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CHOP experts describe research in pediatric heart disease

Physician-researchers from the Cardiac Center at The Children's Hospital of Philadelphia presented new findings on pediatric cardiovascular disease at the American Heart Association's Scientific Sessions 2012 in Los Angeles. They described racial disparities in risk factors for sudden cardiac death, imaging modalities and novel approaches to assessing cardiac anomalies, ventricular assist device use, special considerations in syndromes in adult congenital heart disease, changes in immunosuppressive drugs after pediatric heart transplant, and many other topics.

Children's Hospital clinicians also moderated scientific sessions, participated on expert panels and shared knowledge on career paths. Below are summaries of some of the research presented at abstract sessions.

--Minority and Suburban Children are at Higher Risk of Sudden Cardiac Death--

Among children who suffered sudden cardiac death (SCD), significant risk factors included being black, Hispanic, older than 6 months, and living in the suburbs. Victoria L. Vetter, M.D., and colleagues reviewed a dataset from 16 states from 2005 to 2009 in records maintained by the National Center for the Review and Prevention of Child Deaths. Among 1,099 cases of child cardiovascular deaths, the team identified 63 percent as SCD and 37 percent as non-sudden cardiovascular death. Prior conditions, identified in 49 percent of the children who died, included congenital heart defects, cardiomyopathy and arrhythmia, with most deaths occurring at home or school (30 percent) or in the hospital (40 percent). In comparing SCD to non-sudden death, the researchers found significant differences in race, with SCD at 73 percent of cardiovascular deaths in blacks vs. 61 percent in whites. SCD occurred more frequently in suburban sites than in urban sites. The data may help researchers to better understand and prevent SCD. Victoria L. Vetter et al, Preliminary Analysis of the National Child Death Review Database for Cardiovascular Deaths

--Cardiac MRI Detects Serious Blood Flow Reversal after Heart Surgery in Children--

Cardiac researchers demonstrate that a combination of imaging techniques can identify a serious reversal of blood flow that occurs in some children after reconstructive surgery for complex heart defects. Using time resolved gadolinium angiography (TWIST) and magnetic resonance phase contrast velocity mapping (PC-MRI), Kevin K. Whitehead, M.D., Ph.D. and colleagues describe their experience in identifying blood flow reversal in children who have undergone superior cavopulmonary connections (SCPC) as part of the Fontan procedure for single ventricle heart defects. Identifying flow reversal in the left pulmonary artery (LPA) and right upper lobe branch (RUL) pulmonary artery is important, because these manifestations of systemic to pulmonary arterial collateral flow (CollF) may result in poor outcomes for these patients. A failure to recognize LPA or RUL flow reversal may also cause clinicians to significantly underestimate CollF. The researchers reviewed 112 SCPC patients who had CollF quantified by MRI, and were able to readily identify LPA or RUL flow reversal in 7 percent of these patients.

The CollF burden was much higher for patients with flow reversal than in those without flow reversal.

Kevin K. Whitehead et al, Branch Pulmonary Artery Flow Reversal Can Be Identified by Cardiac Magnetic Resonance and Is Associated with Increased Collateral Flow Burden in Patients with Superior Cavopulmonary Connections.

--Arterial Embolization in Single-Ventricle Patients Improves Systemic Blood Flow in Short Term--

For the first time, cardiology researchers report the acute efficacy of performing embolization of systemic to pulmonary arterial collateral (SPC) vessels in children with single-ventricle disease. Yoav Dori, M.D., and colleagues at The Children's Hospital of Philadelphia used magnetic resonance phase contrast velocity mapping (PC-MRI) to measure blood flow in six patients with superior cavopulmonary connections. The study team performed the measurements both immediately before and after cardiac catheterization with coil and particle embolization of angiographically evident SPC vessels. The researchers measured superior and inferior caval, total pulmonary artery, total pulmonary vein, ascending and descending aortic flows. After embolization, the team found a significant decrease in SPC burden and pulmonary flow and significant increase in systemic blood flow. The findings advance the understanding of treatment of these blood flow abnormalities in single-ventricle patients, although further studies should assess the durability of SPC embolization as well as the effect on Fontan outcomes.

Yoav Dori et al, Acute Efficacy of Systemic to Pulmonary Arterial Embolization

--A Novel 3D Cardiac MRI Improves the View of Children's Aortic Arch Anomalies--

A cardiac research team reports that, compared to standard cardiac MRI techniques, a 3D imaging tool provides superior imaging of aortic arch (Ao) anomalies in children. Kevin K. Whitehead, M.D., Ph.D. and colleagues at Children's Hospital enrolled 26 pediatric patients with suspected Ao anomalies in a study of a 3D, T1-weighted turbo spin echo dark blood with navigator-triggered prospective acquisition correction (3D-SPACE DB) technique. The study team compared the new images to those acquired by the standard clinical protocol, evaluating them for image quality and Ao measurements. The 3D-SPACE DB provided superior imaging in a variety of arch anomalies, including vascular rings, native and repaired coarctation of the aorta (CoA), and aortic dilation. In two CoA cases, the 3D technique showed arch patency when other modalities did not. It also allowed assessment of the airway in vascular rings. Furthermore, 3D SPACE DB can potentially decrease scan times by reducing the number and type of acquisitions acquired.

Kevin K. Whitehead et al, Navigated 3D Dark Blood Provides Superior Imaging in Arch Anomalies in Children

--Review: Pediatric Survival Increases with Greater Use of Ventricular Assist Devices--

Over the past decade, as the use of ventricular assist devices (VADs) has increased in children with heart disease, survival rates have increased as well. Joseph W. Rossano, M.D., and colleagues at The Children's Hospital of Philadelphia performed a retrospective study of patients aged 20 years and younger in the Pediatric Health Information System Database who received VADs from 2000 to 2010. During that decade, clinicians placed 475 VADs in children during Era 1 (2000-2003) and Era 2 (2007-2010). The median age at implantation was 6.0 years, with the proportion of children aged 1 to 12 years increasing from 29 percent in Era 1 to 47 percent in Era 2. The majority of patients had a diagnosis of cardiomyopathy, which increased from 52 percent in Era 1 to 72 percent in Era 2. Co-morbidities included arrhythmias, pulmonary hypertension, acute renal failure and cerebrovascular disease. Of the 475 patients, 247 (52 percent) underwent heart transplantation. Overall 327 children (69 percent) survived, with mortality decreasing from 42 percent in Era 1 to 25 percent in Era 2. The factors independently associated with increased mortality include infancy, acute renal failure, cerebrovascular disease, and the use of extracorporeal membrane oxygenation (ECMO). The decline in mortality was accompanied by an increase in median hospital length of stay (37 days in Era 1 compared to 69 days in Era 2) and increasing hospital charges.

Joseph W. Rossano et al, Decreasing Mortality of Ventricular Assist devices at Children's Hospitals from 2000 to 2010: Improvement at a Cost

--Co-morbid Heart Failure Is Linked to Increased Mortality in Single-Ventricle Patients--

More than one in 10 children with single-ventricle heart disease may also be hospitalized with co-morbid heart failure. A retrospective review by Joseph W. Rossano, M.D., and colleagues at The Children's Hospital of Philadelphia found that this little-studied patient population has a higher mortality rate and longer length of stay (LOS) than single-ventricle children not hospitalized for heart failure. The researchers analyzed data from 2000, 2003 and 2006 in the Health Care Cost and Utilization Project Kids Inpatient Database, a nationwide sampling of pediatric hospitalizations. The analysis included 732 heart failure-related hospitalizations (HFRH) among single-ventricle patients in 2000 and 1,168 HFRH in 2006. HFRH patients had LOS nearly twice as long as non-HFRH patients, and their mortality was 50 percent higher. The HFRH group also had higher rates of morbidities, such as arrhythmias, sepsis and respiratory failure. Non-cardiac morbidities such as cerebrovascular disease, acute renal failure, sepsis and the use of extracorporeal membrane oxygenation (ECMO) were independently associated with hospital mortality.

Joseph W. Rossano et al, The Burden of Heart Failure Related Hospitalizations in Children with Single Ventricle Disease in the United States

--Immunosuppression for Children with Heart Transplants May Avoid Calcineurin Inhibitors--

While calcineurin inhibitors (CNIs) have been the cornerstone of immunosuppression in heart transplant patients, CNIs are toxic to the kidneys and are not effective for cardiac allograft vasculopathy. Joseph Rossano, M.D., director of the heart transplant program at The Children's Hospital of Philadelphia, led a single-center retrospective review to evaluate the efficacy and side effect profile of sirolimus used with or without an antimetabolite in the absence of calcineurin inhibitors. The researchers analyzed records of 17 children (median age, 1.2 years) who underwent heart transplantation between 2002 and 2010. All the patients were changed from CNIs to sirolimus at an average time of almost 6 years post-transplant. The reasons for the change were renal dysfunction in 11 patients, post-transplant lymphoproliferative disorder in 5 patients, and cardiac allograft vasculopathy, or CAV, in 1 patient. All 17 patients are living almost 3 years after the change was made. There was one episode of rejection within the year of the change and 4 episodes in the year after the change. In this small cohort, there was no decrease in renal function or progression of CAV. These patients require monitoring for acute rejection. Further study in larger cohorts should assess longer-term outcomes.

Joseph W. Rossano et al, Calcineurin-Inhibitor Free Sirolimus-based Immunosuppression in Pediatric Heart Transplant Patients

--Patients Who Need a Heart Re-Transplant May Benefit from a Concurrent Kidney Transplant--

Heart transplant patients who require a re-transplant often have new co-morbidities such as kidney disease, and may benefit from a concurrent kidney transplant. Kimberly Lin, M.D., and colleagues at The Children's Hospital of Philadelphia performed a retrospective research study of the United Network of Organ Sharing (UNOS) database to analyze heart re-transplants from 1987 to 2011. Of the 1,660 heart re-transplant patients in the database, 116 had a concurrent kidney transplant. The median age of patients undergoing heart re-transplant was 43 years. Contrary to the researchers' hypothesis, the median survival of patients receiving concurrent kidney transplants was longer (10.5 years) than in patients receiving heart re-transplant alone (6.7 years). The survival benefit of the concurrent kidney transplant group occurred despite older age, a higher burden of diabetes and a longer waiting time for transplantation. Even the subgroup of patients with the poorest kidney function had a survival benefit from a concurrent transplant. The research team concluded that in candidates for heart re-transplantation, kidney failure should not preclude consideration for re-transplantation in those eligible for concurrent kidney transplantation.

Kimberly Y. Lin et al, Heart Re-Transplant Recipients Fare Better with Concurrent Kidney Transplantation than with Heart Re-Transplant Alone


Contact: Joey McCool Ryan
Children's Hospital of Philadelphia

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