Ronnie Thomas Collins

All Publications

• Cardiovascular imaging in Turner syndrome: state-of-the-art practice across the lifespan. Heart (British Cardiac Society) Mortensen, K. H., Young, L., De Backer, J., Silberbach, M., Collins, R. T., Duijnhouwer, A. L., Pandya, B., Gravholt, C. H., Lopez, L., Roos-Hesselink, J. W. 2018; 104 (22): 1823–31

  Abstract

  Cardiovascular imaging is essential to providing excellent clinical care for girls and women with Turner syndrome (TS). Congenital and acquired cardiovascular diseases are leading causes of the lifelong increased risk of premature death in TS. Non-invasive cardiovascular imaging is crucial for timely diagnosis and treatment planning, and a systematic and targeted imaging approach should combine echocardiography, cardiovascular magnetic resonance and, in select cases, cardiac CT. In recent decades, evidence has mounted for the need to perform cardiovascular imaging in all females with TS irrespective of karyotype and phenotype. This is due to the high incidence of outcome-determining lesions that often remain subclinical and occur in patterns specific to TS. This review provides an overview of state-of-the-art cardiovascular imaging practice in TS, by means of a review of the most recent literature, in the context of a recent consensus statement that has highlighted the role of cardiovascular diseases in these females.

  View details for DOI 10.1136/heartjnl-2017-312658

  View details for PubMedID 30228249

• Cardiovascular Health in Turner Syndrome: A Scientific Statement From the American Heart Association. Circulation. Genomic and precision medicine Silberbach, M., Roos-Hesselink, J. W., Andersen, N. H., Braverman, A. C., Brown, N., Collins, R. T., De Backer, J., Eagle, K. A., Hiratzka, L. F., Johnson, W. H., Kadian-Dodov, D., Lopez, L., Mortensen, K. H., Prakash, S. K., Ratchford, E. V., Saidi, A., van Hagen, I., Young, L. T. 2018; 11 (10): e000048

  Abstract

  Girls and women with Turner syndrome face a lifelong struggle with both congenital heart disease and acquired cardiovascular conditions. Bicuspid aortic valve is common, and many have left-sided heart obstructive disease of varying severity, from hypoplastic left-sided heart syndrome to minimal aortic stenosis or coarctation of the aorta. Significant enlargement of the thoracic aorta may progress to catastrophic aortic dissection and rupture. It is becoming increasingly apparent that a variety of other cardiovascular conditions, including early-onset hypertension, ischemic heart disease, and stroke, are the major factors reducing the life span of those with Turner syndrome. The presentations and management of cardiovascular conditions in Turner syndrome differ significantly from the general population. Therefore, an international working group reviewed the available evidence regarding the diagnosis and treatment of cardiovascular diseases in Turner syndrome. It is recognized that the suggestions for clinical practice stated here are only the beginning of a process that must also involve the establishment of quality indicators, structures and processes for implementation, and outcome studies.

  View details for DOI 10.1161/HCG.0000000000000048

  View details for PubMedID 30354301

• Cardiovascular disease in Williams syndrome. Current opinion in pediatrics Collins, R. T. 2018; 30 (5): 609–15

  Abstract

  Williams syndrome is a multisystem disorder seen with some regularity at most pediatric centers and usually fairly often at larger centers. Cardiovascular abnormalities, because of elastin deficiency, are the leading cause of morbidity and mortality in patients with Williams syndrome. The present article presents a review of the most recent developments regarding the cardiovascular issues in Williams syndrome.Cardiovascular abnormalities occur in 80% of patients with Williams syndrome, the majority of which are arterial stenoses. The stenoses seen in Williams syndrome now appear to arise from deficient circumferential arterial growth. Pharmacological therapies aimed at improving the vascular stenoses have shown some promise in animal models. Surgical outcomes for supravalvar aortic stenosis are good at most centers. Transcatheter interventions are largely ineffective in Williams syndrome. Multilevel surgical pulmonary artery reconstruction has excellent results for peripheral pulmonary artery stenosis. Periprocedural risk stratification and management algorithms may decrease the risk of cardiovascular complications.Cardiovascular abnormalities are a major determining factor in the clinical picture and trajectory of patients with Williams syndrome. Advances in surgical techniques, medical therapeutic options, and periprocedural management hold promise for significant improvements in the cardiovascular outcomes of these patients.

  View details for DOI 10.1097/MOP.0000000000000664

  View details for PubMedID 30045083

• Transcatheter Versus Surgical Pulmonary Valve Replacement in Repaired Tetralogy of Fallot. The American journal of cardiology Daily, J. A., Tang, X., Angtuaco, M., Bolin, E., Lang, S. M., Collins, R. T. 2018; 122 (3): 498–504

  Abstract

  Transcatheter pulmonary valve replacement (TC-PVR) is an alternative to surgical PVR (S-PVR) in repaired Tetralogy of Fallot (TOF). The purpose of this study is to compare in-hospital outcomes, hospital costs, and projected 5-year total costs of S-PVR to TC-PVR in patients with repaired TOF. We performed a multicenter, retrospective cohort study of children and adults with TOF ≥ 8 years of age who underwent PVR from January 1, 2010 to December 31, 2016 at 46 centers contributing to the Pediatric Health Information Systems database. Baseline characteristics, in-hospital outcomes, and costs were compared between the two groups. Projected 5-year costs were calculated by combining cost data with published reintervention rates. A total of 194 TC-PVR and 1,072 S-PVR were performed. The baseline characteristics of the TC-PVR and S-PVR groups were not significantly different with the exception of greater age in the TC-PVR group (median age of 17 years vs 15 years, p value <0.001). Discharge mortality, hospital charges and estimated cost, surgical complication rates, and acute kidney failure were not significantly different between the groups. Intensive care unit use, intensive care unit length of stay (LOS), mechanical ventilation use, extracorporeal membrane oxygenation use, and total LOS were lower with TC-PVR than S-PVR. Projected 5-year costs were greater with TC-PVR compared with S-PVR ($64,762 vs $56,536) due to the cost of the transcatheter pulmonary valve and higher reintervention rates. In conclusion, despite longer LOS and greater in-hospital resource utilization for patients with TOF who underwent S-PVR compared with TC-PVR, mortality, and in-hospital costs are the same, and projected 5-year costs are less.

  View details for DOI 10.1016/j.amjcard.2018.04.028

  View details for PubMedID 30201112

• Congenital Heart Surgery on In-Hospital Mortality in Trisomy 13 and 18. Pediatrics Kosiv, K. A., Gossett, J. M., Bai, S., Collins, R. T. 2017; 140 (5)

  Abstract

  Congenital heart disease (CHD) is common in trisomy 13 (T13) and trisomy 18 (T18), but surgical repair has not been offered in most centers. Data on outcomes of congenital heart surgery (CHS) for T13 and T18 are lacking. We sought to determine the impact of CHS on in-hospital mortality in T13 and T18.Data from the 2004 to 2015 Pediatric Health Information System database were used to identify inpatients with T13 or T18 and CHD. Data were restricted to newborns with T13 or T18 admitted at ≤14 days of age. Hospital readmissions were examined to analyze longer-term in-hospital mortality. In-hospital mortality and length of stay were compared between infants with and without CHD and with and without CHS.The study cohort included 1020 infants with T18 and 648 infants with T13. CHD was present in 91% of infants with T18 and 86% of infants with T13. CHS was performed in 7% of each group. In-hospital mortality was decreased in those who underwent CHS (64% lower in T18 [P <.001]; 45% lower in T13 [P = .003]) and remained decreased throughout the 24 months of follow-up. In-hospital mortality was decreased in infants with higher weight, female sex, and older age at admission.CHS is associated with decreased in-hospital mortality in T18 and T13. These results suggest CHS may be beneficial in select cases.

  View details for DOI 10.1542/peds.2017-0772

  View details for PubMedID 29046387

• Peri-procedural risk stratification and management of patients with Williams syndrome. Congenital heart disease Collins Ii, R. T., Collins, M. G., Schmitz, M. L., Hamrick, J. T. 2017; 12 (2): 133–42

  Abstract

  Williams syndrome (WS) is a congenital, multisystem disorder affecting the cardiovascular, connective tissue, and central nervous systems in 1 in 10 000 live births. Cardiovascular involvement is the most common cause of morbidity and mortality in patients with WS, and noninvasive and invasive procedures are common. Sudden cardiovascular collapse in patients with WS is a well-known phenomenon, especially in the peri-procedural period. Detailed guidelines for peri-procedural management of patients with WS are limited. The goal of this review is to provide thoughtful, safe and effective management strategies for the peri-procedural care of patients with WS with careful consideration of hemodynamic impacts of anesthetic strategies. In addition, an expanded risk stratification system for anesthetic administration is provided.

  View details for DOI 10.1111/chd.12447

  View details for PubMedID 28382779

• Propranolol Versus Digoxin in the Neonate for Supraventricular Tachycardia (from the Pediatric Health Information System). The American journal of cardiology Bolin, E. H., Lang, S. M., Tang, X., Collins, R. T. 2017; 119 (10): 1605–10

  Abstract

  Conflicting data exist for the appropriate management of a neonate with supraventricular tachycardia (SVT). We sought to assess postnatal prescribing trends for neonates with SVT and to evaluate if there were therapy-specific mortality and resource utilization benefits. Nationally distributed data from 44 pediatric hospitals in the 2004 to 2015 Pediatric Health Information System database were used to identify patients admitted at ≤2 days of age with structurally normal hearts and treated with an antiarrhythmic medication. Outcome variables were mortality, cost, and length of stay (LOS). Multivariable models and propensity score matching were used. There were 2,657 neonates identified with a median gestational age of 37 weeks (interquartile range 34 to 39). Digoxin and propranolol were most commonly prescribed; digoxin use steadily decreased to 23% of antiarrhythmic medication administrations over the study period, whereas propranolol increased to 77%. Multivariable comparisons revealed that the odds of mortality for neonates on propranolol were 0.32 times those on digoxin (95% confidence interval 0.17 to 0.59; p <0.001); hospital costs were $16,549 lower for propranolol versus digoxin (95% confidence interval $5,502 to $27,596, p = 0.003). No difference was found for LOS. Propensity score matching and subset analyses of patients with only arrhythmia diagnostic codes confirmed mortality benefits for propranolol, although longer LOS was observed. In conclusion, propranolol use for the neonate with SVT is associated with lower in-hospital mortality and hospital costs compared with digoxin.

  View details for DOI 10.1016/j.amjcard.2017.02.017

  View details for PubMedID 28363353

• Advanced cardiovascular imaging in Williams syndrome: Abnormalities, usefulness, and strategy for use. American journal of medical genetics. Part A Hills, J. A., Zarate, Y. A., Danylchuk, N. R., Lepard, T., Chen, J. C., Collins, R. T. 2017; 173 (5): 1194–99

  Abstract

  Extracardiac arterial stenoses are not uncommon in Williams syndrome (WS); however, data on the utility of advanced cardiovascular imaging (CVI) to assess these stenoses are lacking. We retrospectively reviewed the frequency, indication, and diagnostic outcomes of CVI modalities performed in patients with WS evaluated at a single institution between 2001 and 2014. Data were collected and analyzed from 34 patients (56% female) who underwent CVI during the study period. The median age was 10 years (range 1.8-33 years). Excluding echocardiograms, 78 CVI studies "advanced" were performed in the 34 patients (mean 2.3 studies/patient). The most common advanced CVI was renal ultrasound with Doppler (29/34, 85%), followed by computed tomographic angiography (13/34, 38%) and magnetic resonance angiography in (9/34, 26%). Abnormalities were detected in 62% of patients (21/34). For the 20 patients in whom advanced CVI were performed for defined clinical indications, the rate of abnormalities were 73, 70, 57, and 100% when performed for anatomic delineation (15 patients), hypertension (10 patients), bruits (7 patients), and/or decreased peripheral pulses (2 patients), respectively. Advanced CVI in patients with WS reveals abnormalities in the majority of cases, and physical exam findings frequently indicate abnormalities on advanced CVI.

  View details for DOI 10.1002/ajmg.a.38138

  View details for PubMedID 28332295

• Aortic dilation, genetic testing, and associated diagnoses. Genetics in medicine : official journal of the American College of Medical Genetics Zarate, Y. A., Sellars, E., Lepard, T., Tang, X., Collins, R. T. 2016; 18 (4): 356–63

  Abstract

  The aims of this study were to determine the genetic diagnoses most frequently associated with aortic dilation in a large population and to describe the results of genetic testing in the same.A retrospective review of records from patients with known aortic dilation identified through an echocardiogram database was performed. During the study period, different chromosomal microarray platforms and molecular diagnostic techniques were used.A total of 715 patients (mean age, 9.7 years; 67% male) met study inclusion criteria. The overall frequency of underlying presumptive or confirmed genetic diagnoses was 17% (125/715). Molecular evaluation for possible underlying aortopathy-related disorders was performed in 9% of patients (66/715). Next-generation sequencing panels were performed in 16 patients, and pathogenic abnormalities were detected in 4 (25%). Microarrays were conducted in 10% of patients (72/715), with a total of 23 pathogenic copy-number variants identified in 19 patients (26%). Marfan syndrome was the most frequently recognized genetic disorder associated with aortic dilation, but other cytogenetic abnormalities and associated diagnoses also were identified.The differential diagnosis in patients with aortic dilation is broad and includes many conditions outside the common connective tissue disorder spectrum. A genetics evaluation should be considered to assist in the diagnostic evaluation.Genet Med 18 4, 356-363.

  View details for DOI 10.1038/gim.2015.88

  View details for PubMedID 26133393

• Adverse cardiac events in children with Williams syndrome undergoing cardiovascular surgery: An analysis of the Society of Thoracic Surgeons Congenital Heart Surgery Database. The Journal of thoracic and cardiovascular surgery Hornik, C. P., Collins, R. T., Jaquiss, R. D., Jacobs, J. P., Jacobs, M. L., Pasquali, S. K., Wallace, A. S., Hill, K. D. 2015; 149 (6): 1516–22.e1

  Abstract

  Patients with Williams syndrome (WS) undergoing cardiac surgery are at risk for major adverse cardiac events (MACE). Prevalence and risk factors for such events have not been well described. We sought to define frequency and risk of MACE in patients with WS using a multicenter clinical registry.We identified cardiac operations performed in patients with WS using the Society of Thoracic Surgeons Congenital Heart Surgery Database (2000-2012). Operations were divided into 4 groups: isolated supravalvular aortic stenosis, complex left ventricular outflow tract (LVOT), isolated right ventricular outflow tract (RVOT), and combined LVOT/RVOT procedures. The proportion of patients with MACE (in-hospital mortality, cardiac arrest, or postoperative mechanical circulatory support) was described and the association with preoperative factors was examined.Of 447 index operations (87 centers), median (interquartile range) age and weight at surgery were 2.4 years (0.6-7.4 years) and 10.6 kg (6.5-21.5 kg), respectively. Mortality occurred in 20 patients (5%). MACE occurred in 41 patients (9%), most commonly after combined LVOT/RVOT (18 out of 87; 21%) and complex LVOT (12 out of 131; 9%) procedures, but not after isolated RVOT procedures. Odds of MACE decreased with age (odds ratio [OR], 0.99; 95% confidence interval [CI], 0.98-0.99), weight (OR, 0.97; 95% CI, 0.93-0.99), but increased in the presence of any preoperative risk factor (OR, 2.08; 95% CI, 1.06-4.00), and in procedures involving coronary artery repair (OR, 5.37; 95% CI, 2.05-14.06).In this multicenter analysis, MACE occurred in 9% of patients with WS undergoing cardiac surgery. Demographic and operative characteristics were associated with risk. Further study is needed to elucidate mechanisms of MACE in this high-risk population.

  View details for DOI 10.1016/j.jtcvs.2015.02.016

  View details for PubMedID 25791950

  View details for PubMedCentralID PMC4464977

• β-Blockers and angiotensin converting enzyme inhibitors: comparison of effects on aortic growth in pediatric patients with Marfan syndrome. The Journal of pediatrics Phomakay, V., Huett, W. G., Gossett, J. M., Tang, X., Bornemeier, R. A., Collins, R. T. 2014; 165 (5): 951–55

  Abstract

  Angiotensin converting enzyme inhibitors (ACEI) have been shown to decrease aortic growth velocity (AGV) in Marfan syndrome (MFS). We sought to compare the effect of β-blockers and ACEI on AGV in MFS.We retrospectively reviewed all data from all patients with MFS seen at Arkansas Children's Hospital between January 1, 1976 and January 1, 2013. Generalized least squares were used to evaluate AGV over time as a function of age, medication group, and the interaction between the 2. A mixed model was used to compare AGV between medication groups as a function of age, medication group (none, β-blocker, ACEI), and the interaction between the 2.A total of 67 patients with confirmed MFS were identified (34/67, 51% female). Mean age at first encounter was 13 ± 10 years, with mean follow-up of 7.6 ± 5.8 years. There were 839 patient encounters with a median of 10 (range 2-42) encounters per patient. AGV was nearly normal in the β-blocker group, and was less than either the ACEI or untreated groups. The AGV was higher than normal in ACEI and untreated groups (P < .001 for both).β-blocker therapy results in near-normalization of AGV in MFS. ACEI did not decrease AGV in a clinically significant manner.

  View details for DOI 10.1016/j.jpeds.2014.07.008

  View details for PubMedID 25109242

  View details for PubMedCentralID PMC4330566

• Cardiovascular disease in Williams syndrome. Circulation Collins, R. T. 2013; 127 (21): 2125–34

  View details for DOI 10.1161/CIRCULATIONAHA.112.000064

  View details for PubMedID 23716381

• Abnormalities of cardiac repolarization in Williams syndrome. The American journal of cardiology Collins, R. T., Aziz, P. F., Gleason, M. M., Kaplan, P. B., Shah, M. J. 2010; 106 (7): 1029–33

  Abstract

  Williams syndrome (WS) affects 1 in 8,000 live births and has a high risk of sudden death. No previous studies have evaluated corrected QT (QTc) prolongation in WS. Retrospective review of all patients with WS evaluated at our institution from January 1, 1980 to December 31, 2007 was performed. WS was diagnosed by a medical geneticist and/or by fluorescence in situ hybridization. Patients with ≥1 electrocardiogram (ECG) with sinus rhythm and measurable intervals were included. Normal control ECGs were identified from a large clinical database. Corrected JT (JTc) interval was calculated when QRS and QTc intervals were prolonged. QTc interval ≥460 ms and JTc interval >340 ms were defined as prolonged. Prevalence comparisons were made using Fisher's exact test. Statistical probability of <0.05 was considered significant. Of 270 patients identified, 188 had ECGs for review. Complete data were present in 499 of 517 ECGs (patients' mean age 10.3 ± 9.9 years); 1,522 normal ECGs of age-similar patients composed the control group. QTc prolongation prevalences were 2.0% in controls and 13.6% in WS (p <0.0001); in those, JTc prolongation prevalences were 1.8% in controls and 11.7% in WS (p <0.0001). Four patients died during follow-up; 2 had QTc prolongation and 1 died during noncardiac surgery. Another patient with QTc prolongation sustained cardiac arrest during a procedure. In conclusion, cardiac repolarization is prolonged in WS. Presence of prolonged cardiac repolarization may contribute to the high incidence of periprocedural mortality in these patients. All patients with WS should be screened for cardiac repolarization abnormalities, especially before surgery.

  View details for DOI 10.1016/j.amjcard.2010.05.041

  View details for PubMedID 20854969

• Long-term outcomes of patients with cardiovascular abnormalities and williams syndrome. The American journal of cardiology Collins, R. T., Kaplan, P., Somes, G. W., Rome, J. J. 2010; 105 (6): 874–78

  Abstract

  Williams syndrome (WS) is a congenital disorder affecting the vascular, connective tissue, and central nervous systems of 1 in 8,000 live births. Previous reports have reported high frequencies of cardiovascular abnormalities (CVAs) in small numbers of patients with WS. A retrospective review was undertaken of patients with WS evaluated at our institution from January 1, 1980 through December 31, 2007. WS was diagnosed by an experienced medical geneticist and/or by fluorescence in situ hybridization. CVAs were diagnosed using echocardiography, cardiac catheterization, or computed tomographic angiography. Freedom from intervention was determined using Kaplan-Meier analysis. The study group was 270 patients with WS. The age at presentation was 3.3 +/- 5.9 years with follow-up of 8.9 +/- 9.0 years (range 0 to 56.9). CVAs were present in 82% of the patients. The most common lesions were supravalvar aortic stenosis in 45% and peripheral pulmonary stenosis in 37%; 20% had both. Other common lesions included mitral valve prolapse and regurgitation in 15%, ventricular septal defect in 13%, and supravalvar pulmonary stenosis in 12%. Surgical or catheter-based interventions were performed in 21%. The rate of freedom from intervention was 91%, 81%, 78%, 72%, and 62% at 1, 5, 10, 20, and 40 years. Eight patients died. In conclusion, CVAs are common in patients with WS, but supravalvar aortic stenosis and peripheral pulmonary stenosis occurred less frequently in this large cohort than previously reported. In patients with WS and CVAs, interventions are common and usually occur by 5 years of age. Most patients with WS do not require intervention during long-term follow-up, and the overall mortality has been low.

  View details for DOI 10.1016/j.amjcard.2009.10.069

  View details for PubMedID 20211336

• Constitutive activation of the PI3K-AKT pathway and cardiovascular abnormalities in an individual with Kosaki overgrowth syndrome. American journal of medical genetics. Part A Zarate, Y. A., Boccuto, L., Srikanth, S., Pauly, R., Ocal, E., Balmakund, T., Hinkle, K., Stefans, V., Schaefer, G. B., Collins, R. T. 2019

  Abstract

  Kosaki overgrowth syndrome is a recently described syndrome characterized by distinctive facial features, brain white matter lesions, and developmental delay. Germline activating heterozygous PDGFRB mutations have been reported in this condition. Systemic connective tissue-type findings have been described in some individuals. We describe a 19-year-old Caucasian female with a history of hydrocephalus, Dandy-Walker malformation, cervical spine arachnoid cyst, progressive scoliosis, and overgrowth. Her physical exam included distinctive craniofacial dysmorphism, as well as soft and hyperextensible skin. Cardiovascular imaging during adolescence revealed saccular aneurysms in both coronary artery systems and subtle tortuosity of the cervical vertebral arteries. Exome sequencing trio analysis identified a de novo previously reported pathogenic variant in PDGFRB, c.1696T>C (p.[Trp566Arg]). Further functional studies included platelet-derived growth factor cellular metabolic pathway activity that confirmed the variant causes a constitutive activation of the PI3K-AKT pathway. This is the first report to characterize the activating nature of this PDGFRB variant. We also highlight the connective tissue findings seen in Kosaki overgrowth syndrome and recommend baseline echocardiographic evaluation in all individuals with this condition with particular emphasis on coronary arteries.

  View details for DOI 10.1002/ajmg.a.61145

  View details for PubMedID 30941910

• Risk factors associated with the development of double-inlet ventricle congenital heart disease. Birth defects research Paige, S. L., Yang, W., Priest, J. R., Botto, L. D., Shaw, G. M., Collins, R. T., National Birth Defects Prevention Study 2019

  Abstract

  BACKGROUND: Congenital heart disease (CHD) is the most common birth defect group and a significant contributor to neonatal and infant death. CHD with single ventricle anatomy, including hypoplastic left heart syndrome (HLHS), tricuspid atresia (TA), and various double-inlet ventricle (DIV) malformations, is the most complex with the highest mortality. Prenatal risk factors associated with HLHS have been studied, but such data for DIV are lacking.METHODS: We analyzed DIV cases and nonmalformed controls in the National Birth Defects Prevention Study, a case-control, multicenter population-based study of birth defects. Random forest analysis identified potential predictor variables for DIV, which were included in multivariable models to estimate effect magnitude and directionality.RESULTS: Random forest analysis identified pre-pregnancy diabetes, history of maternal insulin use, maternal total lipid intake, paternal race, and intake of several foods and nutrients as potential predictors of DIV. Logistic regression confirmed pre-pregnancy diabetes, maternal insulin use, and paternal race as risk factors for having a child with DIV. Additionally, higher maternal total fat intake was associated with a reduced risk.CONCLUSIONS: Maternal pre-pregnancy diabetes and history of insulin use were associated with an increased risk of having an infant with DIV, while maternal lipid intake had an inverse association. These novel data provide multiple metabolic pathways for investigation to identify better the developmental etiologies of DIV and suggest that public health interventions targeting diabetes prevention and management in women of childbearing age could reduce CHD risk.

  View details for DOI 10.1002/bdr2.1501

  View details for PubMedID 30920163

• Resource Utilization Among Adult Congenital Heart Failure Admissions in Pediatric Hospitals. The American journal of cardiology Chan, J., Collins, R. T., Hall, M., John, A. 2018

  Abstract

  We sought to analyze the trends and resource utilization of adult congenital heart disease (ACHD)-related heart failure admissions at children's hospitals. Heart failure admissions in patients with ACHD continue to rise at both pediatric and adult care facilities. Data from the Pediatric Health Information Systems database (2005 to 2015) were used to identify patients (≥18 years) admitted with congenital heart disease (745.xx-747.xx) and principal diagnosis of heart failure (428.xx). High resource use (HRU) admissions were defined as those over the 90th percentile. There were 562 admissions (55.9% male) across 39 pediatric hospitals. ACHD-related heart failure admissions increased from 4.1% in 2006 to 6.3% in 2015 (p = 0.015). Median hospital charge for ACHD-related heart failure admissions was $59,055 [IQR $26,633 to $156,846]. Total charges increased with more complex anatomic category (p = 0.049). Though HRU admissions represented 10% of ACHD-related heart failure admissions, they accounted for >66% of the total charges. The median total hospital charges for HRU admissions were $1,018,656 [IQR $722,574 to $1,784,743], compared with $58,890 [IQR $26,456 to $145,890] for non-HRU admissions (p < 0.001). Inpatient mortality rate (26.3% vs 4.0%) and the presence of ≥2 comorbidities (68% vs 31%) were higher for HRU admissions (p < 0.001). On multivariable analysis, technology dependence (aOR: 4.4, p < 0.001) and renal comorbidities (aOR: 3.0, p = 0.04) were associated with HRU. In conclusion, heart failure-related ACHD admissions in pediatric hospitals are increasing. Compared with non-HRU, HRU admissions had higher inhospital mortality and greater comorbidities. Additional care strategies to reduce resource use among these patients and improve overall quality of care merits further study.

  View details for DOI 10.1016/j.amjcard.2018.11.033

  View details for PubMedID 30579512

• Aortic complications following pediatric heart transplantation: A case series and review. Annals of pediatric cardiology Lang, S. M., Frazier, E. A., Collins, R. T. ; 9 (1): 42–45

  Abstract

  Aortic complications occur rarely after pediatric orthotopic heart transplantation, but are typically accompanied by catastrophic events. We describe the three cases of major aortic complications in our experience of 329 pediatric heart transplants. This case series and review highlight the important risk factors for aortic complications after heart transplantation.

  View details for DOI 10.4103/0974-2069.171354

  View details for PubMedID 27011691

  View details for PubMedCentralID PMC4782467

• Extracorporeal membrane oxygenation for respiratory failure in the elderly: a review of the Extracorporeal Life Support Organization registry. ASAIO journal (American Society for Artificial Internal Organs : 1992) Mendiratta, P., Tang, X., Collins, R. T., Rycus, P., Brogan, T. V., Prodhan, P. ; 60 (4): 385–90

  Abstract

  Extracorporeal membrane oxygenation (ECMO) support among adults is increasing; however, the role in respiratory failure in the elderly is not clearly defined. The aim of the current study is to investigate survival to hospital discharge among the elderly supported on ECMO. The Extracorporeal Life Support Organization registry database was queried, identifying all elderly patients (≥65 years of age) supported on ECMO for respiratory failure from 1990 to May 2013. The primary outcome was survival to hospital discharge. Clinical characteristics between survivors and nonsurvivors were compared. A total of 368 elderly patients treated with ECMO support for respiratory failure were identified. The median admit-to-initiation-of-ECMO time was 24.5 hours, and median duration of ECMO was 140 hours. Survival at hospital discharge was 41%. Approximately 69% of the overall ECMO usages occurred from 2010 to 2013. Nonsurvivors had significantly higher pre-ECMO peak inspiratory pressures, lower SaO2/FiO2 ratio, and higher rate of diverse complications. Among pre-ECMO therapies, vasodilators, steroids, and inhaled nitric oxide were more frequently used in survivors. Survival-to-hospital discharge rate is lower (41%) in elderly patients treated with ECMO compared with that in all adults (55%). However, given the noted survival, age should not be a firm contraindication for the use of ECMO in older patients but should be considered on a case-by-case basis.

  View details for DOI 10.1097/MAT.0000000000000090

  View details for PubMedID 24830799

• Long-Term Neurodevelopment of Low-Birthweight, Preterm Infants with Patent Ductus Arteriosus. The Journal of pediatrics Collins, R. T., Lyle, R. E., Rettiganti, M., Gossett, J. M., Robbins, J. M., Casey, P. H. 2018

  Abstract

  To evaluate whether the presence of patent ductus arteriosus (PDA) in preterm infants worsens long-term neurodevelopmental outcomes.This was a secondary observational analysis of data from 1090 preterm low-birthweight infants in the Infant Health and Development Program (IHDP), a multicenter longitudinal cohort study of outcomes assessed from 3 to 18 years of age. Multivariable analysis was adjusted for IHDP treatment group (intervention or follow-up), birth weight, maternal race, maternal education, infant sex, maternal preconception weight, Home Observation Measurement of the Environment (HOME) total score at 12 months, neonatal health index, and gestational age.Of the 1090 patients (49% male) included in the analysis, 135 had a PDA. Mean birth weight (1322 g vs 1871 g; P < .0001) and gestational age (30.2 weeks vs 33.4 weeks, P < .0001) were lower and mean ventilator days (11.8 vs 1.3; P < .0001), vasopressor use (12.6% vs 1.2%; P < .0001), and congestive heart failure (8.9% vs 0.1%; P < .0001) were higher in the PDA group. There were no differences between the PDA and no-PDA groups in maternal education level and HOME total score at age 12 months. Multivariable analysis demonstrated no between-group differences in cognitive development or behavioral competence at age 3, 8, and 18 years.The presence of a PDA in moderately preterm, low-birthweight infants does not impact long-term neurodevelopmental outcomes.

  View details for DOI 10.1016/j.jpeds.2018.08.004

  View details for PubMedID 30268404

• Author Response. Pediatrics Collins, R. T., Kosiv, K., Bai, S., Gossett, J. 2018; 141 (5)

  View details for DOI 10.1542/peds.2018-0400B

  View details for PubMedID 29712760

• 50 Years Ago in The Journal of Pediatrics: Trisomy 13 (D1) Syndrome: Studies on Parental Age, Sex Ratio, and Survival. The Journal of pediatrics Collins, R. T., Kosiv, K. 2018; 199: 84

  View details for DOI 10.1016/j.jpeds.2018.01.058

  View details for PubMedID 30049403

• Feasibility of Transthoracic Echocardiography Evaluation of Pulmonary Arteries Following Arterial Switch Operation. Pediatric cardiology Lang, S. M., Crawford, R. L., Shivaram, P., Daily, J. A., Bolin, E. H., Tang, X., Collins, R. T. 2018

  Abstract

  Pulmonary artery (PA) stenosis is the most common late sequela following arterial switch for d-transposition of the great arteries. The purpose of this study was to assess the effectiveness of transthoracic echocardiography in evaluating the pulmonary arteries following repair. This was a retrospective, cross-sectional analysis of all echocardiograms performed on patients following arterial switch operation. A numerical scoring system was devised and used to quantify PA visualization based on 2D images, color mapping, and spectral Doppler. The study cohort included 150 patients. The ability to visualize at least one PA was poorer in patients who were older [> 10 years (47%) vs ≤ 10 years (89%) (p < 0.001)], and who had larger body surface area (BSA) (> 1.25 m2 (40%) vs ≤ 1.25 m2 (90%) (p < 0.001)]. Regardless of age, 2D visualization of the pulmonary arteries was poor for the entire cohort. Of those with at least one non-visualized PA, only 54% had alternative imaging performed or ordered within the 5 years at or prior to their last echocardiogram. In conclusion, PA visualization following arterial switch is worse in patients who are older and in those with larger BSA. In such patients, alternative forms of imaging are more likely to be necessary.

  View details for DOI 10.1007/s00246-018-1924-6

  View details for PubMedID 29882188

• Short-Axis Diastolic Ventricular Area Ratio as a New Index in Screening Patients with Repaired Tetralogy of Fallot. Pediatric cardiology Zakaria, D., Lang, S., Rettiganti, M., Gossett, J. M., Bolin, E., Collins, R. T. 2018

  Abstract

  Right ventricular (RV) end-diastolic volume measured by cardiovascular magnetic resonance imaging (CMR) is a criterion for pulmonary valve replacement in patients with tetralogy of Fallot (TOF). We sought to determine if the ratio of echocardiographic, short-axis RV-to-left ventricular (LV) end-diastolic areas (EDA) could be used to predict RV volume on CMR. We retrospectively reviewed the echocardiograms of all patients with repaired TOF who underwent CMR at our institution from 2011 to 2015 and also had an echocardiogram within 6 months of the CMR. The short-axis RV and LV EDAs were measured and the ratio of the two was calculated. Results were compared with CMR RV end-diastolic volume index (RVEDVi) and RV:LV end-diastolic volume ratio. The sensitivity and specificity values predicting RV volumes > 150 ml/m2 were calculated. Fifty-eight studies met inclusion criteria. There were 47 studies with RVEDVi < 150 ml/m2 and 11 with RVEDVi > 150 ml/m2. RV:LV EDA and CMR RV:LV end-diastolic volume ratio correlated strongly (r = 0.76, p < 0.0001). An RV:LV EDA ≥ 1.57 had a 90% sensitivity to predict RVEDVi > 150 ml/m2 (area under the curve = 0.74, 95% CI 1.5-27.9; p = 0.012). An RV:LV EDA ≥ 1.88 had an 81% specificity to detect RV volume index > 150 ml/m2. Short-axis RV:LV EDA correlates well with an increased RVEDVi as measured by CMR. This new and simple measure can be used to predict optimal timing for CMR in anticipation of pulmonary valve replacement in repaired TOF.

  View details for DOI 10.1007/s00246-018-1905-9

  View details for PubMedID 29767292

• Arterial tortuosity syndrome: 40 new families and literature review. Genetics in medicine : official journal of the American College of Medical Genetics Beyens, A., Albuisson, J., Boel, A., Al-Essa, M., Al-Manea, W., Bonnet, D., Bostan, O., Boute, O., Busa, T., Canham, N., Cil, E., Coucke, P. J., Cousin, M. A., Dasouki, M., De Backer, J., De Paepe, A., De Schepper, S., De Silva, D., Devriendt, K., De Wandele, I., Deyle, D. R., Dietz, H., Dupuis-Girod, S., Fontenot, E., Fischer-Zirnsak, B., Gezdirici, A., Ghoumid, J., Giuliano, F., Diéz, N. B., Haider, M. Z., Hardin, J. S., Jeunemaitre, X., Klee, E. W., Kornak, U., Landecho, M. F., Legrand, A., Loeys, B., Lyonnet, S., Michael, H., Moceri, P., Mohammed, S., Muiño-Mosquera, L., Nampoothiri, S., Pichler, K., Prescott, K., Rajeb, A., Ramos-Arroyo, M., Rossi, M., Salih, M., Seidahmed, M. Z., Schaefer, E., Steichen-Gersdorf, E., Temel, S., Uysal, F., Vanhomwegen, M., Van Laer, L., Van Maldergem, L., Warner, D., Willaert, A., Collins, T. R., Taylor, A., Davis, E. C., Zarate, Y., Callewaert, B. 2018

  Abstract

  PurposeWe delineate the clinical spectrum and describe the histology in arterial tortuosity syndrome (ATS), a rare connective tissue disorder characterized by tortuosity of the large and medium-sized arteries, caused by mutations in SLC2A10.MethodsWe retrospectively characterized 40 novel ATS families (50 patients) and reviewed the 52 previously reported patients. We performed histology and electron microscopy (EM) on skin and vascular biopsies and evaluated TGF-β signaling with immunohistochemistry for pSMAD2 and CTGF.ResultsStenoses, tortuosity, and aneurysm formation are widespread occurrences. Severe but rare vascular complications include early and aggressive aortic root aneurysms, neonatal intracranial bleeding, ischemic stroke, and gastric perforation. Thus far, no reports unequivocally document vascular dissections or ruptures. Of note, diaphragmatic hernia and infant respiratory distress syndrome (IRDS) are frequently observed. Skin and vascular biopsies show fragmented elastic fibers (EF) and increased collagen deposition. EM of skin EF shows a fragmented elastin core and a peripheral mantle of microfibrils of random directionality. Skin and end-stage diseased vascular tissue do not indicate increased TGF-β signaling.ConclusionOur findings warrant attention for IRDS and diaphragmatic hernia, close monitoring of the aortic root early in life, and extensive vascular imaging afterwards. EM on skin biopsies shows disease-specific abnormalities.GENETICS in MEDICINE advance online publication, 11 January 2018; doi:10.1038/gim.2017.253.

  View details for DOI 10.1038/gim.2017.253

  View details for PubMedID 29323665

• Congenital heart disease complexity and childhood cancer risk. Birth defects research Collins, R. T., Von Behren, J., Yang, W., Carmichael, S. L., Reynolds, P., Fisher, P. G., Shaw, G. M. 2018; 110 (17): 1314–21

  Abstract

  Childhood cancer is increased in those with birth defects, including those with congenital heart disease (CHD). Lymphoma risk is increased in children with CHD. This study analyzes the effect of CHD and CHD severity on childhood cancer risk.We analyzed cancer risk in a population-based cohort of children with and without CHD born between 1988 and 2004 by linking data from the California Birth Defects Monitoring Program with data from the California Cancer Registry. We compared cancer risk in children with and without CHD, excluding children with chromosomal anomalies.Of >3 million children in the birth cohort, 65,585 had birth defects (2%), 25,981 with CHD. Cancer occurred in 4,781 (0.15%) children, 43 (0.17%) with CHD. Cancer risk in CHD was increased (hazard ratio [HR]) 2.63, 95% CI: 1.95, 3.55). Leukemia was the most common cancer in those without CHD (1,722/4,738, 36%), central nervous system tumors were second (1,073/4,738, 23%), and lymphoma third (410/4,738, 9%). Among children with CHD, lymphoma and leukemia occurred with the same frequency (12/43, 28% for each). HR for lymphoma was 8.37 (CI: 4.71, 14.86) with CHD versus without. HR for leukemia was 2.05 (CI: 1.16, 3.61) with CHD versus without. CHD complexity was higher in lymphoma (3, interquartile range [IQR]: 2-3) than those with leukemia (1, IQR, 1-2; p < .02).Cancer risk is increased in children with CHD. Lymphoma risk is increased in CHD and is correlated with more complex CHD. These results suggest a shared developmental origin for CHD and lymphoma may be present.

  View details for DOI 10.1002/bdr2.1390

  View details for PubMedID 30328285

• Parental-reported neurodevelopmental issues in Loeys-Dietz syndrome. Research in developmental disabilities Collins, R. T., Flor, J. M., Tang, X., Bange, J. M., Zarate, Y. A. 2018; 83: 153–59

  Abstract

  Loeys-Dietz syndrome (LDS) is a congenital multisystem disorder affecting the cardiovascular and musculoskeletal system. Limited data have reported neurodevelopmental (ND) issues in LDS.To determine the extent of ND issues in patients with LDS.A prospective study was performed of LDS patients or their caregivers. The study included data collected via an online survey of age-specific questions. Standard statistical methods were used for baseline and demographic characteristics, as well as group comparisons.Data were obtained from 67 patients with LDS (54% female). Median age was 14.9 years. Gene mutations included TGFBR1 (39%), TGFBR2 (40%), SMAD3 (7%), and unknown (14%). Motor delays (30%, 18/61) and hypotonia (63%, 37/60) occurred frequently. Physical (62%, 39/62), occupational (41%, 23/56), and speech therapies (34%, 20/58) were common. Feeding issues were common (41%, 23/56). TGFBR1 mutations were more frequent among those with motor delays and feeding issues.Patients with LDS and/or their caregivers report at least one ND problem in most cases, and many require therapies. These data suggest ND disorders should be considered to be part of the phenotype.

  View details for DOI 10.1016/j.ridd.2018.08.003

  View details for PubMedID 30212788

• Impact of Bicuspid Aortic Valve Morphology on Aortic Valve Disease and Aortic Dilation in Pediatric Patients. Pediatric cardiology Ward, R. M., Marsh, J. M., Gossett, J. M., Rettiganti, M. R., Collins, R. T. 2018; 39 (3): 509–17

  Abstract

  Bicuspid aortic valve (BAV) is the most common congenital heart defect. BAV is associated with aortic stenosis and insufficiency, and aortic dilation in adult groups, but data in pediatric groups are limited. We sought to assess the impact of BAV morphology on aortic valve disease and aortic dilation in pediatric patients. We performed a retrospective review of all echocardiograms in patients with isolated BAV who were followed at our institution from July 2002 to July 2012. BAV morphology, aortic valve stenosis and/or insufficiency, and aortic dimensions were measured manually. Comparisons were made between right-left cusp fusion (RL) and right-noncoronary cusp fusion (RN) BAV morphologies. Generalized least square models were fit to analyze the impact of specific variables on aortic dilation. There were 1075 echocardiograms in 366 patients (72% male) with isolated BAV. Aortic valve insufficiency and stenosis were more common in RN (p < 0.001 for both). The median aortic sinus Z score was higher in the RL (0.47; IQR - 0.31 to 1.44) than in the RN group (0.02; - 0.83 to 0.82) (p < 0.001). There was no difference in median ascending aorta Z score between groups. Patients with the highest weights had larger aortas (p < 0.001), but the absolute difference between the highest and lowest weight groups was small (1.5 mm). The impact of BAV morphology on aortic valve disease and aortic dilation in pediatric patients presages that seen in adults. Patient body weight does not make significant clinical impacts on aortic diameters, suggesting that Z scores for aortic diameters should be based on ideal body weights.

  View details for DOI 10.1007/s00246-017-1781-8

  View details for PubMedID 29188316

• Characteristics of Non-postoperative Pediatric Pericardial Effusion: A Multicenter Retrospective Cohort Study from the Pediatric Health Information System (PHIS). Pediatric cardiology Bolin, E. H., Tang, X., Lang, S. M., Daily, J. A., Collins, R. T. 2018; 39 (2): 347–53

  Abstract

  Little is known about the causes and risks of non-postoperative pericardial effusion (PCE) in pediatric patients. We sought to assess the diagnoses most frequently associated with admissions for PCE, and to determine if certain conditions were associated with higher in-hospital mortality and rates of readmission. Nationally distributed data from 44 pediatric hospitals in the 2004-2015 Pediatric Health Information System database were used to identify patients with hospital admissions for International Classification of Disease, Ninth Revision (ICD-9) codes for PCE and/or cardiac tamponade. Children with congenital heart disease were excluded. ICD-9 codes for conditions associated with PCE were grouped into eight categories: neoplastic, renal, autoimmune/inflammatory, pneumonia, viral, bacterial, hypothyroidism, and idiopathic. Multivariable models were used to evaluate odds of in-hospital mortality and readmission within 30 and 90 days. There were 9902 patients who met inclusion criteria. Total in-hospital mortality was 8.2% (n = 813); of those without a neoplastic diagnosis, mortality was 6.5% (n = 493/7543). Idiopathic PCE accounted for the most admissions (36%), followed by neoplasms (24%), pneumonia (20%), and autoimmune/inflammatory disease (19%). In multivariable models, odds of death were highest for neoplasms (adjusted odds ratio 3.83, p < 0.001) and renal disease (adjusted odds ratio 2.86, p < 0.001). Children with a neoplasm, renal disease, and those undergoing pericardiocentesis had the highest rates of readmission at 30 and 90 days. Children admitted with non-postoperative PCE have multiple associated conditions. Neoplasm and renal disease in the setting of PCE are associated with the highest odds of in-hospital mortality among concomitant conditions; children with a neoplasm, renal disease, and those undergoing pericardiocentesis have the highest odds of readmission.

  View details for DOI 10.1007/s00246-017-1762-y

  View details for PubMedID 29086807

• Magnetic Resonance Myocardial Perfusion Imaging: Safety and Indications in Pediatrics and Young Adults. Pediatric cardiology Biko, D. M., Collins, R. T., Partington, S. L., Harris, M., Whitehead, K. K., Keller, M. S., Fogel, M. A. 2018; 39 (2): 275–82

  Abstract

  The purpose of this study was to assess the safety and indications for cardiac magnetic resonance (CMR) with myocardial perfusion imaging (MPI) in a cohort of children and young adults. A retrospective review of 178 children and young adults who underwent CMR with MPI was performed. Studies were categorized based on study protocols as MPI with resting perfusion only, adenosine stress MPI, exercise-induced stress MPI, and MPI for cardiac mass diagnosis. Relevant clinical history, exam indications, and adverse reactions following gadolinium-based contrast agent and adenosine administration were recorded. Studies were reviewed for the presence of myocardial perfusion defects, wall motion abnormalities, and delayed myocardial enhancement. The most common indications from MPI were congenital heart disease (CHD), Kawasaki disease, anomalous coronary artery, or myocardial mass characterization. Of these, 51% were protocoled with adenosine stress, 23% without stress, 6% with exercise stress, and 20% for cardiac mass evaluation. Excluding patients for myocardial mass evaluation, MPI defects were present in 16% (14 with adenosine stress, 1 with exercise stress, 8 on resting studies only). For cardiac mass evaluation, a mass was confirmed in 58%. No adverse reactions occurred with intravenous administration of a gadolinium-based contrast agent. Three self-limited adverse reactions, 2 patients with chest pain, and 1 patient with bradycardia, occurred following adenosine administration. MPI is a safe modality for the evaluation of pediatric and young adults with minimal adverse events. The most common indications for MPI were for the evaluation of CHD, Kawasaki disease, anomalous coronary artery, or myocardial mass characterization.

  View details for DOI 10.1007/s00246-017-1752-0

  View details for PubMedID 29063953

• Knowledge of Appropriate Outpatient Pediatric Echocardiogram Ordering in Primary Care Physicians and Trainees. The American journal of cardiology Lang, S. M., Daily, J. A., FitzGerald, M. R., Tang, X., Best, T. H., Robbins, J. M., Collins, R. T. 2017; 120 (7): 1209–13

  Abstract

  Appropriate Use Criteria (AUC) for the initial use of outpatient pediatric echocardiography were established to aid all clinicians in the evaluation of children with possible heart disease, and limit low diagnostic yield studies. We sought to (1) assess PCPs' and trainees' awareness of the AUC document; (2) compare their knowledge of appropriate echocardiogram ordering with that of pediatric cardiologists; and (3) identify additional medical and nonmedical factors affecting PCP echocardiogram ordering. An online survey with clinical scenarios derived from the AUC guidelines was distributed to PCPs and trainees in Arkansas, and pediatric cardiologists from Arkansas Children's Hospital and Cincinnati Children's Hospital Medical Center. Respondents were also asked to rate whether additional medical and nonmedical factors have "no," "mild," "moderate," or "major" impact on PCP echocardiogram ordering. Survey data were collected from 148 respondents. Awareness of the AUC was significantly lower in PCPs (21.4%) and trainees (14%) than in pediatric cardiologists (90.5%, p <0.001). For all rarely appropriate clinical scenarios, cardiologists had stronger agreement with the AUC document (90.9%) than did the PCP group (50.3%) and trainees (53.3%, p <0.001). The strongest additional factors affecting PCP echocardiogram ordering were parental anxiety, difficulty distinguishing innocent from pathologic murmurs, and legal implications of a missed diagnosis. In conclusion, PCPs and trainees are largely unaware of the existence of the pediatric echocardiogram AUC. Educational strategies to improve appropriate echocardiogram ordering should address not only increasing awareness of AUC, but also other factors affecting decision-making.

  View details for DOI 10.1016/j.amjcard.2017.06.065

  View details for PubMedID 28800832

• Personal Finance for Pediatric Trainees. Clinical pediatrics Daily, J., Collins, R. T., Bolin, E. 2017; 56 (4): 313–15

  View details for DOI 10.1177/0009922816669789

  View details for PubMedID 27681309

• The impact of body weight on the diagnosis of aortic dilation-misdiagnosis in overweight and underweight groups. Echocardiography (Mount Kisco, N.Y.) Braley, K. T., Tang, X., Makil, E. S., Borroughs-Ray, D., Collins, R. T. 2017; 34 (7): 1029–34

  Abstract

  Body surface area (BSA)-indexed Z-scores are used to assess the ascending aorta (AAo) and diagnose aortic dilation (AoD) in children. BSA is directly related to body weight and corresponds to body mass index (BMI). We hypothesized extremes in BMI alter interpretation of aortic size in pediatric patients with AoD.We reviewed all echocardiograms with a diagnosis of AoD performed at our institution from January 2013 through June 2013. Those with an age <2 or >20 years, history of aortic root surgery, or inadequate images were excluded. The aorta was measured by standard methods at the sinus of Valsalva, sinotubular junction, and proximal AAo. Using subject age, height, and gender, hypothetical weights for each subject were calculated to provide BMIs corresponding to the 5th, 50th, 85th, and 95th percentiles. The derived weights were then used to determine hypothetical BSA, and Z-scores were calculated for the subject's aortic diameters in each BMI group.A total of 153 patients met inclusion criteria. Mean age was 11.1±4.6 years (68% male). Mean height was 142.7±27.9 cm, mean weight 44.6±24.8 kg, and mean true BMI was the 62nd centile. Significant differences in all aortic dimension Z-scores were found among normal and underweight, overweight, and obese BMI groups (P<.001 for all comparisons), respectively.Using current recommended methods, AoD will be missed in overweight and obese patients and overdiagnosed in underweight patients. For children of normal weight, a Z-score based on BSA may be reliable. As obesity rates increase, weight-independent Z-scores must be developed.

  View details for DOI 10.1111/echo.13565

  View details for PubMedID 28497541

• Frequency of Development of Aortic Valve Disease in Unrepaired Perimembranous Ventricular Septal Defects. The American journal of cardiology Padiyath, A., Makil, E. S., Braley, K. T., Bolin, E. H., Tang, X., Gossett, J. M., Collins, R. T. 2017; 119 (10): 1670–74

  Abstract

  We sought to determine the natural history of aortic valve disease in patients with unrepaired perimembranous ventricular septal defects (pVSDs) and to identify echocardiographic parameters predictive of increased risk of surgical repair of pVSD because of aortic valve disease. We retrospectively analyzed all echocardiograms of patients with a diagnosis of pVSD at our institution from January 1999 to January 2015. All available echocardiographic data were collected. Patients were excluded if there was another structural cardiac anomaly other than bicuspid aortic valve, small patent foramen ovale, or ductus arteriosus. The prevalences of aortic valve prolapse and regurgitation, as well as aortic valve disease progression, were determined. A total of 2,114 echocardiograms from 657 patients with unrepaired pVSD were reviewed. Median age at the time of echocardiogram was 1.9 years (interquartile range [IQR] 0.2 to 5.4). Median duration of follow-up was 1.7 years (IQR 0.2 to 7.4). pVSD-associated aortic valve disease prompted surgical intervention in 1.5% (10 of 657) of patients. Median age at the time of surgery was 4.8 years (IQR 1.7 to 8.4). A pVSD-to-aortic annulus diameter ratio of 0.66 ± 0.05 was present in 90% (9 of 10) of patients who underwent surgical closure because of pVSD-associated aortic valve disease. In conclusion, pVSD-associated aortic valve disease is uncommon, and progression of aortic regurgitation is rare. These data suggest that the majority of patients with pVSD do not require frequent follow-up and that frequent follow-up can be saved for a subset with echocardiographic markers placing them at higher risk of aortic valve diseases.

  View details for DOI 10.1016/j.amjcard.2017.02.004

  View details for PubMedID 28325571

• Appropriateness and diagnostic yield of inpatient pediatric echocardiograms. Congenital heart disease Lang, S. M., Bolin, E., Daily, J. A., Tang, X., Thomas Collins, R. 2017; 12 (2): 210–17

  Abstract

  Multiple reports have shown echocardiograms for certain indications are neither cost-effective nor of high diagnostic yield. Given the ease with which tests can be obtained at a tertiary academic children's hospital, our aims were to: (1) determine the diagnostic yield of inpatient studies by in-hospital location; (2) evaluate inpatient echocardiograms to determine indications and level of appropriateness; and (3) evaluate the frequency of cardiology involvement prior to those echocardiograms.All initial inpatient echocardiograms interpreted at our institution from February 2009 to December 2014 were reviewed retrospectively. Patient location was grouped as pediatric intensive care (PICU), emergency department (ED), and general floor.There were 727 first-time inpatient echocardiograms that met inclusion criteria. Pathology was identified in 25% of the study echocardiograms, with 11% of all studies demonstrating pathology that could alter patient management (moderate or severe pathology). The studies performed in the PICU and ED had more severe pathology compared with those from the general floor (P < .001, .003; respectively). Few echocardiograms were performed for rarely appropriate indications on the general floor (7%) and PICU (2.2%). Over 75% of general floor echocardiograms performed for a pathologic murmur yielded normal or incidental findings. Cardiology consultation was documented in only 7.5% of general floor studies.The diagnostic yield of inpatient, first-time pediatric echocardiograms is relatively low. The majority of studies that identified pathology were performed on patients located in higher acuity units. General floor echocardiograms for murmurs had a low diagnostic yield, raising the question of cardiology consultation versus direct echocardiogram ordering for subjective physical exam signs.

  View details for DOI 10.1111/chd.12428

  View details for PubMedID 27863016

• Alkaline Phosphatase: A Biomarker of Cardiac Function in Pediatric Patients. Pediatric cardiology Makil, E. S., Tang, X., Frazier, E. A., Collins, R. T. 2017; 38 (4): 762–69

  Abstract

  Myocardial dysfunction and heart failure are common in pediatric patients with congenital and acquired heart disease. Alkaline phosphatase (AP) has been suggested as a biomarker for myocardial dysfunction after Fontan operation. We hypothesized that pediatric patients with myocardial dysfunction requiring orthotopic heart transplant (OHT) have diminished AP compared to normal. A retrospective review was performed in all patients who underwent OHT at Arkansas Children's Hospital between January 2007 and October 2012. Anatomic diagnoses, therapeutic interventions, and ventricular ejection fraction (EF) were recorded. Z scores for AP levels in the study group were determined by comparing the observed AP levels to age- and gender-matched normative values. T tests were performed to compare the mean AP Z score prior to and after OHT. p values <0.05 were considered statistically significant. During the study period, 124 OHTs were performed. Complete study data were available and analyzed from 71/124 patients (mean age at OHT 3.9 years; 51% female). The mean AP Z score was significantly lower in the study group prior to OHT compared to normal (p < 0.0001). The initiation of ACE inhibitor therapy prior to OHT was associated with a significant increase in AP and the ventricular EF (p < 0.001 for both). Treatment with milrinone was associated with an increase in EF. AP is significantly lower in pediatric patients with myocardial dysfunction prior to OHT compared to normal. AP increases significantly after the initiation of therapies to improve myocardial function. Diminished AP is an indicator of myocardial dysfunction in pediatric patients.

  View details for DOI 10.1007/s00246-017-1577-x

  View details for PubMedID 28184975

• How often is congenital heart disease recognized as a significant comorbidity among hospitalized adults with congenital heart disease? International journal of cardiology Robbins, J. M., Onukwube, J., Goudie, A., Collins, R. T. 2017; 235: 42–48

  Abstract

  Despite frequent life-long hemodynamic and electrophysiologic abnormalities, adults with congenital heart defects (CHDs) are often lost to medical follow-up. Using a cohort of adults with CHD receiving hospital care in Arkansas, we sought to determine how often a CHD is recognized and coded during hospital admissions.Data for this study come from the Agency for Healthcare Research and Quality's Arkansas State Inpatient Database (SID) for years 2004 to 2012. Using unique identifiers that link patients across hospitalizations, we created a cohort of 3973 patients≥18years old with an ICD-9 code for a CHD diagnosis noted at discharge during any hospitalization.These 3973 patients had 19,638 hospitalizations. A CHD was listed as the principal diagnosis in 3% of hospitalizations, a secondary diagnosis in 22%, and no CHD was listed in 75% of hospitalizations. Among patients with a critical CHD, no critical CHD was noted in 69% of hospitalizations. Cardiovascular events (heart failure, arrhythmias, cerebrovascular accidents, embolic event, or death) occurred in 60% of hospitalizations of critical CHD patients wherein no critical CHD was recorded.CHDs are rarely acknowledged during hospitalizations of adults with a known CHD even when cardiovascular events occur. Improved awareness, disclosure and attention to comorbid CHDs among patients and providers may improve hospital management and outcomes of cardiovascular events.

  View details for DOI 10.1016/j.ijcard.2017.02.100

  View details for PubMedID 28279500

  View details for PubMedCentralID PMC5427637

• National In-Hospital Outcomes of Pregnancy in Women With Single Ventricle Congenital Heart Disease. The American journal of cardiology Collins, R. T., Chang, D., Sandlin, A., Goudie, A., Robbins, J. M. 2017; 119 (7): 1106–10

  Abstract

  Most patients with single ventricle (SV) congenital heart disease are expected to survive to adulthood. Women with SV are often counseled against pregnancy; however, data on pregnancies in these women are lacking. We sought to evaluate in-hospital outcomes of pregnancy in women with SV. We used nationally representative data from the 1998 to 2012 National Inpatient Sample to identify women ≥18 years of age admitted to the hospital with International Classification of Diseases-9th Revision codes for an intrauterine pregnancy and a diagnosis of hypoplastic left heart syndrome, tricuspid atresia, or common ventricle. A matched comparison group without a diagnosis of congenital heart disease or pulmonary hypertension was identified from the database. National estimates of hospitalizations were calculated. Length of stay, hospital charges, and complications were analyzed and compared between groups. Charge data were adjusted to 2012 dollars. There were 282 admissions of pregnant women with SV (69% with deliveries) and 1,405 admissions in the control group (88% with deliveries). Vaginal delivery was more common in SV (74% vs 71%, p <0.001). Length of stay (4.1 ± 0.91 vs 2.8 ± 0.18 days, p <0.001) and charges ($30,787 ± 8,109 vs $15,536 ± 1,006, p <0.0001) were higher in the SV group. Complications occurred in most SV admissions and were more common in the SV group than in the control group. No deaths occurred. Cardiovascular complications occurred in 25% of pregnancy-related hospitalizations, although in-hospital pregnancy-related death is rare. Vaginal delivery is common in these patients. These data suggest that pregnancy and vaginal delivery can be tolerated in women with SV, although the risk for a cardiovascular event is significantly higher than in the general population.

  View details for DOI 10.1016/j.amjcard.2016.12.015

  View details for PubMedID 28242012

• Diagnostic Yield of Outpatient Pediatric Echocardiograms: Impact of Indications and Specialty. Pediatric cardiology Lang, S. M., Bolin, E., Hardy, S., Tang, X., Collins, R. T. 2017; 38 (1): 162–69

  Abstract

  Multiple reports have shown that echocardiograms are neither cost-effective nor of high diagnostic yield for a number of indications. This study sought to evaluate the impact of indications and provider type on the diagnostic yield of first-time outpatient pediatric echocardiograms. All initial echocardiograms interpreted at our institution from February 2009 to December 2014 were reviewed retrospectively. Positive findings were defined as any abnormality of structure or function. Ordering physicians were grouped as Primary Care, Subspecialist, or Cardiologist. A cost analysis of cardiac consultation versus direct echocardiogram ordering was performed using 2014 Arkansas Medicaid office-based allowables. A total of 7854 echocardiograms had complete data and were included in the study. Median age was 7.2 years (range 2 days to 18.9 years). There were 1179 (15%) abnormal first-time echocardiograms. Diagnostic yields were particularly low for the indications of chest pain (4.9%), syncope (5.3%), and palpitations (9.1%). When ordered by the Cardiology group, echocardiographic yields were increased 35% for all indications (p < 0.001) and 100% for murmurs (p < 0.001) when compared to the Primary Care group. Cost analysis using the model of cardiology consultation rather than direct primary care echocardiogram ordering estimated a 19.6% reduction in medical costs for the most common indication, murmur. The diagnostic yield of outpatient pediatric echocardiograms is low for most indications. Overall, cardiologists had an improved diagnostic yield compared to other ordering physicians. For the indication of murmur, cardiology evaluation before echocardiogram might decrease unnecessary testing and healthcare expenses. This study provides a framework for improving resource utilization in the pediatric population.

  View details for DOI 10.1007/s00246-016-1497-1

  View details for PubMedID 27826707

• Risk Factors for Increased Hospital Resource Utilization and In-Hospital Mortality in Adults With Single Ventricle Congenital Heart Disease. The American journal of cardiology Collins, R. T., Doshi, P., Onukwube, J., Fram, R. Y., Robbins, J. M. 2016; 118 (3): 453–62

  Abstract

  Most patients with single ventricle congenital heart disease are now expected to survive to adulthood. Co-morbid medical conditions (CMCs) are common. We sought to identify risk factors for increased hospital resource utilization and in-hospital mortality in adults with single ventricle. We analyzed data from the 2001 to 2011 Nationwide Inpatient Sample database in patients aged ≥18 years admitted to nonteaching general hospitals (NTGHs), TGHs, and pediatric hospitals (PHs) with either hypoplastic left heart syndrome, tricuspid atresia or common ventricle. National estimates of hospitalizations were calculated. Elixhauser CMCs were identified. Length of stay (LOS), total hospital costs, and effect of CMCs were determined. Age was greater in NTGH (41.5 ± 1.3 years) than in TGH (32.8 ± 0.5) and PH (25.0 ± 0.6; p <0.0001). Adjusted LOS was shorter in NTGH (5.6 days) than in PH (9.7 days; p <0.0001). Adjusted costs were higher in PH ($56,671) than in TGH ($31,934) and NTGH ($18,255; p <0.0001). CMCs are associated with increased LOS (p <0.0001) and costs (p <0.0001). Risk factors for in-hospital mortality included increasing age (odds ratio [OR] 5.250, CI 2.825 to 9.758 for 45- to 64-year old vs 18- to 30-year old), male gender (OR 2.72, CI 1.804 to 4.103]), and the presence of CMC (OR 4.55, CI 2.193 to 9.436) for 2 vs none). No differences in mortality were found among NTGH, TGH, and PH. Cardiovascular procedures were more common in PH hospitalizations and were associated with higher costs and LOS. CMCs increase costs and mortality. In-hospital mortality is increased with age, male gender, and the presence of hypoplastic left heart syndrome.

  View details for DOI 10.1016/j.amjcard.2016.05.020

  View details for PubMedID 27291967

• Aortic dilation in pediatric patients. European journal of pediatrics Zarate, Y. A., Sellars, E., Lepard, T., Carlo, W. F., Tang, X., Collins, R. T. 2015; 174 (12): 1585–92

  Abstract

  Aortic dilation at the level of the aortic root can be caused by a variety of congenital or acquired conditions that lead to weakening of the aortic wall. In this retrospective study, we sought to determine the frequency of different associated diagnoses from children with aortic dilation seen at a single institution. A total of 377 children (68 % male) met study inclusion criteria. Patients were classified based on the suspected or confirmed associated diagnosis in one of the following categories: congenital heart disease (241/377, 64 %), chromosomal (34/377, 9 %), Marfan syndrome (26/377, 7 %), other genetic and non-genetic (22/377, 6 %), Loeys-Dietz syndrome (6/377, 2 %), and unknown (48/377, 13 %). Bicuspid aortic valve was by far the most prevalent congenital heart defect (206/241, 85 %), while Turner syndrome was the most frequent chromosomal abnormality (12/34, 35 %). Patients with Marfan syndrome were more likely to have severe dilation of the ascending aorta (p = 0.002) and to require aortic root replacement surgery (p < 0.001) compared to those in other diagnosis categories.The differential diagnosis of aortic dilation is broad and requires a careful assessment of cardiac anatomy. Evaluation by a clinical geneticist in this setting should be strongly considered given the high frequency of associated genetic conditions.• Aortic dilation is frequent in bicuspid aortic valve and other congenital heart defects. • Aortic dilation can be seen in several connective tissue disorders. Limited information is available in regard to the differential diagnosis of aortic dilation in children.• In patients with aortic dilation concurrent congenital heart disease is frequently diagnosed. • Almost 18 % of cases in the present study had a defined presumptive or confirmed genetic diagnosis. We suggest considering a genetics evaluation in the setting of aortic dilation.

  View details for DOI 10.1007/s00431-015-2575-8

  View details for PubMedID 26070999

• Combining clinical databases with genetic studies to help advance the causation model of congenital heart disease. The Journal of thoracic and cardiovascular surgery Hornik, C. P., Collins, R. T., Jaquiss, R. D., Jacobs, J. P., Jacobs, M. L., Pasquali, S. K., Wallace, A. S., Hill, K. D. 2015; 150 (5): 1380–81

  View details for DOI 10.1016/j.jtcvs.2015.08.006

  View details for PubMedID 26546205

  View details for PubMedCentralID PMC5483952

• Impact of aortic aneurysm on hospitalizations in patients with marfan syndrome: a multi-institutional study. Pediatric cardiology Collins, R. T., Phomakay, V., Zarate, Y. A., Tang, X. 2015; 36 (1): 132–39

  Abstract

  Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder affecting 1 in 3,000 people. Cardiovascular involvement is a prominent feature of MFS, with aortic dissection and/or rupture being the leading cause of death. Advances in the medical and surgical care of patients with MFS have improved survival. Hospital resource utilization and outcomes have not been evaluated in a large population of patients with MFS. We sought to analyze pediatric hospital resource utilization and outcomes in patients with MFS. Nationally distributed data from 43 pediatric hospitals in the 2004-2011 Pediatric Health Information System database were used to identify patients admitted to the hospital with International Classification of Diseases-9th Revision codes for a diagnosis of MFS. Aortic aneurysm (AA) with or without dissection, length of stay (LOS), and hospital charges were determined. During the study period, there were 1,978 admissions in 1,228 patients with MFS. AA was present in 217 (11%) admissions in 188 (15%) patients (63% male). Mean age of patients with AA was 13.8 ± 5.9 years. Aortic dissection or rupture was present in 15 (7% with AA) admissions in 15 (8% with AA) patients (mean age 15.7 ± 5.2 years). Other cardiac diagnoses occurred more commonly in the AA cohort (p < 0.0001), regardless of the reason for admission. Cardiothoracic surgical procedures were performed in 116 AA admissions (53%). Mean LOS, hospital charges per admission, and charges per day were significantly higher in AA cohort compared to those without AA. In-hospital mortality for AA was 2%. The presence of AA in patients with MFS increases hospital resource utilization. Cardiothoracic surgeries are commonly performed in this cohort. Other cardiovascular diagnoses are more prevalent in patients with AA suggesting a more severe phenotype.

  View details for DOI 10.1007/s00246-014-0976-5

  View details for PubMedID 25096902

• Population-based study of hospital costs for hospitalizations of infants, children, and adults with a congenital heart defect, Arkansas 2006 to 2011. Birth defects research. Part A, Clinical and molecular teratology Simeone, R. M., Oster, M. E., Hobbs, C. A., Robbins, J. M., Collins, R. T., Honein, M. A. 2015; 103 (9): 814–20

  Abstract

  Congenital heart defects (CHDs) are common birth defects and are associated with high hospital costs. The objectives of this study were to assess hospitalization costs, across the lifespan, of patients with CHDs in Arkansas.Data from the 2006 to 2011 Healthcare Cost and Utilization Project Arkansas State Inpatient Databases were used. We included hospitalizations of patients whose admission occurred between January 1, 2006, and December 31, 2011, and included a principal or secondary CHD ICD-9-CM diagnosis code (745.0-747.49, except 747.0 and 745.5 for preterm infants). Hospitalizations were excluded if they involved out-of-state residents, normal newborn births, or if missing data included age at admission, state of residence, or hospital charges. Children were defined as those < 18 years-old at time of admission.Between 2006 and 2011, there were 2,242,484 inpatient hospitalizations in Arkansas. There were 9071 (0.4%) hospitalizations with a CHD, including 5,158 hospitalizations of children (2.2% of hospitalizations among children) and 3,913 hospitalizations of adults (0.2% of hospitalizations of adults). Hospital costs for these CHD hospitalizations totaled $355,543,696. The average annual cost of CHD hospitalizations in Arkansas was $59,257,283 during this time period. Infants accounted for 72% of all CHD-related hospital costs; total costs of CHD hospitalizations for children were almost five times those of hospitalization costs for adults with CHD.Hospitalizations with CHDs account for a disproportionate share of hospital costs in Arkansas. Hospitalizations of children with CHD accounted for a higher proportion of total hospitalizations than did hospitalizations of adults with CHD.

  View details for DOI 10.1002/bdra.23379

  View details for PubMedID 26069215

  View details for PubMedCentralID PMC4565745

• Factors associated with inpatient hospitalizations among patients aged 1 to 64 years with congenital heart defects, Arkansas 2006 to 2011. Birth defects research. Part A, Clinical and molecular teratology Simeone, R. M., Oster, M. E., Hobbs, C. A., Robbins, J. M., Thomas Collins, R., Honein, M. A. 2015; 103 (7): 589–96

  Abstract

  Individuals with congenital heart defects (CHDs) have high hospital resource use. We sought to identify factors associated with hospital costs and multiple hospitalizations among individuals with CHDs.Data from the 2006 to 2011 Healthcare Cost and Utilization Project Arkansas State Inpatient Databases were linked across encrypted patient identifiers to develop a cohort of Arkansas residents aged 1 to 64 years who were hospitalized at least once with a CHD during this time period. Infants were excluded because patient identifiers were missing for 18 to 52% each year. CHDs were identified using principal and secondary International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses codes. All hospitalizations of individuals ever admitted with a CHD were included. Mean and median patient-level costs were estimated; the association of hospital costs and patient readmissions were examined with linear and logistic regression.There were 1,185,868 inpatient hospitalizations of Arkansas residents aged 1 to 64 years between 2006 and 2011; these were accrued by 603,925 patients. Of those, 2542 patients (0.42%) had at least one hospitalization with a CHD diagnosis. Total costs for these 2542 patients were $126,999,837 and they accumulated 7898 hospitalizations. Factors associated with increased costs included patient age, CHD type, cardiac procedures, and comorbidities. Factors associated with hospital readmission within 1 year included age, CHD type, expected payer, and comorbidities.Individuals with CHDs in Arkansas experience variation in hospital use and costs by patient characteristics. Future research should investigate factors associated with readmissions, cardiac procedures, and comorbidities, as these are strongly associated with hospital costs. Birth Defects Research (Part A) 103:589-596, 2015. © 2015 Wiley Periodicals, Inc.

  View details for DOI 10.1002/bdra.23402

  View details for PubMedID 26172576

  View details for PubMedCentralID PMC4518202

• Clinical utility of a next generation sequencing panel assay for Marfan and Marfan-like syndromes featuring aortopathy. American journal of medical genetics. Part A Wooderchak-Donahue, W., VanSant-Webb, C., Tvrdik, T., Plant, P., Lewis, T., Stocks, J., Raney, J. A., Meyers, L., Berg, A., Rope, A. F., Yetman, A. T., Bleyl, S. B., Mesley, R., Bull, D. A., Collins, R. T., Ojeda, M. M., Roberts, A., Lacro, R., Woerner, A., Stoler, J., Bayrak-Toydemir, P. 2015; 167A (8): 1747–57

  Abstract

  Aortopathy can be defined as aortic dilation, aneurysm, dissection, and tortuosity. Familial aortopathy may occur secondary to fibrillin-1 (FBN1) mutations in the setting of Marfan syndrome, or may occur as a result of other genetic defects with different, but occasionally overlapping, phenotypes. Because of the phenotypic overlap and genetic heterogeneity of disorders featuring aortopathy, we developed a next generation sequencing (NGS) assay and comparative genomic hybridization (CGH) array to detect mutations in 10 genes that cause thoracic aortic aneurysms (TAAs). Here, we report on the clinical and molecular findings in 175 individuals submitted for aortopathy panel testing at ARUP laboratories. Ten genes associated with heritable aortopathies were targeted using hybridization capture prior to sequencing. NGS results were analyzed, and variants were confirmed using Sanger sequencing. Array CGH was used to detect copy-number variation. Of 175 individuals, 18 had a pathogenic mutation and 32 had a variant of uncertain significance (VUS). Most pathogenic mutations (72%) were identified in FBN1. A novel large SMAD3 duplication and FBN1 deletion were identified. Over half who had TAAs or other aortic involvement tested negative for a mutation, suggesting that additional aortopathy genes exist. We anticipate that the clinical sensitivity of at least 10.3% will rise with VUS reclassification and as additional genes are identified and included in the panel. The aortopathy NGS panel aids in the timely molecular diagnosis of individuals with disorders featuring aortopathy and guides proper treatment.

  View details for DOI 10.1002/ajmg.a.37085

  View details for PubMedID 25944730

• Cardiac diagnoses, procedures, and healthcare utilisation in inpatients with Ellis-van Creveld syndrome. Cardiology in the young O'Connor, M. J., Tang, X., Collins, R. T. 2015; 25 (1): 95–101

  Abstract

  Ellis-van Creveld syndrome is a rare condition associated with a very high incidence of congenital malformations of the heart. Prior reports have suggested increased morbidity and mortality following surgery for congenital malformations of the heart in patients with Ellis-van Creveld syndrome.The Pediatric Health Information System database, an administrative database containing data from 43 free-standing paediatric hospitals in North America, was queried to search for patients with the diagnostic code for Ellis-van Creveld syndrome between 2004 and 2011. Those patients who underwent cardiac procedures were compared with those who did not with respect to measures of healthcare utilisation.A total of 138 admissions occurred in 93 patients with Ellis-van Creveld syndrome during the study period. Of these, 74% had an underlying diagnosis of congenital malformations of the heart. Half of the patients in the sample underwent a cardiac surgical or interventional catheterisation procedure. Patients who underwent a cardiac procedure had a longer hospital length of stay, higher incidence of intensive care unit admission, and higher total and per day hospital charges than patients who did not undergo cardiac surgery during admission.In a large group of inpatients with Ellis-van Creveld syndrome, the prevalence of congenital malformations of the heart was similar to that reported in prior studies. Cardiac surgical and interventional procedures appear to drive a substantial portion of healthcare utilisation in these patients.

  View details for DOI 10.1017/S1047951113001819

  View details for PubMedID 24168757

• Ventricular Hypertrophy on Electrocardiogram Correlates with Obstructive Lesion Severity in Williams Syndrome. Congenital heart disease Phomakay, V., Gossett, J. M., Kaplan, P. B., Swearingen, C. J., Collins, R. T. 2014; 10 (4): 302–9

  Abstract

  Williams syndrome (WS) is a congenital, multisystem developmental disorder affecting 1 in 8000 live births. Cardiovascular abnormalities are present in 80% of WS patients. The present study sought to characterize fully the electrocardiographic findings in WS and correlate findings with anatomic pathology.A retrospective review was performed of the electrocardiograms (ECGs) of patients with WS evaluated at the Children's Hospital of Philadelphia from January 1, 1980 through December 31, 2007. When available, the five most recent ECGs in each patient were evaluated. Ventricular hypertrophy was diagnosed based on previously reported voltage criteria in normal populations.There were 187 patients with 499 ECGs for evaluation. Median age at study ECG was 8.0 years (range 0.1-58.9); median number of ECGs per patient was 2.7 (range 1-5). Heart rate, PR interval, and QRS interval were normal for age. Right ventricular hypertrophy (RVH) was present on 44% (219/499) of ECGs. Left ventricular hypertrophy (LVH) was present on 30% (150/499) of ECGs. Fifty-seven percent (106/187) of subjects had ≥1 ECG demonstrating RVH, and 39% (72/187) had ≥1 ECG demonstrating LVH. The severity of right- and left-sided obstructive lesions correlated with the ECG presence of RVH (P < .0001, odds ratio 21.8) and LVH (P < .001, odds ratio 14.5-61), respectively.Electrocardiographic intervals in patients with WS follow expected trends seen in normal patients. Voltage criteria for RVH and LVH are commonly met on ECGs of patients with WS. The presence of ventricular hypertrophy on ECG in WS correlates with lesion severity.

  View details for DOI 10.1111/chd.12194

  View details for PubMedID 24965515

• Hospital utilization in adults with single ventricle congenital heart disease and cardiac arrhythmias. Journal of cardiovascular electrophysiology Collins, R. T., Fram, R. Y., Tang, X., Robbins, J. M., St John Sutton, M. 2014; 25 (2): 179–86

  Abstract

  The study sought to identify the impact of cardiac arrhythmias on hospitalizations in adults with single ventricle (SV) congenital heart disease (CHD).Surgical advances have dramatically improved survival in patients with CHD. Cardiac arrhythmias and sudden cardiac death are common in adults with CHD.Data from 43 pediatric hospitals in the 2004 to 2011 Pediatric Health Information System database were used to identify patients ≥18 years of age admitted with International Classification of Diseases-9th Revision codes for a diagnosis of either hypoplastic left heart syndrome (HLHS), tricuspid atresia (TA) or common ventricle (CV), and a cardiac arrhythmia. Primary and secondary diagnoses, length of stay (LOS), hospital charges, and interventional procedures were determined. Multilevel models were used to evaluate differences in demographics, diagnoses, and clinical outcomes among the 3 subgroups (HLHS, TA, and CV). Interactions of charges with arrhythmia and admission year were examined using ANOVA. There were 642 admissions in 424 patients with SV CHD and an arrhythmia diagnosis. A single arrhythmia diagnosis was present in 454 admissions (71%). Total hospital charges were $80.7 million with mean charge per admission of $127,296 ± 243,094. The mean charge per hospital day was $16,653 ± 17,516 and increased across the study period (P < 0.01). Arrhythmia distributions were impacted by SV anatomic subtype (P < 0.001). Hospital resource utilization was significantly different among arrhythmia groups (P < 0.001).In adults with SV CHD, arrhythmias are affected by SV anatomic subtype and impact adversely upon hospital resource utilization.

  View details for DOI 10.1111/jce.12294

  View details for PubMedID 24102747

• Severe neonatal presentation of Kleefstra syndrome in a patient with hypoplastic left heart syndrome and 9q34.3 microdeletion. Birth defects research. Part A, Clinical and molecular teratology Campbell, C. L., Collins, R. T., Zarate, Y. A. 2014; 100 (12): 985–90

  Abstract

  Kleefstra syndrome arises from haploinsufficiency of EHMT1 caused by either microdeletions at 9q34.3 or intragenic mutations. Patients with Kleefstra syndrome have multisystem involvement including intellectual disability, hypotonia, and characteristic facial features.We report on the severe neonatal presentation of the first case of Kleefstra syndrome associated with hypoplastic left heart syndrome and multicystic renal disease in a patient with a 9q34.3 microdeletion.Array-CGH analysis revealed a 2.1 Mb deletion at 9q34.3, including EHMT1 and NOTCH1.Kleefstra syndrome is a multisystem disorder with a high frequency of congenital heart disease and less frequently, renal defects. Mortality has rarely been documented, particularly in infancy. Based on the present case and the extant literature, a routine echocardiogram and renal ultrasound should be ordered in all cases of Kleefstra syndrome. The cardiac changes seen in this patient could be the result of the haploinsufficiency of EHMT1, NOTCH1, or their combined effect.

  View details for DOI 10.1002/bdra.23324

  View details for PubMedID 25380126

• Cardiovascular and genitourinary anomalies in patients with duplications within the Williams syndrome critical region: phenotypic expansion and review of the literature. American journal of medical genetics. Part A Zarate, Y. A., Lepard, T., Sellars, E., Kaylor, J. A., Alfaro, M. P., Sailey, C., Schaefer, G. B., Collins, R. T. 2014; 164A (8): 1998–2002

  Abstract

  Williams syndrome results from a microdeletion of approximately 1.5 Mb of chromosome 7q11.23. Several patients have been reported with the reciprocal microduplication in association with a variety of phenotypic features including cognitive impairment and typical facial features, though only a few have had birth defects. We report on three probands with duplications within 7q11.23 of variable sizes; two with cardiovascular involvement including aortic dilation and the other with unilateral renal and gonadal agenesis. We offer a comparison with previously reported cases of duplications of 7q11.23. In light of the present cases, we recommend undertaking echocardiographic and renal ultrasound evaluation of patients with documented 7q11.23 duplications. Further, this cytogenetic abnormality should be part of the differential diagnosis for patients with aortic dilation, as well as those with unilateral renal and gonadal agenesis.

  View details for DOI 10.1002/ajmg.a.36601

  View details for PubMedID 24844942

• Primary purulent pericarditis and secondary endocarditis: a case report. Cardiology in the young Bielefeld, K., O'Connor, M. J., Collins, R. T. 2014; 24 (3): 563–66

  Abstract

  Purulent pericarditis is a rare diagnosis to be made. It is exceedingly rare as a primary infection. We describe the case of an 18-month-old boy who presented with primary purulent pericarditis and developed a secondary endocarditis. Current literature on the subject is reviewed and discussed.

  View details for DOI 10.1017/S1047951113000930

  View details for PubMedID 24480459

• Duplication of the ALDH1A2 gene in association with pentalogy of Cantrell: a case report. Journal of medical case reports Steiner, M. B., Vengoechea, J., Collins, R. T. 2013; 7: 287

  Abstract

  The pentalogy of Cantrell is rare clustering of congenital defects, first described by Cantrell and colleagues in 1958. The exact pathogenesis for the pentalogy remains unknown and no specific genetic abnormalities have been correlated; however, a failure of embryogenesis has been suspected. The microduplication of chromosome 15q21.3 (57,529,846 to 58,949,448) found in our patient with pentalogy of Cantrell has not been described previously.We describe a case of a newborn Caucasian male baby with prenatally diagnosed pentalogy of Cantrell and a novel maternally inherited copy number variant detected by chromosome microarray analysis. Among the genes within the duplicated region is ALDH1A2, encoding the enzyme retinaldehyde dehydrogenase type 2.Vital for retinoic acid synthesis during early development, ALDH1A2 has previously been demonstrated in animal models to have a strong association with congenital heart disease and diaphragmatic hernia, two key elements comprising pentalogy of Cantrell. It is possible that perturbation of retinoic acid levels during development secondary to this microduplication could underlie the pathology observed in the current case of pentalogy of Cantrell.

  View details for DOI 10.1186/1752-1947-7-287

  View details for PubMedID 24377748

  View details for PubMedCentralID PMC3917519

• Impact of anatomical subtype and medical comorbidities on hospitalizations in adults with single ventricle congenital heart disease. International journal of cardiology Collins, R. T., Fram, R. Y., Tang, X., Robbins, J. M., Sutton, M. S. 2013; 168 (5): 4596–4601

  Abstract

  Most patients with single ventricle congenital heart disease (SV) are now expected to survive to adulthood. Medical comorbidities are common in SV.We used data from 43 pediatric hospitals in the 2004 to 2011 Pediatric Health Information System database to identify patients ≥18 years of age admitted with International Classification of Diseases-9th Revision codes for a diagnosis of either hypoplastic left heart syndrome (HLHS), tricuspid atresia (TA) or common ventricle (CV). Primary (PD) and secondary diagnoses (SD), length of stay (LOS) and hospital charges were determined. Multilevel models were used to evaluate differences in demographics, diagnoses, and admission outcomes among the three subgroups (HLHS, TA, and CV). Interactions of charges with PD and admission year were examined using ANOVA.There were 801 SV patients with 1330 admissions during the study period. Mean age was 24.8±6.2 years (55% male) and mean LOS was 6.8±11.3 days. Total hospital charges were $135 million with mean charge per admission of $101,131±205,808. The mean charge per day was $15,407±16,437. Hospital charges correlated with PD group (p<0.001). Admission rate remained stable (~180/year) from 2006 to 2011. LOS decreased (p=0.0308) and hospital charges per day increased across the study period (p<0.001). PD was non-cardiac in 28% of admissions. Liver-related conditions were more common in patients with HLHS (p<0.001).Hospitalization costs in adults with SV are significant and are impacted by comorbid medical conditions. Hospitalization rates for adults with SV are not increasing. Gastroenterologic comorbidities including protein-losing enteropathy (PLE) are common in HLHS.

  View details for DOI 10.1016/j.ijcard.2013.07.164

  View details for PubMedID 23938215

• Comparison of electrocardiographic QTc duration in patients with supravalvar aortic stenosis with versus without Williams syndrome. The American journal of cardiology McCarty, H. M., Tang, X., Swearingen, C. J., Collins, R. T. 2013; 111 (10): 1501–4

  Abstract

  Cardiovascular abnormalities in Williams syndrome (WS) are largely attributable to elastin haploinsufficiency resulting from a large deletion of the elastin-containing region on chromosome 7q11.23. The risk of sudden death in patients with WS is 25- to 100-fold greater than that in the general population. The corrected QT (QTc) interval is prolonged in 14% of patients with WS. Patients with nonsyndromic supravalvar aortic stenosis (NSVAS) have elastin mutations resulting in elastin haploinsufficiency and a vascular phenotype nearly identical to that of WS. No previous studies have evaluated the QTc duration in NSVAS. A retrospective review of all electrocardiograms (ECGs) performed on consecutive patients with NSVAS at Arkansas Children's Hospital from January 1, 1985 to January 1, 2012 was completed. ECGs with nonsinus rhythm or unmeasurable intervals were excluded. The ECGs were read by 1 reader who was unaware of previous readings. A QTc interval of ≥460 ms was defined as prolonged. The NSVAS cohort was compared to previously published WS and control groups using the mixed model for continuous electrocardiographic variables and the generalized estimating equation for binary indicators for prolonged QTc. The generalized estimating equation used bootstrapping with 1,000 replicates. A total of 300 ECGs (median 6, range 1 to 27) from the 35 identified patients with NSVAS met the inclusion criteria. A total of 482 ECGs from patients with WS and 1,522 ECGs from controls were included. The mean age of the patients with NSVAS at ECG was 7.3 ± 6.9 years; 64% were male. The mean QTc duration was 409 ± 20 ms in the NSVAS group, 418 ± 17 ms in the control group (p <0.001), and 436 ± 27 ms in the WS group (p <0.001 compared to the control group). The prevalence of QTc prolongation was 0.3% in the NSVAS group, 2.0% in the control group (p <0.001), and 14.8% in the WS group (p <0.001 compared to controls). No patients with NSVAS died. In conclusion, cardiac repolarization is normal in patients with NSVAS. Elastin haploinsufficiency does not appear to be the etiology of QTc prolongation in patients with WS. The possible contribution of other genes on 7q11.23 to QTc prolongation in WS should be investigated.

  View details for DOI 10.1016/j.amjcard.2013.01.308

  View details for PubMedID 23433766

  View details for PubMedCentralID PMC3984918

• An unusual presentation of necrotizing enterocolitis on an echocardiogram. Pediatric cardiology Abraham, B. P., Sachdeva, R., Vyas, P. G., Thomas Collins, R. 2012; 33 (8): 1427–29

  Abstract

  This report describes the spontaneous intracardiac air contrast found on the echocardiogram of a 5 day-old term neonate with Down syndrome and a complete atrioventricular septal defect who had experienced sudden-onset tachypnea and systemic desaturation. The stream of air contrast was tracked coming from the hepatic veins, and a diagnosis of necrotizing enterocolitis was suspected. An abdominal radiograph and ultrasound confirmed the diagnosis.

  View details for DOI 10.1007/s00246-012-0254-3

  View details for PubMedID 22391766

• Ellis-van Creveld syndrome and congenital heart defects: presentation of an additional 32 cases. Pediatric cardiology O'Connor, M. J., Collins, R. T. 2012; 33 (4): 491; discussion 491–92

  View details for DOI 10.1007/s00246-012-0155-5

  View details for PubMedID 22286269

• Mitral valve diseases in Williams syndrome-case report and review of the literature. Echocardiography (Mount Kisco, N.Y.) Collins, R. T. 2012; 29 (3): 373; author reply 374

  View details for DOI 10.1111/j.1540-8175.2011.01624_1.x

  View details for PubMedID 22432646

• Long-term survival of patients with resting obstructive hypertrophic cardiomyopathy: more questions than answers. Journal of the American College of Cardiology Collins, R. T., Gossett, J. M., Swearingen, C. J. 2012; 59 (19): 1730; author reply 1730–31

  View details for DOI 10.1016/j.jacc.2012.01.041

  View details for PubMedID 22554606

• Relation of ventricular ectopic complexes to QTc interval on ambulatory electrocardiograms in Williams syndrome. The American journal of cardiology Collins, R. T., Aziz, P. F., Swearingen, C. J., Kaplan, P. B. 2012; 109 (11): 1671–76

  Abstract

  Williams syndrome (WS) is a congenital, developmental disorder affecting 1 in 8,000 live births. The corrected QT (QTc) interval is prolonged in 13% of patients with WS. No data exist characterizing the ambulatory electrocardiographic findings in WS. A retrospective review of all patients with WS evaluated at our institution from January 1, 1980 to December 31, 2007 was performed. Patients with ≥1 ambulatory electrocardiogram (AECG) with sinus rhythm and measurable intervals were included. QTc measurements were made at the minimum and maximum heart rate. Logistic regression analysis was used to evaluate the correlation of ventricular ectopic complexes with QTc measurements. A statistical probability of p <0.05 was considered significant. Of 270 patients identified, 32 had AECGs available for review. Complete data were available for 56 AECGs from 26 patients (15 female; 58%). Their mean age was 15.6 ± 7.2 years at the initial AECG and 20.6 ± 8.6 years for all AECGs. The QTc interval increased with increasing heart rate. Ventricular premature complexes occurred in 40 (73%) of 56 AECGs and 21 (81%) of 26 patients. Ventricular tachycardia occurred in 5 (9%) of 56 AECGs and 4 (15%) of 26 patients. The mean length of ventricular tachycardia was 3.6 ± 0.5 beats at a rate of 171 ± 40 beats/min. The QTc interval at the minimum heart rate correlated directly with age (p <0.001), total ventricular premature complexes (p = 0.007), ventricular couplets (p = 0.002), and ventricular tachycardia (p = 0.011). The QTc interval at the maximum heart rate correlated directly with age (p <0.001), total ventricular premature complexes (p = 0.016), and ventricular couplets (p = 0.006). In conclusion, the QTc interval correlated with ventricular ectopic complexes in patients with WS. The type of ventricular ectopic complexes suggested an alternate etiology of the QTc prolongation seen in WS from that seen in congenital long QT syndrome.

  View details for DOI 10.1016/j.amjcard.2012.01.395

  View details for PubMedID 22459308

• Conjoined hearts in thoracopagus twins. Pediatric cardiology Thomas Collins, R., Weinberg, P. M., Gruber, P. J., St John Sutton, M. G. 2012; 33 (2): 252–57

  Abstract

  This study aimed to identify the anatomic and pathologic structural cardiac abnormalities in conjoined twins and to focus on those that have prevented the successful separation of conjoined hearts. A retrospective review was undertaken to examine consecutive cases of thoracopagus conjoined twins with conjoined hearts evaluated at The Children's Hospital of Philadelphia from 1 January 1980 through 6 October 2008. The records included autopsy and surgical findings as well as clinical reports. The study group included nine sets of conjoined twins with a mean gestational age at birth of 33.8 ± 5.5 weeks. Three twin pairs were stillborn. Five twin pairs died afterward. One pair died of cardiopulmonary failure. The median age at death was 22 days (range, 0-345 days). Major congenital heart disease was present in 94.4% (17/18) of the hearts, and 72.2% (13/18) of the hearts had single-ventricle physiology. Total anomalous pulmonary venous return occurred in 39% (7/18) of the cases. The clinical outcome for thoracopagus twins with conjoined hearts remains poor because of inability to separate conjoined and single ventricles. Surgical nonintervention and palliative care should be strongly considered for these patients.

  View details for DOI 10.1007/s00246-011-0125-3

  View details for PubMedID 22271385

• Contemporary management of congenital malformations of the heart in infants with Ellis - van Creveld syndrome: a report of nine cases. Cardiology in the young O'Connor, M. J., Rider, N. L., Thomas Collins, R., Hanna, B. D., Holmes Morton, D., Strauss, K. A. 2011; 21 (2): 145–52

  Abstract

  Ellis - van Creveld syndrome is an autosomal recessive disorder manifest by short-limb dwarfism, thoracic dystrophy, postaxial polydactyly, dysplastic nails and teeth, and an approximately 60% incidence of congenital malformations of the heart. Despite patients with Ellis - van Creveld syndrome being regarded as having a high surgical risk, few data are available regarding their outcomes following surgery for congenital malformations of the heart in the current era.In this retrospective report, we summarise the clinical observations and outcomes of nine infants with Ellis - van Creveld syndrome who underwent surgery for congenital malformations of the heart between 2004 and 2009.We identified 15 patients with Ellis - van Creveld syndrome during the study period; 11 (73%) had haemodynamically significant congenital malformations of the heart warranting surgery. In two of these patients, surgery was not performed. Of the nine patients who underwent surgery, all of whom were infants, eight (89%) had various forms of an atrioventricular septal defect and one patient (11%) had hypoplastic left heart syndrome (mitral and aortic atresia). Among the nine patients who underwent surgery, four (44%) died at a median of 102 days with a range of 25-149 days post-operatively, mostly from respiratory failure. Respiratory morbidity was seen in all surviving patients, of whom three underwent tracheostomy.Surgery for congenital malformations of the heart can be successful in infants with Ellis - van Creveld syndrome, but mortality is high and post-operative respiratory morbidity should be expected.

  View details for DOI 10.1017/S1047951110001587

  View details for PubMedID 21070693

• Clinical significance of prolonged QTc interval in Williams syndrome. The American journal of cardiology Collins, R. T. 2011; 108 (3): 471–73

  View details for DOI 10.1016/j.amjcard.2011.03.071

  View details for PubMedID 21550581

• Atrioventricular valve dyssynchrony resulting from severe mitral regurgitation. Circulation Collins, R. T., Peyvandi, S., Cohen, M. S. 2011; 123 (6): 686–90

  View details for DOI 10.1161/CIRCULATIONAHA.110.966044

  View details for PubMedID 21321185

  View details for PubMedCentralID PMC3513947

• Images in cardiovascular medicine. Mitral arcade: a rare cause of fatigue in an 18-year-old female. Circulation Collins, R. T., Ryan, M., Gleason, M. M. 2010; 121 (15): e379–83

  View details for DOI 10.1161/CIR.0b013e3181db1ee4

  View details for PubMedID 20404264

• Stenosis of the thoracic aorta in Williams syndrome. Pediatric cardiology Collins, R. T., Kaplan, P., Rome, J. J. 2010; 31 (6): 829–33

  Abstract

  Williams syndrome (WS) is a multisystem congenital disorder affecting 1/8000 live births. Our objective was to review our experience with stenosis of the thoracic aorta (STA) in these patients. A retrospective review was undertaken of consecutive WS patients at The Children's Hospital of Philadelphia from January 1, 1980, through December 31, 2007. WS was diagnosed by an experienced medical geneticist and/or by fluorescence in situ hybridization. Stenosis was diagnosed with either echocardiography or cardiac catheterization. Freedom from intervention was determined using Kaplan-Meier analysis. From a total cohort of 270 patients, 37 (14%) patients with STA were identified and comprised the study group. Age at presentation was 2.1 + or - 4.0 years, and follow-up was 11.8 + or - 12.6 years (range 0-51). Long-segment STA was more common (89%) than discrete STA. Severity of STA was mild in 18, moderate in 10, and severe in 9 patients. Branch pulmonary artery stenosis was seen in 62% (23 of 37) of STA patients, and supravalvar aortic stenosis was seen in 54% (20 of 37) STA patients. Nine (24%) patients underwent intervention for STA: 8 cases were severe, and 1 case was moderate. Restenosis resulting in reintervention occurred in 5 of 9 (56%) patients, with 4 of 5 (80%) patients undergoing multiple reinterventions. Freedom from intervention was 89, 82, and 73% at 1, 5, and 20 years, respectively. One patient died. STA is common in WS and is generally the long-segment type. In patients with STA, interventions are common and usually occur by 5 years of age. Reintervention for STA occurs frequently.

  View details for DOI 10.1007/s00246-010-9713-x

  View details for PubMedID 20411252

• Cardiovascular abnormalities, interventions, and long-term outcomes in infantile Williams syndrome. The Journal of pediatrics Collins, R. T., Kaplan, P., Somes, G. W., Rome, J. J. 2010; 156 (2): 253–58.e1

  Abstract

  To determine the prevalence of cardiovascular abnormalities (CVA) and outcomes in patients with Williams syndrome presenting before 1 year of age.A retrospective review was undertaken of consecutive patients with WS at our institution from January 1, 1980, through December 31, 2007. WS was diagnosed by an experienced medical geneticist and/or by fluorescence in situ hybridization. CVA were diagnosed with the use of echocardiography, cardiac catheterization, or computerized tomographic angiography. Freedom from intervention was determined using Kaplan-Meier analysis.The study group was 129 patients with CVA. Age at presentation was 127 +/- 116 days, with follow-up of 8.0 +/- 7.5 years (0 to 42 years). The most common lesions were peripheral pulmonary artery stenosis (62%) and supravalvar aortic stenosis (57%). Other CVA were common. CV interventions were performed in 29%, with 58% of those before 1 year. Freedom from intervention was 85%, 73%, and 66% at 1, 5, and 25 years, respectively. Four patients died.CVA are the most common manifestations of infantile Williams syndrome and occur with greater frequency than previously reported. In those with CVA, interventions are common and usually occur by 5 years of age. Most of these patients do not require intervention on long-term follow-up, and overall mortality is low.

  View details for DOI 10.1016/j.jpeds.2009.08.042

  View details for PubMedID 19846117

• Asymptomatic anomalous right coronary artery from the pulmonary trunk. Cardiology in the young Thomas Collins, R., Davis, E., Stephens, P. 2009; 19 (4): 391–92

  View details for DOI 10.1017/S1047951109990217

  View details for PubMedID 19493367

• Noninvasive assessment of subclinical atherosclerosis in children and adolescents: recommendations for standard assessment for clinical research: a scientific statement from the American Heart Association. Hypertension (Dallas, Tex. : 1979) Urbina, E. M., Williams, R. V., Alpert, B. S., Collins, R. T., Daniels, S. R., Hayman, L., Jacobson, M., Mahoney, L., Mietus-Snyder, M., Rocchini, A., Steinberger, J., McCrindle, B. 2009; 54 (5): 919–50

  Abstract

  Deterioration in endothelial function and arterial stiffness are early events in the development of cardiovascular diseases. In adults, noninvasive measures of atherosclerosis have become established as valid and reliable tools for refining cardiovascular risk to target individuals who need early intervention. With limited pediatric data, the use of these techniques in children and adolescents largely has been reserved for research purposes. Therefore, this scientific statement was written to (1) review the current literature on the noninvasive assessment of atherosclerosis in children and adolescents, (2) make recommendations for the standardization of these tools for research, and (3) stimulate further research with a goal of developing valid and reliable techniques with normative data for noninvasive clinical evaluation of atherosclerosis in pediatric patients. Precise and reliable noninvasive tests for atherosclerosis in youth will improve our ability to estimate future risk for heart attack and stroke. Currently, large longitudinal studies of cardiovascular risk factors in youth, such as the Bogalusa and Muscatine studies, lack sufficient adult subjects experiencing hard outcomes, such as heart attack and stroke, to produce meaningful risk scores like those developed from Framingham data.

  View details for DOI 10.1161/HYPERTENSIONAHA.109.192639

  View details for PubMedID 19729599

• Pre-hypertension and hypertension in pediatrics: don't let the statistics hide the pathology. The Journal of pediatrics Collins, R. T., Alpert, B. S. 2009; 155 (2): 165–69

  View details for DOI 10.1016/j.jpeds.2009.02.006

  View details for PubMedID 19619748

• Letter to editor in response to "Prevention of pediatric graft coronary artery disease: atorvastatin", by Chin et al. Pediatric transplantation Collins, R. T., Hanna, B., Shaddy, R. E. 2009; 13 (1): 141

  View details for PubMedID 19172670

• Racial and socioeconomic disparities in arterial stiffness and intima media thickness among adolescents. A commentary on Thurston and Matthews (68(5), 2009, 807-813). Social science & medicine (1982) Collins, R. T., Alpert, B. S. 2009; 69 (11): 1580–81; discussion 1582–83

  View details for DOI 10.1016/j.socscimed.2009.09.010

  View details for PubMedID 19782457

• Arterial stiffness is increased in American adolescents compared to Japanese counterparts. Pediatric cardiology Collins, R. T., Somes, G. W., Alpert, B. S. 2009; 30 (6): 794–99

  Abstract

  Cardiovascular disease is increased in US groups versus Japanese counterparts. Increased arterial stiffness is an important predictor of cardiovascular risk. Pulse wave velocity correlates well with arterial stiffness. Gender and ethnic differences in biracial US adolescent groups have been described. No data are available evaluating differences in arterial stiffness between US and Japanese subjects. Previously published data from an adolescent (12-17 years of age) Japanese cohort were used as an historical control and were compared to an adolescent cohort from the United States. The same simple noninvasive oscillometric technique was used in each cohort to measure brachial-ankle pulse wave velocity (baPWV) as an index of arterial stiffness. The US group was a cross-sectional, biracial (64% African American, 56% female) sample of 162 subjects. The Japanese group was a cross-sectional (48% female) sample of 820 Japanese subjects. All subjects in both cohorts were normotensive (BP < 95% for gender, height, and age) adolescents (12-17 years of age). Subjects were analyzed in four groups on the basis of gender and age (12-14 and 15-17 years of age). In both individual cohorts, the mean baPWV was higher in males versus females and the baPWV increased with age. The mean baPWV was higher in all US groups versus Japanese counterparts (p < 0.0001). The mean systolic and diastolic blood pressures were higher in all Japanese groups versus US counterparts (p < 0.005). Differences in arterial stiffness are present and detectable between normotensive US and Japanese adolescent subjects. Increased arterial stiffness among these adolescent groups correlates with known adult risk for cardiovascular events among the same ethnic and gender groups.

  View details for DOI 10.1007/s00246-009-9437-y

  View details for PubMedID 19357905

• Images in cardiovascular medicine. Partial anomalous left pulmonary artery. Circulation Collins, R. T., Weinberg, P. M., Goldmuntz, E., Harris, M. 2009; 119 (17): 2405–7

  View details for DOI 10.1161/CIRCULATIONAHA.108.835942

  View details for PubMedID 19414658

• Images in cardiovascular medicine. Pulmonary artery sling in an asymptomatic 15-year-old boy. Circulation Collins, R. T., Weinberg, P. M., Ewing, S., Fogel, M. 2008; 117 (18): 2403-2406

  View details for DOI 10.1161/CIRCULATIONAHA.107.744169

  View details for PubMedID 18458183

• Thoracopagus conjoined twins. Circulation Collins, R. T., Bhatti, T. R., Huff, D. S., Weinberg, P. M. 2008; 118 (14): 1496

  View details for DOI 10.1161/CIRCULATIONAHA.108.789941

  View details for PubMedID 18824656

• Differences in arterial compliance among normotensive adolescent groups: Collins arterial compliance in adolescents. Pediatric cardiology Collins, R. T., Somes, G. W., Alpert, B. S. 2008; 29 (5): 929–34

  Abstract

  Decreased arterial compliance is an important predictor of cardiovascular risk. Pulse wave velocity correlates well with arterial compliance. Gender and ethnic differences in adult populations have been described. However, few data are available evaluating arterial compliance in adolescent subjects. Using a simple noninvasive oscillometric technique, brachial-ankle pulse wave velocity (baPWV) was measured as an index of arterial stiffness. Measurements were performed on a cross-sectional (65% African American, 52% female) sample of 205 normotensive (blood pressure <95% for gender, height, and age) adolescents with a mean age of 15.9 years (range, 12-21 years). The 205 adolescent subjects include 106 females and 99 males. In these adolescents, the mean baPWV was higher for males (1,096 cm/s) than for females (1,039 cm/s; p < 0.0024; 95% confidence interval [CI], 0.2051-0.9349), and for African Americans (1,080 cm/s) than for whites (1,040 cm/s; p < 0.0438; 95% CI, 0.0112-0.7888). Multiple regression analyses found a three-way interaction among gender, ethnicity, and age. The effect of age on baPWV was greater among African Americans (slope = 18.1 cm/s/year) and males (slope = 21.6) than among whites (slope = 11.0) and females (slope = 11.3), although these differences did not reach statistical significance. Differences in arterial compliance are already present and detectable in normotensive adolescent subjects. Decreased arterial compliance among adolescent groups correlates with the known adult risk for cardiovascular events among the same ethnic and gender groups.

  View details for DOI 10.1007/s00246-008-9239-7

  View details for PubMedID 18437445

• Assessment of vascular function: pulse wave velocity. The Journal of pediatrics Alpert, B. S., Collins, R. T. 2007; 150 (3): 219–20

  View details for DOI 10.1016/j.jpeds.2006.12.042

  View details for PubMedID 17307531