Marfan Syndrome (MFS) is a relatively common inherited disorder of connective tissue caused by mutations in the gene for fibrillin-1. In this study, we hope to learn more about early heart disease in people with Marfan syndrome and other related diseases. We will do this by looking at blood samples to determine whether there are differences in certain proteins that reflect the genes of people with and without these disorders.
For many patients, the transition from pediatric to adult care can be confusing and overwhelming. Lurie Children’s Heart Center and the Bluhm Cardiovascular Institute at Northwestern Medicine have partnered to launch a first-of-its-kind program to help guide adolescents during the transition years. Transition refers to all of the planning, preparation and skill building that leads up to and surrounds the actual transfer of care, including choosing a new physician, transferring medical records, communicating treatment histories and navigating insurance coverage. The Cardiovascular Bridge programs are designed as a partnership between the patient, family, pediatric and adult cardiac providers to successfully bridge the medical needs of young patients with heart disease.
The first Cardiovascular Bridge Program has successfully launched for patients 16-26 years old with bicuspid aortic valve disease and aortopathy. Additional programs will be developed in coming years, expanding services to cardiomyopathy, adult congenital heart disease, transplant/extracorporeal support and preventive cardiovascular medicine. A fundamental aspect of the program is the specialty clinics designed to bring pediatric and adult cardiologists, nurses and other health care professionals together in a single setting, allowing young patients to start building relationships with the adult healthcare team they will continue to see in the future.
The main goals of the program are to:
Increase understanding of their condition
Identify and address individual barriers to transition
Learn to navigate the adult healthcare system and insurance needs
Become more involved and independent in their health care
Develop relationships and learn to communicate with adult providers
Develop skills necessary to be successful in future
Another significant aspect of the programs is to understand and optimize clinical outcomes for these high-risk cardiac populations through research. Lurie Children's Heart Center Research Core and the Bluhm Clinical Trials Unit have joined resources to coordinate research efforts across a patient’s lifespan from childhood, through adolescence and young adulthood, into adulthood. These research endeavors will help guide the best courses of care for a patient and give physician-scientists opportunities to better understand the natural history and mechanisms of heart disease.
Lurie Children's Cardiac Imaging team is leading several research inititatives. Learn more.
The multidisciplinary MR/CT program is leading research to reduce MR imaging exam time and minimize anesthesia or sedation used during imaging exams. In the multi-year NIH/NHLBI funded study, Functional Cardiovascular 4D MRI in Congenital Heart Disease, Lurie Children's cardiologist Joshua Robinson, MD, and radiologist Cythia Rigsby, MD, are collaborating with Northwestern bioengineers to develop a comprehensive 20-minute 4D MR exam that might replace the standard 60-90 minute MRI protocol. In addition to studying how the new technique may reduce exposure to anesthesia, the team is investigating how 4D visualization of complex blood flow dynamics may predict progression of cardiovascular disease. Learn more about medical imaging research.
Clinically silent genetic diseases may be responsible for as many as 25% of sudden unexplained deaths between 1 and 35 years of age. Given this high genetic incidence, a sudden unexpected death in a family member is a signal that other relatives may also be at risk for sudden death. Pediatric cardiac electrophysiologist R. Gregory Webster, MD, is engaged in research focusing on two issues that might prevent optimal evaluation of first-degree relatives of victims. First, we do not yet understand which clinical tests will lead to a diagnosis in the family. Second, no studies have evaluated how often genetic mutations are new mutations in the deceased child versus familial mutations present in the family. Dr. Webster’s research is a partnership between Lurie Children’s, medical examiners in Illinois and the Cardiovascular Genetics Center at Northwestern University. This collaboration provides a unique ability to identify clinical and genetic risk factors for sudden unexplained death in young persons and their family members.
“Pediatric Heart Transplant Study (PHTS)” – Dr. Elfriede Pahl
The Pediatric Heart Transplant Study (PHTS) is a multi-center event driven study that was initiated by the University of Alabama at Birmingham on January 1, 1993 with the primary purpose being to examine the risk factors and outcome events following listing of a patient for a pediatric cardiac transplantation. The goal is to advance our state of knowledge and to disseminate this information via presentations at national meetings and by generating manuscripts for publication in peer-reviewed journals. By utilizing 17 different standardized questionnaires, outcomes data is collected at 52 transplant centers across the country for the purpose of determining risk factors and combining experience to improve the outcomes of heart transplantation. This dataset will also allow hospitals, including Lurie Children’s, to monitor performance on quality metrics surrounding heart transplantation and it can also serve as the core for the quality-improvement within the Heart Center for these patients.
“Quantitative Detection of Circulating Donor-Specific DNA in Heart Transplant Recipients” – Dr. Elfriede Pahl
Early detection of rejection is a major focus of organ transplant care. Detection of donor DNA after transplantation has been proposed as a means of detecting acute rejection in for heart transplant patients. In a pilot study, and in the on-going multi-center study, a proprietary approach has been applied to quantifying donor specific cell free DNA present in transplant recipient’s plasma, with high temporal resolution surrounding the time of transplant surgery as well as during episodes of rejection, in contrast to baseline levels from blood obtained at time of routine surveillance biopsies. The purpose of this study is to evaluate and continue to develop a non-invasive method of detection of transplant rejection by isolating donor specific DNA in plasma of organ transplant patients.
The Marfan Trial was a multi-center clinical trial that compared the effects of beta blocker therapy (atenolol) to those of angiotensin II receptor blocker therapy (losartan) in individuals with Marfan syndrome. The study found that losartan is as effective as atenolol in leading to a significant decline in body size-indexed aortic root dimension over time. The study also showed a stronger response in younger age groups, suggesting that beginning therapy early in the disease course may be provide a greater benefit. Read the press release to learn more.
The Marfan Trial genetic ancillary study aims to assess how genetic and phenotypic variations affect response to treatment in patients with Marfan syndrome receiving atenolol and losartan.
The Marfan Quality of Life Study aims to describe the quality of life for individuals with Marfan syndrome to normative data using standardized tools. The study is currently closed, but results are not yet available.
The Circulating TGF-β levels in Marfan syndrome study aims to determine if circulating TGF-β levels correlate with specific treatment arms in the Marfan Trial (i.e., atenolol versus losartan). The study is currently closed, but results are not yet available.
The Development of a Blood Test for Marfan Syndrome is a multicenter study which aims to identify differences in proteins that reflect genetic abnormalities in people with Marfan syndrome. The hope is to develop a non-genetic biomarker test to identify patients at high risk for aortic complications. Joseph Camarda, MD, and Elizabeth Cappella, APRN-NP, are the local investigators collaborating on this ongoing study.
Neurocognitive & Neurodevelopmental Cardiology
“National Pediatric Cardiology Quality Improvement Collaborative (NPC-QIC) – A Collaborative Initiative to Improve Care of Children with Complex Congenital Heart Disease” – Dr. George Verghes
The purpose of this study is to collect data on infants with single ventricles such as patients with Hypoplastic Left Heart Syndrome (HLHS) which is a condition where the left side of the heart is critically underdeveloped. Multiple institutions in the United States will be collecting data on patients with single ventricles to create a database that will ultimately improve care and outcomes. Data will be collected on patients who have undergone the Norwood procedure and information related to their plan of care, nutrition, and outcome following the Glenn procedure will be collected. The information will be analyzed and used to help create evidence-based guidelines for the treatment and care of these patients and to improve said treatments and subsequent outcomes for these patients.
Non-Invasive Cardiac Imaging
4D MRI Research
The multidisciplinary MR/CT program is researching ways to reduce MR imaging exam time and minimize anesthesia or sedation used during imaging exams. In the multi-year NIH/NHLBI funded study, Functional Cardiovascular 4D MRI in Congenital Heart Disease, Lurie Children's cardiologists and radiologists are collaborating with Northwestern bioengineers to develop a comprehensive 20-minute 4D MR exam that might replace the standard 60-90 minute MRI protocol. In addition to studying how the new technique may reduce exposure to anesthesia, the team is investigating how 4D visualization of complex blood flow dynamics may predict progression of cardiovascular disease. The visualization is shown below.
The goal of this study is to develop a database of pre- and post-natal cardiac evaluations to learn more about fetal echocardiograms and fetal abnormality diagnosis. The data collected from the fetal echocardiogram will be used by Lurie Children’s cardiology physicians to ensure that the fetal diagnoses are accurate when compared to babies’ echocardiogram heart diagnosis after birth. The database will help physicians determine areas for improvement in care and diagnosis for mothers and their children born with different congenital heart diseases.
The Preventive Cardiology Program at Lurie Children’s is very pleased to have joined a nationwide study based at Duke University, the CASCADE Familial Hypercholesterolemia Registry. To date, we have enrolled over 58 FH patients.
Familial Hypercholesterolemia (FH) is one of the most common life-threatening family disorders. Individuals with FH remain vastly under-diagnosed and under-treated and are at an increased risk for heart disease and heart attacks at a young age. However, FH is manageable with the right care.
The FH Foundation is a patient-centered nonprofit organization dedicated to education, advocacy, and research of Familial Hypercholesterolemia. The FH Foundation has launched a national FH patient registry, the CASCADE FH Registry. This study is designed to collect comprehensive data on individuals with confirmed or suspected FH on a longitudinal basis. The CASCADE FH Registry will serve as a key instrument to support health service planning, increase knowledge on the disorder and pool data for epidemiological, clinical and outcomes research, as well as for surveillance of therapy effectiveness.
The risks and benefits of mild, moderate, or vigorous exercise for hypertrophic cardiomyopathy (HCM) or long QT syndrome (LQTS) patients remain unknown, though many of these patiQualents are prescribed exercise restrictions from their physicians. LIVE-HCM/LQTS is designed to determine how exercise and other lifestyle choices affect the well-being of people living with HCM and LQTS. Knowledge gained from this study may help people with HCM or LQTS in the future to decide what type of activities to participate in, and how clinicians may better advise their patients about exercise.
“Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) – Dr. Philip T. Thrush
Lurie Children’s Hospital participates in the pediatric portion of the INTERMACs registry called Pedimacs. This registry gathers clinical and laboratory information on patients that receive ventricular-assist devices/mechanical circulatory support devices for end-stage heart failure. We are one of 167 active sites and 20,917 subjects enrolled study-wide. The registry and analyze clinical and laboratory data from patients who are receiving MCSDs for end-stage heart failure as well as their outcomes following implantation of legally utilized MCSDs. These results are expected to facilitate clinical evaluation and patient management while aiding better device development.'
“Improving Pediatric and Adult Congenital Treatment (IMPACT) Registry”
Improvements in medicine and new surgical procedures over the last 30 years have resulted in an increasing number of pediatric congenital heart disease patients surviving into adulthood. It is estimated that 50% of pediatric patients diagnosed with congenital heart disease undergo corrective treatment in their first year of life. Results of surgical procedures are tracked in registries and have shown valuable trends in delivery of care. There are no such catheterization registries and, as a result, the outcomes and variability of these has not been monitored. This study aims to collect data on children and adults with congenital heart disease (CHD) who are undergoing a cardiac catheterization. The collection and analysis of the data collected will be used to learn more and improve treatment of CHD.
“Pediatric Cardiac Critical Care Consortium (PC4)”
The Pediatric Cardiac Critical Care Consortium (PC4) aims to improve the quality of care for patients with critical pediatric and congenital cardiovascular disease in North America and abroad. Formed in 2009 with National Institutes of Health funding, PC4 is a unique collaborative of leaders in pediatric cardiac critical care, cardiac surgery, and cardiology representing a diverse group of centers caring for these vulnerable patients. The core pillars of collaborative quality improvement serve as the foundation for PC4: purposeful collection of specific clinical data on outcomes and practice; timely performance feedback to clinicians, and continuous improvement based on empirical analysis and collaborative learning. PC4 will be an international leader in the effort to improve care to critically ill patients with pediatric and congenital heart disease. Dr. Costello serves on the Executive Committee of PC4.