Current Pediatric and Congenital Heart Research
Our current research efforts span all types of pediatric and adult congenital cardiovascular topics. See our current research efforts, including clinical trials and collaborations and more, below
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Nitric Oxide Pathway Biomarkers to Assess Prognosis and Individualize Care in Fontan Patients
Major Goals: The major goal of this project is to study the nitric oxide (NO) metabolic pathway to identify biomarkers for predicting death and hospitalization and therapy targets in Fontan patients.
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Overview
The topic of this research is to understand how heart rhythm is generated and to discover the reasons when the rhythm becomes irregular. It uses bioengineering principles to create gene and stem cell-based therapies for cardiac arrhythmias. Dr. Cho's lab works together with engineers and clinicians to develop paradigm-changing therapies for the neediest patients, pediatric and congenital heart disease patients who are dependent on an implanted pacemaker to sustain their lives every day. These bioengineered therapies can be extrapolated to larger cohorts of adult patients, and deliver significant clinical impact.
Somatic cell reprogramming of the heart’s muscle cells to create new pacemaker cells
The heart rhythm originates from a tiny yet highly specialized heart tissue called the sinoatrial (SA) node. The SA node harbors the natural pacemaker cells which send small electrical signal that triggers each heartbeat. Using genetic engineering technologies, Dr. Cho's lab is developing methods to turn ordinary heart muscle cells (called cardiomyocytes) to new pacemaker cells that mimic the natural SA node pacemaker cells that we are born with. The idea is to permanently reprogram the gene expression profile of the cardiomyocytes toward pacemaker cells by brief expression of reprogramming factors, without modifying the genome. The project is designed to discover mechanisms of somatic cell reprogramming, and identify agents for translational projects.
Patterning myocardial specification of human pluripotent stem cells
Pluripotent stem cells can give rise to many organ-specific cells. This project is designed to harness stem cell engineering technologies and guide differentiation of human pluripotent stem cells toward cardiac lineage. The goal is to define pathways to generate specific cardiomyocytes that populate the ventricles, the atria or the cardiac conduction system. The emphasis is on generation of conduction system myocytes for modeling of human heart rhythm diseases. This project is coupled to the “self-organization” project to study 3D architecture of the stem cell-engineered cardiac organoids as disease modeling platforms and therapeutic modality.
Self-organization of the heart’s pacemaker tissue
The goal of this project is to gain insights into how the SA node structure is formed in the first place, and how the node maintains its form to fulfill its function. One of the major aims is to discover what makes the SA node become naturally fibrotic and how the SA node achieves the ‘ideal’ degree of fibrosis. Understanding the principles of the SA node formation will help us define key structural molecules that become dysregulated in sinus node dysfunction, a significant clinical problem that affects both young and old.
Preclinical development of cardiac biological pacemakers
The explicit and ultimate goal of the lab's mechanistic projects is to develop paradigm-changing therapies for pediatric and adult patients with heart rhythm diseases. One of the immediate goals is to advance bioengineered pacemaker cells and organoids as pacemakers in the clinical setting. Current cardiac pacing is entirely device-dependent. For pediatric and congenital heart disease patients, implanted pacemaker devices are far from ideal and sometimes inadequate. This project takes advantage of clinically-relevant small and large animal models of heart rhythm disease as testbeds, and develop biological pacemakers as therapeutic alternatives to implantable devices. The goal is to demonstrate long-term safety and efficacy data in animal models toward a first-in-human trial.
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To determine the role of B,1-4 galactosyltransferase in colorectal cancer
Major Goals: B,1-4 galactosyltransferase is elevated in human colorectal cancer and is implicated in the generation of a novel “lipid second messenger“. We will determine whether this protein/enzyme could serve as a biomarker in this disease.
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Adult biomarkers in neonatal brain injury and development
Major Goals: Determine if circulating levels of brain injury biomarkers are dependent on gestational age and correlate with brain injury imaging (HUS and MRI) and 24 month neurodevelopmental outcomes in premature neonates and neonates with birth related HIE.
Blood test to aid treatment decisions for perinatal asphyxiation
Major Goals: A verified blood test will be developed to determine severity in perinatal asphyxiation
Renal Anhydramnios Fetal Therapy (RAFT) Trial
Major Goals: The purpose of this proposal is to conduct a pilot nonrandomized, prospective multicenter clinical trial to determine the safety, feasibility, and efficacy of Renal Anhydramnios Fetal Therapy (RAFT), prenatal serial amnioinfusions to preserve lung function in early pregnancy renal anhydramios (EPRA).
Role of IGF axis in pulmonary hypertension
Major Goals: Determine the role of the IGF axis of proteins in pulmonary artery hypertension as an indicator of disease severity and their role in the mechanistic pathobiology of pulmonary hypertension.
Role of Cyclohexanone Toxicity in Mediating Congenital Cardiac Surgery Outcomes
Major Goals: We will determine the role of the medical plastic contaminant cyclohexanone in congenital heart surgery outcomes, methods for removal from the cardiopulmonary bypass circuit and mechanisms of effects on injury, learning and memory.
PHora: A Clinical Decision Support Tool for Patients with Pulmonary Arterial Hypertension
Major Goals: Develop and deploy a well calibrated, validated, easy to use clinical decision support system (PHORA). That will facilitate rapid adoption by providers (pediatric & adult) into clinical practice and which learns “best intervention patterns”, that can be incorporated into practice guidelines
Advanced therapeutic hypothermia efficacy network modeling in neonatal HIE
Major Goals: Using a holistic and integrative approach, including deep clinical and community-based data, and molecular biomarkers of multiple biologic pathways, analyzed using a fully connected parsimonious neural network will best describe relationships with longitudinal outcomes, and be able to predict response to therapeutic hypothermia (TH) in individual patients. Our model will be validated with new enrollment of neonates with hypoxic-ischemic encephalopathy (HIE) treated with TH from 3 centers.
Children are not Small Adults: The Pediatric Pulmonary Hypertension Risk Score
Major Goals: The overall goals of this application are to 1) complete the development of the Pediatric PH Risk Calculator; 2) enrich the PPHNet Registry with enrollment and phenotypic data collection from new pediatric patients to validate the Pediatric Risk model with the newly enrolled patient cohort. Advanced analytics such as Bayesian modeling will be used to develop an optimized Risk Model. An independent dataset will inform the operating characteristics and refinement of the Calculator prior to dissemination to clinicians in the field. A pediatric specific severity/mortality risk model will be a tremendous advancement for the PH community of caregivers and families by offering improved prognostication, more tailored management of the clinical course of children with PH, and targeted selection of PH patients for future pediatric clinical trials.
Multicenter epidemiology and prediction of neonatal CHD-associated necrotizing enterocolitis
Major Goals: To describe the incidence and clinical risk factors associated with necrotizing enterocolitis (NEC) in neonates requiring cardiac surgery, and develop a risk prediction model that may help reduce the incidence of NEC.
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Mechanisms of Left Side Obstructive Lesion Development: Exome Sequencing of Left-Side Obstructive Lesions in Congenital Heart Disease
Major Goals: Using a group of patients with six deeply phenotyped groups of left side obstructive lesions, identify common candidate causative genes and pathways.
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Phenotypic and mechanistic differentiation of coronary microvascular dysfunction
Major Goals: The aim of this research is to delineate distinct phenotypes of coronary microvascular disease, to determine the expected responses to therapy for each phenotype, and to use these findings to inform registry and randomized controlled trial design.
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Mechanisms of Right Ventricular Dysfunction in Scleroderma-associated PAH
Major Goal: To examine determinants of RV dysfunction in Scleroderma
Co-investigators: Dr. Paul Hassoun; Dr. David Kass
Pathogenesis and in vivo suppression of thin filament-based cardiomyopathies
Major Goal: to understand how human cardiomyopathy mutations located at conserved interfaces between thin filament subunits lead to disease.
Principal Investigator: Dr. Anthony Cammarto
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The therapeutic role of LOXL2 in pulmonary hypertension
Major Goal: To investigate the role for lysyl oxidase-like 2 (LOXL2) as a novel target in pulmonary hypertension.
Lysyl oxidase like 2: A novel target in aging associated vascular stiffening
Major Goal: To examine the mechanisms of by which LOXL2 is regulated in the vasculature, and the mechanisms by which LOXL2 mediates vascular stiffening in aging.
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pECGrepository Research
Major Goal: We have created a repository of de-identified ECG interpretations submitted to the educational app, pECGreview, for use in research seeking to optimize training in ECG interpretation.
For a complete list of available pediatric clinical trials, please visit our clinical trial database. You can also search by condition, researcher or doctor's name.
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Association of Biomarkers and Postoperative Delirium in Children After Cardiac Bypass Surgery
Major Goal: To examine the association between changes in plasma biomarkers and delirium occurrence in children undergoing cardiac surgery requiring cardiopulmonary bypass.
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Biomarkers of Brain Injury in Critically-Ill Children on Extracorporeal Membrane Oxygenation (BEAM)
Major Goals: The major goals of this NIH/NINDS-funded study are to develop and refine a brain injury multimarker panel for accurate neurologic monitoring at the bedside and early classification of mortality and disability outcomes that will allow real-time neuroprotective interventions during the ECMO course of critically ill children with cardiorespiratory failure requiring extracorporeal life support.
Evaluation of Response to Human Antithrombin-III in Pediatric Patients Supported on ECMO
Major Goals: The major goals of this study are to determine the proportion of pediatric patients on ECMO support with low antithrombin activity and develop a population pharmacokinetic model for pooled antithrombin in pediatric patients supported on ECMO that may be used to optimize dosing of pooled antithrombin in these critically ill children.
ARDS in Children and ECMO Initiation Strategies Impact on Neurodevelopment (ASCEND) (PI: Ryan Barbaro)
Major Goals: The overall objective of this study is to compare short and long-term patient outcomes in two groups of children: one group managed with a mechanical ventilation protocol that reserves the use of extracorporeal membrane oxygenation (ECMO) until protocol failure to another group supported on ECMO per usual care. (JHU – Participating Site)
TITRE - Trial of Indication-based Transfusion of Red Blood Cells in ECMO (PI: Lynn Sleeper)
Major Goals: The overarching goal of this project is to determine whether restricting red blood cell transfusion according to an indication-based strategy for those with bleeding and/or deficit of tissue oxygen delivery, compared with transfusion based on center-specific hemoglobin or hematocrit thresholds, can reduce organ dysfunction, and improve later neurodevelopment in critically ill children receiving ECMO support.(Bembea – Research Monitor)
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Fontan Outcome Registry Using CMR Examinations (FORCE)
Major Goals: Understand how parameters on cardiac magnetic resonance imaging are associated with clinical outcomes in patients with Fontan circulation (multicenter study).
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Chilled Platelet Study (CHIPS)
Major Goal: Non-inferiority multi-center blinded and randomized study to evaluate cold platelets versus standard temperature patients in children and adults undergoing bypass surgery.
Clinical incidence and Descriptive Analysis of Malignant Hyperthermia: A Multi-Institutional Retrospective Data Analysis
Major Goal: Multi-center study to evaluate the true incidence of Malignant Hyperthermia.
Blood product utilization in pediatric cardiac surgical patients
Major Goal: Evaluate optimal practices regarding blood product utilization in pediatric cardiac surgical patients.
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Congenital Heart Surgeons’ Society (CHSS) Studies in Congenital Heart Disease
Congenital Heart Disease Biorepository
Major Goals: Biological specimens are collected from patients with congenital heart disease and stored in a biobank for future scientific research. Enrollment is ongoing.
Minimally Invasive Metabolic Monitoring Using Doubly Labelled Water
Major Goals: Build personalized growth curves for single ventricle patients between the first and second stages of palliation using energy expenditure calculated from ingested stable isotopes.
The Effect of Post-Operative Telemedicine Wound Appointments on Patient Cost, Satisfaction, and Compliance
Major Goals: Evaluation of telemedicine as a superior approach to postoperative wound evaluation.
Identifying Biomarkers Associated with Growth in Children with CHD
Major Goals: Using a cohort of patients with congenital heart disease, biomarkers associated with growth and failure to thrive were evaluated (manuscript submitted).
Towards the Use of Image-Based Computational Models to Improve Durability of Bioprosthetic Pulmonary Valves
Major Goals: Retrospective study of bioprosthetic pulmonary valve durability as a function of the position of implantation.
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Longeveron Mesenchymal Stem Cells (LMSCs) Delivered During Stage II Surgery for Hypoplastic Left Heart Syndrome (ELPIS II)
Major Goal: Evaluate whether allogenic human mesenchymal stem cells (MSCs) treatment will benefit patients with hypoplastic left heart syndrome. Use Cardiac magnetic resonance imaging to examine myocardial structure and function among participants enrolled in the trial at baseline and pre-determined follow-up periods.
A Phase 4, Open-Label, Non-randomized, Multicenter Study to Evaluate Safety and Efficacy of Intravenous Administration of OPTISON for Contrast-Enhanced Echocardiography
Goal: Identify the dose of OPTISON and to evaluate its efficacy and safety after intravenous administration in children and adolescents undergoing transthoracic echocardiography.
The Post-Acute Sequelae of COVID-19 (PASC) Investigator Consortium: Adult Acute/Recovery Cohort Study: NIH Phase II RECOVER Initiative
Goal: Investigate long-term and delayed impacts of COVID-19 using multicenter data including clinical information, laboratory tests and analyses of participants in various stages of recovery following SARS-CoV-2 infection.
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Collaborative Study of Long-term Outcomes of COVID-19 in Kids (CLOCK)
Major Goals: The objective of the CLOCK consortium is to participate in the NIH RECOVER initiative (pediatric cohort) to study the long-term effects of SARS-CoV-2 infection in children, particularly as they relate to post-acute sequelae of COVID-19 (PASC).
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Renal Anhydramnios Fetal Therapy (RAFT) Trial
Major Goals: The purpose of this proposal is to conduct a pilot nonrandomized, prospective multicenter clinical trial to determine the safety, feasibility, and efficacy of Renal Anhydramnios Fetal Therapy (RAFT), prenatal serial amnioinfusions to preserve lung function in early pregnancy renal anhydramios (EPRA).
Steroids to reduce Systemic Inflammation after Neonatal Heart Surgery (Stress trial)
Major Goals: The objective of the STRESS trial to participate in multi-center NIH sponsored study to assess the effect of steroids at time of neonatal heat surgery.
Advanced cardiac therapies improving outcomes network to improve the health of pediatric and congenital heart disease patient with heart failure (ACTION network clinical trial)
Major Goals: The objective of the ACTION network consortium is to participate in a pediatric cohort to study the short and long-term outcome of pediatric and congenital patients with heart failure
National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions (GenTAC)
Major Goals: The objective of GenTAC consortium is to participate in a NIH pediatric and cohort study the genetics causes, incidence and clinical outcomes of patients with thoracic aortic aneurysms. (Enrollment is now closed)
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Cardiovascular Outcomes Research in Perioperative Medicine - COR-PM
Major Goal: To establish a new conference geared at bringing junior clinician-scientists in the wider field of perioperative medicine from around the world together in an innovative way.
Medical Device Design
Danielle Gottlieb-Sen
Prospective Measurement of Impedance during Cardiac Catheterization to Build a Non-Invasive Cardiac Output Algorithm
Major Goals: Using a custom built bioimpedance and NIRS-based device, we will prospectively evaluate the relationship between monitored waveform data and gold standard monitors. In addition, we aim to build algorithms predictive of cardiac output for patients with congenital heart disease.
Investigating Bio-Impedance and Near Infrared Spectroscopy Waveform Characteristics in Healthy Infants
Major Goals: Using a custom-build bioimpedance and NIRS-based device, we will evaluate waveform characteristics in healthy newborns.
A Study to Determine the Optimal Detector-Emitter NIRS Configuration in Pediatric Patients
Major Goals: Using a custom-built benchtop model and computational models, we will configure a novel device for early detection of necrotizing enterocolitis in newborns with congenital heart disease.
Data Science and Informatics
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Characterization and prediction of disease progression in early-stage hypertrophic cardiomyopathy using personalized, image-based computational models and machine learning
Major Goals: Understand changes in myocardial structure and mechanics in early stage hypertrophic cardiomyopathy using cardiac magnetic resonance imaging, computer modeling, and machine learning.
Outcomes Modeling and Decision Making for Hereditary Thoracic Aortic Disease Using the Collaborative for Longitudinal Aortic Imaging in the Young (CLARITY)
Major Goals:
- Predict and compare clinical outcomes of varying thresholds for aortic replacement surgery using a patient-level simulation model for Marfan syndrome and Loeys-Dietz syndrome.
- Predict clinical outcomes in the highest-risk subcohort, those with mutations in COL3A1causing Vascular Ehlers-Danlos syndrome, using a patient-level simulation model.
- Predict aortic dissection from cross-sectional imaging.
- Describe the longitudinal changes in cardiovascular features in patients with or at risk of aortic disease.
- Understand factors associated with adverse outcomes in patients with or at risk of aortic disease
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A data science approach to identify and manage Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 infection and Kawasaki disease in pediatric patients
Major Goals: The primary objective of this study is to design and validate a predictive decision support system for the identification, treatment and management of SARS-CoV-2 associated with multisystem inflammatory syndrome in children (MIS-C). To develop this system, we will adapt and retrain machine learning algorithms which we have previously trained in patients with Kawasaki Disease, a pediatric inflammatory vasculopathy with multiple similarities to MIS-C. This study, performed in collaboration with the International Kawasaki Disease Registry (IKDR) consortium, will consist of two phases, first a large-scale data collection and algorithm development effort and second, the prospective evaluation of the performance and clinical utility of the algorithm ahead of large-scale deployment.
Computational simulation of the potential improvement in clinical outcomes of cardiovascular diseases with the use of a personalized predictive medicine approach
Major Goals: The current medical paradigm is to treat most patients according to standard clinical guidelines, which in the majority of cases results in all patients with a similar condition receiving substantially similar treatment, this is in opposition to personalized approaches which use prediction models to assign treatment. We aim to quantify the potential benefits of using a personalized approach by simulating the outcomes of predictive allocation in ~120 previously published NHLBI randomized controlled trials. We will compare the simulated outcomes of predictive allocation to a secondary simulation where all patients are treated similarly and thus determine under what circumstances and to what extent, would predictive allocation result in a net benefit at the population level.
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Retrospective Analysis of Cardiac Output Monitoring to Identify Predictive Physiologic Patterns in Patients with Congenital Heart Disease
Major Goals: Using previously collected clinical data, we will look for correlates of cardiac output in patients with congenital heart disease undergoing cardiac catheterization.
Retrospective Analysis of Low Cardiac Output Syndrome in Pediatric Patients Who Underwent Cardiopulmonary Bypass
Major Goals: Using previously collected clinical data, we will evaluate low cardiac output syndrome in patients who underwent palliative and corrective heart surgery.
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A data science approach to identify and manage Multisystem Inflammatory Syndrome in Children (MIS-C) associated with SARS-CoV-2 infection and Kawasaki disease in pediatric patients
Goal: Design and validate a predictive decision support system for the identification, treatment and management of SARS-CoV-2 associated with multisystem inflammatory syndrome.
Microsoft, Inc. and GE Healthcare
Computational and research resource support for Artificial Intelligence initiative developments in cardiac imaging and digital health platformsGoal: Provide a medical imaging annotation tool integrated in Precision Medicine Analytics Platform (PMAP) that can drastically reduce the time needed for high quality annotation of supervised learning medical imaging projects.
Computational simulation of the potential improvement in clinical outcomes of cardiovascular diseases with the use of a personalized predictive medicine approach
Goal: Quantify the potential benefits of using a personalized design approach by simulating the outcomes of predictive allocation in ~120 previously published cardiovascular randomized controlled trials from the National Heart, Lung, and Blood Institute.