Research at the Heart Institute

Our multidisciplinary team of pediatric subspecialists is advancing our understanding of how the Fontan circulation affects quality of life, school performance and development, as well as its impact on other organs in the body.

• As one of the first dedicated multidisciplinary clinics for children and adolescents with Fontan circulation, our team described how we created the clinic, what sort of issues our screen protocol uncovered and what interventions we recommend.
• Because achieving developmental milestones and maximizing school performance are so highly linked to quality of life, we were among the first to explore and describe the relationships between physiologic and neuropsychologic functioning.
• Our team has partnered with the bioengineering department to use cardiac MRI to evaluate the Fontan circulation and associate patterns of flow propagation with clinical outcomes, hoping to one day use MRI to predict adverse events.
• The Heart Institute team helped develop a multicenter learning network called the Fontan Outcomes Network that focuses on improving quality of life for patients with Fontan physiology.
• A recent study from Heart Institute researchers described the impact of a novel treatment for children and adolescents with Fontan physiology from a cardiac ultrasound (echocardiography) standpoint.
• From our unique perspective of living at an increased altitude, we’ve looked at how living in Colorado impacts outcomes for patients with single ventricle heart conditions.  
• A $2.4 million award from the U.S. Department of Defense enables our team to study hypoplastic left heart syndrome (HLHS). The research explores changes in HLHS heart muscle cells that predispose them to failure, the effects of low oxygen, and various drug therapies to see if any improve heart muscle cell contraction.

• The CICU team has run an international survey on the use of vasopressin in patients with single ventricle CHD and is finalizing two clinical studies on the use of vasopressin in this patient population.
• The CICU team is pioneering the application of novel multi-omics technology to explore the complex mechanisms underlying acute postoperative organ injury and the molecular determinants of transition from acute injury to chronic multiorgan dysfunction. 
• A multidisciplinary Cardiac Arrest Reduction and Excellence (CARE) Team was established to decrease the incidence of cardiac arrest and optimize resuscitation practices. Initially launched in the CICU, the debriefing, simulation and resuscitation education has now spread throughout the entire Heart Institute.
• CICU team members are part of a multicentric research study on high-fidelity simulation.
• Our investigators and informatics team led automated data extraction for the first multicenter study from the PCICS Research Innovation Group.
• Our CICU team continues to run clinical research projects on nutrition and outcomes. 

Kawasaki disease (KD) is the number one acquired heart disease in the developed country. Our Kawasaki Disease Clinic is a multidisciplinary clinic between the Heart Institute and our Infectious Disease Program. The collaboration between these two departments has enabled us to take a unified approach in caring for these patients and improved our treatment plan. We are actively involved in the following KD research to help improve patient quality, management and outcomes:

• Participation in the American College of Cardiology Quality Network (ACC QNet) to improve outpatient quality metrics in taking care of KD patients
• American Heart Association-funded grant to study microRNA in distinguishing KD from other febrile illness; a study that has helped us differentiate KD and other childhood febrile illnesses  
• International Kawasaki Disease Registry (IKDR): collection of data on outcomes in KD coronary artery aneurysms and medical management.
• Kawasaki Disease Comparative Effectiveness (KIDCARE) Trial: a randomized trial of second intravenous immunoglobulin versus infliximab for resistant KD 

Multisystem inflammatory syndrome in children (MIS-C) is a severe multisystem hyperinflammatory illness temporally associated with preceding severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection or exposure. Patients have cardiac dysfunction and coronary artery dilations or aneurysms similar to KD patients. Our research has demonstrated that MIS-C patients have better recovery and outcomes after receiving dual therapy (intravenous immunoglobulin and infliximab) at diagnosis. MIS-C patients are less likely to require additional therapy, have decreased development of heart dysfunction, have a more rapid decline in inflammation, and have a decreased intensive care unit length of stay. Children’s Colorado is participating in the Long-Term Outcomes in Multisystem Inflammatory Syndrome in Children (MUSIC study) national clinical trial.   

Read some of our recently published Kawasaki research studies

Our researchers are actively involved in interventional cardiology research that enables us to provide advanced treatment options to our patients. Because we believe that all children should benefit from our research insights, we collaborate with and share our expertise with pediatric experts nationwide.

• Our three core attending physicians are authors on numerous peer-reviewed manuscripts over the last 18 months and over 20 invited lectures at national and international meetings. They have 10 scientific abstracts accepted for publication at major national and international conferences from 2022 to 2023.
• We are among the leading study recruiters in five multicenter trials for cutting-edge equipment and procedures. We have access to all FDA-approved and in-trial percutaneous pulmonary valve devices in the United States.  
• We are leading the way in the use of virtual reality in cath lab case planning and the use of percutaneous ECMO for rescue therapy due to COVID-related illness. We have developed and are publishing on risk-benefit scoring for pediatric and ACHD interventional procedures.
• We are developing novel methods to minimize risk and procedural complexity in percutaneous valve implantation and, with the University of Colorado Inworks Innovation Initiative, have developed novel methods of analyzing 4D CT data to define the behavior of the right ventricular outflow tract.  
• We are pioneering the use of Optical Coherence Tomography in CHD as well as the novel use of computational fluid dynamics. 

Our laboratory resources:

• We have the only in-house 3D printing workshop based on interventional angiography in the country. We have a flow dynamics and valve and stent bench testing lab on campus and are linked with the biomedical engineering school on a number of undergraduate and postgraduate student projects.  
• We have a dedicated flow dynamics lab with an aim to minimize the need for animal and human testing by simulating complex congenital physiology on a benchtop. This led to several patents and collaborative projects across the University of Colorado system.  
• Our clinician researchers hold several competitive grand awards for innovative imaging and tissue engineering projects. 

Children’s Colorado is a national leader in CHD research and a member of Cardiac Networks United, a group of collaboratives aimed at improving the outcomes of patients with congenital and acquired heart disease. These collaboratives include:

• Pediatric Cardiac Critical Care Consortium (PC4)
• Pediatric Acute Care Cardiology Collaborative (PAC3)
• Cardiac Neurodevelopmental Outcomes Collaborative (CNOC)
• National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC)
• Advanced Cardiac Therapies Improving Outcomes Network (ACTION)
• PediPERForm Learning Network (PLN)
• Fontan Outcomes Network
• Congenital Cardiac Research Collaborative (CCRC) 

Through our work in these multi-institutional collaboratives, we have helped improve the care of patients with CHD, not only at Children’s Colorado, but across the nation. Our work in these networks has allowed us to identify practice variation between centers and best practices for diagnosing, treating and preventing morbidity and mortality. 

Through our participation in the Cardiac Networks United, we have successfully decreased the incidence of CICU cardiac arrest, improved outcomes for our single ventricle population and improved outcomes for our patients with ventricular assist devices. We are currently participating in multicenter quality improvement initiatives to:

• Identify and improve healthcare equity and decrease disparities
• Decrease opioid and benzodiazepine exposure in CICU patients
• Decrease emergent transfers from the acute care unit to the cardiac intensive care unit
• Define best practices for treating chylothorax
• Implement programs in the early postoperative period to enhance long-term neurodevelopmental outcomes