Rajesh Punn, M.D.

All Publications

• Right Ventricular and Outflow Tract Functional Characteristics After Repair of Tetralogy of Fallot with Major Aortopulmonary Collaterals. Pediatric cardiology Long, Z. B., Punn, R., Zhang, Y., Arunamata, A. A., Asija, R., Ma, M., Hanley, F. L., McElhinney, D. B. 2024

  Abstract

  This study describes right ventricle (RV) characteristics and right ventricle to pulmonary artery (RV-PA) conduit function pre- and post-repair in patients with tetraology of Fallot with major aortopulmonary collaterals (TOF/MAPCAs). We reviewed patients who underwent single-stage, complete unifocalization, and repair of TOF/MAPCAs between 2006 and 2019 with available pre- and early postoperative echocardiograms. For a subset of patients, 6-12 month follow-up echocardiogram was available. RV and left ventricle (LV) characteristics and RV-PA conduit function were reviewed. Wilcoxon signed rank test and McNemar's test were used. 170 patients were reviewed, 46 had follow-up echocardiograms. Tricuspid valve annular plane systolic excursion (TAPSE) Z-scores were reduced from pre- (Z-score 0.01) to post-repair (Z-score -4.5, p < 0.001), improved but remained abnormal at follow-up (Z-score -4.0, p < 0.001). RV fractional area change (FAC) and LV ejection fraction were not significantly different before and after surgery. Conduit regurgitation was moderate or greater in 11% at discharge, increased to 65% at follow-up. RV-PA conduit failure (severe pulmonary stenosis or severe pulmonary regurgitation) was noted in 61, and 63% had dilated RV (diastolic RV area Z-score > 2) at follow-up. RV dilation correlated with the severe conduit regurgitation (p = 0.018). Longitudinal RV function was reduced after complete repair of TOF/MAPCAs, with decreased TAPSE and preserved FAC and LV ejection fraction. TAPSE improved but did not normalize at follow-up. Severe RV-PA conduit dysfunction was observed prior to discharge in 11% of patients and in 61% at follow-up. RV dilation was common at follow-up, especially in the presence of severe conduit regurgitation.

  View details for DOI 10.1007/s00246-024-03412-0

  View details for PubMedID 38360921

  View details for PubMedCentralID 6035101

• Cannula Positioning in an Infant on Venoarterial Extracorporeal Membrane Oxygenation: A Rare Cause of Reverse Differential Cyanosis. CASE (Philadelphia, Pa.) Ramachandra, R., Ellison, G. A., Su, F., Punn, R. 2024; 8 (1): 21-24

  Abstract

  • Reverse differential cyanosis in patients on VA-ECMO via carotid cannulation is very rare. • A malpositioned aortic cannula can cause cerebral perfusion with deoxygenated blood. • Checking oxygen saturations in the lower extremity alone can be falsely reassuring. • Document simultaneous upper and lower extremity saturations for all patients on VA-ECMO. • Echo is a useful diagnostic tool to confirm cannula position and guide adjustment.

  View details for DOI 10.1016/j.case.2023.09.006

  View details for PubMedID 38264621

  View details for PubMedCentralID PMC10801703

• Tricuspid valve annular tilt for assessment of pre- and post-intervention right ventricular volume in patients undergoing transcatheter pulmonary valve replacement. Cardiology in the young Reddy, C. D., Yokota, R., Punn, R. 2023: 1-7

  Abstract

  Transcatheter pulmonary valve replacement serves as a successful alternative to surgical replacement of a right ventricle to pulmonary artery conduit. Guidelines for recommending transcatheter pulmonary valve replacement depend on MRI right ventricular volumes, which have been correlated to the echocardiographic measure of right ventricular annular tilt. We aim to assess whether right ventricular annular tilt can be a clinically useful alternative tool in the acute and long-term periods after transcatheter pulmonary valve replacement to assess right ventricular health.We reviewed 70 patients who underwent transcatheter pulmonary valve replacement at a single institution. Echocardiographic measurements were obtained prior to transcatheter pulmonary valve replacement, immediately after transcatheter pulmonary valve replacement, and within 6 months to 1 year after transcatheter pulmonary valve replacement. Right ventricular annular tilt measures the angle of the tricuspid valve plane relative to the mitral valve plane at end-diastole in the apical four-chamber view. Right ventricular fractional area change, right ventricular systolic strain, tissue Doppler velocity, and tricuspid annular plane systolic excursion Z-scores were obtained using published methods.Right ventricular annular tilt decreased significantly immediately after transcatheter pulmonary valve replacement (p = 0.0004), and this reduction in right ventricular volume persisted at the mid-term follow-up (p < 0.0001). Fractional area change did not change significantly after transcatheter pulmonary valve replacement while right ventricular global strain improved at mid-term follow-up despite no significant difference immediately after transcatheter pulmonary valve replacement.Right ventricular annular tilt decreases both immediately after transcatheter pulmonary valve replacement and at mid-term follow-up. Right ventricular strain also improved after transcatheter pulmonary valve replacement, corresponding to the improved volume load. Right ventricular annular tilt can be considered as an additional echocardiographic factor to assess right ventricular volume and remodeling after transcatheter pulmonary valve replacement.

  View details for DOI 10.1017/S1047951123001452

  View details for PubMedID 37309189

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

  Abstract

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

  View details for DOI 10.1016/j.ahj.2023.02.006

  View details for PubMedID 36796574

• Targeted Neonatal Echocardiography in Patients With Hemodynamic Instability. Pediatrics Rahde Bischoff, A., Bhombal, S., Altman, C. A., Fraga, M. V., Punn, R., Rohatgi, R. K., Lopez, L., McNamara, P. J. 2022; 150 (Suppl 2)

  Abstract

  Targeted neonatal echocardiography (TNE) has been increasingly used at the bedside in neonatal care to provide an enhanced understanding of physiology, affecting management in hemodynamically unstable patients. Traditional methods of bedside assessment, including blood pressure, heart rate monitoring, and capillary refill are unable to provide a complete picture of tissue perfusion and oxygenation. TNE allows for precision medicine, providing a tool for identifying pathophysiology and to continually reassess rapid changes in hemodynamics. A relationship with cardiology is integral both in training as well as quality assurance. It is imperative that congenital heart disease is ruled out when utilizing TNE for hemodynamic management, as pathophysiology varies substantially in the assessment and management of patients with congenital heart disease. Utilizing TNE for longitudinal hemodynamic assessment requires extensive training. As the field continues to grow, guidelines and protocols for training and indications are essential for ensuring optimal use and providing a platform for quality assurance.

  View details for DOI 10.1542/peds.2022-056415I

  View details for PubMedID 36317979

• Hemodynamic and Echocardiographic Predictors of Mortality in Pediatric Patients on Venoarterial Extracorporeal Membrane Oxygenation - A Multicenter Investigation. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Punn, R., Falkensammer, C. B., Blinder, J. J., Fifer, C. G., Thorsson, T., Perens, G., Federman, M., Gupta, P., Best, T., Arya, B., Chan, T., Sherman-Levine, S., Smith, S. N., Axelrod, D. M., Roth, S. J., Tacy, T. A. 2022

  Abstract

  BACKGROUND: Veno-arterial extracorporeal membrane oxygenation (ECMO) supports patients with advanced cardiac dysfunction; however, mortality occurs in a significant subset of patients. We performed a multicenter, prospective study to determine hemodynamic and echocardiographic (echo) predictors of mortality in children placed on ECMO for cardiac support.METHODS: Over eight years, six heart centers prospectively assessed echo and hemodynamic variables on full and minimum ECMO flow. We enrolled 63 patients ranging in age 1 day - 16 years. Hemodynamic measurements included: heart rate, vasoactive inotropic score, arterio-venous oxygen difference, pulse pressure, and lactate. Echo variables included: shortening/ejection fraction (EF), right ventricular fractional area change, outflow tract Doppler-derived stroke distance (VTI), and degree of atrioventricular valve regurgitation (AVVR). Patients were stratified into those who were able to wean in 48 hours from assessment and survived without a ventricular assist device (VAD) or orthotopic heart transplant (OHT) (successful wean group), and the remaining constituted the unsuccessful wean group. For each patient, we compared the variable from full versus minimum ECMO flow for each group.RESULTS: Thirty-eight formed the unsuccessful group (2 VAD, 4 OHT, 24 deaths, 60%) and 25 comprised the successful wean group. At minimum flow higher EF (53 +/- 16 vs 40 +/- 20%, p = 0.0094), less mitral regurgitation (MR) (0.8 +/- 0.9 vs 1.4 +/- 0.9, p = 0.0329), and lower central venous pressure (CVP) (12.0 +/- 3.9 vs 14.7 +/- 5.4 mmHg) along with higher VTI (9.0 +/- 2.9 vs 6.8 +/- 3.7 cm, p = 0.0154) correlated with the successful wean group. A longer duration of ECMO (p < 0.0002, 8 vs 5 days) associated with the unsuccessful group. Multivariate logistical regression predicted minimum flow EF and VTI to independently predict successful wean with a cut-off value by ROC analysis of EF >41% and VTI >7.9 cm (AUC = 0.712-0.729, p=0.0005-0.0010).CONCLUSION: Diminished VTI or EF during ECMO weaning predicts the need for OHT or VAD support or death in children on ECMO for cardiac dysfunction. Increased post-wean CVP or MR along with a prolonged ECMO course also predicted these adverse outcomes. We propose that these measurements should be utilized to help discriminate who will require alternative methods of circulatory support for survival.

  View details for DOI 10.1016/j.echo.2022.10.005

  View details for PubMedID 36228840

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

  Abstract

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

  View details for DOI 10.1016/j.echo.2022.08.007

  View details for PubMedID 35973561

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

  Abstract

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

  View details for DOI 10.1017/S1047951122001536

  View details for PubMedID 35747949

• Left Subclavian Artery Isolation with Right Aortic Arch and D-Transposition of the Great Arteries. CASE (Philadelphia, Pa.) Hansen, K., Dhillon, G., Ma, M., Maskatia, S. A., Su, L., Vasanawala, S., Punn, R. 1800; 5 (6): 392-398

  View details for DOI 10.1016/j.case.2021.09.010

  View details for PubMedID 34993370

• Prenatally diagnosed pseudoaneurysms of the mitral-aortic intervalvular fibrous area. Ultrasound in obstetrics & gynecology : the official journal of the International Society of Ultrasound in Obstetrics and Gynecology Hogan, W. J., Punn, R., Dean, P., Strainic, J., Rychik, J., Williams, R. V., Moon-Grady, A. J., Silverman, N. H. 2021

  Abstract

  The mitral-aortic intervalvular fibrosa (MAIVF) is an avascular, fibrous structure that provides continuity between the anterior leaflet of the mitral valve and the aortic valve. Pseudoaneurysms of this area are rare and more commonly have been described in adult patients following trauma, cardiac surgery, or endocarditis.1,2 Limited case studies describe the occurrence in children following cardiac surgery3, 9 or endocarditis,4,5 with few case reports describing the congenital nature of these pseudoaneurysms.4,6-9 Here, we describe 5 cases of congenital pseudoaneurysms in the MAIVF area identified prenatally, with an additional 6 cases diagnosed postnatally. This is an unusual finding of varying clinical significance that can be isolated or associated with complex congenital heart disease, but importantly, can be identified and monitored in the fetus. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/uog.24762

  View details for PubMedID 34494326

• Longitudinal Assessment of Right Ventricular Function in Hypoplastic Left Heart Syndrome. Pediatric cardiology Balasubramanian, S., Smith, S. N., Srinivasan, P., Tacy, T. A., Hanley, F. L., Chen, S., Wright, G. E., Peng, L. F., Punn, R. 2021

  Abstract

  Overall survival of patients with hypoplastic left heart syndrome (HLHS) has shown continued improvement. Right ventricular (RV) dysfunction, in the long term, adversely affects prognosis in these patients. This study examines changes in echocardiographic markers of RV function in a longitudinal cohort. We retrospectively reviewed patients with HLHS managed at our institution from 7/1994 to 1/2016. Follow-up included surgical and clinical data, and echocardiographic measures. Measures of RV function preceding and following all three stages of single ventricular palliation were collected. Freedom from transplant-free survival was assessed by Kaplan-Meier analysis. Multivariable associations with time to death or transplant were explored using the Cox proportional hazards model. A total of 120 patients with HLHS were identified. Norwood operation was performed in all patients. The probability of survival for the cohort was 71±4.4%, 69±4.5% and 66±4.7% at 1, 2 and 5years respectively after stage I Norwood operation. RV fractional area change (FAC), compared to post-Norwood was decreased at all subsequent stages with the greatest change noted post-superior cavo-pulmonary shunt from 40.7±9.3% to 31.1±8.3% (p<0.001). Similarly, tricuspid valve annular systolic excursion (TAPSE) Z-score declined from -2.9±1.3 to -9.7±1.3 (p<0.001) with a decrement at every stage of evaluation. In comparison to patients with post-Norwood RV FAC>35% and TAPSE Z-score>-5, patients with RV FAC ≤ 35% and TAPSE Z-score ≤ -5 had a significantly lower transplant-free survival (p<0.0001). In patients with HLHS undergoing staged palliation, decrement in RV function manifests longitudinally. Post-Norwood RV FAC and TAPSE Z-score appear to be early markers of poor outcome in this population.

  View details for DOI 10.1007/s00246-021-02624-y

  View details for PubMedID 33987707

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

  Abstract

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

  View details for DOI 10.1016/j.jpeds.2021.01.004

  View details for PubMedID 33453199

• A Fetal Risk Stratification Pathway for Neonatal Aortic Coarctation Reduces Medical Exposure. The Journal of pediatrics Maskatia, S. A., Kwiatkowski, D., Bhombal, S., Davis, A. S., McElhinney, D. B., Tacy, T. A., Algaze, C., Blumenfeld, Y., Quirin, A., Punn, R. 2021

  Abstract

  To test the hypothesis that a fetal stratification pathway will effectively discriminate between infants at different levels of risk for surgical coarctation and reduce unnecessary medicalization.We performed a pre-post non-randomized study in which we prospectively assigned fetuses with prenatal concern for coarctation to one of three risk categories and implemented a clinical pathway for postnatal management. Postnatal clinical outcomes were compared with a historical control group that were not triaged based on the pathway.The study cohort included 109 fetuses, 57 treated along the fetal coarctation pathway, and 52 historical controls. Among mild-risk fetuses, 3% underwent surgical coarctation repair (0% of those without additional heart defects), compared with 27% of moderate-risk and 63% of high-risk. Combined fetal aortic, mitral and isthmus z-score best discriminated which patients underwent surgery, AUC=0.78(0.66,0.91). Patients triaged according to the fetal coarctation pathway had reduced delivery location changes (76% vs 55%, p=0.025), and umbilical venous catheter placement (74% vs 51%, p=0.046) compared with historical controls. Trends towards shorter intensive care unit stay, hospital stay and time to enteral feeding did not reach statistical significance.A stratified risk-assignment pathway effectively identifies a group of fetuses with low rate of surgical coarctation, and reduces unnecessary medicalization in infants who do not undergo aortic surgery. Incorporation of novel measurements or imaging techniques may improve specificity of high-risk criteria.

  View details for DOI 10.1016/j.jpeds.2021.06.047

  View details for PubMedID 34181988

• Recent outcomes of the extracardiac Fontan procedure in patients with hypoplastic left heart syndrome ANNALS OF PEDIATRIC CARDIOLOGY Arunamata, A., Tacy, T. A., Kache, S., Mainwaring, R. D., Ma, M., Maeda, K., Punn, R. 2020; 13 (3): 186–93

  View details for DOI 10.4103/apc.APC_5_20

  View details for Web of Science ID 000552113300002

• Recent outcomes of the extracardiac Fontan procedure in patients with hypoplastic left heart syndrome. Annals of pediatric cardiology Arunamata, A., Tacy, T. A., Kache, S., Mainwaring, R. D., Ma, M., Maeda, K., Punn, R. 2020; 13 (3): 186-193

  Abstract

  To investigate patient-related factors, echocardiographic, and anatomic variables associated with immediate and long-term clinical outcomes after extracardiac Fontan procedure at our institution.Retrospective review of preoperative cardiac catheterizations and echocardiograms as well as medical records of all children with hypoplastic left heart syndrome (HLHS) who underwent Fontan between June 2002 and December 2018.Seventy-seven patients with HLHS were included (age 4 years [1.5-11.7]). Seventy patients (91%) received a nonfenestrated Fontan and 57 patients (74%) underwent Fontan without cardiopulmonary bypass (CPB). Presence of a Fontan fenestration (P = 0.69) and use of CPB (P = 0.79) did not differ between those with <2 weeks compared to those with ≥2 weeks of chest tube drainage. There were no differences in either pre- or intra-operative hemodynamics between patients who weighed <15 kg compared to those who weighed ≥15 kg at time of surgery; incidence of death, transplant, and transplant listing were similar between weight groups. Inferior vena cava (IVC) diameter z-score did not differ among patients with and without chylous chest tube drainage (P = 0.78), with and without development of protein losing enteropathy (P = 0.23), or death/heart transplant/transplant listing compared to survivors without transplant (P = 0.26).In HLHS patients undergoing Fontan, preoperative weight and IVC diameter appeared to have no influence on immediate postoperative outcomes. Performing the Fontan off CPB and with a fenestration also conferred no added clinical benefit. These observations should be considered when deciding optimal timing for Fontan completion.

  View details for DOI 10.4103/apc.APC_5_20

  View details for PubMedID 32863652

  View details for PubMedCentralID PMC7437630

• The Natural and Unnatural History of Ventricular Septal Defects Presenting in Infancy: An Echocardiography-Based Review. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Cox, K., Algaze-Yojay, C., Punn, R., Silverman, N. 2020

  Abstract

  BACKGROUND: Ventricular septal defect (VSD), the most common congenital heart defect, accounts for 40% of heart malformations. Despite this prevalence, there remains no consensus on the utility of echocardiography to guide modern-era treatment. In this study, we evaluated patients with isolated VSDs to test the hypothesis that echocardiographic evidence of left ventricular (LV) volume overload and type of VSD are associated with surgical intervention and to identify useful echocardiographic indicators for management of VSDs in infants and children.METHODS: We reviewed 350 patients with VSDs diagnosed during the first year of life. Echocardiographic measurements were made at the time of diagnosis and at the endpoint. The VSD area was calculated using inner edge to inner edge dimensions obtained from two planes and indexed to body surface area. Aortic annulus dimension, left atrium to aortic root ratio, LV end-diastolic diameter, left atrial volume, VSD velocity-time integral, ejection fraction, and pulmonary to systemic blood flow ratio (Qp:Qs) were measured using conventional methods.RESULTS: One hundred seventy-seven muscular (50.5%) and 162 perimembranous (46%) VSDs accounted for the vast majority of defects. Only seven (4%) muscular defects required surgical closure, while 76 (47%) perimembranous defects required surgery. Indexed VSD area, VSD to aortic valve ratio, indexed left atrium volume, LV end-diastolic diameter, VSD velocity-time integral, and Qp:Qs at diagnosis were significantly different between the surgical and nonsurgical groups. Ventricular septal defect area > 50mm2/m2 at initial diagnosis was independently associated with risk for surgery (P=.0055).CONCLUSIONS: Indexed VSD area is an echocardiographic variable that can be easily measured at diagnosis and can provide insight into the likelihood of requiring surgical intervention regardless of the type and location of the defect.

  View details for DOI 10.1016/j.echo.2020.01.013

  View details for PubMedID 32249125

• Circulating whole genome miRNA expression corresponds to progressive right ventricle enlargement and systolic dysfunction in adults with tetralogy of Fallot. PloS one Weldy, C. S., Syed, S. A., Amsallem, M., Hu, D., Ji, X., Punn, R., Taylor, A., Navarre, B., Reddy, S. 2020; 15 (11): e0241476

  Abstract

  INTRODUCTION: The adult congenital heart disease population with repaired tetralogy of Fallot (TOF) is subject to chronic volume and pressure loading leading to a 40% probability of right ventricular (RV) failure by the 3rd decade of life. We sought to identify a non-invasive signature of adverse RV remodeling using peripheral blood microRNA (miRNA) profiling to better understand the mechanisms of RV failure.METHODS: Demographic, clinical data, and blood samples were collected from adults with repaired TOF (N = 20). RNA was isolated from the buffy coat of peripheral blood and whole genome miRNA expression was profiled using Agilent's global miRNA microarray platform. Fold change, pathway analysis, and unbiased hierarchical clustering of miRNA expression was performed and correlated to RV size and function assessed by echocardiography performed at or near the time of blood collection.RESULTS: MiRNA expression was profiled in the following groups: 1. normal RV size (N = 4), 2. mild/moderate RV enlargement (N = 11) and 3. severe RV enlargement (N = 5). 267 miRNAs were downregulated, and 66 were upregulated across the three groups (fold change >2.0, FDR corrected p<0.05) as RV enlargement increased and systolic function decreased. qPCR validation of a subset of these miRNAs identified increasing expression of miRNA 28-3p, 433-3p, and 371b-3p to be associated with increasing RV size and decreasing RV systolic function. Unbiased hierarchical clustering of all patients based on miRNA expression demonstrates three distinct patient clusters that largely coincide with progressive RV enlargement. Pathway analysis of dysregulated miRNAs demonstrates up and downregulation of cell cycle pathways, extracellular matrix proteins and fatty acid synthesis. HIF 1alpha signaling was downregulated while p53 signaling was predicted to be upregulated.CONCLUSION: Adults with TOF have a distinct miRNA profile with progressive RV enlargement and dysfunction implicating cell cycle dysregulation and upregulation in extracellular matrix and fatty acid metabolism. These data suggest peripheral blood miRNA can provide insight into the mechanisms of RV failure and can potentially be used for monitoring disease progression and to develop RV specific therapeutics to prevent RV failure in TOF.

  View details for DOI 10.1371/journal.pone.0241476

  View details for PubMedID 33175850

• UTILIZATION OF FUNCTIONAL ECHOCARDIOGRAPHY AND NEAR-INFRARED SPECTROSCOPY TO CHARACTERIZE DUCTAL HEMODYNAMICS IN THE PREMATURE NEONATE Ringle, M., Chock, V. Y., Stauffer, K., Lopez, L., Punn, R., Bhombal, S. BMJ PUBLISHING GROUP. 2020: A49

  View details for DOI 10.1136/jim-2019-WMRC.115

  View details for Web of Science ID 000507513300115

• Cardiac Dysfunction Identified by Strain Echocardiography Is Associated With Illness Severity in Pediatric Sepsis. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Patel, M. D., Mariano, K. n., Dunbar, T. n., Cornell, T. T., Punn, R. n., Haileselassie, B. n. 2020

  Abstract

  Sepsis-induced myocardial dysfunction has been associated with illness severity and mortality in pediatrics. Although early sepsis-induced myocardial dysfunction diagnosis could aid in hemodynamic management, current echocardiographic metrics for assessing biventricular function are limited in detecting early impairment. Strain echocardiography is a validated quantitative measure that can detect subtle perturbations in left ventricular and right ventricular function. This investigation evaluates the utility of strain echocardiography in pediatric sepsis and compares with to conventional methods.Retrospective, observational study comparing left ventricular and right ventricular strain. Strain was compared with ejection fraction and fractional shortening and established sepsis severity of illness markers.Tertiary care medical-surgical PICU from July 2013 to January 2018.Seventy-nine septic children and 28 healthy controls.None.Compared with healthy controls, patients with severe sepsis demonstrated abnormal left ventricular strain (left ventricular longitudinal strain: -13.0% ± 0.72; p = 0.04 and left ventricular circumferential strain: -16.5% ± 0.99; p = 0.046) and right ventricular (right ventricular longitudinal strain = -14.3% ± 6.3; p < 0.01) despite normal fractional shortening (36.0% ± 1.6 vs 38.1% ± 1.1; p = 0.5129) and ejection fraction (60.7% ± 2.2 vs 65.3% ± 1.5; p = 0.33). There was significant association between depressed left ventricular longitudinal strain and increased Vasotrope-Inotrope Score (r = 0.52; p = 0.034). Worsening left ventricular circumferential strain was correlated with higher lactate (r = 0.31; p = 0.03) and higher Pediatric Risk of Mortality-III score (r = 0.39; p < 0.01). Depressed right ventricular longitudinal strain was associated with elevated pediatric multiple organ dysfunction score (r = 0.44; p < 0.01) CONCLUSIONS:: Compared with healthy children, pediatric septic patients demonstrated abnormal left ventricular and right ventricular strain concerning for early signs of cardiac dysfunction. This was despite having normal ejection fraction and fractional shortening. Abnormal strain was associated with abnormal severity of illness markers. Strain echocardiography may have utility as an early indicator of sepsis-induced myocardial dysfunction in pediatric sepsis.

  View details for DOI 10.1097/PCC.0000000000002247

  View details for PubMedID 32084099

• Postoperative Recovery of Left Ventricular Function following Repair of Large Ventricular Septal Defects in Infants. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Adamson, G. T., Arunamata, A., Tacy, T. A., Silverman, N. H., Ma, M., Maskatia, S. A., Punn, R. 2019

  Abstract

  INTRODUCTION: Early postoperative left ventricular (LV) dysfunction is observed following repair of large ventricular septal defects (VSDs), but the frequency and rate of recovery of LV function are unknown. This study aims to characterize the incidence and rate of recovery of postoperative LV dysfunction following repair of large VSDs and to improve understanding of LV mechanics before and after VSD repair.METHODS: Infants who underwent surgical repair of an isolated large VSD were included. Pre- and postoperative echocardiographic images were reviewed, and LV function was assessed by both conventional echocardiography and speckle-tracking strain analyses. Postoperative LV dysfunction was defined as an LV ejection fraction (LVEF)<50% using the 5/6 area-length method. Echocardiograms were reviewed to assess LVEF and LV volume through 1-year follow-up.RESULTS: Of 104 infants evaluated (median age, 0.31 [0.22, 0.56] years), all had normal preoperative LVEF and 39 (38%) had postoperative LV dysfunction. Follow-up echocardiograms were available in 31 (80%) patients, all of whom had LVEF>50% within 9months of surgery. Lower preoperative apical four-chamber longitudinal strain (A4LS) and greater LV end-diastolic volume indexed to body surface area1.38 were independently associated with postoperative LV dysfunction. An absolute preoperative A4LS < 16.7% (area under the curve=0.87; 95% CI, 0.78-0.95; P<.001) was most strongly associated with postoperative dysfunction.CONCLUSIONS: Infants with LV dysfunction following repair of large VSDs recover function within 9months. Preoperative A4LS can be helpful to detect subclinical LV dysfunction in the setting of a large hemodynamically significant VSD and guide postoperative expectations for providers and families.

  View details for DOI 10.1016/j.echo.2019.10.003

  View details for PubMedID 31866322

• Serial assessment of postoperative ventricular mechanics in young children with tetralogy of Fallot: Comparison of transannular patch and valve-sparing repair CONGENITAL HEART DISEASE Annavajjhala, V., Punn, R., Tacy, T. A., Hanley, F. L., McElhinney, D. B. 2019; 14 (5): 691–99

  View details for DOI 10.1111/chd.12772

  View details for Web of Science ID 000490040700002

• Cardiac Segmental Strain Analysis in Pediatric Left Ventricular Noncompaction Cardiomyopathy JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Arunamata, A., Stringer, J., Balasubramanian, S., Tacy, T. A., Silverman, N. H., Punn, R. 2019; 32 (6): 763-+

  View details for DOI 10.1016/j.echo.2019.01.014

  View details for Web of Science ID 000470058700009

• Role of echocardiography in the assessment of right ventricular function in the pediatric population PEDIATRIC ANESTHESIA Kamra, K., Punn, R. 2019; 29 (5): 530–38

  View details for DOI 10.1111/pan.13641

  View details for Web of Science ID 000468217100018

• Role of echocardiography in the assessment of right ventricular function in the pediatric population. Paediatric anaesthesia Kamra, K., Punn, R. 2019

  Abstract

  This review article summarizes the use of echocardiography in the evaluation of right ventricle with special emphasis on pediatric patients. After reading this article, the anesthesiologists will develop a better understanding of anatomy and echocardiographic parameters for hemodynamic and functional assessment of the right ventricle. This knowledge will assist with the perioperative management of patients with cardiopulmonary disorder. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30934152

• Fetal Echocardiographic Parameters and Surgical Outcomes in Congenital Left-Sided Cardiac Lesions. Pediatric cardiology Edwards, L. A., Arunamata, A. n., Maskatia, S. A., Quirin, A. n., Bhombal, S. n., Maeda, K. n., Tacy, T. A., Punn, R. n. 2019

  Abstract

  This study aimed to evaluate fetal echocardiographic parameters associated with neonatal intervention and single-ventricle palliation (SVP) in fetuses with suspected left-sided cardiac lesions. Initial fetal echocardiograms (1/2002-1/2017) were interpreted by the contemporary fetal cardiologist as coarctation of the aorta (COA), left heart hypoplasia (LHH), hypoplastic left heart syndrome (HLHS), mitral valve hypoplasia (MVH) ± stenosis, and aortic valve hypoplasia ± stenosis (AS). The cohort comprised 68 fetuses with suspected left-sided cardiac lesions (COA n = 15, LHH n = 9, HLHS n = 39, MVH n = 1, and AS n = 4). Smaller left ventricular (LV) length Z score, aortic valve Z score, ascending aorta Z score, and aorta/pulmonary artery ratio; left-to-right shunting at the foramen ovale; and retrograde flow in the aortic arch were associated with the need for neonatal intervention (p = 0.005-0.04). Smaller mitral valve (MV) Z score, LV length Z score, aortic valve Z score, ascending aorta Z score, aorta/pulmonary artery ratio, and LV ejection fraction, as well as higher tricuspid valve-to-MV (TV/MV) ratio, right ventricular-to-LV (RV/LV) length ratio, left-to-right shunting at the foramen ovale, abnormal pulmonary vein Doppler, absence of prograde aortic flow, and retrograde flow in the aortic arch were associated with SVP (p < 0.001-0.008). The strongest independent variable associated with SVP was RV/LV length ratio (stepwise logistical regression, p = 0.03); an RV/LV length ratio > 1.28 was associated with SVP with a sensitivity of 76% and specificity of 96% (AUC 0.90, p < 0.001). A fetal RV/LV length ratio of > 1.28 may be a useful threshold for identifying fetuses requiring SVP.

  View details for DOI 10.1007/s00246-019-02155-7

  View details for PubMedID 31338561

• Cerebrovascular Blood Flow in Patients with Tetralogy of Fallot: Prediction for Early Surgical Intervention. Prenatal diagnosis Campbell, M. n., Ronai, C. n., Punn, R. n., Tacy, T. n., Tworetzky, W. n., Madriago, E. n. 2019

  Abstract

  Children with tetralogy of Fallot (TOF) require initial intervention at varying times reflecting a spectrum of obstruction to pulmonary blood flow. In utero, fetal patients with right sided obstructive lesions demonstrate increased middle cerebral artery (MCA) pulsatility index (PI). We sought to determine whether MCA flow patterns are associated with the degree of pulmonary obstruction and the consequential need for early surgical intervention (ESI).We performed a multi-center retrospective study evaluating patients with a prenatal diagnosis of TOF. All echocardiographic fetal studies performed from 16 weeks gestational age through delivery were reviewed between 2001 and 2015 with subsequent postnatal medical chart review.82 patients met inclusion criteria. Patients who ultimately required ESI (n=30) demonstrated an increased MCA PI z-score (-0.68 vs -1.32, p=0.02) compared to those who did not (n=52). An elevated MCA PI in patients with TOF was associated with ESI after 24 weeks gestational age (-0.36 vs -1.22, p=0.02).Fetal patients with TOF demonstrate altered MCA flow that correlates with need for ESI. This effect is blunted earlier in gestation which may reflect cerebral autoregulation. MCA PI may be a beneficial tool in helping determine perinatal management and counseling for patients with TOF.

  View details for DOI 10.1002/pd.5561

  View details for PubMedID 31525255

• Cardiac Segmental Strain Analysis in Pediatric Left Ventricular Noncompaction Cardiomyopathy. Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography Arunamata, A. n., Stringer, J. n., Balasubramanian, S. n., Tacy, T. A., Silverman, N. H., Punn, R. n. 2019

  Abstract

  Left ventricular noncompaction cardiomyopathy (LVNC) is characterized by prominent left ventricular trabeculations, often leading to myocardial dysfunction and death or heart transplantation. Although diagnostic echocardiographic criteria exist for LVNC, segmental speckle-tracking strain patterns have not been described in pediatric LVNC. The objectives of this study were to characterize segmental noncompaction, evaluate segmental speckle-tracking strain, and characterize peak strain values in children with LVNC with adverse clinical outcomes.Echocardiographic noncompaction/compaction ratios and segmental radial, circumferential, and longitudinal strain were measured retrospectively in children with LVNC (January 2000 to June 2013). Segmental strain of the cohort was compared with that in control subjects matched by age and body surface area.One hundred one pediatric patients with LVNC were included (median age 2.8 years; range, 0-19.4 years); 71 patients survived (benign group) and 30 patients did not survive or required heart transplantation (adverse group). The adverse group was younger at diagnosis (P = .03), with lower ejection fractions (P < .0001) compared with the benign group. Both groups demonstrated increased noncompaction/compaction ratios within apical segments, with significantly increased involvement in antero- and inferolateral midpapillary segments in the adverse group (P < .005). Radial, circumferential, and longitudinal strain of nearly all left ventricular segments were significantly decreased in the adverse compared with the benign group and in pediatric LVNC patients compared with control subjects. Global radial (7.4 ± 9.7% vs 19.6 ± 16.5%, P < .0001), circumferential (-8.4 ± 7.0% vs -18.9 ± 6.9%, P < .0001), and longitudinal (-7.1 ± 5.2% vs -11.8 ± 5.3%, P < .0001) strain were all significantly decreased in the adverse group compared with the benign group.Segmental radial, circumferential, and longitudinal strain are decreased in pediatric patients with LVNC compared with control subjects and lowest in those with adverse compared with benign outcomes. LVNC appears to be a global disease affecting deformation in all regions, including compacted myocardial segments.

  View details for PubMedID 30926406

• A Retrospective Evaluation of Echocardiograms to Establish Normative Inferior Vena Cava and Aortic Measurements for Children Younger Than 6 Years JOURNAL OF ULTRASOUND IN MEDICINE Stenson, E. K., Punn, R., Ramsi, M., Kache, S. 2018; 37 (9): 2225–32

  Abstract

  The ability to plot the inferior vena cava (IVC) size on a normal curve for pediatric patients may prove beneficial. First, in patients with normal cardiac anatomy who present in shock, assessing IVC size may be valuable for evaluating the degree of dehydration. Second, in children with heart disease, understanding how a child's IVC size compares to normal could be particularly beneficial for patients with right heart disease. We sought to create normal curves for the IVC and aorta in children younger than 6 years.Data were gathered from 347 echocardiograms of healthy children younger than 6 years in a retrospective study at a quaternary care children's hospital. From the subcostal long- and short-axis images, maximum diameters in the transverse and longitudinal views were obtained for both the IVC and the aorta.Both IVC and aortic dimensions increased in a linear fashion and had excellent correlations with the body surface area, body mass, and height (IVC, r = 0.78-0.81; P < .0001; aorta, r = 0.82-0.86; P < .0001).In children younger than 6 years, the IVC and aorta increase linearly as the children grow. Such normal curves will be beneficial for assessing a pediatric patient's hydration status or right heart function in patients with congenital heart disease.

  View details for PubMedID 29480561

• Impact of Fetal Somatic Growth on Pulmonary Valve Annulus Z-Scores During Gestation and Through Birth in Patients with Tetralogy of Fallot PEDIATRIC CARDIOLOGY Arunamata, A., Balasubramanian, S., Punn, R., Quirin, A., Tacy, T. A. 2018; 39 (6): 1181–87

  View details for DOI 10.1007/s00246-018-1878-8

  View details for Web of Science ID 000441721000016

• Interstage evaluation of homograft-valved right ventricle to pulmonary artery conduits for palliation of hypoplastic left heart syndrome JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Sandeep, N., Punn, R., Balasubramanian, S., Smith, S. N., Reinhartz, O., Zhang, Y., Wright, G. E., Peng, L. F., Wise-Faberowski, L., Hanley, F. L., McElhinney, D. B. 2018; 155 (4): 1747-+

  Abstract

  Palliation of hypoplastic left heart syndrome with a standard nonvalved right ventricle to pulmonary artery conduit results in an inefficient circulation in part due to diastolic regurgitation. A composite right ventricle pulmonary artery conduit with a homograft valve has a hypothetical advantage of reducing regurgitation, but may differ in the propensity for stenosis because of valve remodeling.This retrospective cohort study included 130 patients with hypoplastic left heart syndrome who underwent a modified stage 1 procedure with a right ventricle to pulmonary artery conduit from 2002 to 2015. A composite valved conduit (cryopreserved homograft valve anastomosed to a polytetrafluoroethylene tube) was placed in 100 patients (47 aortic, 32 pulmonary, 13 femoral/saphenous vein, 8 unknown), and a nonvalved conduit was used in 30 patients. Echocardiographic functional parameters were evaluated before and after stage 1 palliation and before the bidirectional Glenn procedure, and interstage interventions were assessed.On competing risk analysis, survival over time was better in the valved conduit group (P = .040), but this difference was no longer significant after adjustment for surgical era. There was no significant difference between groups in the cumulative incidence of bidirectional Glenn completion (P = .15). Patients with a valved conduit underwent more interventions for conduit obstruction in the interstage period, but this difference did not reach significance (P = .16). There were no differences between groups in echocardiographic parameters of right ventricle function at baseline or pre-Glenn.In this cohort of patients with hypoplastic left heart syndrome, inclusion of a valved right ventricle to pulmonary artery conduit was not associated with any difference in survival on adjusted analysis and did not confer an identifiable benefit on right ventricle function.

  View details for PubMedID 29223842

• High human herpesvirus 6 viral load in pediatric allogeneic hematopoietic stem cell transplant patients is associated with detection in end organs and high mortality PEDIATRIC TRANSPLANTATION Winestone, L. E., Punn, R., Tamaresis, J. S., Buckingham, J., Pinsky, B. A., Waggoner, J. J., Kharbanda, S. 2018; 22 (2)

  Abstract

  Human Herpes Virus 6 (HHV-6) reactivation occurs in approximately half of patients following allogeneic hematopoietic stem cell transplant (HSCT). While encephalitis and delayed engraftment are well-documented complications of HHV-6 following HSCT, the extent to which HHV-6 viremia causes disease in children is controversial. We performed a retrospective review of HHV-6 reactivation and possible manifestations in pediatric allogeneic HSCT patients at a single institution. Of 89 children and young adults who underwent allogeneic HSCT over a three-and-a-half-year period, 34 patients reactivated HHV-6 early post-transplant. Unrelated donor stem cell source and lack of antiviral prophylaxis were risk factors for the development of HHV-6 viremia. Viremia correlated with the presence of acute graft-versus-host disease, but not chronic graft-versus-host disease. We identified two subgroups within the viremic patients-a high-risk viremic and tissue-positive group that reactivated HHV-6 and had suspected end-organ disease and a low-risk viremic but asymptomatic group that reactivated HHV-6 but did not exhibit symptoms or signs of end-organ disease. Peak viral load was found to be strongly associated with mortality. Prospective studies in larger numbers of patients are needed to further investigate the role of HHV-6 in causing symptomatic end-organ disease as well as the association of viral load with mortality.

  View details for PubMedID 29181879

  View details for PubMedCentralID PMC5820136

• Impact of Fetal Somatic Growth on Pulmonary Valve Annulus Z-Scores During Gestation and Through Birth in Patients with Tetralogy of Fallot. Pediatric cardiology Arunamata, A. n., Balasubramanian, S. n., Punn, R. n., Quirin, A. n., Tacy, T. A. 2018

  Abstract

  Previous studies have suggested reduced pulmonary valve annulus (PVA) growth and progression of pulmonary outflow obstruction in fetuses with tetralogy of Fallot (TOF). The goals of this study were to (1) investigate the trajectory of PVA growth in utero, and (2) compare two methods of z-score determination for fetal and postnatal PVA size by echocardiography in order to improve prenatal counseling for patients with TOF. Fetal echocardiograms (FE) at a single institution with a diagnosis of TOF between 8/2008 and 12/2015 were retrospectively reviewed. Patients included had at least 2 FEs and 1 immediate postnatal echocardiogram (TTE). Fetal and postnatal demographic, clinical, and echocardiographic data were collected. Fetal body surface area (BSA) was calculated by estimating fetal weight and height; z-scores were determined based on fetal gestational age (GA) and BSA for both FEs and TTEs. Fetal PVA z-scores by GA or BSA were then compared to postnatal PVA z-scores by BSA. Twenty-two patients with 44 FEs and 22 TTEs were included. GA at the first FE was 23 weeks ± 3.4 and 32 weeks ± 3.1 at the second FE. There was no difference in PVA z-scores (by BSA) between the first and second FE (p = 0.34), but a decrease in PVA z-scores (by BSA) between the second FE and TTE (- 1.6 ± 0.5 vs. - 2.0 ± 0.7; p = 0.01). Repeat comparison with fetal PVA z-scores indexed to GA revealed no difference in z-scores between the first and second FE, but an increase in PVA z-scores between the second FE (by GA) and TTE (by BSA) (- 4.1 ± 1.0 vs. - 2.0 ± 0.7; p < 0.0001). The rate of PVA growth between the two FEs (23 µm/day ± 9.8) and between the second FE and TTE (28 µm/day ± 42) remained comparable (p = 0.57); however, the rate of BSA increase was greater in later gestation (9 cm2/day ± 3 vs. 20 cm2/day ± 11; p = 0.001). In patients with TOF, the rate of PVA growth appears to remain consistent through gestation; however, somatic growth rate increases in late gestation. Fetal PVA z-scores indexed to GA are thus inaccurate in predicting postnatal PVA z-scores typically indexed to BSA. This observation should be considered during prenatal consultation and delivery planning.

  View details for PubMedID 29632959

• Left Ventricular Systolic Myocardial Deformation: A Comparison of Two- and Three-Dimensional Echocardiography in Children JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Balasubramanian, S., Punn, R., Smith, S. N., Houle, H., Tacy, T. A. 2017; 30 (10): 974–83

  Abstract

  The clinical applicability and reliability of three-dimensional (3D) speckle-tracking echocardiography has not been well studied in pediatric patients. The aim of this study was to compare two-dimensional (2D) echocardiography and 3DE real-time full-volume-derived strain and rotation indices in healthy children and patients with dilated cardiomyopathy (DCM).Children with either normal function or DCM were prospectively recruited in an outpatient setting, and deformation indices, including circumferential, radial, and longitudinal strain and torsion, were measured by 2D and 3D echocardiography. Control subjects were compared with patients using the Mann-Whitney U test, correlations between 2D and 3D measurements were analyzed using Spearman correlation analysis, and reproducibility analyses are reported using intraclass correlation coefficients and coefficient of variations.The study cohort consisted of 15 patients (47%) with DCM and 17 control subjects (53%). The median age of the cohort was 13.4 years (range, 5.7-19.3 years). By both 2D and 3D analysis, magnitudes of global longitudinal (P = .01), circumferential (P = .007), and radial (P = .004) strain were significantly lower in patients with DCM in comparison with control subjects. Using receiver operating characteristic curves, lower values of absolute circumferential (area under the curve = 0.95, P < .0001) and longitudinal (area under the curve = 0.93, P < .0001) strain were associated with left ventricular dysfunction. No difference was noted in torsion between control subjects and patients. Three-dimensional analysis was superior to 2D analysis in terms of intraobserver, interobserver, and test-retest reliability.Left ventricular deformation shows significant changes while torsion is preserved in outpatients with DCM compared with control subjects. Three-dimensional global strain can discriminate subtle left ventricular dysfunction and has better reproducibility in comparison with 2D echocardiography. High-resolution 3D imaging is a useful clinical assessment tool for cardiac performance and may overcome some of the limitations of 2D analysis.

  View details for DOI 10.1016/j.echo.2017.06.006

  View details for Web of Science ID 000412186600008

  View details for PubMedID 28802483

• Echocardiography-Derived Left Ventricular Outflow Tract Gradient and Left Ventricular Posterior Wall Thickening Are Associated with Outcomes for Anatomic Repair in Congenitally Corrected Transposition of the Great Arteries. Journal of the American Society of Echocardiography Moodley, S., Balasubramanian, S., Tacy, T. A., Chan, F., Hanley, F. L., Punn, R. 2017

  Abstract

  Congenitally corrected transposition of the great arteries is a rare form of congenital heart disease. Management is controversial; options include observation, physiologic repair, and anatomic repair. Assessment of morphologic left ventricle preparedness is key in timing anatomic repair. This study's purpose was to review the modalities used to assess the morphologic left ventricle preoperatively and to determine if any echocardiographic variables are associated with outcomes.A retrospective review of patients with congenitally corrected transposition of the great arteries eligible for anatomic repair at Lucile Packard Children's Hospital from 2000 to 2016 was conducted. Inclusion criteria were (1) presurgical echocardiography, magnetic resonance imaging, and cardiac catheterization and (2) clinical follow-up information. Echocardiographic measurements included left ventricular (LV) single-plane Simpson's ejection fraction, LV eccentricity index, LV posterior wall thickening, pulmonary artery band (PAB)/LV outflow tract (LVOT) pressure gradient, and LV and right ventricular strain. Magnetic resonance imaging measurements included LV mass, ejection fraction, eccentricity index, and LV thickening. LV pressure, PAB/LVOT gradient, right ventricular pressure, pulmonary vascular resistance, and Qp/Qs constituted catheterization data. Outcomes included achieving anatomic repair within 1 year of assessment in patients with LVOT obstruction or within 1 year of pulmonary artery banding and freedom from death, transplantation, or heart failure at last follow-up.Forty-one patients met the inclusion criteria. PAB/LVOT gradients of 85.2 ± 23.4 versus 64.0 ± 32.1 mm Hg (P = .0282) by echocardiography and 60.1 ± 19.4 versus 35.9 ± 18.9 mm Hg (P = .0030) by catheterization were associated with achieving anatomic repair and freedom from death, transplantation, and heart failure. Echocardiographic LV posterior wall thickening of 35.4 ± 19.8% versus 20.6 ± 15.0% (P = .0017) and MRI LV septal wall thickening of 37.1 ± 18.8% versus 19.3 ± 18.8% (P = .0306) were associated with achieving anatomic repair. Inter- and intraobserver variability for echocardiographic measurements was very good.PAB/LVOT gradient and LV posterior wall thickening are highly reproducible echocardiographic measurements that reflect morphologic LV performance and can be used in assessing patients with congenitally corrected transposition of the great arteries undergoing anatomic repair.

  View details for DOI 10.1016/j.echo.2017.03.019

  View details for PubMedID 28579248

• LVOT-VTI is a Useful Indicator of Low Ventricular Function in Young Patients. Pediatric cardiology Navaratnam, M., Punn, R., Ramamoorthy, C., Tacy, T. A. 2017

  Abstract

  Left ventricular outflow tract velocity time integral (LVOT-VTI), a Doppler-derived measure of stroke distance, is used as a surrogate marker of cardiac function in adults. LVOT-VTI is easily obtained, independent of ventricular geometry and wall motion abnormalities. We investigated the relationship between LVOT-VTI and conventional measures of function in young patients by comparing controls to children with dilated cardiomyopathy (DCM). Sixty-two healthy and 52 DCM patients over 1 year were studied retrospectively. The average pulsed (PW) and continuous wave (CW) LVOT-VTIs from apical views were measured from three cycles. Body surface area (BSA) and Ejection fraction (EF) were obtained. We compared LVOT-VTIs between study and control groups and assessed BSA's impact on LVOT-VTI. The entire cohort was classified into three levels of LV function which were compared. We determined LVOT-VTI cutoff values that indicated an EF <50%. The mean PW-LVOT-VTI in the DCM group was significantly lower than that of the normal group (0.15 vs. 0.18 m; p < 0.0012). The mean CW-LVOT-VTI was significantly lower in DCM (0.20 vs. 0.24 m; p < 0.0001). There was no impact of BSA on LVOT-VTI except when comparing BSA and CW-LVOT-VTI in the normal group. There was a positive relationship between LVOT-VTI and EF for PW (Rs = 0.29, p = 0.0022) and CW (Rs = 0.22, p = 0.0364) and a difference in mean LVOT-VTI between EF groups (p < 0.0001). ROC analysis demonstrated that PW-LVOT-VTI <0.17 m (AUC = 0.73; p < 0.0001) and CW-LVOT-VTI <0.22 m (AUC = 0.76; p < 0.0001) was associated with EF <50%. This study indicates that LVOT-VTI can be a useful alternative measure of LV performance in children over 1 year.

  View details for DOI 10.1007/s00246-017-1630-9

  View details for PubMedID 28534242

• Major Aortopulmonary Collateral Arteries With Anatomy Other Than Pulmonary Atresia/Ventricular Septal Defect. Annals of thoracic surgery Patrick, W. L., Mainwaring, R. D., Reinhartz, O., Punn, R., Tacy, T., Hanley, F. L. 2017

  Abstract

  Major aortopulmonary collateral arteries (MAPCAs) are frequently found in association with pulmonary atresia with ventricular septal defect (PA/VSD). However, some patients with MAPCAs do not have PA/VSD but have a variety of other "atypical" anatomic diagnoses.This was a retrospective review of patients with MAPCAs and atypical anatomy. The 50 patients with MAPCAs could be divided into two subgroups: (1) single ventricle anatomy (n = 33) and (2) two ventricle anatomy (n = 17).The 33 patients with MAPCAs and single ventricle included 15 with unbalanced complete atrioventricular canal (CAVC), 6 with pulmonary atresia-intact ventricular septum, and 12 with other forms of single ventricle. The initial cardiac operation included unifocalization/shunt in 24 patients and creation of aortopulmonary window or central shunt in 9 patients. There were seven operative and eight late deaths. Sixteen patients have had a bidirectional Glenn procedure and 6 had a Fontan procedure. The 17 patients with MAPCAs and two ventricles included 5 with CAVC, 4 with corrected transposition, 3 with double outlet right ventricle, 3 with scimitar syndrome, and 2 with complex D-transposition. The initial cardiac operation included single-stage complete repair in 5 patients, unifocalization/shunt in 10 patients, and aortopulmonary window in 2 patients. There were two operative and two late deaths. Thirteen patients have achieved complete repair status.The data demonstrate the wide diversity of anatomy seen in patients with MAPCAs when evaluating diagnoses other than PA/VSD. Two-thirds of the patients had single ventricle and was associated with a relatively high mortality.

  View details for DOI 10.1016/j.athoracsur.2017.02.029

  View details for PubMedID 28527961

• Pericardial Effusion Following Hematopoietic Cell Transplantation in Children and Young Adults Is Associated with Increased Risk of Mortality. Biology of blood and marrow transplantation Cox, K., Punn, R., Weiskopf, E., Pinsky, B. A., Kharbanda, S. 2017

  Abstract

  Hematopoietic cell transplantation (HCT) is curative for many pediatric malignant and nonmalignant disorders but is associated with significant morbidity and mortality, including the development of pericardial effusion (PEF). We report the results of a retrospective chart review performed to assess the incidence, risk factors, and prognostic significance of PEF in pediatric HCT recipient at Lucile Packard Children's Hospital of Stanford University. A total of 119 patients undergoing HCT between January 2010 and December 2013 were selected through the hospital's Pediatric Stem Cell Transplant Program database. A retrospective chart review, including review of documentation, correspondence, imaging reports, laboratory values, and death records, was performed to collect data. The overall incidence of PEF in our population was 21%. Risk factors for the development of PEF included unrelated donor transplants and cord blood as the stem cell source (P = .005), whereas HLA mismatch approached significance (P = .05). The risk for development of PEF was found to not be significantly associated with acute or chronic graft-versus-host disease (GVHD), age at transplantation, sex, conditioning regimen, or viral reactivation status. Of interest, 6 of the 119 patients were found to have transplant-associated thrombotic microangiopathy (TA-TMA). Four of those 6 patients developed PEF, suggesting TA-TMA as a risk factor for PEF. Eight of the 25 patients who developed PEF (32%) required pericardiocentesis. Five out of the 8 patients requiring pericardiocentesis died owing to causes unrelated to the procedure or to PEF itself. Pericardial fluid testing in 4 of these patients (50%) was positive for human herpesvirus 6, Epstein-Barr virus, cytomegalovirus, and/or adenovirus. Finally, of significant interest, patients with PEF had a statistically significant higher likelihood of mortality compared with those without PEF (44% versus 17%; P = .007).

  View details for DOI 10.1016/j.bbmt.2017.03.028

  View details for PubMedID 28390986

• Changing Management of the Patent Ductus Arteriosus: Effect on Neonatal Outcomes and Resource Utilization. American journal of perinatology Chock, V. Y., Goel, V. V., Palma, J. P., Luh, T. M., Wang, N. A., Gaskari, S., Punn, R., Silverman, N. H., Benitz, W. E. 2017

  Abstract

  Objective This historical cohort study investigated how a shift toward a more conservative approach of awaiting spontaneous closure of the patent ductus arteriosus (PDA) in preterm infants has affected neonatal outcomes and resource utilization. Methods We retrospectively studied very low birth weight infants diagnosed with a PDA by echocardiogram (ECHO) in 2006-2008 (era 1), when medical or surgical PDA management was emphasized, to those born in 2010-2012 (era 2) when conservative PDA management was encouraged. Multiple regression analyses adjusted for gestational age were performed to assess differences in clinical outcomes and resource utilization between eras. Results More infants in era 2 (35/89, 39%) compared with era 1 (22/120, 18%) had conservative PDA management (p < 0.01). Despite no difference in surgical ligation rate, infants in era 2 had ligation later (median 24 vs. 8 days, p < 0.0001). There was no difference in clinical outcomes between eras, while number of ECHOs per patient was the only resource measure that increased in era 2 (median 3 vs. 2 ECHOs, p = 0.003). Conclusion In an era of more conservative PDA management, no increase in adverse clinical outcomes or significant change in resource utilization was found. Conservative PDA management may be a safe alternative for preterm infants.

  View details for DOI 10.1055/s-0037-1601442

  View details for PubMedID 28376547

• Institution of Veno-arterial Extracorporeal Membrane Oxygenation Does Not Lead to Increased Wall Stress in Patients with Impaired Myocardial Function PEDIATRIC CARDIOLOGY Koth, A. M., Axelrod, D. M., Reddy, S., Roth, S. J., Tacy, T. A., Punn, R. 2017; 38 (3): 539-546

  Abstract

  The effect of veno-arterial extracorporeal membrane oxygenation (VA ECMO) on wall stress in patients with cardiomyopathy, myocarditis, or other cardiac conditions is unknown. We set out to determine the circumferential and meridional wall stress (WS) in patients with systemic left ventricles before and during VA ECMO. We established a cohort of patients with impaired myocardial function who underwent VA ECMO therapy from January 2000 to November 2013. Demographic and clinical data were collected and inotropic score calculated. Measurements were taken on echocardiograms prior to the initiation of VA ECMO and while on full-flow VA ECMO, in order to derive wall stress (circumferential and meridional), VCFc, ejection fraction, and fractional shortening. A post hoc sub-analysis was conducted, separating those with pulmonary hypertension (PH) and those with impaired systemic output. Thirty-three patients met inclusion criteria. The patients' median age was 0.06 years (range 0-18.7). Eleven (33%) patients constituted the organ failure group (Gr2), while the remaining 22 (66%) patients survived to discharge (Gr1). WS and all other echocardiographic measures were not different when comparing patients before and during VA ECMO. Ejection and shortening fraction, WS, and VCFc were not statistically different comparing the survival and organ failure groups. The patients' position on the VCFc-WS curve did not change after the initiation of VA ECMO. Those with PH had decreased WS as well as increased EF after ECMO initiation, while those with impaired systemic output showed no difference in those parameters with initiation of ECMO. The external workload on the myocardium as indicated by WS is unchanged by the institution of VA ECMO support. Furthermore, echocardiographic measures of cardiac function do not reflect the changes in ventricular performance inherent to VA ECMO support. These findings are informative for the interpretation of echocardiograms in the setting of VA ECMO. ECMO may improve ventricular mechanics in those with PH as the primary diagnosis.

  View details for DOI 10.1007/s00246-016-1546-9

  View details for Web of Science ID 000398030200013

• Institution of Veno-arterial Extracorporeal Membrane Oxygenation Does Not Lead to Increased Wall Stress in Patients with Impaired Myocardial Function. Pediatric cardiology Koth, A. M., Axelrod, D. M., Reddy, S., Roth, S. J., Tacy, T. A., Punn, R. 2016

  Abstract

  The effect of veno-arterial extracorporeal membrane oxygenation (VA ECMO) on wall stress in patients with cardiomyopathy, myocarditis, or other cardiac conditions is unknown. We set out to determine the circumferential and meridional wall stress (WS) in patients with systemic left ventricles before and during VA ECMO. We established a cohort of patients with impaired myocardial function who underwent VA ECMO therapy from January 2000 to November 2013. Demographic and clinical data were collected and inotropic score calculated. Measurements were taken on echocardiograms prior to the initiation of VA ECMO and while on full-flow VA ECMO, in order to derive wall stress (circumferential and meridional), VCFc, ejection fraction, and fractional shortening. A post hoc sub-analysis was conducted, separating those with pulmonary hypertension (PH) and those with impaired systemic output. Thirty-three patients met inclusion criteria. The patients' median age was 0.06 years (range 0-18.7). Eleven (33%) patients constituted the organ failure group (Gr2), while the remaining 22 (66%) patients survived to discharge (Gr1). WS and all other echocardiographic measures were not different when comparing patients before and during VA ECMO. Ejection and shortening fraction, WS, and VCFc were not statistically different comparing the survival and organ failure groups. The patients' position on the VCFc-WS curve did not change after the initiation of VA ECMO. Those with PH had decreased WS as well as increased EF after ECMO initiation, while those with impaired systemic output showed no difference in those parameters with initiation of ECMO. The external workload on the myocardium as indicated by WS is unchanged by the institution of VA ECMO support. Furthermore, echocardiographic measures of cardiac function do not reflect the changes in ventricular performance inherent to VA ECMO support. These findings are informative for the interpretation of echocardiograms in the setting of VA ECMO. ECMO may improve ventricular mechanics in those with PH as the primary diagnosis.

  View details for DOI 10.1007/s00246-016-1546-9

  View details for PubMedID 28005156

• Near-infrared spectroscopy for detection of a significant patent ductus arteriosus. Pediatric research Chock, V. Y., Rose, L. A., Mante, J. V., Punn, R. 2016; 80 (5): 675-680

  Abstract

  Near-infrared spectroscopy (NIRS) may assist with characterization of a hemodynamically significant patent ductus arteriosus (hsPDA) by measuring cerebral and renal saturation (Csat and Rsat) levels. We hypothesized that Csat and Rsat in preterm infants with an hsPDA would be decreased compared to those with no PDA or nonsignificant PDA.This non a-priori designed study retrospectively investigated clinical and ECHO characteristics of preterm infants <29 wk gestation who underwent routine NIRS monitoring. Logistic regression assessed association between NIRS measures and an hsPDA by ECHO.Of 47 infants, 21 had a confirmed hsPDA by ECHO, 14 had a nonsignificant PDA, and 12 had no ECHO performed due to low clinical suspicion for PDA. Logistic regression adjusted for gestational age found that lower Rsat was associated with an hsPDA by ECHO (OR 0.9, 95% CI 0.83-0.98, P = 0.01). Using ROC curves, Rsat < 66% identified an hsPDA with a sensitivity of 81% and specificity of 77%, while Csat was not significant.Low Rsat < 66% was associated with the presence of an hsPDA in the preterm infant. Csat may be preserved if cerebral autoregulation is largely intact. Bedside NIRS monitoring may reasonably increase suspicion for a significant PDA in the preterm infant.

  View details for DOI 10.1038/pr.2016.148

  View details for PubMedID 27603562

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

  Abstract

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

  View details for DOI 10.1016/j.athoracsur.2015.09.050

  View details for PubMedID 26652138

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

  Abstract

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

  View details for DOI 10.1016/j.athoracsur.2015.09.050

  View details for Web of Science ID 000370339700033

• Pericardial Effusion Following Hematopoietic Cell Transplantation in Children Is Associated with Increased Risk of Mortality Cox, K., Punn, R., Schnorr, E., Kharbanda, S. ELSEVIER SCIENCE INC. 2016: S240

  View details for DOI 10.1016/j.bbmt.2015.11.654

  View details for Web of Science ID 000370910300340

• Double-Switch Repair of Corrected Transposition in Association With Criss-Cross Atrial Morphology ANNALS OF THORACIC SURGERY Zeigler, S., Mainwaring, R. D., Punn, R., Petrossian, E., Hanley, F. L. 2016; 101 (3): 1208–10

  Abstract

  Corrected transposition is a relatively uncommon congenital heart defect characterized by discordance at both the atrioventricular and ventriculoarterial levels. A rare subset of patients with corrected transposition also have criss-cross atrial morphology. We report the surgical treatment of 2 patients with corrected transposition in association with criss-cross atrial morphology, emphasizing the novel atrial baffle required for this operation.

  View details for PubMedID 26897215

• Assessment of Speckle-Tracking Echocardiography-Derived Global Deformation Parameters During Supine Exercise in Children PEDIATRIC CARDIOLOGY Liu, M. Y., Tacy, T., Chin, C., Obayashi, D. Y., Punn, R. 2016; 37 (3): 519-527

  Abstract

  Exercise echocardiography is an underutilized tool in pediatrics with current applications including detecting segmental wall abnormalities, assessing the utility of global ventricular function, and measuring pulmonary hemodynamics. No prior study has applied speckle-tracking echocardiography (STE) during exercise echocardiography in children. The aim of this study was to determine the feasibility of measuring speckle-tracking-derived peak systolic velocities, global longitudinal and circumferential strain, and global strain rates at various phases of exercise. Ninety-seven healthy children underwent cardiopulmonary exercise testing using supine cycle ergometry. The exercise stress test consisted of baseline pulmonary function testing, monitoring of blood pressure and heart rate responses, electrocardiographic recordings, and oxygen saturations while subjects pedaled against a ramp protocol based on body weight. Echocardiographic measurements and specifically speckle-tracking analysis were performed during exercise at baseline, at a heart rate of 160 beats per minute and at 10 min after exercise. Peak systolic velocity, peak systolic strain, and peak systolic strain rate at these three phases were compared in the subjects in which all measurements were accurately obtained. We were able to complete peak velocity, strain, and strain rate measurements in all three exercise phases for 36 out of the 97 subjects tested. There was no significant difference between the feasibility of measuring circumferential versus longitudinal strain (p = 0.25, B-corrected = 0.75). In the 36 subjects studied, the magnitude of circumferential strain values decreased from -18.3 ± 4.8 to -13.7 ± 4.0 % from baseline to HR 160 (p < 0.0001, B-corrected < 0.0001), before returning to -19.6 ± 4.4 % at recovery (p = 0.19 when compared to baseline). Longitudinal strain did not vary significantly from baseline to HR 160 (from -17.7 ± 4.4 to -16.6 ± 4.4 %, p = 0.16); likewise the average recovery strain was no different from those values (-18.4 ± 3.6 %; p = 0.34). Peak circumferential and longitudinal strain rates increased from baseline to HR 160, but neither decreased to baseline levels after 10 min of recovery, which correlated with heart rate variations with exercise. We studied the effects of frame rate on deformation measurements and we observed no difference between measurements taken at lower (<60 frames per second, fps) and higher (≥60 fps) frame rates. This study shows that it is technically difficult to retrospectively measure peak velocities, strain, and strain rate in exercising pediatric subjects with STE. The majority of subjects that were excluded from the study had inadequate echocardiographic images when tachycardic from increased respiratory effort and body movements near peak exercise. Improvements in technique and higher image frame rates could make application of STE to pediatric cardiopulmonary testing more successful in the future.

  View details for DOI 10.1007/s00246-015-1309-z

  View details for Web of Science ID 000373308800012

• Assessment of Speckle-Tracking Echocardiography-Derived Global Deformation Parameters During Supine Exercise in Children. Pediatric cardiology Liu, M. Y., Tacy, T., Chin, C., Obayashi, D. Y., Punn, R. 2016; 37 (3): 519-527

  Abstract

  Exercise echocardiography is an underutilized tool in pediatrics with current applications including detecting segmental wall abnormalities, assessing the utility of global ventricular function, and measuring pulmonary hemodynamics. No prior study has applied speckle-tracking echocardiography (STE) during exercise echocardiography in children. The aim of this study was to determine the feasibility of measuring speckle-tracking-derived peak systolic velocities, global longitudinal and circumferential strain, and global strain rates at various phases of exercise. Ninety-seven healthy children underwent cardiopulmonary exercise testing using supine cycle ergometry. The exercise stress test consisted of baseline pulmonary function testing, monitoring of blood pressure and heart rate responses, electrocardiographic recordings, and oxygen saturations while subjects pedaled against a ramp protocol based on body weight. Echocardiographic measurements and specifically speckle-tracking analysis were performed during exercise at baseline, at a heart rate of 160 beats per minute and at 10 min after exercise. Peak systolic velocity, peak systolic strain, and peak systolic strain rate at these three phases were compared in the subjects in which all measurements were accurately obtained. We were able to complete peak velocity, strain, and strain rate measurements in all three exercise phases for 36 out of the 97 subjects tested. There was no significant difference between the feasibility of measuring circumferential versus longitudinal strain (p = 0.25, B-corrected = 0.75). In the 36 subjects studied, the magnitude of circumferential strain values decreased from -18.3 ± 4.8 to -13.7 ± 4.0 % from baseline to HR 160 (p < 0.0001, B-corrected < 0.0001), before returning to -19.6 ± 4.4 % at recovery (p = 0.19 when compared to baseline). Longitudinal strain did not vary significantly from baseline to HR 160 (from -17.7 ± 4.4 to -16.6 ± 4.4 %, p = 0.16); likewise the average recovery strain was no different from those values (-18.4 ± 3.6 %; p = 0.34). Peak circumferential and longitudinal strain rates increased from baseline to HR 160, but neither decreased to baseline levels after 10 min of recovery, which correlated with heart rate variations with exercise. We studied the effects of frame rate on deformation measurements and we observed no difference between measurements taken at lower (<60 frames per second, fps) and higher (≥60 fps) frame rates. This study shows that it is technically difficult to retrospectively measure peak velocities, strain, and strain rate in exercising pediatric subjects with STE. The majority of subjects that were excluded from the study had inadequate echocardiographic images when tachycardic from increased respiratory effort and body movements near peak exercise. Improvements in technique and higher image frame rates could make application of STE to pediatric cardiopulmonary testing more successful in the future.

  View details for DOI 10.1007/s00246-015-1309-z

  View details for PubMedID 26671508

• A Pilot Study Assessing ECG versus ECHO Ventriculoventricular Optimization in Pediatric Resynchronization Patients. Journal of cardiovascular electrophysiology Punn, R., Hanisch, D., Motonaga, K. S., Rosenthal, D. N., Ceresnak, S. R., Dubin, A. M. 2016; 27 (2): 210-216

  Abstract

  Cardiac resynchronization therapy indications and management are well described in adults. Echocardiography (ECHO) has been used to optimize mechanical synchrony in these patients; however, there are issues with reproducibility and time intensity. Pediatric patients add challenges, with diverse substrates and limited capacity for cooperation. Electrocardiographic (ECG) methods to assess electrical synchrony are expeditious but have not been extensively studied in children. We sought to compare ECHO and ECG CRT optimization in children.Prospective, pediatric, single-center cross-over trial comparing ECHO and ECG optimization with CRT. Patients were assigned to undergo either ECHO or ECG optimization, followed for 6 months, and crossed-over to the other assignment for another 6 months. ECHO pulsed-wave tissue Doppler and 12-lead ECG were obtained for 5 VV delays. ECG optimization was defined as the shortest QRSD and ECHO optimization as the lowest dyssynchrony index. ECHOs/ECGs were interpreted by readers blinded to optimization technique. After each 6 month period, these data were collected: ejection fraction, velocimetry-derived cardiac index, quality of life, ECHO-derived stroke distance, M-mode dyssynchrony, study cost, and time. Outcomes for each optimization method were compared.From June 2012 to December 2013, 19 patients enrolled. Mean age was 9.1 ± 4.3 years; 14 (74%) had structural heart disease. The mean time for optimization was shorter using ECG than ECHO (9 ± 1 min vs. 68 ± 13 min, P < 0.01). Mean cost for charges was $4,400 ± 700 less for ECG. No other outcome differed between groups.ECHO optimization of synchrony was not superior to ECG optimization in this pilot study. ECG optimization required less time and cost than ECHO optimization.

  View details for DOI 10.1111/jce.12863

  View details for PubMedID 26515428

• Cardioplegia Dose Effect on Immediate Postoperative Alterations in Coronary Artery Flow Velocities After Congenital Cardiac Surgery. Pediatric cardiology Davidson, H., Punn, R., Tacy, T. A. 2016; 37 (2): 364-371

  Abstract

  Abnormalities in coronary artery (CA) flow detected by echocardiography are increasingly used to guide clinical decisions in patient management. Increased CA flow has been seen postoperatively in congenital cardiac surgery. This study sought to determine immediate postoperative changes in left anterior descending (LAD) CA flow velocities, and to investigate possible factors associated with these changes. CA flow in the proximal LAD was sampled with pulsed-wave Doppler during trans-esophageal echocardiography imaging in the immediate preoperative and postoperative studies in 46 subjects. The peak velocity, velocity time integral (VTI), VTI corrected for heart rate (VTIc), and VTI rate pressure product (VTIrpp) were determined. The percent change in each measure between the preoperative and postoperative study was calculated and compared to age, body surface area (BSA), cardiopulmonary bypass time, cross-clamp time, and number of cardioplegia (CP) doses. The pH, oxygen saturation, temperature, and hemoglobin concentration (Hb) were compared for those with and without increased flow characteristics. There was an overall increase in LAD flow parameters in subjects who underwent congenital cardiac surgery. There was a significant and positive correlation of percent change in VTI, VTIc, and VTIrrp with number of CP doses and lower Hb. We propose that this phenomenon is likely of multifactorial origin, involving autoregulatory mechanism disturbance. The imaging and measurement of LAD flow velocities are feasible, reliable, and is positively correlated with number of CP doses. Interpretation of postoperative LAD flow velocities should be made in the context of intraoperative events since heart rate, blood pressure, and Hb concentration also influence CA flow parameters.

  View details for DOI 10.1007/s00246-015-1285-3

  View details for PubMedID 26481223

• Routine intra-operative trans-oesophageal echocardiography yields better outcomes in surgical repair of CHD. Cardiology in the young Madriago, E. J., Punn, R., Geeter, N., Silverman, N. H. 2016; 26 (2): 263-268

  Abstract

  Trans-oesophageal echocardiographic imaging is valuable in the pre- and post-operative evaluation of children and adults with CHD; however, the frequency by which trans-oesophageal echocardiography guides the intra-operative course of patients is unknown.We retrospectively reviewed 1748 intra-operative trans-oesophageal echocardiograms performed between 1 October, 2005 and 31 December, 2010, and found 99 cases (5.7%) that required return to bypass, based in part upon the intra-operative echocardiographic findings.The diagnoses most commonly requiring further repair and subsequent imaging were mitral valve disease (20.9%), tricuspid valve disease (16.0%), atrioventricular canal defects (12.0%), and pulmonary valve disease (14.1%). The vast majority of those requiring immediate return to bypass benefited by avoiding subsequent operations and longer lengths of hospital stay. A total of 14 patients (0.8%) who received routine imaging required further surgical repair within 1 week, usually due to disease that developed over ensuing days. Patients who had second post-operative trans-oesophageal echocardiograms in the operating room rarely required re-operations, confirming the benefit of routine intra-operative imaging.This study represents a large single institutional review of intra-operative trans-oesophageal echocardiography, and confirms its applicability in the surgical repair of patients with CHD. Routine imaging accurately identifies patients requiring further intervention, does not confer additional risk of mortality or prolonged length of hospital stay, and prevents subsequent operations and associated sequelae in a substantial subset of patients. This study demonstrates the utility of echocardiography in intra-operative monitoring of surgical repair and highlights patients who are most likely to require return to bypass, as well as the co-morbidities of such manipulations.

  View details for DOI 10.1017/S1047951115000098

  View details for PubMedID 25730612

• Hemoptysis as a rare presentation of cor triatriatum sinister JOURNAL OF THORACIC AND CARDIOVASCULAR SURGERY Said, S. M., Ibrahimiye, A. N., Punn, R., Hanley, F. L. 2015; 150 (5): E73–E75

  View details for PubMedID 26344680

• Diagnosis of Anomalous Aortic Origin of the Left Coronary Artery in a Pediatric Patient. World journal for pediatric & congenital heart surgery Arunamata, A., Buccola Stauffer, K. J., Punn, R., Chan, F. P., Maeda, K., Balasubramanian, S. 2015; 6 (3): 470-473

  Abstract

  Anomalous aortic origin of the left coronary artery is rare and confers increased risk of sudden cardiac death. Accurate diagnosis is crucial and often requires many diagnostic modalities. This case report highlights the echocardiographic characteristics and pitfalls in diagnosing the anomaly in addition to the advantages of using computed tomography and magnetic resonance imaging in a pediatric patient.

  View details for DOI 10.1177/2150135114558689

  View details for PubMedID 26180168

• Fate of Right Ventricle to Pulmonary Artery Conduits After Complete Repair of Pulmonary Atresia and Major Aortopulmonary Collaterals ANNALS OF THORACIC SURGERY Mainwaring, R. D., Patrick, W. L., Punn, R., Palmon, M., Reddy, V. M., Hanley, F. L. 2015; 99 (5): 1685-1691

  Abstract

  Surgical repair of pulmonary atresia with ventricular septal defect and major aortopulmonary collaterals (PA/VSD/MAPCAs) requires insertion of a conduit from the right ventricle to the reconstructed pulmonary arteries. Although there is extensive literature on conduit longevity for many forms of congenital heart defects, there is currently limited information for PA/VSD/MAPCAs. It is likely that conduits will have a different longevity in PA/VSD/MAPCAs because pulmonary artery pressures are higher after unifocalization than in other congenital heart defects. The purpose of this study was to evaluate the fate of right ventricle to pulmonary artery conduits after complete repair of PA/VSD/MAPCAs.This was a retrospective review of 103 infants who underwent complete repair of PA/VSD/MAPCAs with insertion of an aortic homograft conduit. The average age at complete repair was 5.1 ± 2.8 months, average conduit size was 13 ± 2 mm, and average conduit z score was a positive 1.6 ± 0.9.Conduit z scores were linearly correlated with increasing homograft conduit size. The average longevity of small homografts (8 to 11 mm) was 15 ± 4 months, medium homografts (12 to 14 mm) was 39 ± 7 months, and large homografts (15 to 17 mm) was 50 ± 14 months. There was a negative correlation between increasing pulmonary artery pressure and conduit longevity.Conduit z scores and conduit size worked synergistically to predict the longevity of right ventricle to pulmonary artery conduits after complete repair of PA/VSD/MAPCAs. Pulmonary artery pressure was an additional modifier of longevity. These data provide a framework for expectations of aortic homograft conduits used in the repair of PA/VSD/MAPCAs.

  View details for DOI 10.1016/j.athoracsur.2014.12.071

  View details for PubMedID 25805573

• Diminished exercise capacity and chronotropic incompetence in pediatric patients with congenital complete heart block and chronic right ventricular pacing. Heart rhythm Motonaga, K. S., Punn, R., Axelrod, D. M., Ceresnak, S. R., Hanisch, D., Kazmucha, J. A., Dubin, A. M. 2015; 12 (3): 560-565

  Abstract

  Chronic right ventricular (RV) pacing has been associated with decreased exercise capacity and left ventricular (LV) function in adults with congenital complete atrioventricular block (CCAVB), but not in children.The purpose of this study was to evaluate the exercise capacity and LV function in pediatric patients with CCAVB receiving chronic RV pacing.We prospectively evaluated pediatric patients with isolated CCAVB receiving atrial synchronous RV pacing for at least 5 years. Supine bicycle ergometry was performed, and LV ejection fraction (EF) was evaluated by echocardiography.Ten CCAVB subjects and 31 controls were matched for age, gender, and body surface area. CCAVB subjects had normal resting EF (63.1% ± 4.0%) and had been paced for 7.9 ± 1.4 years. Exercise testing demonstrated reduced functional capacity in CCAVB patients compared to controls with a lower VO2peak (26.0 ± 6.6 mL/kg/min vs 39.9 ± 7.0 mL/kg/min, P <.001), anaerobic threshold (15.6 ± 3.9 mL/kg/min vs 18.8 ± 2.7 mL/kg/min, P = .007), and oxygen uptake efficiency slope (1210 ± 406 vs 1841 ± 452, P <.001). Maximum heart rate (165 ± 8 bpm vs 185 ± 9 bpm, P <.001) and systolic blood pressure (159 ± 17 mm Hg vs 185 ± 12 mm Hg, P <.019) also were reduced in CCAVB patients despite maximal effort (respiratory exchange ratio 1.2 ± 0.1). EF was augmented with exercise in controls but not in CCAVB patients (13.2% ± 9.3% vs 0.2% ± 4.8% increase, P <.001).Clinically asymptomatic children with chronic RV pacing due to CCAVB have significant reductions in functional capacity accompanied by chronotropic incompetence and inability to augment EF with exercise.

  View details for DOI 10.1016/j.hrthm.2014.11.036

  View details for PubMedID 25433143

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

  Abstract

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

  View details for DOI 10.1016/j.echo.2014.11.010

  View details for Web of Science ID 000352144400004

  View details for PubMedID 25555521

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

  Abstract

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

  View details for DOI 10.1016/j.echo.2014.11.010

  View details for PubMedID 25555521

• Ventricular lead redundancy to prevent cardiovascular events and sudden death from lead fracture in pacemaker-dependent children. Heart rhythm Ceresnak, S. R., Perera, J. L., Motonaga, K. S., Avasarala, K., Malloy-Walton, L., Hanisch, D., Punn, R., Maeda, K., Reddy, V. M., Doan, L. N., Kirby, K., Dubin, A. M. 2015; 12 (1): 111-116

  Abstract

  Children requiring a permanent epicardial pacemaker(PM) traditionally have a single lead placed on the right ventricle. Lead failure in pacemaker dependent(PMD) children, however, can result in cardiovascular events(CVE) and death.To determine if redundant ventricular lead systems(RVLS) can safeguard against CVE and death in PMD children.Single-center study of PMD patients undergoing placement of RVLS from 2002-2013. Patients ≤ 21 years of age who were PMD were included. Patients with biventricular systems(BiV) systems placed for standard resynchronization indications were excluded. RVLS patients were compared to PMD patients with only a single pacing lead on the ventricle(SiV).769 patients underwent PM/ICD placement with 76 BiV implants and there were 49 PMD patients(6%). 13 patients underwent implantation of a RVLS. There was no difference between the RVLS group(n=13) and SiV PMD control group(n=24) with regard to age(RVLS 9.5±5.8 vs. SiV 9.4±6.7 years; p=0.52), weight(RVLS 38.2±32.6 vs. SiV 35.2±29.3 kg; p=0.62), indication for pacing, procedural complications or time to follow-up. There were 2 lead fractures (17%) in the RVLS group(mean follow-up 3.8±2.9 years) with no deaths or presentations with CVE. The SiV control group had 3 lead fractures (13%)(mean follow-up 2.8±2.9 years), with no deaths, but all 3 patients presented with CVE and required emergent PM placement.RVLS systems should be considered in children who are PMD and require permanent epicardial pacing. BiV pacing and RVLS may decrease the risk of CVEs in the event of lead failure in PMD patients.

  View details for DOI 10.1016/j.hrthm.2014.09.056

  View details for PubMedID 25277988

• Predictors of Mortality in Pediatric Patients on Venoarterial Extracorporeal Membrane Oxygenation PEDIATRIC CRITICAL CARE MEDICINE Punn, R., Axelrod, D. M., Sherman-Levine, S., Roth, S. J., Tacy, T. A. 2014; 15 (9): 870-877

  Abstract

  Currently, there are no established echocardiographic or hemodynamic predictors of mortality after weaning venoarterial extracorporeal membrane oxygenation in children. We wished to determine which measurements predict mortality.Over 3 years, we prospectively assessed six echo and six hemodynamic variables at 3-5 circuit rates while weaning extracorporeal membrane oxygenation flow. Hemodynamic measurements were heart rate, inotropic score, arteriovenous oxygen difference, pulse pressure, oxygenation index, and lactate. Echo variables included shortening/ejection fraction, outflow tract Doppler-derived stroke distance (velocity-time integral), degree of atrioventricular valve regurgitation, longitudinal strain (global longitudinal strain), and circumferential strain (global circumferential strain).Cardiovascular ICU at Lucille Packard Children's Hospital Stanford, CA.Patients were stratified into those who died or required heart transplant (Gr1) and those who did not (Gr2). For each patient, we compared the change for each variable between full versus minimum extracorporeal membrane oxygenation flow for each group.None.We enrolled 21 patients ranging in age from 0.02 to 15 years. Five had dilated cardiomyopathy, and 16 had structural heart disease with severe ventricular dysfunction. Thirteen of 21 patients (62%) comprised Gr1, including two patients with heart transplants. Eight patients constituted Gr2. Gr1 patients had a significantly greater increase in oxygenation index (35% mean increase; p < 0.01) off extracorporeal membrane oxygenation compared to full flow, but no change in velocity-time integral or arteriovenous oxygen difference. In Gr2, velocity-time integral increased (31% mean increase; p < 0.01), with no change in arteriovenous oxygen difference or oxygenation index. Pulse pressure increased modestly with flow reduction only in Gr1 (p < 0.01).Failure to augment velocity-time integral or an increase in oxygenation index during the extracorporeal membrane oxygenation weaning is associated with poor outcomes in children. We propose that these measurements should be performed during extracorporeal membrane oxygenation wean, as they may discriminate who will require alternative methods of circulatory support for survival.

  View details for DOI 10.1097/PCC.0000000000000236

  View details for PubMedID 25230312

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

  Abstract

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

  View details for DOI 10.1093/ajh/hpu034

  View details for Web of Science ID 000342853700013

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

  Abstract

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

  View details for DOI 10.1093/ajh/hpu034

  View details for PubMedID 24627445

• Coronary sinus obstruction after atrioventricular canal defect repair. Congenital heart disease Peng, D. M., Sun, H. Y., Hanley, F. L., Olson, I., Punn, R. 2014; 9 (4): E121-4

  Abstract

  The coronary sinus can become obstructed with any instrumentation at or near the ostium such as in atrioventricular canal defect repairs. This complication may lead to a wide range of consequences including dyspnea, angina, myocardial infarction, and sudden death. The following report illustrates the importance of careful perioperative echocardiographic evaluation of the coronary sinus in procedures that may affect the sinus and its ostium.

  View details for DOI 10.1111/chd.12096

  View details for PubMedID 23682752

• Surgical repair of anomalous aortic origin of a coronary artery†. European journal of cardio-thoracic surgery Mainwaring, R. D., Reddy, V. M., Reinhartz, O., Petrossian, E., Punn, R., Hanley, F. L. 2014; 46 (1): 20-26

  Abstract

  Anomalous aortic origin of a coronary artery (AAOCA) is a rare congenital heart defect that has been associated with myocardial ischaemia and sudden death. There is an ongoing controversy over the indications for surgical intervention and the efficacy of that treatment compared with the natural history. The purpose of this study was to evaluate the medium-term results of surgical repair of AAOCA.Seventy-six patients underwent surgical repair of AAOCA at our institution from 1999 to 2013. There were 55 males and 21 females, and the median age at surgery was 15 years. Forty-seven (62%) of the 76 patients had an anomalous right coronary artery, 27 had an anomalous left coronary and 2 had an eccentric single coronary ostia. Forty-one patients had preoperative symptoms of myocardial ischaemia.Surgical repair was accomplished by unroofing of an intramural coronary in 55, reimplantation in 7 and pulmonary artery translocation in 14. There has been no early or late mortality, with a median duration of follow-up of 6 years. One patient presented with severe myocardial ischaemia and subsequently underwent heart transplantation a year following AAOCA surgery. The remaining patients have all remained free of cardiac symptoms.The results of this study demonstrate two major principles. First, surgical repair of AAOCA is quite safe in centres that take care of a significant number of patients with this entity. Secondly, the surgery is highly effective in eliminating symptoms of myocardial ischaemia. The growing amount of data on postoperative patients suggests that surgical repair can prevent the adverse events seen in the untreated 'natural' history. Based on these observations, it is our current recommendation that all teenagers identified with AAOCA should undergo surgical repair.

  View details for DOI 10.1093/ejcts/ezt614

  View details for PubMedID 24431169

• Evaluation of Risk Factors for Prediction of Outcome in Fetal Spectrum of Atrioventricular Septal Defects CONGENITAL HEART DISEASE Bader, R. S., Punn, R., Silverman, N. H. 2014; 9 (4): 286-293

  Abstract

  Atrioventricular septal defects (AVSD) are very commonly diagnosed in utero. Heterotaxy/chromosomal abnormalities frequently coexist with AVSD. However, outcomes of fetal AVSD are not precisely known. We attempted to define mortality risk factors in AVSD.We retrospectively searched our database, electronic records, and echocardiograms with diagnosis of fetal AVSD from 2003 to 2012. We investigated the following risk factors: atrial situs, heart rate/rhythm, ventricular dominance/morphology, atrioventricular valve regurgitation, cardiothoracic ratio, ejection fraction, and extracardiac anomalies.Forty-five fetuses with a median gestational age of 28 weeks (17.5-37.1) were determined to have AVSD during the 10 years, of which 12 were either lost to follow-up (6) or underwent termination (6). There were 16 deaths (48%); two died in utero. Isomerism was identified in 17 of 45 (37%) fetuses (11 left atrial, 6 right atrial isomerism) and chromosomal abnormalities were identified in 12 (27%). Twenty-eight of 33 fetuses, not lost to follow-up or terminated, had extracardiac anomalies which had associated increased mortality (57% vs. 0%, P = .04). Heart block (75% vs. 43%, P = .12), left ventricular noncompaction (80% vs. 43%, P = .17), and isomerism (63% vs. 41%, P = .28) were associated with mortality but without statistical significance. Twenty-five of 45 (56%) had unbalanced AVSD. Positional abnormalities of the great arteries or semilunar valve stenosis were present in 20/45 (44%) while venous anomalies were present in 16/45 (36%). Presence of ventricular dominance, atrioventricular valve regurgitation, elevated cardiothoracic ratio, or diminished ejection fraction were not associated with mortality.Overall mortality rate for fetuses with AVSD was 48%. The presence of extracardiac anomalies is an independent risk factor for prediction of fetal or neonatal demise. Heart block, isomerism, and noncompaction in fetal AVSD appear to be associated with poor outcomes as well but did not reach statistical significance. This information is useful for counseling parents with fetus AVSD.

  View details for DOI 10.1111/chd.12136

  View details for Web of Science ID 000340525400012

  View details for PubMedID 24102719

• Predictors of bronchopulmonary dysplasia or death in premature infants with a patent ductus arteriosus. Pediatric research Chock, V. Y., Punn, R., Oza, A., Benitz, W. E., Van Meurs, K. P., Whittemore, A. S., Behzadian, F., Silverman, N. H. 2014; 75 (4): 570-575

  Abstract

  Background:Preterm infants with a PDA are at risk for death or development of BPD. However, PDA treatment remains controversial. We investigated if PDA treatment and other clinical or echocardiographic (ECHO) factors were associated with the development of death or BPD.Methods:We retrospectively studied clinical and ECHO characteristics of preterm infants with birth weight <1500 g and ECHO diagnosis of a PDA. Logistic regression and classification and regression tree (CART) analyses were performed to assess variables associated with the combined outcome of death or BPD.Results:Of 187 preterm infants with a PDA, 75% were treated with indomethacin or surgery and 25% were managed conservatively. Death or BPD occurred in 80 (43%). Logistic regression found lower gestational age (OR 0.5), earlier year of birth during the study period (OR 0.9), and larger ductal diameter (OR 4.3) were associated with the decision to treat the PDA, while gestational age was the only variable associated with death or BPD (OR 0.6, 95% CI 0.5-0.8).Conclusion:Only lower gestational age and not PDA treatment or ECHO score was associated with the adverse outcome of death or BPD. Further investigation of PDA management strategies and effects on adverse outcomes of prematurity is needed.Pediatric Research (2013); doi:10.1038/pr.2013.253.

  View details for DOI 10.1038/pr.2013.253

  View details for PubMedID 24378897

• Supine cycling in pediatric exercise testing: disparity in performance measures. Pediatric cardiology May, L. J., Punn, R., Olson, I., Kazmucha, J. A., Liu, M. Y., Chin, C. 2014; 35 (4): 705-710

  Abstract

  Supine cycling may be an important alternative modality for exercise testing. Subtle differences in supine and upright exercise physiology have been suggested but not fully explored in the pediatric population. The aim of this study was to compare peak and submaximal metabolic data in the upright and supine exercise positions. Healthy children (N = 100) performed cardiopulmonary exercise tests using supine and upright cycle ergometry. Recruitment was governed by grant funding and not based on sample size calculations. Subjects exercised to exhaustion. Paired Student's t-tests were used to compare upright and supine data; simple linear regression analyses examined correlations between the two modalities. Peak heart rate was similar in both testing positions. Although peak oxygen uptake (peak VO2), oxygen uptake at anaerobic threshold (VO2@AT), VO2 when the respiratory exchange ratio is consistently at or above 1.0 (VO2@RER1.0), and the oxygen uptake efficiency slope were significantly higher in the upright position, no difference was considered of practical significance when applying Cohen's effect size criteria. Therefore, it may be reasonable for pediatric exercise laboratories to use established normative data and predictions for upright cycling position and apply them to metabolic measures obtained in supine exercise testing. Supine cycling with submaximal parameters may allow objective assessment of exercise capacity in children who undergo exercise echocardiography or cannot perform upright exercise testing.

  View details for DOI 10.1007/s00246-013-0841-y

  View details for PubMedID 24253612

• Ebstein anomaly and Trisomy 21: A rare association. Annals of pediatric cardiology Siehr, S. L., Punn, R., Priest, J. R., Lowenthal, A. 2014; 7 (1): 67-69

  Abstract

  This is a case report of a patient with Trisomy 21 with Ebstein anomaly, a ventricular septal defect, and acquired pulmonary vein stenosis; a rare combination, diagnosed during a routine neonatal examination.

  View details for DOI 10.4103/0974-2069.126569

  View details for PubMedID 24701093

  View details for PubMedCentralID PMC3959069

• Ebstein anomaly and Trisomy 21: A rare association ANNALS OF PEDIATRIC CARDIOLOGY Siehr, S. L., Punn, R., Priest, J. R., Lowenthal, A. 2014; 7 (1): 67–69

  View details for DOI 10.4103/0974-2069.126569

  View details for Web of Science ID 000218591300017

• Transcatheter Device Closure of a Congenital Aortic-Left Atrial Tunnel CONGENITAL HEART DISEASE Sun, H. Y., Buccola, K. J., Punn, R., Silverman, N. H., Peng, L. F., Perry, S. B., Balasubramanian, S. 2014; 9 (1): E23-E26

  Abstract

  Rare cases of aortic-left atrial tunnel exist in the literature. This case report highlights the echocardiographic characterization of this vascular anomaly and provides the first description of an aortic-left atrial tunnel closed by interventional cardiac catheterization in a pediatric patient.

  View details for DOI 10.1111/chd.12059

  View details for Web of Science ID 000329916300010

  View details for PubMedID 23601836

• Transcatheter device closure of a congenital aortic-left atrial tunnel. Congenital heart disease Sun, H. Y., Buccola, K. J., Punn, R., Silverman, N. H., Peng, L. F., Perry, S. B., Balasubramanian, S. 2014; 9 (1): E23-6

  Abstract

  Rare cases of aortic-left atrial tunnel exist in the literature. This case report highlights the echocardiographic characterization of this vascular anomaly and provides the first description of an aortic-left atrial tunnel closed by interventional cardiac catheterization in a pediatric patient.

  View details for DOI 10.1111/chd.12059

  View details for PubMedID 23601836

• LONGITUDINAL PLASMA ENDOTHELIN-1 LEVELS IN PREMATURE INFANTS WITH AND WITHOUT BRONCHOPULMONARY DYSPLASIA Johnson, C., Chitkara, R., McCarthy, E., Fineman, J. R., Sun, C., Kim, L., Hintz, S. R., Van Meurs, K. P., Punn, R., Milla, C. E., Feinstein, J. A. LIPPINCOTT WILLIAMS & WILKINS. 2014: 179–80

  View details for Web of Science ID 000336284900134

• Systemic hypertension in an infant with unrepaired tetralogy of Fallot: case report CARDIOLOGY IN THE YOUNG Khoury, M., Kallile, M., May, J., Punn, R. 2013; 23 (5): 746-748

  Abstract

  Patients with severe right ventricular outflow tract obstruction in tetralogy of Fallot typically have right-to-left shunting, resulting in low pulmonary blood flow and cyanosis. Here we present the case of an infant with tetralogy of Fallot and severe pulmonary valve stenosis, complicated by systemic hypertension, the presence of which altered flow dynamics and possibly prevented cyanosis.

  View details for DOI 10.1017/S1047951112001837

  View details for Web of Science ID 000323882900017

  View details for PubMedID 23149090

• Echocardiographic Predictors of Early Postsurgical Myocardial Dysfunction in Pediatric Patients With Aortic Valve Insufficiency PEDIATRIC CARDIOLOGY Lowenthal, A., Tacy, T. A., Behzadian, F., Punn, R. 2013; 34 (6): 1335-1343

  Abstract

  In chronic aortic insufficiency (AI), left-ventricular (LV) dysfunction must be detected early to allow timely surgery. Strain and strain rate have been used for this purpose in adults, but the value of this method in pediatric AI has not been established. Forty patients with moderate to severe AI were included in this retrospective study. LV function was assessed by strain analysis and conventional echocardiography both before and after surgery. Of the 32 patients with preserved preoperative ejection fraction (EF; >50 %), 8 had postoperative dysfunction (<50 %). Mean conventional indices of global LV systolic performance for the entire cohort of patients with AI were predominantly in the normal range before surgery. Preoperative values for LV global longitudinal strain (GLS) and strain rate (GLSr) were normal. After surgery, there was a significant decrease in shortening and EF. There was a significant decrease from preoperative to postoperative values for both GLS (-16.07 ± 3.82 vs. -11.06 ± 3.88; p < 0.0001) and GLSr (-0.89 ± 0.24 vs. -0.72 ± 0.27; p = 0.0021). A preoperative GLS of -15.3  (AUC = 0.83, CI = 0.69-0.98, p < 0.0001) and a GLSr of -0.79/s (AUC = 0.86, CI = 0.73-0.98, p < 0.0001) were determined to be predictors of early postoperative dysfunction after surgical repair of moderate to severe AI. A preoperative GLS value of ≤-15.3  and GLSr value of -0.79/s or less are predictors of postoperative ventricular dysfunction, which is defined by EF <50 %. GLS and GLSr value determination may be useful as part of the echocardiographic assessment AI and may help determine the optimal timing of surgery in pediatric patient with at least moderate AI.

  View details for DOI 10.1007/s00246-013-0646-z

  View details for Web of Science ID 000321919400006

  View details for PubMedID 23389100

• Decremental Left Ventricular Deformation after Pulmonary Artery Band Training and Subsequent Repair in Ventriculoarterial Discordance JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Sun, H. Y., Behzadian, F., Punn, R., Tacy, T. A. 2013; 26 (7): 765-774

  Abstract

  BACKGROUND: Patients with ventriculoarterial discordance, such as congenitally corrected and d-transposition of the great arteries, may undergo a morphologic left ventricular (LV) training strategy consisting of surgical pulmonary artery band (PAB) placement and subsequent anatomic repair to establish ventriculoarterial concordance. The purpose of this study was to characterize morphologic LV function and deformation longitudinally using speckle-tracking strain analysis in patients with ventriculoarterial discordance who underwent LV training. METHODS: Twenty-nine patients (12 with d-transposition of the great arteries and 17 with congenitally corrected transposition of the great arteries) who underwent LV training with PAB placement were evaluated retrospectively. LV ejection fraction and global and regional longitudinal strain and strain rate were measured before and 7 ± 5 days after PAB placement and subsequent anatomic repair. RESULTS: PAB placement caused reductions in the mean LV ejection fraction from 76.1 ± 10.2% to 66.7 ± 7.8% (P < .001), in mean global strain from -17.7 ± 9% to -13.3 ± 7.5% (P = .01), and in mean lateral wall strain from -23.3 ± 12.8% to -17.5 ± 10.3% (P = .01). After anatomic repair (a median of 21 months after PAB placement; range, 0.5-104 months), mean LV ejection fraction decreased further from 63.3 ± 8.6% to 52.4 ± 14.9% (P < .05). Mean global strain declined from -17.6% ± 4.4 to -12.6 ± 4% (P = .01), and mean lateral wall strain decreased from -18.2 ± 11.4% to -12.6 ± 5.3% (P = .04). CONCLUSIONS: In patients with ventriculoarterial discordance undergoing PAB placement for LV training and anatomic repair, the morphologic left ventricle demonstrated decremental systolic function and global longitudinal deformation acutely. Frequent functional assessment is warranted to understand long-term myocardial mechanics in these patients.

  View details for DOI 10.1016/j.echo.2013.03.017

  View details for Web of Science ID 000321051000011

  View details for PubMedID 23623593

• Aortic valve disease in pulmonary atresia and major aortopulmonary collaterals. Annals of thoracic surgery Mainwaring, R. D., Dimeling, G., Punn, R., Hanley, F. L. 2013; 95 (6): 2122-2125

  Abstract

  Aortic valve disease in association with pulmonary atresia, ventricular septal defect, and major aortopulmonary collaterals (PA/VSD/MAPCAs) is an extremely rare combination of congenital heart defects. The presence of aortic stenosis or insufficiency or both imposes an additional physiologic burden that complicates the management of PA/VSD/MAPCAs. This report summarizes our experience with 7 patients who underwent surgical repair of this rare combination of defects.This was a retrospective review of patients who had both aortic valve disease and PA/VSD/MAPCAs. Four patients had predominantly aortic stenosis, 2 patients had aortic insufficiency, and 1 had mixed stenosis and insufficiency. Anatomically, this corresponded to a dysplastic trileaflet valve in 4, bicuspid valve in 2, and quadricuspid valve in 1.Four of the 7 patients underwent aortic valve surgery at the time of their first operation for PA/VSD/MAPCAs. The remaining 3 patients had aortic valve surgery at subsequent operations. All 7 patients are alive, with a median duration of follow-up of 3 years. One patient has required aortic valve replacement 2 years after repair of an insufficient bicuspid valve.This manuscript summarizes our experience with 7 patients who had the rare combination of aortic valve disease and PA/VSD/MAPCAs. Although aortic valve disease has been reported for other conotruncal defects, we believe this is the first report of its presence in association with PA/VSD/MAPCAs.

  View details for DOI 10.1016/j.athoracsur.2013.03.070

  View details for PubMedID 23643545

• Physiologic and molecular characterization of a murine model of right ventricular volume overload. American journal of physiology. Heart and circulatory physiology Reddy, S., Zhao, M., Hu, D., Fajardo, G., Katznelson, E., Punn, R., Spin, J. M., Chan, F. P., Bernstein, D. 2013; 304 (10): H1314-27

  Abstract

  Pulmonary insufficiency (PI) is a common long-term sequel after repair of tetralogy of Fallot, causing progressive right ventricular (RV) dilation and failure. We describe the physiologic and molecular characteristics of the first murine model of RV volume overload. PI was created by entrapping the pulmonary valve leaflets with sutures. Imaging, catheterization, and exercise testing were performed at 1, 3, and 6 mo and compared with sham controls. RNA from the RV free wall was hybridized to Agilent whole genome oligonucleotide microarrays. Volume overload resulted in RV enlargement, decreased RV outflow tract shortening fraction at 1 mo followed by normalization at 3 and 6 mo (39 ± 2, 44 ± 2, and 41 ± 2 vs. 46 ± 3% in sham), early reversal of early and late diastolic filling velocities (E/A ratio) followed by pseudonormalization (0.87 ± 0.08, 0.82 ± 0.08, and 0.96 ± 0.08 vs. 1.04 ± 0.03; P < 0.05), elevated end-diastolic pressure (7.6 ± 0.7, 6.9 ± 0.8, and 7 ± 0.5 vs. 2.7 ± 0.2 mmHg; P < 0.05), and decreased exercise duration (26 ± 0.4, 26 ± 1, and 22 ± 1.3 vs. 30 ± 1.1 min; P < 0.05). Subendocardial RV fibrosis was evident by 1 mo. At 1 mo, 372 genes were significantly downregulated. Mitochondrial pathways and G protein-coupled receptor signaling were the most represented categories. At 3 mo, 434 genes were upregulated and 307 downregulated. While many of the same pathways continued to be downregulated, TNF-α, transforming growth factor-β(1) (TGF-β(1)), p53-signaling, and extracellular matrix (ECM) remodeling transitioned from down- to upregulated. We describe a novel murine model of chronic RV volume overload recapitulating aspects of the clinical disease with gene expression changes suggesting early mitochondrial bioenergetic dysfunction, enhanced TGF-β signaling, ECM remodeling, and apoptosis.

  View details for DOI 10.1152/ajpheart.00776.2012

  View details for PubMedID 23504182

• Physiologic and molecular characterization of a murine model of right ventricular volume overload. American journal of physiology. Heart and circulatory physiology Reddy, S., Zhao, M., Hu, D., Fajardo, G., Katznelson, E., Punn, R., Spin, J. M., Chan, F. P., Bernstein, D. 2013; 304 (10): H1314-27

  View details for DOI 10.1152/ajpheart.00776.2012

  View details for PubMedID 23504182

• Surgical Reconstruction of Pulmonary Stenosis With Ventricular Septal Defect and Major Aortopulmonary Collaterals ANNALS OF THORACIC SURGERY Mainwaring, R. D., Punn, R., Reddy, V. M., Hanley, F. L. 2013; 95 (4): 1417-1421

  Abstract

  Pulmonary stenosis with ventricular septal defect and major aortopulmonary collaterals (PS/VSD/MAPCAs) is an extremely rare form of congenital heart defect. Although it has been assumed that PS/VSD/MAPCAs would be similar to pulmonary atresia (PA) with VSD/MAPCA, there are currently no data to support this conjecture. This study reviewed our surgical experience with reconstruction of PS/VSD/MAPCA.This was a retrospective review of 25 patients (14 boys, 11 girls) who were born with PS/VSD/MAPCA and underwent surgical reconstruction. Preoperative pulmonary angiography was used to define the central branch pulmonary arteries and MAPCA. Patients were a median age of 4 months at the first operation.There was one operative death (4%) in this cohort of 25 patients, and complete repair was achieved in the 24 survivors (96%). There were two distinct subgroups of patients: 11 demonstrated cyanosis in the neonatal timeframe and underwent an initial procedure to augment pulmonary blood flow (+PBF). The remaining 14 patients formed the second group (-PBF). The median age at the first operation was 0.8 months in the +PBF group and 5.2 months in the -PBF group (p<0.005). Complete repair was achieved in 91% of patients in the +PBF group and in 100% in the -PBF group; however, the average number of procedures to achieve complete repair was 2.8 in the +PBF group vs 1.0 in the -PBF group (p<0.005).Outcomes for PS/VSD/MAPCAs as a whole were excellent, with a low surgical mortality and high rate of complete repair. There were two identifiable subgroups with distinctive differences required in their surgical management. These results provide a prognostic outlook for patients with PS/VSD/MAPCAs that can be compared and contrasted with PA/VSD/MAPCAs.

  View details for DOI 10.1016/j.athoracsur.2013.01.007

  View details for Web of Science ID 000317150600039

  View details for PubMedID 23434256

• PREDICTORS OF MORTALITY IN PEDIATRIC PATIENTS ON VENOUS-ARTERIAL EXTRACORPOREAL MEMBRANE OXYGENATION 62nd Annual Scientific Session of the American-College-of-Cardiology Punn, R., Axelrod, D., Roth, S., Tacy, T. ELSEVIER SCIENCE INC. 2013: E436–E436

  View details for Web of Science ID 000316555200436

• Surgical reconstruction of peripheral pulmonary artery stenosis in Williams and Alagille syndromes 38th Annual Meeting of the Western-Thoracic-Surgical-Association Monge, M. C., Mainwaring, R. D., Sheikh, A. Y., Punn, R., Reddy, V. M., Hanley, F. L. MOSBY-ELSEVIER. 2013: 476–81

  Abstract

  Peripheral pulmonary artery stenosis is a rare congenital heart defect frequently found in association with Williams and Alagille syndromes. Controversy exists regarding the optimal treatment of peripheral pulmonary artery stenosis, with most centers favoring catheter-based interventions. In contrast, we have preferentially used surgical reconstruction of peripheral pulmonary artery stenosis. The purpose of the present study was to review our experience with surgical reconstruction of peripheral pulmonary artery stenosis.We performed a retrospective review of patients who underwent surgical reconstruction of peripheral pulmonary artery stenosis. A total of 16 patients were identified: 7 had Williams syndrome, 6 had Alagille syndrome, and 3 had no identifiable syndrome. Detailed pulmonary angiography was performed in all patients to define stenoses at the main, branch, lobar, and segmental arterial levels. The mean preoperative right ventricular/left ventricular pressure ratio was 0.88 ± 0.07. The surgical approach was a median sternotomy with cardiopulmonary bypass. All peripheral stenoses were augmented with pulmonary artery homograft tissue. The median age at surgery was 14 months, and concomitant procedures were performed in 9 of the 16 patients.There was 1 operative mortality (6%). The mean right ventricular/left ventricular pressure ratio decreased to 0.40 ± 0.04 postoperatively (P < .005), representing a 55% reduction compared with the preoperative values. The patients were followed up for a median of 5 years. No late mortality occurred and reoperation was not required.The data have demonstrate that this comprehensive surgical approach to the treatment of peripheral pulmonary artery stenosis was associated with low early and no late mortality. Surgical reconstruction of the peripheral pulmonary artery stenosis resulted in a significant decrease in right ventricular pressure. We hypothesize that this reduction in right ventricular pressures will confer a long-term survival advantage for this cohort of patients.

  View details for DOI 10.1016/j.jtcvs.2012.09.102

  View details for Web of Science ID 000313634700030

  View details for PubMedID 23228407

• Insights into dyssynchrony in Hypoplastic Left Heart Syndrome HEART RHYTHM Motonaga, K. S., Miyake, C. Y., Punn, R., Rosenthal, D. N., Dubin, A. M. 2012; 9 (12): 2010-2015

  Abstract

  Cardiac resynchronization therapy has been proposed for treatment of hypoplastic left heart syndrome (HLHS) patients with right ventricular (RV) failure. The role of dyssynchrony, however, is poorly understood in this population.The purpose of this study was to better understand the relationship between electrical and mechanical dyssynchrony in HLHS using 3-dimensional electrical mapping, tissue Doppler indices of wall motion, and vector velocity imaging.Eleven HLHS subjects with normal RV function and ten normal subjects (age 3-18 years) were studied. Electrical and mechanical activation times and dyssynchrony indices (electrical dyssynchrony index, mechanical dyssynchrony index) were calculated using 3-dimensional electrical mapping, tissue Doppler indices, and vector velocity imaging.No differences in measures of electrical dyssynchrony were seen when comparing HLHS patients and normal patients (electrical activation time 63.3 ± 22.8 ms vs 56.2 ± 11.2 ms, P = .38; electrical dyssynchrony index 13.7 ± 6.3 ms vs 11.6 ± 3.0 ms, P = .34). However, measures of mechanical dyssynchrony were markedly abnormal in HLHS patients despite normal RV function (mechanical activation time 16 ± 11.3 ms vs 0.9±1.9 ms, P = .01; mechanical dyssynchrony index 7.5 ± 5.5 vs 0.4 ± 0.8, P<.01).Patients with HLHS and preserved RV systolic function have normal electrical activation when compared to patients with normal right and left ventricles. In contrast, these patients demonstrate mechanical dyssynchrony compared to patients with normal right and left ventricles. This finding raises important questions about the indications for cardiac resynchronization therapy in this patient population.

  View details for DOI 10.1016/j.hrthm.2012.08.031

  View details for Web of Science ID 000311791900029

  View details for PubMedID 23085485

• Surgical outcomes for patients with pulmonary atresia/major aortopulmonary collaterals and Alagille syndrome 25th Annual Meeting of the European-Association-for-Cardio-Thoracic-Surgery (EACTS) Mainwaring, R. D., Sheikh, A. Y., Punn, R., Reddy, V. M., Hanley, F. L. OXFORD UNIV PRESS INC. 2012: 235–41

  Abstract

  Pulmonary atresia with major aortopulmonary collateral arteries (PA/MAPCAs) is a complex congenital heart defect that has undergone significant advances in treatment over the past 15 years. A small subset of patients with PA/MAPCAs have associated Alagille syndrome, which can have an adverse impact on many other organ systems. The purpose of this study was to review our institutional outcomes for the surgical patients with PA/MAPCAs and Alagille syndrome.This was a retrospective review of patients with PA/MAPCA's and Alagille who underwent surgical reconstruction from November 2001 to August 2011. Fifteen patients were identified in our data base. Thirteen had pulmonary atresia with ventricular septal defect (PA/VSD) and two had pulmonary atresia with intact ventricular septum (PA-IVS).There has been no early or late mortality in this cohort of 15 patients with PA/MAPCA' and Alagille syndrome. The patients have undergone a total of 38 cardiac surgical procedures. Ten of the 13 patients with PA/VSD have achieved complete repair, including unifocalization, a right ventricle to pulmonary artery conduit and closure of all intra-cardiac shunts. The three unrepaired patients with PA/VSD remain potential candidates for eventual complete repair, while the two patients with PA-IVS remain viable candidates for a single ventricle pathway. The patients in this series have also undergone 12 major non-cardiac procedures.The data demonstrate that surgical reconstruction of PA/MAPCAs can be successfully achieved in patients with Alagille syndrome. The longer-term prognosis remains guarded on the basis of the multi-organ system involvement of Alagille syndrome.

  View details for DOI 10.1093/ejcts/ezr310

  View details for Web of Science ID 000306365600013

  View details for PubMedID 22402453

• Supine Exercise Echocardiographic Measures of Systolic and Diastolic Function in Children JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Punn, R., Obayashi, D. Y., Olson, I., Kazmucha, J. A., Depucci, A., Hurley, M. P., Chin, C. 2012; 25 (7): 773-781

  Abstract

  Echocardiography has been used to determine ventricular function, segmental wall motion abnormality, and pulmonary artery pressure before and after peak exercise. No prior study has investigated systolic and diastolic function using echocardiography at various phases of exercise in children. The aim of this study was to determine the fractional shortening (FS), systolic-to-diastolic (S/D) ratio, heart rate-corrected velocity of circumferential fiber shortening (VCFc), circumferential wall stress (WS), ratio of mitral passive inflow to active inflow (E/A), ratio of passive inflow by pulsed-wave to tissue Doppler (E/E'), and right ventricular-to-right atrial pressure gradient from tricuspid valve regurgitation jet velocity (RVP) and time duration at various phases of exercise in children.In an 8-month period (December 2007 to July 2008), 100 healthy children were evaluated, and 97 participants aged 8 to 17 years who performed complete cardiopulmonary exercise stress tests using supine cycle ergometry were prospectively enrolled. The participants consisted of 48 female and 49 male subjects with various body sizes, levels of exercise experience, and physical capacities. The cardiopulmonary exercise stress test consisted of baseline pulmonary function testing, continuous gas analysis and monitoring of blood pressure and heart rate responses, electrocardiographic recordings, and oxygen saturation measurement among participants who pedaled against a ramp protocol based on body weight. All participants exercised to exhaustion. Echocardiography was performed during exercise at baseline, at a heart rate of 130 beats/min, at a heart rate of 160 beats/min, at 5 min after exercise, and at 10 min after exercise. FS, S/D ratio, VCFc, WS, E/A, E', E/E', and RVP at these five phases were compared in all subjects.All echocardiographic parameters differed at baseline from 160 beats/min (P < .0001) except E/E', which remained at 5.4 to 5.8. Specifically, FS (from 37% to 46%), S/D ratio, VCFc (from 1.1 to 1.6), WS (from 200 to 258 g/cm(2)), E' (from 0.2 to 0.3), and RVP (from 18 to 35 mm Hg) increased from baseline to 160 beats/min and then subsequently decreased to at or near baseline, while tricuspid valve regurgitation duration decreased (from 370 to 178 msec).Normal values for systolic and diastolic echocardiographic measurements of function are now available. FS, VCFc, WS, and RVP increase with exercise and then return to near baseline levels. The E/E' ratio is unaltered with exercise in normal subjects.

  View details for DOI 10.1016/j.echo.2012.03.007

  View details for Web of Science ID 000305701600013

  View details for PubMedID 22521368

• Tissue Doppler-Derived Measurement of Isovolumic Myocardial Contraction in the Pediatric Population PEDIATRIC CARDIOLOGY Punn, R., Behzadian, F., Tacy, T. A. 2012; 33 (5): 720-727

  Abstract

  Multiple echocardiographic techniques have been utilized to quantify systolic function. The shortening and ejection fraction remain the most commonly used and accepted methods. However, these measures are affected by altered loading conditions, and are not applicable when ventricular geometry differs from the prolate ellipsoid typical of a left ventricle. Mitral valve annular acceleration during isovolumic contraction (IVA) has been proposed as a load independent index of left ventricular contractility. However, published values for IVA demonstrating normal function vary. In addition, the value of IVA which may discern impaired systolic function has not been established. The purpose of this study is to determine a threshold IVA value for abnormal left ventricular function in the pediatric population. Structurally/functionally normal control (n = 90) and dilated cardiomyopathy (study = 64) patients were compared for differences in left ventricular: wall stress (WS), velocity of circumferential fiber shortening (VCFc), ejection fraction (EF), ejection force, and pulsed wave-derived medial and lateral wall IVA. No difference in body surface area (p = 0.61) or gender (p = 0.53) was noted. Left ventricular ejection fraction, ejection force, VCFc, and IVA were significantly lower and WS was significantly higher in the study group (p < 0.01). The medial IVA was 1.71 ± 0.89 m/s(2) for an EF <40%, 1.74 ± 0.70 m/s(2) for an EF = 40-50%, 2.46 ± 0.89 m/s(2) for an EF >50%. The lateral IVA was 1.81 ± 1.03 m/s(2) for an EF <40%, 2.07 ± 0.78 m/s(2) for an EF = 40-50%, 2.54 ± 0.99 m/s(2) for an EF >50%. ROC analysis demonstrated a medial IVA of 1.97 m/s(2) as the cut-off for predicting an EF <50% with a 77% sensitivity of and specificity of 66% (AUC = 0.75, CI = 0.67-0.83, p < 0.01). ROC analysis demonstrated a lateral IVA of 2.31 m/s(2) as the cut-off for predicting an EF <50% with a 73% sensitivity of and specificity of 63% (AUC = 0.72, CI = 0.63-0.82, p < 0.01). IVA lateral of 1.93 m/s(2) or less was associated with heart transplant and death. ICC analysis demonstrated some interobserver variability in IVA measurement (0.57-0.65). The normal IVA of the medial and lateral mitral valve annulus measure over 1.97 m/s(2) and 2.31 m/s(2), respectively; values less than this cut-off are associated with EF <50%. Despite some problems with reproducibility IVA remains a promising method of screening for diminished ventricular contractility in the setting of abnormal geometry.

  View details for DOI 10.1007/s00246-012-0200-4

  View details for Web of Science ID 000304458900006

  View details for PubMedID 22349669

• Imaging of the Aorta: Embryology and Anatomy SEMINARS IN ULTRASOUND CT AND MRI Murillo, H., Lane, M. J., Punn, R., Fleischmann, D., Restrepo, C. S. 2012; 33 (3): 169-190

  Abstract

  This review focuses on the embryology and anatomy of the aorta with some imaging examples. Dividing the aorta by segments of unique function and embryogenesis facilitates organizing the group of potential anomalies encountered. A basic understanding of the embryologic development of the aorta and its major branches helps in understanding and recognizing typical and atypical anatomic findings. Diagnostic imaging of the aorta and its major branches can be accomplished by invasive and noninvasive methods, based on the clinical scenario and the age of the patient. In this review, computed tomography and magnetic resonance imaging examples are emphasized.

  View details for DOI 10.1053/j.sult.2012.01.013

  View details for Web of Science ID 000305094700002

  View details for PubMedID 22624964

• Is There a Rote for Cardiac Resynchronization Therapy in Pediatric Pulmonary Hypertension? 32nd Annual Meeting and Scientific Sessions of the International-Society-for-Heart-and-Lung-Transplantation / Meeting of the ISHLT Academy - Core Competencies in Mechanical Circulatory Support Motonaga, K. S., MIYAKE, C. Y., Punn, R., Rosenthal, D. N., Feinstein, J. A., Dubin, A. M. ELSEVIER SCIENCE INC. 2012: S29–S29

  View details for Web of Science ID 000302207900059

• Late Repair of the Native Pulmonary Valve in Patients With Pulmonary Insufficiency After Surgery for Tetralogy of Fallot ANNALS OF THORACIC SURGERY Mainwaring, R. D., Pirolli, T., Punn, R., Hanley, F. L. 2012; 93 (2): 677-679

  Abstract

  Pulmonary regurgitation developing late after tetralogy of Fallot repair is now recognized as a serious threat to the long-term welfare of these patients. This article summarizes our experience with 5 patients who underwent reoperations for treatment of severe pulmonary regurgitation after transannular patch repair of tetralogy of Fallot. In each case, the intraoperative findings revealed anatomy favorable for valve repair and enabled preservation of the native pulmonary valves.

  View details for DOI 10.1016/j.athoracsur.2011.09.016

  View details for Web of Science ID 000299540200069

  View details for PubMedID 22269747

• Echocardiographic Diagnosis and Prognosis of Fetal Left Ventricular Noncompaction JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Arunamata, A., Punn, R., Cuneo, B., Bharati, S., Silverman, N. H. 2012; 25 (1): 112-120

  Abstract

  Left ventricular noncompaction (LVNC) has rarely been described in the fetus.The presence of associated congenital heart disease and rhythm disturbance was identified and the presence of heart failure was assessed using the cardiovascular profile score in all fetuses with LVNC presenting from January 1999 to July 2010. The left ventricle was divided into 12 segments-four segments each at the base, midpapillary, and apical regions-in the short-axis view to calculate the noncompaction/compaction ratio for each segment.Of 24 fetuses with LVNC included in the study, 22 had significant congenital heart disease, and 15 had complete heart block. Of the 16 patients with adequate follow-up and not electively terminated, 12 (81%) died or progressed to heart transplantation. The average noncompaction/compaction ratios were 2.02 in patients who died or underwent heart transplantation and 1.67 in survivors (P = .2034). Fifty-seven of 93 measured segments (61%) of the left ventricle in the patients who died or underwent heart transplantation had noncompaction/compaction ratios ≥ 2 compared with five of 17 measured segments (29%) in survivors (P = .0837). The average cardiovascular profile score was 6. The apical region had greater involvement of noncompaction than the midpapillary and basal regions, with ratios of 2.27, 2.14, and 1.10, respectively (P = .00035).Fetuses with LVNC have a poor prognosis that may be related to associated congenital heart disease, increased segmental involvement of noncompaction, and complete heart block and can be predicted by the cardiovascular profile score.

  View details for DOI 10.1016/j.echo.2011.09.019

  View details for Web of Science ID 000298276500013

  View details for PubMedID 22014428

• Novel Electrocardiogram Manifestations of a Tension Pneumothorax PEDIATRIC CARDIOLOGY Punn, R., Seslar, S. P. 2011; 32 (8): 1258-1259

  View details for DOI 10.1007/s00246-011-0067-9

  View details for Web of Science ID 000296733100039

  View details for PubMedID 21811813

• Surgical Results in Patients With Pulmonary Atresia-Major Aortopulmonary Collaterals in Association With Total Anomalous Pulmonary Venous Connection ANNALS OF THORACIC SURGERY Mainwaring, R. D., Reddy, M., Reinhartz, O., Punn, R., Tacy, T., Hanley, F. L. 2011; 92 (5): 1756-1760

  Abstract

  Pulmonary atresia and major aortopulmonary collaterals (PA/MAPCAs) is a complex form of congenital heart disease. One to two percent of patients with PA/MAPCAs will also have total anomalous pulmonary venous connection (TAPVC). This study summarizes our surgical experience with this rare combination of life-threatening congenital heart defects.A retrospective review was performed to identify patients who had surgery for PA/MAPCAs in association with TAPVC. From November 2001 to March 2011, 9 patients presented with this combination of defects. Eight of the 9 patients had heterotaxy with an unbalanced atrioventricular canal and functional single ventricle. The ninth patient had double outlet right ventricle (two ventricles). Timing of surgical intervention was typically predicated on the degree of pulmonary venous obstruction. The median age at surgery was 14 days. All nine patients had surgical correction of TAPVC, unifocalization of MAPCA's into a central confluence, and placement of a shunt.There was one early mortality (< 30 days) and two late mortalities. For the 6 survivors, 5 have subsequently undergone a bidirectional Glenn procedure, and 3 had completion of their Fontan. Two patients are currently at the bidirectional Glenn stage; one is a good candidate for Fontan completion while the other is not suitable. The sixth patient is awaiting further assessment.The PA/MAPCAs, in association with TAPVC, is a challenging combination of defects. The data suggest that the combination of PA/MAPCAs and TAPVC can be undertaken with a reasonable midterm prognosis.

  View details for DOI 10.1016/j.athoracsur.2011.06.020

  View details for Web of Science ID 000296925400045

  View details for PubMedID 21944736

• QTc prolongation in children following congenital cardiac disease surgery CARDIOLOGY IN THE YOUNG Punn, R., Lamberti, J. J., Balise, R. R., Seslar, S. P. 2011; 21 (4): 400-410

  Abstract

  IntroductionQTc prolongation has been reported in adults following cardiopulmonary bypass; however, this phenomenon has not been studied in children with congenital cardiac disease. This study's aim was to formally assess QTc in children undergoing cardiac surgery.Pre-operative and post-operative electrocardiograms during hospital stays were prospectively analysed on 107 consecutive patients under 18 years of age undergoing cardiac surgery. QTc was measured manually in leads II, V4, and V5. Measurements of 440 and 480 milliseconds were used to categorise patients. Peri-procedural data included bypass and cross-clamp time, medications, and electrolyte measurements. Outcome data included arrhythmias, length of mechanical ventilation, and hospital stay. Patients with post-operative new bundle branch block or ventricularly paced rhythm were excluded.In all, 59 children were included, out of which 26 had new QTc over 440 milliseconds and 6 of 59 had new QTc over 480 milliseconds post-operatively. The mean increase in post-operative QTc was 25 milliseconds, p=0.0001. QTc over 480 was associated with longer cross-clamp time, p=0.003. Other risk factors were not associated with post-operative QTc prolongation. This phenomenon was transient with normalisation occurring in 67% of patients over 60 hours on average. One patient with post-operative QTc over 440 milliseconds developed ventricular tachycardia. There was no correlation between prolonged QTc and duration of mechanical ventilation, or hospital stay.ConclusionA significant number of children undergoing cardiac surgery showed transient QTc prolongation. The precise aetiology of QT prolongation was not discerned, though new QTc over 480 milliseconds was associated with longer cross-clamp time. In this cohort, transient QTc prolongation was not associated with adverse sequela.

  View details for DOI 10.1017/S1047951111000175

  View details for Web of Science ID 000293593800005

  View details for PubMedID 21362209

• Fetal Predictors of Urgent Balloon Atrial Septostomy in Neonates with Complete Transposition JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Punn, R., Silverman, N. H. 2011; 24 (4): 425-430

  Abstract

  In complete transposition of the great vessels, a restrictive patent foramen ovale leads to inadequate circulatory mixing and severe cyanosis. Urgent balloon atrial septostomy (BAS) improves mixing and bridges neonates to surgery. Several studies have determined risk factors in utero for poor postnatal outcomes in complete transposition of the great vessels, particularly a restrictive patent foramen ovale and ductus arteriosus. In addition to these risk factors, we studied two new features, a hypermobile septum and reverse diastolic patent ductus arteriosus shunt, to determine which patients will require an urgent BAS.We reviewed all 26 fetuses from 2001 to 2010 with complete transposition of the great vessels and closely examined the patent foramen ovale and septum primum for hypermobility, restriction, flat appearance, or redundancy. We defined hypermobility as a septum primum flap that oscillates between both atria. We also examined the ductus size and shunting pattern to evaluate whether these features contributed to urgent BAS.In total, 14 of 26 fetuses required urgent BAS with improved cyanosis. Nine fetuses had an urgent BAS and a hypermobile septum, and 12 fetuses had no urgent BAS or hypermobile septum. Eight fetuses had an urgent BAS and a reverse diastolic patent ductus arteriosus, and 11 fetuses had no urgent BAS or reverse diastolic patent ductus arteriosus. A hypermobile septum and reverse diastolic patent ductus arteriosus had a significant association with urgent BAS (P < .01, sensitivity = 0.64 and 0.57, specificity = 1.0 and 0.92, positive predictive value = 1.0 and 0.89, negative predictive value = 0.71 and 0.65). No fetus had a restrictive patent foramen ovale/ductus arteriosus.A hypermobile septum and reverse diastolic patent ductus arteriosus are new prenatal findings to help predict the need for an urgent BAS postnatally in patients with complete transposition of the great vessels.

  View details for DOI 10.1016/j.echo.2010.12.020

  View details for Web of Science ID 000288781700011

  View details for PubMedID 21324642

• The Echocardiographic Evaluation of Left Ventricular Non-compaction Pediatric Ultrasound Today Punn R, Silverman N 2011; 16 (6): 109-28
• Annular Tilt as a Screening Test for Right Ventricular Enlargement in Patients with Tetralogy of Fallot JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Punn, R., Behzadian, F., Tacy, T. A. 2010; 23 (12): 1297-1302

  Abstract

  Right ventricular end-diastolic volume (RVEDV) greater than 150 mL/m² is a risk factor for sudden death in patients with tetralogy of Fallot (TOF) after repair. Because of its anterior placement and abnormal geometry, two-dimensional echocardiography is limited to a qualitative assessment of RVEDV. Cardiac magnetic resonance imaging (CMRI) and computed tomography angiography (CTA) are the accepted standards for quantifying RVEDV. This study evaluated the ability of a novel echocardiographic measure, the right ventricular annular tilt (RVAT), to identify patients with increased RVEDV.All patients with repaired TOF with an echocardiogram and CMRI or CTA were included in this retrospective study. The RVAT was determined by measuring the angle of the tricuspid valve plane relative to the mitral valve plane at end-diastole in the apical 4-chamber view in study (n = 38) and age-matched control (n = 74) patients. The RVEDV measurements were obtained by CMRI (n = 32) or CTA (n = 6). The study and control patients' ages were no different (11.3 and 11.8 years, P = .73).The study group RVAT was significantly higher than the control group RVAT (17.4 vs. 0.1 degrees; P < .0001). RVAT values greater than 20 degrees had a mean RVEDV of 166 ± 60 mL/m², whereas RVAT less than 20 degrees had a mean RVEDV of 122 ± 25 mL/m² (P = .0370). Receiver operating characteristic analysis demonstrated an RVAT of 17.9 degrees as the cutoff for predicting a RVEDV of greater than 150 mL/m² with a sensitivity of 75% and specificity of 73% (area under the curve = 0.76; confidence interval, 0.56-0.96; P = .0063). Intraclass correlation analysis demonstrated minimal interobserver and intraobserver variability when measuring RVAT (0.99 and 0.92).An RVAT less than 20 degrees is associated with an RVEDV less than 150 mL/m². RVAT is a useful echocardiographic technique for detecting increased RVEDV in patients with TOF and may help discern which patients should undergo RVEDV quantification by CMRI or CTA.

  View details for DOI 10.1016/j.echo.2010.09.002

  View details for Web of Science ID 000284624900012

  View details for PubMedID 20950999

• Newborn with Persistent Truncus Arteriosus and Interrupted Aortic Arch Demonstrating Reverse Left Subclavian Artery Flow PEDIATRIC CARDIOLOGY Chan, E. L., Tacy, T. A., Punn, R. 2010; 31 (8): 1254-1256

  View details for DOI 10.1007/s00246-010-9817-3

  View details for Web of Science ID 000284157400025

  View details for PubMedID 20957476

• Anomalies Associated With a Prominent Azygos Vein on Echocardiography in the Pediatric Population JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Punn, R., Olson, I. 2010; 23 (3): 282-285

  Abstract

  Prominent azygos veins (PAVs) have been described with interrupted inferior venae cavae (IVCs) with heterotaxy. At the authors' institution, cases of PAVs with uninterrupted IVCs have been noted. The aim of this study was to determine the occurrence rate of PAVs and associated lesions by echocardiography.All patients with PAVs were collected; those with interrupted and uninterrupted IVCs were assigned to groups 1 and 2. Normal controls were assigned to group 3.Among 15,849 patients from January 1, 2001, to March 31, 2008, 55 (0.3%) had PAVs, 42 (76%) in group 1 and 13 (24%) in group 2. Heterotaxy was prominent in group 1, whereas patients in group 2 had no heterotaxy. Patients in group 2 had more structurally normal hearts than those in group 1 (46% vs 14%, P<.01), partial anomalous pulmonary venous return, and one single ventricle. IVC measurements were the same in groups 2 and 3 (P=.65).This study demonstrates that a PAV without IVC interruption is not associated with heterotaxy. Patients with PAVs should be carefully examined for partial anomalous pulmonary venous return.

  View details for DOI 10.1016/j.echo.2009.11.025

  View details for Web of Science ID 000275221900007

  View details for PubMedID 20138465

• Response to "Chromosomal Abnormalities and Neuromuscular Disorders Predict Severity and Outcome of Noncompaction in Addition to Cardiac Comorbidities" JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Punn, R., Silverman, N. H. 2010; 23 (3): 338–39

  View details for DOI 10.1016/j.echo.2010.01.016

  View details for Web of Science ID 000275221900016

• Cardiac Segmental Analysis in Left Ventricular Noncompaction: Experience in a Pediatric Population JOURNAL OF THE AMERICAN SOCIETY OF ECHOCARDIOGRAPHY Punn, R., Silverman, N. H. 2010; 23 (1): 46-53

  Abstract

  Echocardiography has been used to diagnose and describe left ventricular noncompaction (LVNC). No other study has investigated LVNC using the 16-segment model described by the American Heart Association and the American Society of Echocardiography in children, some of whom have congenital heart disease. Using the ratio of noncompaction to compaction, the authors analyzed the 16 segments and determined if severity was correlated with poor outcomes in a pediatric population.The 16-segment noncompaction/compaction ratio, shortening, and ejection fractions were measured retrospectively in all children with LVNC at a single institution from January 1, 2000, to June 30, 2008.Forty-four patients had LVNC, an incidence of 0.3% of laboratory admissions. Twenty-eight patients (64%) who remained alive were assigned to group 1, and 16 patients (36%) who either died or were transplanted constituted group 2. Group 2 had more patients with significant associated congenital heart disease than group 1 (50% vs 18%, P < .05). We found similar regions of involvement in the 16-segment model with sparing of basal segments and involvement of the midpapillary and apical regions (P < .001); however, patients in group 2 were noted to have more segments involved (6 vs 4, P < .05), lower shortening fractions (16% vs 29%, P < .001), and lower ejection fractions (24% vs 47%, P < .001). The ejection fraction was inversely related to the number of segments (r = -0.63, P < .01), suggesting that more noncompaction portends a worse outcome.In younger patients with noncompaction, poor outcomes such as low ejection fractions, death, and transplantation are related to the number of left ventricular segments involved. There is more associated congenital heart disease in the pediatric population, which carries a poorer prognosis than the disease reported in adult populations.

  View details for DOI 10.1016/j.echo.2009.09.003

  View details for Web of Science ID 000273052600011

  View details for PubMedID 19857942

• Echocardiography in patients with left ventricular inflow lesions. Pediatric Ultrasound Today. Punn R, Silverman NH 2008; 13 (1): 3-23
• Case report: Rhabdomyolysis induced by mibefradil in a patient treated with cyclosporine and simvastatin JOURNAL OF CLINICAL PHARMACOLOGY Wombolt, D. G., Jackson, A., Punn, R., Smith, S., McCune, T. R., Williams, P. B. 1999; 39 (3): 310-312

  View details for Web of Science ID 000078782800015

  View details for PubMedID 10073331