Title: Procalcitonin in the Pediatric Cardiac Surgical Patient Evaluation of a New Marker of Infection
Principal Investigator: Kevin O. Maher, MD
In this research study, we want to look at the difficulty in identify infections in children who have heart surgery. We also want to look at differentiating between actual infections and the normal post-surgery course that patients go through. We use a number of tools in the Intensive Care Unit to pick out children at risk for an infection. These tools are the physical examination, a fever, white blood cell count, and C-reactive Protein (CRP) level. When a patient has an infection, they usually have a fever, have a high white blood cell count, and have an increased CRP level. However, these are not always correct. The identification of infection remains a challenge and the laboratory markers of infection (white blood cell count and CRP) that are used now are not perfect.
A new marker of infection, Procalcitonin (PCT), has been found and has been tested in adults and children. PCT has recently been approved by the Food and Drug Administration (FDA) as a marker of infection. PCT has been shown to be a more accurate marker of infection for some groups of patients.
Prior work on a small number of children shows that PCT increases shortly just from heart surgery itself, even without infection. There is little information published about how accurate PCT is for identifying infection in the child heart population. In order to use PCT in our patients, we need to know what the normal levels of PCT are after surgery. Thus, when an infection does happen, we can identify it. We also need to take PCT levels when patients are thought to have infections. We will then need to watch for an infection over the next few days to see if the PCT level rises and can actually predict the presence an infection.
By doing this study, we hope to find out two things. First, we hope to find out the PCT response to heart surgery in children by taking blood before surgery and each day for four days after surgery. These blood draws will help us figure out the typical PCTresponse, the normal increase in PCT after heart surgery, and when the PCT level returns to baseline.
Second, we hope to determine the accuracy of PCT as a marker of infection. Whenever we think a patient may have an infection, it is routine care to take some blood and run lab tests such as a white blood cell count, blood culture, and a C-reactive protein level. Patients in the study will also have an additional 10 drops of blood taken for a PCT level at the same time as the routine blood draw. Even though patients may show signs of an infection, the routine blood test do not always come back positive for an infection. We will compare the routine blood test results (positive or negative for an infection) with the PCT level taken at the same time. If most patients with an infection also have a rise in PCT and those patients without an infection have a normal PCT, then we will prove that PCT is a good, accurate marker for infection in our patients.
This research will help us study infection in our patients. It will help distinguish patients with infection, what the risk factors are, how they are treated, and the response to infection. This information will potentially allow us to use an improved test for identifying infection in a high-risk population of children. Patients in the research project will continue to receive the standard of care treatment after heart surgery and there will be no changes in their care during the study.
Title: BNP Levels in the Non-Cardiac Pediatric Emergency Department Patient
Principal Investigator: Kevin O. Maher, MD
B-type Natriuretic Peptide (BNP) is a hormone that is made by the pumping chambers of the heart. The BNP level can be measured and is used as a marker for heart problems in adults. When adults go to the Emergency Department, the BNP level is frequently used to help decide if a patient is having heart problems or lung problems. Elevated BNP levels are very good at detecting heart problems in the adults.
Deciding if a child has a heart problem or a lung problem can be very difficult, especially in infants. Several studies have demonstrated that BNP levels are elevated when children have heart disease. Many patients admitted to Children’s Healthcare of Atlanta with heart problems have very high BNP levels that correlate with their heart disease. We are planning to look at children who go to the Emergency Room.
The overall goal of the study is to be able to prove that obtaining BNP levels in pediatric patients can be used to identify heart problems. We already know that kids with heart problems have high BNP levels. We need to prove that children who come to the Emergency Room for non-cardiac problems still have normal BNP levels. Patients with fever, asthma, colds, infections, etc. should have normal BNP levels, and the children with heart problems will have high BNP levels.When this is proven, we will be able to use BNP as a marker to diagnose children with heart disease and differentiate them from patients who have lung problems or other non-heart related problems.
The proposed research has the potential to advance human health for the child with heart disease. These children often have non-specific findings of fussiness, shortness of breath and poor feeding. Making the correct diagnosis of heart disease can be very difficult, especially when children are evaluated in non-pediatric center. The ability to have a sensitive marker of heart disease for children will improve the care of children with heart disease.
Title: Quality of Life After Radiofrequency Ablation
Principal Investigator: Margaret Strieper, D.O.
Currently, radiofrequency ablation (RFA) has replaced the long-term use of antiarrhythmic medication for symptomatic tachycardia (a fast heart rate). RFA has eliminated the need for arrhythmia surgery in the pediatric population. Although the popularity of RFA in the pediatric population has increased, there is still a lack of available safety and efficacy data in children. In addition, there is very little evidence to support the overall risk/benefit ratio including information involving the effects of RFA on the reported quality of life in the children undergoing this procedure.
In 1996, Hlatky and Vaughn (Circulation, Vol. 94) concluded that quality of life is an important measure in clinical studies and should be included in clinical trials. By studying the effects of treatment on quality of life, the value of medical care may be validated for the caregiver as well as external payers and the public. A prospective study is needed to determine the actual physical and emotional effect of ablation. Armed with quality of life data, researchers at Children's can develop a holistic, age-appropriate care plan and thus successfully meet the physical and emotional needs of these children.
Title: Identifying Down Syndrome Heart Defect Candidate Genes
Principal Investigators: Stephanie Sherman, Lora Bean and Kenneth Dooley, M.D.
The purpose of this study is to identify genetic variants on chromosome 21 that contribute to CHD susceptibility using a candidate gene approach in a DS population with complete AVSDs. This study, taking advantage of the vast array of genomic resources available for chromosome 21, will use molecular approaches to identify candidate genes for DS CHDs within a 10 Mb heart defect critical region.
Compared to the general population, individuals with Down syndrome (DS) are at a 500-fold increased risk for complete atrioventricular septal defects (AVSDs), a severe form of congenital heart defect (CHD). The purpose of this study is to identify genetic variants on chromosome 21 that contribute to CHD susceptibility using a candidate gene approach in a DS population with complete AVSDs. This study will take advantage of the vast array of genomic resources available for chromosome 21 and the extensive infrastructure established by the National Down Syndrome Project (NDSP; S. Sherman, PI), to identify candidate genes for DS CHDs . Specifically we will:
- Expand our current Down syndrome with complete AVSD case and Down syndrome without CHD control populations to facilitate association studies.
- Ascertain a total of 400 cases of DS with complete AVSD.
- Collect biological samples from probands and parents, clinical data from the probands, and interview data that focus on environmental exposures and maternal health factors from parents.
- Identify candidate genes within the 10 Mb Down syndrome heart critical region that may contribute to the risk of congenital heart defects in Down syndrome.
Title: Safety of Sports for Patients with Implantable Cardioverter-Defibrillators - A Multicenter Registry
Principal Investigator: Rachel Lampert, M.D.
Principal Investigator: Peter Fischbach, M.D.
Risk of arrhythmia during sports participation:The frequency and relative risk of an ICD shock delivered during sports in unknown. However, it is likely that shocks during sports could be common. In the Physician’s Health Study exercise substantially increased the relative risk of sudden cardiac death,4 and in a series of young victims of sudden cardiac death, the relative risk for athletes was 2.5,5most of whom die during exercise.5,6 Exercise is known to exacerbate ventricular arrhythmias in hypertrophic cardiomyopathy, Arrhythmogenic right ventricular dysphasia, and the long QT syndrome.7 Moderate exertion can trigger sustained ventricular arrhythmias in patients with ICDs.8,9
The risk of exercise in patients with ICDs stems from their underlying Arrhythmogenic myocardial substrate and not from the ICD itself. However, if the ICD effectively terminates arrhythmias during sporting activities, without adverse sequelae, participation in athletics becomes an issue of quality of life. Some data indicate that ICD shocks can decrease quality of life,10 yet restriction from sports may have similar impact.
Title: Neurodevelopmental Outcomes in Hypoplastic Left Heart Syndrome—correlation with cerebral Non-invasive infrared spectroscopy(NIRS)
Principal Investigator: William Mahle, M.D.
As recently as 15 years ago, a monograph dedicated to complex congenital heart disease (CHD) would not have included issues related to long-term neurological outcomes for many forms of CHD, and certainly not for hypoplastic left heart syndrome (HLHS). Medical stabilization with prostaglandin, and non-invasive diagnosis with echocardiography have less than a 25 year track record; hence, the oldest survivors with complex CHD are only now approaching young adulthood. The relatively recent and incredibly rapid advancements in the management of infants born with HLHS are perhaps one of the most exciting achievements in our field.At the same time, these surgical successes and improvements in perioperative care have created a growing population of early survivors, in whom there is an increasing recognition of neurodevelopmental disabilities and an uncertain future. Reducing the morbidity of complex congenital heart disease, especially for the central nervous system, is the next important battle we face in the successful management of children with complex CHD.
After the initial descriptions of reconstructive surgery and transplantation for HLHS in the early 1980s, considerable efforts and resources have been devoted to improving outcome for these patients. In the staged reconstruction pathway, the greatest focus has been on improving operative survival of the stage I procedure. In the past 10 years, increasing numbers of centers have reported hospital survival of greater than 70% for all patients, and over 90% for those with standard risk--a considerable improvement from the experience only ten years earlier.(1)However, tempering these reports have been several early studies generating concern regarding the neurodevelopmental outcome for the survivors of both treatment strategies.