Congenital, Hereditary, and Neonatal Diseases and Abnormalities Commons^™

Maternal Coxsackievirus B Induced Dysregulation Of Sumoylation Processes As A Potential Cause Of Hypoplastic Left Heart Syndrome, Bailey Kemp, Sarah Severson

Undergraduate Research Symposium 2018

Hypoplastic Left Heart Syndrome (HLHS) is a life-threatening congenital heart defect with unknown etiology. Here we hypothesize that HLHS has etiologic roots in maternal asymptomatic coxsackievirus B infection. Coxsackievirus has been demonstrated to disrupt normal distribution of small ubiquitin-like modifiers (SUMO) in the cell. The vital cardiac transcription factor, Nkx2-5, has been shown to be dependent on SUMOylation for proper function. Specifically, co-localization of SUMO and Nkx2.5 has been identified, as well as decreased SUMOylation associated with Nkx2-5 mutants. As Nxk2-5 is essential for fetal heart development and mutations in the gene for this vital transcription factor have been linked …

Oseltamivir-Warfarin Interaction In Hypoplastic Left Heart Syndrome: Case Report And Review., Jonathan B. Wagner, Susan M. Abdel-Rahman

Manuscripts, Articles, Book Chapters and Other Papers

An 8-year-old boy with hypoplastic left heart syndrome with a previous history of thrombosis within the inferior vena cava receiving stable warfarin dosing for anticoagulation was diagnosed with influenza B. He was subsequently placed on oseltamivir therapy according to the Centers for Disease Control and Prevention clinical practice guidelines. During the hospitalization, his international normalized ratio steadily increased to supratherapeutic levels and returned to baseline after discontinuation of oseltamivir therapy. This case represents a drug-drug interaction that has not been previously reported in children or adolescents. An extensive review of the pharmacokinetic and pharmacodynamic literature did not uncover a definitive …

Variation In Feeding Practices Following The Norwood Procedure., Linda M. Lambert, Nancy A. Pike, Barbara Medoff-Cooper, Victor Zak, Victoria L. Pemberton, Lisa Young-Borkowski, Martha L. Clabby, Kathryn N. Nelson, Richard G. Ohye, Bethany Trainor, Karen Uzark, Nancy Rudd, Louise Bannister, Rosalind Korsin, David S. Cooper, Christian Pizarro, Sinai C. Zyblewski, Bronwyn H. Bartle, Richard V. Williams, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To assess variation in feeding practice at hospital discharge after the Norwood procedure, factors associated with tube feeding, and associations among site, feeding mode, and growth before stage II.

STUDY DESIGN: From May 2005 to July 2008, 555 subjects from 15 centers were enrolled in the Pediatric Heart Network Single Ventricle Reconstruction Trial; 432 survivors with feeding data at hospital discharge after the Norwood procedure were analyzed.

RESULTS: Demographic and clinical variables were compared among 4 feeding modes: oral only (n = 140), oral/tube (n = 195), nasogastric tube (N-tube) only (n = 40), and gastrostomy tube (G-tube) only …

Multicenter Study Comparing Shunt Type In The Norwood Procedure For Single-Ventricle Lesions: Three-Dimensional Echocardiographic Analysis., Gerald R. Marx, Girish S. Shirali, Jami C. Levine, Lin T. Guey, James F. Cnota, Jeanne M. Baffa, William L. Border, Steve Colan, Gregory Ensing, Mark K. Friedberg, David J. Goldberg, Salim F. Idriss, J Blaine John, Wyman W. Lai, Minmin Lu, Shaji C. Menon, Richard G. Ohye, David Saudek, Pierre C. Wong, Gail D. Pearson, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The Pediatric Heart Network's Single Ventricle Reconstruction (SVR) trial randomized infants with single right ventricles (RVs) undergoing a Norwood procedure to a modified Blalock-Taussig or RV-to-pulmonary artery shunt. This report compares RV parameters in the 2 groups using 3-dimensional echocardiography.

METHODS AND RESULTS: Three-dimensional echocardiography studies were obtained at 10 of 15 SVR centers. Of the 549 subjects, 314 underwent 3-dimensional echocardiography studies at 1 to 4 time points (pre-Norwood, post-Norwood, pre-stage II, and 14 months) for a total of 757 3-dimensional echocardiography studies. Of these, 565 (75%) were acceptable for analysis. RV volume, mass, mass:volume ratio, ejection fraction, …

Interstage Mortality After The Norwood Procedure: Results Of The Multicenter Single Ventricle Reconstruction Trial., Nancy S. Ghanayem, Kerstin R. Allen, Sarah Tabbutt, Andrew M. Atz, Martha L. Clabby, David S. Cooper, Pirooz Eghtesady, Peter C. Frommelt, Peter J. Gruber, Kevin D. Hill, Jonathan R. Kaltman, Peter C. Laussen, Alan B. Lewis, Karen J. Lurito, L Luann Minich, Richard G. Ohye, Julie V. Schonbeck, Steven M. Schwartz, Rakesh K. Singh, Caren S. Goldberg, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: For infants with single ventricle malformations undergoing staged repair, interstage mortality is reported at 2% to 20%. The Single Ventricle Reconstruction trial randomized subjects with a single morphologic right ventricle undergoing a Norwood procedure to a modified Blalock-Taussig shunt (MBTS) or a right ventricle-to-pulmonary artery shunt (RVPAS). The aim of this analysis was to explore the associations of interstage mortality and shunt type, and demographic, anatomic, and perioperative factors.

METHODS: Participants in the Single Ventricle Reconstruction trial who survived to discharge after the Norwood procedure were included (n = 426). Interstage mortality was defined as death postdischarge after the …

Risk Factors For Hospital Morbidity And Mortality After The Norwood Procedure: A Report From The Pediatric Heart Network Single Ventricle Reconstruction Trial., Sarah Tabbutt, Nancy Ghanayem, Chitra Ravishankar, Lynn A. Sleeper, David S. Cooper, Deborah U. Frank, Minmin Lu, Christian Pizarro, Peter Frommelt, Caren S. Goldberg, Eric M. Graham, Catherine Dent Krawczeski, Wyman W. Lai, Alan Lewis, Joel A. Kirsh, Lynn Mahony, Richard G. Ohye, Janet Simsic, Andrew J. Lodge, Ellen Spurrier, Mario Stylianou, Peter Laussen, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: We sought to identify risk factors for mortality and morbidity during the Norwood hospitalization in newborn infants with hypoplastic left heart syndrome and other single right ventricle anomalies enrolled in the Single Ventricle Reconstruction trial.

METHODS: Potential predictors for outcome included patient- and procedure-related variables and center volume and surgeon volume. Outcome variables occurring during the Norwood procedure and before hospital discharge or stage II procedure included mortality, end-organ complications, length of ventilation, and hospital length of stay. Univariate and multivariable Cox regression analyses were performed with bootstrapping to estimate reliability for mortality.

RESULTS: Analysis included 549 subjects prospectively …

Variation In Perioperative Care Across Centers For Infants Undergoing The Norwood Procedure., Sara K. Pasquali, Richard G. Ohye, Minmin Lu, Jonathan Kaltman, Christopher A. Caldarone, Christian Pizarro, Carolyn Dunbar-Masterson, J William Gaynor, Jeffrey P. Jacobs, Aditya K. Kaza, Jane Newburger, John F. Rhodes, Mark Scheurer, Eric Silver, Lynn A. Sleeper, Sarah Tabbutt, James Tweddell, Karen Uzark, Winfield Wells, William T. Mahle, Gail D. Pearson, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: In the Single Ventricle Reconstruction trial, infants undergoing the Norwood procedure were randomly allocated to undergo a right ventricle-to-pulmonary artery shunt or a modified Blalock-Taussig shunt. Apart from shunt type, subjects received the local standard of care. We evaluated variation in perioperative care during the Norwood hospitalization across 14 trial sites.

METHODS: Data on preoperative, operative, and postoperative variables for 546 enrolled subjects who underwent the Norwood procedure were collected prospectively on standardized case report forms, and variation across the centers was described.

RESULTS: Gestational age, birth weight, and proportion with hypoplastic left heart syndrome were similar across sites. …

Cause, Timing, And Location Of Death In The Single Ventricle Reconstruction Trial., Richard G. Ohye, Julie V. Schonbeck, Pirooz Eghtesady, Peter C. Laussen, Christian Pizarro, Peter Shrader, Deborah U. Frank, Eric M. Graham, Kevin D. Hill, Jeffrey P. Jacobs, Kirk R. Kanter, Joel A. Kirsh, Linda M. Lambert, Alan B. Lewis, Chitra Ravishankar, James S. Tweddell, Ismee A. Williams, Gail D. Pearson, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: The Single Ventricle Reconstruction trial randomized 555 subjects with a single right ventricle undergoing the Norwood procedure at 15 North American centers to receive either a modified Blalock-Taussig shunt or right ventricle-to-pulmonary artery shunt. Results demonstrated a rate of death or cardiac transplantation by 12 months postrandomization of 36% for the modified Blalock-Taussig shunt and 26% for the right ventricle-to-pulmonary artery shunt, consistent with other publications. Despite this high mortality rate, little is known about the circumstances surrounding these deaths.

METHODS: There were 164 deaths within 12 months postrandomization. A committee adjudicated all deaths for cause and recorded the …

Intermediate-Term Mortality And Cardiac Transplantation In Infants With Single-Ventricle Lesions: Risk Factors And Their Interaction With Shunt Type., James S. Tweddell, Lynn A. Sleeper, Richard G. Ohye, Ismee A. Williams, Lynn Mahony, Christian Pizarro, Victoria L. Pemberton, Peter C. Frommelt, Scott M. Bradley, James F. Cnota, Jennifer Hirsch, Paul M. Kirshbom, Jennifer S. Li, Nancy Pike, Michael Puchalski, Chitra Ravishankar, Jeffrey P. Jacobs, Peter C. Laussen, Brian W. Mccrindle, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: The study objective was to identify factors associated with death and cardiac transplantation in infants undergoing the Norwood procedure and to determine differences in associations that might favor the modified Blalock-Taussig shunt or a right ventricle-to-pulmonary artery shunt.

METHODS: We used competing risks methodology to analyze death without transplantation, cardiac transplantation, and survival without transplantation. Parametric time-to-event modeling and bootstrapping were used to identify independent predictors.

RESULTS: Data from 549 subjects (follow-up, 2.7 ± 0.9 years) were analyzed. Mortality risk was characterized by early and constant phases; transplant was characterized by only a constant phase. Early phase factors associated …

Does Initial Shunt Type For The Norwood Procedure Affect Echocardiographic Measures Of Cardiac Size And Function During Infancy?: The Single Vventricle Reconstruction Trial., Peter C. Frommelt, Lin T. Guey, L Luann Minich, Majeed Bhat, Tim J. Bradley, Steve D. Colan, Greg Ensing, Jessica Gorentz, Haleh Heydarian, J Blaine John, Wyman W. Lai, Jami C. Levine, William T. Mahle, Stephen G. Miller, Richard G. Ohye, Gail D. Pearson, Girish S. Shirali, Pierre C. Wong, Meryl S. Cohen, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The Pediatric Heart Network trial comparing outcomes in 549 infants with single right ventricle undergoing a Norwood procedure randomized to modified Blalock-Taussig shunt or right ventricle-pulmonary artery shunt (RVPAS) found better 1-year transplant-free survival in those who received RVPAS. We sought to compare the impact of shunt type on echocardiographic indices of cardiac size and function up to 14 months of age.

METHODS AND RESULTS: A core laboratory measured indices of cardiac size and function from protocol exams: early after Norwood procedure (age 22.5 ± 13.4 days), before stage II procedure (age 4.8 ± 1.8 months), and at 14 …

Early Developmental Outcome In Children With Hypoplastic Left Heart Syndrome And Related Anomalies: The Single Ventricle Reconstruction Trial., Jane W. Newburger, Lynn A. Sleeper, David C. Bellinger, Caren S. Goldberg, Sarah Tabbutt, Minmin Lu, Kathleen A. Mussatto, Ismee A. Williams, Kathryn E. Gustafson, Seema Mital, Nancy Pike, Erica Sood, William T. Mahle, David S. Cooper, Carolyn Dunbar-Masterson, Catherine Dent Krawczeski, Alan Lewis, Shaji C. Menon, Victoria L. Pemberton, Chitra Ravishankar, Teresa W. Atz, Richard G. Ohye, J William Gaynor, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Survivors of the Norwood procedure may experience neurodevelopmental impairment. Clinical trials to improve outcomes have focused primarily on methods of vital organ support during cardiopulmonary bypass.

METHODS AND RESULTS: In the Single Ventricle Reconstruction trial of the Norwood procedure with modified Blalock-Taussig shunt versus right-ventricle-to-pulmonary-artery shunt, 14-month neurodevelopmental outcome was assessed by use of the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Development-II. We used multivariable regression to identify risk factors for adverse outcome. Among 373 transplant-free survivors, 321 (86%) returned at age 14.3 ± 1.1 (mean ± SD) months. Mean …

Prenatal Diagnosis And Risk Factors For Preoperative Death In Neonates With Single Right Ventricle And Systemic Outflow Obstruction: Screening Data From The Pediatric Heart Network Single Ventricle Reconstruction Trial(∗)., Andrew M. Atz, Thomas G. Travison, Ismee A. Williams, Gail D. Pearson, Peter C. Laussen, William T. Mahle, Amanda L. Cook, Joel A. Kirsh, Mark Sklansky, Svetlana Khaikin, Caren Goldberg, Michele Frommelt, Catherine Krawczeski, Michael D. Puchalski, Jeffrey P. Jacobs, Jeanne M. Baffa, Jack Rychik, Richard G. Ohye, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: The purpose of this analysis was to assess preoperative risk factors before the first-stage Norwood procedure in infants with hypoplastic left heart syndrome and related single-ventricle lesions and to evaluate practice patterns in prenatal diagnosis, as well as the role of prenatal diagnosis in outcome.

METHODS: Data from all live births with morphologic single right ventricle and systemic outflow obstruction screened for the Pediatric Heart Network's Single Ventricle Reconstruction Trial were used to investigate prenatal diagnosis and preoperative risk factors. Demographics, gestational age, prenatal diagnosis status, presence of major extracardiac congenital abnormalities, and preoperative mortality rates were recorded.

RESULTS: …

Design And Rationale Of A Randomized Trial Comparing The Blalock-Taussig And Right Ventricle-Pulmonary Artery Shunts In The Norwood Procedure., Richard G. Ohye, J William Gaynor, Nancy S. Ghanayem, Caren S. Goldberg, Peter C. Laussen, Peter C. Frommelt, Jane W. Newburger, Gail D. Pearson, Sarah Tabbutt, Gil Wernovsky, Lisa M. Wruck, Andrew M. Atz, Steve D. Colan, James Jaggers, Brian W. Mccrindle, Ashwin Prakash, Michael D. Puchalski, Lynn A. Sleeper, Mario P. Stylianou, Lynn Mahony, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: The initial palliative procedure for patients born with hypoplastic left heart syndrome and related single right ventricle anomalies, the Norwood procedure, remains among the highest risk procedures in congenital heart surgery. The classic Norwood procedure provides pulmonary blood flow with a modified Blalock-Taussig shunt. Improved outcomes have been reported in a few small, nonrandomized studies of a modification of the Norwood procedure that uses a right ventricle-pulmonary artery shunt to provide pulmonary blood flow. Other nonrandomized studies have shown no differences between the two techniques.

METHODS: The Pediatric Heart Network designed a randomized clinical trial to compare outcomes for …

Survival After Bidirectional Cavopulmonary Anastomosis: Analysis Of Preoperative Risk Factors., Mark A. Scheurer, Elizabeth G Hill, Nagavardhan Vasuki, Scott Maurer, Eric M. Graham, Varsha Bandisode, Girish S. Shirali, Andrew M. Atz, Scott M. Bradley

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVE: Prognostic factors for survival after bidirectional cavopulmonary anastomosis for functionally single ventricle are not well defined. We analyzed preoperative hemodynamic and echocardiographic data to determine risk factors for death or transplantation at least 1 year after bidirectional cavopulmonary anastomosis.

METHODS: Data for all patients who underwent bidirectional cavopulmonary anastomosis before 5 years of age at our institution from September 1995 through June 2005 were analyzed. Available preoperative echocardiograms and catheterizations were reviewed. Survivors were compared with those who died or underwent transplantation. Bivariable associations between demographic and clinical risk factors and survival status (alive without transplantation vs dead or …