Clinical Focus

  • Pediatric Cardiology
  • Echocardiography, Marfan Syndrome, Kawasaki Disease, Familial Hyperlipidemia

Academic Appointments

Administrative Appointments

  • Director of Research in the Non-Invasive Imaging Laboratory, Lucile Pachard Children’s Hospital, Stanford University (2016 - Present)
  • Assistant Professor of Pediatrics (Cardiology), Stanford School of Medicine (2011 - Present)
  • Director of Pediatric Vascular Research Laboratory, Lucile Packard Children's Hospital, Stanford University (2011 - Present)
  • Assistant Professor, Harvard School of Medicine (2009 - 2011)
  • Instructor in Pediatrics, Harvard School of Medicine (2004 - 2009)

Professional Education

  • Fellowship:Columbia University (2004) NY
  • Medical Education:Istanbul University CMF Medicine (1996) Turkey
  • Residency:SUNY - Stony Brook (2000) NY
  • Internship:SUNY - Stony Brook (1998) NY
  • Board Certification: Pediatric Cardiology, American Board of Pediatrics (2004)
  • Board Certification: Pediatrics, American Board of Pediatrics (2000)

Research & Scholarship

Current Research and Scholarly Interests

Assessment of Vascular Health by non-invasive modalities in children
Echocardiography and outcomes in congenital heart disease

Clinical Trials

  • On-Line Intervention to Lower Cardiovascular Risk in Pediatric Heart Transplant Patients Recruiting

    Pediatric heart transplant patients have a high-risk cardiovascular profile affecting their long-term outcomes and survival. Currently, no effective cardiovascular preventative care is provided for this pediatric population, in part, due to the fact that clinic-based programs are not easily accessible to children and their families. However, tele-health has been show to improve medical outcomes by making care more accessible to these patients. This study aims to meet the urgent need for an effective and sustainable delivery of preventative care to pediatric heart transplant patients using a diet and exercise intervention program delivered live over the internet direct to these patients' homes.

    View full details

  • Vascular Health and Exercise Performance of Overweight Children Not Recruiting

    The purpose of this study is to assess exercise performance in 20 healthy children 10-19 years of age with a body mass index greater than 85th percentile and to evaluate the effect of dietary and exercise intervention over 12 weeks.

    Stanford is currently not accepting patients for this trial. For more information, please contact Seda Tierney, MD, 650-736-7747.

    View full details


2017-18 Courses


All Publications

  • 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


    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


    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

  • 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


    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

  • 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., 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. 2017; 10 (11)


    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: Unique identifier: NCT00123071.

    View details for DOI 10.1161/CIRCIMAGING.116.006007

    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


    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

  • 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., Selamet Tierney, E. S. 2016


    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 PubMedID 28029346

  • 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


    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

  • 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


    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

  • 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


    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., Tierney, E. S. 2015; 167 (3): 533-9 e1


    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


    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

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


    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

  • 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


    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


    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

  • 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


    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

  • 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


    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

  • 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


    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


    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; 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


    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

  • 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


    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

  • 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


    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


    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: 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


    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


    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

  • Echocardiographic predictors of left ventricular dysfunction after aortic valve surgery in children with chronic aortic regurgitation. Congenital heart disease Selamet Tierney, E. S., Gal, D., Gauvreau, K., Zhou, J., Soluk, Y., McElhinney, D. B., Colan, S. D., Geva, T. 2013; 8 (4): 308-315


    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 PubMedID 23075071

  • 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


    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


    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

  • 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


    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

  • 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-?


    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


    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

  • Erratum to: Tricuspid Atresia With Progressive Ductal Restriction in a Fetus. Pediatric cardiology 2012

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

    View details for PubMedID 22972518

  • 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


    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


    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


    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


    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


    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


    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


    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


    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


    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


    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


    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


    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


    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