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Studies in Progress

  • Using hierarchical clustering machine learning to discover new subgroups in single ventricle heart patients, enhancing treatment strategies.

  • Establishing standard CMR imaging results for Fontan patients to improve diagnosis and treatment.

  • Developing automated tools to analyze 4D flow MRI data, aiding early detection of Fontan failure.

  • Exploring how weight affects heart characteristics and function in adults with Fontan circulation.

  • Studying blood flow efficiency in the Fontan circuit to predict long-term health outcomes.

  • Investigating factors behind 'supranormal' exercise capacity in some Fontan patients to improve overall patient care.

  • Pulmonary atresia with intact ventricular septum (PA/IVS) is a serious congenital heart defect in which the heart cannot pump blood to the lungs. Coronary artery abnormalities are common in PA/IVS, including a subset known as right ventricular-dependent coronary circulation (RVDCC) that are thought to be at higher-risk for early mortality. Using the FORCE dataset, we aim to better understand the characteristics that separate patients with RVDCC from those who do not have RVDCC, as well as define other predictors of clinical outcomes.

  • The goal of this work is to describe the change in the conduit cross-sectional area over time. Additionally, the relationship between the conduit cross-sectional area and exercise performance will be examined. Finally, the effect of conduit cross-sectional area on major adverse events such as death or need for heart transplantation will be examined.

  • Atrial tachycardia (AT) is a common long-term complication of those with Fontan physiology and significantly contributes to morbidity in this population, including hemodynamic instability, thromboembolism, and progressive heart failure. However, understanding the prevalence, predictors, treatment and outcomes of AT in this population remains incomplete. This study will use data from the FORCE registry to evaluate AT's impact on Fontan patients with the intent to improve prevention, management, and therapeutic approaches.

  • In neonates born with single ventricle disease, such as hypoplastic left heart syndrome (HLHS), surgical palliation is necessary for survival. An evolving alternative to an initial Norwood procedure, is the hybrid stage I palliation (HSIP), which combines patent ductus arteriosus (PDA) stenting and pulmonary artery (PA) banding or catheter-based occlusion techniques. This approach avoids cardiopulmonary bypass in the neonatal period and is particularly useful for high-risk patients with additional non-cardiac anomalies or physiologic insults. The long-term impact of HSIP on PA growth, hemodynamics, and subsequent Fontan completion remains uncertain. This study aims to evaluate the longitudinal clinical and imaging outcomes of Fontan patients who underwent HSIP, offering new insights into pulmonary vascular development and risk stratification.

  • Determine the attributable effect of EC Fontan as compared to LT Fontan on indexed cardiac output as measured by cardiac MRI.

  • Exploring novel cardiac and hepatic fibrosis biomarkers for Fontan-associated liver disease.

  • Analyzing ventricular performance and blood flow to anticipate health outcomes in Fontan patients.

  • Methods paper describing the innovations required to launch a AI-enabled registry so that others can replicate the success of FORCE.

  • Utilizing machine learning to automate and standardize ventricular size and function measurements in CMR exams.

  • Investigating the impact of ventricular interaction on systemic RV dysfunction in HLHS patients post-Fontan.

  • Using MRI and simulations to study heart shape and function in hypoplastic left heart syndrome.

  • The Fontan procedure is a critical surgery for patients with single-ventricle heart defects, but it often leads to complications like atrioventricular valve regurgitation (AVVR), where the heart's valves do not close properly, causing blood to flow backward and strain the heart. This study aims to identify the best method for measuring AVVR severity by comparing traditional ultrasound (echocardiography) and advanced cardiovascular magnetic resonance (CMR) with 4D flow. Using data from a large group of Fontan patients, we will assess which method provides the most accurate measurement and evaluate how AVVR severity affects heart function, exercise capacity, and long-term outcomes. This research could guide more effective treatments, potentially improving care and quality of life for individuals with single-ventricle heart defects post-Fontan.

  • Improving outcomes for patients with single ventricle hearts requires careful study of how blood flow and the main pumping chamber (systemic ventricle) works before surgery. A problem called atrioventricular valve regurgitation (AVVR), where blood leaks backward, can make the heart work harder and lead to worse health. Using advanced heart imaging like 4D flow MRI, we can measure how much energy is lost during flow and how the heart relaxes between beats (diastolic function). This study will use these advanced imaging tools to compare patients with and without AVVR and diastolic dysfunction, helping cardiologists find patterns that can guide treatments and improve care.

  • Hypoplastic left heart syndrome (HLHS) is a severe congenital heart condition where one of the pumping chambers of the heart does not develop. There are certain types of HLHS that may have worse outcomes secondary to abnormalities in heart function or blood supply to the muscle of the heart. As a result of this abnormal blood flow, we hypothesize that these patients develop scarring of the heart. Scarred tissue can be differentiated from healthy tissue by using Cardiac MRI (CMR) contrast-based images. We hypothesize that patients with these abnormal CMR findings will have lower survival and increased cardiac events.

  • Children born with single ventricle heart disease often undergo a series of surgeries, ending with the Fontan operation. Even after successful surgery, many patients face long-term challenges with how their hearts fill with blood between beats (called diastolic function). Doctors usually measure this filling with a few simple numbers, but these may miss important details. In this project, researchers will use advanced computer techniques, including machine learning, to study the full shape of heart filling curves from thousands of patients in the FORCE registry. By grouping patients based on patterns in these curves, the team hopes to identify new “filling types” that may be linked to better or worse long-term outcomes, such as heart failure or survival. This research could help doctors predict which Fontan patients are at higher risk and allow more personalized treatment strategies to improve long-term health.

  • Item description

  • The study will use CMR images to create pressure volume loops of the ventricle

  • Developing a risk score for sudden cardiac death in Fontan patients to guide clinical decisions.

  • Applying machine learning to segment Fontan baffles and pulmonary arteries for improved outcome prediction.

  • Examining the impact of aortic reconstruction on heart performance in Fontan patients using 4D imaging.

  • Identifying factors predicting diastolic dysfunction in Fontan patients to enhance clinical management.

  • Creating a comprehensive model to predict death/transplant risk in patients post-Fontan operation.

  • Using AI to identify early predictors of cardiac complications in single ventricle patients post-Fontan.

  • Patients who have undergone the Fontan procedure, a complex surgery for single-ventricle congenital heart disease, face increasing risks of heart failure and other complications as they grow older. While advanced imaging like cardiac MRI can help identify at-risk patients, it is expensive, time-consuming, and not always accessible, especially in resource-limited settings. The electrocardiogram (ECG) is a widely available and low-cost tool that, with the help of artificial intelligence (AI), can be used to predict outcomes in these patients. This project aims to validate a deep learning model that uses ECG data to identify Fontan patients at higher risk of poor outcomes, such as heart failure or death, and potentially improve care worldwide.

  • This proposal aims to evaluate the prevalence and consequences of neo-aortic valve insufficiency (AI) and neo-aortic root dilation in patients after a Norwood and/or Damus-Kaye-Stansel procedure in univentricular patients. Chronic AI can lead to ventricular dysfunction and dilation, with additional subsequent risk of developing coronary malperfusion, heart failure, atrioventricular valve dysfunction and arrhythmia, which can worsen prognosis. However, while the natural history and management of AI are well-established in patients with two ventricles, the lack of data in the single ventricle Fontan population poses challenges for clinicians to effectively care for these patients. Using clinical, imaging, and hemodynamic assessments from the FORCE registry, we will analyze the effect of neo-AI on cardiac performance and clinical outcomes in single ventricle patients. The end goals of this research are to enhance risk stratification and refine criteria for early surgical intervention in single ventricle patients with aortic valve dysfunction. This research could potentially lead to improved outcomes and quality of life for these patients through better-
    informed treatment approaches.

  • Post Fontan many individuals develop low fitness and heart failure (HF) over time. The exact cause of this is unknown. A subgroup of patients, High Performing Fontan (HPF), continue to do well, and have higher fitness than others with this diagnosis. We will use a large database (FORCE registry) of Fontan patients that stores imaging and clinical data, including pre-operative data to understand why some Fontan patients are able to have high level of fitness and better survival than others. This project will help us understand the drivers of fitness in Fontan patients and achieve better outcomes. This knowledge will improve the care, quality of life and prolong life span in Fontan Patients.

  • Cardiac magnetic resonance imaging (CMR) is commonly used to assess patients following Fontan surgery. During CMR studies, a contrast agent called gadolinium is sometimes administered to evaluate for late gadolinium enhancement (LGE) of the heart muscle, which indicates fibrosis or scarring. Previous research studies have shown an association between LGE and worse ventricular function and abnormal heart rhythms following Fontan operation. However, these studies were conducted at single centers and included only a small number of patients, limiting the researchers’ ability to fully understand the risks associated with LGE. This project aims to examine a very large group of patients with LGE imaging following the Fontan procedure from multiple centers. Our hope is to better understand the risks associated with LGE to improve patient hazard stratification. Specifically, we aim to recognize anatomic and clinical factors associated with the development of LGE and to further understand if certain cardiac regions or patterns of LGE are associated with higher risks. This will allow for improved patient counseling and clinical management.

  • In the single ventricle population, linking PHN (baby data) and FORCE (teen/adult data) will offer unique and unparalleled opportunities for research in the single ventricle population, from birth to adult. Once linked, we can better understand what happens to babies that have early problems with heart and valve function. We can also identify risk factors from the baby data to help us understand some of the special heart problems in the teenager and adult Fontan patients. This will allow for improved patient counseling and clinical management.

  • This study will compare how the modern style Fontan operations (lateral tunnel versus extracardiac conduit) impact outcomes.

  • This project investigates if stroke work, a cardiac MRI-derived measure of heart pump function, can predict exercise capacity and complications in patients with Fontan circulation.

  • This study aims to assess the hemodynamic outcomes of a novel iteration of the Fontan operation. We will analyze the effects of this innovative technique to determine its impact on heart function and overall patient health.

  • This study explores the long-term impact of creating a small hole (fenestration) during the Fontan procedure. While fenestration helps reduce pressure and improves short-term recovery, its long-term effects are unclear. The goal is to inform better decision-making and management of the fenestration in older Fontan patients.

  • This study investigates the impact of atrioventricular valve regurgitation on heart function and clinical outcomes in single ventricle patients after the Fontan procedure. We aim to identify risk factors for valve failure by analyzing clinical data, heart imaging, and exercise tests.

  • Patients with single ventricle congenital heart disease undergo staged palliation culminating in a direct connection between the inferior vena cava and the pulmonary artery (“Fontan”). In about half of cases a synthetic conduit is used to make this connection. This conduit does not grow as the patient grows, and it may become smaller over time. The effect of this conduit size on the overall health of patients with Fontan physiology remains unknown.

  • The Fontan procedure was originally developed to treat tricuspid atresia, a congenital condition where the left ventricle is the only pumping chamber of the heart. Over time, the procedure has been expanded to treat various congenital heart conditions, including those with a single left ventricle, a single right ventricle, or both ventricles that require single-ventricle palliation for other reasons. Studies have shown that a dominant right ventricle is linked to higher long-term risks including Fontan failure and the need for heart transplant. However, not all patients with the same type of ventricle are alike. This study will take a deep dive into the types of dominant ventricle (left, right, or balanced/mixed) and the underlying heart conditions in efforts to better understand what drives the differences. By comparing patients across both types of ventricle and diagnoses, we hope to identify risk factors for cardiac function and health outcomes and better tailor management strategies in Fontan patients.

  • In children with complex congenital heart disease, such as single ventricle physiology, abnormal blood vessels called aortopulmonary (AP) collaterals may form and affect blood flow between the heart and lungs. These vessels can impact heart function, liver health, and recovery after cardiac surgery. This study will examine how AP collaterals affect the heart and other organs and whether closing them improves health outcomes. We will use data from a large national registry of patients with single ventricle hearts who’ve had completed a multi-staged heart surgery, including the Fontan operation. Our aim is to define the correlation between AP collateral burden and outcomes such as heart function, organ health, and exercise ability. We hope to better understand how and when to treat these collaterals to help patients with Fontan circulation live healthier and longer lives.

  • The Fontan operation is the final stage of a series of surgical procedures to treat babies born with one working pumping chamber in the heart (single ventricle heart disease). The changes in how blood flows in the Fontan circulation can damage the liver over time, this is known as Fontan-associated liver disease (FALD). FALD is a major concern for patients, as it is associated with a worse long-term outlook and patients can do worse after a heart transplant. Most patients with a Fontan circulation have detectable liver disease within 10 years of their final Fontan operation, however some patients have more severe FALD than others, and we do not understand the basis of this variation.
    In the Fontan circulation, the inferior vena cava (IVC) which normally carries blood from the lower half of the body back to heart, is connected directly to the lungs so that the single pump only needs to send blood to the body. In this study, we will be assessing the relationship between IVC flow and additional liver parameters and severity of FALD.

Prospective Trials

Leveraging the FORCE infrastructure and human network, FORCE creates a unique opportunity to design and execute prospective clinical trails.

“Trials within a registry” or “registry clinical trials” have the following advantages:

Dramatically reduce the data collection burden, as key variables of interest and outcomes metrics are already being collected

Order of magnitude decreased costs to run the trial

Reduced paperwork burden as data use agreements have already been signed and executed

Utilizes robust data quality and auditing processes that already exist

Leverages a team of center PIs who already passionate about Fontan patients and work well together