Clinical Focus

  • Pediatric Cardiology
  • Williams syndrome
  • Marfan syndrome
  • Loeys-Dietz syndrome
  • Connective tissue disorders

Academic Appointments

Administrative Appointments

  • Co-director, Cardiogenomics (2020 - Present)
  • Director, Cardiovascular Connective Tissue Disorders Program, Lucile Packard Children's Hospital Stanford (2017 - Present)

Boards, Advisory Committees, Professional Organizations

  • Fellow, American College of Cardiology (2021 - Present)
  • Diplomate, American Heart Association (2005 - Present)
  • Fellow, American Academy of Pediatrics (2002 - Present)
  • Professional Advisory Board Member, Williams Syndrome Association (2013 - Present)
  • Editorial Board Member, American Journal of Cardiology (2018 - Present)

Professional Education

  • Board Certification: American Board of Pediatrics, Pediatric Cardiology (2016)
  • Board Certification: American Board of Pediatrics, Pediatrics (2016)
  • Fellowship: Children's Hospital of Philadelphia Pediatric Residency (2010) PA
  • Fellowship: Children's Hospital of Philadelphia Pediatric Residency (2009) PA
  • Residency: University of Tennessee Health Science Center Pediatric Residency (2006) TN
  • Board Certification: American Board of Internal Medicine, Adult Congenital Heart Disease (2015)
  • Medical Education: University of Tennessee College of Medicine (2002) TN

Current Research and Scholarly Interests

My research endeavors are focused on populations with connective tissue disorders that manifest as cardiovascular abnormalities, such as Williams, Marfan, and Loeys-Dietz syndromes. Additionally, as a member of the California Center of BD-Steps II, I study birth defects associated with congenital heart disease.

2020-21 Courses

Stanford Advisees

All Publications

  • A clinical scoring system for early onset (neonatal) Marfan syndrome. Genetics in medicine : official journal of the American College of Medical Genetics Zarate, Y. A., Morris, S. A., Blackshare, A., Algaze, C. A., Connor, B. S., Kim, A. J., Yutzey, K. E., Miller, E. M., Weaver, K. N., Collins, R. T. 2022


    PURPOSE: This study aimed to develop objective diagnostic criteria for early onset Marfan syndrome (eoMFS) to facilitate early diagnosis and timely interventions.METHODS: On the basis of an extensive literature review and the responses from a survey distributed among providers with expertise in the diagnosis and management of eoMFS, we developed an age-based, diagnostic scoring system encompassing 10 features common to eoMFS (9 clinical+ 1 laboratory) and divided them into cardiac, systemic, and FBN1 (on the basis of the location of the pathogenic FBN1 variant) scores.RESULTS: In total, 77 individuals with eoMFS (13 newly reported) and 49 individuals diagnosed with classical Marfan syndrome during early childhood were used to validate the criteria. Median cardiac (8 vs 0, P < .001), systemic (11 vs 3, P < .001), FBN1 (5 vs 0, P < .001), and total (23 vs 4, P < .001) scores were significantly higher in individuals with eoMFS than in those without. A proposed clinical score (cardiac+ systemic) cutoff of ≥14 points showed excellent sensitivity (100%), specificity (92%), and reliability (correctly classified= 94%).CONCLUSION: Distinct from classical Marfan syndrome in phenotype and morbidity, eoMFS can be diagnosed clinically using an objective scoring system encompassing the typical physical features and cardiac disease manifestations. Although genetic testing can be suggestive of eoMFS, genetic testing alone is insufficient for diagnosis.

    View details for DOI 10.1016/j.gim.2022.03.016

    View details for PubMedID 35420547

  • The Importance of Formalized, Lifelong Physician Career Development: Making the Case for a Paradigm Shift. Academic medicine : journal of the Association of American Medical Colleges Collins, R. T., Sanford, R. 2021


    The value of structured development processes has been recognized and implemented in formal physician training programs such as residencies and fellowships. Physicians are seemingly viewed as a "finished product" upon completing formal training. In recent years, a number of academic medical centers have implemented formalized early-career development programs for physicians, largely those who have a major research focus. However, beyond the early stage of physicians' careers, formalized and intentional physician career development programs are rare. The lack of a philosophy of intentional, career-long individual development at academic medical centers reflects a narrow understanding of the implicit contract between employers and employees. The resulting gap leads the vast majority of physicians to fall short of their potential, further leading to long-term loss for the academic medical centers, their physicians, and society as a whole. Based on the framework of analyze-design-develop-implement-evaluate, the authors propose a robust, iterative model for physician career development that goes beyond skills and knowledge maintenance, toward leveraging a broad range of individual capabilities, needs, and contexts along the career lifespan. The model provides a means for harnessing physicians' strengths and passions in concert with the needs of their organization to create greater physician fulfillment and success, which in turn would benefit the patients they care for and the academic medical centers in which they work.

    View details for DOI 10.1097/ACM.0000000000004191

    View details for PubMedID 34074898

  • A validated model for prediction of survival to 6months in patients with trisomy 13 and 18. American journal of medical genetics. Part A Kosiv, K. A., Long, J., Lee, H. C., Collins, R. T. 2021


    Congenital heart disease is exceedingly prevalent in trisomy 13 and 18. Improved survival following congenital heart surgery has been reported, however, mortality remains significantly elevated. Utilizing inpatient data on trisomy 13 and 18 from the 2003-2016 Pediatric Health Information System database, a survival model was developed and validated using data from the California Perinatal Quality Care Collaborative and the California Office of Statewide Health Planning and Development. The study cohort included 1,761 infants with trisomy 13 and 18. Two models predicting survival to 6 months of age were developed and tested. The initial model performed excellently, with a c-statistic of 0.87 and a c-statistic of 0.76 in the validation cohort. After excluding procedures performed on the day of death, the revised model's c-statistic was 0.76. Certain variables, including cardiac surgery, gastrostomy, parenteral nutrition, and mechanical ventilation, are predictive of survival to 6 months of age. This study presents a model, which potentially can inform decision-making regarding congenital heart surgery.

    View details for DOI 10.1002/ajmg.a.62044

    View details for PubMedID 33403783

  • Cardiac involvement in classical or hypermobile Ehlers-Danlos syndrome is uncommon. Genetics in medicine : official journal of the American College of Medical Genetics Paige, S. L., Lechich, K. M., Tierney, E. S., Collins, R. T. 2020


    PURPOSE: Cardiac-valvular and vascular Ehlers-Danlos syndrome (EDS) have significant cardiovascular issues. The prevalence and significance of such abnormalities in classical (cEDS) or hypermobile EDS (hEDS) remain unclear. We report the prevalence of cardiac abnormalities in patients with cEDS and hEDS.METHODS: We identified 532 pediatric patients with potential EDS evaluated at our institution from January 2014 through April 2019 by retrospective chart review. Ninety-five patients (12 cEDS and 83 hEDS patients) met 2017 EDS diagnostic criteria and had an echocardiogram. One patient was excluded due to complex congenital heart disease, and two were excluded due to lack of images. We reviewed echocardiograms for all structural abnormalities.RESULTS: Of these 95 patients, 1 had mild aortic root dilation, and 1 had mild ascending aorta dilation in the setting of a bicuspid aortic valve. Eleven patients (11.6%) had a cardiac valve abnormality, all of which were trivial to mild. None of the patients required cardiac intervention.CONCLUSION: Our results demonstrate that aortic dilation and valvular anomalies are uncommon in cEDS or hEDS patients. Given the lack of evidence, we do not recommend echocardiographic evaluation and surveillance in patients with cEDS and hEDS in the absence of clinical findings or positive family history.

    View details for DOI 10.1038/s41436-020-0856-8

    View details for PubMedID 32518415

  • Maternal dietary fat intake and the risk of congenital heart defects in offspring. Pediatric research Collins, R. T., Yang, W., Carmichael, S. L., Bolin, E. H., Nembhard, W. N., Shaw, G. M., National Birth Defects Prevention Study 2020


    BACKGROUND: Fatty acids are crucial in embryologic development, including cardiogenesis. The impact of maternal periconceptional dietary fat intake on the risk of congenital heart defects (CHDs) has not been clearly elucidated. We hypothesized that maternal dietary fat intake during pregnancy is associated with risk of CHDs in offspring.METHODS: We analyzed CHD cases and nonmalformed controls from the National Birth Defects Prevention Study, a case-control, multicenter population-based study of birth defects. We used multivariable logistic regression to analyze the association between maternal periconceptional dietary fat intake and occurrence of CHDs.RESULTS: We examined 11,393 infants with CHDs (cases) and 11,029 infants without birth defects (controls). Multivariable analysis of maternal dietary fat intake adjusted for maternal energy intake demonstrated modest change in risk for 2 of the 25 CHDs analyzed; otherwise there was no association. Maternal dietary fat intake unadjusted for total energy was associated with increased risk for several CHDs.CONCLUSIONS: After adjusting for total energy intake, maternal periconceptional dietary fat intake has a modest association with risk of a few specific CHDs. If maternal dietary fat intake does impact CHD risk, the effect is minimal.IMPACT: In this large, case-control study, after adjusting for total caloric intake, maternal periconceptional dietary fat intake was not associated with increased odds of congenital heart defects.This study investigates the hypothesis that women's periconceptional fat intake alters the risk of congenital heart defects in offspring.Our results raise questions about the role maternal fat intake may play in cardiogenesis and risk of congenital heart defects. Additionally, they raise the question about whether maternal lipid metabolism, as opposed to fat intake, may influence cardiac development.

    View details for DOI 10.1038/s41390-020-0813-x

    View details for PubMedID 32120376

  • Leadership in Medicine AMERICAN JOURNAL OF CARDIOLOGY Collins, R. 2019; 124 (4): 650-651
  • Outcomes of Pulmonary Artery Reconstruction in Williams Syndrome ANNALS OF THORACIC SURGERY Collins, R., Mainwaring, R. D., MacMillen, K. L., Hanley, F. L. 2019; 108 (1): 146–53
  • Outcomes of pulmonary artery reconstruction in Williams syndrome. The Annals of thoracic surgery Collins, R. T., Mainwaring, R. D., MacMillen, K. L., Hanley, F. L. 2019


    BACKGROUND: To evaluate the short- and mid-term outcomes of surgical pulmonary artery reconstruction in patients with Williams syndrome.METHODS: We performed a retrospective cohort study of all patients with Williams syndrome who underwent surgical pulmonary artery reconstruction at Lucile Packard Children's Hospital between January 2001 and May 2018.RESULTS: There were 25 WS patients (52% female) who underwent pulmonary artery reconstruction during the study period. Median age at surgery was 2.4 years (IQR: 0.9, 4.5). Median preoperative right ventricular (RV) pressure was 80 mmHg (IQR: 70, 90) and aortic (Ao) pressure was 96 mmHg (IQR: 90, 107), with an RV:Ao pressure of 0.8 (IQR: 0.7, 1.0). Median number of pulmonary arterioplasty patches was 16.5 (IQR: 6.5, 24). Median postoperative RV pressure was 27 mmHg (IQR 20, 31) and Ao pressure was 90 mmHg (IQR: 87, 105), with an RV:Ao of 0.27 (IQR: 0.22, 0.35). The postoperative RV pressure and RV:Ao were significantly lower than preoperative (p<0.0001 for both). There was one postoperative death (1/25, 4%). In a median follow-up of 2.6 years (IQR: 0.94, 3.4), one patient (1/24, 4.2%) has undergone right ventricular outflow tract aneurysm repair, and two (2/24, 8.3%) have undergone balloon dilation of the pulmonary arteries.CONCLUSIONS: Multilevel, surgical pulmonary artery reconstruction addressing severe extra-pericardial stenoses is highly effective in patients with WS. This technique results in immediate normalization of right ventricular pressure and has a low rate of reintervention in mid-term follow-up.

    View details for PubMedID 30885853

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

    View details for DOI 10.1002/bdr2.1390

    View details for Web of Science ID 000448368300002

  • Cardiovascular disease in Williams syndrome. Current opinion in pediatrics Collins, R. T. 2018; 30 (5): 609-615


    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


    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

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


    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 PubMedID 30228249

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


    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

  • 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)


    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

  • 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): 1605-1610


    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): 1194-1199


    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

  • 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): 133-142


    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

  • 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


    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


    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): 951-5


    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


    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): 874-8


    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

  • Virtual Transcatheter Interventions for Peripheral Pulmonary Artery Stenosis in Williams and Alagille Syndromes. Journal of the American Heart Association Lan, I. S., Yang, W., Feinstein, J. A., Kreutzer, J., Collins, R. T., Ma, M., Adamson, G. T., Marsden, A. L. 2022: e023532


    Background Despite favorable outcomes of surgical pulmonary artery (PA) reconstruction, isolated proximal stenting of the central PAs is common clinical practice for patients with peripheral PA stenosis in association with Williams and Alagille syndromes. Given the technical challenges of PA reconstruction and the morbidities associated with transcatheter interventions, the hemodynamic consequences of all treatment strategies must be rigorously assessed. Our study aims to model, assess, and predict hemodynamic outcomes of transcatheter interventions in these patients. Methods and Results Isolated proximal and "extensive" interventions (stenting and/or balloon angioplasty of proximal and lobar vessels) were performed in silico on 6 patient-specific PA models. Autoregulatory adaptation of the cardiac output and downstream arterial resistance was modeled in response to intervention-induced hemodynamic perturbations. Postintervention computational fluid dynamics predictions were validated in 2 stented patients and quantitatively assessed in 4 surgical patients. Our computational methods accurately predicted postinterventional PA pressures, the primary indicators of success for treatment of peripheral PA stenosis. Proximal and extensive treatment achieved median reductions of 14% and 40% in main PA systolic pressure, 27% and 56% in pulmonary vascular resistance, and 10% and 45% in right ventricular stroke work, respectively. Conclusions In patients with Williams and Alagille syndromes, extensive transcatheter intervention is required to sufficiently reduce PA pressures and right ventricular stroke work. Transcatheter therapy was shown to be ineffective for long-segment stenosis and pales hemodynamically in comparison with published outcomes of surgical reconstruction. Regardless of the chosen strategy, a virtual treatment planning platform could identify lesions most critical for optimizing right ventricular afterload.

    View details for DOI 10.1161/JAHA.121.023532

    View details for PubMedID 35253446

  • Regionalization of Congenital Heart Surgery: Can We Make it Reality? The Annals of thoracic surgery Bolin, E. H., Nembhard, W. N., Collins, R. T. 2021; 112 (2): 685

    View details for DOI 10.1016/j.athoracsur.2020.10.070

    View details for PubMedID 33422483

  • Comparison of Postoperative, In-Hospital Outcomes After Complete Repair of Tetralogy of Fallot Between 22q11.2 Deletion Syndrome and Trisomy 21. Pediatric cardiology Nissen, T. E., Zaniletti, I., Collins, R. T., Greiten, L. E., Prodhan, P., Seib, P. M., Bolin, E. H. 2021


    22q11.2 deletion syndrome (22q11) and trisomy 21 (T21) are frequently associated with tetralogy of Fallot (TOF). We hypothesized that there are differences in postoperative length of stay (LOS) and occurrence of postoperative interventions after complete repair of TOF when comparing children with 22q11 to those with T21. Using the Pediatric Health Information System, we performed a retrospective cohort study of patients who underwent complete repair of TOF from 2004 to 2019. Three groups were identified: 22q11, T21, and controls (those without a coded genetic syndrome). Outcomes were postoperative LOS and composite occurrence (yes/no) of at least one postoperative intervention. Bivariate and multivariate comparisons were made among groups; odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using the control group as the comparator. There were 6924 subjects (n = 493 22q11, n = 455 T21, n = 5976 controls). In bivariate analysis, 22q11 was associated with a longer LOS compared to T21 (OR 2.37 [2.16, 2.60] vs. 1.25 [1.12, 1.39], p < 0.001), and 22q11 more often underwent postoperative intervention (OR 3.42 [CI 2.56, 4.57] vs. 1.38 [CI 0.91, 2.11]; p < 0.001). In multivariate analysis, 22q11 was also associated with longer LOS (adjusted OR 1.35 [1.26, 1.44] vs. 1.12 [1.04, 1.20]; p < 0.001), but there was no difference in the adjusted odds of postoperative intervention. Children with 22q11 are more likely to experience adverse outcomes after repair of TOF compared to those with T21; the differences are most pronounced for LOS.

    View details for DOI 10.1007/s00246-021-02683-1

    View details for PubMedID 34331082

  • Impact of Modified Anesthesia Management for Pediatric Patients With Williams Syndrome. Journal of cardiothoracic and vascular anesthesia Schmidt, A. R., Collins, R. T., Adusumelli, Y., Ramamoorthy, C., Weng, Y., MacMillen, K. L., Navaratnam, M. 2021


    OBJECTIVE: This study compared the percent change in systolic blood pressure and the incidence of adverse cardiac events (ACEs; defined as cardiac arrest, cardiopulmonary resuscitation, arrhythmias, or ST-segment changes) during anesthesia induction in patients with Williams syndrome (WS) before and after implementation of a perioperative management strategy.DESIGN: Retrospective observational cohort study.SETTING: Single quaternary academic referral center.PARTICIPANTS: The authors reviewed the records of all children with WS at the authors' institution who underwent general anesthesia for cardiac catheterization, diagnostic imaging, or any type of surgery between November 2008 and August 2019. The authors identified 142 patients with WS, 48 of whom underwent 118 general anesthesia administrations. A historic group (HG) was compared with the intervention group (IG).INTERVENTIONS: Change in perioperative management (three-stage risk stratification: preoperative intravenous hydration, intravenous anesthesia induction, and early use of vasoactives).MEASUREMENTS AND MAIN RESULTS: The authors determined event rates within 60 minutes of anesthesia induction. Standardized mean difference (SMD) was calculated (SMD >0.2 suggests clinically meaningful difference). Sixty-seven general anesthesia encounters were recorded in the HG (mean age, 4.8 years; mean weight, 16.3 kg) and 51 in the IG (mean age, 6.0 years; mean weight, 18.2 kg). The change in systolic blood pressure was -17.5% (-30.0, -5.0) in the HG versus -9% (-18.0, 5.0) in the IG (p = 0.015; SMD = 0.419), and the incidence of ACEs was 6% in the HG and 2% in the IG (p = 0.542; SMD = 0.207).CONCLUSIONS: Preoperative risk stratification, preoperative intravenous hydration, intravenous induction, and early use of continuous vasoactives resulted in greater hemodynamic stability, with a 2% incidence of ACEs.

    View details for DOI 10.1053/j.jvca.2021.04.019

    View details for PubMedID 34049787

  • The Outcomes of Surgical Separation in Thoracopagus Twins with Conjoined Hearts: An Analysis of the Literature. Pediatric cardiology Collins, R. T., O'Connor, M. J. 2021; 42 (4): 875-882


    We sought to perform a comprehensive review of reported cases of conjoined thoracopagus twins with cardiovascular conjunction to determine the overall survival after separation and factors that might be associated with survival. We performed a systematic review of cases of thoracopagus twins with conjoined cardiovascular systems reported in the English medical literature using Embase, PubMed, Web of Science, and Scopus. We employed standard statistical methods to analyze differences among groups. We identified 102 unique cases of thoracopagus twins (69% female) with some degree of cardiovascular conjunction who had undergone surgical separation. We identified 6 distinct types of cardiovascular union. Median age was 47 days (IQR 12, 120). Survival to at least hospital discharge occurred in 51% (105/204). Median age at separation was lower in emergent (9 days, IQR 1, 25) versus elective cases (93 days, IQR 49, 180) (p < 0.0001). Survival to hospital discharge was higher in those who underwent elective separation (70%, 93/132 total children versus 17%, 12/72) (p < 0.0001). Survival was associated with the type of cardiovascular union (p < 0.0001). The separation of thoracopagus twins with cardiovascular conjunction is higher than expected. Increased survival is associated with elective separation, older age, and shared pericardium only. These findings suggest survival could be improved with better delineation of degree of union and delayed separation.

    View details for DOI 10.1007/s00246-021-02555-8

    View details for PubMedID 33856497

  • Pulmonary arteries of Williams syndrome patients exhibit altered serotonin metabolism genes and degenerated medial layer architecture. Pediatric research Ma, X., Collins, R. T., Goodman, A., Hanley, F. L., Riemer, R. K. 2021


    BACKGROUND: Williams-Beuren syndrome (WS) is characterized by cardiovascular abnormalities associated with a multigene deletion on 7q11.23, in particular elastin (ELN). Peripheral pulmonary artery stenosis (PPAS) frequently affects pediatric patients with WS. Molecular investigation of WS pulmonary arterial (PA) tissue is limited by tissue scarcity.METHODS: We compared transcriptomes, tissue architecture, and localized changes in protein expression in PA tissue from patients with WS (n=8) and donors (n=5).RESULTS: Over 100 genes were differentially expressed at the ≥4-fold level, including genes related to the serotonin signaling pathway: >60-fold downregulation of serotonin transporter SLC6A4 and >3-fold upregulation of serotonin receptor HTR2A. Histologic examination revealed abnormal elastin distribution and smooth muscle cell morphology in WS PA, with markedly shorter, disorganized elastin fibers, and expanded proteoglycan-rich extracellular matrix between muscle layers.CONCLUSIONS: There were significant abnormalities in the PA expression of genes regulating serotonin signaling, metabolism, and receptors in WS. Those changes were associated with distinct changes in the arterial structure and may play a role in the stenosis-promoting effects of elevated shear stress at PA bifurcations in WS.IMPACT: Serotonin pathway signaling is significantly altered in the pulmonary arteries of patients with Williams syndrome and severe peripheral arterial stenosis. The present study compares the histological and biochemical characteristics of pulmonary arteries from patients with Williams syndrome to those of controls, something that has not, to our knowledge, been done previously. It demonstrates marked abnormalities in the pulmonary arteries of patients with Williams syndrome, especially significant pathologic alterations in the signaling of the serotonin pathway. The findings of this study provide direction for the development of potential therapies to treat pulmonary artery stenosis in patients with Williams syndrome.

    View details for DOI 10.1038/s41390-020-01359-5

    View details for PubMedID 33531674

  • Tele-Clinic Visits in Pediatric Patients with Marfan Syndrome using Parentally-Acquired Echo. The Journal of pediatrics Chen, A. n., Punn, R. n., Collins, R. T., Chen, J. H., Stauffer, K. J., Wang, R. n., Alexander, S. n., MacMillen Lechich, K. n., Murphy, D. J., Chung, S. n., Selamet Tierney, E. S. 2021


    To test feasibility of tele-clinic visits using parentally-acquired vital signs and focused echocardiographic (echo) images in patients with Marfan syndrome.We included patients with MFS 5-19 years old followed in our clinic. We excluded patients with MFS and history of prior aortic root (AoR) surgery, cardiomyopathy, arrhythmia, or AoR≥4.5 cm. We trained parents in-person to acquire focused echo images on their children using a hand-held device as well as how to use a stadiometer, scale, blood pressure (BP) machine, and a digital stethoscope. Prior to tele-clinic visits, parents obtained the echo images and vital signs. We compared tele-clinic and on-site clinic visit data. Parental and clinic echoes were independently analyzed.Fifteen patient/parent pairs completed tele-clinic visits, conducted at a median of 7.0 [IQR 3.0-9.9] months from the in-person training session. Parents took a median of 70 [IQR 60-150] minutes to obtain the height, weight, heart rate, BP, cardiac sounds, and echo images prior to tele-clinic visits. Systolic BP was higher on-site than at home (median +13 mmHg, p=0.014). Height, weight, diastolic BP, heart rate, and AoR measurements were similar.This study provides information for implementing tele-clinic visits using parentally-acquired vital signs and echo images in MFS patients. The results show that tele-clinic visits are feasible and that parents were able to obtain focused echo images on their children.

    View details for DOI 10.1016/j.jpeds.2021.01.004

    View details for PubMedID 33453199

  • Pericardial Effusion in Children Admitted With Kawasaki Disease: A Multicenter Retrospective Cohort Study From the Pediatric Health Information System. Clinical pediatrics Schexnayder, A. G., Tang, X., Collins, R. T., Schexnayder, S. M., Bolin, E. H. 2021; 60 (1): 9-15


    Pericardial effusion (PCE) can be associated with Kawasaki disease (KD). We performed a multicenter, retrospective cohort study of the Pediatric Health Information System of children admitted with KD to determine the association between PCE and adverse outcomes. A total of 17 422 patients were in the cohort, of which 440 (3%) had PCE. PCE was associated with longer hospital length of stay (adjusted odds ratio [aOR] = 1.23; P < .01) and risk of readmission at 30 days (aOR = 1.42; P = .03). Black children were more likely to have a PCE (aOR = 1.54, P < .01) and longer length of stay (aOR = 1.05; P < .001). These data may support delayed discharge in children with PCE and KD in the hopes of preventing readmission. Special consideration needs to be given to how black children with KD are managed.

    View details for DOI 10.1177/0009922820927021

    View details for PubMedID 33297737

  • Clinical Significance of Screening Electrocardiograms for the Administration of Propranolol for Problematic Infantile Hemangiomas. International journal of pediatrics Phillips, J. D., Merrill, T., Gardner, J. R., Thomas Collins, R. 2., Sanchez, J., Johnson, A. B., Eble, B. K., Hartzell, L. D., Kincannon, J. M., Richter, G. T. 2021; 2021: 6657796


    Objective: Low-dose nonselective beta blockade is an effective treatment for problematic infantile hemangioma (PIH). Screening electrocardiograms (ECG) are performed prior to the initiation of propranolol to minimize the risk of exacerbating undiagnosed heart block. How ECG results affect subsequent propranolol usage and patient management remains unclear. We examined the value of ECG prior to propranolol therapy in a quaternary pediatric hospital.Methods: A retrospective chart review was performed on all infants who received propranolol (2mg/kg/day divided three times daily) to treat PIH at Arkansas Children's Hospital from Sept. 2008 to Sept. 2015. All available demographic, historical, and clinical data were obtained. ECGs and echocardiographic data were reviewed and summarized. A pediatric cardiologist read all ECGs.Results: A total of 333 patients (75% female) received propranolol therapy. ECG information was available for 317 (95%). Abnormal findings were present on 44/317 (13.9%) of study ECGs. The most common abnormal finding was "voltage criteria for ventricular hypertrophy" (n = 35, 76.1%). Two patients had abnormal rhythms; one had first-degree atrioventricular (AV) block, and one had occasional premature atrial contractions. Of the 31 patients who underwent echocardiograms, 20 (35%) were abnormal. 2.9% of infants with PIH treated with propranolol required a follow-up with a cardiologist. No patient was precluded from taking propranolol due to the findings on screening ECG.Conclusions: Screening ECGs prior to propranolol therapy are abnormal in nearly 14% of patients with PIH but are unlikely to preclude therapy. In the absence of prior cardiac history, this cohort offers further evidence suggesting that screening ECGs may be of limited value in determining the safety of propranolol in otherwise healthy infants with PIH.

    View details for DOI 10.1155/2021/6657796

    View details for PubMedID 33679994

  • Implementation of a statewide, multisite fetal tele-echocardiography program: evaluation of more than 1100 fetuses over 9 years. Journal of perinatology : official journal of the California Perinatal Association Bolin, E. H., Collins, R. T., Best, T. H., Zakaria, D., Lang, S. M., Boushka, M. G., Renno, M. S., Heil, L. L., Lowery, C. L., Bornemeier, R. A. 2020; 40 (10): 1524-1530


    We sought to describe the implementation and effectiveness of a statewide fetal tele-echocardiography program serving a resource-limited population.In 2009, our heart center established six satellite clinics for fetal tele-echocardiography around the state. We retrospectively reviewed all fetal tele-echocardiograms performed through 2018. Yearly statewide prenatal detection rates of operable congenital heart disease were queried from the Society of Thoracic Surgeons database.In 1164 fetuses, fetal tele-echocardiography identified all types of congenital heart disease, with a sensitivity of 74% and specificity of 97%. For the detection of ductal-dependent congenital heart disease, fetal tele-echocardiography was 100% sensitive and specific. Between 2009 and 2018, annual statewide prenatal detection rates of congenital heart disease requiring heart surgery in the first 6 months of life rose by 159% (17-44%; R2 = 0.88, p < 0.01).The present study provides a framework for an effective, large-scale fetal tele-echocardiography program.

    View details for DOI 10.1038/s41372-020-0677-2

    View details for PubMedID 32382116

  • Surgical repair of coronary artery ostial stenosis in patients with Williams and elastin arteriopathy syndromes. The Journal of thoracic and cardiovascular surgery Mainwaring, R. D., Collins, R. T., Patrick, W. L., Martin, E., MacMillen, K. L., Hanley, F. L. 2020


    OBJECTIVE: Patients with Williams and elastin arteriopathy syndromes often have similar cardiac phenotypes characterized by supravalvar aortic stenosis (SVAS), peripheral pulmonary artery stenosis (PPAS), and coronary artery ostial stenosis (CAOS). SVAS and/or PPAS result in a marked increase in myocardial oxygen demand, whereas CAOS may limit myocardial oxygen supply. This combination predisposes to myocardial ischemic events and sudden cardiac arrest. The purpose of this study was to review our experience with the surgical repair of CAOS in patients with Williams and elastin arteriopathy syndromes.METHODS: This was a retrospective review of 16 patients with Williams (n=11) or elastin arteriopathy (n=5) who underwent surgical repair of CAOS as a concomitant procedure with SVAS and/or PPAS repair. Eleven patients had moderate or severe SVAS, and 10 had PPAS. The median age at surgery was 9months (range, 3-108months).RESULTS: Seven patients had repair of the left main and right coronary ostia, 6 the left main, and 3 the right coronary ostium. Median duration of aortic crossclamp was 56minutes and cardiopulmonary bypass time was 454minutes. The median SVAS gradient decreased from 70 to 12mm Hg and pulmonary artery pressure decreased from 120 to 30mm Hg. There was 1 operative mortality (6%). The remaining 15 patients were discharged from the hospital and are alive at a median of 17months' follow-up.CONCLUSIONS: The data demonstrate that patients with Williams and elastin arteriopathy syndromes presenting with SVAS and/or PPAS plus CAOS can undergo successful repair of all hemodynamic issues simultaneously.

    View details for DOI 10.1016/j.jtcvs.2020.08.070

    View details for PubMedID 32977964

  • Aortic Geometry in Patients with Duplication 7q11.23 Compared to Healthy Controls. Pediatric cardiology Lechich, K. M., Zarate, Y. A., Daily, J. A., Collins, R. T. 2020; 41 (6): 1199-1205


    The aim of this study was to compare the size and geometry of the aorta in patients with 7q11.23 duplication (Dup7) to healthy controls. We retrospectively reviewed all echocardiograms in all patients with Dup7 evaluated at our institutions from June 2017 through September 2019. All standard aortic diameter measurements were made and recorded. Z-scores for the measurements were calculated. For comparison, a set of control echocardiograms was developed by randomly selecting 24 normal echocardiograms in age-matched patients who had undergone echocardiograms for an indication of either chest pain or syncope. In 58 echocardiograms from 21 Dup7 patients, all aortic measurements were increased compared to controls (p < 0.0001). Effacement of the sinotubular junction (STJ) of the aorta was present in all Dup7 patients. Our novel STJ-to-aortic annulus ratio of ≥ 1.15 had a 98.28% sensitivity (95% CI 90.76-99.96) and 100% specificity (95% CI 85.75-100) for distinguishing Dup7 from controls with a positive predictive value of 100% and a negative predictive value of 96.00% (95% CI 77.47-99.41). All patients in our study with Dup7 had echocardiographic evidence of aortopathy. Effacement of the STJ was present in all Dup7 patients. The STJ-to-annulus ratio is a better indicator of aortopathy in Dup7 than the aortic Z-score.

    View details for DOI 10.1007/s00246-020-02375-2

    View details for PubMedID 32474735

  • The success and failure of the adult congenital heart. Heart failure reviews Collins, R. T. 2020; 25 (4): 553-554

    View details for DOI 10.1007/s10741-020-09941-z

    View details for PubMedID 32130569

  • Letter to the Editor. Journal of paediatrics and child health Lang, S. M., Bolin, E. H., Daily, J. A., Collins, R. T. 2020; 56 (4): 659-660

    View details for DOI 10.1111/jpc.14854

    View details for PubMedID 32307779

  • Pulmonary Artery Reconstruction Following Failed Pulmonary Artery Stents. The Annals of thoracic surgery Mainwaring, R. D., Collins, R. T., MacMillen, K. L., Palmon, M., Hanley, F. L. 2020


    BACKGROUND: Pulmonary artery stents are widely deployed in patients with stenoses ; in the branch pulmonary arteries. However, stents do not address more peripheral sites of ; stenosis and invariably develop in-stent restenosis. The purpose of this study was to review our ; experience with pulmonary artery reconstruction following failed pulmonary artery stents.METHODS: This was a retrospective study of 56 patients who underwent pulmonary artery reconstruction following failed pulmonary artery stents. These patients had undergone a median of two previous surgical procedures (range 0-5) and two pulmonary artery stents (range 1-4).RESULTS: The median age at stent surgery was 5 years (range 0.3 to 23.6 years). The majority of stents (79%) were completely removed and patch augmented. The minority of stents (21%) were felt to be unremovable and thus were split longitudinally and reconstructed using; pulmonary artery homograft. There was one operative mortality (1.8%). The mean pulmonary artery-to-aortic pressure ratio decreased from a pre-operative value of 0.91 ± 0.21 to a post-operative value of 0.31 ± 0.07 (p < 0.001). The median hospital length of stay was 10 days. The median duration of follow-up is 1.8 years. There has been no mid-term mortality. Six patients have undergone balloon dilation post-operatively for residual pulmonary artery stenosis.CONCLUSIONS: Pulmonary artery reconstruction resulted in a significant decrease in pulmonary artery-to-aortic pressure ratios. The subsequent need for re-intervention on the ; pulmonary arteries has been relatively low (11% to date). These results suggest that patients with ; pulmonary artery stents can be successfully treated with surgical reconstruction.

    View details for DOI 10.1016/j.athoracsur.2020.01.007

    View details for PubMedID 32084373

  • A Predictive Model for Intracardiac Pressures in Patients Free from Rejection or Allograft Vasculopathy After Pediatric Heart Transplantation. Transplantation Mills, M. F., Long, J., Qin, F., Collins, R. T., Rosenthal, D. N., Almond, C. S., Hollander, S. A. 2020


    BACKGROUND: Despite the routine use of hemodynamic assessment in pediatric heart transplant (HT) patients, expected intracardiac pressure measurements in patients free of significant complications are incompletely described. A better understanding of the range of intracardiac pressures in these HT patients is important for the clinical interpretation of these indices and consequent management of patients.METHODS: We conducted a retrospective chart review of pediatric HT recipients who had undergone HT between January 2010 and December 2015 at Lucile Packard Children's Hospital. We analyzed intracardiac pressures measured in the first 12 months after HT. We excluded those with rejection, graft coronary artery disease, mechanical support, or hemodialysis. We used a longitudinal General Additive Model (GAM) with bootstrapping technique to generate age and donor-recipient size specific curves to characterize filling pressures through 1-year post-HT.RESULTS: Pressure measurements from the right atrium (RA), pulmonary artery (PA), and pulmonary capillary wedge (PCWP) were obtained in 85 patients during a total of 829 catheterizations. All pressure measurements were elevated in the immediate post-HT period and decreased to a stable level by post-HT day 90. Pressure measurements were not affected by age group, donor-recipient size differences, or ischemic time.CONCLUSION: Intracardiac pressures are elevated in the early post-HT period and decrease to levels typical of the native heart by 90 days. Age, donor-to-recipient size differences, and ischemic time do not contribute to differences in expected intracardiac pressures in the first year post-HT.

    View details for DOI 10.1097/TP.0000000000003166

    View details for PubMedID 32044891

  • Surgical repair of peripheral pulmonary artery stenosis in patients without williams or alagille syndromes. Seminars in thoracic and cardiovascular surgery Martin, E. n., Mainwaring, R. D., Collins, R. T., MacMillen, K. L., Hanley, F. L. 2020


    Peripheral pulmonary artery stenosis (PPAS) is a relatively rare form of congenital heart disease typically associated with genetic syndromes, such as Williams or Alagille syndromes. However, some patients present with severe stenosis without associated syndromes. The purpose of the study was to review our surgical experience in such patients. This was a retrospective review of 30 patients who underwent surgical repair for peripheral pulmonary artery stenosis. Concomitant anatomical diagnoses in 20 patients (67%) included: supravalvar aortic stenosis (n=8), tetralogy of Fallot (n=4), d-transposition of the great arteries (n=2), truncus arteriosus (n=2), hypoplastic left heart syndrome (n=2), ventricular septal defect (n=1), and patent ductus arteriosus (n=1). Additional medical diagnoses in 15 patients (50%) included: elastin arteriopathy (n=9), pulmonary artery calcinosis (n=1), arterial tortuosity syndrome (n=1), DiGeorge syndrome (n=1) and Noonan syndrome (n=1). Median age at surgery was 3.6 years (IQR 1.6-7.4 years). Seventeen patients (57%) had prior cardiac operations, and 16 patients (53%) previously underwent percutaneous intervention. With surgery, mean right ventricle-to-aortic systolic pressure ratio decreased from 0.95±0.2 to 0.28±0.08 (p<0.0001). Median duration of cardiopulmonary bypass was 369 minutes. There was 100% survival to hospital discharge, with no mortality at mean follow-up of 2.3 years. No patient required reoperation, while 4 underwent balloon dilation. Freedom from pulmonary artery catheter-based reintervention was 95% and 80% at 12 and 36 months, respectively. Patients with peripheral pulmonary artery stenosis without either Williams or Alagille syndrome can successfully undergo surgical repair with a significant reduction in right ventricle-to-aortic pressure ratios.

    View details for DOI 10.1053/j.semtcvs.2020.01.003

    View details for PubMedID 31958550

  • Rationale and design of CH STRONG: Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinG. American heart journal Farr, S. L., Klewer, S. E., Nembhard, W. N., Alter, C. n., Downing, K. F., Andrews, J. G., Collins, R. T., Glidewell, J. n., Benavides, A. n., Goudie, A. n., Riehle-Colarusso, T. n., Overman, L. n., Riser, A. P., Oster, M. E. 2020; 221: 106–13


    Studies of outcomes among adults with congenital heart defects (CHDs) have focused on those receiving cardiac care, limiting generalizability. The Congenital Heart Survey To Recognize Outcomes, Needs, and well-beinG (CH STRONG) will assess comorbidities, health care utilization, quality of life, and social and educational outcomes from a US population-based sample of young adults living with CHD.Individuals with CHD born between 1980 and 1997 were identified using active, population-based birth defects surveillance systems from 3 US locations (Arkansas [AR]; Arizona [AZ]; and Atlanta, Georgia [GA]) linked to death records. Individuals with current contact information responded to mailed survey materials during 2016 to 2019. Respondents and nonrespondents were compared using χ2 tests.Sites obtained contact information for 74.6% of the 9,312 eligible individuals alive at recruitment. Of those, 1,656 returned surveys, either online (18.1%) or via paper (81.9%), for a response rate of 23.9% (AR: 18.3%; AZ: 30.7%; Atlanta, GA: 28.0%; P value < .01). For 20.0% of respondents, a proxy completed the survey, with 63.9% reporting that the individual with CHD was mentally unable. Among respondents and nonrespondents, respectively, sex (female: 54.0% and 47.3%), maternal race/ethnicity (non-Hispanic white: 74.3% and 63.0%), CHD severity (severe: 33.8% and 27.9%), and noncardiac congenital anomalies (34.8% and 38.9%) differed significantly (P value < .01); birth year (1991-1997: 56.0% and 57.5%) and presence of Down syndrome (9.2% and 8.9%) did not differ.CH STRONG will provide the first multisite, population-based findings on long-term outcomes among the growing population of US adults with CHD.

    View details for DOI 10.1016/j.ahj.2019.12.021

    View details for PubMedID 31986287

  • The Limited Benefit of Follow-Up Echocardiograms After Repair of Tetralogy of Fallot. Pediatric cardiology Xu, J., Guthrey, C., Dalby, S., Tang, X., Daily, J., Collins, R. T. 2019; 40 (8): 1722-1727


    Tetralogy of Fallot (ToF) is the most common cyanotic congenital heart disease, making up 10% of all congenital heart defects. Annual follow-up echocardiograms are recommended in patients with repaired ToF, but evidence-based guidelines do not exist. We hypothesized that most echocardiograms performed in asymptomatic patients with repaired ToF and no physical exam change do not result in an actionable change (AC) in management. We retrospectively reviewed records of all patients with ToF and prior complete repair at our institution between January 2000 and September 2015. Changes in echocardiograms resulting in hospital admission, medication addition/change, cardiac catheterization, or surgical procedure were identified via chart review. These changes were referred to as an AC. A total of 1135 echocardiograms were reviewed from 233 patients (160 with initial complete repair, 70 with prior shunt, and 3 with other initial surgery). The median number of echocardiograms per patient was 5. Of the 1135 echocardiograms, 15 (1.3%) were associated with AC. Of the 15 patients with AC echocardiograms, 9 underwent a shunt prior to complete repair (9/70, 12.9%) and 6 had undergone an initial complete repair (6/160, 3.8%). The median age at AC was 6.3 years (IQR 4.4, 6.8) in the shunt group and 0.90 years (IQR 0.87, 1.1) in the initial complete repair group. In asymptomatic patients with repaired ToF and no physical exam change, echocardiograms rarely lead to a change in clinical management. In conclusion, the likelihood and timing of AC echocardiograms and reinterventions vary based on the type of initial surgery.

    View details for DOI 10.1007/s00246-019-02210-3

    View details for PubMedID 31535184

  • Adverse Pregnancy and Neonatal Outcomes Among Marshallese Women Living in the United States MATERNAL AND CHILD HEALTH JOURNAL Nembhard, W. N., Ayers, B. L., Collins, R., Shan, X., Rabie, N. Z., Chang, D., Robbins, J. M., McElfish, P. A. 2019; 23 (11): 1525–35


    Objective Despite heterogeneity among Pacific Islanders, most studies aggregate them regardless of origin. Thus, limited information is available about perinatal outcomes among various subgroups of Pacific Islanders in the United States, including immigrants from the Republic of the Marshall Islands. We sought to evaluate perinatal outcomes among Marshallese women. Methods We conducted a cross-sectional study of women with at least one singleton live birth between 1997 and 2013 in two Arkansas counties using birth certificate data from the Arkansas Department of Health. Unadjusted and adjusted prevalence ratios (PR) and 95% confidence intervals (CI) were calculated from modified Poisson regression models. Results Of the 91,662 singleton births in both counties during the study period, 2488 were to Marshallese women. In adjusted analyses, Marshallese women had higher prevalence of "other medical risk factors" (PR = 1.47; 95% CI 1.30, 1.65) than NH White women. Marshallese women had higher rates of precipitous labor and fetal distress during labor compared to NH White women (PR = 2.65; 95% CI 2.22, 3.17 and 1.89; 95% CI 1.62, 2.21, respectively). Marshallese were also more likely to have tocolysis (PR = 1.43; 95% CI 1.16, 1.76), forceps (PR = 1.68; 95% CI 1.16, 2.43) or vacuum (PR = 1.89; 95% CI 1.60, 2.22) used in delivery and cesarean section (PR = 1.13; 95% CI 1.01, 1.27). Marshallese infants had higher rates of anemia (PR = 3.10; 95% CI 2.01, 4.77), birth injury (PR = 2.13; 95% CI 1.50, 3.03), assisted ventilation < 30 min (PR = 2.11; 95% CI 1.64, 2.71), preterm birth (PR = 1.67; 95% CI 1.50, 1.83), and small-for-gestational age (PR = 1.25; 95% CI 1.12, 1.39) than NH White infants. Conclusions Marshallese women and infants had higher rates of adverse perinatal outcomes compared to their NH White counterparts. Additional studies are needed to determine if perinatal outcomes among the Marshallese differed from other Pacific Islander subgroups.

    View details for DOI 10.1007/s10995-019-02775-8

    View details for Web of Science ID 000503226100011

    View details for PubMedID 31228148

  • Nuclear radiation and prevalence of structural birth defects among infants born to women from the Marshall Islands. Birth defects research Nembhard, W. N., McElfish, P. A., Ayers, B., Collins, R. T., Shan, X., Rabie, N. Z., Zarate, Y. A., Maity, S., Cen, R., Robbins, J. A. 2019; 111 (16): 1192-1204


    With their unique history of exposure to extensive nuclear testing between 1946 and 1958, descendants of Marshall Island residents may have underappreciated genetic abnormalities, increasing their risk of birth defects.We conducted a retrospective cohort study of resident women with at least one singleton live birth between 1997 and 2013 in northwest Arkansas using state birth certificate data linked to data from the Arkansas Reproductive Health Monitoring System, a statewide birth defects registry. We calculated unadjusted and adjusted prevalence ratios (PR) and 95% confidence intervals (CI) from modified Poisson regression analyses for non-Hispanic (NH) whites, NH-blacks, Hispanics and Marshallese, using NH-whites as the reference group.Of the 91,662 singleton births during the study period, 2,488 were to Marshallese women. Due to the relatively small number of Marshallese births, we could not calculate prevalence estimates for some defects. Marshallese infants had higher rates of congenital cataracts (PR = 9.3; 95% CI: 3.1, 27.9). Although the number of defects was low, Marshallese infants also had higher rates of truncus arteriosus (PR = 44.0; 95% CI: 2.2, 896.1).Marshallese infants may have increased risk of specific birth defects, but estimates are unstable because of small sample size so results are inconclusive. Larger population-based studies would allow for further investigation of this potential risk among Marshallese infants.

    View details for DOI 10.1002/bdr2.1551

    View details for PubMedID 31313527

    View details for PubMedCentralID PMC7927675

  • Comparison of inhospital outcomes of pediatric heart transplantation between single ventricle congenital heart disease and cardiomyopathy. Pediatric transplantation Bradford, T. T., Daily, J. A., Lang, S. M., Gossett, J. M., Tang, X., Collins, R. T. 2019; 23 (6): e13495


    Data investigating the impact of household income and other factors on SV patient status-post-Fontan palliation after heart transplantation are lacking. We aim to evaluate factors affecting outcomes after OHT in this population. The PHIS database was interrogated for either SV or myocarditis/primary CM who were 4 years or older who underwent a single OHT. There were 1599 patients with a median age of 13.2 years (IQR: 9.3-16.1). Total hospital costs were significantly higher in the SV group ($408 000 vs $294 000, P < 0.0001), but as median household income increased, the risk of inhospital mortality, post-transplant LOS, and LOS-adjusted total hospital costs all decreased. The risk of inhospital mortality increased 6.5% per 1 year of age increase at the time of transplant. Patients in the SV group had significantly more diagnoses than those in the CM group (21 vs 15, P < 0.0001) and had longer total hospital LOSs as a result of longer post-transplant courses (25 days vs 15, P < 0.0001). Increased median household income and younger age are associated with decreased resource utilization and improved inhospital mortality in SV CHD patients who undergo OHT. In conclusion, earlier consideration of OHT in this population, coupled with improved selection criteria, may increase survival in this population.

    View details for DOI 10.1111/petr.13495

    View details for PubMedID 31169342

  • 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., Natl Birth Defects Prevention 2019; 111 (11): 640–48

    View details for DOI 10.1002/bdr2.1501

    View details for Web of Science ID 000473561000003

  • 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. 2019; 179 (6): 1047–52
  • Dichotomizing the spectrum of ductal shunt places long-term outcomes research at risk Reply JOURNAL OF PEDIATRICS Collins, R., Lyle, R. E., Casey, P. H. 2019; 209: 257-258

    View details for DOI 10.1016/j.jpeds.2019.02.007

    View details for Web of Science ID 000468615300050

    View details for PubMedID 30853198

  • Real-Time Transthoracic Vector Flow Imaging of the Heart in Pediatric Patients. Progress in pediatric cardiology Collins, R. T., Laughlin, M. E., Lang, S. M., Bolin, E. H., Daily, J. A., Jensen, H. A., Jensen, M. O. 2019; 53: 28-36


    In children with congenital heart defects, Doppler ultrasound is the standard, bedside imaging modality. However, precise characterization of blood flow is challenging due to angle-dependent and one-dimensional velocity estimation. Contrast agent free Vector Flow Imaging is a new ultrasound technology that enables angle-independent visualization of the detailed flow field. Two piglets, one with normal cardiac anatomy and one with congenital heart disease comprised of valvular pulmonary stenosis, a dilated main pulmonary artery, and an incomplete atrioventricular canal defect, were imaged transthoracically and epicardially using a BK Ultrasound bk5000 with built-in vector flow imaging and a 5MHz linear probe. Subsequently, two children, one with normal cardiac anatomy and one with congenital heart disease comprised of aortic valve stenosis and coarctation of the aorta were imaged transthoracically. Transthoracic two-dimensional echocardiography and vector flow imaging were readily performed in both animals and were limited only by the geometry of the porcine thorax. In addition, transthoracic vector flow imaging was successfully performed in both children, and abnormal flow secondary to cardiac anomalies was visible. Adequate penetration was obtained to a depth of 6.5 cm. Our group has previously demonstrated for the first time that transthoracic vector flow imaging echocardiography is feasible and practicable in pediatric-sized patients, and this paper describes examples of these concepts and in-depth comparisons with traditional imaging modalities. This paper demonstrates that commercially available vector flow imaging technology can be utilized in pediatric cardiac applications as a bedside transthoracic imaging modality, providing advanced detail of blood flow patterns within the cardiac chambers, across valves, and in the great arteries.

    View details for DOI 10.1016/j.ppedcard.2019.02.003

    View details for PubMedID 31662599

    View details for PubMedCentralID PMC6818513

  • 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


    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 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


    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 PubMedID 30920163

  • Resource Utilization Among Adult Congenital Heart Failure Admissions in Pediatric Hospitals AMERICAN JOURNAL OF CARDIOLOGY Chan, J., Collins, R., Hall, M., John, A. 2019; 123 (5): 839–46
  • Effect of pericardial effusion on outcomes in children admitted with systemic lupus erythematosus: a multicenter retrospective cohort study from the United States. Lupus Dalby, S. T., Tang, X., Daily, J. A., Sukumaran, S., Collins, R. T., Bolin, E. H. 2019; 28 (3): 389-395


    We sought to describe characteristics of children admitted with pericardial effusion (PCE) and systemic lupus erythematosus (SLE) and determine the association between PCE and outcomes of interest.We performed a retrospective cohort study of the Pediatric Health Information System (PHIS). Patients were included if they were admitted to a PHIS participating hospital from 2004 to 2015 with a diagnosis of SLE and age ≤18 years. Children with congenital heart disease or who had undergone heart surgery were excluded. PCE was the primary predictor variable; multivariable analysis was used to evaluate the effect of PCE on the following outcomes: mortality, length of stay (LOS), and readmission within 30 days.There were 5679 admissions, of which 705 (12.4%) had PCE. Median age at admission was 15 years (interquartile range: 13-17). There were no significant differences for age or sex between patients admitted either with or without PCE. A significantly higher percentage of children in the PCE group were black compared with those without PCE (43% vs. 31%, p < 0.001). In multivariable analysis, the odds of a black patient having PCE were 1.7 higher than non-black patients ( p < 0.001). In-hospital mortality was 2.5 times higher in children with PCE compared with those without PCE ( p = 0.027). Those with PCE also had 1.5 greater odds of readmission within 30 days ( p < 0.001). PCE was not associated with increased LOS (0.99, p = 0.753).PCE is common in admissions of children with SLE. There are disproportionately more black patients with SLE affected by PCE than non-black. PCE is associated with significantly higher mortality and rates of readmission.

    View details for DOI 10.1177/0961203319828523

    View details for PubMedID 30744520

  • Sacrificing the Future for the Sake of the Present. Annals of surgery Collins, R. T., Shin, A. Y., Hanley, F. L. 2019

    View details for DOI 10.1097/SLA.0000000000003432

    View details for PubMedID 31425297

  • 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


    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 PubMedID 30579512

  • Utility of Follow-Up Annual Echocardiograms in Patients With Complete Transposition of the Great Arteries After Arterial Switch Operations AMERICAN JOURNAL OF CARDIOLOGY Shivaram, P., Padiyath, A., Bai, S., Gossett, J. M., Collins, R. 2018; 122 (11): 1972-1976


    The arterial switch operation (ASO) in complete transposition of the great arteries (TGA) has increased long-term survival. Annual follow-up echocardiograms are recommended, but evidence-based guidelines do not exist. We sought to assess how often a patient with TGA after ASO who had no symptoms or change in physical exam underwent an intervention based solely on echocardiographic changes. We retrospectively reviewed all records from patients with TGA and a history of ASO followed at our institution between November 1983 and January 2015. Changes in echocardiograms resulting in hospital admission, significant medication change, interventional catheterization, or surgical procedure were identified through the surgical and cardiac catheterization laboratory databases and patient charts. These changes were referred to as an actionable change (AC). Interventions were defined as being driven by either clinical (change in physical exam, patient and/or parental concerns) or echocardiographic findings. A total of 1,792 echocardiograms from 149 patients were reviewed. Median number of echocardiograms per patient was 12 (1 to 34). Of the 1,792 echocardiograms, 20 (1.12%) were associated with AC. The most common intervention for an AC was cardiac catheterization (13 of 20, 65%). Most AC (15 of 20, 75%) occurred in the first decade after ASO. AC occurred in 83% (5 of 6) of those with a history of both ASO and arch repair. Annual echocardiograms in patients with TGA after ASO are rarely useful and are unnecessary. In conclusion, decreasing surveillance of asymptomatic patients to biennial follow-up echocardiograms in asymptomatic patients without physical examination changes is safe and would decrease medical expenses.

    View details for DOI 10.1016/j.amjcard.2018.08.044

    View details for Web of Science ID 000453637000024

    View details for PubMedID 30318419

  • 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


    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

  • 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: 153-159


    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

  • 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


    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


    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

  • 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

  • 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): 509-517


    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): 347-353


    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): 275-282


    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

  • 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


    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. n., Yang, W. n., Carmichael, S. L., Reynolds, P. n., Fisher, P. G., Shaw, G. M. 2018; 110 (17): 1314–21


    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 PubMedID 30328285

  • 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): 1209-1213


    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

  • 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): 1029-1034


    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): 1670-1674


    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

  • 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


    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

  • 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): 762-769


    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

  • Personal Finance for Pediatric Trainees. Clinical pediatrics Daily, J., Collins, R. T., Bolin, E. 2017; 56 (4): 313-315

    View details for DOI 10.1177/0009922816669789

    View details for PubMedID 27681309

  • 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): 1106-1110


    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

  • 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): 210-217


    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

  • 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): 162-169


    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


    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 complications following pediatric heart transplantation: A case series and review. Annals of pediatric cardiology Lang, S. M., Frazier, E. A., Collins, R. T. 2016; 9 (1): 42-5


    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

  • 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


    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): 1380-1

    View details for DOI 10.1016/j.jtcvs.2015.08.006

    View details for PubMedID 26546205

    View details for PubMedCentralID PMC5483952

  • 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


    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

  • 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


    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

  • 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


    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

  • 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


    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

  • 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): 132-9


    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

  • 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


    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


    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

  • 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


    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

  • 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): 563-6


    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

  • 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. 2014; 60 (4): 385-90


    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

  • 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


    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

  • 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


    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): 4596-601


    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


    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): 1427-9


    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

  • 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): 1671-6


    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

  • 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 1730-1

    View details for DOI 10.1016/j.jacc.2012.01.041

    View details for PubMedID 22554606

  • 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 491-2

    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

  • Conjoined hearts in thoracopagus twins. Pediatric cardiology Thomas Collins, R., Weinberg, P. M., Gruber, P. J., St John Sutton, M. G. 2012; 33 (2): 252-7


    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

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

    View details for DOI 10.1016/j.amjcard.2011.03.071

    View details for PubMedID 21550581

  • 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


    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

  • 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

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


    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

  • 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

  • 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): 253-8.e1


    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

  • 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): 1580-1; discussion 1582-3

    View details for DOI 10.1016/j.socscimed.2009.09.010

    View details for PubMedID 19782457

  • 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


    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

  • Asymptomatic anomalous right coronary artery from the pulmonary trunk. Cardiology in the young Thomas Collins, R., Davis, E., Stephens, P. 2009; 19 (4): 391-2

    View details for DOI 10.1017/S1047951109990217

    View details for PubMedID 19493367

  • 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): 165-9

    View details for DOI 10.1016/j.jpeds.2009.02.006

    View details for PubMedID 19619748

  • 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): 794-9


    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

  • 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

  • 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


    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

  • 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

  • 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