quantifying-inferior-vena-cava-compliance-distensibility-an-vivo

Quantifying Inferior Vena Cava Compliance and Distensibility in an <i>In Vivo</i> Ovine Model Using 3D Angiography

Synthetic vascular grafts overcome some challenges of allografts, autografts, and xenografts but are often more rigid and less compliant than the native ...

wireless-telemetry-device-implantation-fontan-ovine-model-for

Wireless Telemetry Device Implantation in a Fontan Ovine Model for Continuous and Long-Term Hemodynamic Monitoring

While the Fontan procedure drastically improves life expectancy for patients with single ventricle, it is well recognized that the resulting circulation ...

surgical-implantation-wireless-system-for-portal-vein-pressure

Surgical Implantation of a Wireless System for Portal Vein Pressure Monitoring in a Chronic Fontan Ovine Model

The Fontan circulation is characterized by nonpulsatile pulmonary blood flow and chronic systemic venous congestion, which has been associated with ...

Nationwide Children's Hospital

The Ohio State University College of Medicine

Abigail Wexner Research Institute at Nationwide Children's Hospital

Children born with single ventricle physiology who undergo Fontan palliation face a diverse set of long-term complications. However, patient follow-up has in large part been limited to single institutional experiences without uniform application of diagnostic modalities to screen for relevant outcomes. Additionally, the use of different graft materials and variable surgical technique as part of the Fontan procedure has further complicated the evaluation of single ventricle patients. The purpose of this review is to define the changes in the Fontan pathway specific to the graft material used and its relationship to patient outcomes. As a means of introduction, we briefly review the historical evolution of the Fontan procedure with a focus on the intent behind design changes and incorporation of different biomaterials. We further delineate changes to the Fontan pathway which include the development of stenosis, differential growth, thrombosis, and calcification. Ultimately, the recognition of the changes noted within the Fontan pathway need to be assessed relative to their impact on patient hemodynamics, functional capacity, and Fontan-associated comorbidities.

Evaluating the Longevity of the Fontan Pathway.

A 15-year-old girl with a history of complex congenital heart disease and prior pulmonary valve replacement presented with suspected endocarditis. PET/CT imaging with 18F-FDG was performed to evaluate the potential presence of intracardiac vegetations after previously inconclusive findings from CT angiography, transthoracic echocardiography, and transesophageal echocardiography. PET/CT detected heterogeneous, asymmetric, increased 18F-FDG uptake in the region of the pulmonary valve prosthesis, typical for infection, and confirmed diagnosis of bacterial infective endocarditis. This report highlights the utility of 18F-FDG PET/CT imaging to complement the Duke criteria for determining the diagnosis and therapeutic management of pediatric patients with infective endocarditis.

Utility of 18F-FDG PET/CT Imaging in Diagnosing Pulmonary Prosthetic Valve Endocarditis in a Pediatric Patient.

In the field of congenital heart surgery, tissue-engineered vascular grafts (TEVGs) are a promising alternative to traditionally used synthetic grafts. Our group has pioneered the use of TEVGs as a conduit between the inferior vena cava and the pulmonary arteries in the Fontan operation. The natural history of graft remodeling and its effect on hemodynamic performance has not been well characterized. In this study, we provide a detailed analysis of the first U.S. clinical trial evaluating TEVGs in the treatment of congenital heart disease. We show two distinct phases of graft remodeling: an early phase distinguished by rapid changes in graft geometry and a second phase of sustained growth and decreased graft stiffness. Using clinically informed and patient-specific computational fluid dynamics (CFD) simulations, we demonstrate how changes to TEVG geometry, thickness, and stiffness affect patient hemodynamics. We show that metrics of patient hemodynamics remain within normal ranges despite clinically observed levels of graft narrowing. These insights strengthen the continued clinical evaluation of this technology while supporting recent indications that reversible graft narrowing can be well tolerated, thus suggesting caution before intervening clinically.

Hemodynamic performance of tissue-engineered vascular grafts in Fontan patients.

Publisher Correction: Hemodynamic performance of tissue-engineered vascular grafts in Fontan patients.

To date, there has been limited investigation of bioabsorbable atrial septal defect (ASD) or patent foramen ovale (PFO) closure devices using clinically relevant large animal models. The purpose of this study is to explore the function and safety of a bioabsorbable ASD occluder (BAO) system for PFO and/or secundum ASD transcatheter closure. Using a sheep model, the intra-atrial septum was evaluated by intracardiac echo (ICE). If a PFO was not present, atrial communication was created via transseptal puncture. Device implantation across the intra-atrial communication was performed with fluoroscopic and ICE guidance. Our 1st generation device consisted of a main structure of thin Poly(L-lactide-co-epsilon-caprolactone) (PLCL) fibers, and an internal Poly glycolic acid (PGA) fabric. Four procedures validated procedure feasibility. Subsequently, device design was modified for improved transcatheter delivery. The 2nd generation device has a two-layered structure and was implanted in six sheep. Results showed procedural success in 9/10 (90%) animals. With deployment, the 1st generation device did not reform into its original disk shape and did not conform nicely along the atrial septum. The 2nd generation device was implanted in six animals, 3 out of 6 survived out to 1 year. At 1 year post implantation, ICE confirmed no residual shunting. By necropsy, biomaterials had partially degraded, and histology of explanted samples revealed significant device endothelialization and biomaterial replacement with a collagen layer. Our results demonstrate that our modified 2nd generation BAO can be deployed via minimally invasive percutaneous transcatheter techniques. The BAO partially degrades over 1 year and is replaced by host native tissues. Future studies are needed prior to clinical trials.

Pre-clinical Evolution of a Novel Transcatheter Bioabsorbable ASD/PFO Occluder Device.

The development and translation of regenerative medicine approaches for the treatment of hypoplastic left heart syndrome (HLHS) provides a promising alternative to the current standard of care. We review the strategies that have been pursued to date and those that hold the greatest promise in moving forward. Significant challenges remain. Continued scientific advances and technological breakthroughs will be required if we are to translate this technology to the clinic and move from palliative to curative treatment.

The Potential Role of Regenerative Medicine on the Future Management of Hypoplastic Left Heart Syndrome.

Patients with single ventricle heart defects requires a series of staged open-heart procedures, termed Fontan palliation. However, while lifesaving, these operations are associated with significant morbidity and early mortality. The attendant complications are thought to arise in response to the abnormal hemodynamics induced by Fontan palliation, although the pathophysiology underlying these physicochemical changes in cardiovascular and other organs remain unknown. Here, we investigated the microRNA (miRNA) content in serum and serum-derived extracellular vesicles (EVs) by sequencing small RNAs from a physiologically relevant sheep model of the Fontan operation. The differential expression analysis identified the enriched miRNA clusters in (1) serum vs. serum-derived EVs and (2) pre-Fontan EVs vs. post-Fontan EVs. Metascape analysis showed that the overexpressed subset of EV miRNAs by Fontan procedure target liver-specific cells, underscoring a potentially important pathway involved in the liver dysfunction that occurs as a consequence of Fontan palliation. We also found that post-Fontan EV miRNAs were associated with senescence and cell death, whereas pre-Fontan EV miRNAs were associated with stem cell maintenance and epithelial-to-mesenchymal transition. This study shows great potential to identify novel circulating EV biomarkers from Fontan sheep serum that may be used for the diagnosis, prognosis, and therapeutics for patients that have undergone Fontan palliation.

Computational analysis of serum-derived extracellular vesicle miRNAs in juvenile sheep model of single stage Fontan procedure.

Patch augmentation of the right ventricular outflow tract (RVOT) and pulmonary artery (PA) arterioplasty are relatively common procedures in the surgical treatment of patients with congenital heart disease. To date, several patch materials have been applied with no agreed upon clinical standard. Each patch type has unique performance characteristics, cost, and availability. There are limited data describing the various advantages and disadvantages of different patch materials. We performed a review of studies describing the clinical performance of various RVOT and PA patch materials and found a limited but growing body of literature. Short-term clinical performance has been reported for a multitude of patch types, but comparisons are limited by inconsistent study design and scarce histologic data. Standard clinical criteria for assessment of patch efficacy and criteria for intervention need to be applied across patch types. The field is progressing with improvements in outcomes due to newer patch technologies focused on reducing antigenicity and promoting neotissue formation which may have the ability to grow, remodel, and repair.

Patch Materials for Pulmonary Artery Arterioplasty and Right Ventricular Outflow Tract Augmentation: A Review.

Whole blood analysis can evaluate numerous parameters, including pH, pCO₂, pO₂, HCO₃ - , base excess, glucose, electrolytes, lactate, blood urea nitrogen, creatinine, bilirubin, and hemoglobin. This valuable tool enables clinicians to make more informed decisions about patient care. However, the current body of literature describing perioperative whole blood analysis in Dorset sheep () is small, so clinicians lack adequate information to guide their decision-making when evaluating test results. We evaluated arterial and venous whole blood pH, bicarbonate, pCO₂, lactate, creatinine, and blood urea nitrogen before and for the first 24 hours after surgery in 2 cohorts of male and female  s undergoing one of 2 major cardiovascular procedures, a Single-Stage Fontan or an inferior vena cava to pulmonary artery extracardiac conduit implantation (IP-ECC). The cohort undergoing a Single-Stage Fontan, which is the more complex procedure, exhibited greater deviation from baseline measurements than did the cohort undergoing the IP-ECC for lactate, bicarbonate, and creatinine. The cohort undergoing the IP-ECC showed no significant deviation from baseline for any parameters, potentially indicating a better safety margin than expected when compared with the Single-Stage Fontan. Together, these results indicate the clinical value of arterial and venous whole blood measurements in perioperative management of sheep and can provide a reference for clinicians managing sheep after significant cardiovascular procedures.

Perioperative Evaluation of Arterial and Venous Whole Blood in the Lamb () Fontan Model.

Our goal was to conduct a hemodynamic analysis of a novel animal model of Fontan physiology. Poor late-term outcomes in Fontan patients are believed to arise from Fontan-induced hemodynamics, but the mechanisms remain poorly understood. Recent advances in surgical experimentation have resulted in the development of a chronic sheep model of Fontan physiology; however, detailed analysis of this model is lacking.

ArticleTotal : 3	Year
Publication title Cited by 2	2024
Publication title Cited by 1	2025
Publication title	2025

Article	Year
Evaluating the Longevity of the Fontan Pathway. Pediatric cardiology\| PubMed ID: 33161457	2020
Utility of 18F-FDG PET/CT Imaging in Diagnosing Pulmonary Prosthetic Valve Endocarditis in a Pediatric Patient. Clinical nuclear medicine\| PubMed ID: 33883489	2021
Hemodynamic performance of tissue-engineered vascular grafts in Fontan patients. NPJ Regenerative medicine\| PubMed ID: 34294733	2021
Publisher Correction: Hemodynamic performance of tissue-engineered vascular grafts in Fontan patients. NPJ Regenerative medicine\| PubMed ID: 34385470	2021
Pre-clinical Evolution of a Novel Transcatheter Bioabsorbable ASD/PFO Occluder Device. Pediatric cardiology\| PubMed ID: 34981140	2022
The Potential Role of Regenerative Medicine on the Future Management of Hypoplastic Left Heart Syndrome. Journal of cardiovascular development and disease\| PubMed ID: 35448083	2022
Computational analysis of serum-derived extracellular vesicle miRNAs in juvenile sheep model of single stage Fontan procedure. Extracellular vesicle\| PubMed ID: 36330420	2022
Patch Materials for Pulmonary Artery Arterioplasty and Right Ventricular Outflow Tract Augmentation: A Review. Pediatric cardiology\| PubMed ID: 37149833	2023
Perioperative Evaluation of Arterial and Venous Whole Blood in the Lamb () Fontan Model. Comparative medicine\| PubMed ID: 38508687	2024
Investigation of a chronic single-stage sheep Fontan model. JTCVS open\| PubMed ID: 39534321	2024

John M. Kelly

Biography

JoVE Journal Publications

Other Publications