Eight clinical researchers selected as finalists for Outstanding Investigator Award at Cardiology 2015

Pediatric cardiology researchers and clinicians from numerous centers from around the world are gathering at the Cardiology 2015: the 18th Annual Update on Pediatric and Congenital Cardiovascular Disease conference, sponsored by The Children's Hospital of Philadelphia and Phoenix Children's Hospital on Feb. 11 to Feb. 15 in Scottsdale, Ariz. Among the many scientists who are presenting research at the event, the conference organizers chose 8 clinical researchers as finalists for the Outstanding Investigator Award. The following news briefs summarize their presentations of research in congenital heart disease (CHD). All presentations occur at the Hyatt Regency Scottsdale Resort and Spa at Gainey Ranch.

Risk of White-Matter Injury Before Infant Cardiac Surgery Linked to Oxygen Flow in Brain
Recent research in infants with critical CHD has shown that a longer period between birth and surgery increases the risk of injury to the brain's white matter, a condition called periventricular leukomalacia (PVL). This study of 35 neonates with critical CHD at The Children's Hospital of Philadelphia analyzed cerebral physiology during the vulnerable preoperative period. The newborns had two-ventricle anatomy or single-ventricle anatomy, with or without arch obstruction. In all groups, cerebral tissue oxygen saturation decreased from time-of-birth until surgery. The findings suggest that the increased risk for PVL stems from oxygen demand and a natural increase in cerebral oxygen metabolism not being met by oxygen delivery. Therapeutic strategies to shorten the time to surgery, or to increase cerebral oxygen delivery or decrease cerebral oxygen demand could mitigate the risk for PVL.
Jennifer M. Lynch, Ph.D., et al, The Children's Hospital of Philadelphia and the University of Pennsylvania; Pre-operative Cerebral Hemodynamics from Birth Until Surgery in Infants with Critical Congenital Heart Disease [abstract 1007, Thurs., Feb. 12.]

Practice Changes Reduce Radiation Exposure in Pediatric Cardiac Cath Procedures
This study analyzed practice changes in the pediatric cardiac catheterization laboratory at Children's Mercy Hospital, aimed at reducing patient and provider exposure to ionizing radiation. After a 30-day trial and education period, the center implemented changes in technical and clinical practice such as weight-based reductions in preset fluoroscopy and angiography frame rates, more consistent use of collimators and shields, and increased use of stored fluoroscopy and virtual magnification. This quality improvement study analyzed all 353 cardiac catheterization procedures, 6 months before and 8 months after instituting the changes. The mean cumulative skin dose per minute of radiation decreased significantly, from 91.30 (plus or minus 166.23) cGy-cm2/min. to 58.42 (plus or minus 98.79) cGy-cm2/min. There were significant reductions across all age and weight subgroups. In addition, radiation exposure to physicians decreased by 46 percent from 2011 to 2012.
Nichole Gubbins, M.D., et al, Children's Mercy Hospital, University of Missouri-Kansas City; Radiation Dose Reduction in the Pediatric Interventional Cardiovascular Laboratory: A Quality Improvement Study [abstract 878, Thurs., Feb. 12.]

In Animal Model, CPR with a Hemodynamic Target Improves 24-Hour Survival
This study compared a goal-directed cardiopulmonary resuscitation (CPR) method using a hemodynamic coronary perfusion pressure (CPP) target to the American Heart Association's CPR Guideline that targets depth of chest compressions. A team from The Children's Hospital of Philadelphia randomized 16 3-month-old pigs in an animal model of ventricular fibrillation (VF) cardiac arrest to two groups. In the Blood Pressure Targeted Care (BP care) group, the researchers aimed for chest compressions with a systolic blood pressure goal of 100 mmHg, with vasopressors titrated to maintain CPP above 20 mmHg. In the AHA Guideline care group, the chest compression was targeted to 51 mm depth with standard Advanced Cardiovascular Life Support vasopressor dosing. The animals received manual CPR for 10 minutes before the first defibrillation attempt. At 24 hours, the BP care group had a significantly higher survival and survival with more favorable neurologic outcome than the AHA Guideline care group. The BP care group had significantly higher CPP and significantly lower chest compression depth. Goal-directed resuscitation improved 24-survival outcomes in this relevant animal model of VF cardiac arrest.
Maryam Y. Naim, M.D., et al, The Children's Hospital of Philadelphia; Hemodynamic Targeted CPR Improves 24-Hour Survival from Ventricular Fibrillation Cardiac Arrest[abstract 914, Fri., Feb. 13.]

No Link Found Between Pre-Operative Enteral Feeding and NEC in Newborn Cardiac Surgery
Newborns with congenital heart disease are at greater risk for necrotizing enterocolitis (NEC), which has resulted in delayed perioperative enteral feeding practices. This single-center study investigated whether pre-operative enteral feeding posed increased risk for NEC in newborns that undergo cardiac surgery. Researchers from the Medical University of South Carolina performed a retrospective chart review of all 120 newborns who underwent cardiac surgery from Feb. 2011 to July 2013. In that cohort, 70 newborns (58 percent) received pre-operative feeds, and 11 newborns (9.2 percent) developed NEC. In both univariate and multivariate analysis, the team found no association between pre-operative enteral feeding and NEC. This finding suggests that prospective studies should investigate the safety and potential benefits of early perioperative enteral feeding.
Carly J. Scahill, D.O., et al, Medical University of South Carolina; Relationship Between Pre-Operative Feeding and Necrotizing Enterocolitis in Neonates Undergoing Cardiac Surgery [abstract 895, Fri., Feb. 13.]

Gene Variant Linked to Postsurgical Survival Preserves Infants' Ventricular Function
This research group previously showed that a genetic variant of vascular endothelial growth factor A (VEGFA) is associated with higher transplant-free survival after surgery for CHD in infants, but the underlying biological mechanisms remained unknown. This single-center study at The Children's Hospital of Philadelphia tested the hypothesis that better systemic ventricular function was associated with this genetic variant. The study team analyzed a cohort of 422 non-syndromic CHD patients who had cardiac surgery with cardiopulmonary bypass before 6 months of age. Genetic and echocardiographic data were available for 355 of these subjects, of whom 33 (9.9 percent) developed worse systemic ventricular function at a mean follow-up of 13.5 years. The researchers found that the VEGFA gene variant was significantly associated with preserved ventricular function. Decreased systemic ventricular function was significantly associated with heart transplantation or death. Further studies should validate this genotype-phenotype association and investigate the role of increased VEGF production, which is associated with this gene variant.
Constantine D. Mavroudis, M.D., M.Sc., et al, The Children's Hospital of Philadelphia; A Vascular Endothelial Growth Factor A (VEGFA) Genetic Variant is Associated with Improved Ventricular Function and Transplant-Free Survival after Surgery for Non-syndromic Congenital Heart Defects (CHD) [abstract 923, Thurs., Feb. 12.]

Validation of Novel Scoring Method for Predicting Outcomes after Pediatric Cardiac Surgery
This study group from Wayne State University previously validated a novel vasoactive-ventilation-renal (VVR) score as a robust predictor of outcome in acyanotic infants after CHD surgery. The current study sought to validate the score prospectively in a broader population, including older children and those with single-ventricle anatomy or mixing lesions. The VVR incorporates three organ systems most affected by cardiac surgery: respiratory (represented by ventilation index), cardiac (vasoactive inotrope score), and renal (increase in creatinine from baseline). The researchers analyzed 92 patients having a median age of 0.65 years (range of 3 days to 17.9 years), of whom 17 patients had single-ventricle physiology or residual mixing lesions. Compared to admission and peak measurements, results were strongest in predicting postoperative outcomes when the VVR was measured 48 hours after ICU admission. The 48-hour VVR is likely superior to traditionally used predictive tools, such as serum lactate and vasoactive inotrope score (VIS) in predicting postoperative outcomes in children with CHD.
Kyle G. Miletic, B.S., et al, Wayne State University School of Medicine; Prospective Validation of a Novel Vasoactive-Ventilation-Renal Score that Predicts Outcomes Following Pediatric Cardiac Surgery[abstract 912, Fri., Feb. 13.]

HLHS Epidemiology and Outcomes in Sweden Over 20 Years
Swedish researchers analyzed the changing epidemiology and outcome in hypoplastic left heart syndrome (HLHS) over the 20 years since 1993, when the Norwood procedure was first performed in Sweden. A team from Queen Silvia Children's Hospital and Karolinska University Hospital performed a national retrospective cohort study using registry data for all patients undergoing Norwood surgery from 1993 to 2013. They also analyzed data from 1997 to 2010 on all live-born infants with HLHS. Of the 139 patients who underwent the surgery over two decades, 79 (57 percent) were alive in August 2014. Transplantation-free survival increased for each 5-year period, with five-year postoperative survival rates at 88 percent for boys and 73 percent for girls, for children born from 2008 to 2013. Significant risk factors for mortality were lower birthweight and female sex. Of the 141 live-borns with HLHS from 1997 to 2010, the proportion who underwent surgery increased from 62 percent to 83 percent. The prenatal detection rate rose from 41 percent (1997-2001) to 78 percent (2007-2010), while the proportion of fetuses with HLHS who were terminated increased from 32 percent to 67 percent. The increasing termination rate was counterbalanced by an increasing proportion of live-borns undergoing surgery and improved rates of postoperative survival. The improvement in postoperative survival has implications for prenatal counseling.
Mats Mellander, et al, Queen Silvia Children's Hospital, University of Gothenburg, Sweden; Hypoplastic Left Heart Syndrome: Epidemiology and Outcome in Sweden 1993-2013—A National Cohort Study [abstract 941, Thurs., Feb. 12.]

Autonomic Neurovascular Control in Fontan Patients: Potential Mechanisms for Reduced Exercise Capacity
Survivors of the Fontan procedure have decreased exercise capacity compared to healthy controls. A research team from the Heart Institute of Sao Paulo University investigated peripheral neurovascular control mechanisms related to impaired functional capacity in Fontan patients. This prospective study enrolled twenty clinically stable Fontan patients (9 males, aged 21±1years) and 18 healthy controls (9 males, aged 23±1years). The study team evaluated the muscle sympathetic nerve activity by microneurography, forearm blood flow by venous occlusion plethysmography, functional capacity by cardiopulmonary exercise test and plasmatic catecholamine level. The researchers concluded 1) The increased muscle sympathetic nerve activity and the higher plasmatic level of norepinephrine explain the decreased peripheral vascular conductance as well as the lower peripheral blood flow, and 2) The already known diminished functional capacity in Fontan patients involves not only a suboptimal cardiac function, but also alterations of the peripheral neurovascular control.
Aida R. Turquetto, R.T., et al, Heart Institute of Sao Paulo University, Medical School; Autonomic Neurovascular Control in Fontan Patients: Potential Mechanisms for Reduced Exercise Capacity [abstract 958, Fri., Feb. 13.]