Computational Fluid Dynamics in Congenital Heart Disease

Computational fluid dynamics has been applied to the design, refinement, and assessment of surgical procedures and medical devices. This tool calculates flow patterns and pressure changes within a virtual model of the cardiovascular system. In the field of paediatric cardiac surgery, computational fluid dynamics is being used to elucidate the optimal approach to staged reconstruction of specific defects and study the haemodynamics of the resulting anatomical configurations after reconstructive or palliative surgery. In this paper, we review the techniques and principal findings of computational fluid dynamics studies as applied to a few representative forms of congenital heart disease

Computational Analysis of Hybrid Norwood Circulation with Distal Aortic Arch Obstruction and Reverse Blalock-Taussig Shunt

BACKGROUND: The hemodynamics characteristics of the hybrid Norwood (HN) procedure differ from those of the conventional Norwood and are not fully understood. We present a multi-scale model of HN circulation to understand local hemodynamics and effects of aortic arch stenosis and a reverse Blalock-Taussig shunt (RBTS) on coronary and carotid perfusion. METHODS: Four 3-dimensional models of four HN anatomic variants were developed, with and without 90% distal preductal arch stenosis and with and without a 4-mm RBTS. A lumped parameter model of the circulation was coupled to a local 3-dimensional computational fluid dynamics model. Outputs from the lumped parameter model provided waveform boundary conditions for the computational fluid dynamics model. RESULTS: A 90% distal arch stenosis reduced pressure and net flow-rate through the coronary and carotid arteries by 30%. Addition of the RBTS completely restored pressure and flow rate to baseline in these vessels. Zones of flow stagnation, flow reversal, and recirculation in the presence of stenosis were rendered more orderly by addition of the RBTS. In the absence of stenosis, presence of the shunt resulted in extensive zones of disturbed flow within the RBTS and arch. CONCLUSIONS: We found that a 4-mm × 21-mm RBTS completely compensated for the effects of a 90% discrete stenosis of the distal aortic arch in the HN. Placed preventatively, the RBTS and arch displayed zones with thrombogenic potential showing recirculation and stagnation that persist for a substantial fraction of the cardiac cycle, indicating that anticoagulation should be considered with a prophylactic RBTS

COVAD survey 2 long-term outcomes: unmet need and protocol

Vaccine hesitancy is considered a major barrier to achieving herd immunity against COVID-19. While multiple alternative and synergistic approaches including heterologous vaccination, booster doses, and antiviral drugs have been developed, equitable vaccine uptake remains the foremost strategy to manage pandemic. Although none of the currently approved vaccines are live-attenuated, several reports of disease flares, waning protection, and acute-onset syndromes have emerged as short-term adverse events after vaccination. Hence, scientific literature falls short when discussing potential long-term effects in vulnerable cohorts. The COVAD-2 survey follows on from the baseline COVAD-1 survey with the aim to collect patient-reported data on the long-term safety and tolerability of COVID-19 vaccines in immune modulation. The e-survey has been extensively pilot-tested and validated with translations into multiple languages. Anticipated results will help improve vaccination efforts and reduce the imminent risks of COVID-19 infection, especially in understudied vulnerable groups

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background: Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods: The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings: We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation: Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding: Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Immunoglobulin, glucocorticoid, or combination therapy for multisystem inflammatory syndrome in children: a propensity-weighted cohort study

Background Multisystem inflammatory syndrome in children (MIS-C), a hyperinflammatory condition associated with SARS-CoV-2 infection, has emerged as a serious illness in children worldwide. Immunoglobulin or glucocorticoids, or both, are currently recommended treatments. Methods The Best Available Treatment Study evaluated immunomodulatory treatments for MIS-C in an international observational cohort. Analysis of the first 614 patients was previously reported. In this propensity-weighted cohort study, clinical and outcome data from children with suspected or proven MIS-C were collected onto a web-based Research Electronic Data Capture database. After excluding neonates and incomplete or duplicate records, inverse probability weighting was used to compare primary treatments with intravenous immunoglobulin, intravenous immunoglobulin plus glucocorticoids, or glucocorticoids alone, using intravenous immunoglobulin as the reference treatment. Primary outcomes were a composite of inotropic or ventilator support from the second day after treatment initiation, or death, and time to improvement on an ordinal clinical severity scale. Secondary outcomes included treatment escalation, clinical deterioration, fever, and coronary artery aneurysm occurrence and resolution. This study is registered with the ISRCTN registry, ISRCTN69546370. Findings We enrolled 2101 children (aged 0 months to 19 years) with clinically diagnosed MIS-C from 39 countries between June 14, 2020, and April 25, 2022, and, following exclusions, 2009 patients were included for analysis (median age 8·0 years [IQR 4·2–11·4], 1191 [59·3%] male and 818 [40·7%] female, and 825 [41·1%] White). 680 (33·8%) patients received primary treatment with intravenous immunoglobulin, 698 (34·7%) with intravenous immunoglobulin plus glucocorticoids, 487 (24·2%) with glucocorticoids alone; 59 (2·9%) patients received other combinations, including biologicals, and 85 (4·2%) patients received no immunomodulators. There were no significant differences between treatments for primary outcomes for the 1586 patients with complete baseline and outcome data that were considered for primary analysis. Adjusted odds ratios for ventilation, inotropic support, or death were 1·09 (95% CI 0·75–1·58; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids and 0·93 (0·58–1·47; corrected p value=1·00) for glucocorticoids alone, versus intravenous immunoglobulin alone. Adjusted average hazard ratios for time to improvement were 1·04 (95% CI 0·91–1·20; corrected p value=1·00) for intravenous immunoglobulin plus glucocorticoids, and 0·84 (0·70–1·00; corrected p value=0·22) for glucocorticoids alone, versus intravenous immunoglobulin alone. Treatment escalation was less frequent for intravenous immunoglobulin plus glucocorticoids (OR 0·15 [95% CI 0·11–0·20]; p<0·0001) and glucocorticoids alone (0·68 [0·50–0·93]; p=0·014) versus intravenous immunoglobulin alone. Persistent fever (from day 2 onward) was less common with intravenous immunoglobulin plus glucocorticoids compared with either intravenous immunoglobulin alone (OR 0·50 [95% CI 0·38–0·67]; p<0·0001) or glucocorticoids alone (0·63 [0·45–0·88]; p=0·0058). Coronary artery aneurysm occurrence and resolution did not differ significantly between treatment groups. Interpretation Recovery rates, including occurrence and resolution of coronary artery aneurysms, were similar for primary treatment with intravenous immunoglobulin when compared to glucocorticoids or intravenous immunoglobulin plus glucocorticoids. Initial treatment with glucocorticoids appears to be a safe alternative to immunoglobulin or combined therapy, and might be advantageous in view of the cost and limited availability of intravenous immunoglobulin in many countries. Funding Imperial College London, the European Union's Horizon 2020, Wellcome Trust, the Medical Research Foundation, UK National Institute for Health and Care Research, and National Institutes of Health

Experimental Study Of Anisotropic Stress/Strain Relationships Of The Piglet Great Vessels And Relevance To Pediatric Congenital Heart Disease

Background Determining material mechanical properties of neonatal aorta and pulmonary artery will aid understanding tissue behavior when subjected to abnormal hemodynamics of congenital heart disease. Methods Aorta and pulmonary arteries were harvested from 6 neonatal piglets (mean weight 3.5 kg). Tissue samples from ventral and dorsal aspects of ascending aorta (AA) and descending aorta (DA), innominate artery (IA), left subclavian artery (LScA), main pulmonary artery (MPA), and left pulmonary artery (LPA) and right pulmonary artery (RPA) were obtained in three orientations: circumferential, diagonal, and longitudinal. Samples were subjected to uniaxial tensile testing. True strain-Cauchy stress curves were individually fitted for each orientation to calibrate the Fung model, and to measure tissue stiffness (10% strain). Results All samples, for all orientations, demonstrated nonlinear hyperelastic strain-stress response to uniaxial tensile testing (Holzapfel-Gasser and fitted-Fung models R2 \u3e 0.95). For each vessel segment, stiffness was not significantly different among orientations. Stiffness values in all orientations, including ventral/dorsal samples, were compared between AA \u3e MPA (p = 0.08), DA \u3e MPA (p \u3c 0.01), and DA \u3e AA (p = 0.35). Comparison of circumferential orientation samples showed AA and DA are significantly stiffer than MPA (p \u3c 0.05), and MPA stiffness was similar to that of the RPA but slightly greater than LPA. Also, dorsal circumferential samples of all segments were slightly stiffer than ventral (p = 0.21). Dorsal aspect of AA was slightly stiffer in all orientations (p = 0.248). Conclusions The neonatal aorta and pulmonary artery exhibit hyperelastic biomechanical behavior with an anisotropic effect. Differences between aorta and pulmonary artery may play a role in native tissue behavior, ventricular and arterial mechanical coupling, and risk of deformation due to abnormal hemodynamics of congenital heard disease

Computational Fluid Dynamics in Congenital Heart Disease

Computational fluid dynamics has been applied to the design, refinement, and assessment of surgical procedures and medical devices. This tool calculates flow patterns and pressure changes within a virtual model of the cardiovascular system. In the field of paediatric cardiac surgery, computational fluid dynamics is being used to elucidate the optimal approach to staged reconstruction of specific defects and study the haemodynamics of the resulting anatomical configurations after reconstructive or palliative surgery. In this paper, we review the techniques and principal findings of computational fluid dynamics studies as applied to a few representative forms of congenital heart disease

Computational Fluid Dynamics In Congenital Heart Disease

Computational fluid dynamics has been applied to the design, refinement, and assessment of surgical procedures and medical devices. This tool calculates flow patterns and pressure changes within a virtual model of the cardiovascular system. In the field of paediatric cardiac surgery, computational fluid dynamics is being used to elucidate the optimal approach to staged reconstruction of specific defects and study the haemodynamics of the resulting anatomical configurations after reconstructive or palliative surgery. In this paper, we review the techniques and principal findings of computational fluid dynamics studies as applied to a few representative forms of congenital heart disease. © 2012 Cambridge University Press