.8%) with a median age at surgery of 11.3 years (0.04 - 17.9). Indications for surgery were stenosis in 32 (55.2%), regurgitation in 13 (22.4%) and mixed aortic valve disease in 13 (22.4%) patients. Survival at 10 and 25 years was 96.2% and 93.9%, respectively. There was one (1.7%) hospital death and two (3.4%) late deaths. Freedom from pulmonary autograftrelated reintervention (the aortic root prosthesis) was 93.9% and 69.7% at 10 and 25 years, respectively. Eleven patients underwent reoperations on the autograft at a median followup of 16.1 years. Aortic valve-sparing surgery was performed in 6 patients and a Bentall procedure in 4 patients (3 mechanical, 1 homograft). Over the study period, twice as many patients (34.5%) required pulmonary homograftrelated (right ventricular outflow tract) reintervention (10 transcatheter, 10 surgical conduit replacement). Freedom from homograft-related reintervention was 73% and 50.4% at 10 and 25 years, respectively. CONCLUSION: The Ross procedure is associated with excellent long term survival. Late reintervention for the homograft was more common than for the pulmonary autograft in our cohort.
578 INFLAMMATORY AND HEMOSTATIC RESPONSE TO CARDIAC SURGERY WITH CARDIOPULMONARY BYPASS IN CHILDREN: IMPACT OF INTRAOPERATIVE MANAGEMENT
S307
cytokines (EST: -0.016 (-0.023; -0.009) nat.log pg/ml IL-10 per mg/kg of steroids, p<0.001). Elevation of plateletderived microparticles was highest in patients with low sensitivity to heparin (EST: +1.6 (+0.5; +2.6) nat.log x10E6 microparticle/ml per 100U/kg predicted heparin requirement, p¼0.004) and in those receiving a greater volume of allogeneic platelet transfusions (EST: +0.19 (+0.12; +0.25) nat.log x10E6 microparticle/ml per 10 ml/kg, p¼0.004). Markers of thrombin generation were highest for patients receiving more allogeneic blood product transfusions, patients with low heparin sensitivity and those with lower antifactor Xa activity measured at the end of CPB. Finally, a network analysis recapitulating the associations between the various physiological markers outlined a strong association between the different markers of inflammation and thrombin generation, with multiple cross-associations. The link between inflammation and thrombin generation was primarily potentiated by the association of IL-6 and IL-8 with prothrombin fragment 1.2. Anticoagulation activity, as measured by anti-factor Xa activity, was a critical suppressor of the cross-talk between inflammation and thrombosis (Figure). CONCLUSION: CPB in children is associated with severe hemodilution, release of inflammatory cytokines, leukocyte and platelet activation and thrombin generation. Modifiable risk factors associated with the magnitude of these changes might be targets for the development of future protective strategies in this vulnerable population.
C Manlhiot, CE Gruenwald, HM Holtby, ML Rand, L Stenyk, K Westcott, AK Chan, GS Van Arsdell, CA Caldarone, SM Schwartz, V Sivarajan, BW McCrindle Toronto, Ontario BACKGROUND:
Cardiac surgery with cardiopulmonary bypass (CPB) is associated with a severe and potentially damaging physiological reaction primarily affecting inflammation and hemostasis. The extent of this physiological reaction and associated factors have not been determined in children with heart disease undergoing cardiac operations. METHODS: A total of 248 pediatric patients undergoing cardiac surgery were included in an observational study. RESULTS: CPB initiation was associated with severe hemodilution in all patients, with decreases of 39%, 56% and 45% in hemoglobin, platelet count and antithrombin, respectively. It was most severe in the youngest patients and those undergoing more complex operations. Inflammatory cytokines were universally affected by CPB, as were levels of leukocytes-derived and platelet-derived microparticles. CPB was associated with a significant increase in prothrombin fragment 1.2, thrombin-antithrombin complex and Ddimer levels in the blood. Release of inflammatory cytokines was highest for patients with low sensitivity to heparin (EST: +0.50 (+0.15; +0.86) nat.log pg/ml IL-10 and EST: +0.39 (+0.12; +0.67) nat.log pg/ml IL-6 per 100U/kg predicted heparin requirement, p¼0.006). Patients receiving steroids preoperatively experienced smaller increases in inflammatory
Canadian Institutes of Health Research
579 COMPUTATIONAL FLUID DYNAMICS MODELS OF HEALTHY AND FAILING FONTAN CIRCULATIONS MG Doyle, F Alvarado, W Zhang, O Honjo, H Ide, RD Weisel, LW Tse, CH Amon Toronto, Ontario
S308 BACKGROUND:
Failing Fontan circulation is a clinical diagnosis and can be characterized by elevated Fontan pressures and reduced cardiac output. For many of these patients, heart transplant is the only viable treatment option, and there are currently no minimally invasive medical devices available to bridge these patients to transplant. The goal of our study is to design, build, and test such a device. As a first step in the design process, we have developed representative computational models of blood flow in the total cavopulmonary connection (TCPC) in both healthy and failing Fontan cases, which are described in this abstract. METHODS: Measurements made from angiograms of paediatric Fontan patients were used to develop an average three-dimensional computational model of the TCPC. Computational fluid dynamics simulations were performed in ANSYS Fluent (ANSYS, Inc., Canonsburg, PA, USA) for both healthy and failing Fontan circulations. Representative boundary conditions were defined for our model at the superior vena cava and extracardiac conduit (inlets) and the left and right pulmonary arteries (outlets) based on data from our patient cohort. At the inlets, we specified flow rates based on cardiac outputs of 1.8 L/min for the healthy case and 0.94 L/min for the failing case and a 65%/35% flow split between the extracardiac conduit and the superior vena cava. At the outlets, we specified pressures of 11 mm Hg for the healthy case and 18 mm Hg for the failing case. RESULTS: Results for healthy and failing Fontan circulations are presented in Figure 1 as streamlines of the blood flow through the TCPC. As expected, the velocities were higher in the healthy case than in the failing case, and the pressures (not shown) were lower in the healthy case than in the failing case. CONCLUSION: We have successfully developed a computational model to predict the blood flow in the TCPC for both healthy and failing Fontan circulations. Our calculated pressures and flow rates were consistent with expected values and fit within relevant physiological ranges. These models are a first step in the design process to develop a medical device for short-term minimally-invasive treatment for failing Fontan circulation as a bridge to heart transplant.
Canadian Journal of Cardiology Volume 31 2015
580 ADULTS WITH REPAIRED COARCTATION: REFINING THE NEED FOR MRI IMAGING V Pinphanichakarn, T Sehgal, S Islam, J Windram, AS Mackie, IF Vonder Muhll Edmonton, Alberta BACKGROUND:
Guidelines for the management of adult congenital heart disease recommend evaluation of patients with repaired coarctation (rCoA) by MRI or CT at least once in adulthood and repeated at intervals of 5 years or less. The incidence of pathology identified by this approach is uncertain. In an era of rationalization of healthcare costs, it is desirable to identify a low-risk subset of patients that may not require advanced tomographic imaging. Our objective was to determine the yield of MRI in detecting recoarctation or aneurysm in rCoA. We hypothesized that clinical assessment could identify patients at high risk for recoarctation or aneurysm, and conversely that prediction rules could be developed to identify those at low risk of complications. METHOD: We performed a retrospective study in adults post surgical repair of aortic coarctation who had undergone MRI imaging. Recoarctation was defined as a ratio of the minimal aortic diameter/aortic diameter at the diaphragm of <0.6. Aneurysm was defined as a ratio of the widest diameter of the proximal descending aorta/ aortic diameter at the diaphragm of >1.5. An optimal repair was defined as no imaging evidence of recoarctation or aneurysm. RESULTS: 74 consecutive patients with rCoA underwent MRI, mean age 32 years (range 18-69), 60% male. Recoarctation or aneurysm was identified in 17 patients (23%). Clinical predictors of recoarctation or aneurysm were upper-lower blood pressure gradient (ULG)>20 mmHg (OR 9.5, 95% CI 2.1- 43.7, p¼0.004) and a history of reintervention after coarctation repair (OR 4.7, 1.4- 15.6, p¼0.01). A prediction rule combining clinical factors (repair before age 5 without need for reintervention, no Dacron patch, no ULG and no hypertension) had a positive predictive value of 95% (95% CI 77%100%) for identifying patients with an optimal repair. In our cohort, 22 patients satisfied the prediction rule, representing 30% of the sample. CONCLUSION: Routine MRI imaging after repair of aortic coarctation is of moderate yield with 23% of patients having recoarctation or aneurysm. The strongest predictors of these complications are ULG>20 mmHg and a history of reintervention. Imaging should routinely be performed in such patients. Our clinical risk predictor (repair before age 5 without need for intervention, absence of Dacron patch, absence of ULG and absence of hypertension) has excellent predictive value for identifying an optimal repair. This tool has the potential to identify a subset of patients who are at low risk of complications and may not require imaging.