Heart Research

Researchers studying the biology of the pediatric heart hope to help the next generation of children overcome heart disease. The following project is in development:

Electrical Stimulation of Pediatric Cardiac-Derived c-kit+ Progenitor Cells Improves Retention and Cardiac Function in Right Ventricular Heart Failure
Principal investigator: Joshua T. Maxwell, PhD

Cardiac stem cells, otherwise known as progenitor cells, have shown promise in treating several problematic and sometimes lethal conditions like heart failure. Our HeRO investigators have been among the leaders in strategies to utilize these cardiac progenitor cells to reverse heart failure or to prevent it.

Dr. Maxwell and his colleagues employed a novel technique to enhance the efficacy of these cardiac progenitor cells, or CPCs, in a study published in Stem Cells. Leveraging early work from animal models, Maxwell’s team demonstrated that electrical stimulation of cardiac derived c-kit progenitor cells, taken from the pediatric patient at the time of newborn heart surgery, could improve the cardiac function and retention of the cells.

In well-designed experiments, Dr. Maxwell and his colleagues demonstrated the mechanism by which electrical stimulation improves CPC function. The impact of electrical stimulation can be seen in important clinical parameters in this model, including improved contractility of the right ventricle and lessened dilation of the right ventricle as a response to injury. Electrical stimulation of the CPCs also reduced fibrosis in the heart.

This work will support ongoing basic translational and clinical work in our Heart Center. We are currently undertaking a first-in-human trial of c-kit cardiac progenitor cells in hypoplastic left heart syndrome. The work of Dr. Maxwell and his colleagues has immediate applicability to these clinical trials and may impact direct patient care in the future.

Heart researchers are conducting clinical trials to discover new treatments and techniques in several areas of children’s heart care.

Visit clinicaltrials.gov to find a Children’s clinical trial. Search for “Children’s Healthcare of Atlanta” and your child’s condition.

Placing Stem Cells Into the Hearts of Babies With Congenital Heart Disease

Principal investigator: Michael Davis, PhD, Director of the HeRO Center and Professor of Biomedical Engineering at Georgia Tech and Emory University

In this groundbreaking trial, surgeons at Children’s will implant patient-derived stem cells into the hearts of babies with hypoplastic left heart syndrome (HLHS) while they are undergoing surgical repair. The cells are collected during a baby’s first surgery within the first few days of life and then implanted into the heart three to five months later during the second of three HLHS surgeries. In the future, Dr. Davis and his research partners hope to gather quantitative data on the behavior of stem cells to create a large data repository of cell signals. By studying the signals, otherwise known as protein secretions of the cell, the team aims to determine how effective certain cells are in treating diseases.

COVID-19 and the heart

COVID-19 has significantly impacted children in Georgia, and researchers at Children’s are playing a critical role in understanding the cardiovascular impact of COVID-19. We are participating in two important national studies of COVID-19 and Multisystem Inflammatory Syndrome in Children (MIS-C) through two NIH studies, Pragmatic and Implementation Studies for the Management of Pain to Reduce Opioid Prescribing (PRISM) and MUSIC, An Observational Cohort Study to Determine Late Outcomes and Immunological Responses After Infection With SARS-CoV-2 in Children With and Without Multisystem Inflammatory Syndrome (MIS-C).

An Observational Cohort Study to Determine Late Outcomes and Immunological Responses After Infection With SARS-CoV-2 in Children With and Without Multisystem Inflammatory Syndrome (MIS-C)

Principal investigator: William Mahle, MD, Pediatric Cardiologist

The study will enroll a minimum of 250 children with COVID-19 and/or MIS-C at more than 20 U.S. centers. MIS-C is a complication that follows a COVID-19 infection, which often impacts the heart. The study is designed to understand how the immune system responds to the COVID-19 infection and whether some aspects of the immune response contribute to the symptoms and complications. Much of the work analyzing the samples will be performed by Ignacio Sanz, MD, Chief of the Division of Rheumatology at Emory University, and Jeremy Boss, PhD, Chair of the Department of Microbiology at Emory University.

Long-Term Outcomes After the Multisystem Inflammatory Syndrome in Children (MIS-C) Study

Principal investigator: Matt Oster, MD, Pediatric Cardiologist

The goal of this research, conducted across 29 different sites as part of the Pediatric Heart Network, is to determine the spectrum and duration of coronary artery involvement, left ventricular (LV) systolic function, arrhythmias or conductions system disturbances within the first year from MIS-C illness onset, and to define the associated clinical and laboratory factors.

COVID-19-Related Multisystem Inflammatory Syndrome in Children (MIS-C) Affects Left Ventricular Function and Global Strain Compared With Kawasaki Disease 

Principal investigator: Mansi Gaitonde, MD

Clinical observations of the cardiac impact of MIS-C during the COVID-19 pandemic suggest more myocardial (heart muscle) involvement than typically occurs in Kawasaki disease (KD). Dr. Gaitonde and a team of researchers sought to formally evaluate this by performing a detailed cardiac functional analysis comparing contemporary MIS-C cases with a historical control group of KD cases. Left ventricular systolic function parameters were significantly reduced in MIS-C compared to KD, including ejection fraction, global longitudinal strain (GLS) and global circumferential strain. Of the MIS-C patients with depressed left ventricular function on admission, 75% had improvement in ejection fraction but still had reduced GLS values at hospital discharge. In summary, children with MIS-C appeared to have higher rates of myocardial dysfunction evidenced by reduced ejection fraction and reduced strain values compared to KD, and while the majority of MIS-C patients had recovery of ejection fraction, the strain values remained reduced beyond the acute infection. The implications of this in the long-term recovery period from MIS-C remain to be understood.

Anesthesiology

A Pilot Study of Thrombin Generation Changes in Neonates Undergoing Placement of a Blalock-Taussig Shunt

Principal investigator: Nina Ann Guzzetta, MD, Pediatric Cardiac Anesthesiologist

A Blalock-Taussig (BT) shunt is a device that redirects blood flow into pulmonary circulation, which moves deoxygenated blood away from the heart to the lungs and returns oxygen-rich blood back to the heart. It’s often placed in newborns with right-sided obstructive heart defects to improve blood flow. In the immediate hours after BT shunt surgery, it’s not uncommon for the newborn to experience complications due to blood clotting problems. This study explores the changes in thrombin generation, a critical part of clot formation, in newborns who undergo the surgery.

Catheterization lab

Comparison Between Surgical vs. Balloon Angioplasty vs. Intravascular Stent Placement for Recurrent or Native Coarctation of the Aorta

Principal investigator: Dennis Kim, MD, PhD, Pediatric Cardiologist

This study compares the safety and efficacy of three methods for treating coarctation, a narrowing of the aorta: surgical angioplasty, balloon angioplasty and stent placement. Angioplasty is a procedure that’s used to open arteries that are narrowed or blocked by plaque, a fatty buildup. It can be performed using a traditional open heart procedure or a catheter-based procedure—a minimally invasive technique that uses a thin, flexible tube inserted through a small incision and threaded to the blocked area. Balloon angioplasty has a small balloon on the tip of the catheter that’s inflated at the blockage to compress the plaque against the artery wall. A stent is a small, expandable tube that’s inserted into the artery during angioplasty to hold open the artery.

Cardiac Intensive Care 

Gut Microbiome and its Association with Growth Trajectories in Infants with Congenital Heart Disease

Principal investigator: Michael Fundora, MD, Pediatric Cardiologist

This study examines if good bacteria influences growth and how it changes during the hospital course in babies with congenital heart disease. In partnership with Jinbing Bai, PhD, assistant professor at the Emory University School of Nursing and expert on the microbiome, Dr. Fundora will recruit 50 babies from the Children's Heart Center's cardiac intensive care unit (CICU) and 50 control babies from Emory Midtown, and match them to each other to compare their gut microbiome before and after surgery, and at discharge. The goal is to observe if there is disruption in the microbiome before and after surgery, how it changes during that period and determine its relationship to weight gain, head circumference and length, to see if there is any evidence the microbiome has an impact on growth. If so, future larger trials may lead to an interventions to promote weight gain after surgery which is associated with better outcomes. This research is funded by the Emory School of Medicine I3 Nexis award at $75,000 for two years.

Children’s Cardiologist Publishes COVID-19 Vaccination and Myocarditis Research

Dr. Matthew Oster, pediatric cardiologist at the Children’s Heart Center, led a descriptive study looking at data from the Vaccine Adverse Event Reporting System (VAERS) through the Centers for Disease Control and Prevention (CDC) to understand the risks and outcomes of myocarditis after mRNA-based COVID-19 vaccination through Moderna and Pfizer. Myocarditis is inflammation of the heart from viral infection. This data was collected across the U.S. from more than 190 million individuals ages 12 and up. From this population, there were 1,991 reports of myocarditis and 1,626 met the case definition for the condition. Findings showed that the risk of myocarditis after receiving mRNA-based COVID-19 vaccines was increased across multiple age and sex groups. Males made up 82% of cases, and rates of myocarditis were highest after the second vaccination dose in adolescent males ages 12-17 and young men ages 18-24. Of those with myocarditis who were hospitalized, 87% had resolution of presenting symptoms at hospital discharge. The study was published in JAMA on January 25, 2022.

Children’s Cardiologist Partners with Georgia Tech for IV Safety Study

Children’s cardiologist Zahidee (Saidie) Rodriguez, MD, partnered with Georgia Tech engineers to research a newly developed sensory device that significantly improves IV safety. This device helps nurses detect and reduce infiltration, which is unintended IV leakage that is common in children due to small vein size.

We’re widely recognized for our MRI studies of the heart and our heart echocardiography (ultrasound) program. Our dedicated core laboratory, the CIRC, is developing new strategies to evaluate the heart under conditions of stress or exercise.

Our researchers are working with colleagues at Georgia Tech to use imaging technology to create a 3D reconstruction of the heart. This will help us continue to improve the way we plan and carry out heart surgery in young patients.

The Cardiovascular Imaging Research Core (CIRC) lab was established in 2011 to conduct cardiac imaging research studies and incorporate novel and non-traditional imaging techniques into clinical practice. CIRC provides non-invasive cardiac imaging support for investigators engaged in clinical research involving fetuses, neonates, infants, children and adolescents. Our dedicated team of physicians, scientists, sonographers and research coordinators is experienced in utilizing cardiac imaging modalities and techniques not typically seen in the clinical setting.

The CIRC has dedicated laboratory space on both the Egleston and Scottish Rite hospital campuses. It is one of only a few labs in the country with the infrastructure to provide support for pediatric cardiac imaging research. In addition to cardiology, CIRC services have been used by several other clinical services, including but not limited to cardiothoracic surgery, nephrology, hematology-oncology, neurology, genetics, gastroenterology and infectious diseases.   

Research services offered by CIRC include:

• Imaging protocol development
• Clinical site training and quality monitoring
• Image analysis
• Image transmission
• Data management
• Research quality imaging
• Cardiac MRI logistical and analysis support

Testing offered through CIRC includes:

• Echocardiography
  • 2D, spectral and color Doppler
  • 3D echocardiography
  • Tissue Doppler imaging
  • Strain and strain-rate imaging
• Vascular function assessment
• Cardiac computerized tomography including 3D reconstruction and digital printing
• Cardiac magnetic resonance imaging, including 4D flow
• Exercise stress testing
• Stress echocardiograms
• Electrocardiograms (EKG)
• Holter monitoring

Multicenter Core Lab Capabilities at CIRC

In 2016, CIRC created an infrastructure to serve as a multicenter core lab. Cardiac imaging studies from multiple centers can now be sent to CIRC for off-line analysis using a vendor-neutral software. Sites participating in the study upload images to our picture archiving and communication system (PACS) using a cloud-based technology. Our experienced team provides unbiased, centralized analysis of the deidentified images using a specialized software that minimizes errors that may result when images are collected from multiple centers using different imaging machines. CIRC staff maintains an electronic research database for the studies, as well as an image repository for all studies analyzed.

Collaborations

Our national research collaborations include:

• Pediatric Heart Network
• Fetal Heart Society
• Children’s Oncology Group
• Cardiac Genetics Registry
• FORCE (Fontan collaborative)
• American College of Cardiology Quality Network
• Society of Pediatric Echocardiography

Meet the team

• Ritu Sachdeva, MD, FACC, FASE, Medical Director
• Sassan Hashemi, MD, Imaging Scientist
• David Cox, RDCS, Cardiac Sonographer Supervisor
• Amanda Harding, RDCS, Senior Cardiac Sonographer
• Deanna Hill, CCRP, Research Coordinator
• Jaimee Housey, RDCS, Cardiac Sonographer
• Guadalupe Izaguirre, BS, Research Coordinator
• Joan Lipinski, MHS, RDCS, FASE, Manager of Echocardiography and CIRC
• Gemma Morrow, RDCS, Senior Cardiac Sonographer
• Brian Schlosser, BS, RDCS, RDMS, FASE, Clinical Educator
• Anna Kate Shaw, RDCS, Cardiac Sonographer

Researchers are exploring areas in which heart disease and neurological development impact one another. Our findings will help us develop new therapies to improve the quality of life for children with heart disease—everything from medications and traditional psychological therapy techniques to at-home strategies to help families.

Learning and social interaction

Research shows that a large percentage of children with congenital heart disease face academic challenges, including attention problems and difficulties planning and executing important daily tasks, known as executive function. In addition, there’s emerging evidence that these children may have problems interacting with their peers, which can have a serious impact in adolescence and young adulthood. Peer interaction is an important part of a child’s emotional development, including self-esteem and identity.

By evaluating children at 1 year old and again at 2 years old, we’re better able to understand the causes of these problems and develop therapies to improve outcomes.

Infant brain injury

Our researchers are analyzing infant brain injury and exploring the causes of the inflammatory process with MRI and the latest translational tools. In preliminary results, we’ve found that more than 50% of newborns who require open heart surgery have injury to the white matter in their brain. We’re exploring how signals within the body, called cytokines, may contribute to this process. Researchers need to gather more information to understand the factors that contribute to early brain injury, but this research could help us prevent it more effectively.

More and more children with heart problems are living decades beyond what was expected in previous generations. But sometimes this success comes at a high price: neurological problems, lingering heart problems and damaged organs due to years of poor blood flow.

The Center for Cardiac Outcomes Research is exploring ways to meet the long-term needs of children with heart disease and their families.

Research goals are to:

• Determine what improves the quality of life for most children with heart disease.
• Prevent future complications related to a child’s heart condition.
• Use electronic medical records to do research and improve long-term follow-up care for these children.

Researchers are involved in dozens of projects that include public health policy, clinical review and technical innovation. One current project is evaluating whether all newborns should receive screening that can detect previously missed heart defects—whether the rare chance that the screening catches a defect justifies the additional cost of the test. This is an example of how studies measure both what’s medically effective and what’s cost effective.

In addition, the research team is exploring clinical practices to determine whether there are trends of consistently good long-term outcomes or if treatment at a certain point of children’s development results in better outcomes when they’re adults.

From Buzzy—an electronic “bee” that takes away the pain of injections—to a heart valve that grows with a child, we look for new ways to make medical devices that make children more comfortable at the Children’s Heart Center.

Most medical equipment is designed and intended for adults, but children have different needs—both physical and emotional. In addition, because kids are always growing, these medical devices often lack flexibility. That means children have to go through multiple rounds of surgery to replace outgrown heart stents and valves, along with numerous other implants. These surgeries put them at needless risk for bleeding, infection and clots.

In partnership with Georgia Tech and Emory University, we created the Children's Healthcare of Atlanta Pediatric Technology Center to address the special needs of children. This program, funded with a $1.8 million grant from the U.S. Food and Drug Administration (FDA), is a joint effort among doctors, scientists and engineers to find ways to build equipment, implants and devices that are scaled and designed for kids.

Our first projects include developing a:

• Smartphone attachment that allows real-time video consultation for ear infections.
• Renal dialysis device to replace existing machines meant for adults.
• Gel that delays the re-fusion of a child’s skull after surgery for craniosynostosis—a condition in which the stitches in an infant’s head prematurely fuse, causing abnormal head shape and facial features.

Researchers are also looking at a number of high- and low-tech healthcare solutions for kids, from a new eye chart that uses hand motions instead of the alphabet to a quick test for pneumonia that uses a modified whistle or kazoo.

Children’s investigators have been addressing key topics in heart failure and heart transplantation.

Use of Ventricular Assist Device (VAD) to Support Patients Before Transplantation

Dr. Butto presented important work at the 2020 American Heart Association meeting that looks at the best approach to transplant listing after VAD implant. Her analysis of a large dataset found that it may be best to wait several weeks after a VAD is implanted before proceeding with a heart transplant in children. The likely explanation for this benefit is that the child can rehabilitate and enhance his nutritional status before receiving the transplant.

Principal investigator: Arene Butto, MD, Pediatric Heart Failure Physician

Dr. Butto presented important work at the 2020 American Heart Association meeting that looks at the best approach to transplant listing after VAD implant. Her analysis of a large dataset found that it may be best to wait several weeks after a VAD is implanted before proceeding with a heart transplant in children. The likely explanation for this benefit is that the child can rehabilitate and enhance his nutritional status before receiving the transplant.

Studying Heart Failure in Children and Young Adults With Congenital Heart Disease Using the Pediatric Care Consortium

Principal investigator: Lazaros Kochilas, MD, Pediatric Cardiologist

Dr. Kochilas and his team leveraged the large database, Pediatric Cardiac Care Consortium, housed at Children’s and Emory University, to understand how heart failure impacts children and young adults with CHD.

Our areas of interest include:

• Mechanical support of the failing heart
• Heart failure management
• Blood group incompatible transplants (donor and recipient don’t have compatible blood types)
• Noninvasive markers of transplant rejection
• Antibody-mediated rejection, which occurs when a transplant recipient’s own antibodies attack (reject) the new transplant
• Re-transplantation