Dataset Information

In-Silico and In-Vitro Analysis of the Novel Hybrid Comprehensive Stage II Operation for Single Ventricle Circulation.

ABSTRACT: Single ventricle (SV) anomalies account for one-fourth of all congenital heart disease cases. The existing palliative treatment for this anomaly achieves a survival rate of only 50%. To reduce the trauma associated with surgical management, the hybrid comprehensive stage II (HCSII) operation was designed as an alternative for a select subset of SV patients with the adequate antegrade aortic flow. This study aims to provide better insight into the hemodynamics of HCSII patients utilizing a multiscale Computational Fluid Dynamics (CFD) model and a mock flow loop (MFL). Both 3D-0D loosely coupled CFD and MFL models have been tuned to match baseline hemodynamic parameters obtained from patient-specific catheterization data. The hemodynamic findings from clinical data closely match the in-vitro and in-silico measurements and show a strong correlation (r = 0.9). The geometrical modification applied to the models had little effect on the oxygen delivery. Similarly, the particle residence time study reveals that particles injected in the main pulmonary artery (MPA) have successfully ejected within one cardiac cycle, and no pathological flows were observed.

SUBMITTER: Das A

PROVIDER: S-EPMC9952694 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature

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In-Silico and In-Vitro Analysis of the Novel Hybrid Comprehensive Stage II Operation for Single Ventricle Circulation.

Das Arka A Hameed Marwan M Prather Ray R Farias Michael M Divo Eduardo E Kassab Alain A Nykanen David D DeCampli William W

Bioengineering (Basel, Switzerland) 20230119 2

Single ventricle (SV) anomalies account for one-fourth of all congenital heart disease cases. The existing palliative treatment for this anomaly achieves a survival rate of only 50%. To reduce the trauma associated with surgical management, the hybrid comprehensive stage II (HCSII) operation was designed as an alternative for a select subset of SV patients with the adequate antegrade aortic flow. This study aims to provide better insight into the hemodynamics of HCSII patients utilizing a multis ...[more]

PMID: 36829630

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Project description:To determine sildenafil exposure and hemodynamic effect in children after stage II single-ventricle surgery.Prospective, dose escalation trial.Single-center, pediatric catheterization laboratory.Twelve children poststage II single-ventricle surgical palliation and undergoing elective cardiac catheterization: median age 1.9 years (range, 0.8, 4.0), weight 11?kg (8, 13), nine females, and 10 with a single right ventricle.Catheterization and echocardiography performed before and immediately after single-dose IV sildenafil (0.125, 0.25, 0.35, or 0.45?mg/kg over 20?min).Peak sildenafil and desmethyl sildenafil concentration, change in hemodynamic parameters measured by cardiac catheterization and echocardiography including indexed pulmonary vascular resistance, and myocardial performance.Maximum sildenafil concentrations ranged from 92 to 775?ng/mL and were above the in vitro threshold needed for 77% phosphodiesterase type 5 (PDE-5) inhibition in 80% of subjects and 90% inhibition in 80% of subjects with doses ?0.35?mg/kg. Sildenafil lowered pulmonary vascular resistance index in all 12 subjects (median pulmonary vascular resistance index 2.2 [range, 1.6, 7.9]; decreased to 1.7 [1.2, 5.4] WU × m; p < 0.01) with no dose-response effect. Sildenafil improved pulmonary blood flow (+8% [0, 20], p = 0.04) and saturations (+2% [0, 16], p = 0.04) in those with baseline pulmonary vascular resistance index ? 2 WU × m (n = 7). Change in saturations correlated inversely with change in pulmonary vascular resistance index (r = 0.74, p < 0.01). Sildenafil also lowered mean blood pressure (-12% [-20, +10]; p = 0.04). There was no change in cardiac index and no effect on myocardial performance. There were no adverse events.Sildenafil demonstrated nonlinear exposure with high interindividual variability but was well tolerated and effectively lowered pulmonary vascular resistance index in all subjects. Sildenafil did not acutely improve myocardial performance or increase cardiac index.

Project description:ObjectivesTo define whether adults with a Fontan circulation, who have lifelong venous congestion and limited cardiac output, have impaired glomerular filtration rate (GFR) or elevated urinary biomarkers of kidney injury.MethodsWe measured circulating cystatin C and creatinine (n=70) and urinary creatinine, albumin, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl glucosaminidase (NAG) (n=59) in ambulatory adult Fontan patients and 20 age-matched and sex-matched controls. Urinary biomarkers were normalised to urine creatinine concentration. Survival free from non-elective cardiovascular hospitalisation was compared by estimated GFR and urinary biomarker levels using survival analysis.ResultsCystatin C GFR was lower in the Fontan group compared with controls (114.2±22.8 vs 136.3±12.8 mL/min/1.73 m2, p<0.0001); GFR<90 mL/min/1.73 m2 in 14.3% vs 0% of controls. Albumin-to-creatinine ratio (ACR), KIM-1 and NAG were elevated compared with controls; ACR=23.2 (7.6-38.3) vs 3.6 (2.5-5.7) mg/g, p<0.0001; NAG=1.8 (1.1-2.6) vs 1.1 (0.9-1.6) U/g, p=0.02; KIM-1=0.91 (0.52-1.45) vs 0.33 (0.24-0.74) ng/mg, p=0.001. Microalbuminuria, ACR>30 mg/g, was present in 33.9% of the Fontan patients but in none of the controls. Over median 707 (IQR 371-942)-day follow-up, 31.4% of patients had a clinical event. Higher KIM-1 and NAG were associated with higher risk of non-elective hospitalisation or death (HR/+1 SD=2.1, 95% CI 1.3 to 3.3, p=0.002; HR/+1 SD=1.6, 95% CI 1.05 to 2.4, p=0.03, respectively); cystatin C GFR was associated with risk of the outcome (HR/+1 SD=0.66, 95% CI 0.48 to 0.90, p=0.009) but creatinine-based GFR was not (HR/+1 SD=0.91, 95% CI 0.61 to 1.38, p=0.66). Neither ACR nor NGAL was associated with events.ConclusionsThe Fontan circulation is commonly associated with reduced estimated GFR and evidence for glomerular and tubular injury. Those with lower cystatin C GFR and tubular injury are at increased risk of adverse outcomes.

Dataset Information

In-Silico and In-Vitro Analysis of the Novel Hybrid Comprehensive Stage II Operation for Single Ventricle Circulation.

Publications

In-Silico and In-Vitro Analysis of the Novel Hybrid Comprehensive Stage II Operation for Single Ventricle Circulation.

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