Seda Tierney

All Publications

• Cardiology Consult for the General Pediatrician after Cardiac Manifestations from a SARS-CoV-2 Infection. Current pediatric reviews Amdani, S., Altman, C. A., Chowdhury, D., Ronai, C., Soma, D., Archer, J. M., Tierney, S., Renno, M. S., Miller, J., Nguyen, Q., Glickstein, J. S., Orr, W. B. 2024

  Abstract

  The novel Coronavirus Disease 2019 (COVID-19), caused by the SARS-CoV-2 virus, created a need for evidence-based guidelines for the evaluation, management, and follow-up after infection. Data have become rapidly available, creating a challenge for medical providers to stay abreast of the ever-evolving recommendations. This document, written collaboratively by pediatric cardiovascular experts, pediatricians, and sports medicine specialists, is focused on SARS-- CoV-2-related pediatric cardiac manifestations. It aims to provide a systemic review of high-yield literature related to all cardiovascular entities as a tool for primary pediatric clinicians to utilize as they consider the cardiac consequences of acute SARS-CoV-2 infection, MIS-C, vaccine-related myocarditis, return-to-play, and long COVID-19 syndrome.

  View details for DOI 10.2174/0115733963314978240923110844

  View details for PubMedID 39360535

• Addressing Disparities in Pediatric Congenital Heart Disease: A Call for Equitable Health Care. Journal of the American Heart Association Chowdhury, D., Elliott, P. A., Asaki, S. Y., Amdani, S., Nguyen, Q. T., Ronai, C., Tierney, S., Levy, V. Y., Puri, K., Altman, C. A., Johnson, J. N., Glickstein, J. S. 2024: e032415

  Abstract

  While significant progress has been made in reducing disparities within the US health care system, notable gaps remain. This article explores existing disparities within pediatric congenital heart disease care. Congenital heart disease, the most common birth defect and a leading cause of infant death, has garnered substantial attention, revealing certain disparities within the US health care system. Factors such as race, ethnicity, insurance coverage, socioeconomic status, and geographic location are all commonalities that significantly affect health disparities in pediatric congenital heart disease. This comprehensive review sheds light on disparities from diverse perspectives in pediatric care, demonstrates the inequities and inequalities leading to these disparities, presents effective solutions, and issues a call to action for providers, institutions, and the health care system. Recognizing and addressing these disparities is imperative for ensuring equitable care and enhancing the long-term well-being of children affected by congenital heart disease. Implementing robust, evidence-based frameworks that promote responsible and safe interventions is fundamental to enduring change.

  View details for DOI 10.1161/JAHA.123.032415

  View details for PubMedID 38934870

• Mental Health Care for Children with Heart Disease and Their Families: Practical Approaches and Considerations for the Pediatric and Pediatric Cardiology Clinician. Pediatric cardiology McCormick, A. D., Puri, K., Asaki, S. Y., Amdani, S., Chowdhury, D., Glickstein, J. S., Tierney, S., Ibeziako, P., Cousino, M. K., Ronai, C. 2024

  Abstract

  Mental health conditions are a common comorbidity among children living with heart disease. Children with congenital heart disease are more likely to have a mental health condition than their unaffected peers or peers with other chronic illnesses, and mental health risk persists across their lifetime. While poorer mental health in adults with congenital heart disease is associated with worse overall health outcomes, the association between mental health and cardiac outcomes for children with heart disease remains unknown. Despite this, it is suspected that mental health conditions go undiagnosed in children with heart disease and that many affected children and adolescents do not receive optimal mental health care. In this article, we review mental health in congenital heart disease across the lifespan, across domains of care, and across diagnoses. Further directions to support mental health care for children and adolescents with heart disease include practical screening and access to timely referral and mental health resources.

  View details for DOI 10.1007/s00246-024-03518-5

  View details for PubMedID 38753034

  View details for PubMedCentralID 6825971

• Bilateral Ductus Arteriosus With Anomalous Origin of the Right Pulmonary Artery and Coarctation oftheAorta. JACC. Case reports Issapour, A., Gallegos, F. N., Taylor, A. C., Martin, E., Tierney, S. 2024; 29 (8): 102304

  Abstract

  We present a full-term neonate with a postnatal diagnosis with a left aortic arch, bilateral ducti, and discontinuous branch pulmonary arteries with right pulmonary artery arising from right duct. Upon left ductal constriction, the patient experienced coarctation of the aorta, illustrating the importance of careful and serial interrogation of rare cardiac anatomy.

  View details for DOI 10.1016/j.jaccas.2024.102304

  View details for PubMedID 38774800

• Vascular health years after a hypertensive disorder of pregnancy: The EPOCH Study. American heart journal Miller, H. E., Tierney, S., Stefanick, M. L., Mayo, J. A., Sedan, O., Rosas, L. G., Melbye, M., Boyd, H. A., Stevenson, D. K., Shaw, G. M., Winn, V. D., Hlatky, M. A. 2024

  Abstract

  Preeclampsia is associated with a two-fold increase in a woman's lifetime risk of developing atherosclerotic cardiovascular disease (ASCVD), but the reasons for this association are uncertain. The objective of this study was to examine the associations between vascular health and a hypertensive disorder of pregnancy among women ≥ 2 years postpartum.Pre-menopausal women with a history of either a hypertensive disorder of pregnancy (cases: preeclampsia or gestational hypertension) or a normotensive pregnancy (controls) were enrolled. Participants were assessed for standard ASCVD risk factors and underwent vascular testing, including measurements of blood pressure, endothelial function, and carotid artery ultrasound. The primary outcomes were blood pressure, ASCVD risk, reactive hyperemia index measured by EndoPAT and carotid intima-medial thickness. The secondary outcomes were augmentation index normalized to 75 beats per minute and pulse wave amplitude measured by EndoPAT, and carotid elastic modulus and carotid beta-stiffness measured by carotid ultrasound.Participants had a mean age of 40.7 years and were 5.7 years since their last pregnancy. In bivariate analyses cases (N=68) were more likely than controls (N=71) to have hypertension (18% vs. 4%, p=0.034), higher calculated ASCVD risk (0.6 vs 0.4, p=0.02), higher blood pressures (systolic: 118.5 vs. 111.6 mm Hg, p=0.0004; diastolic: 75.2 vs 69.8 mm Hg, p=0.0004), and higher augmentation index values (7.7 vs. 2.3 p=0.03). They did not, however, differ significantly in carotid intima-media thickness (0.5 vs. 0.5, p=0.29) or reactive hyperemia index (2.1 vs 2.1, p=0.93), nor in pulse wave amplitude (416 vs 326, p=0.11), carotid elastic modulus (445 vs 426, p=0.36), or carotid beta stiffness (2.8 vs 2.8, p=0.86).Women with a prior hypertensive disorder of pregnancy had higher ASCVD risk and blood pressures several years postpartum, but did not have more endothelial dysfunction or subclinical atherosclerosis.

  View details for DOI 10.1016/j.ahj.2024.03.004

  View details for PubMedID 38484963

• Echogenomics: Echocardiography in Heritable Aortopathies. Current cardiology reports Hunter-Adamson, L., Tierney, S. 2024

  Abstract

  The aim of this article is to review the current echocardiographic considerations in the diagnosis and monitoring of patients with inherited aortopathies.Aortic dilation is a key feature in heritable aortopathies, and dissection is a leading cause of morbidity and mortality. New genetic and histopathologic findings are helpful in better understanding these conditions. Non-invasive imaging modalities, including echocardiogram, computerized tomography, and magnetic resonance imaging, are essential in monitoring these patients, as well as providing new prognostic factors of arterial stiffness that may help with risk stratification in the future. Diagnosis of heritable aortopathies should be considered with identification of aortic root dilation, particularly in children and young adults, or when there is a family history of aortic disease. Recent adult consensus guidelines highlight the importance of underlying genotype and phenotypic features when considering prophylactic surgical intervention. There are currently no consensus pediatric guidelines.

  View details for DOI 10.1007/s11886-024-02024-7

  View details for PubMedID 38372858

  View details for PubMedCentralID 7217141

• Cardiac Biomarkers Aid in Differentiation of Kawasaki Disease from Multisystem Inflammatory Syndrome in Children Associated with COVID-19. Pediatric cardiology Walton, M., Raghuveer, G., Harahsheh, A., Portman, M. A., Lee, S., Khoury, M., Dahdah, N., Fabi, M., Dionne, A., Harris, T. H., Choueiter, N., Garrido-Garcia, L. M., Jain, S., Dallaire, F., Misra, N., Hicar, M. D., Giglia, T. M., Truong, D. T., Tierney, E. S., Thacker, D., Nowlen, T. T., Szmuszkovicz, J. R., Norozi, K., Orr, W. B., Farid, P., Manlhiot, C., McCrindle, B. W. 2023

  Abstract

  Kawasaki disease (KD) and Multisystem Inflammatory Syndrome in Children (MIS-C) associated with COVID-19 show clinical overlap and both lack definitive diagnostic testing, making differentiation challenging. We sought to determine how cardiac biomarkers might differentiate KD from MIS-C. The International Kawasaki Disease Registry enrolled contemporaneous KD and MIS-C pediatric patients from 42 sites from January 2020 through June 2022. The study population included 118 KD patients who met American Heart Association KD criteria and compared them to 946 MIS-C patients who met 2020 Centers for Disease Control and Prevention case definition. All included patients had at least one measurement of amino-terminal prohormone brain natriuretic peptide (NTproBNP) or cardiac troponin I (TnI), and echocardiography. Regression analyses were used to determine associations between cardiac biomarker levels, diagnosis, and cardiac involvement. Higher NTproBNP (≥ 1500 ng/L) and TnI (≥ 20 ng/L) at presentation were associated with MIS-C versus KD with specificity of 77 and 89%, respectively. Higher biomarker levels were associated with shock and intensive care unit admission; higher NTproBNP was associated with longer hospital length of stay. Lower left ventricular ejection fraction, more pronounced for MIS-C, was also associated with higher biomarker levels. Coronary artery involvement was not associated with either biomarker. Higher NTproBNP and TnI levels are suggestive of MIS-C versus KD and may be clinically useful in their differentiation. Consideration might be given to their inclusion in the routine evaluation of both conditions.

  View details for DOI 10.1007/s00246-023-03338-z

  View details for PubMedID 38157048

  View details for PubMedCentralID 6831036

• Obesity and Outcomes of Kawasaki Disease and COVID-19-Related Multisystem Inflammatory Syndrome in Children. JAMA network open Khoury, M., Harahsheh, A. S., Raghuveer, G., Dahdah, N., Lee, S., Fabi, M., Selamet Tierney, E. S., Portman, M. A., Choueiter, N. F., Elias, M., Thacker, D., Dallaire, F., Orr, W. B., Harris, T. H., Norozi, K., Truong, D. T., Khare, M., Szmuszkovicz, J. R., Pagano, J. J., Manlhiot, C., Farid, P., McCrindle, B. W. 2023; 6 (12): e2346829

  Abstract

  Obesity may affect the clinical course of Kawasaki disease (KD) in children and multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19.To compare the prevalence of obesity and associations with clinical outcomes in patients with KD or MIS-C.In this cohort study, analysis of International Kawasaki Disease Registry (IKDR) data on contemporaneous patients was conducted between January 1, 2020, and July 31, 2022 (42 sites, 8 countries). Patients with MIS-C (defined by Centers for Disease Control and Prevention criteria) and patients with KD (defined by American Heart Association criteria) were included. Patients with KD who had evidence of a recent COVID-19 infection or missing or unknown COVID-19 status were excluded.Patient demographic characteristics, clinical features, disease course, and outcome variables were collected from the IKDR data set. Using body mass index (BMI)/weight z score percentile equivalents, patient weight was categorized as normal weight (BMI <85th percentile), overweight (BMI ≥85th to <95th percentile), and obese (BMI ≥95th percentile). The association between adiposity category and clinical features and outcomes was determined separately for KD and MIS-C patient groups.Of 1767 children, 338 with KD (median age, 2.5 [IQR, 1.2-5.0] years; 60.4% male) and 1429 with MIS-C (median age, 8.7 [IQR, 5.3-12.4] years; 61.4% male) were contemporaneously included in the study. For patients with MIS-C vs KD, the prevalence of overweight (17.1% vs 11.5%) and obesity (23.7% vs 11.5%) was significantly higher (P < .001), with significantly higher adiposity z scores, even after adjustment for age, sex, and race and ethnicity. For patients with KD, apart from intensive care unit admission rate, adiposity category was not associated with laboratory test features or outcomes. For patients with MIS-C, higher adiposity category was associated with worse laboratory test values and outcomes, including a greater likelihood of shock, intensive care unit admission and inotrope requirement, and increased inflammatory markers, creatinine levels, and alanine aminotransferase levels. Adiposity category was not associated with coronary artery abnormalities for either MIS-C or KD.In this international cohort study, obesity was more prevalent for patients with MIS-C vs KD, and associated with more severe presentation, laboratory test features, and outcomes. These findings suggest that obesity as a comorbid factor should be considered at the clinical presentation in children with MIS-C.

  View details for DOI 10.1001/jamanetworkopen.2023.46829

  View details for PubMedID 38064213

• Maternal Diabetes and Cardiovascular Health in the Offspring. Pediatric cardiology Jodah, R., Arunamata, A., Kipps, A. K., Chen, S., Stauffer, K. J., Selamet Tierney, E. S. 2023

  Abstract

  Pulse wave velocity (PWV) has been explored to predict cardiovascular health in adults. Less is known about neonatal PWV. We evaluated the association between arterial stiffness of neonates of mothers (NoM) with diabetes and childhood health.Neonatal brachial-femoral PWV (bfPWV) was measured after birth and neonates followed for a median of 5.2 years [1 month-6.6 years]. 36 pregnant women with pregestational diabetes mellitus PGDM (n= 12), gestational diabetes mellitus (GDM) (n = 13), and controls (n= 11) were enrolled. Neonates were similar in weight, gestational age, and delivery mode. 26 neonates had follow-up data including weight, height and blood pressure.More mothers with PGDM had poor glycemic control compared to mothers with GDM (83% vs. 8%; p =0.0002). PWV was higher in NoM with PGDM than controls (3.4± 0.5 vs. 2.6±0.8 m/s; p= 0.04). At follow-up, children of mothers with diabetes (n= 16) had higher weight percentile (78.5 ± 27.9 vs 49.5± 34.6%; p= 0.02) and diastolic blood pressure (DBP) (68± 13.6 vs 57.3± 4.3mmHg; p=0.01) than controls (n = 10). No correlation emerged between neonatal PWV and childhood body mass index (BMI) or maternal HbA1c. Results suggest maternal diabetes affect neonatal arterial stiffness and childhood blood pressure; however, the mechanism is unclear. The long-term implications of these findings warrant further investigation.

  View details for DOI 10.1007/s00246-023-03333-4

  View details for PubMedID 37930377

• Outpatient Pediatric Cardiology Follow-Up of Patients with Multisystem Inflammatory Syndrome in Children (MIS-C): A Single-Institution, Medium-Term Follow-Up Study. Pediatric cardiology Jose, J. T., Tierney, E. S. 2023

  Abstract

  We are continuing to learn about the multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2 infection. There are many published studies regarding the acute management of MIS-C; however, there is still much to learn regarding the long-term outcomes of patients with MIS-C. In this study, we report the outcomes of patients admitted at our institution with MIS-C and the follow-up practices in Pediatric Cardiology over the last three years. We included patients who were admitted at Lucile Packard Children's Hospital between January 1, 2020 and October 31, 2022, who met the CDC criteria for MIS-C, and were followed in the Pediatric Cardiology Outpatient Clinic at our institution. There were 25 patients who met our inclusion criteria. Eighteen patients (72%) had their initial follow-up visit within 1-2 weeks of discharge and seven patients (28%) had their initial follow-up visit within 4-6 weeks of discharge. Six patients out of the 25 (24%) had decreased left ventricular ejection fraction (LVEF < 50%) during their hospitalization. No patients had left main coronary artery aneurysm (z-score > 2.5), two patients (8%) had proximal right coronary artery aneurysm (z-score > 2.5), and one patient (4%) had left anterior descending coronary artery aneurysm (z-score > 2.5) during hospitalization. Patients who were admitted with the diagnosis of MIS-C showed normalization of left ventricular dysfunction at their initial follow-up visit as early as 2-4 weeks after discharge. In this cohort of MIS-C patients, a 4-6-week window for the first follow-up visit after discharge seems reasonable.

  View details for DOI 10.1007/s00246-023-03298-4

  View details for PubMedID 37749261

  View details for PubMedCentralID 5669166

• Kawasaki Disease in the Time of COVID-19 and MIS-C - The International Kawasaki Disease Registry. The Canadian journal of cardiology Harahsheh, A. S., Shah, S., Dallaire, F., Manlhiot, C., Khoury, M., Lee, S., Fabi, M., Mauriello, D., Selamet Tierney, E. S., Sabati, A. A., Dionne, A., Dahdah, N., Choueiter, N., Thacker, D., Giglia, T. M., Truong, D. T., Jain, S., Portman, M., Orr, W. B., Harris, T. H., Szmuszkovicz, J. R., Farid, P., McCrindle, B. W. 2023

  Abstract

  Patients with Multisystem Inflammatory Syndrome in Children (MIS-C) and Kawasaki disease (KD) have overlapping clinical features. We compared demographics/clinical presentation, management, and outcomes of patients by evidence of prior SARS-CoV-2 infection.The International KD Registry (IKDR) enrolled KD and MIS-C patients from sites from North, Central and South America, Europe, Asia and Middle East. Evidence of prior infection was defined as: Positive (+ve household contact or positive PCR/serology), Possible (suggestive clinical features of MIS-C and/or KD with negative PCR or serology but not both), Negative (negative PCR and serology and no known exposure), and Unknown (incomplete testing and no known exposure).Of 2345 enrolled patients SARS-CoV-2 status was Positive for 1541 (66%) patients, Possible 89 (4%), Negative 404 (17%) and Unknown for 311 (13%) patients. Clinical outcomes varied significantly between the groups, with more patients in the Positive/Possible groups presenting with shock, having admission to Intensive Care, receiving inotropic support, and having longer hospital stays. Regarding cardiac abnormalities, patients in the Positive/Possible groups had a higher prevalence of left ventricular dysfunction, while patients in the Negative and Unknown groups had more severe coronary artery abnormalities. results CONCLUSION: : There appears to be a spectrum of clinical features from MIS-C to KD with a great deal of heterogeneity, and one primary differentiating factor is evidence for prior acute SARS CoV2 infection/exposure. SARS-CoV-2 Positive/Possible patients had more severe presentations and required more intensive management, with a greater likelihood of ventricular dysfunction but less severe coronary artery adverse outcomes, in keeping with MIS-C.

  View details for DOI 10.1016/j.cjca.2023.06.001

  View details for PubMedID 37290536

• Design and Rationale of RE-ENERGIZE FONTAN: RandomizEd Exercise iNtERvention desiGned to maximIZE fitness in FONTAN patients. American heart journal Tierney, E. S., Palaniappan, L., Leonard, M., Long, J., Myers, J., Dávila, T., Lui, M. C., Kogan, F., Olson, I., Punn, R., Desai, M., Schneider, L. M., Wang, C. H., Cooke, J. P., Bernstein, D. 2023

  Abstract

  In this manuscript, we describe the design and rationale of a randomized controlled trial in pediatric Fontan patients to test the hypothesis that a live-video-supervised exercise (aerobic+resistance) intervention will improve cardiac and physical capacity; muscle mass, strength, and function; and endothelial function. Survival of children with single ventricles beyond the neonatal period has increased dramatically with the staged Fontan palliation. Yet, long-term morbidity remains high. By age 40, 50% of Fontan patients will have died or undergone heart transplantation. Factors that contribute to onset and progression of heart failure in Fontan patients remain incompletely understood. However, it is established that Fontan patients have poor exercise capacity which is associated with a greater risk of morbidity and mortality. Furthermore, decreased muscle mass, abnormal muscle function, and endothelial dysfunction in this patient population is known to contribute to disease progression. In adult patients with two ventricles and heart failure, reduced exercise capacity, muscle mass, and muscle strength are powerful predictors of poor outcomes, and exercise interventions can not only improve exercise capacity and muscle mass, but also reverse endothelial dysfunction. Despite these known benefits of exercise, pediatric Fontan patients do not exercise routinely due to their chronic condition, perceived restrictions to exercise, and parental overprotection. Limited exercise interventions in children with congenital heart disease have demonstrated that exercise is safe and effective; however, these studies have been conducted in small, heterogeneous groups, and most had few Fontan patients. Critically, adherence is a major limitation in pediatric exercise interventions delivered on-site, with adherence rates as low as 10%, due to distance from site, transportation difficulties, and missed school or workdays. To overcome these challenges, we utilize live-video conferencing to deliver the supervised exercise sessions. Our multidisciplinary team of experts will assess the effectiveness of a live-video-supervised exercise intervention, rigorously designed to maximize adherence, and improve key and novel measures of health in pediatric Fontan patients associated with poor long-term outcomes. Our ultimate goal is the translation of this model to clinical application as an "exercise prescription" to intervene early in pediatric Fontan patients and decrease long-term morbidity and mortality.

  View details for DOI 10.1016/j.ahj.2023.02.006

  View details for PubMedID 36796574

• COVID-19 Positive Versus Negative Complete Kawasaki Disease: A Study from the International Kawasaki Disease Registry. Pediatric cardiology Jose, J., Tierney, E. S., Harahsheh, A. S., Dahdah, N., Raghuveer, G., Friedman, K. G., Khoury, M., Hicar, M. D., Merves, S. A., Dallaire, F., Farid, P., Manlhiot, C., Runeckles, K., Misra, N., Portman, M., Ballweg, J. A., Lee, S., Jain, S. S., Harris, T. H., Szmuszkovicz, J. R., Orr, W., Larios, G., McCrindle, B. W. 2023: 1-9

  Abstract

  To determine clinical differences for children with complete Kawasaki disease (KD) with and without evidence of preceding SARS-CoV-2 infection. From January 2020, contemporaneous patients with complete KD criteria were classified as either SARS-CoV-2 positive (KDCOVID+; confirmed household exposure, positive PCR and/or serology) or SARS-CoV-2 negative (KDCOVID-; negative testing and no exposure) and compared. Of 744 patients in the International Kawasaki Disease Registry, 52 were KDCOVID- and 61 were KDCOVID+. KDCOVID+ patients were older (median 5.5 vs. 3.7 years; p < 0.001), and all additionally met diagnostic criteria for multisystem inflammatory syndrome in children (MIS-C). They were more likely to have abdominal pain (60% vs. 35%; p = 0.008) and headache (38% vs. 10%; p < 0.001) and had significantly higher CRP, troponin, and BUN/creatinine, and lower hemoglobin, platelets, and lymphocytes. KDCOVID+ patients were more likely to have shock (41% vs. 6%; p < 0.001), ICU admission (62% vs. 10%; p < 0.001), lower left ventricular ejection fraction (mean lowest LVEF 53% vs. 60%; p < 0.001), and to have received inotropic support (60% vs. 10%; p < 0.001). Both groups received IVIG (2 doses in 22% vs. 18%; p = 0.63), but KDCOVID+ were more likely to have received steroids (85% vs. 35%; p < 0.001) and anakinra (60% vs. 10%; p = 0.002). KDCOVID- patients were more likely to have medium/large coronary artery aneurysms (CAA, 12% vs. 0%; p = 0.01). KDCOVID+ patients differ from KDCOVID-, have more severe disease, and greater evidence of myocardial involvement and cardiovascular dysfunction rather than CAA. These patients may be a distinct KD phenotype in the presence of a prevalent specific trigger.

  View details for DOI 10.1007/s00246-023-03109-w

  View details for PubMedID 36786810

  View details for PubMedCentralID PMC9926414

• Emerging Insights into the Pathophysiology of Multi-system Inflammatory Syndrome in Children Associated with COVID-19. The Canadian journal of cardiology Lin, J., Harahsheh, A. S., Raghuveer, G., Jain, S., Chouieter, N. F., Garrido-Garcia, L. M., Dahdah, N., Portman, M. A., Misra, N., Khoury, M., Fabi, M., Elias, M. D., Dionne, A., Lee, S., Selamet Tierney, E. S., Ballweg, J. A., Manlhiot, C., McCrindle, B. W. 2023

  Abstract

  Multisystem inflammatory syndrome in children (MIS-C) has emerged as a rare, delayed hyperinflammatory response to SARS-CoV-2 infection, and causes severe morbidity in the pediatric age group. While MIS-C shares many clinical similarities to Kawasaki disease (KD), important differences in epidemiologic, clinical, immunologic and potentially genetic factors exist and suggest potential differences in pathophysiology and points to be explored and explained. Epidemiologic features include male predominance, peak age of 6-12 years, and specific racial and/or ethnicity predilections. MIS-C is characterized by fever, prominent gastrointestinal symptoms, mucocutaneous manifestations, respiratory symptoms, and neurological complaints, and patients often present with shock. Cardiac complications are frequent and include ventricular dysfunction, valvular regurgitation, pericardial effusion, coronary artery dilation and aneurysms, conduction abnormalities, and arrhythmias. Emerging evidence regarding potential immunologic mechanisms suggest that an exaggerated T-cell response to a superantigen on the SARS-CoV-2 spike glycoprotein, as well as the formation of autoantibodies against cardiovascular, gastrointestinal, and endothelial antigens, are major contributors to the inflammatory milieu of MIS-C. Further studies are needed to determine both shared and distinct immunologic pathway(s) that underlie the pathogenesis of MIS-C versus both acute SARS-CoV-2 infcction and KD. There is evidence to suggest that the rare risk of more benign mRNA vaccine -associated myopericarditis is outweighed by a reduced risk of more severe MIS-C. In the current review, we synthesize the published literature to describe associated factors and potential mechanisms regarding an increased risk of MIS-C and cardiac complications, provide insights into the underlying immunologic pathophysiology, and define similarities and differences with KD.

  View details for DOI 10.1016/j.cjca.2023.01.002

  View details for PubMedID 36626979

• Outpatient monitoring of patients with multisystem inflammatory syndrome (MIS-C): A mini review. Frontiers in pediatrics Jose, J. T., Selamet Tierney, E. S. 2022; 10: 1069632

  Abstract

  As we learn more about the novel multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19 infection, the protocols for long-term follow-up have evolved and only some of these protocols have been published. Here, we review the current literature on follow-up guidelines in MIS-C patients.We conducted a PUBMED search of all articles published on "MIS-C" and the term "follow-up" between 2020 and 2022. Inclusion criteria were that (1) the study was an observational study or case series, and (2) the study population included pediatric population who met the diagnostic criteria for MIS-C.There were 206 publications on MIS-C and follow-up in the last 2 years with 11 studies that fit the inclusion criteria. These papers were representing 11 different centers and encompassed a total of 343 participants. Seven of the 11 studies had participants follow-up with their cardiologist within 1 month of discharge. Between 12% and 62% of patients within each study had depressed left ventricular ejection fraction (LVEF) at admission. At the initial follow-up visit, five studies showed a normal LVEF in all patients while the other seven studies showed 2%-13% patients continuing to have depressed LVEF. In eight of the 11 studies, 9%-52% of patients had coronary artery dilation at admission. At their initial follow-up visit, 3%-28% of patients continued to have coronary artery dilation.There is some institutional variation in the outpatient follow-up protocols in patients diagnosed with MIS-C. A standardized follow-up guidelines might be helpful to monitor long-term prognosis of these patients.

  View details for DOI 10.3389/fped.2022.1069632

  View details for PubMedID 36568433

  View details for PubMedCentralID PMC9768426

• Can 10 000 Healthy Steps a Day Slow Aortic Root Dilation in Pediatric Patients With Marfan Syndrome? Journal of the American Heart Association Selamet Tierney, E. S., Chung, S., Stauffer, K. J., Brabender, J., Collins, R. T., Folk, R., Li, W., Murthy, A. K., Murphy, D. J., Esfandiarei, M. 2022: e027598

  Abstract

  Background Stiffer aortas are associated with a faster rate of aortic root (AoR) dilation and higher risk of aortic dissection in patients with Marfan syndrome. We have previously shown that mild aerobic exercise reduces aortic stiffness and rate of AoR dilation in a Marfan mouse model. In this study, we investigated if these results could be translated to pediatric patients with Marfan syndrome. Methods and Results We enrolled 24 patients with Marfan syndrome aged 8 to 19 years to participate in a 6-month physical activity intervention, excluding those with ventricular dysfunction or prior history of aortic surgery. We instructed patients to take 10 000 steps per day, tracked by an activity tracker. At baseline and 6 months, we measured AoR dimension, arterial stiffness, endothelial function, physical activity indices, inflammatory biomarkers, and coping scores. Controls consisted of 15 age-matched patients with Marfan syndrome. Twenty-four patients with Marfan syndrome (median age, 14.4 years [interquartile range {IQR}, 12.2-16.8], 14 male patients) were enrolled. Baseline assessment demonstrated that the majority of these patients were sedentary and had abnormal arterial health. Twenty-two patients completed the intervention and took an average of 7709±2177 steps per day (median, 7627 [IQR, 6344-9671]). Patients wore their Garmin trackers at a median of 92.8% (IQR, 84%-97%) of their intervention days. AoR Z score in the intervention group had a significantly lower rate of change per year compared with the controls (rate of change, -0.24 versus +0.008; P=0.01). Conclusions In this clinical intervention in pediatric patients with Marfan syndrome, we demonstrated that a simple physical activity intervention was feasible in this population and has the potential to decrease the AoR dilation rate. REGISTRATION URL: https://www.clinicaltrials.gov; Unique identifier: NCT03567460.

  View details for DOI 10.1161/JAHA.122.027598

  View details for PubMedID 36453629

• Quality Improvement in a Pediatric Echocardiography Laboratory: A Collaborative Process. Children (Basel, Switzerland) Sganga, D., Behera, S., Beattie, M. J., Stauffer, K. J., Burlinson, A., Lopez, L., Tierney, E. S. 2022; 9 (12)

  Abstract

  Transthoracic echocardiography (TTE) is an essential tool for diagnosis and management of congenital heart disease. Pediatric echocardiography presents unique challenges including complex anatomy, variable patient cooperation and provider expertise. Diagnostic errors inevitably occur. We designed a collaborative and stepwise quality improvement (QI) process to address diagnostic errors within our laboratory. We retrospectively reviewed medical records to identify diagnostic TTE errors in 100 consecutive cardiac surgery patients ≤ 5 years old (July 2020-January 2021). We identified 18 diagnostic errors. Most errors had minor impact (14/18), and 13 were preventable or possibly preventable. We presented these results to our sonographers and faculty and requested input on preventing and managing diagnostic errors. Our root cause analysis based on their responses yielded 7 areas for improvement (imaging, reporting, systems, time, environment, people, QI processes). Our faculty and sonographers chose QI processes and imaging as initial areas for intervention. We defined our SMART goal as a 10% reduction in diagnostic errors. We implemented interventions focused on QI processes. On initial follow up in May 2022, we identified 7 errors in 70 patients (44% reduction in error rate). Utilizing a stepwise and team-based approach, we successfully developed QI initiatives in our echocardiography laboratory. This approach can serve as a model for a collaborative QI process in other institutions.

  View details for DOI 10.3390/children9121845

  View details for PubMedID 36553289

  View details for PubMedCentralID PMC9776848

• Paediatrician's guide to post-operative care for biventricular CHD: a review. Cardiology in the young Arthur, L., Renno, M. S., Altman, C. A., Batlivala, S. P., Glickstein, J., Johnson, J. N., Miller, J. R., Nguyen, Q., Selamet Tierney, E. S., Ronai, C. 2022: 1-7

  Abstract

  IMPORTANCE: Paediatricians play an integral role in the lifelong care of children with CHD, many of whom will undergo cardiac surgery. There is a paucity of literature for the paediatrician regarding the post-operative care of such patients.OBSERVATIONS: The aim of this manuscript is to summarise essential principles and pertinent lesion-specific context for the care of patients who have undergone surgery or intervention resulting in a biventricular circulation.CONCLUSIONS AND RELEVANCE: Familiarity with common issues following cardiac surgery or intervention, as well as key details regarding specific lesions and surgeries, will aid the paediatrician in providing optimal care for these patients.

  View details for DOI 10.1017/S1047951122002955

  View details for PubMedID 36165406

• Paediatrician's guide to post-operative care for functionally univentricular CHD: a review. Cardiology in the young Ronai, C., Batlivala, S. P., Nguyen, Q., Renno, M. S., Arthur, L., Glickstein, J., Johnson, J. N., Miller, J. R., Altman, C. A., Selamet Tierney, E. S. 2022: 1-7

  Abstract

  IMPORTANCE: Single ventricle CHD affects about 5 out of 100,000 newborns, resulting in complex anatomy often requiring multiple, staged palliative surgeries. Paediatricians are an essential part of the team that cares for children with single ventricle CHD. These patients often encounter their paediatrician first when a complication arises, so it is critical to ensure the paediatrician is knowledgeable of these issues to provide optimal care.OBSERVATIONS: We reviewed the subtypes of single ventricle heart disease and the various palliative surgeries these patients undergo. We then searched the literature to detail the general paediatrician's approach to single ventricle patients at different stages of surgical palliation.CONCLUSIONS AND RELEVANCE: Single ventricle patients undergo staged palliation that drastically changes physiology after each intervention. Coordinated care between their paediatrician and cardiologist is requisite to provide excellent care. This review highlights what to expect when these patients are seen by their paediatrician for either well child visits or additional visits for parental or patient concern.

  View details for DOI 10.1017/S1047951122002943

  View details for PubMedID 36148873

• Minute Stroke Distance is a More Reproducible Measurement Than Cardiac Output in the Assessment of Fetal Ventricular Systolic Function. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Sun, H. Y., Selamet Tierney, E. S., Tacy, T. A., Punn, R. 2022

  Abstract

  Echocardiographic quantification of fetal cardiac output (CO) aids clinical decision-making in the management of various cardiac and extracardiac diseases. Small variability in measuring semilunar valve dimension significantly reduces the reproducibility of the calculated CO. We propose minute stroke distance or velocity-time integral (VTI) as a more reproducible measure reflecting fetal ventricular systolic function. We hypothesized that right and left ventricular minute VTI increase predictably with estimated fetal weight (EFW) and are more reproducible than CO.571 singleton fetuses without cardiovascular pathology between 16-36 weeks gestation were reviewed retrospectively. 22 fetuses with pathology resulting in low or high cardiac output states were also assessed for comparison. VTI was measured in both ventricular outflow tracts at the level of the semilunar valve, excluding a Doppler insonation angle >30°. Heart rate, semilunar valve dimension, and VTI determined minute VTI and CO. Inter-/intra-rater variability were evaluated in a random 10% subset.Minute VTI and CO measurements were feasible in 67-89% of fetuses in this retrospective study. Minute VTI and CO increased with EFW non-linearly (R=0.61 - 0.94). The mean inter-/intra-rater variability for VTI, 6% and 5.7%, were significantly less than for CO, 25% and 23.7% (p<0.001 for all).Minute VTI is an easily measured, highly reproducible method of quantifying fetal ventricular systolic function. Variability in calculated CO from valve measurement differences is minimized by solely using VTI. Nomograms of minute VTI provide an efficient and precise assessment of fetal systolic function, and may be utilized to track fetuses in disease states with low or high cardiac output.

  View details for DOI 10.1016/j.echo.2022.08.007

  View details for PubMedID 35973561

• Physicians' Self-reported Exercise Testing and Physical Activity Recommendations in Kawasaki Patients. Pediatric cardiology Hansen, K., Grady, S., McCrindle, B. W., Harahsheh, A. S., Elias, M. D., Dahdah, N., Selamet Tierney, E. S. 2022

  Abstract

  Recommendations for management of patients with Kawasaki disease (KD) and coronary artery aneurysms (CAA) include physical activity (PA) promotion. This study aimed to characterize self-reported practices of KD providers to evaluate practice variation in use of cardiopulmonary exercise testing (CPET) and PA recommendations. We developed a REDCap survey with different clinical scenarios of KD patients. It was completed by members of the International Kawasaki Disease Registry (IKDR) and community pediatric cardiologists. Twenty-eight physicians responded; 63% practiced in the US, 63% practiced in an academic setting, 48% were general pediatric cardiologists, and 55% were IKDR members. Most respondents (69%) followed < 50 KD patients. The great majority (93%) agreed that patients with no CAA do not require CPET and could be cleared for all PA. For patients with small CAA, 43% of respondents recommended CPET and 75% cleared for all PA if CAAs regressed completely, but only 32% cleared if CAA persisted. For patients with medium CAA, 66% respondents cleared for PA if CAA regressed, and only 7% if CAA persisted; with 66% and 75% recommending CPET, respectively. For patients with large/giant CAA, 81% of respondents recommended CPET. No respondents felt comfortable clearing their patients with persistent large/giant CAA for PA and 19% would restrict from the entire physical education program. There is practice variation in use of CPET in KD patients with CAAs. Providers are hesitant to promote PA in KD patients with CAA despite known benefits and current guidelines.

  View details for DOI 10.1007/s00246-022-02984-z

  View details for PubMedID 35953605

• Association of Acute Anti-inflammatory Treatment With Medium-term Outcomes for Coronary Artery Aneurysms in Kawasaki Disease. CJC pediatric and congenital heart disease Friedman, K. G., McCrindle, B. W., Runeckles, K., Dahdah, N., Harahsheh, A. S., Khoury, M., Lang, S., Manlhiot, C., Tremoulet, A. H., Raghuveer, G., Selamet Tierney, E. S., Jone, P., Li, J. S., Szmuszkovicz, J. R., Norozi, K., Jain, S. S., Yetman, A. T., Newburger, J. W., International Kawasaki Disease Registry, Altman, C. A., Anderson, B. R., Beckley, M., Braunlin, E., Burns, J. C., Carr, M. R., Choueiter, N. F., Colyer, J. H., Dallaire, F., De Ferranti, S. D., Desjardins, L., Elias, M. D., Ferris, A., Gewitz, M., Giglia, T. M., Greenway, S. C., Harris, K. C., Hill, K. D., Hite, M., Kimball, T. R., Kutty, S., Lai, L., Lee, S., Lin, M., Low, T., Mackie, A. S., Mawad, W., McHugh, K. E., Mondal, T., Myers, K., Portman, M. A., Renaud, C., Scuccimarri, R., Sexson Tejitel, S. K., Texter, K. M., Thacker, D., Wagner-Lees, S., Wong, K., Wu, M., Zadokar, V. 2022; 1 (4): 174-183

  Abstract

  Background: The impact of adjunctive anti-inflammatory treatment on outcomes for patients with Kawasaki disease (KD) and coronary artery aneurysms (CAAs) is unknown.Methods: Using data from the International KD Registry in patients with ≥ medium CAA we evaluate associations of treatment with outcomes and major adverse cardiac events (MACE).Results: Medium or large CAA was present in 527 (32%) patients. All were treated with intravenous immunoglobulin (IVIG), 70% were male, and the median age was 1.3 years (interquartile range: 0.4-4.0 years). The most common acute therapies included single IVIG alone in 243 (46%), multiple IVIG in 100 (19%), multiple IVIG+ corticosteroids in 75 (14%), and multiple IVIG+ infliximab+ corticosteroids in 44 (8%) patients. Patients who received therapy beyond single IVIG had a larger CA z-score at baseline (P < 0.001) and a higher rate of bilateral CAA (P< 0.001). Compared with IVIG alone, early adjunctive treatments (within 3 days of initial IVIG) were not associated with time to CAA regression or MACE, whereas later adjunctive therapy was associated with MACE and longer time to CAA regression. Patients receiving IVIG plus steroids vs IVIG alone had a trend towards shorter time to CAA regression and lower risk of MACE (P= 0.07). A larger CAA z-score at baseline was the strongest predictor of an increase in the CAA z-score over follow-up, lower likelihood of CAA regression, and higher risk of MACE.Conclusions: Persistence of CAA and MACE are more strongly associated with baseline severity CAA than with acute adjuvant anti-inflammatory therapy. Patients who received late adjunctive therapy are at higher risk for worse outcomes.

  View details for DOI 10.1016/j.cjcpc.2022.05.007

  View details for PubMedID 37969928

• Pediatric Heart Network Trial of Losartan vs. Atenolol in Children and Young Adults with Marfan Syndrome: Impact on Prescription Practices. Pediatric cardiology Robertson, D. M., Truong, D. T., Cox, D. A., Carmichael, H. L., Ou, Z., Minich, L. L., Williams, R. V., Selamet Tierney, E. S. 2022

  Abstract

  The Pediatric Heart Network (PHN) trial showed similar efficacy of beta-blockers (BB) and angiotensin receptor blockers (ARB) for aortic root dilation in Marfan syndrome, but the impact on prescription practices is unknown. We hypothesized BB and ARB prescriptions would increase after the trial results were published (2014). Prescription data (2007-2016) were obtained from outpatient encounters (IBM Marketscan) for Marfan syndrome patients (6months-25years old). Excluding 2014 as a washout period, we analyzed two intervals: 2007-2013 and 2015-2016. Medication categories included BB, ARB, angiotensin converting enzyme inhibitors (ACEI), combination (BB/ARB and/or BB/ACEI), and no drug. Interrupted time-series analysis assessed immediate level change after publication and change in slope for the trend pre- and post-publication. Odds ratios (OR) and 95% confidence intervals from logistic regressions and generalized estimating equation methods accounted for correlation of prescriptions within patients. In 1499 patients (age 14.1±6.1years, 59% female) seen 2007-2013, BB trended lower [OR 0.91 (0.89, 0.93), p<0.001] and ARB trended higher [OR 1.12 (1.07, 1.18), p<0.001], while combination, ACEI, and no drug remained stable. This trend persisted, but was not significant, for BB [OR 0.54 (0.27, 1.08), p=0.37] and ARB [OR 1.91 (0.55, 6.69), p=0.31] in 2015-2016. Combination, ACEI, and no drug remained similar. In short term follow-up, changes in prescription practices following publication of the PHN trial were not statistically significant. This may be due to a change seen prior to publication with early adoption of ARBs that was maintained after confirmation of their effectiveness.

  View details for DOI 10.1007/s00246-022-02976-z

  View details for PubMedID 35902413

• Intraoperative epicardial echocardiography or transoesophageal echocardiography in CHD: how much does it matter? Cardiology in the young Stauffer, K. J., Brabender, J., Reddy, C. D., Selamet Tierney, E. S., Lopez, L., Maeda, K., Navaratnam, M., Punn, R. 2022: 1-8

  Abstract

  BACKGROUND: Intraoperative imaging determines the integrity of surgical repairs. Transoesophageal echocardiography represents standard care for intraoperative imaging in CHD. However, some conditions preclude its use, and epicardial echocardiography is used alternatively. Minimal literature exists on the impact of epicardial echocardiography versus transoesophageal echocardiography. We aimed to evaluate accuracy between the two modalities and hypothesised higher imaging error rates for epicardial echocardiography.METHODS: We retrospectively reviewed all epicardial echocardiograms performed over 16 years and compared them to an age- and procedure-matched, randomly selected transoesophageal echocardiography cohort. We detected un- or misidentified cardiac lesions during the intraoperative imaging and evaluated patient outcomes. Data are presented as a median with a range, or a number with percentages, with comparisons by Wilcoxon two-sample test and Fisher's exact test.RESULTS: Totally, 413 patients comprised the epicardial echocardiography group with 295 transoesophageal echocardiography matches. Rates of imaging discrepancies, re-operation, and incision infection were similar. About 13% of epicardial echocardiography patients had imaging discrepancies versus 16% for transoesophageal (p = 0.2352), the former also had smaller body sizes (p < 0.0001) and more genetic abnormalities (33% versus 19%, p < 0.0001). Death/mechanical support occurred more frequently in epicardial echocardiography patients (16% versus 6%, p < 0.0001), while hospitalisations were longer (25 versus 19 days, p = 0.0003).CONCLUSIONS: Diagnostic accuracy was similar between patients undergoing epicardial echocardiography and transoesophageal echocardiography, while rates of death and mechanical support were increased in this inherently higher risk patient population. Epicardial echocardiography provides a reasonable alternative when transoesophageal echocardiography is not feasible.

  View details for DOI 10.1017/S1047951122001536

  View details for PubMedID 35747949

• Aortic root dilation in adult patients with Marfan syndrome: Does aortic root stiffness matter? JTCVS open Cox, K., Oquendo, Y. A., Liang, D., Selamet Tierney, E. S. 2022; 10: 113-120

  Abstract

  Objective: Aortic root (AoR) size remains an imperfect predictor of rate of aortic dilation in Marfan syndrome (MFS). Indicators of vascular phenotype such as aortic stiffness have been proposed as additional predictors. In this study we assessed the rate of AoR dilation and stiffness in adult patients with MFS.Methods: We performed a retrospective chart review. We included adult patients with MFS (aged 20-40years) with at least 2 local echocardiograms 6months apart (no aortic surgery in-between). A blinded observer analyzed the echocardiograms. AoR dilation rate and stiffness were calculated.Results: Thirty-two patients (53% women; median age, 21.1; interquartile range [IQR], 19-24years at first echocardiogram) were included. AoR dilation rate in the entire cohort was 0 to 8mm/year (median, 0.465; IQR, 0.23-1.45mm/year). Multiple linear regression analysis showed that baseline AoR stiffness was associated with AoR dilation rate (beta=0.0004; P<.001 for elastic modulus), whereas baseline age and baseline AoR dimension were not. Eighteen of these 32 patients (56%) eventually had AoR surgery (Sx) and 14 did not have surgery (NSx). At baseline, Sx and NSx patients were similar in age. AoR dimension was larger (Sx, 4.27cm; IQR, 4.05-4.49cm vs NSx, 3.73cm; IQR, 3.37-4.09cm; P=.011) and AoR stiffness was higher in Sx patients (beta stiffness index: median, 23.2; IQR, 17.8-28.6 vs median, 15.6; IQR, 11.6-19.7; P=.024). AoR dilation rate was greater in Sx patients, independent of baseline AoR dimension (1.63±0.41mm/year vs 0.38±0.08mm/year; P=.01).Conclusions: Our results showed that AoR dilation rate varies among adult patients with MFS and is associated with baseline AoR stiffness, measured by echocardiography. Further studies are warranted to determine how aortic stiffness can be implemented clinically to refine management in patients with MFS.

  View details for DOI 10.1016/j.xjon.2022.04.011

  View details for PubMedID 36004220

• Exercise Capacity and Training Programs in Paediatric Fontan Patients: A Systematic Review. CJC pediatric and congenital heart disease Herrmann, J. E., Selamet Tierney, E. S. 2022; 1 (3): 108-118

  Abstract

  Exercise training programs can effectively enhance exercise capacity in adults with congenital heart disease, including Fontan patients. However, few studies have explored the impact of exercise training exclusively on paediatric Fontan cohorts. This study systematically reviews exercise capacity in paediatric Fontan patients and the impact of training programs on their cardiovascular health.Medline and Embase were searched for articles published between January 1990 and November 2021. Studies were included in which data could be analyzed discretely for patients who had undergone the Fontan procedure and were ≤20 years old at the time of study. Cardiopulmonary exercise parameters were extracted from all studies, and training protocols were collected from training programs.The studies demonstrated that Fontan patients exhibit significantly diminished peak exercise capacity relative to healthy peers. We identified 9 training programs that exclusively studied Fontan patients ≤20 years. The programs ranged from 6 weeks to 12 months in duration, with 8 programs incorporating aerobic activity and 1 focused only on inspiratory muscle training. At least 1 measure of maximal or submaximal exercise capacity improved significantly within each program in which statistical analysis was performed, with no reported adverse events. There were 2 additional training programs in which the patients were predominantly (>65%), but not exclusively, Fontan patients.Overall, the results indicate that exercise training programs can safely and effectively improve at least 1 measure of exercise capacity in paediatric Fontan patients.

  View details for DOI 10.1016/j.cjcpc.2022.04.005

  View details for PubMedID 37970491

  View details for PubMedCentralID PMC10642096

• Molecular characterization and investigation of the role of genetic variation in phenotypic variability and response to treatment in a large pediatric Marfan syndrome cohort. Genetics in medicine : official journal of the American College of Medical Genetics Meester, J. A., Peeters, S., Van Den Heuvel, L., Vandeweyer, G., Fransen, E., Cappella, E., Dietz, H. C., Forbus, G., Gelb, B. D., Goldmuntz, E., Hoskoppal, A., Landstrom, A. P., Lee, T., Mital, S., Morris, S., Olson, A. K., Renard, M., Roden, D. M., Singh, M. N., Selamet Tierney, E. S., Tretter, J. T., Van Driest, S. L., Willing, M., Verstraeten, A., Van Laer, L., Lacro, R. V., Loeys, B. L. 1800

  Abstract

  PURPOSE: In a large cohort of 373 pediatric patients with Marfan syndrome (MFS) with a severe cardiovascular phenotype, we explored the proportion of patients with MFS with a pathogenic FBN1 variant and analyzed whether the type/location of FBN1 variants was associated with specific clinical characteristics and response to treatment. Patients were recruited on the basis of the following criteria: aortic root z-score > 3, age 6 months to 25 years, no prior or planned surgery, and aortic root diameter < 5 cm.METHODS: Targeted resequencing and deletion/duplication testing of FBN1 and related genes were performed.RESULTS: We identified (likely) pathogenic FBN1 variants in 91% of patients. Ectopia lentis was more frequent in patients with dominant-negative (DN) variants (61%) than in those with haploinsufficient variants (27%). For DN FBN1 variants, the prevalence of ectopia lentis was highest in the N-terminal region (84%) and lowest in the C-terminal region (17%). The association with a more severe cardiovascular phenotype was not restricted to DN variants in the neonatal FBN1 region (exon 25-33) but was also seen in the variants in exons 26 to 49. No difference in the therapeutic response was detected between genotypes.CONCLUSION: Important novel genotype-phenotype associations involving both cardiovascular and extra-cardiovascular manifestations were identified, and existing ones were confirmed. These findings have implications for prognostic counseling of families with MFS.

  View details for DOI 10.1016/j.gim.2021.12.015

  View details for PubMedID 35058154

• Every child with congenital heart disease should be exercising. Current opinion in cardiology Hansen, K., Tierney, S. 2021

  Abstract

  PURPOSE OF REVIEW: Historically, children with congenital heart disease have been restricted from exercise, contributing to a sedentary lifestyle as well as increased cardiovascular risk factors. Given the large benefits and small risks of exercise in this population, guidelines have recently shifted towards exercise promotion. However, these recommendations have yet not gained traction and children with congenital heart disease continue to live sedentary lives. The purpose of this review is to summarize the current literature on exercise and exercise promotion in this population.RECENT FINDINGS: New literature reinforces the importance of recommending exercise and improving exercise capacity both in congenital heart disease in general and for specific lesions. Exercise recommendations should be individualized based on functional parameters using a structured methodology to approach the evaluation, risk classification, and prescriptions of exercise and physical activity.SUMMARY: Regular exercise is essential for children with congenital heart disease and providers must take an active role in providing exercise recommendations for their patients. Exercise promotion remains a challenge, necessitating novel approaches to promote exercise. Further studies are needed to improve the risk stratification of patients with congenital heart disease, assess the long-term outcomes of specific exercise interventions, and inform individualized recommendations to encourage children with congenital heart disease to safely engage in exercise and establish healthy lifelong habits that will decrease their cardiovascular risk.

  View details for DOI 10.1097/HCO.0000000000000931

  View details for PubMedID 34608879

• Nomenclature for Pediatric and Congenital Cardiac Care: Unification of Clinical and Administrative Nomenclature - The 2021 International Paediatric and Congenital Cardiac Code (IPCCC) and the Eleventh Revision of the International Classification of Diseases (ICD-11). World journal for pediatric & congenital heart surgery Jacobs, J. P., Franklin, R. C., Beland, M. J., Spicer, D. E., Colan, S. D., Walters, H. L., Bailliard, F., Houyel, L., St Louis, J. D., Lopez, L., Aiello, V. D., Gaynor, J. W., Krogmann, O. N., Kurosawa, H., Maruszewski, B. J., Stellin, G., Weinberg, P. M., Jacobs, M. L., Boris, J. R., Cohen, M. S., Everett, A. D., Giroud, J. M., Guleserian, K. J., Hughes, M. L., Juraszek, A. L., Seslar, S. P., Shepard, C. W., Srivastava, S., Cook, A. C., Crucean, A., Hernandez, L. E., Loomba, R. S., Rogers, L. S., Sanders, S. P., Savla, J. J., Tierney, E. S., Tretter, J. T., Wang, L., Elliott, M. J., Mavroudis, C., Tchervenkov, C. I. 2021: 21501351211032919

  Abstract

  Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC. The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.

  View details for DOI 10.1177/21501351211032919

  View details for PubMedID 34304616

• Nomenclature for Pediatric and Congenital Cardiac Care: Unification of Clinical and Administrative Nomenclature - The 2021 International Paediatric and Congenital Cardiac Code (IPCCC) and the Eleventh Revision of the International Classification of Diseases (ICD-11). Cardiology in the young Jacobs, J. P., Franklin, R. C., Beland, M. J., Spicer, D. E., Colan, S. D., Walters, H. L., Bailliard, F., Houyel, L., St Louis, J. D., Lopez, L., Aiello, V. D., Gaynor, J. W., Krogmann, O. N., Kurosawa, H., Maruszewski, B. J., Stellin, G., Weinberg, P. M., Jacobs, M. L., Boris, J. R., Cohen, M. S., Everett, A. D., Giroud, J. M., Guleserian, K. J., Hughes, M. L., Juraszek, A. L., Seslar, S. P., Shepard, C. W., Srivastava, S., Cook, A. C., Crucean, A., Hernandez, L. E., Loomba, R. S., Rogers, L. S., Sanders, S. P., Savla, J. J., Tierney, E. S., Tretter, J. T., Wang, L., Elliott, M. J., Mavroudis, C., Tchervenkov, C. I. 2021; 31 (7): 1057-1188

  Abstract

  Substantial progress has been made in the standardization of nomenclature for paediatric and congenital cardiac care. In 1936, Maude Abbott published her Atlas of Congenital Cardiac Disease, which was the first formal attempt to classify congenital heart disease. The International Paediatric and Congenital Cardiac Code (IPCCC) is now utilized worldwide and has most recently become the paediatric and congenital cardiac component of the Eleventh Revision of the International Classification of Diseases (ICD-11). The most recent publication of the IPCCC was in 2017. This manuscript provides an updated 2021 version of the IPCCC.The International Society for Nomenclature of Paediatric and Congenital Heart Disease (ISNPCHD), in collaboration with the World Health Organization (WHO), developed the paediatric and congenital cardiac nomenclature that is now within the eleventh version of the International Classification of Diseases (ICD-11). This unification of IPCCC and ICD-11 is the IPCCC ICD-11 Nomenclature and is the first time that the clinical nomenclature for paediatric and congenital cardiac care and the administrative nomenclature for paediatric and congenital cardiac care are harmonized. The resultant congenital cardiac component of ICD-11 was increased from 29 congenital cardiac codes in ICD-9 and 73 congenital cardiac codes in ICD-10 to 318 codes submitted by ISNPCHD through 2018 for incorporation into ICD-11. After these 318 terms were incorporated into ICD-11 in 2018, the WHO ICD-11 team added an additional 49 terms, some of which are acceptable legacy terms from ICD-10, while others provide greater granularity than the ISNPCHD thought was originally acceptable. Thus, the total number of paediatric and congenital cardiac terms in ICD-11 is 367. In this manuscript, we describe and review the terminology, hierarchy, and definitions of the IPCCC ICD-11 Nomenclature. This article, therefore, presents a global system of nomenclature for paediatric and congenital cardiac care that unifies clinical and administrative nomenclature.The members of ISNPCHD realize that the nomenclature published in this manuscript will continue to evolve. The version of the IPCCC that was published in 2017 has evolved and changed, and it is now replaced by this 2021 version. In the future, ISNPCHD will again publish updated versions of IPCCC, as IPCCC continues to evolve.

  View details for DOI 10.1017/S104795112100281X

  View details for PubMedID 34323211

• The Impact of Maternal Preeclampsia and Hyperglycemia on the Cardiovascular Health of the Offspring: A Systematic Review and Meta-Analysis. American journal of perinatology Hoodbhoy, Z., Mohammed, N., Nathani, K. R., Sattar, S., Chowdhury, D., Maskatia, S., Tierney, S., Hasan, B., Das, J. K. 2021

  Abstract

  OBJECTIVES: The objective of this review was to assess the impact of maternal preeclampsia or hyperglycemia on the body composition and cardiovascular health in the offspring.STUDY DESIGN: We conducted a systematic review utilizing PubMed, EBSCO, CINAHLPlus, Cochrane Library, and Web of Science to include all studies assessing the impact of preeclampsia/eclampsia and/or gestational/pregestational diabetes mellitus on the health of the offspring (children <10 years of age). The health measures included anthropometry, cardiac dimensions and function, and vascular function. We performed a meta-analysis using Review Manager software and computed net risk ratio (RR) with 95% confidence interval (CI) for dichotomous data and mean difference (MD) with 95% CI for continuous data.RESULTS: There were 6,376 studies in total, of which 45 were included in the review and 40 in the meta-analysis. The results demonstrated higher birth weight (MD: 0.12kg; 95% CI: 0.06-0.18) and systolic and diastolic blood pressure (BP; MD: 5.98mmHg; 95% CI: 5.64-6.32 and MD: 3.27mmHg; 95% CI: 0.65-5.89, respectively) in the offspring of mothers with gestational diabetes compared to controls. In contrast, the offspring of mothers with preeclampsia had lower birth weight (MD: -0.41kg; 95% CI: -0.7 to -0.11); however, they had increased systolic (MD: 2.2mmHg; 95% CI: 1.28-3.12) and diastolic BP (MD: 1.41mmHg; 95% CI: 0.3-2.52) compared to controls. There is lack of data to conduct a meta-analysis of cardiac morphology, functional, and vascular imaging parameters.CONCLUSION: These findings suggest that the in-utero milieu can have a permanent impact on the body composition and vascular health of the offspring. Future work warrants multicenter prospective studies to understand the mechanism and the actual effect of exposure to maternal hyperglycemia and high BP on the cardiovascular health of the offspring and long-term outcomes.KEY POINTS: · Adverse in-utero exposures may have an impact on cardiovascular risk in children.. · Maternal hyperglycemia/preeclampsia lead to changes in birthweight and BP.. · Limited echocardiographic and vascular imaging data in these cohorts necessitates future work..

  View details for DOI 10.1055/s-0041-1728823

  View details for PubMedID 33940650

• 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

  Abstract

  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

• Variation in Pharmacological Management of Kawasaki Patients with Coronary Artery Aneurysms. The Journal of pediatrics Selamet Tierney, E. S., Runeckles, K., Tremoulet, A. H., Dahdah, N., Portman, M. A., Mackie, A. S., Harahsheh, A. S., Lang, S. M., Choueiter, N. F., Li, J. S., Manlhiot, C., Low, T., Mathew, M., Friedman, K. G., Raghuveer, G., Norozi, K., Szmuszkovicz, J. R., McCrindle, B. W. 2021

  Abstract

  To evaluate practice variation in pharmacological management in the International Kawasaki Disease Registry (IKDR).Practice variation in intravenous immunoglobulin (IVIG) therapy, anti-inflammatory agents, statins, beta-blockers, antiplatelet therapy, and anticoagulation was described.We included 1,627 patients from 30 IKDR centers with maximum coronary artery aneurysm (CAA) z-scores 2.5-4.99 in 848, 5.0-9.99 in 349, and ≥10.0 (large/giant) in 430 patients. All centers reported IVIG and acetylsalicylic acid (ASA) as primary therapy and use of additional IVIG or steroids as needed. In 23/30 centers (77%) infliximab was also used; 11 of these 23 centers reported using it in <10% of their patients, and three centers used it in >20% of patients. Non-steroidal anti-inflammatory agents were used in >10% of patients in only nine centers. Beta-blocker (8.8%, all patients) and abciximab (3.6%, all patients) were mainly prescribed in large/giant CAA patients. Statins (2.7%, all patients) were mostly used in one center and only in large/giant CAA patients. ASA was the primary antiplatelet modality for 99% of patients, used in all centers. Clopidogrel (18%, all patients) was used in 24 centers, 11 of which used it in >50% of their large/giant CAA patients.In the IKDR, IVIG and ASA therapy as primary therapy is universal with common use of a second dose of IVIG for persistent fever. There is practice variation among centers for adjunctive therapies and anticoagulation strategies, likely reflecting ongoing knowledge gaps. Randomized controlled trials nested in a high-quality collaborative registry may be an efficient strategy to reduce practice variation.

  View details for DOI 10.1016/j.jpeds.2021.08.072

  View details for PubMedID 34474088

• Risk Factors for Mortality and Circulatory Outcome Among Neonates Prenatally Diagnosed With Ebstein Anomaly or Tricuspid Valve Dysplasia: A Multicenter Study. Journal of the American Heart Association Freud, L. R., McElhinney, D. B., Kalish, B. T., Escobar-Diaz, M. C., Komarlu, R., Puchalski, M. D., Jaeggi, E. T., Szwast, A. L., Freire, G., Levasseur, S. M., Kavanaugh-McHugh, A., Michelfelder, E. C., Moon-Grady, A. J., Donofrio, M. T., Howley, L. W., Selamet Tierney, E. S., Cuneo, B. F., Morris, S. A., Pruetz, J. D., van der Velde, M. E., Kovalchin, J. P., Ikemba, C. M., Vernon, M. M., Samai, C., Satou, G. M., Gotteiner, N. L., Phoon, C. K., Silverman, N. H., Tworetzky, W. 2020: e016684

  Abstract

  Background In a recent multicenter study of perinatal outcome in fetuses with Ebstein anomaly or tricuspid valve dysplasia, we found that one third of live-born patients died before hospital discharge. We sought to further describe postnatal management strategies and to define risk factors for neonatal mortality and circulatory outcome at discharge. Methods and Results This 23-center, retrospective study from 2005 to 2011 included 243 fetuses with Ebstein anomaly or tricuspid valve dysplasia. Among live-born patients, clinical and echocardiographic factors were evaluated for association with neonatal mortality and palliated versus biventricular circulation at discharge. Of 176 live-born patients, 7 received comfort care, 11 died <24hours after birth, and 4 had insufficient data. Among 154 remaining patients, 38 (25%) did not survive to discharge. Nearly half (46%) underwent intervention. Mortality differed by procedure; no deaths occurred in patients who underwent right ventricular exclusion. At discharge, 56% of the cohort had a biventricular circulation (13% following intervention) and 19% were palliated. Lower tricuspid regurgitation jet velocity (odds ratio [OR], 2.3 [1.1-5.0], 95% CI, per m/s; P=0.025) and lack of antegrade flow across the pulmonary valve (OR, 4.5 [1.3-14.2]; P=0.015) were associated with neonatal mortality by multivariable logistic regression. These variables, along with smaller pulmonary valve dimension, were also associated with a palliated outcome. Conclusions Among neonates with Ebstein anomaly or tricuspid valve dysplasia diagnosed in utero, a variety of management strategies were used across centers, with poor outcomes overall. High-risk patients with low tricuspid regurgitation jet velocity and no antegrade pulmonary blood flow should be considered for right ventricular exclusion to optimize their chance of survival.

  View details for DOI 10.1161/JAHA.120.016684

  View details for PubMedID 33076749

• The benefit of exercise in children with congenital heart disease. Current opinion in pediatrics Selamet Tierney, E. S. 2020

  Abstract

  PURPOSE OF REVIEW: Children and adolescents with congenital heart disease (CHD) often have decreased exercise capacity and muscle mass. Exercise has numerous health benefits and can improve exercise capacity and muscle mass. As such, guidelines recommend 60 min of daily physical activity in the majority of pediatric CHD patients. Despite these known benefits and guidelines, children and adolescents with CHD often do not exercise regularly. The purpose of this review is to summarize the current literature on exercise in this population.RECENT FINDINGS: With recent advancements in the field, clinical focus in pediatric cardiology has expanded from improving mortality to improving long-term outcomes and quality of life. As part of this paradigm shift, there is ongoing research on safety, impact, and effective delivery of exercise to this population with the overarching goal of promoting an active lifestyle.SUMMARY: Exercise interventions are generally safe, feasible, and beneficial in children and adolescents with CHD. There is growing evidence demonstrating the benefits and utility of exercise as a prescription rather than restriction in pediatric CHD patients. Novel approaches are needed for effective delivery of exercise in this population. Further studies are warranted for assessment of long-term benefits of exercise in pediatric CHD patients.

  View details for DOI 10.1097/MOP.0000000000000942

  View details for PubMedID 32868597

• 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

  Abstract

  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

• Healthy Hearts via Live Video Conferencing: An Exercise and Diet Intervention in Pediatric Heart Transplant Patients JAHA Chen, A. C., Ramirez, F., Rosenthal, D. N., Couch, S. C., Berry, S., Stauffer, K. J., Brabender, J., McDonald, N., Lee, D., Barkoff, L., Nourse, S. E., Kazmucha, J., Wang, C. J., Olson, I., Tierney, E. S. 2020

  View details for DOI 10.1161/JAHA.119.013816

• Telehealth in Pediatric Heart Transplant Patients: Exercise, Nutrition, and Parental Imaging. Pediatric clinics of North America Chen, A. C., Selamet Tierney, E. S. 2020; 67 (4): 635–39

  Abstract

  Telehealth is a promising new tool in medicine that has changed the landscape of medical care. The benefits of telehealth technology are immense, including improved access to care and potential savings in monetary and opportunity costs. Current challenges of incorporating telehealth services into regular clinical care include licensure and regulatory barriers, difficulty obtaining insurance reimbursements, and high costs of setting up successful telehealth infrastructures. These challenges threaten telehealth's future scalability and expansion to reach all patients in need.

  View details for DOI 10.1016/j.pcl.2020.04.005

  View details for PubMedID 32650860

• "Echo pause" for postoperative transthoracic echocardiographic surveillance. Echocardiography (Mount Kisco, N.Y.) Cox, K., Arunamata, A., Krawczeski, C. D., Reddy, C., Kipps, A. K., Long, J., Roth, S. J., Axelrod, D. M., Hanley, F., Shin, A., Selamet Tierney, E. S. 2019

  Abstract

  BACKGROUND: No guidelines exist for inpatient postoperative transthoracic echocardiographic (TTE) surveillance in congenital heart disease. We prospectively evaluated indications for postoperative TTEs in patients with congenital heart disease to identify areas to improve upon (Phase 1) and then assessed the impact of a simple pilot intervention (Phase 2).METHODS: We included patients with RACHS-1 (Risk Adjustment for Congenital Heart Surgery) scores of 2 and 3 to keep the cohort homogenous. During Phase 1, we collected data prospectively to identify postoperative TTEs for which there were no new findings and no associated clinical management decisions ("potentially redundant" TTEs). During Phase 2, prior to placement of a TTE order, an "Echo Pause" was performed during rounds to prompt review of prior TTE results and indication for the current order. The number of "potentially redundant" TTEs during Phase 1 vs. Phase 2 was compared.RESULTS: During Phase 1, 98 postoperative TTEs were performed on 51 patients. Potentially "redundant" TTEs were identified in two main areas: (a) TTEs ordered to evaluate pericardial effusion and (b) TTEs ordered with the indication of "postoperative," "follow-up," or "discharge" in the setting of a prior complete postoperative TTE and no apparent change in clinical status. During Phase 2, 101 TTEs were performed on 63 patients. The number of "potentially redundant" TTEs decreased from 14/98 (14%) to 5/101 (5%) (P=.026).CONCLUSION: Our results suggest that the number of "potentially redundant" TTEs during inpatient postoperative surveillance of patients with congenital heart disease can be decreased by a simple intervention during rounds such as an "Echo Pause."

  View details for DOI 10.1111/echo.14505

  View details for PubMedID 31628768

• A Review of Psychosocial Factors of Marfan Syndrome: Adolescents, Adults, Families, and Providers. Journal of pediatric genetics Nielsen, C., Ratiu, I., Esfandiarei, M., Chen, A., Selamet Tierney, E. S. 2019; 8 (3): 109–22

  Abstract

  The purpose of this article was to review the current literature on psychosocial implications of Marfan syndrome (MFS) and its impact on adolescents, adults, their families and to provide important considerations for providers. Since the previous reviews in 2015, numerous studies have been published that are included in the current review. This literature review was conducted using PubMed, Medline, PsychINFO, ERIC, Web of Science, and Academic Search Premier databases and only articles that studied psychosocial factors that influence MFS patients as adolescents, adults, family members, or their interactions with providers were included in this review. Of the 522 articles reviewed, 41 were selected based on the inclusion and exclusion criteria. All articles were peer-reviewed. MFS has various implications that can impact one's life; studies have shown that MFS causes a negative impact on an individual's formative years, quality of life, reproductive decision-making, work participation, and satisfaction with life. Clinicians and multidisciplinary teams should be aware of these factors to provide support focusing on coping strategies for the patient and their family.

  View details for DOI 10.1055/s-0039-1693663

  View details for PubMedID 31406616

• Impact of Treatment Modality on Vascular Function in Coarctation of the Aorta: The LOVE-COARCT Study JOURNAL OF THE AMERICAN HEART ASSOCIATION Martins, J. D., Zachariah, J., Tierney, E., Uyen Truong, Morris, S. A., Kutty, S., de Ferranti, S. D., Guarino, M., Thomas, B., Oliveira, D., Marinho, A., Antonio, M., Gauvreau, K., Jalles, N., Geva, T., Carmo, M. M., Prakash, A., Antonio, M., Martins, J. D., Mateus, T., Medroa, L., Pinto, F. F., Selas, M., de Ferranti, S. D., Gauvreau, K., Geva, T., Hass, C., Lock, J. E., Newburger, J., Prakash, A., Reichman, J., Rhodes, J., Kutty, S., Chen, A., Tierney, S. S., Truong, U., Castela, E., Marinho, A., Morris, S. A., Zachariah, J., Guarino, M., Carmo, M. M., Antonio, M., Jalles, N. T., Thomas, B., Oliveira, D. C., LOVE-COARCT Study 2019; 8 (7)

  View details for DOI 10.1161/JAHA.118.011536

  View details for Web of Science ID 000484574300022

• Parental Acquisition of Echocardiographic Images in Pediatric Heart Transplant Patients Using a Handheld Device: A Pilot Telehealth Study JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Dykes, J. C., Kipps, A. K., Chen, A., Nourse, S., Rosenthal, D. N., Tierney, E. 2019; 32 (3): 404–11

  View details for DOI 10.1016/j.echo.2018.10.007

  View details for Web of Science ID 000459902800012

• Absent or Excessive Corpus Luteum Number Is Associated With Altered Maternal Vascular Health in Early Pregnancy HYPERTENSION von Versen-Hoeynck, F., Narasimhan, P., Tierney, E., Martinez, N., Conrad, K. P., Baker, V. L., Winn, V. D. 2019; 73 (3): 680–90

  View details for DOI 10.1161/HYPERTENSIONAHA.118.12046

  View details for Web of Science ID 000458554900024

• Healthy hearts in pediatric heart transplant patients with an exercise and diet intervention via live video conferencing-Design and rationale PEDIATRIC TRANSPLANTATION Chen, A. C., Rosenthal, D. N., Couch, S. C., Berry, S., Stauffer, K. J., Brabender, J., McDonald, N., Lee, D., Barkoff, L., Nourse, S. E., Kazmucha, J., Wang, C., Olson, I., Tierney, E. 2019; 23 (1)

  View details for DOI 10.1111/petr.13316

  View details for Web of Science ID 000457579500010

• Comparison of Initial Pediatric Outpatient Echocardiogram Indications between Community and Academic Practice. The Journal of pediatrics Balasubramanian, S., Ramirez, F. D., Bui, Y., Selamet Tierney, E. S., Behera, S. K. 2019

  Abstract

  OBJECTIVE: To compare the appropriateness and diagnostic yield of initial outpatient transthoracic echocardiography (TTE) between a community pediatric cardiology practice and an academic children's hospital.STUDY DESIGN: Initial outpatient pediatric TTE ordered by pediatric cardiologists between January and March 2014 at a community practice (Packard Children's Health Alliance [PCHA]; n=238) and an academic tertiary center (Lucile Packard Children's Hospital [LPCH]; n=76) were evaluated based on appropriate use criteria (AUC) released in December 2014. Multivariate logistic regression was used to identify predictors of "rarely appropriate" indications and abnormal TTE findings.RESULTS: Of 314 TTEs, 165 (52.5%) were classified as "appropriate," 40 (12.7%) were classified as "may be appropriate," 100 (31.9%) were classified as "rarely appropriate," and 9 (2.9%) were unclassifiable. The proportion of abnormal findings did not differ between the 2 practice settings (5.3% for LPCH vs 7.6% for PCHA; P=.61). TTEs performed at PCHA were significantly more likely to be "rarely appropriate" (OR, 2.57; 95% CI, 1.28-5.15; P=.008). Children aged <1 year (OR, 1.90; 95% CI, 1.03-3.50; P=.04) and ordering providers with<10 years since the completion of their fellowship (OR, 2.15; 95% CI, 1.20-3.87; P=.01) were associated with "rarely appropriate" indications. "Appropriate" TTEs were associated with abnormal findings (OR, 8.69; 95% CI, 1.77-42.68; P=.008).CONCLUSION: The community practice was independently associated with greater inappropriate ordering of initial outpatient pediatric TTEs compared with the academic practice. The assessment of practice patterns following AUC release should account for physician and practice-related factors that could influence differences in TTE ordering patterns.

  View details for DOI 10.1016/j.jpeds.2018.11.057

  View details for PubMedID 30661793

• Absent or Excessive Corpus Luteum Number Is Associated With Altered Maternal Vascular Health in Early Pregnancy. Hypertension (Dallas, Tex. : 1979) von Versen-Hoynck, F., Narasimhan, P., Selamet Tierney, E. S., Martinez, N., Conrad, K. P., Baker, V. L., Winn, V. D. 2019: HYPERTENSIONAHA11812046

  Abstract

  Identifying modifiable factors that contribute to preeclampsia risk associated with assisted reproduction can improve maternal health. Vascular dysfunction predates clinical presentation of preeclampsia. Therefore, we examined if a nonphysiological hormonal milieu, a modifiable state, affects maternal vascular health in early pregnancy. Blood pressure, endothelial function, circulating endothelial progenitor cell numbers, lipid levels, and corpus luteum (CL) hormones were compared in a prospective cohort of women with infertility history based on number of CL: 0 CL (programmed frozen embryo transfer [FET], N=18); 1 CL (spontaneous conception [N=16] and natural cycle FET [N=12]); or >3 CL associated with in vitro fertilization [N=11]. Women with 0 or >3 CL lacked the drop in mean arterial blood pressure compared with those with 1 CL (both P=0.05). Reactive hyperemia index was impaired in women with 0 CL compared with 1 CL ( P=0.04) while baseline pulse wave amplitude was higher with > 3 CL compared with 1 CL ( P=0.01) or 0 CL ( P=0.01). Comparing only FET cycles, a lower reactive hyperemia index and a higher augmentation index is noted in FETs with suppressed CL compared with FETs in a natural cycle (both P=0.03). The number of angiogenic and nonangiogenic circulating endothelial progenitor cell numbers was lower in the absence of a CL in FETs ( P=0.01 and P=0.03). Vascular health in early pregnancy is altered in women with aberrant numbers of CL (0 or >3) and might represent insufficient cardiovascular adaptation contributing to an increased risk of preeclampsia.

  View details for PubMedID 30636549

• Challenges With Left Ventricular Functional Parameters: The Pediatric Heart Network Normal Echocardiogram Database. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Frommelt, P. C., Minich, L. L., Trachtenberg, F. L., Altmann, K. n., Camarda, J. n., Cohen, M. S., Colan, S. D., Dragulescu, A. n., Frommelt, M. A., Johnson, T. R., Kovalchin, J. P., Lin, L. n., Mahgerefteh, J. n., Nutting, A. n., Parra, D. A., Pearson, G. D., Pignatelli, R. n., Sachdeva, R. n., Soriano, B. D., Spurney, C. n., Srivastava, S. n., Statile, C. J., Stelter, J. n., Stylianou, M. n., Thankavel, P. P., Tierney, E. S., van der Velde, M. E., Lopez, L. n. 2019

  Abstract

  The reliability of left ventricular (LV) systolic functional indices calculated from blinded echocardiographic measurements of LV size has not been tested in a large cohort of healthy children. The objective of this study was to estimate interobserver variability in standard measurements of LV size and systolic function in children with normal cardiac anatomy and qualitatively normal function.The Pediatric Heart Network Normal Echocardiogram Database collected normal echocardiograms from healthy children ≤18 years old distributed equally by age, gender, and race. A core lab used two-dimensional echocardiograms to measure LV dimensions from which a separate data coordinating center calculated LV volumes and systolic functional indices. To evaluate interobserver variability, two independent expert pediatric echocardiographic observers remeasured LV dimensions on a subset of studies, while blinded to calculated volumes and functional indices.Of 3,215 subjects with measurable images, 552 (17%) had a calculated LV shortening fraction (SF) < 25% and/or LV ejection fraction (EF) < 50%; the subjects were significantly younger and smaller than those with normal values. When the core lab and independent observer measurements were compared, individual LV size parameter intraclass correlation coefficients were high (0.81-0.99), indicating high reproducibility. The intraclass correlation coefficients were lower for SF (0.24) and EF (0.56). Comparing reviewers, 40/56 (71%) of those with an abnormal SF and 36/104 (35%) of those with a normal SF based on core lab measurements were calculated as abnormal from at least one independent observer. In contrast, an abnormal EF was less commonly calculated from the independent observers' repeat measures; only 9/47 (19%) of those with an abnormal EF and 8/113 (7%) of those with a normal EF based on core lab measurements were calculated as abnormal by at least one independent observer.Although blinded measurements of LV size show good reproducibility in healthy children, subsequently calculated LV functional indices reveal significant variability despite qualitatively normal systolic function. This suggests that, in clinical practice, abnormal SF/EF values may result in repeat measures of LV size to match the subjective assessment of function. Abnormal LV functional indices were more prevalent in younger, smaller children.

  View details for DOI 10.1016/j.echo.2019.05.025

  View details for PubMedID 31351792

• Echocardiographic surveillance in children after tetralogy of Fallot repair: Adherence to guidelines? International journal of cardiology Annavajjhala, V. n., Valente, A. M., Lopez, L. n., Sachdeva, R. n., Glickstein, J. S., Natarajan, S. S., Buddhe, S. n., Altmann, K. n., Soriano, B. D., Colquitt, J. L., Altman, C. A., Sasaki, N. n., Sakarovitch, C. n., Tacy, T. A., Geva, T. n., Selamet Tierney, E. S. 2019

  Abstract

  Longitudinal clinical surveillance by transthoracic echocardiography (TTE) is an established practice in children with repaired tetralogy of Fallot (TOF). Non-Invasive Imaging Guidelines recommends a list of reporting elements that should be addressed during routine TTE in this population. In this study, we assessed the adherence to these recommendations.This was a multi-center (n = 8) retrospective review of TTE reports in children ≤11 years of age who have had complete TOF repair. We included 10 patients from each participating center (n = 80) and scored 2 outpatient follow-up TTE reports on each patient. The adherence rate was based on completeness of TTE reporting elements derived from the guidelines.We reviewed 160 TTE reports on 80 patients. Median age was 4.4 months (IQR 1.5-6.6) and 3.6 years (IQR 1.3-6.4) at the time of complete surgical repair and first TTE report, respectively. The median adherence rate to recommended reporting elements was 61% (IQR 53-70). Of the 160 reports, 9 (7%) were ≥80% adherent and 40 (25%) were ≥70% adherent. Quantitative measurements of right ventricular outflow tract (RVOT), right ventricular (RV) size and function, and branch pulmonary arteries were least likely to be reported.Overall adherence to the most recent published imaging guidelines for surveillance of children with repaired TOF patients was suboptimal, especially for reporting of RVOT, RV size and function, and branch pulmonary arteries. Further studies are needed to explore the barriers to adherence to guidelines and most importantly, whether adherence is associated with clinical outcomes.

  View details for DOI 10.1016/j.ijcard.2019.09.075

  View details for PubMedID 31668657

• Vascular Health of Children Conceived via In Vitro Fertilization. The Journal of pediatrics Zhang, W. Y., Selamet Tierney, E. S., Chen, A. C., Ling, A. Y., Fleischmann, R. R., Baker, V. L. 2019

  Abstract

  To evaluate whether in vitro fertilization (IVF) has an effect on the cardiovascular health of offspring.This was a cross-sectional pilot study. We performed vascular health assessment for 17 children aged 10-14 years who were conceived via IVF with autologous oocytes at Stanford University. Carotid artery ultrasound evaluated intima-media thickness and stiffness, carotid-femoral pulse wave velocity determined segmental arterial stiffness, and endothelial pulse amplitude testing assessed endothelial function. We compared IVF offspring with control adolescents assessed in the same laboratory, with all comparisons adjusted for age, sex, and race/ethnicity.All participants had normal body mass index and blood pressure. Compared with controls, IVF children had thicker common carotid artery intima-media thickness (0.44 ± 0.03 mm vs 0.38 ± 0.03 mm; P < .01), higher elastic modulus (395.29 ± 185.33 mm Hg vs 242.79 ± 37.69 mm Hg; P = .01), higher βstiffness (2.65 ± 0.38 vs 2.28 ± 0.23; P < .01), and higher peak velocity (142.29 ± 31.62 cm/s vs 117.71 ± 32.69 cm/s; P = .04). The mean endothelial pulse amplitude testing reactive hyperemia index was not significantly different between IVF and controls. The mean pulse wave velocity was 4.69 ± 0.51 m/s compared with the controls 4.60 ± 0.57 m/s (P = .11), with 8 (47%) having abnormal values.In an assessment of endothelial function and arterial properties of children conceived via IVF, we found that children conceived via IVF seem to have evidence of abnormal vascular health. Further studies with larger sample size and long-term follow-up are warranted.

  View details for DOI 10.1016/j.jpeds.2019.07.033

  View details for PubMedID 31443895

• Maternal Vascular Health in Pregnancy and Postpartum After Assisted Reproduction. Hypertension (Dallas, Tex. : 1979) von Versen-Höynck, F. n., Häckl, S. n., Selamet Tierney, E. S., Conrad, K. P., Baker, V. L., Winn, V. D. 2019: HYPERTENSIONAHA11913779

  Abstract

  Although most pregnancies after assisted reproduction are associated with a favorable outcome for the mother and infant, reports of abnormal vascular adaptation in early pregnancy and emerging maternal and perinatal pathology warrant further investigations. Herein we extended our previous work and further examined whether perturbations of blood pressure and endothelial function during the first trimester in conceptions with nonphysiological corpus luteum (CL) numbers would persist through the third trimester of pregnancy and into the postpartum period. We investigated both maternal and perinatal outcomes. Participants were grouped according to CL number and method of conception: 0 CL (programmed autologous frozen-thawed embryo transfer, N=10-18); 1 CL (spontaneous conception [N=16] and natural cycle frozen-thawed embryo transfer [N=12]); or >3 CL associated with autologous fresh embryo transfer [N=8-12]. Augmentation index was higher during the third trimester in the absence of a CL compared to 1 CL (P=0.03) and in frozen-thawed embryo transfer in a programmed compared to a natural cycle (P=0.02). Moreover, baseline pulse-wave amplitude was higher in >3 CL conceptions at all time points (all P<0.05). The incidence of preeclampsia and preeclampsia with severe features was significantly higher in the absence of a CL compared to the presence of one or >3 CL (P=0.045 and P=0.03). Infants from conceptions with >3 CL had lower birth weights (P=0.02) and a higher rate of low birth weight offspring (P=0.008). Deficient vascular adaptation during early gestation in conceptions with nonphysiological CL numbers might predispose women to adverse pregnancy outcomes, for example, preeclampsia.

  View details for DOI 10.1161/HYPERTENSIONAHA.119.13779

  View details for PubMedID 31838910

• Parental Acquisition of Echocardiographic Images in Pediatric Heart Transplant Patients Using a Handheld Device: A Pilot Telehealth Study. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Dykes, J. C., Kipps, A. K., Chen, A., Nourse, S., Rosenthal, D. N., Selamet Tierney, E. S. 2018

  Abstract

  BACKGROUND: Pediatric heart transplant patients (PedHtx) require frequent monitoring by echocardiography (echo); however, they often live far from hospitals with pediatric echo services, resulting in urgent/emergent transfers to specialized institutions. Our primary objective was to evaluate the feasibility of parental acquisition of echo images to assess left ventricular (LV) systolic function in PedHtx using a handheld echo device. Secondary objectives included retesting for skill maintenance and in patients with decreased LV systolic function.METHODS: During a routine clinic visit, parents received 1-hour training with a handheld echo device to acquire images in parasternal short-axis and apical views. Parents recorded images on their children at training completion and 24hours later at home. An independent echocardiographer assessed clinic, training, and home echos for LV systolic function.RESULTS: Fifteen PedHtx (mean age of 12.6years of age; range, 4.1-16.7) were enrolled. All parents could acquire home images adequate for qualitative assessment of LV systolic function with no discrepancy compared with clinical echos. LV ejection fraction (LVEF) could be calculated (5/6 area-length method) in 86% of training and 43% of home echos with <10% difference in LVEF measurements between home and clinic echos. Five parents repeated home echos >12months later. All home echos were adequate for qualitative assessment of LV systolic function (LVEF measurable in two). Additionally, five heart failure patients with decreased LV systolic function (mean age of 8.6years; range 1.9-15.1) were enrolled. All home echos were adequate for qualitative assessment of LV systolic function (LVEF measurable in one).CONCLUSIONS: Our results suggest that parental home echo acquisition using a handheld echo device is feasible and adequate for qualitative assessment of LV systolic function in PedHtx. However, quantitative assessment of LV systolic function, especially in patients with dysfunction, and retention of the skill set without additional training are suboptimal.

  View details for PubMedID 30598367

• Healthy hearts in pediatric heart transplant patients with an exercise and diet intervention via live video conferencing-Design and rationale. Pediatric transplantation Chen, A. C., Rosenthal, D. N., Couch, S. C., Berry, S., Stauffer, K. J., Brabender, J., McDonald, N., Lee, D., Barkoff, L., Nourse, S. E., Kazmucha, J., Wang, C. J., Olson, I., Selamet Tierney, E. S. 2018: e13316

  Abstract

  BACKGROUND: Pediatric heart transplant (PedHtx) patients have increased cardiovascular risk profiles that affect their long-term outcomes and quality of life. We designed a 12- to 16-week diet and exercise intervention delivered via live video conferencing to improve cardiovascular health. Our methodology and baseline assessment of the first 13 enrolled patients are reported.METHODS: Inclusion criteria are as follows: (a) 8-19years old; (b) heart transplant >12months; (c) ability to fast overnight; (d) cardiac clearance by cardiologist; and (e) presence of an adult at home during exercise sessions for patients <14years old. Exclusion criteria are as follows: (a) acute illness; (b) latex allergy; (c) transplant rejection <3months ago; and (d) multi-organ transplantation. The intervention consists of one diet and three exercise sessions weekly via live video conferencing. Study visits are conducted at baseline, intervention completion, and end of maintenance period.RESULTS: A total of 13 participants (15.2 [2.3]years) have been enrolled. Median percent-predicted VO2 max was 56.8 [20.7]% (10 patients <70%). Ten patients had abnormal endothelial function (reactive hyperemia index <1.9; 1.4 [0.325]) and 11 patients had stiff arteries (pulse wave velocity ≧5.5m/s for 15-19years, ≧4.5m/s for 8-14years; 5.6 [0.7]m/s). Patients had suboptimal diets (saturated fat: 22.7 [23.8]g/d, sodium: 2771 [1557]mg/d) and were sedentary at a median of 67.5 [13.8]% of their time.CONCLUSIONS: Baseline assessment confirms that PedHtx patients have abnormal cardiac, vascular, and functional health indices, poor dietary habits, and are sedentary. These results support the rationale to test the feasibility and impact of a non-pharmacologic lifestyle intervention in this patient population.

  View details for PubMedID 30393915

• Frequency of Ventricular Arrhythmias and Other Rhythm Abnormalities in Children and Young Adults With the Marfan Syndrome AMERICAN JOURNAL OF CARDIOLOGY Mah, D. Y., Sleeper, L. A., Crosson, J. E., Czosek, R. J., Love, B. A., McCrindle, B. W., Muino-Mosquera, L., Olson, A. K., Pilcher, T. A., Tierney, E., Shah, M. J., Wechsler, S. B., Young, L. T., Lacro, R. V. 2018; 122 (8): 1429-1436

  Abstract

  Patients with the Marfan syndrome (MFS) are at risk for sudden death. The contribution of arrhythmias is unclear. This study examines the prevalence of arrhythmias in children with the MFS and their relation to clinical and/or echocardiographic factors. Data from the Pediatric Heart Network randomized trial of atenolol versus losartan in MFS were analyzed (6 months to 25 years old, aortic root diameter z-score > 3.0, no previous aortic surgery and/or dissection). Baseline 24-hour ambulatory electrocardiographic monitoring was performed. Significant ventricular ectopy (VE) and supraventricular ectopy (SVE) were defined as ≥10 VE or SVE/hour, or the presence of high-grade ectopy. Three-year composite clinical outcome of death, aortic dissection, or aortic root replacement was analyzed. There were 274 analyzable monitors on unique patients from 11 centers. Twenty subjects (7%) had significant VE, 13 (5%) significant SVE; of these, 2 (1%) had both. None had sustained ventricular or supraventricular tachycardia. VE was independently associated with increasing number of major Ghent criteria (odds ratio [OR] = 2.13/each additional criterion, p = 0.03) and greater left ventricular end-diastolic dimension z-score (OR = 1.47/each 1 unit increase in z-score, p = 0.01). SVE was independently associated with greater aortic sinotubular junction diameter z-score (OR = 1.56/each 1 unit increase in z-score, p = 0.03). The composite clinical outcome (14 events) was not related to VE or SVE (p ≥ 0.3), but was independently related to heart rate variability (higher triangular index). In conclusion, in this cohort, VE and SVE were rare. VE was related to larger BSA-adjusted left ventricular size. Routine ambulatory electrocardiographic monitoring may be useful for risk stratification in select MFS patients.

  View details for DOI 10.1016/j.amjcard.2018.07.006

  View details for Web of Science ID 000450698500019

  View details for PubMedID 30115424

  View details for PubMedCentralID PMC6497148

• Rationale and design of Long-term Outcomes and Vascular Evaluation after Successful Coarctation of the Aorta Treatment study ANNALS OF PEDIATRIC CARDIOLOGY Martins, J. D., Zachariah, J., Tierney, E., Truong, U., Morris, S. A., Kutty, S., de Ferranti, S. D., Rhodes, J., Antonio, M., Guarino, M., Thomas, B., Oliveira, D., Gauvreau, K., Jalles, N., Geva, T., Carmo, M., Prakash, A. 2018; 11 (3): 282–96

  Abstract

  Coarctation of the aorta (CoA) can be treated using surgery, balloon angioplasty, or stent implantation. Although short-term results are excellent with all three treatment modalities, long-term cardiovascular (CV) morbidity and mortality remain high, likely due to persistently abnormal vascular function. The effects of treatment modality on long-term vascular function remain uncharacterized. The goal of this study is to assess vascular function in this patient population for comparison among the treatment modalities.We will prospectively assess vascular Afunction in large and small arteries fusing multiple noninvasive modalities and compare the results among the three groups of CoA patients previously treated using surgery, balloon angioplasty, or stent implantation after frequency matching for confounding variables. A comprehensive vascular function assessment protocol has been created to be used in 7 centers. Our primary outcome is arterial stiffness measured by arterial tonometry. Inclusion and exclusion criteria have been carefully established after consideration of several potential confounders. Sample size has been calculated for the primary outcome variable.Treatment modalities for CoA may have distinct impact on large and small arterial vascular function. The results of this study will help identify the treatment modality that is associated with the most optimal level of vascular function, which, in the long term, may reduce CV risk.

  View details for PubMedID 30271019

  View details for PubMedCentralID PMC6146860

• Utility of serial 12-lead electrocardiograms in children with Marfan syndrome. Cardiology in the young Arunamata, A. A., Nguyen, C. T., Ceresnak, S. R., Dubin, A. M., Olson, I. L., Murphy, D. J., Selamet Tierney, E. S. 2018: 1–5

  Abstract

  OBJECTIVES: The goal of this study was to assess the utility of serial electrocardiograms in routine follow-up of paediatric Marfan patients.METHODS: Children ⩽18 years who met the revised Ghent criteria for Marfan syndrome and received a 12-lead electrocardiogram and echocardiogram within a 3-month period were included. Controls were matched by age, body surface area, gender, race, and ethnicity, and consisted of patients assessed in clinic with a normal cardiac evaluation. Demographic, clinical, echocardiographic, and electrocardiographic data were collected.RESULTS: A total of 45 Marfan patients (10.8 [2.4-17.1] years) and 37 controls (12.8 [1.3-17.1] years) were included. Left atrial enlargement and left ventricular hypertrophy were more frequently present on 12-lead electrocardiogram of Marfan patients compared with controls (12 (27%) versus 0 (0%), p<0.001; and 8 (18%) versus 0 (0%), p=0.008, respectively); however, only two patients with left atrial enlargement on 12-lead electrocardiogram were confirmed to have left atrial enlargement by echocardiogram, and one patient had mild left ventricular hypertrophy by echocardiogram, not appreciated on 12-lead electrocardiogram. QTc interval was longer in Marfan patients compared with controls (427±16 versus 417±22 ms, p=0.03), with four Marfan patients demonstrating borderline prolonged QTc intervals for gender.CONCLUSIONS: While Marfan patients exhibited a higher frequency of left atrial enlargement and left ventricular hypertrophy on 12-lead electrocardiograms compared with controls, these findings were not supported by echocardiography. Serial 12-lead electrocardiograms in routine follow-up of asymptomatic paediatric Marfan patients may be more appropriate for a subgroup of Marfan patients only, specifically those with prolonged QTc interval at their baseline visit.

  View details for PubMedID 29972109

• Influence of Aortic Stiffness on Aortic-Root Growth Rate and Outcome in Patients With the Marfan Syndrome. The American journal of cardiology Selamet Tierney, E. S., Levine, J. C., Sleeper, L. A., Roman, M. J., Bradley, T. J., Colan, S. D., Chen, S., Campbell, M. J., Cohen, M. S., De Backer, J., Heydarian, H., Hoskoppal, A., Lai, W. W., Liou, A., Marcus, E., Nutting, A., Olson, A. K., Parra, D. A., Pearson, G. D., Pierpont, M. E., Printz, B. F., Pyeritz, R. E., Ravekes, W., Sharkey, A. M., Srivastava, S., Young, L., Lacro, R. V., Pediatric Heart Network Investigators 2018; 121 (9): 1094–1101

  Abstract

  The Pediatric Heart Network randomized trial of atenolol versus losartan in the Marfan syndrome showed no treatment differences in the rates of aortic-root growth or clinical outcomes. In this report we present treatment effects on aortic stiffness and determine whether baseline aortic stiffness predicts aortic-root growth and clinical outcomes. Echocardiograms at 0, 6, 12, 24, and 36 months from 608 subjects (6 months to 25 years) who met original Ghent criteria and had a maximum aortic-root z-score (ARz) >3 were centrally reviewed. Stiffness index (SI) and elastic modulus (EM) were calculated for aortic root and ascending aorta. Data were analyzed using multivariable mixed effects modeling and Cox regression. Heart rate-corrected aortic-root SI over 3 years decreased with atenolol but did not change with losartan (-0.298±0.139 vs 0.141±0.139/year, p=0.01). In the entire cohort, above-median aortic-root SI (>9.1) and EM (>618mmHg) predicted a smaller annual decrease in ARz (p ≤0.001). Upper-quartile aortic-root EM (>914mmHg) predicted the composite outcome of aortic-root surgery, dissection, or death (hazard ratio 2.17, 95% confidence interval 1.02 to 4.63, p=0.04). Crude 3-year event rates were 10.4% versus 3.2% for higher versus lower EM groups. In conclusion, atenolol was associated with a decrease in aortic-root SI, whereas losartan was not. Higher baseline aortic-root SI and EM were associated with a smaller decrease in ARz and increased risk for clinical outcomes. These data suggest that noninvasive aortic stiffness measures may identify patients at higher risk of progressive aortic enlargement and adverse clinical outcomes, potentially allowing for closer monitoring and more aggressive therapy.

  View details for DOI 10.1016/j.amjcard.2018.01.016

  View details for PubMedID 29631804

• The 2017 Seventh World Congress of Pediatric Cardiology & Cardiac Surgery: week in review: imaging. Cardiology in the young Selamet Tierney, E. S. 2017; 27 (10): 1991-1996

  Abstract

  The Imaging Program at the 7th World Congress highlighted the versatility and diagnostic power of the current and upcoming imaging tools in Pediatric Cardiology and Cardiac Surgery. Several experts presented interesting as well as practical data on the use of 2D and 3D Echocardiography, magnetic resonance imaging and computed tomography in the fetus, child, and adult with congenital heart disease. Bridging sessions coupled use of these imaging modalities and screening practices in patients with acquired heart disease. Hot topics included nomenclature of ventricular septal defects, the challenging diagnosis of double outlet right ventricle, cardiac tumors, and imaging of aortapathies. Several talks concentrated on the quantitative assessment of ventricular function and reviewed numerous exciting new modalities that currently serve as research tools. In summary, Imaging Sessions truly represented how far we have advanced the field of Imaging in Pediatric Cardiology and Cardiovascular Surgery.

  View details for DOI 10.1017/S1047951117002165

  View details for PubMedID 29286273

• Reproducibility of Left Ventricular Dimension Versus Area Versus Volume Measurements in Pediatric Patients With Dilated Cardiomyopathy CIRCULATION-CARDIOVASCULAR IMAGING Tierney, E., Hollenbeck-Pringle, D., Lee, C. K., Altmann, K., Dunbar-Masterson, C., Golding, F., Lu, M., Miller, S. G., Molina, K., Natarajan, S., Taylor, C. L., Trachtenberg, F., Colan, S. D., Pediat Heart Network Investigators 2017; 10 (11)

  View details for DOI 10.1161/CIRCIMAGING.116.006007

  View details for Web of Science ID 000415963900002

• Non-cardiac targets to treat heart failure in children: Anemia, Exercise, Nutrition, Proceedings from the 4th International Conference on Cardiomyopathy in Children, Bethesda, May 17, 2017 PROGRESS IN PEDIATRIC CARDIOLOGY Kaufman, B. D., Dennis, K., Tierney, S. E. 2017; 46: 7–10

  View details for DOI 10.1016/j.ppedcard.2017.07.003

  View details for Web of Science ID 000426221300003

• Peripheral Endothelial Function After Arterial Switch Operation for D-looped Transposition of the Great Arteries. Pediatric cardiology Sun, H. Y., Stauffer, K. J., Nourse, S. E., Vu, C., Selamet Tierney, E. S. 2017; 38 (5): 1010-1015

  Abstract

  Coronary artery re-implantation during arterial switch operation in patients with D-looped transposition of the great arteries (D-TGA) can alter coronary arterial flow and increase shear stress, leading to local endothelial dysfunction, although prior studies have conflicting results. Endothelial pulse amplitude testing can predict coronary endothelial dysfunction by peripheral arterial testing. This study tested if, compared to healthy controls, patients with D-TGA after arterial switch operation had peripheral endothelial dysfunction. Patient inclusion criteria were (1) D-TGA after neonatal arterial switch operation; (2) age 9-29 years; (3) absence of known cardiovascular risk factors such as hypertension, diabetes, hypercholesterolemia, vascular disease, recurrent vasovagal syncope, and coronary artery disease; and (4) ability to comply with overnight fasting. Exclusion criteria included (1) body mass index ≥85th percentile, (2) use of medications affecting vascular tone, or (3) acute illness. We assessed endothelial function by endothelial pulse amplitude testing and compared the results to our previously published data in healthy controls (n = 57). We tested 20 D-TGA patients (16.4 ± 4.8 years old) who have undergone arterial switch operation at a median age of 5 days (0-61 days). Endothelial pulse amplitude testing indices were similar between patients with D-TGA and controls (1.78 ± 0.61 vs. 1.73 ± 0.54, p = 0.73).In our study population of children and young adults, there was no evidence of peripheral endothelial dysfunction in patients with D-TGA who have undergone arterial switch operation. Our results support the theory that coronary arterial wall thickening and abnormal vasodilation reported in these patients is a localized phenomenon and not reflective of overall atherosclerotic burden.

  View details for DOI 10.1007/s00246-017-1609-6

  View details for PubMedID 28345114

• Maternal Arterial Stiffness and Fetal Cardiovascular Physiology in Diabetic Pregnancies. Ultrasound in obstetrics & gynecology Moodley, S., Arunamata, A., Stauffer, K. J., Nourse, S. E., Chen, A., Quirin, A., Selamet Tierney, E. S. 2017

  Abstract

  In mothers with pre-gestational or gestational diabetes, abnormal arterial stiffness (stiffer arteries) has been reported. The impact of abnormal maternal arterial stiffness on fetal placental and cardiovascular physiology is unknown. The purpose of the study was to determine the impact of maternal diabetes on maternal arterial stiffness and the association with fetal cardiovascular physiology as measured by fetal echocardiography.Between December 2013 and January 2017 we conducted a prospective study on diabetic (otherwise healthy) and non-diabetic, healthy pregnant mothers (at 20-28 gestational weeks and 18-40 years of age) who had a normal fetal cardiac echocardiogram and obstetric ultrasound. Clinical data were collected by means of a patient questionnaire, measurement of blood pressure, height and weight, arterial augmentation index and fetal placental and cardiovascular parameters by fetal echocardiography. Descriptive statistics were calculated. Comparisons were made using parametric and non-parametric tests between controls and diabetic mothers.Twenty-three healthy pregnant controls and 43 diabetic pregnant women (n = 22 pre-gestational, n = 21 gestational) were included in the study. Maternal arterial augmentation index was higher in those with diabetes compared to healthy controls (12.4 ± 10.6% versus 4.6 ± 7.9%; p = 0.003). Fetal aortic valve velocity time integral was higher in fetuses whose mothers had diabetes compared to non-diabetic mothers (7.7 ± 1.9 cm versus 6.3 ± 2.9 cm; p = 0.022). Left ventricular myocardial performance index was lower in diabetic pregnancies compared to controls (0.40 ± 0.09 versus; 0.46 ± 0.11 p = 0.02). Umbilical artery resistance index was lower in diabetic pregnancies with hemoglobin A1C levels ≥6.5% compared to those with HbA1c levels <6.5 (HbA1c ≥6.5%: 0.69 ± 0.06, n = 15 versus HbA1c <6.5%: 0.76 ± 0.08, n = 21; p = 0.009) but not at higher HbA1C cut-offs. A correlation between arterial augmentation index and velocity time integral, myocardial performance index or umbilical artery resistance index was not found.Arterial stiffness is higher in pregnant women with diabetes compared to controls. Fetuses of diabetic mothers show altered cardiovascular parameters with higher velocity time integral and lower left ventricular myocardial performance index, markers of myocardial function. Placental function assessed by umbilical artery resistance was normal despite differences between groups. Arterial stiffness did not correlate with placental or fetal cardiovascular variables. Instead, the findings likely represent a shared response to the environment of abnormal glucose metabolism. The clinical significance of these findings is yet to be determined.

  View details for DOI 10.1002/uog.17528

  View details for PubMedID 28508434

• Acute Treatment for Kawasaki Disease: Challenges for Current and Future Therapies JOURNAL OF PEDIATRICS McCrindle, B. W., Tierney, E. 2017; 184: 7–10

  View details for PubMedID 28233548

• Right-Dominant Unbalanced Atrioventricular Septal Defect: Echocardiography in Surgical Decision Making. Journal of the American Society of Echocardiography Arunamata, A., Balasubramanian, S., Mainwaring, R., Maeda, K., Selamet Tierney, E. S. 2017; 30 (3): 216-226

  Abstract

  Management of right-dominant atrioventricular septal defect (AVSD) remains a challenge given the spectrum of ventricular hypoplasia. The purpose of this study was to assess whether reported echocardiographic indices and additional measurements were associated with operative strategy in right-dominant AVSD.A blinded observer retrospectively reviewed preoperative echocardiograms of patients who underwent surgery for right-dominant AVSD (January 2000 to July 2013). Ventricular dimensions, atrioventricular valve index (AVVI; left valve area/right valve area), and right ventricular (RV)/left ventricular (RV/LV) inflow angle were measured. A second observer measured a subset of studies to assess agreement. Pearson correlation analysis was performed to examine the relationship between ventricular septal defect size (indexed to body surface area) and RV/LV inflow angle in systole. A separate validation cohort was identified using the same methodology (August 2013 to July 2016).Of 46 patients with right-dominant AVSD (median age, 1 day; range, 0-11 months), overall survival was 76% at 7 years. Twenty-eight patients (61%) underwent single-ventricle palliation and had smaller LV dimensions and volumes, AVVIs (P = .005), and RV/LV inflow angles in systole (P = .007) compared with those who underwent biventricular operations. Three patients undergoing biventricular operations underwent transplantation or died and had lower indexed LV end-diastolic volumes compared with the remaining patients (P = .005). Interobserver agreement for the measured echocardiographic indices was good (intraclass correlation coefficient = 0.70-0.95). Ventricular septal defect size and RV/LV inflow angle in systole had a strong negative correlation (r = -0.7, P < .001). In the validation cohort (n = 12), RV/LV inflow angle in systole ≤ 114° yielded sensitivity of 100% and AVVI ≤ 0.70 yielded sensitivity of 88% for single-ventricle palliation.Mortality remains high among patients with right-dominant AVSD. RV/LV inflow angle in systole and AVVI are reproducible measurements that may be used in conjunction with several echocardiographic parameters to support suitability for a biventricular operation in right-dominant AVSD.

  View details for DOI 10.1016/j.echo.2016.10.017

  View details for PubMedID 27939051

• Practice Patterns in Postoperative Echocardiographic Surveillance after Congenital Heart Surgery in Children: A Single Center Experience JOURNAL OF PEDIATRICS Arunamata, A., Axelrod, D. M., Kipps, A. K., McElhinney, D. B., Shin, A. Y., Hanley, F. L., Olson, I. L., Roth, S. J., Tierney, E. S. 2017; 180: 87-?

  Abstract

  To review current institutional practice and describe factors contributing to variation in inpatient postoperative imaging surveillance after congenital heart surgery.We reviewed records of all children who underwent congenital heart surgery from June to December 2014. Number and primary indications for postoperative transthoracic echocardiograms (TTEs), providers involved, cardiovascular intensive care unit (CVICU) and total hospital length of stay, and Risk-Adjustment for Congenital Heart Surgery-1 scores were recorded.A total of 253 children (age at surgery: 8 months [2 days-19 years]) received 556 postoperative TTEs (median 1 TTE/patient [1-14]), and 23% had ≥3 TTEs. Fifteen of 556 TTEs (2.7%) revealed a new abnormal finding. The majority of TTEs (59%) were performed in the CVICU (1.5 ± 1.1 TTEs/week/patient), with evaluation of function as the most common indication (44%). Attending physician practice >10 years was not associated with fewer TTEs (P = .12). Patients with ≥3 TTEs had higher Risk-Adjustment for Congenital Heart Surgery-1 scores (P = .001), longer CVICU lengths of stay (22 vs 3 days; P < .0001), longer overall hospitalizations (28 vs 7 days; P < .0001), and a higher incidence of mechanical circulatory support (10% vs 0%; P < .0001) than those with <3 TTEs. Eight patients with ≥3 TTEs did not survive, compared with 3 with <3 TTEs (P = .0004).There was wide intra-institutional variation in echocardiographic use among similar complexity surgeries. Frequency of postoperative echocardiographic surveillance was associated with degree of surgical complexity and severity of postoperative clinical condition. Few studies revealed new abnormal findings. These results may help establish evidence-based guidelines for inpatient echocardiographic surveillance after congenital heart surgery.

  View details for DOI 10.1016/j.jpeds.2016.09.061

  View details for Web of Science ID 000390028100018

• Assessment of Progressive Pathophysiology After Early Prenatal Diagnosis of the Ebstein Anomaly or Tricuspid Valve Dysplasia AMERICAN JOURNAL OF CARDIOLOGY Tierney, E. S., McElhinney, D. B., Freud, L. R., Tworetzky, W., Cuneo, B. F., Escobar-Diaz, M. C., Ikemba, C., Kalish, B. T., Komarlu, R., Levasseur, S. M., Puchalski, M. D., Satou, G. M., Silverman, N. H., Moon-Grady, A. J. 2017; 119 (1): 106-111

  Abstract

  In fetuses with Ebstein anomaly or tricuspid valve dysplasia (EA/TVD), poor hemodynamic status is associated with worse neonatal outcome. It is not known whether EA/TVD fetuses with more favorable physiology earlier in gestation progress to more severe disease in the third trimester. We evaluated if echocardiographic indexes in EA/TVD fetuses presenting <24 weeks of gestation are reliable indicators of physiologic status later in pregnancy. This multicenter, retrospective study included 51 fetuses presenting at <24 weeks of gestation with EA/TVD and serial fetal echocardiograms ≥4 weeks apart. We designated the following as markers of poor outcome: absence of anterograde flow across the pulmonary valve, pulmonary valve regurgitation, cardiothoracic area ratio >0.48, left ventricular (LV) dysfunction, or tricuspid valve (TV) annulus Z-score >5.6. Median gestational age at diagnosis was 21 weeks (range, 18 to 24). Eighteen fetuses (35%) had no markers for poor hemodynamic status initially, whereas only 7 of these continued to have no markers of poor outcome in the third trimester. Nine of 27 fetuses (33%) with anterograde pulmonary blood flow on the first echocardiogram developed pulmonary atresia; 7 of 39 (18%) developed new pulmonary valve regurgitation. LV dysfunction was present in 2 (4%) patients at <24 weeks but in 14 (37%) later (p <0.001). The TV annulus Z-score and cardiothoracic area both increased from diagnosis to follow-up. In conclusion, progressive hemodynamic compromise was common in this cohort. Our study highlights that care must be taken in counseling before 24 weeks, as the absence of factors associated with poor outcome early in pregnancy may be falsely reassuring.

  View details for DOI 10.1016/j.amjcard.2016.09.022

  View details for Web of Science ID 000391246900017

• Reproducibility of Left Ventricular Dimension Versus Area Versus Volume Measurements in Pediatric Patients With Dilated Cardiomyopathy. Circulation. Cardiovascular imaging Selamet Tierney, E. S., Hollenbeck-Pringle, D. n., Lee, C. K., Altmann, K. n., Dunbar-Masterson, C. n., Golding, F. n., Lu, M. n., Miller, S. G., Molina, K. n., Natarajan, S. n., Taylor, C. L., Trachtenberg, F. n., Colan, S. D. 2017; 10 (11)

  Abstract

  Multiple echocardiographic methods are used to measure left ventricular size and function. Clinical management is based on individual evaluations and longitudinal trends. The Pediatric Heart Network VVV study (Ventricular Volume Variability) in pediatric patients with dilated cardiomyopathy has reported reproducibility of several of these measures, and how disease state and number of beats impact their reproducibility. In this study, we investigated the impact of observer and sonographer variation on reproducibility of dimension, area, and volume methods to determine the best method for both individual and sequential evaluations.In 8 centers, echocardiograms were obtained on 169 patients prospectively. During the same visit, 2 different sonographers acquired the same imaging protocol on each patient. Each acquisition was analyzed by 2 different observers; first observer analyzed the first acquisition twice. Intraobserver, interobserver, interacquisition, and interobserver-acquisition (different observers and different acquisition) reproducibility were assessed on measurements of left ventricular end-diastolic dimension, area, and volume. Left ventricular shortening fraction, ejection fraction, mass, and fractional area change were calculated. Percent difference was calculated as (interobservation difference/mean)×100. Interobserver reproducibility for both acquisitions was better for both volume and dimension measurements (P≤0.002) compared with area measurements, whereas intraobserver, interacquisition (for both observers), and interobserver-acquisition reproducibilities (for both observer-acquisition sets) were best for volume measurements (P≤0.01). Overall, interobserver-acquisition percent differences were significantly higher than interobserver and interacquisition percent differences (P<0.001).In pediatric patients with dilated cardiomyopathy, compared with dimension and area methods, left ventricular measurements by volume method have the best reproducibility in settings where assessment is not performed by the same personnel.URL: https://www.clinicaltrials.gov. Unique identifier: NCT00123071.

  View details for PubMedID 29133477

  View details for PubMedCentralID PMC5705043

• Pediatric Echocardiography by Work Relative Value Units: Is Study Complexity Adequately Captured? Journal of the American Society of Echocardiography Balasubramanian, S., Kipps, A. K., Smith, S. N., Tacy, T. A., Selamet Tierney, E. S. 2016; 29 (11): 1084-1091

  Abstract

  Present resource-based relative value unit (RVU) assignment for echocardiography is based on Current Procedural Terminology (CPT) codes, which do not incorporate complexity of diagnosis, time spent for image acquisition, or interpretation of echocardiograms. The objective of this study was to determine whether CPT-based RVU assignment accurately reflects physician effort in performing and interpreting pediatric echocardiographic examinations.Cardiac complexity category (CCC) and physician time for study interpretation of 123 echocardiograms (June to September 2013) were prospectively assigned. Categories included (1) focused effusion/function evaluation, (2) normal anatomy/focused preterm infant studies, (3) acquired heart disease, (4) congenital heart disease excluding single ventricles, (5) single ventricles including heterotaxy syndrome, and (6) hearts on mechanical support. Subsequently, a random sample of echocardiograms (March to August 2013) were retrospectively analyzed, and each study was assigned a CCC and an extrapolated median interpretation time (MIT) on the basis of prospective data collection. Assigned work RVUs based on CPT codes were recorded. Comparisons were made between CCC and time for study interpretation, work RVUs, number of images acquired, and total scan time.A total of 933 echocardiograms were analyzed: 198 (21%), 174 (19%), 98 (11%), 359 (35%), 84 (9%), and 20 (2%) studies in CCCs 1 to 6, respectively. Total scan time, MIT, number of images, and work RVUs were different among CCCs (P < .0001). However, among the more complex studies (CCCs 2-5), work RVUs were similar, while number of images obtained and MIT were different (P < .001). Correlation analysis showed no association between work RVUs and CCC, total scan, or number of images per study. Compared with older patients, work RVUs of studies in children <2 years of age were lower, while all other markers of study complexity were higher (P < .05).Current CPT-based assignment of work RVUs does not discriminate study complexity and physician effort. The results of this study highlight the need for a refined system that accurately assesses physician effort in pediatric echocardiography.

  View details for DOI 10.1016/j.echo.2016.05.015

  View details for PubMedID 27405593

• Assessment of Progressive Pathophysiology After Early Prenatal Diagnosis of the Ebstein Anomaly or Tricuspid Valve Dysplasia. American journal of cardiology Selamet Tierney, E. S., McElhinney, D. B., Freud, L. R., Tworetzky, W., Cuneo, B. F., Escobar-Diaz, M. C., Ikemba, C., Kalish, B. T., Komarlu, R., Levasseur, S. M., Puchalski, M. D., Satou, G. M., Silverman, N. H., Moon-Grady, A. J. 2016

  Abstract

  In fetuses with Ebstein anomaly or tricuspid valve dysplasia (EA/TVD), poor hemodynamic status is associated with worse neonatal outcome. It is not known whether EA/TVD fetuses with more favorable physiology earlier in gestation progress to more severe disease in the third trimester. We evaluated if echocardiographic indexes in EA/TVD fetuses presenting <24 weeks of gestation are reliable indicators of physiologic status later in pregnancy. This multicenter, retrospective study included 51 fetuses presenting at <24 weeks of gestation with EA/TVD and serial fetal echocardiograms ≥4 weeks apart. We designated the following as markers of poor outcome: absence of anterograde flow across the pulmonary valve, pulmonary valve regurgitation, cardiothoracic area ratio >0.48, left ventricular (LV) dysfunction, or tricuspid valve (TV) annulus Z-score >5.6. Median gestational age at diagnosis was 21 weeks (range, 18 to 24). Eighteen fetuses (35%) had no markers for poor hemodynamic status initially, whereas only 7 of these continued to have no markers of poor outcome in the third trimester. Nine of 27 fetuses (33%) with anterograde pulmonary blood flow on the first echocardiogram developed pulmonary atresia; 7 of 39 (18%) developed new pulmonary valve regurgitation. LV dysfunction was present in 2 (4%) patients at <24 weeks but in 14 (37%) later (p <0.001). The TV annulus Z-score and cardiothoracic area both increased from diagnosis to follow-up. In conclusion, progressive hemodynamic compromise was common in this cohort. Our study highlights that care must be taken in counseling before 24 weeks, as the absence of factors associated with poor outcome early in pregnancy may be falsely reassuring.

  View details for DOI 10.1016/j.amjcard.2016.09.022

  View details for PubMedID 27793395

• Patterns of Carotid Intima-Media Thickness Progression in Kawasaki Patients: A Crystal Ball for Long-Term Vascular Health? JOURNAL OF THE AMERICAN HEART ASSOCIATION Haley, J., Tierney, E. 2016; 5 (7)

  View details for PubMedID 27381761

• Diagnosing Neonatal Aortic Coarctation in the Setting of Patent Ductus Arteriosus. Annals of thoracic surgery Peng, D. M., Punn, R., Maeda, K., Selamet Tierney, E. S. 2016; 101 (3): 1005-1010

  Abstract

  In neonates, it is challenging to diagnose aortic coarctation in the setting of a patent ductus arteriosus (PDA). Frequently, serial echocardiograms are performed, and diagnosis is delayed until the PDA closes. The purpose of this study was to identify echocardiographic predictors of neonatal coarctation in the presence of a PDA in cases in which diagnosis is uncertain.We retrospectively identified neonates diagnosed with possible but not definitive coarctation in the presence of a PDA by echocardiography (January 2004 through August 2013). The carotid-subclavian artery index (CSAi) was defined as the distal transverse arch diameter divided by the distance between the left common carotid and left subclavian arteries. Medical records were reviewed to identify patients who underwent coarctation repair within 1 year. A separate validation group was identified with the same methodology (September 2013 through April 2015).Thirty-three patients were identified (median age 1, range 0-8 days). Twelve patients (36%) underwent coarctation repair. The coarctation group had smaller aortic and mitral valves, distal transverse arch, and isthmus z scores, larger right innominate artery, and longer transverse arch compared with the remaining group (p < 0.05). The CSAi was lower in the coarctation group (p = 0.014), and a cutoff of less than 0.85 yielded a sensitivity of 0.83 and specificity of 0.86 for coarctation (area under the receiver operating characteristic curve, 0.91). In the validation group (n = 12; median follow-up, 316 days), none of the 8 patients with a CSAi of greater than 0.85 have required surgery. The intraclass correlation coefficient for CSAi was 0.79 (95% confidence interval, 0.18 to 0.95).The CSAi, a simple and reproducible measure, can identify neonates at risk for aortic coarctation even in the presence of a PDA, prevent multiple echocardiographic evaluations, and hence guide appropriate resource utilization.

  View details for DOI 10.1016/j.athoracsur.2015.09.050

  View details for PubMedID 26652138

• Diagnosing Neonatal Aortic Coarctation in the Setting of Patent Ductus Arteriosus ANNALS OF THORACIC SURGERY Peng, D. M., Punn, R., Maeda, K., Tierney, E. S. 2016; 101 (3): 1005-1011

  Abstract

  In neonates, it is challenging to diagnose aortic coarctation in the setting of a patent ductus arteriosus (PDA). Frequently, serial echocardiograms are performed, and diagnosis is delayed until the PDA closes. The purpose of this study was to identify echocardiographic predictors of neonatal coarctation in the presence of a PDA in cases in which diagnosis is uncertain.We retrospectively identified neonates diagnosed with possible but not definitive coarctation in the presence of a PDA by echocardiography (January 2004 through August 2013). The carotid-subclavian artery index (CSAi) was defined as the distal transverse arch diameter divided by the distance between the left common carotid and left subclavian arteries. Medical records were reviewed to identify patients who underwent coarctation repair within 1 year. A separate validation group was identified with the same methodology (September 2013 through April 2015).Thirty-three patients were identified (median age 1, range 0-8 days). Twelve patients (36%) underwent coarctation repair. The coarctation group had smaller aortic and mitral valves, distal transverse arch, and isthmus z scores, larger right innominate artery, and longer transverse arch compared with the remaining group (p < 0.05). The CSAi was lower in the coarctation group (p = 0.014), and a cutoff of less than 0.85 yielded a sensitivity of 0.83 and specificity of 0.86 for coarctation (area under the receiver operating characteristic curve, 0.91). In the validation group (n = 12; median follow-up, 316 days), none of the 8 patients with a CSAi of greater than 0.85 have required surgery. The intraclass correlation coefficient for CSAi was 0.79 (95% confidence interval, 0.18 to 0.95).The CSAi, a simple and reproducible measure, can identify neonates at risk for aortic coarctation even in the presence of a PDA, prevent multiple echocardiographic evaluations, and hence guide appropriate resource utilization.

  View details for DOI 10.1016/j.athoracsur.2015.09.050

  View details for Web of Science ID 000370339700033

• Anatomic Factors Associated With Truncal Valve Insufficiency and the Need for Truncal Valve Repair. World journal for pediatric & congenital heart surgery Patrick, W. L., Mainwaring, R. D., Carrillo, S. A., Ma, M., Reinhartz, O., Petrossian, E., Selamet Tierney, E. S., Reddy, V. M., Hanley, F. L. 2016; 7 (1): 9-15

  Abstract

  Truncus arteriosus is a complex and heterogeneous form of congenital heart defect. Many of the risk factors from several decades ago, including late repair and interrupted aortic arch, have been mitigated through better understanding of the entity and improved surgical techniques. However, truncal valve dysfunction remains an important cause of morbidity and mortality. The purpose of this study was to evaluate the anatomic factors associated with truncal valve dysfunction and the need for truncal valve surgery.This was a retrospective review of 72 infants who underwent repair of truncus arteriosus at our institution. The median age at surgery was nine days, and the median weight was 3.1 kg. Preoperative assessment of truncal valve insufficiency by echocardiography revealed no or trace insufficiency in 30, mild in 25, moderate in 10, and severe in 7. The need for truncal valve surgery was dictated by the severity of truncal valve insufficiency.Sixteen (22%) of the 72 patients undergoing truncus arteriosus repair had concomitant truncal valve surgery. Anatomic factors associated with the need for truncal valve surgery included an abnormal number of truncal valve cusps (P < .005), presence of valve dysplasia (P < .005), and the presence of an anomalous coronary artery pattern (P < .005). Fifteen (94%) of the sixteen patients who underwent concomitant surgery had two or all three of these anatomic factors (sensitivity = 94%, specificity = 85%).This study demonstrates that the presence of specific anatomic factors was closely associated with the presence of truncal valve insufficiency and the need for concomitant truncal valve surgery. Preoperative evaluation of these anatomic factors may provide a useful tool in determining who should undergo concomitant truncal valve surgery.

  View details for DOI 10.1177/2150135115608093

  View details for PubMedID 26714988

• Live Video Diet and Exercise Intervention in Overweight and Obese Youth: Adherence and Cardiovascular Health. journal of pediatrics Nourse, S. E., Olson, I., Popat, R. A., Stauffer, K. J., Vu, C. N., Berry, S., Kazmucha, J., Ogareva, O., Couch, S. C., Urbina, E. M., Selamet Tierney, E. S. 2015; 167 (3): 533-539 e1

  Abstract

  To evaluate adherence of overweight and obese adolescents to a live video lifestyle intervention. The impact on vascular and functional health was also assessed.Twenty adolescents 14.5 ± 2.1 years of age with body mass index z-score 1.94 ± 0.43 were enrolled. The 12-week intervention included 3-times-weekly videoconference sessions with a trainer and weekly diet consultations. Adherence was evaluated by completion rate and percentage of sessions attended. Vascular health indices and traditional cardiovascular risk factors were obtained at baseline and study end.Seventeen participants (85%) completed the intervention. The participants attended 93 ± 11% of scheduled sessions. Reasons for absences included illness/injury (23%), school activities (21%), holidays (18%), forgetting the appointment (8%), Internet connectivity issues (7%), and family emergency (7%). Significant changes were observed in waist-hip ratio (0.87 ± 0.08 vs 0.84 ± 0.08, P = .03), total (159 ± 27 vs 147 ± 23 mg/dL, P = .004) and low-density lipoprotein cholesterol levels (91 ± 20 vs 81 ± 18 mg/dL, P = .004), volume of inspired oxygen per heartbeat at peak exercise (69 ± 16 vs 72 ± 15%, P = .01), and functional movement score (13 ± 2 vs 17 ± 1, P < .001). Participants with abnormal vascular function at baseline showed improvement in endothelial function and arterial stiffness indices (P = .01 and P = .04, respectively).A 12-week live video intervention promotes adherence among overweight and obese adolescents and shows promise for improving vascular and functional health. Integrating telehealth into preventive care has the potential to improve cardiovascular health in the youth at risk.

  View details for DOI 10.1016/j.jpeds.2015.06.015

  View details for PubMedID 26154402

• Outcomes and Predictors of Perinatal Mortality in Fetuses With Ebstein Anomaly or Tricuspid Valve Dysplasia in the Current Era A Multicenter Study CIRCULATION Freud, L. R., Escobar-Diaz, M. C., Kalish, B. T., Komarlu, R., Puchalski, M. D., Jaeggi, E. T., Szwast, A. L., Freire, G., Levasseur, S. M., Kavanaugh-McHugh, A., Michelfelder, E. C., Moon-Grady, A. J., Donofrio, M. T., Howley, L. W., Tierney, E. S., Cuneo, B. F., Morris, S. A., Pruetz, J. D., van der Velde, M. E., Kovalchin, J. P., Ikemba, C. M., Vernon, M. M., Samai, C., Satou, G. M., Gotteiner, N. L., Phoon, C. K., Silverman, N. H., McElhinney, D. B., Tworetzky, W. 2015; 132 (6): 481-489

  Abstract

  Ebstein anomaly and tricuspid valve dysplasia are rare congenital tricuspid valve malformations associated with high perinatal mortality. The literature consists of small, single-center case series spanning several decades. We performed a multicenter study to assess the outcomes and factors associated with mortality after fetal diagnosis in the current era.Fetuses diagnosed with Ebstein anomaly and tricuspid valve dysplasia from 2005 to 2011 were included from 23 centers. The primary outcome was perinatal mortality, defined as fetal demise or death before neonatal discharge. Of 243 fetuses diagnosed at a mean gestational age of 27±6 weeks, there were 11 lost to follow-up (5%), 15 terminations (6%), and 41 demises (17%). In the live-born cohort of 176 live-born patients, 56 (32%) died before discharge, yielding an overall perinatal mortality of 45%. Independent predictors of mortality at the time of diagnosis were gestational age <32 weeks (odds ratio, 8.6; 95% confidence interval, 3.5-21.0; P<0.001), tricuspid valve annulus diameter z-score (odds ratio, 1.3; 95% confidence interval, 1.1-1.5; P<0.001), pulmonary regurgitation (odds ratio, 2.9; 95% confidence interval, 1.4-6.2; P<0.001), and a pericardial effusion (odds ratio, 2.5; 95% confidence interval, 1.1-6.0; P=0.04). Nonsurvivors were more likely to have pulmonary regurgitation at any gestational age (61% versus 34%; P<0.001), and lower gestational age and weight at birth (35 versus 37 weeks; 2.5 versus 3.0 kg; both P<0.001).In this large, contemporary series of fetuses with Ebstein anomaly and tricuspid valve dysplasia, perinatal mortality remained high. Fetuses with pulmonary regurgitation, indicating circular shunt physiology, are a high-risk cohort and may benefit from more innovative therapeutic approaches to improve survival.

  View details for DOI 10.1161/CIRCULATIONAHA.115.015839

  View details for Web of Science ID 000359666500003

  View details for PubMedID 26059011

• The Reproducibility and Absolute Values of Echocardiographic Measurements of Left Ventricular Size and Function in Children Are Algorithm Dependent JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Margossian, R., Chen, S., Sleeper, L. A., Tani, L. Y., Shirali, G., Golding, F., Tierney, E. S., Altmann, K., Campbell, M. J., Szwast, A., Sharkey, A., Radojewski, E., Colan, S. D. 2015; 28 (5): 549-U137

  Abstract

  Several quantification algorithms for measuring left ventricular (LV) size and function are used in clinical and research settings. The aims of this study were to investigate the effects of measurement algorithm and beat averaging on the reproducibility of measurements of the left ventricle and to assess the magnitude of agreement among the algorithms in children with dilated cardiomyopathy.Echocardiograms were obtained in 169 children from eight clinical centers. Inter- and intrareader reproducibility was assessed on measurements of LV volumes using the biplane Simpson, modified Simpson, and 5/6 × area × length (5/6AL) algorithms. Percentage error was calculated as inter- or intrareader difference/mean × 100. Single-beat measurements and the three-beat average (3BA) were compared. Intraclass correlation coefficients were calculated to assess agreement.Single-beat interreader reproducibility was lowest (percentage error was highest) using biplane Simpson; 5/6AL and modified Simpson were similar but significantly better than biplane Simpson (P < .05). Single-beat intrareader reproducibility was highest using 5/6AL (P < .05). The 3BA improved reproducibility for almost all measures (P < .05). Reproducibility in both single-beat and 3BA values fell with greater LV dilation and systolic dysfunction (P < .05). Intraclass correlation coefficients were >0.95 across measures, although absolute volume and mass values were systematically lower for biplane Simpson compared with modified Simpson and 5/6AL.The reproducibility of LV size and functional measurements in children with dilated cardiomyopathy is highest using the 5/6AL algorithm and can be further improved by using the 3BA. However, values derived from different algorithms are not interchangeable.

  View details for DOI 10.1016/j.echo.2015.01.014

  View details for Web of Science ID 000353894400008

  View details for PubMedID 25728351

• Pediatric Interventions Using Noninvasive Vascular Health Indices HYPERTENSION Ridha, M., Nourse, S. E., Tierney, E. S. 2015; 65 (5): 949-U508

  View details for DOI 10.1161/HYPERTENSIONAHA.114.04926

  View details for Web of Science ID 000352490400082

  View details for PubMedID 25801875

• Echocardiographic measures associated with early postsurgical myocardial dysfunction in pediatric patients with mitral valve regurgitation. Journal of the American Society of Echocardiography Arunamata, A., Selamet Tierney, E. S., Tacy, T. A., Punn, R. 2015; 28 (3): 284-293

  Abstract

  The assessment of left ventricular (LV) systolic function using conventional echocardiographic measures is problematic in the setting of mitral regurgitation (MR) given that altered loading conditions can mask underlying ventricular dysfunction. The purpose of this study was to characterize LV function and deformation before and after effective mitral valve repair or replacement to determine echocardiographic measures associated with early postoperative myocardial dysfunction.Baseline LV function was assessed retrospectively by conventional echocardiography and speckle-tracking strain analysis pre- and postoperatively in patients diagnosed with MR between January 2000 and March 2013, excluding patients with less than mild to moderate MR preoperatively, left-sided obstructive lesions, large septal defects, or more than mild MR postoperatively.Forty-six pediatric patients were evaluated (average age, 8.2 ± 6.4 years). Thirteen patients had normal preoperative ejection fractions but significant postoperative dysfunction (defined as an ejection fraction < 50%). Compared with the 33 patients with normal postoperative function, age (11.5 ± 7.1 vs 7.3 ± 5.7 years, P = .04), global circumferential strain (-13.2 ± 5.6% vs -17.1 ± 4.6%, P = .02), and global circumferential strain rate (-0.94 ± 0.40 vs -1.36 ± 0.42 sec(-1), P = .004) were found to be statistically different. Using receiver operating characteristic curves, an older preoperative age (area under the curve, 0.67; P = .03), lower global circumferential strain magnitude (area under the curve, 0.74; P = .007), and lower global circumferential strain rate magnitude (area under the curve, 0.80; P = .0004) were determined to be factors associated with early postoperative LV dysfunction after surgical repair of MR.Strain measurements may be useful as part of the echocardiographic assessment of patients with MR and can guide timing for surgical repair in the pediatric population.

  View details for DOI 10.1016/j.echo.2014.11.010

  View details for PubMedID 25555521

• Carotid Artery Intima-Media Thickness Measurements in the Youth: Reproducibility and Technical Considerations JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Tierney, E. S., Gauvreau, K., Jaff, M. R., Gal, D., Nourse, S. E., Trevey, S., O'Neill, S., Baker, A., Newburger, J. W., Colan, S. D. 2015; 28 (3): 309-316

  Abstract

  Carotid artery intima-media thickness (CIMT), a marker of atherosclerosis, is increased in youth at risk for future cardiovascular disease. Some pediatric studies have used CIMT as a primary outcome in clinical trials, yet data are limited on the standardization of methodology in children. The goal of this study was to evaluate reproducibility of CIMT measurements using two different measurement techniques.Carotid artery ultrasound studies of children and adolescents obtained as a component of a research study in Kawasaki syndrome were retrospectively analyzed. The CIMTs of both common carotid arteries (CCAs) were measured by one of two sonographers at the time in the cardiac cycle when resolution subjectively was determined to be optimal (Opt-CIMT). These sonographers blindly remeasured a random sample of studies of their own and each other's, using the same method. Another observer made CIMT measurements using exclusively frames on the R wave (R-CIMT). A fourth observer independently measured a random sample of studies twice with the R-CIMT method.Carotid artery images from 184 subjects (mean age, 14.7 ± 2.2 years) were analyzed. The intraclass correlation coefficient for interobserver variability was 0.86 (95% confidence interval [CI], 0.69-0.94) compared with 0.85 (95% CI, 0.65-0.93) for the right and 0.86 (95% CI, 0.67-0.94) versus 0.95 (95% CI, 0.87-0.98) for the left CCA for Opt-CIMT and R-CIMT, respectively. R-CIMT was significantly thicker than Opt-CIMT (right CCA, 0.439 ± 0.030 vs 0.428 ± 0.024 mm, P < .001; left CCA, 0.446 ± 0.030 vs 0.434 ± 0.025 mm, P < .001).Pediatric CIMT measurements have excellent reproducibility when the same methodology is applied but vary significantly throughout the cardiac cycle. This report highlights the need to standardize CIMT measurements in the youth and supports the use of electrocardiographic timing, as recommended in adults, in pediatric longitudinal studies.

  View details for DOI 10.1016/j.echo.2014.10.004

  View details for Web of Science ID 000352144400007

  View details for PubMedID 25459501

• Echocardiographic Measures Associated With Early Postsurgical Myocardial Dysfunction in Pediatric Patients With Mitral Valve Regurgitation JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Arunamata, A., Tierney, E. S., Tacy, T. A., Punn, R. 2015; 28 (3): 284-293

  Abstract

  The assessment of left ventricular (LV) systolic function using conventional echocardiographic measures is problematic in the setting of mitral regurgitation (MR) given that altered loading conditions can mask underlying ventricular dysfunction. The purpose of this study was to characterize LV function and deformation before and after effective mitral valve repair or replacement to determine echocardiographic measures associated with early postoperative myocardial dysfunction.Baseline LV function was assessed retrospectively by conventional echocardiography and speckle-tracking strain analysis pre- and postoperatively in patients diagnosed with MR between January 2000 and March 2013, excluding patients with less than mild to moderate MR preoperatively, left-sided obstructive lesions, large septal defects, or more than mild MR postoperatively.Forty-six pediatric patients were evaluated (average age, 8.2 ± 6.4 years). Thirteen patients had normal preoperative ejection fractions but significant postoperative dysfunction (defined as an ejection fraction < 50%). Compared with the 33 patients with normal postoperative function, age (11.5 ± 7.1 vs 7.3 ± 5.7 years, P = .04), global circumferential strain (-13.2 ± 5.6% vs -17.1 ± 4.6%, P = .02), and global circumferential strain rate (-0.94 ± 0.40 vs -1.36 ± 0.42 sec(-1), P = .004) were found to be statistically different. Using receiver operating characteristic curves, an older preoperative age (area under the curve, 0.67; P = .03), lower global circumferential strain magnitude (area under the curve, 0.74; P = .007), and lower global circumferential strain rate magnitude (area under the curve, 0.80; P = .0004) were determined to be factors associated with early postoperative LV dysfunction after surgical repair of MR.Strain measurements may be useful as part of the echocardiographic assessment of patients with MR and can guide timing for surgical repair in the pediatric population.

  View details for DOI 10.1016/j.echo.2014.11.010

  View details for Web of Science ID 000352144400004

  View details for PubMedID 25555521

• Adrenergic receptor genotype influences heart failure severity and ß-blocker response in children with dilated cardiomyopathy. Pediatric research Reddy, S., Fung, A., Manlhiot, C., Selamet Tierney, E. S., Chung, W. K., Blume, E., Kaufman, B. D., Goldmuntz, E., Colan, S., Mital, S. 2015; 77 (2): 363-369

  Abstract

  Adrenergic receptor (ADR) genotypes are associated with heart failure (HF) and β-blocker response in adults. We assessed the influence of ADR genotypes in children with dilated cardiomyopathy (DCM).Ninety-one children with advanced DCM and 44 with stable DCM were genotyped for three ADR genotypes associated with HF risk in adults: α2cdel322-325, β1Arg389, and β2Arg16. Data were analyzed by genotype and β-blocker use. Mean age at enrollment was 8.5 y.One-year event-free survival was 51% in advanced and 80% in stable DCM. High-risk genotypes were associated with higher left ventricular (LV) filling pressures, higher systemic and pulmonary vascular resistance, greater decline in LV ejection fraction (P < 0.05), and a higher frequency of mechanical circulatory support while awaiting transplant (P = 0.05). While β-blockers did not reduce HF severity in the overall cohort, in the subset with multiple high-risk genotypes, those receiving β-blockers showed better preservation of cardiac function and hemodynamics compared with those not receiving β-blockers (interaction P < 0.05).Our study identifies genetic risk markers that may help in the identification of patients at risk for developing decompensated HF and who may benefit from early institution of β-blocker therapy before progression to decompensated HF.

  View details for DOI 10.1038/pr.2014.183

  View details for PubMedID 25406899

  View details for PubMedCentralID PMC4298011

• Reliability of echocardiographic measurements of left ventricular systolic function in potential pediatric heart transplant donors. journal of heart and lung transplantation Chen, S., Selamet Tierney, E. S., Khush, K. K., Nguyen, J., Goldstein, B. A., May, L. J., Hollander, S. A., Kaufman, B. D., Rosenthal, D. N. 2015; 34 (1): 100-106

  Abstract

  Echocardiogram reports, but not images, are usually available for the evaluation of potential donor hearts. To assess the reliability of local reports of potential pediatric heart donors, we compared echocardiographic measurements of left ventricular (LV) systolic function between local hospitals and a central echocardiography laboratory.We identified all potential donors aged <18 years managed by the California Transplant Donor Network from 2009 to 2013. Echocardiograms and reports were obtained from local hospitals. All studies were reviewed in a central laboratory by an experienced pediatric cardiologist blinded to local reports. Local and central measurements of fractional shortening (FS) were compared using the Bland-Altman method (mean difference ± 2 standard deviations). LV function was categorized based on FS as normal or mild, moderately, or severely depressed.There were 70 studies from 59 donors with local and central measurements of FS. The mean difference between local and central FS was 3.9 ± 9.0. The limits of agreement ranged from -14.2 to 22. Twenty-five studies had discordant measurements of LV function, with 17 discordant by 1 category and 8 by 2 or more categories. Of 55 studies categorized as normal by local measurement, 6 were moderately to severely depressed by central review. Of 15 studies categorized as depressed by local measurement, 3 were normal by central review.Local and central measurements of LV systolic function were discordant in 36% of studies. Given such discordance, efforts to obtain and view actual echocardiographic images should be part of the standard evaluation of potential pediatric heart donors.

  View details for DOI 10.1016/j.healun.2014.08.019

  View details for PubMedID 25307622

  View details for PubMedCentralID PMC4278954

• Feasibility of Neonatal Pulse Wave Velocity and Association with Maternal Hemoglobin A(1c) NEONATOLOGY Chen, S., Chetty, S., Lowenthal, A., Evans, J. M., Vu, C., Stauffer, K. J., Lyell, D., Tierney, E. S. 2015; 107 (1): 20-26

  Abstract

  Use of non-invasive peripheral arterial tonometry to assess arterial stiffness has not been studied in neonates. Perinatal factors impact childhood vascular health, but the effect in neonates remains to be examined.To examine the feasibility of pulse wave velocity (PWV) among healthy term neonates, and to evaluate the effects of perinatal factors on neonatal PWV.Pregnant women with singleton gestation presenting for routine care were enrolled. Postnatally, PWV measurements of their neonates were obtained using an arterial tonometer. A variability index was calculated for each PWV measurement. Intra- and inter-observer reproducibility were illustrated with Bland-Altman plots. Medical records were reviewed. Relationships between neonatal PWV and perinatal factors were examined.PWV measurements were attempted in 76 neonates and successfully obtained in 67 (88%). Using PWV measurements with a variability index ≤0.25 (48 neonates), the intra-class coefficient was 0.69. The mean differences (limits of agreement) for intra- and inter-rater reproducibility were 0.02 (-3.64 to 3.60) and 0.34 (-2.23 to 2.39), respectively. Median neonatal PWV was 2.80 m/s (range 0.60-8.40). Neonates of mothers with HgbA1c ≥6% had significantly higher PWV than neonates of mothers with HgbA1c <6% (4.12 m/s, 95% CI 3.22-5.02, vs. 2.78 m/s, 95% CI 2.28-3.28, p = 0.02).Neonatal PWV using peripheral arterial tonometry is feasible and reproducible when using measurements with a variability index ≤0.25. Neonates of mothers with increased HgbA1c had higher PWV, suggesting an effect of maternal hyperglycemia on neonatal vasculature. The long-term implications of this finding warrant further investigation. © 2014 S. Karger AG, Basel.

  View details for DOI 10.1159/000366467

  View details for Web of Science ID 000346246300004

• Feasibility of neonatal pulse wave velocity and association with maternal hemoglobin a1c. Neonatology Chen, S., Chetty, S., Lowenthal, A., Evans, J. M., Vu, C., Stauffer, K. J., Lyell, D., Selamet Tierney, E. S. 2015; 107 (1): 20-26

  Abstract

  Use of non-invasive peripheral arterial tonometry to assess arterial stiffness has not been studied in neonates. Perinatal factors impact childhood vascular health, but the effect in neonates remains to be examined.To examine the feasibility of pulse wave velocity (PWV) among healthy term neonates, and to evaluate the effects of perinatal factors on neonatal PWV.Pregnant women with singleton gestation presenting for routine care were enrolled. Postnatally, PWV measurements of their neonates were obtained using an arterial tonometer. A variability index was calculated for each PWV measurement. Intra- and inter-observer reproducibility were illustrated with Bland-Altman plots. Medical records were reviewed. Relationships between neonatal PWV and perinatal factors were examined.PWV measurements were attempted in 76 neonates and successfully obtained in 67 (88%). Using PWV measurements with a variability index ≤0.25 (48 neonates), the intra-class coefficient was 0.69. The mean differences (limits of agreement) for intra- and inter-rater reproducibility were 0.02 (-3.64 to 3.60) and 0.34 (-2.23 to 2.39), respectively. Median neonatal PWV was 2.80 m/s (range 0.60-8.40). Neonates of mothers with HgbA1c ≥6% had significantly higher PWV than neonates of mothers with HgbA1c <6% (4.12 m/s, 95% CI 3.22-5.02, vs. 2.78 m/s, 95% CI 2.28-3.28, p = 0.02).Neonatal PWV using peripheral arterial tonometry is feasible and reproducible when using measurements with a variability index ≤0.25. Neonates of mothers with increased HgbA1c had higher PWV, suggesting an effect of maternal hyperglycemia on neonatal vasculature. The long-term implications of this finding warrant further investigation. © 2014 S. Karger AG, Basel.

  View details for DOI 10.1159/000366467

  View details for PubMedID 25301402

• Atenolol versus Losartan in Children and Young Adults with Marfan's Syndrome NEW ENGLAND JOURNAL OF MEDICINE Lacro, R. V., Dietz, H. C., Sleeper, L. A., Yetman, A. T., Bradley, T. J., Colan, S. D., Pearson, G. D., Tierney, E. S., Levine, J. C., Atz, A. M., Benson, D. W., Braverman, A. C., Chen, S., De Backer, J., Gelb, B. D., Grossfeld, P. D., Klein, G. L., Lai, W. W., Liou, A., Loeys, B. L., Markham, L. W., Olson, A. K., Paridon, S. M., Pemberton, V. L., Pierpont, M. E., Pyeritz, R. E., Radojewski, E., Roman, M. J., Sharkey, A. M., Stylianou, M. P., Wechsler, S. B., Young, L. T., Mahony, L. 2014; 371 (22): 2061-2071

  Abstract

  Aortic-root dissection is the leading cause of death in Marfan's syndrome. Studies suggest that with regard to slowing aortic-root enlargement, losartan may be more effective than beta-blockers, the current standard therapy in most centers.We conducted a randomized trial comparing losartan with atenolol in children and young adults with Marfan's syndrome. The primary outcome was the rate of aortic-root enlargement, expressed as the change in the maximum aortic-root-diameter z score indexed to body-surface area (hereafter, aortic-root z score) over a 3-year period. Secondary outcomes included the rate of change in the absolute diameter of the aortic root; the rate of change in aortic regurgitation; the time to aortic dissection, aortic-root surgery, or death; somatic growth; and the incidence of adverse events.From January 2007 through February 2011, a total of 21 clinical centers enrolled 608 participants, 6 months to 25 years of age (mean [±SD] age, 11.5±6.5 years in the atenolol group and 11.0±6.2 years in the losartan group), who had an aortic-root z score greater than 3.0. The baseline-adjusted rate of change in the mean (±SE) aortic-root z score did not differ significantly between the atenolol group and the losartan group (-0.139±0.013 and -0.107±0.013 standard-deviation units per year, respectively; P=0.08). Both slopes were significantly less than zero, indicating a decrease in the aortic-root diameter relative to body-surface area with either treatment. The 3-year rates of aortic-root surgery, aortic dissection, death, and a composite of these events did not differ significantly between the two treatment groups.Among children and young adults with Marfan's syndrome who were randomly assigned to losartan or atenolol, we found no significant difference in the rate of aortic-root dilatation between the two treatment groups over a 3-year period. (Funded by the National Heart, Lung, and Blood Institute and others; ClinicalTrials.gov number, NCT00429364.).

  View details for DOI 10.1056/NEJMoa1404731

  View details for Web of Science ID 000345580000005

  View details for PubMedID 25405392

• Arterial applanation tonometry: feasibility and reproducibility in children and adolescents. American journal of hypertension Lowenthal, A., Evans, J. M., Punn, R., Nourse, S. E., Vu, C. N., Popat, R. A., Selamet Tierney, E. S. 2014; 27 (9): 1218-1224

  Abstract

  Aortic pulse wave velocity (PWV) and augmentation index (AIx) are markers of vascular health and have recently been used in pediatric clinical trials. However, there are limited data on standardization of these measurements in pediatrics. The objective of this study was to prospectively test the feasibility and reproducibility of PWV and AIx in children and adolescents.We performed arterial tonometry on 2 different days within 2 weeks in 40 healthy subjects aged 10-19 years. PWV and AIx were measured in triplicate on each visit.The visits were separated by a mean of 3.08±3.7 days. We obtained PWV in 77 of 80 (96%) visits and AIx in 76 of 80 (95%) visits in triplicate. Intraclass correlation coefficients (ICCs) for PWV were 0.61 (95% confidence interval (CI) = 0-0.86) when at least 2 measurements and 0.92 (95% CI = 0-1) when 3 measurements were obtained at each visit that met the quality criteria established for adults by the manufacturer (n = 17 and 3 paired visits, respectively). For AIx, ICCs were 0.78 (95% CI = 0.58-0.88) and 0.81 (95% CI = 0.63-0.90) when measurements with an operator index ≥80, a measure of the quality of the waveform, were included (n = 39 and 36 paired visits, respectively).Arterial applanation tonometry is feasible and reproducible in healthy children and adolescents. AIx has excellent intervisit reproducibility, whereas the intervisit reproducibility of PWV relies on acquisition of multiple measurements that meet quality criteria established for adults. These results have implications for the methodology of future pediatric clinical trials in a population at increasingly higher risk for premature atherosclerosis.

  View details for DOI 10.1093/ajh/hpu034

  View details for PubMedID 24627445

• Arterial Applanation Tonometry: Feasibility and Reproducibility in Children and Adolescents AMERICAN JOURNAL OF HYPERTENSION Lowenthal, A., Evans, J. M., Punn, R., Nourse, S. E., Vu, C. N., Popat, R. A., Tierney, E. S. 2014; 27 (9): 1218-1224

  Abstract

  Aortic pulse wave velocity (PWV) and augmentation index (AIx) are markers of vascular health and have recently been used in pediatric clinical trials. However, there are limited data on standardization of these measurements in pediatrics. The objective of this study was to prospectively test the feasibility and reproducibility of PWV and AIx in children and adolescents.We performed arterial tonometry on 2 different days within 2 weeks in 40 healthy subjects aged 10-19 years. PWV and AIx were measured in triplicate on each visit.The visits were separated by a mean of 3.08±3.7 days. We obtained PWV in 77 of 80 (96%) visits and AIx in 76 of 80 (95%) visits in triplicate. Intraclass correlation coefficients (ICCs) for PWV were 0.61 (95% confidence interval (CI) = 0-0.86) when at least 2 measurements and 0.92 (95% CI = 0-1) when 3 measurements were obtained at each visit that met the quality criteria established for adults by the manufacturer (n = 17 and 3 paired visits, respectively). For AIx, ICCs were 0.78 (95% CI = 0.58-0.88) and 0.81 (95% CI = 0.63-0.90) when measurements with an operator index ≥80, a measure of the quality of the waveform, were included (n = 39 and 36 paired visits, respectively).Arterial applanation tonometry is feasible and reproducible in healthy children and adolescents. AIx has excellent intervisit reproducibility, whereas the intervisit reproducibility of PWV relies on acquisition of multiple measurements that meet quality criteria established for adults. These results have implications for the methodology of future pediatric clinical trials in a population at increasingly higher risk for premature atherosclerosis.

  View details for DOI 10.1093/ajh/hpu034

  View details for Web of Science ID 000342853700013

• Using high-dose omega-3 fatty acid supplements to lower triglyceride levels in 10- to 19-year-olds. Clinical pediatrics de Ferranti, S. D., Milliren, C. E., Denhoff, E. R., Steltz, S. K., Selamet Tierney, E. S., Feldman, H. A., Osganian, S. K. 2014; 53 (5): 428-438

  Abstract

  Omega-3 fatty acids supplements lower triglyceride (TG) levels in adults; little pediatric information is available. We evaluated their effect in hypertriglyceridemic adolescents.Twenty-five patients aged 10 to 19 years with TG levels 150 to 1000 mg/dL were randomized to 6 months double-blind trial of Lovaza (~3360 mg docosahexaenoic acid + eicosapentaenoic acid per day) versus placebo.Baseline mean TG levels were 227 mg/dL (standard deviation = 49). TG levels declined at 3 months in the Lovaza group by 54 ± 27 mg/dL (mean ± standard error; P = .02) and by 34 ± 26 mg/dL (P = .16) in the placebo group. The difference in TG lowering between groups was not significant (P = .52). There were no between-group differences in endothelial function, blood pressure, body mass index, C-reactive protein, or side effects.High-dose omega-3 fatty acid supplements are well tolerated in adolescents. However, declines in TG levels did not differ significantly from Placebo in this small study.

  View details for DOI 10.1177/0009922814528032

  View details for PubMedID 24707021

  View details for PubMedCentralID PMC4353654

• Reliability of Echocardiographic Measurements of Left Ventricular Function in Potential Pediatric Heart Transplant Donors Chen, S., Tierney, E., Khush, K. K., Nguyen, J., Goldstein, B., May, L. J., Rosenthal, D. ELSEVIER SCIENCE INC. 2014: S224

  View details for DOI 10.1016/j.healun.2014.01.583

  View details for Web of Science ID 000333866700607

• Variability of M-Mode Versus Two-Dimensional Echocardiography Measurements in Children With Dilated Cardiomyopathy PEDIATRIC CARDIOLOGY Lee, C. K., Margossian, R., Sleeper, L. A., Canter, C. E., Chen, S., Tani, L. Y., Shirali, G., Szwast, A., Tierney, E. S., Campbell, M. J., Golding, F., Wang, Y., Altmann, K., Colan, S. D. 2014; 35 (4): 658-667

  Abstract

  M-mode and 2-dimensional (2D) echocardiographic imaging are routinely used to quantify left-ventricular (LV) size and function in pediatric patients with dilated cardiomyopathy (DCM). The reproducibility of and correlation between these techniques are unknown. This analysis sought to compare interreader, intrareader, and interacquisition reproducibility of M-mode versus 2D measurements in pediatric DCM patients. The Ventricular Volume Variability study of the Pediatric Heart Network is a multicenter, prospective, observational study assessing the course of chronic DCM in children. Two sonographers performed baseline image acquisitions locally, and two readers performed measurements at the echocardiographic core laboratory. One reader repeated measurements 1 month later. These data were used to assess reproducibility and agreement between M-mode and 2D measurements. One hundred sixty-nine subjects were enrolled. M-mode had similar or greater reproducibility in both intrareader and interreader settings for LV dimensions, shortening fraction (SF), and most wall thicknesses. In contrast, 2D reproducibility was similar or better for nearly all variables in the interacquisition setting but not for SF. Interacquisition variability was approximately twice the intrareader variability. LV dimensions by either modality consistently had high reproducibility and had the highest agreement between modalities. In pediatric DCM patients, variability of linear echocardiographic assessment could be minimized by relying on a single reader and using a consistent method (M-mode or 2D) for serial measurements, preferably M-mode when SF is the primary variable of interest. Except for LV dimensions, M-mode and 2D values should not be used interchangeably due to poor agreement.

  View details for DOI 10.1007/s00246-013-0835-9

  View details for Web of Science ID 000333165400015

  View details for PubMedID 24265000

• Predictors of disease progression in pediatric dilated cardiomyopathy. Circulation. Heart failure Molina, K. M., Shrader, P., Colan, S. D., Mital, S., Margossian, R., Sleeper, L. A., Shirali, G., Barker, P., Canter, C. E., Altmann, K., Radojewski, E., Tierney, E. S., Rychik, J., Tani, L. Y. 2013; 6 (6): 1214-1222

  Abstract

  Despite medical advances, children with dilated cardiomyopathy (DCM) remain at high risk of death or need for cardiac transplantation. We sought to identify predictors of disease progression in pediatric DCM.The Pediatric Heart Network evaluated chronic DCM patients with prospective echocardiographic and clinical data collection during an 18-month follow-up. Inclusion criteria were age <22 years and DCM disease duration >2 months. Patients requiring intravenous inotropic/mechanical support or listed status 1A/1B for transplant were excluded. Disease progression was defined as an increase in transplant listing status, hospitalization for heart failure, intravenous inotropes, mechanical support, or death. Predictors of disease progression were identified using Cox proportional hazards modeling and classification and regression tree analysis. Of the 127 patients, 28 (22%) had disease progression during the 18-month follow-up. Multivariable analysis identified older age at diagnosis (hazard ratio=1.14 per year; P<0.001), larger left ventricular (LV) end-diastolic M-mode dimension z-score (hazard ratio=1.49; P<0.001), and lower septal peak systolic tissue Doppler velocity z-score (hazard ratio=0.81; P=0.01) as independent predictors of disease progression. Classification and regression tree analysis stratified patients at risk of disease progression with 89% sensitivity and 94% specificity based on LV end-diastolic M-mode dimension z-score ≥7.7, LV ejection fraction <39%, LV inflow propagation velocity (color M-mode) z-score <-0.28, and age at diagnosis ≥8.5 months.In children with chronic stable DCM, a combination of diagnosis after late infancy and echocardiographic parameters of larger LV size and systolic and diastolic function predicted disease progression.URL: http://www.clinicaltrials.gov. Unique identifier: NCT00123071.

  View details for DOI 10.1161/CIRCHEARTFAILURE.113.000125

  View details for PubMedID 24132734

• Vascular Health in Kawasaki Disease JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Tierney, E. S., Gal, D., Gauvreau, K., Baker, A. L., Trevey, S., O'Neill, S. R., Jaff, M. R., de Ferranti, S., Fulton, D. R., Colan, S. D., Newburger, J. W. 2013; 62 (12): 1114-1121

  Abstract

  Our objective was to compare the indices of vascular health in KD patients to those of control subjects.Background: Literature on peripheral vascular health after Kawasaki disease (KD) is conflicting.Subjects were patients 11-29 years with KD onset >12 months prior to study visit (n=203) and healthy control subjects (n=50). We measured endothelial function (EndoPAT-Index), intima-media thickness (IMT) of right and left common carotid arteries (RCCA and LCCA), and fasting lipid-profile and C-reactive protein (CRP). KD patients were classified according to their worst-ever coronary artery (CA) status: Group I-always normal CAs (n=136, 67%); Group II-CA z-scores ≥ 2 but <3 (n=20, 10%); Group III-CA aneurysm z-scores ≥ 3 but <8mm (n=40, 20%), and Group IV-giant CA aneurysm, defined as ≥ 8mm (n=7, 3%).At a median of 11.6y (1.2 - 26 years) after KD onset, compared to controls, KD patients had a higher peak velocity in the LCCA (p=0.04) and higher pulsatility index of both RCCA and LCCA (p=0.006 and p=0.05, respectively). However, there were no differences in the EndoPAT index, carotid IMT or stiffness. Mean IMT of LCCA tended to differ across the KD subgroups and control group (p=0.05), with a higher mean in Group IV. Otherwise the KD subgroups and control group had similar vascular health indices.In contrast to some earlier reports, our study in North American children and young adults demonstrated that KD patients whose maximum CA dimensions were either always normal or mildly ectatic have normal vascular health indices, providing reassurance regarding peripheral vascular health in this population.

  View details for DOI 10.1016/j.jacc.2013.04.090

  View details for Web of Science ID 000324047800014

  View details for PubMedID 23835006

• Tricuspid atresia with progressive ductal restriction in a fetus. Pediatric cardiology Lowenthal, A., Lal, A., Selamet Tierney, E. S., Tacy, T. A. 2013; 34 (6): 1499-1501

  Abstract

  We report a unique case of tricuspid and pulmonary atresia with idiopathic progressive ductus arteriosus restriction in utero. Diligent predelivery planning and a controlled delivery environment led to a favorable outcome.

  View details for DOI 10.1007/s00246-012-0391-8

  View details for PubMedID 22729970

• Tricuspid Atresia With Progressive Ductal Restriction in a Fetus PEDIATRIC CARDIOLOGY Lowenthal, A., Lal, A., Tierney, E. S., Tacy, T. A. 2013; 34 (6): 1499-1501

  Abstract

  We report a unique case of tricuspid and pulmonary atresia with idiopathic progressive ductus arteriosus restriction in utero. Diligent predelivery planning and a controlled delivery environment led to a favorable outcome.

  View details for DOI 10.1007/s00246-012-0391-8

  View details for Web of Science ID 000321919400028

• Echocardiographic Predictors of Left Ventricular Dysfunction after Aortic Valve Surgery in Children with Chronic Aortic Regurgitation CONGENITAL HEART DISEASE Tierney, E. S., Gal, D., Gauvreau, K., Zhou, J., Soluk, Y., McElhinney, D. B., Colan, S. D., Geva, T. 2013; 8 (4): 308-315

  Abstract

  OBJECTIVE: Postoperative left ventricular dysfunction is associated with poor prognosis in adults with severe chronic aortic regurgitation and published practice guidelines aim to minimize this risk. However, only limited information exists in pediatrics. The goal of this study was to define preoperative risk factors for postoperative left ventricular dysfunction in children with chronic aortic regurgitation. METHODS: Patients fulfilling the following criteria were included in this study: (1) age at preoperative echocardiogram ≤18 years; (2) ≥moderate aortic regurgitation; (3) ≤mild aortic valve stenosis; (4) no additional valve disease/shunt; (5) underwent aortic valve surgery for aortic regurgitation; and (6) available preoperative and ≥6-month postoperative echocardiograms with adequate information. Primary outcome was postoperative left ventricular dysfunction defined as ejection fraction z-score < -2. RESULTS: Median ages at diagnosis and surgery of the 53 eligible patients were 6.9 (0.04-17.2) and 13 years (1.2-22.4), respectively. Compared with patients whose postoperative left ventricular ejection fraction was normal, those with left ventricular ejection fraction z-score < -2 (n = 10) had significantly higher preoperative left ventricular end-diastolic and systolic volumes and dimensions and lower indices of systolic function. Preoperative left ventricular ejection fraction z-score < -1 was the most sensitive (89%; confidence interval [CI] 52, 100) but least specific (58%; CI 41, 73), whereas left ventricular end-systolic diameter z-score ≥ 5 was the most specific (95%; CI 84, 99) but least sensitive (60%; CI 26, 88) outcome identifier. A combination of shortening fraction z-score < -1 or end-systolic diameter z-score ≥ 5 best identified postoperative left ventricular dysfunction with an area of 0.819 under the receiver-operator characteristic curve. CONCLUSION: Lower indices of left ventricular systolic function and severity of dilation identify children at risk for postoperative left ventricular dysfunction after aortic valve surgery. These identifiers are similar to predictors defined in adult patients albeit with different threshold values.

  View details for DOI 10.1111/chd.12009

  View details for Web of Science ID 000326501000014

• Echocardiographic methods, quality review, and measurement accuracy in a randomized multicenter clinical trial of marfan syndrome. Journal of the American Society of Echocardiography Selamet Tierney, E. S., Levine, J. C., Chen, S., Bradley, T. J., Pearson, G. D., Colan, S. D., Sleeper, L. A., Campbell, M. J., Cohen, M. S., De Backer, J., Guey, L. T., Heydarian, H., Lai, W. W., Lewin, M. B., Marcus, E., Mart, C. R., Pignatelli, R. H., Printz, B. F., Sharkey, A. M., Shirali, G. S., Srivastava, S., Lacro, R. V. 2013; 26 (6): 657-666

  Abstract

  The Pediatric Heart Network is conducting a large international randomized trial to compare aortic root growth and other cardiovascular outcomes in 608 subjects with Marfan syndrome randomized to receive atenolol or losartan for 3 years. The authors report here the echocardiographic methods and baseline echocardiographic characteristics of the randomized subjects, describe the interobserver agreement of aortic measurements, and identify factors influencing agreement.Individuals aged 6 months to 25 years who met the original Ghent criteria and had body surface area-adjusted maximum aortic root diameter (ROOTmax) Z scores > 3 were eligible for inclusion. The primary outcome measure for the trial is the change over time in ROOTmaxZ score. A detailed echocardiographic protocol was established and implemented across 22 centers, with an extensive training and quality review process.Interobserver agreement for the aortic measurements was excellent, with intraclass correlation coefficients ranging from 0.921 to 0.989. Lower interobserver percentage error in ROOTmax measurements was independently associated (model R(2) = 0.15) with better image quality (P = .002) and later study reading date (P < .001). Echocardiographic characteristics of the randomized subjects did not differ by treatment arm. Subjects with ROOTmaxZ scores ≥ 4.5 (36%) were more likely to have mitral valve prolapse and dilation of the main pulmonary artery and left ventricle, but there were no differences in aortic regurgitation, aortic stiffness indices, mitral regurgitation, or left ventricular function compared with subjects with ROOTmaxZ scores < 4.5.The echocardiographic methodology, training, and quality review process resulted in a robust evaluation of aortic root dimensions, with excellent reproducibility.

  View details for DOI 10.1016/j.echo.2013.02.018

  View details for PubMedID 23582510

• Expanding the Phenotype of Cardiovascular Malformations in Adams-Oliver Syndrome AMERICAN JOURNAL OF MEDICAL GENETICS PART A Algaze, C., Esplin, E. D., Lowenthal, A., Hudgins, L., Tacy, T. A., Tierney, E. S. 2013; 161A (6): 1386-1389

  Abstract

  We describe a newborn with a phenotype consistent with Adams-Oliver syndrome and truncus arteriosus. Although cardiovascular malformations associated with this syndrome have been previously published in the literature, this is the first description of truncus arteriosus in a patient with Adams-Oliver syndrome. We review other reports of Adams-Oliver syndrome previously described with cardiovascular malformations, consider possible genetic and embryologic mechanisms, and emphasize the need for cardiology consultation when a diagnosis of Adams-Oliver syndrome is suspected in the differential diagnosis. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ajmg.a.35864

  View details for Web of Science ID 000320649700021

• Expanding the phenotype of cardiovascular malformations in Adams-Oliver syndrome. American journal of medical genetics. Part A Algaze, C., Esplin, E. D., Lowenthal, A., Hudgins, L., Tacy, T. A., Selamet Tierney, E. S. 2013; 161 (6): 1386-9

  Abstract

  We describe a newborn with a phenotype consistent with Adams-Oliver syndrome and truncus arteriosus. Although cardiovascular malformations associated with this syndrome have been previously published in the literature, this is the first description of truncus arteriosus in a patient with Adams-Oliver syndrome. We review other reports of Adams-Oliver syndrome previously described with cardiovascular malformations, consider possible genetic and embryologic mechanisms, and emphasize the need for cardiology consultation when a diagnosis of Adams-Oliver syndrome is suspected in the differential diagnosis. © 2013 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ajmg.a.35864

  View details for PubMedID 23613382

• Characteristics of children and young adults with Marfan syndrome and aortic root dilation in a randomized trial comparing atenolol and losartan therapy. American heart journal Lacro, R. V., Guey, L. T., Dietz, H. C., Pearson, G. D., Yetman, A. T., Gelb, B. D., Loeys, B. L., Benson, D. W., Bradley, T. J., De Backer, J., Forbus, G. A., Klein, G. L., Lai, W. W., Levine, J. C., Lewin, M. B., Markham, L. W., Paridon, S. M., Pierpont, M. E., Radojewski, E., Selamet Tierney, E. S., Sharkey, A. M., Wechsler, S. B., Mahony, L. 2013; 165 (5): 828-835 e3

  Abstract

  The Pediatric Heart Network designed a clinical trial to compare aortic root growth and other short-term cardiovascular outcomes in children and young adults with Marfan syndrome randomized to receive atenolol or losartan. We report here the characteristics of the screened population and enrolled subjects.Between 2007 and 2011, 21 clinical sites randomized 608 subjects, aged 6 months to 25 years who met the original Ghent criteria and had a body surface area-adjusted aortic root diameter z-score >3.0. The mean age at study entry was 11.2 years, 60% were male, and 25% were older teenagers and young adults. The median aortic root diameter z-score was 4.0. Aortic root diameter z-score did not vary with age. Mitral valve prolapse and mitral regurgitation were more common in females. Among those with a positive family history, 56% had a family member with aortic surgery, and 32% had a family member with a history of aortic dissection.Baseline demographic, clinical, and anthropometric characteristics of the randomized cohort are representative of patients in this population with moderate to severe aortic root dilation. The high percentage of young subjects with relatives who have had aortic dissection or surgery illustrates the need for more definitive therapy; we expect that the results of the study and the wealth of systematic data collected will make an important contribution to the management of individuals with Marfan syndrome.

  View details for DOI 10.1016/j.ahj.2013.02.019

  View details for PubMedID 23622922

• Predictors of Disease Progression in Pediatric Dilated Cardiomyopathy Molina, K., Sleeper, L., Mital, S., Colan, S., Shrader, P., Barker, P., Margossian, R., Shirali, G., Altmann, K., Canter, C., Radojewski, E., Tierney, E., Rychik, J., Tani, L. LIPPINCOTT WILLIAMS & WILKINS. 2012

  View details for Web of Science ID 000208885000101

• Erratum to: Tricuspid Atresia With Progressive Ductal Restriction in a Fetus. Pediatric cardiology Lowenthal, A., Lal, A., Selamet Tierney, E. S., Tacy, T. A. 2012

  View details for DOI 10.1007/s00246-012-0512-4

  View details for PubMedID 22972518

• The Ventricular Volume Variability Study of the Pediatric Heart Network: Study Design and Impact of Beat Averaging and Variable Type on the Reproducibility of Echocardiographic Measurements in Children with Chronic Dilated Cardiomyopathy JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Colan, S. D., Shirali, G., Margossian, R., Gallagher, D., Altmann, K., Canter, C., Chen, S., Golding, F., Radojewski, E., Camitta, M., Carboni, M., Rychik, J., Stylianou, M., Tani, L. Y., Tierney, E. S., Wang, Y., Sleeper, L. A. 2012; 25 (8): 842-?

  Abstract

  Clinical trials often rely on echocardiographic measures of left ventricular size and function as surrogate end points. However, the quantitative impact of factors that affect the reproducibility of these measures is unknown. To address this issue, the National Heart, Lung, and Blood Institute-funded Pediatric Heart Network designed a longitudinal observational study of children with known or suspected dilated cardiomyopathy aged 0 to 22 years from eight pediatric clinical centers.Clinical data were collected together with 150 echocardiographic indices of left ventricular size and function. Separate observers performed duplicate echocardiographic imaging. Multiple observers performed measurements from three cardiac cycles to enable assessment of intraobserver and interobserver variability. The impacts of beat averaging (BA), observer type (local vs core), and variable type (areas, calculations, dimensions, slopes, time intervals, and velocities) on measurement reproducibility were studied. The outcome measure was percentage error (100 × difference/mean).Of 173 enrolled subjects, 131 met criteria for dilated cardiomyopathy. BA, variable type and observer type all influenced percentage error (P < .0001). Core interobserver percentage error (medians, 11.4%, 10.2%, and 9.3% for BA using one, two, and three beats, respectively) was approximately twice the intraobserver percentage error (medians, 6.3%, 4.9%, and 4.2% for BA using one, two, and three beats, respectively). Slopes and calculated variables exhibited high percentage error despite BA. Chamber dimensions, areas, velocities, and time intervals exhibited low percentage error.This comprehensive evaluation of quantitative echocardiographic methods will provide a valuable resource for the design of future pediatric studies. BA and a single core lab observer improve the reproducibility of echocardiographic measurements in children with dilated cardiomyopathy. Certain measurements are highly reproducible, while others, despite BA, are poorly reproducible.

  View details for DOI 10.1016/j.echo.2012.05.004

  View details for Web of Science ID 000306657900008

  View details for PubMedID 22677278

• Mutations in ZIC3 and ACVR2B are a common cause of heterotaxy and associated cardiovascular anomalies CARDIOLOGY IN THE YOUNG Ma, L., Tierney, E. S., Lee, T., Lanzano, P., Chung, W. K. 2012; 22 (2): 194-201

  Abstract

  Heterotaxy syndrome is caused by left-right asymmetry disturbances and is associated with abnormal lateralisation of the abdominal and thoracic organs. The heart is frequently involved and the severity of the abnormality usually determines the outcome.We performed a direct sequence analysis of the coding sequence of genes including Zinc Finger Protein of the Cerebellum 3, Left-Right Determination Factor 2, Activin A Receptor Type IIB, and Cryptic in 47 patients with laterality defects and congenital cardiac disease.Of the 47 patients, 31 (66%) had atrioventricular septal defects, 34 (72%) had abnormal systemic venous return, 25 (53%) had transposed or malposed great arteries, and 20 (43%) had pulmonary venous abnormalities. We identified two novel genetic changes in Zinc Finger Protein of the Cerebellum 3, and these variants were not present in 100 ethnically matched control samples. One previously reported missense mutation in Activin A Receptor Type IIB was identified in two unrelated subjects. The genetic changes identified in this study are all located in conserved regions and are predicted to affect protein function in left-right axis formation and cardiovascular development.Mutations in Zinc Finger Protein of the Cerebellum 3 and Activin A Receptor Type IIB were identified in 4 of the 47 patients with heterotaxy syndrome for a yield of approximately 8.5%. Our results expand the mutation spectrum of monogenic heterotaxy syndrome with associated cardiac anomalies and suggest that there are other causes of heterotaxy yet to be identified.

  View details for DOI 10.1017/S1047951111001181

  View details for Web of Science ID 000300995900012

  View details for PubMedID 21864452

  View details for PubMedCentralID PMC3678527

• Diastolic function in children with Kawasaki disease. International journal of cardiology Selamet Tierney, E. S., Newburger, J. W., Graham, D., Baker, A., Fulton, D. R., Colan, S. D. 2011; 148 (3): 309-312

  Abstract

  Coronary artery dilation (CAD) and left ventricular systolic dysfunction are recognized complications of Kawasaki Disease (KD). Diastolic function assessed by echocardiography in the KD patient population and its interrelationship to the KD course, systolic dysfunction, and CAD is less well characterized. The purpose of this study was to determine whether diastolic function is impaired in KD patients and whether there are any clinical correlates.All KD patients with an echocardiogram recording of tissue Doppler velocities were included. Patients were analyzed based on CAD (Group I: patients who had CAD during their disease course; Group II: patients who never had CAD). In addition, we compared measures of diastolic function in patients with echocardiograms 0-30 days (n=35) and >30 days (n=72) post-IVIG treatment.116 patients (80 males) were included (mean age, 7.7±6.7 years; mean time since KD onset, 4.0±5.6 years). Group I (41 patients, 36%), compared to Group II, had decreased E'(lateral) and longer mitral early deceleration time. E'(lateral) and E'(septal) were significantly decreased in patients 0-30 days vs. >30 days post-IVIG, whereas mitral early deceleration time was not significantly different.Our results demonstrate that there is impaired relaxation in KD patients in the early phase of the disease and in KD patients with CAD during the disease course.

  View details for DOI 10.1016/j.ijcard.2009.11.014

  View details for PubMedID 19945179

• Comparison of Impact of Prenatal Versus Postnatal Diagnosis of Congenitally Corrected Transposition of the Great Arteries AMERICAN JOURNAL OF CARDIOLOGY Wan, A. W., Jevremovic, A., Tierney, E. S., McCrindle, B. W., Dunn, E., Manlhiot, C., Wald, R. M., Kingdom, J. P., Jaeggi, E. T., Nield, L. E. 2009; 104 (9): 1276-1279

  Abstract

  Congenitally corrected transposition of the great arteries (CCTGA) in the absence of major cardiac anomalies is thought to have a good outcome, although this has not been well documented. The objective of the present study was to compare the characteristics and outcomes of patients with a prenatal diagnosis of CCTGA to the characteristics and outcomes of those diagnosed postnatally. The optimal outcome was defined as intervention-free survival. All patients with CCTGA diagnosed prenatally and postnatally from 1999 to 2006 at 2 tertiary care institutions were reviewed. Patients with a single ventricle, heterotaxy, or valvar atresia were excluded. The differences between groups were assessed using the t test and chi-square test. A total of 54 patients (16 prenatal with 14 live born and 39 postnatal) were included. The patients diagnosed prenatally were diagnosed at a median gestational age of 20 weeks (range 16 to 37). Two deaths in each group were due to heart failure. The intervention-free survival rate for the prenatal and postnatal groups at 1, 6, and 36 months was 79%, 45%, and 30% and 85%, 61%, and 23%, respectively (p = NS). Of 37 patients, 14 (38%) underwent an arterial switch plus atrial baffling so that the morphologic left ventricle supported the systemic circulation, and 6 (16%) underwent repair of associated lesions so the morphologic right ventricle supported the systemic circulation; 4 (11%) of the 37 patients had pacemaker only. Prenatal patients with >1 fetal echocardiogram (12 of 14) did not have progression before birth. In conclusion, CCTGA has a >70% risk of intervention in the first 3 years after birth. The outlook is guarded and has an important effect on prenatal counseling.

  View details for DOI 10.1016/j.amjcard.2009.06.047

  View details for Web of Science ID 000271487100021

  View details for PubMedID 19840576

• Endothelial Pulse Amplitude Testing: Feasibility and Reproducibility in Adolescents JOURNAL OF PEDIATRICS Tierney, E. S., Newburger, J. W., Gauvreau, K., Geva, J., Coogan, E., Colan, S. D., de Ferranti, S. D. 2009; 154 (6): 901-905

  Abstract

  To test prospectively the reproducibility and feasibility of endothelial pulse amplitude testing (Endo-PAT), a novel Food and Drug Administration-approved technology, in healthy adolescents.We performed Endo-PAT testing on 2 different days separated by no more than 7 days in 30 healthy fasting adolescents, ages 13 to 19 years, to assess reproducibility and feasibility. The reported level of discomfort, as measured on a pain scale of 1 to 5, was documented.The mean difference in paired Endo-PAT indices was 0.12 (95% CI, -0.09-0.33; P = .24; intraclass correlation coefficient, 0.78), and the within-subject variation of Endo-PAT index was 0.16. The Endo-PAT index on test days 1 and 2 were 1.91 +/- 0.57 and 1.78 +/- 0.51 (mean plus or minus SD), respectively. All attempted studies (100%) were completed (95% CI, 88%-100%), and all completed studies (100%) could be analyzed (95% CI, 88%-100%). The median pain score was 1 on both days.In healthy adolescents, Endo-PAT is feasible and has excellent reproducibility. This technology may provide an easy and reliable means of assessing endothelial function in the pediatric population.

  View details for DOI 10.1016/j.jpeds.2008.12.028

  View details for Web of Science ID 000266685800030

  View details for PubMedID 19217124

• Truncus Arteriosus: Diagnostic Accuracy, Outcomes, and Impact of Prenatal Diagnosis PEDIATRIC CARDIOLOGY Swanson, T. M., Tierney, E. S., Tworetzky, W., Pigula, F., McElhinney, D. B. 2009; 30 (3): 256-261

  Abstract

  Limited data exist on the impact of prenatal diagnosis and outcomes of fetal truncus arteriosus (TA). We sought to assess prenatal diagnostic accuracy and prenatal outcomes in fetuses with TA and compare postnatal outcomes in neonates with prenatally and postnatally diagnosed TA. Records were reviewed for patients diagnosed with TA in utero or at

  View details for DOI 10.1007/s00246-008-9328-7

  View details for Web of Science ID 000264884500007

  View details for PubMedID 19015910

• Mitral valve replacement in infants and children 5 years of age or younger: Evolution in practice and outcome over three decades with a focus on supra-annular prosthesis implantation JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Tierney, E. S., Pigula, F. A., Berul, C. I., Lock, J. E., del Nido, P. J., McElhinney, D. B. 2008; 136 (4): 954-U8

  Abstract

  Successful mitral valve replacement in young children is limited by the lack of small prosthetic valves. Supra-annular prosthesis implantation can facilitate mitral valve replacement with a larger prosthesis in children with a small annulus, but little is known about its effect on the outcomes of mitral valve replacement in young children.One hundred eighteen children underwent mitral valve replacement at 5 years of age or younger from 1976-2006. Mitral valve replacement was supra-annular in 37 (32%) patients.Survival was 74% +/- 4% at 1 year and 56% +/- 5% at 10 years but improved over time (10-year survival of 83% +/- 7% from 1994-2006). Factors associated with worse survival included earlier mitral valve replacement date, age less than 1 year, complete atrioventricular canal, and additional procedures at mitral valve replacement, but not supra-annular mitral valve replacement. As survival improved during our more recent experience, the risks of supra-annular mitral valve replacement became apparent; survival was worse among patients with a supra-annular prosthesis after 1991. A pacemaker was placed in 18 (15%) patients within 1 month of mitral valve replacement and was less likely in patients who had undergone supra-annular mitral valve replacement. Among early survivors, freedom from redo mitral valve replacement was 72% +/- 5% at 5 years and 45% +/- 7% at 10 years. Twenty-one patients with a supra-annular prosthesis underwent redo mitral valve replacement. The second prosthesis was annular in 15 of these patients and upsized in all but 1, but 5 required pacemaker placement for heart block.Supra-annular mitral valve replacement was associated with worse survival than annular mitral valve replacement in our recent experience. Patients with supra-annular mitral valve replacement were less likely to have operative complete heart block but remained at risk when the prosthesis was subsequently replaced.

  View details for DOI 10.1016/j.jtcvs.2007.12.076

  View details for Web of Science ID 000260314800023

  View details for PubMedID 18954636

• Ventricular function deteriorates with recurrent coarctation in hypoplastic left heart syndrome 44th Annual Meeting of the Society-of-Thoracic-Surgeons Larrazabal, L. A., Tierney, E. S., Brown, D. W., Gauvreau, K., Vida, V. L., Bergersen, L., Pigula, F. A., del Nido, P. J., Bacha, E. A. ELSEVIER SCIENCE INC. 2008: 869–74

  Abstract

  Recurrent coarctation (re-CoA) after stage I palliation in hypoplastic left heart syndrome (HLHS) is deleterious. We studied whether re-CoA had an effect on ventricular systolic function.Retrospectively reviewed were HLHS patients surviving stage I Norwood palliation (stage I) and cavopulmonary shunt (CPS) between January 2004 and February 2007. Echocardiographic right ventricular fractional area change (RV-FAC) was used to evaluate ventricular systolic function after stage I, before CPS, and before Fontan procedures. Cardiac catheterization and magnetic resonance imaging data before CPS were reviewed to assess re-CoA, using a coarctation index (CI = isthmus diameter/descending aortic diameter).Fifty-one patients were included, and 21 had a CI of less than 0.75 (mean, 0.82 +/- 0.19; 21). Twelve patients required arch balloon dilation between CPS and Fontan. The change of RV-FAC for all patients between stage I and CPS was -2.2% +/- 9.6%. Pearson correlation coefficient demonstrated a significant correlation between lower CI values and lower RV-FAC at the pre-CPS echocardiogram (r = .35, p = 0.03); and lower CI values and greater decrease in RV-FAC between stage I and pre-CPS evaluation (r = 0.40, p = 0.018). At follow-up pre-Fontan, RV-FAC for patients who underwent balloon dilation for re-CoA recovered to a level that was inferior but not significantly different from that of patients who did not need balloon dilation.Recurrent aortic arch obstruction after stage I for HLHS is associated with worse RV systolic function at the time of stage II operation. Timely intervention on the re-CoA results in recovery of RV function.

  View details for DOI 10.1016/j.athoracsur.2008.04.074

  View details for Web of Science ID 000258619100023

  View details for PubMedID 18721575

• Echocardiographic predictors of mitral stenosis-related death or intervention in infants AMERICAN HEART JOURNAL Tierney, E. S., Graham, D. A., McElhinney, D. B., Trevey, S., Freed, M. D., Colan, S. D., Geva, T. 2008; 156 (2): 384-390

  Abstract

  The purpose of this study is to identify independent echocardiographic predictors of mitral stenosis (MS)-related death or intervention in infants. Congenital MS is a rare and morphologically heterogeneous lesion with variable prognosis. Among patients diagnosed with MS in early infancy, echocardiographic factors associated with MS-related intervention or death have not been determined.The clinical and echocardiographic data of patients diagnosed with MS at age <6 months by echocardiography between 1986 and 2004 were reviewed. The primary outcome was a composite end point of either mitral valve (MV) intervention (catheter or surgery) or death related to MS. Multiple variables from the initial echocardiogram were analyzed for association with outcomes. Seventy-one patients (median age at diagnosis 63 days) fulfilled the inclusion criteria. Multivariate analysis identified higher initial MV mean inflow gradient (P = .009) and lower left ventricular (LV) diastolic length Z-score (P = .006) at presentation as predictors of intervention or death. Among patients with an initial MV inflow gradient < 2 mm Hg, none reached an end point, whereas, among patients with an initial mean gradient >/= 5.5 mm Hg, the risk of intervention or death was 85%. Among patients with a gradient > 2 and < 5.5 mm Hg, an end point was reached in 38%, and an LV diastolic length Z-score

  View details for DOI 10.1016/j.ahj.2008.03.019

  View details for Web of Science ID 000258333400034

  View details for PubMedID 18657675

• Changes in left heart hemodynamics after technically successful in-utero aortic valvuloplasty ULTRASOUND IN OBSTETRICS & GYNECOLOGY Tierney, E. S., Wald, R. M., McElhinney, D. B., Marshall, A. C., Benson, C. B., Colan, S. D., Marcus, E. N., Marx, G. R., Levine, J. C., Wilkins-Haug, L., Lock, J. E., Tworetzky, W. 2007; 30 (5): 715-720

  Abstract

  Severe aortic stenosis in the mid-gestation fetus can progress to hypoplastic left heart syndrome (HLHS). @ In-utero aortic valvuloplasty is an innovative therapy to promote left ventricular growth and function and potentially to prevent HLHS. This study evaluated the effects of mid-gestation fetal balloon aortic valvuloplasty on subsequent fetal left ventricular function and left heart Doppler characteristics.We reviewed fetuses with aortic stenosis that underwent attempted in-utero aortic valvuloplasty between 2000 and 2006. Pre-intervention and the latest post-intervention fetal echocardiograms were analyzed to characterize changes in left heart function and Doppler characteristics in utero.Forty-two fetuses underwent attempted aortic valvuloplasty during the study period, 12 of which were excluded from analysis secondary to inadequate follow-up data, termination or fetal demise. Study fetuses (n = 30) underwent pre-intervention echocardiography at a median gestational age of 23 weeks, and were followed for a median of 66 +/- 23 days post-intervention. In 26 fetuses, aortic valvuloplasty was technically successful. Among these 26, left heart physiology was abnormal pre-intervention and improved or normalized after intervention in most cases: biphasic mitral inflow was present in 5/25 (20%) cases pre-intervention and in 21/23 (91%) post-intervention (P < 0.001); moderate or severe mitral regurgitation was present in 14/26 (54%) cases pre-intervention and in 5/23 (22%) post-intervention (P = 0.02); bidirectional flow across the patent foramen ovale was present in 0/26 cases pre-intervention and in 6/25 (24%) post-intervention (P = 0.01); antegrade flow in the transverse arch was present in 0/25 cases pre-intervention and in 17/26 (65%) post-intervention (P < 0.001). The left ventricular ejection fraction increased from 19 +/- 10% pre-intervention to 39 +/- 14% post-intervention (P < 0.001). These changes were not observed in control fetuses (n = 18).Fetal aortic valvuloplasty, when technically successful, improves left ventricular systolic function and left heart Doppler characteristics.

  View details for DOI 10.1002/uog.5132

  View details for Web of Science ID 000250732900006

  View details for PubMedID 17764106

• Bidirectional cavopulmonary anastomosis: Impact on diastolic ventricular function indices PEDIATRIC CARDIOLOGY Tierney, E. S., Glickstein, J. S., Altmann, K., Solowiejczyk, D. E., Mosca, R. S., Quaegebeur, J. M., Kleinman, C. S., Printz, B. F. 2007; 28 (5): 372-378

  Abstract

  Systolic ventricular function has been demonstrated to remain unchanged following bidirectional cavopulmonary anastomosis (BCPA). The effects of BCPA on diastolic ventricular performance have not been critically assessed. The objective of this study was to evaluate the changes in diastolic ventricular function indices early after BCPA. Nineteen patients were enrolled prospectively. Transthoracic echocardiograms were performed at a median of 4 days prior to and 5 days subsequent to BCPA. Diastolic and systolic echocardiographic indices of ventricular performance were measured for the dominant ventricle. End diastolic volume decreased postoperatively (71.1 +/- 21.1 vs 68.08 +/- 17.9 ml/m2, p = 0.05). Tei index increased postoperatively (0.51 +/- 0.2 vs 0.62 +/- 0.1, p = 0.002), whereas inflow Doppler E velocity (70.3 +/- 13 vs 56.3 +/- 24.7 cm/sec, p = 0.04), E/A ratio (1.18 +/- 0.52 vs 0.84 +/- 0.2, p = 0.02), tissue Doppler E' velocity (9.5 +/- 2.5 vs 6.4 +/- 3.2 cm/sec, p = 0.03) and diastolic flow propagation velocity (56.5 +/- 12 vs 52.8 +/- 11 cm/sec, p = 0.04) all decreased. There was no change in ventricular mass, area change fraction, heart rate, or inflow Doppler A or tissue Doppler A' and S' velocities. This study demonstrated that diastolic indices of ventricular performance are altered indicating decreased diastolic function early following BCPA. Whether this observation is a result of a change in ventricular mass:volume ratio, loading conditions of the ventricle, ventricular geometry, or the effects of cardiopulmonary bypass remains to be determined.

  View details for DOI 10.1007/s00246-006-0122-0

  View details for Web of Science ID 000249504200008

  View details for PubMedID 17687592

• Are patients with Kawasaki disease at risk for premature atherosclerosis? JOURNAL OF PEDIATRICS Selarnet Tierney, E. S., Newburger, J. W. 2007; 151 (3): 225-228

  View details for DOI 10.1016/j.jpeds.2007.05.01

  View details for Web of Science ID 000249442800002

  View details for PubMedID 17719924

• Variants of the CFC1 gene in patients with laterality defects associated with congenital cardiac disease CARDIOLOGY IN THE YOUNG Tierney, E. S., Marans, Z., Rurkin, M. B., Chung, W. K. 2007; 17 (3): 268-274

  Abstract

  This study was designed to assess the frequency and types of genetic variants in CFC1 in children with laterality disorders associated with cardiovascular involvement.Laterality syndromes are estimated to comprise 3% of neonates with congenital cardiac disease. Genetic predisposition in some cases of laterality defects has been suggested by associated chromosomal anomalies and familial aggregation, often within consanguineous families, suggesting autosomal recessive inheritance. Mice with induced homozygous mutations in cfc1, and heterozygous CFC1 mutations in humans, have been associated with laterality defects.Direct sequence analysis of the coding sequence of CFC1 was performed in 42 subjects with laterality defects and congenital cardiac disease.We identified 3 synonymous coding variants, 3 non-synonymous coding variants (N21H, R47Q, and R78W), and 2 intronic variants in CFC1. The N21H variant was observed in 3 of 19 affected Caucasians, and the R47Q variant in another 2. Neither polymorphism was observed in Caucasian controls. Furthermore, all subjects with the N21H polymorphism had double outlet right ventricle. Transmission of both the N21H and R47Q polymorphisms from unaffected parents was demonstrated, and all three non-synonymous variants had significant allele frequencies in unaffected African-American subjects, suggesting that other factors must also contribute to laterality defects.Three non-synonymous variants in CFC1 were identified, the N21H variant being associated with laterality defects in Caucasians, but not fully penetrant. One or more of these non-synonymous missense variants may act as a susceptibility allele in conjunction with other genes, and/or environmental factors, to cause laterality defects.

  View details for DOI 10.1017/S1047951107000455

  View details for Web of Science ID 000247220000005

  View details for PubMedID 17445335

• Beta-blocker therapy does not alter the rate of aortic root dilation in pediatric patients with Marfan syndrome JOURNAL OF PEDIATRICS Tierney, E. S., Feingold, B., Printz, B. F., Park, S. C., Graham, D., Kleinman, C. S., Mahnke, C. B., Timchak, D. M., Neches, W. H., Gersony, W. M. 2007; 150 (1): 77-82

  Abstract

  To test the hypothesis that chronic beta-blocker therapy in pediatric patients with Marfan syndrome alters the rate of aortic root dilation. Beta-blockade has been advocated as preventive therapy for Marfan syndrome based on reports indicating a decreased rate of aortic root dilation in treated patients.Patients with Marfan syndrome (n = 63) followed at Children's Hospital of Pittsburgh or Children's Hospital of New York-Presbyterian who had > or =18 months of echocardiographic follow-up were studied. All clinical data and 213 serial echocardiograms were reviewed, and aortic root dimensions were measured. Patients were divided into 2 groups for comparison: untreated (n = 34) and treated (n = 29).At study entry, the 2 study groups were comparable in terms of age, sex, body surface area (BSA), aortic root measurements, heart rate, and corresponding z scores. Follow-up duration in each group was similar. At last follow-up, heart rates and heart rate z scores were lower in the treated group. Rates of change of aortic root measurements (P = .52) and the corresponding z scores were not statistically different between the 2 group at the study's end.This study suggests that that beta-blocker therapy does not significantly alter the rate of aortic root dilation in children with Marfan syndrome. Based on these data, the recommendation of lifetime beta-blocker therapy instituted during childhood should be reassessed.

  View details for DOI 10.1016/j.jpeds.2006.09.003

  View details for Web of Science ID 000243450500018

  View details for PubMedID 17188619

• Pulmonary position cryopreserved homografts: Durability in pediatric Ross and non-Ross patients JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Tierney, E. S., Gersony, W. M., Altmann, K., Solowiejczyk, D. E., Bevilacqua, L. M., Khan, C., Krongrad, E., Mosca, R. S., Quaegebeur, J. M., Apfel, H. D. 2005; 130 (2): 282-286

  Abstract

  The purpose of this study was to evaluate the outcome and risk factors for implant failure in pediatric patients who underwent pulmonary position homograft placement for right ventricular outflow tract obstruction compared with conduit placement as a component of the Ross operation. Actuarial 5-year survivals for cryopreserved right ventricle-to-pulmonary artery homografts range from 55% to 94% at all ages. It is not known whether there is a difference in homograft durability when utilized for right ventricular outflow tract obstruction or as part of the Ross operation.The records of all pediatric patients receiving a right ventricle-to-pulmonary artery homograft from July 1989 through October 2003 were reviewed. Ninety-eight consecutive patients were studied (26 Ross, 72 non-Ross). In addition to Ross versus non-Ross comparisons, other potential risk factors for homograft failure analyzed included age at operation, follow-up time, type of surgery, and homograft type and size.Ross and non-Ross patients were comparable in age at the time of the operation and follow-up time. Homograft failure rates were 12% and 51% for Ross and non-Ross patients, respectively. Freedom from reintervention was 93% in the Ross and 66% in the non-Ross group at 5 years (P = .019). On multivariate analysis, non-Ross operation and age less than 2 years were significant predictors of homograft failure.1. Pediatric patients undergoing the Ross operation have longer homograft survival than pediatric patients treated for right ventricular outflow tract obstruction, independent of age. 2. Homografts placed in patients less than 2 years of age have shorter homograft survival.

  View details for DOI 10.1016/j.jtcvs.2005.04.003

  View details for Web of Science ID 000231069700009

  View details for PubMedID 16077388

• Complete atresia of coronary ostia in pulmonary atresia and intact ventricular septum PEDIATRIC CARDIOLOGY Selamet, S. E., Hsu, D. T., Thaker, H. M., Gersony, W. M. 2004; 25 (1): 67-69

  Abstract

  We describe the clinical course, echocardiography, angiography, and histopathology of a female infant with pulmonary atresia and intact ventricular septum (PA/IVS) with complete coronary ostial atresia and right ventricle-dependent coronary circulation who survived for 7 weeks after palliative surgery. The patient expired from myocardial insufficiency while waiting for a donor heart. Postmortem examination demonstrated atretic coronary ostia, ventricular sinusoids, and myocardial infarctions of various ages. This report suggests that neonates with PA/IVS who have this extreme form of coronary abnormality may potentially be managed medically and surgically until cardiac transplantation is available.

  View details for DOI 10.1007/s00246-003-0517-0

  View details for Web of Science ID 000188455300016

  View details for PubMedID 12947508