Clinical Research Directory

Influence of Personalized Lung Volume Optimization Maneuver on Lung Function and Cardiac Performance in Children

The goal of this randomized interventional clinical trial is to learn if a standardized lung volume optimization maneuver (LVOM) is beneficial in 1. study) children undergoing biventricular repair of their congenital heart disease (CHD) with cardiopulmonary bypass and 2. study) in children with severe respiratory failure at risk for or need for ECMO. The main questions it aims to answer are: Main hypotheses of CHD study: Does a standardized PEEP-Titration maneuver, to optimize end-expiratory lung volume improve: * cardiac performance * lung function Does it make a difference in: * length of ventilation * ventilation/perfusion mismatch of the lung * need for vasopressor support? Main hypotheses of ECMO study: Does a LVOM in children/infants with severe respiratory failure /ARDS * improve lung compliance and gas exchange * facilitate lung protective ventilation according to PALICC-2 guidelines * improve lung aeration and V/Q-matching assessed with EIT Does it make a difference in * need for ECMO * duration of ECMO runs * hemodynamics stability

Chest X-Rays for Early Detection of Congenital Heart Disease in Newborns

Congenital heart disease (CHD) is a common condition affecting newborns that can be serious if not caught early. While echocardiograms are the best way to diagnose CHD, they are not always immediately available. Chest X-rays are widely available and are often the first test used when a newborn has breathing problems, a heart murmur, or a bluish skin tint. The purpose of this study is to determine how accurate standard chest X-rays are at finding congenital heart disease in newborns. Researchers will observe 60 newborns (up to 28 days old) admitted to the Neonatal Intensive Care Unit (NICU) who have signs or symptoms that suggest they might have a heart problem. Each baby in the study will receive a standard chest X-ray within 24 hours of their clinical presentation. Within 72 hours, they will also receive an echocardiogram, which is the standard, definitive test used to confirm if there is a heart defect. By comparing the initial chest X-ray results to the final echocardiogram results, researchers hope to figure out exactly which X-ray patterns are best at predicting specific heart diseases. This could help doctors make faster decisions about treating newborns, potentially reducing delays in diagnosis and improving care.

Genetics of Congenital Heart Disease

Congenital heart disease (CHD) is the most common type of birth defect but the cause for the majority of cardiac birth defects remains unknown. Numerous epidemiologic studies have demonstrated evidence that genetic factors likely play a contributory, if not causative, role in CHD. While numerous genes have been identified by us and other investigators using traditional genetic approaches, these genes account for a minority of the non-syndromic CHDs. Therefore, we are now utilizing whole genome sequencing (WGS), with the addition of more traditional genetic techniques such as chromosomal microarray or traditional linkage analysis, to identify genetic causes of familial and isolated CHD. With WGS we are able to sequence all of the genetic material of an individual and apply different data analysis techniques based on whether we are analyzing a multiplex family or a cohort of trios (mother, father and child with CHD) with a specific isolated CHD. Therefore, WGS is a robust method for identification of novel genetic causes of CHD which will have important diagnostic and therapeutic consequences for these children.

Precision Medicine in the CICU: Identifying Proteomic Biomarkers

Congenital Heart disease (CHD) is a leading cause of childhood death. Substantial morbidity and mortality relates to the postoperative course. For example, only 70% of neonates survive to hospital discharge after their first complex surgery for single ventricle heart disease. Adverse systemic inflammatory responses are highly exaggerated in some children postoperatively. This inflammation is pathological, results in leaky blood vessels and fluid overload, toxin release as well as cell damage contributing to lung, heart and kidney injury. Reasons why some children develop this amplified systemic inflammatory response after heart surgery while others do not are poorly understood. Mechanisms for how cardiopulmonary bypass and surgery drive this inflammation are also inadequately characterized. Currently, there are no existing methods to predict patients at high-risk for acute adverse postoperative complications, let alone adjust our management to mitigate these effects. Instead, our postoperative care approach is a one-size fits all, reactive process 'after' patients become inflamed or adverse events occur. Proteins in a patient's blood participate in and reflect acute inflammatory responses. In other pediatric conditions, protein biomarkers have been shown to both predict and monitor inflammation and adverse outcomes, and importantly predict responsiveness to anti-inflammatory drug therapies. This is the premise of precision medicine. Personalizing treatment to each individual patient. New technologies now allow the levels of tens of thousands of proteins to be measured from a few drops of blood. In this proposal the investigators will identify predictors of adverse events after heart surgery by quantifying protein levels and their changes after surgery. It is now possible to detect those proteins with the greatest variability in the postoperative course over time, and between patients, as well as those that are associated with adverse outcomes. The most informative proteins will yield insights into the causes of the inflammatory response. The investigators anticipate identifying protein plasma biomarkers in pathways associated with inflammation, metabolism, blood vessel function and the immune system as these may be key mechanisms involved. Advanced understanding of these mechanisms is critical to deriving targeted therapies to prevent or mitigate inflammatory responses. The investigators will also collect patient clinical data, such as age, cardiac anatomy, and duration of surgery. By combining this clinical information with blood protein profiles, the investigators will be able to develop a model predicting patients at highest risk for adverse postoperative events using machine learning approaches. The overarching goal of this research integrating clinical and bench research is ultimately to translate precision medicine approaches to the Cardiac ICU. Guiding personalized care of high-risk patients by enabling clinicians to anticipate outcomes and tailor decision-making at the bedside will undoubtably improve outcomes in CHD.

Perioperative Lidocaine for Lung Protection in Infants Undergoing Cardiac Surgery

Cardiopulmonary bypass-associated pulmonary injury is a common complication after infant cardiac surgery and may contribute to impaired oxygenation, prolonged mechanical ventilation, and longer intensive care stay. Lidocaine has anti-inflammatory and membrane-stabilizing properties and may attenuate perioperative lung injury. This investigator-initiated, randomized, placebo-controlled, double-blind trial will evaluate whether perioperative intravenous lidocaine reduces postoperative pulmonary injury in infants undergoing corrective non-palliative congenital cardiac surgery with cardiopulmonary bypass.

Psychological Trauma, Post-Traumatic Stress Disorder, and Resilience in Adults With Congenital Heart Disease

The purpose of this study, entitled "Psychological trauma, post-traumatic stress disorder, and resilience in adults with congenital heart disease in a large population sample", is to evaluate for exposures during a lifetime with congenital heart disease that may be associated with higher likelihood of developing PTSD. Primary aim: \- Identify individual patient characteristics (medical, psychosocial, socioeconomic, etc.) that are associated with a diagnosis of PTSD. Secondary aims: * Calculate the prevalence of those meeting PTSD criteria in the ACHD population using the "gold standard" diagnostic clinician interview, while using the same data to validate a PTSD screening self-report survey in the ACHD population. * Determine the role of resilience in ACHD patients using a validated screening survey to assess its protective role toward PTSD. Hypotheses: * There are certain exposures (e.g. post-surgical pain, ICU delirium, bullying due to CHD) that are associated with a higher incidence and odds of meeting PTSD criteria. * "Gold standard" diagnostic interviews will most accurately estimate the prevalence of PTSD in ACHD which has been overestimated on prior screening-based studies, although the scope of the problem is still great. * Patients with a higher resilience score will show an association with a lower risk of PTSD.

Influence of Lung Volume Optimization Maneuver in Ventilated Children on Cardiac Output and Lung Compliance in Children With Congenital Heart Disease Undergoing Surgical Repair

The goal of this randomized interventional clinical trial is to learn if a standardized lung volume optimization maneuver (LVOM) is beneficial in children undergoing biventricular repair of their congenital heart disease (CHD) with cardiopulmonary bypass. Main hypotheses: Does a standardized PEEP-Titration maneuver, to optimize end-expiratory lung volume improve: * cardiac performance * lung function Does it make a difference in: * length of ventilation * ventilation/perfusion mismatch of the lung * need for vasopressor support?

Longitudinal Validation of CIRC Technologies

Cardiovascular disease is the leading cause of death worldwide. Advanced cardiovascular imaging using Magnetic Resonance Imaging (MRI) has proven to be effective in providing gold standard myocardial tissue characterization. Moreover, the intrinsic advantage of MRI's lack of exposure to ionizing radiation is particularly beneficial. At the same time, blood work can be very useful in early detection of certain cardiomyopathy, such as amyloid. However, there is a lack of agreement of on which markers are the most sensitive. This multi-study will allow the unique opportunity to form a more comprehensive understanding for various cardiovascular diseases. The study team has developed novel cardiac MRI techniques that leverages endogenous tissue properties to reveal a milieu of deep tissue phenotypes including myocardial inflammation, fibrosis, metabolism, and microstructural defects. Among these phenotypes, myocardial microstructure has proven to be most sensitive to early myocardial tissue damage and is predictive of myocardial regeneration. In this study, the investigators aim to further study the importance of cardiac microstructure revealed by MRI in patient and healthy population and compare this novel technology with conventional clinical biomarkers.

An Observational Study to Learn More About How Safe Rivaroxaban is And How Well it Works in Children With Congenital Heart Disease Who Had a Heart Surgery Called the Fontan Procedure

This is an observational study in which the data from children with congenital heart disease will be collected and studied. These children will include those who are prescribed rivaroxaban by their doctors after a heart surgery called the Fontan procedure. Congenital heart disease (CHD) is a heart problem that some children are born with. It sometimes requires a surgery called the Fontan procedure to improve the blood flow in the body. The Fontan procedure can increase the risk of the formation of blood clots in the blood vessels (called thrombosis), which might lead to death. The study drug, rivaroxaban, is an approved treatment for preventing the formation of blood clots. It is a type of anticoagulant that prevents the blood from clotting by blocking a protein responsible for it. Rivaroxaban can increase the risk of bleeding. A previous study suggested that the number of major bleeding episodes did not differ much while taking rivaroxaban compared to aspirin in children with CHD who had undergone the Fontan procedure. However, there is limited information available for Japanese patients. To better understand the safety and potential risks of this drug in children, more knowledge is needed about the use of rivaroxaban in the real world. The main purpose of this study is to learn more about the occurrence of major bleeding or non-major bleeding in children who were treated with rivaroxaban. Major bleeding is defined as a serious or life-threatening bleeding episode that can have an impact on a person's health and requires medical attention. Non-major bleeding is defined as a type of bleeding that may negatively impact a person's health if not treated. The data will be collected from December 2023 to June 2026. Researchers will observe each participant for up to 30 days after stopping the treatment or for a maximum of 2 years. In this study, only available data from regular health visits will be collected. No visits or tests are required as part of this study. Researchers will use the medical records or interview the children and/or their guardians during regular visits.

Exercise MRI to Evaluate Cardiorespiratory Fitness in Children With Heart Disease

There are many barriers to heart-healthy lifestyles in pediatric patients with acquired and congenital heart disease. Investigators want to further understand how participants heart and skeletal muscles work together during exercise and evaluate the impact on cardiac function. To do this, the investigators will use magnetic resonance imaging (MRI) to scan the heart and skeletal muscles during exercises to assess blood flow, oxygenation and function.

Autologous Induced Pluripotent Stem Cells of Cardiac Lineage for Congenital Heart Disease

The goal of this clinical trial is to test the safety of lab-grown heart cells made from stem cells in subjects with congenital heart disease. The main questions it aims to answer are: * Is this product safe to deliver to humans * Is the conduct of this trial feasible Participants will be asked to: * Agree to testing and monitoring before and after product administration * Receive investigational product * Agree to lifelong follow-up Researchers will compare subjects from the same pool to see if there is a difference between treated and untreated subjects.

ATrial Tachycardia PAcing Therapy in Congenital Heart

Congenital heart disease (CHD) affects approximately 1% of newborns in the US, with 25% of those affected having critical conditions requiring open heart surgery within one year of birth. Surgical and medical advances have allowed many patients to live beyond their fourth and fifth decades of life. Unfortunately, cardiac arrhythmias are a relatively common sequela due to cardiac anomalies and surgical scars in addition to residual volume and pressure load on the heart. Atrial arrhythmias, including sinus node dysfunction and intra-atrial re-entrant tachycardia (IART) are among the more common abnormalities found in adults with repaired CHD. The presence of IART significantly increases morbidity and mortality, and anti-arrhythmic medications have been shown to be a sub-optimal treatment strategy with the majority of patients requiring multi-drug therapy. Catheter ablation procedures remain a treatment option, but are less successful for some patient demographics. In the mid-1990's, pacemakers with atrial anti-tachycardia pacing (ATP) capabilities were developed, primarily for the management of atrial flutter and fibrillation in adults with structurally normal hearts. Given the need for pacemakers in the CHD population to manage sinus node dysfunction and atrioventricular node conduction block, the adoption of atrial anti-tachycardia pacemakers began to gain favor. However, there is limited data available comparing the safety and effectiveness of ATP therapy between various demographics of CHD patients. In the current study, the investigators aim to determine if ATP is an effective treatment strategy for IART, specifically within particular sub-populations of CHD patients. Additionally, investigators hope to delineate any significant differences in efficacy of ATP treatment between adult and pediatric congenital heart patients. The research team will accomplish our goals with a retrospective, multi-center study in which data is collected from existing electronic medical records and pacemaker interrogations. Following data collection, the investigators will employ statistical analyses to determine if certain CHD demographics are statistically significant predictors of ATP therapy outcomes. The purpose of this prospective/retrospective study is to determine how effective atrial anti-tachycardia therapies are with the congenital heart patients who are known to have atrial arrhythmias. As this population ages, we know that arrhythmic burden increases and medications are increased or changed for symptomatic improvement. Patients will be enrolled at the time of anti tachycardia device (ATD) placement or when device therapies are turned on. Patients will need a minimum of 5 years of clinical history prior to implantation and after implantation (unless patient is very young). Data will be collected both retrospectively and prospectively. The research team will consent patients at the time of clinical evaluations and scheduled follow-ups (usually 3 - 6 months). If therapy is effective, investigators will determine the specific programming which was successful. If therapy was ineffective, investigators will also determine if a change in programing was made and if this improved ATP efficacy. Investigators will also determine the arrhythmia burden. Cardioversion and medications before and after ATD implantation will be the key determinants of arrhythmia burden in this study.

Autus Valve Continued Access Study (CAS)

Prospective, single-arm, multi-center, continued access study of the Autus Size-Adjustable Valve in pediatric patients aged 18 months to 16 years requiring surgical pulmonary valve replacement. The Autus Valve may be expanded pre-implant to match the subject's body size. Subjects will be evaluated prior to the Autus Valve implant procedure, immediately post-implantation, at hospital discharge, 30 days, 6 months, and annually through 10 years. The Autus Valve may be expanded post-implant via transcatheter balloon dilation to accommodate growth of the subject.

Autus Valve Pivotal Study

Prospective, single-arm, multi-center study to evaluate safety and effectiveness of the Autus Size-Adjustable Valve in pediatric patients aged 18 months to 16 years requiring surgical pulmonary valve replacement. The Autus Valve may be expanded pre-implant to match the subject's body size. Subjects will be evaluated prior to the Autus Valve implant procedure, immediately post-implant, at hospital discharge, 30 days, 6 months, and annually through 10 years. The Autus Valve may be expanded post-implant via transcatheter balloon dilation to accommodate growth of the subject. In subjects who undergo a post-implant valve expansion, follow-up will continue for a minimum of 1 year after the post-implant valve expansion procedure.

A Study of Hemodynamic Cardiopulmonary Exercise for CHD

The purpose of this study is to compare the difference in the ability to detect hemodynamic abnormalities between invasive hemodynamic assessments performed at rest versus exercise, to assess the correlation between invasive and noninvasive (Doppler-derived) rest-exercise hemodynamic indices and to compare the association between indices of disease severity and hemodynamic abnormalities identified at rest versus exercise.

Fetal Electrophysiologic Abnormalities in High-Risk Pregnancies Associated With Fetal Demise

Each year world-wide, 2.5 million fetuses die unexpectedly in the last half of pregnancy, 25,000 in the United States, making fetal demise ten-times more common than Sudden Infant Death Syndrome. This study will apply a novel type of non-invasive monitoring, called fetal magnetocardiography (fMCG) used thus far to successfully evaluate fetal arrhythmias, in order to discover potential hidden electrophysiologic abnormalities that could lead to fetal demise in five high-risk pregnancy conditions associated with fetal demise.

EXCOR Active Driving System for the EXCOR Pediatric VAD IDE Study

The purpose of this study is to evaluate the device performance and monitor the safety and effectiveness of the Berlin Heart EXCOR Active Driving System while being used with the approved EXCOR Pediatric Ventricular Assist Device. EXCOR Active Driving System is intended for use with the approved EXCOR Pediatric VAD. The EXCOR Pediatric VAD is intended to provide mechanical circulatory support as a bridge to cardiac transplantation for pediatric patients. Pediatric candidates with severe isolated left ventricular or biventricular dysfunction who are candidates for cardiac transplant and require circulatory support may be treated using the EXCOR Pediatric. EXCOR Active is intended for use in a clinical setting. EXCOR Active can be used in any kind of hospital unit (e.g. OR, ICU, intermediate care unit or general care unit). The driving unit may be moved between clinical units using the caddy or baby buggy; however, a patient must always be accompanied by a person trained in the use of the manual pump and emergency procedures during transport in the event of an emergency. The driving unit can be transported during operation.

Starlight Cardiovascular Lifeline Ductus Arteriosus Stent IDE Study

Starlight Cardiovascular, Inc. is sponsoring a prospective, multi-center, study to evaluate safety and effectiveness of the Lifeline Ductus Arteriosus Stent System. The study device is a stent that is designed to maintain patency of the Ductus Arteriosus for children who need blood flow through that part of the heart.

Fontan Associated Liver Disease and the Evaluation of Biomarkers for Disease Severity Assessment

Background: In Fontan Associated Liver Disease (FALD), congestion of blood in the liver causes cirrhosis. This condition can cause death. Researchers want to understand what triggers this process and find new treatments for it. Objective: To understand how long-term congestion of blood in the liver causes liver scarring that eventually leads to cirrhosis. Eligibility: People aged 18 and older who are at risk of developing FALD from the Fontan procedure. Design: Participants will be screened with: Medical history Physical exam Blood and urine tests Liver ultrasound. This uses sound waves to take pictures of the body. Participants will have an outpatient visit within 12 weeks after screening. Within 24 weeks later, they will have a 3-day hospital stay. About 2 weeks later, they will have a follow-up visit. Visits will include repeats of the screening tests and: Heart tests Stool collection Questionnaires MRI of the liver. Participants will lie on a bed that slides in and out of the scanner. They will receive a contrast agent injected into a vein. While in the scanner, they will also have an MRCP to view the bile ducts and the pancreatic duct. Fibroscan exam. This is an ultrasound that uses a special probe to look at the toughness of the liver. Upper endoscopy. This uses a thin scope to look inside the upper digestive tract. Liver biopsy. This will be taken through large vein in the neck or through the chest. Just before the biopsy, participants will have pressure measurements inside their liver. For this, a catheter will be inserted into a neck vein and guided into the liver.

Extracellular Vesicle Micro RNA Profiling in Congenital Heart Disease: Fetal-Maternal Regulation in Neonatal Thrombosis

Newborns with congenital heart disease (CHD) are at increased risk of developing postpartum and postoperative blood clots after cardiac surgery. The molecular mechanisms that are responsible for the clotting profile predisposing children to blood clots in the early stages of life are currently not well described. The goal of this proposal is to prospectively collect plasma samples from ten (10) neonates with antenatal diagnosis of severe congenital heart disease (CHD) to better understand mechanisms responsible for abnormal clotting in the perioperative period.

Non-Invasive Electrocardiographic Imaging for Personalized Arrhythmia Care in Congenital Heart Disease

To assess the accuracy and clinical utility of a novel non-invasive ECGI mapping system in identifying arrhythmogenic regions of interest in patients with congenital heart disease.

Pediatric Adhesion and New Dermal Approach Study

The purpose of this study is to see if the Zio® monitor device can be worn by children for up to 14-days and to determine if the skin preparation process will provide good adherence to the skin and clear signal quality. The Zio® monitor (Study Device) is an adhesive patch that is worn on the upper left chest for a specified period of time and is similar to a band aid. The Study Device contains a battery-powered heart monitor and will look at the heart rhythm and rate.

Skin Pigment/Pulse Oximeter in Congenital Heart Disease (CHD)

Recent retrospective studies have demonstrated differences between pulse oximeter values (SpO2) and measured arterial oxygen saturation (SaO2) in patients identifying as Black or Hispanic. These retrospective studies have limitations because self-reported race is likely not an accurate metric for level of skin pigmentation and the retrospective nature of these studies may impact the accuracy of simultaneous measures of arterial oxygen saturation and pulse oximeter values. The few prospective studies that have evaluated this issue have utilized color-matching techniques to quantify skin pigmentation, and fewer studies have directly measured skin pigmentation in relation it to pulse oximeter accuracy. The aim of this study is to prospectively measure pulse oximeter accuracy in relation to measured levels of skin pigmentation in the congenital heart disease population.

Remote Monitoring in Pregnant Women With Congenital Heart Disease Using Wrist Wearables

Congenital heart disease (CHD) includes a wide variety of types of disease, including congenital abnormalities of the heart valves. This can range from bicuspid aortic valve and other aortic valve deformities to more complex disease such as tetralogy of Fallot. For many kinds of CHD, the optimal timing of interventions remains unclear. For instance, in tetralogy of Fallot, there is still equipoise about when to offer pulmonary valve replacement (PVR), while in aortic regurgitation, some patients can remain stable for many years. The primary focus of this study is to use continuous physiologic data (CPD), obtained using wearable biosensors (a type of biometric monitoring technology), to develop improved biomarkers of disease progression and prognosis from patients with congenital heart disease (CHD) who are pregnant while they are at home as well as looking at patients' experience and interaction with wearable biosensor technology at home.