Clinical Trials

  • Remodulin as Add-on Therapy for the Treatment of Persistent Pulmonary Hypertension of the Newborn Not Recruiting

    This study assessed the safety and treatment effect of intravenous (IV) Remodulin as an add-on therapy in neonates with persistent pulmonary hypertension of the newborn (PPHN).

    Stanford is currently not accepting patients for this trial. For more information, please contact Keeley Phillips, 650-723-8922.

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All Publications

  • Role of left atrial hypertension in pulmonary hypertension associated with bronchopulmonary dysplasia Frontiers in Pediatrics Sullivan, R. T., Tandel, M. D., Bhombal, S., Adamson, G. T., Boothroyd, D. B., Tracy, M., Moy, A., Hopper, R. K. 2022: 1012136


    Left atrial hypertension (LAH) may contribute to pulmonary hypertension (PH) in premature infants with bronchopulmonary dysplasia (BPD). Primary causes of LAH in infants with BPD include left ventricular diastolic dysfunction or hemodynamically significant left to right shunt. The incidence of LAH, which is definitively diagnosed by cardiac catheterization, and its contribution to PH is unknown in patients with BPD-PH. We report the prevalence of LAH in an institutional cohort with BPD-PH with careful examination of hemodynamic contributors and impact on patient outcomes. This single-center, retrospective cohort study examined children <2 years of age with BPD-PH who underwent cardiac catheterization at Lucile Packard Children's Hospital Stanford. Patients with unrepaired simple shunt congenital heart disease (CHD) and pulmonary vein stenosis (only 1 or 2 vessel disease) were included. Patients with complex CHD were excluded. From April 2010 to December 2021, 34 patients with BPD-PH underwent cardiac catheterization. We define LAH as pulmonary capillary wedge pressure (PCWP) or left atrial pressure (LAP) of at least 10 mmHg. In this cohort, median PCWP was 8 mmHg, with LAH present in 32% (n = 11) of the total cohort. A majority (88%, n = 30) of the cohort had severe BPD. Most patients had some form of underlying CHD and/or pulmonary vein stenosis: 62% (n = 21) with an atrial septal defect or patent foramen ovale, 62% (n = 21) with patent ductus arteriosus, 12% (n = 4) with ventricular septal defect, and 12% (n = 4) with pulmonary vein stenosis. Using an unadjusted logistic regression model, baseline requirement for positive pressure ventilation at time of cardiac catheterization was associated with increased risk for LAH (odds ratio 8.44, 95% CI 1.46-48.85, p = 0.02). Small for gestational age birthweight, sildenafil use, and CHD were not associated with increased risk for LAH. LAH was associated with increased risk for the composite outcome of tracheostomy and/or death, with a hazard ratio of 6.32 (95% CI 1.72, 22.96; p = 0.005). While the etiology of BPD-PH is multifactorial, LAH is associated with PH in some cases and may play a role in clinical management and patient outcomes.

    View details for DOI 10.3389/fped.2022.1012136

    View details for PubMedCentralID PMC9615143

  • Call to action: gender equity in neonatology. Journal of perinatology : official journal of the California Perinatal Association Machut, K. Z., Bhombal, S., Escobedo, M., Kataria-Hale, J., Kushnir, A., Lingappan, K., Oji-Mmuo, C. N., Owens, L., Savich, R., Song, C., Wright, R., Dammann, C. E. 2022

    View details for DOI 10.1038/s41372-022-01390-w

    View details for PubMedID 35411019

  • The impact of prematurity and associated comorbidities on clinical outcomes in neonates with congenital heart disease. Seminars in perinatology Bhombal, S., Chock, V. Y., Shashidharan, S. 2022: 151586


    Prematurity is a common risk factor in children, affecting approximately 10% of live births, globally. It is more common in children with critical congenital heart disease (CCHD) and carries important implications in this group of patients. While outcomes have been improving over the years, even late preterm birth is associated with worse outcomes in children born with critical congenital heart disease compared to those without. Infants with both prematurity and CCHD are at particularly high risk for important comorbidities, including: necrotizing enterocolitis, intraventricular hemorrhage, white matter injury, neurodevelopmental anomalies and retinopathy of prematurity. Lesion-specific intensive care management of these infants, interventional and peri-operative management specifically tailored to their needs, and multidisciplinary care all have the potential to improve outcomes in this challenging group.

    View details for DOI 10.1016/j.semperi.2022.151586

    View details for PubMedID 35525603

  • REAL-TIME ULTRASOUND GUIDANCE TO INCREASE SUCCESS OF UMBILICAL VENOUS CANNULATION Kozyak, B., Fraga, M., Juliano, C., Bhombal, S., Munson, D., Brandsma, E., Stoller, J., Jain, A., Kesman, R., Meshkati, M., Noh, C., DeWitt, A., Costarino, A., Hehir, D., Groves, A. LIPPINCOTT WILLIAMS & WILKINS. 2022: 522
  • Real-Time Ultrasound Guidance for Umbilical Venous Cannulation in Neonates With Congenital Heart Disease. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Kozyak, B. W., Fraga, M. V., Juliano, C. E., Bhombal, S., Munson, D. A., Brandsma, E., Stoller, J. Z., Jain, A., Kesman, R., Meshkati, M., Noh, C. Y., Dewitt, A. G., Costarino, A. T., Hehir, D. A., Groves, A. M. 2022


    Umbilical venous cannulation is the favored approach to perinatal central access worldwide but has a failure rate of 25-50% and the insertion technique has not evolved in decades. Improving the success of this procedure would have broad implications, particularly where peripherally inserted central catheters are not easily obtained and in neonates with congenital heart disease, in whom umbilical access facilitates administration of inotropes and blood products while sparing vessels essential for later cardiac interventions. We sought to use real-time, point-of-care ultrasound to achieve central umbilical venous access in patients for whom conventional, blind placement techniques had failed.Multicenter case series, March 2019-May 2021.Cardiac and neonatal ICUs at three tertiary care children's hospitals.We identified 32 neonates with congenital heart disease, who had failed umbilical venous cannulation using traditional, blind techniques.Real-time ultrasound guidance and liver pressure were used to replace malpositioned catheters and achieve successful placement at the inferior cavoatrial junction.In 32 patients with failed prior umbilical venous catheter placement, real-time ultrasound guidance was used to successfully "rescue" the line and achieve central position in 23 (72%). Twenty of 25 attempts (80%) performed in the first 48 hours of life were successful, and three of seven attempts (43%) performed later. Twenty-four patients (75%) were on prostaglandin infusion at the time of the procedure. We did not identify an association between patient weight or gestational age and successful placement.Ultrasound guidance has become standard of care for percutaneous central venous access but is a new and emerging technique for umbilical vessel catheterization. In this early experience, we report that point-of-care ultrasound, together with liver pressure, can be used to markedly improve success of placement. This represents a significant advance in this core neonatal procedure.

    View details for DOI 10.1097/PCC.0000000000002919

    View details for PubMedID 35250003

  • Establishing a risk assessment framework for point-of-care ultrasound. European journal of pediatrics Conlon, T. W., Yousef, N., Mayordomo-Colunga, J., Tissot, C., Fraga, M. V., Bhombal, S., Suryawanshi, P., Villanueva, A. M., Siassi, B., Singh, Y. 2021


    Point-of-care ultrasound (POCUS) refers to the use of portable ultrasound (US) applications at the bedside, performed directly by the treating physician, for either diagnostic or procedure guidance purposes. It is being rapidly adopted by traditionally non-imaging medical specialties across the globe. Recent international evidence-based guidelines on POCUS for critically ill neonates and children were issued by the POCUS Working Group of the European Society of Pediatric and Neonatal Intensive Care (ESPNIC). Currently there are no standardized national or international guidelines for its implementation into clinical practice or even the training curriculum to monitor quality assurance. Further, there are no definitions or methods of POCUS competency measurement across its varied clinical applications.Conclusion: The Hippocratic Oath suggests medical providers do no harm to their patients. In our continued quest to uphold this value, providers seeking solutions to clinical problems must often weigh the benefit of an intervention with the risk of harm to the patient. Technologies to guide diagnosis and medical management present unique considerations when assessing possible risk to the patient. Frequently risk extends beyond the patient and impacts providers and the institutions in which they practice. POCUS is an emerging technology increasingly incorporated in the care of children across varied clinical specialties. Concerns have been raised by clinical colleagues and regulatory agencies regarding appropriate POCUS use and oversight. We present a framework for assessing the risk of POCUS use in pediatrics and suggest methods of mitigating risk to optimize safety and outcomes for patients, providers, and institutions. What is Known: The use POCUS by traditionally non-imaging pediatric specialty physicians for both diagnostic and procedural guidance is rapidly increasing. Although there are international guidelines for its indications, currently there is no standardized guidance on its implementation in clinical practice. What is New: Although standards for pediatric specialty-specific POCUS curriculum and training to competency have not been defined, POCUS is likely to be most successfully incorporated in clinical care when programmatic infrastructural elements are present. Risk assessment is a forward-thinking process and requires an imprecise calculus that integrates considerations of the technology, the provider, and the context in which medical care is delivered.Medicolegal considerations vary across countries and frequently change, requiring providers and institutions to understand local regulatory requirements and legal frameworks to mitigate the potential risks of POCUS.

    View details for DOI 10.1007/s00431-021-04324-4

    View details for PubMedID 34846557

  • Cardiac Dysfunction in Neonatal HIE Is Associated with Increased Mortality and Brain Injury by MRI. American journal of perinatology Altit, G., Bonifacio, S. L., Guimaraes, C. V., Bhombal, S., Sivakumar, G., Yan, B., Chock, V., Meurs, K. V. 2021


    OBJECTIVE: Describe the association between cardiac dysfunction and death or moderate-to-severe abnormalities on brain magnetic resonance imaging (MRI) in neonates undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE).STUDY DESIGN: Retrospective study in neonates with moderate or severe HIE undergoing therapeutic hypothermia between 2008 and 2017. Primary outcome was death or moderate-to-severe brain injury using the Barkovich score. Conventional and speckle-tracking echocardiography measures were extracted from available echocardiograms to quantify right (RV) and left (LV) ventricular functions.RESULTS: A total of 166 newborns underwent therapeutic hypothermia of which 53 (36.5%) had echocardiography performed. Ten (19%) died prior to hospital discharge, and 11 (26%) had moderate-to-severe brain injury. There was no difference in chronologic age at echocardiography between the normal and adverse outcome groups (22 [±19] vs. 28 [±21] hours, p=0.35). Cardiac findings in newborns with abnormal outcome included lower systolic and diastolic blood pressure (BP) at echocardiography (p=0.004) and decreased tricuspid annular plane systolic excursion (a marker of RV systolic function; p=0.01), while the ratio of systolic pulmonary artery (PA) pressure to systolic BP indicated isosystemic pressures (>2/3 systemic) in both groups. A multilogistic regression analysis, adjusting for weight and seizure status, indicated an association between abnormal outcome and LV function by longitudinal strain, as well as by ejection fraction.CONCLUSION: Newborns who died or had moderate-to-severe brain injury had a higher incidence of cardiac dysfunction but similar PA pressures when compared with those who survived with mild or no MRI abnormalities.KEY POINTS: · Newborns with HIE with functional LV/RV dysfunction are at risk for death or brain injury.. · All neonates with HIE had elevated pulmonary pressure, but neonates with poor outcome had RV dysfunction.. · When evaluating newborns with HIE by echocardiography, beyond estimation of pulmonary pressure, it is important to assess biventricular function..

    View details for DOI 10.1055/s-0041-1735618

    View details for PubMedID 34492719

  • End-organ saturations correlate with aortic blood flow estimates by echocardiography in the extremely premature newborn - an observational cohort study. BMC pediatrics Altit, G., Bhombal, S., Chock, V. Y. 2021; 21 (1): 312


    BACKGROUND: Near-infrared spectroscopy (NIRS) measures of cerebral saturation (Csat) and renal saturation (Rsat) in extreme premature newborns may be affected by systemic blood flow fluctuations. Despite increasing clinical use of NIRS to monitor tissue saturation in the premature infant, validation of NIRS measures as a correlate of blood flow is still needed. We compared echocardiography (ECHO) derived markers of ascending aorta (AscAo) and descending aorta (DesAo) blood flow with NIRS measurements obtained during the ECHO.METHODS: Newborns <29weeks' gestation (2013-2017) underwent routine NIRS monitoring. Csat, Rsat and systemic saturation at the time of ECHO were retrospectively analyzed and compared with Doppler markers of aortic flow. Renal and cerebral fractional tissue oxygen extraction (rFTOE and cFTOE, respectively) were calculated. Mixed effects models evaluated the association between NIRS and Doppler markers.RESULTS: Forty-nine neonates with 75 Csat-ECHO and 62 Rsat-ECHO observations were studied. Mean post-menstrual age was 28.3±3.8weeks during the ECHO. Preductal measures including AscAo velocity time integral (VTI) and AscAo output were correlated with Csat or cFTOE, while postductal measures including DesAo VTI, DesAo peak systolic velocity, and estimated DesAo output were more closely correlated with Rsat or rFTOE.CONCLUSIONS: NIRS measures are associated with aortic blood flow measurements by ECHO in the extremely premature population. NIRS is a tool to consider when following end organ perfusion in the preterm infant.

    View details for DOI 10.1186/s12887-021-02790-1

    View details for PubMedID 34253175

  • Cerebral saturation reflects anterior cerebral artery flow parameters by Doppler ultrasound in the extremely premature newborn. Journal of perinatology : official journal of the California Perinatal Association Altit, G., Bhombal, S., Chock, V. Y. 2021


    BACKGROUND: Near-infrared spectroscopy measures cerebral saturation (Csat), although correlation with cerebral blood flow remains unclear in premature newborns at risk for intraventricular hemorrhage (IVH).OBJECTIVES: Compare Doppler markers of anterior cerebral artery (ACA) flow with Csat obtained during head ultrasound (HUS).METHOD: Newborns <29 weeks (2013-2017) underwent Csat monitoring with clinical acquisition of HUS. ACA Doppler markers were measured (with and without pressure) and Resistive Index (RI) was calculated. Mixed effects models evaluated the association between Csat and Doppler markers.RESULTS: 98 neonates with 175 Csat-HUS observations were analyzed. Age at birth was 26.2±1.5 weeks, with post-menstrual age of 26.9±1.7 weeks at HUS. Csat was associated with RI without pressure (p=0.045), RI with pressure (p=0.019), and peak systolic velocity with pressure (p=0.036). Severe IVH (n=27 [15%]) was associated with lower Csat (60±11% vs 68±9%, p=0.01).CONCLUSION: Csat was associated with ACA Doppler measurements in extremely premature neonates.

    View details for DOI 10.1038/s41372-021-01145-z

    View details for PubMedID 34247188

  • The evolution of cardiac point of care ultrasound for the neonatologist. European journal of pediatrics Singh, Y., Bhombal, S., Katheria, A., Tissot, C., Fraga, M. V. 2021


    Cardiac point of care ultrasound (POCUS) is increasingly being utilized in neonatal intensive care units to provide information in real time to aid clinical decision making. While training programs and scope of practice have been well defined for other specialties, such as adult critical care and emergency medicine, there is a lack of structure for neonatal cardiac POCUS. A more comprehensive and advanced hemodynamic evaluation by a neonatologist has previously published its own clinical guidelines and specific rigorous training programs have been established to achieve competency in neonatal hemodynamics. However, it is becoming increasingly evident that access and training for basic cardiac assessment by ultrasound enhances bedside clinical care for specific indications. Recently, expert consensus POCUS guidelines for use in neonatal and pediatric intensive care endorsed by the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) have been published to guide the clinicians in using POCUS for specific indications, though the line between cardiac POCUS and advanced hemodynamic evaluation remains somewhat fluid.Conclusion: This article is focused on neonatal cardiac POCUS and its evolution, value, and limitations in the modern neonatal clinical practice. Cardiac POCUS can provide physiological and hemodynamic information in making clinical decisions while dealing with neonatal emergencies. However, it should be applied only for the specific indications and should be performed by a clinician trained in cardiac POCUS. There is an urgent need of developing cardiac POCUS curriculum and certification to support a widespread and safe use in neonates. What is Known: International training guidelines and curriculum have been published for neonatologist-performed echocardiography (NPE) or targeted neonatal echocardiography (TNE). International evidence-based guidelines for use of point of care ultrasound (POCUS) in neonates and children have been recently published. What is New: Cardiac POCUS is increasingly being incorporated in neonatal practice for emergency situations. However, one must be aware of its specific indications and limitations, especially for the neonatal clinical practice. Cardiac POCUS and NPE/TNE are continuum of cardiac imaging with different indications and training requirements.

    View details for DOI 10.1007/s00431-021-04153-5

    View details for PubMedID 34125292

  • Status of Multidisciplinary Collaboration in Neonatal Cardiac Care in the United States. Pediatric cardiology Levy, V. Y., Bhombal, S., Villafane, J., McBride, M. E., Chung, S., Figueroa, M., Hopper, A., Johnson, J. N., Costello, J. M., Neonatal Cardiac Care Collaborative(NeoC3) 2021


    While outcomes for neonates with congenital heart disease have improved, it is apparent that substantial variability exists among centers with regard to the multidisciplinary approach to care for this medically fragile patient population. We endeavored to understand the landscape of neonatal cardiac care in the United States. A survey was distributed to physicians who provide neonatal cardiac care in the United States regarding (1) collaborative efforts in care of neonates with congenital heart disease (CHD); (2) access to neonatal cardiac training; and (3) barriers to the implementation of protocols for neonatal cardiac care. Responses were collected from 10/2018 to 6/2019. We received responses from 172 of 608 physicians (28% response rate) from 89 centers. When compared to responses received from physicians at low-volume centers (<300 annual bypass cases), those at high-volume centers reported more involvement from the neurodevelopmental teams (58% vs. 29%; P=0.012) and a standardized transition to outpatient care (68% vs. 52%; P=0.038). While a majority of cardiothoracic surgery and anesthesiology respondents reported multidisciplinary involvement, less than half of cardiology and neonatology supported this statement. The most commonly reported obstacles to multidisciplinary engagement were culture (61.6%) and logistics (47.1%). Having a standardized neonatal cardiac curriculum for neonatal fellows was positively associated with the perception that multidisciplinary collaboration was "always" in place (53% vs. 40%; P=0.09). There is considerable variation among centers in regard to personnel involved in neonatal cardiac care, related education, and perceived multidisciplinary collaboration among team members. The survey findings suggest the need to establish concrete standards for neonatal cardiac surgical programs, with ongoing quality improvement processes.

    View details for DOI 10.1007/s00246-021-02586-1

    View details for PubMedID 33870440

  • 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


    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

  • Blood pressure goals: Is cerebral saturation the new mean arterial pressure? American journal of perinatology McKim, K. J., Lucafo, S., Bhombal, S., Bain, L., Chock, V. Y. 2021


    To correlate hypotension and cerebral saturation from near-infrared spectroscopy (cNIRS) in neonates on dopamine.Retrospective review of neonates receiving dopamine between August 2018-2019 was performed. Hypotension thresholds included mean arterial pressure (MAP) of postmenstrual age (PMA) ± 5mmHg, 30mmHg, and gestational age (GA) ± 5mmHg. Time below threshold MAP was compared to time with cerebral hypoxia (cNIRS <55%).Hypotension occurred 6-33% of time on dopamine in 59 cases. Hypotension did not correlate with abnormal cNIRS overall, within PMA subgroups, or by outcomes. Hypotensive periods with MAP

    View details for DOI 10.1055/a-1704-1851

    View details for PubMedID 34814195

  • Where Does Innovation in Critical Care Ultrasound Come From? Perhaps a Look in the Mirror. Pediatric critical care medicine : a journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies Su, E., Bhombal, S., Fraga, M. V. 2020; 21 (10): 919–20

    View details for DOI 10.1097/PCC.0000000000002445

    View details for PubMedID 33009311

  • Comprehensive Echocardiographic Assessment of Ventricular Function and Pulmonary Pressure in the Neonatal Omphalocele Population. American journal of perinatology Dal Col, A. K., Bhombal, S., Tacy, T. A., Hintz, S. R., Feinstein, J., Altit, G. 2020


    OBJECTIVE: Pulmonary hypertension (PH) has been described in the neonatal omphalocele population. This study was aimed to describe cardiac function and PH severity using echocardiography in newborns with giant omphalocele (GO) and with non-GO and determine if right ventricular (RV) dysfunction is associated with mortality.STUDY DESIGN: Retrospective, single-center analysis of first echocardiography among neonatal omphalocele patients born between 2004 and 2017 was conducted. Multivariate logistic and univariate Cox's regression was constructed to measure hazard ratio (HR) for death outcome.RESULTS: There were 32 newborns, of whom 18 were GO and 7 died. GO had increased systolic pulmonary arterial to systolic systemic blood pressure ratio (97% [isosystemic] vs. 73% [three-fourths systemic] p=0.03). RV performance parameters (tricuspid annular plane excursion, HR=0.40; fractional area change, HR=0.90; and RV peak global longitudinal strain, HR=1.39) were associated with mortality. These RV performance parameters remained associated in a multiple logistic regression accounting for gestational age and GO status. The overall population had abnormal eccentricity index and pulmonary artery acceleration time to RV ejection time ratio, two markers of PH.CONCLUSION: Patients with omphalocele have increased pulmonary pressure, with GO being worse than non-GO. RV dysfunction at initial echocardiography was significantly associated with mortality.

    View details for DOI 10.1055/s-0040-1708048

    View details for PubMedID 32198744

  • Diminished right ventricular function at diagnosis of pulmonary hypertension is associated with mortality in bronchopulmonary dysplasia. Pulmonary circulation Altit, G., Bhombal, S., Feinstein, J., Hopper, R. K., Tacy, T. A. 2019; 9 (3): 2045894019878598


    Pulmonary vascular disease and resultant pulmonary hypertension (PH) have been increasingly recognized in the preterm population, particularly among patients with bronchopulmonary dysplasia (BPD). Limited data exist on the impact of PH severity and right ventricular (RV) dysfunction at PH diagnosis on outcome. The purpose of this study was to evaluate if echocardiography measures of cardiac dysfunction and PH severity in BPD-PH were associated with mortality. The study is a retrospective analysis of the echocardiography at three months or less from time of PH diagnosis. Survival analysis using a univariate Cox proportional hazard model is presented and expressed using hazard ratios (HR). We included 52 patients with BPD and PH of which 16 (31%) died at follow-up. Average gestational age at birth was 26.3 ± 2.3 weeks. Echocardiography was performed at a median of 43.3 weeks (IQR: 39.0-54.7). The median time between PH diagnosis and death was 117 days (range: 49-262 days). Multiple measures of PH severity and RV performance were associated with mortality (sPAP/sBP: HR 1.02, eccentricity index: HR 2.02, tricuspid annular plane systolic excursion Z-score: HR 0.65, fractional area change: HR 0.88, peak longitudinal strain: HR 1.22). Hence, PH severity and underlying RV dysfunction at PH diagnosis were associated with mortality in BPD-PH patients. While absolute estimation of pulmonary pressures is not feasible in every screening echocardiography, thorough evaluation of RV function and other markers of PH may allow to discriminate the most at-risk population and should be considered as standard add-ons to the current screening at 36 weeks.

    View details for DOI 10.1177/2045894019878598

    View details for PubMedID 31662848

    View details for PubMedCentralID PMC6792284

  • Moving Beyond the Stethoscope: Diagnostic Point-of-Care Ultrasound in Pediatric Practice. Pediatrics Conlon, T. W., Nishisaki, A., Singh, Y., Bhombal, S., De Luca, D., Kessler, D. O., Su, E. R., Chen, A. E., Fraga, M. V. 2019


    Diagnostic point-of-care ultrasound (POCUS) is a growing field across all disciplines of pediatric practice. Machine accessibility and portability will only continue to grow, thus increasing exposure to this technology for both providers and patients. Individuals seeking training in POCUS should first identify their scope of practice to determine appropriate applications within their clinical setting, a few of which are discussed within this article. Efforts to build standardized POCUS infrastructure within specialties and institutions are ongoing with the goal of improving patient care and outcomes.

    View details for DOI 10.1542/peds.2019-1402

    View details for PubMedID 31481415

  • Diminished right ventricular function at diagnosis of pulmonary hypertension is associated with mortality in bronchopulmonary dysplasia PULMONARY CIRCULATION Altit, G., Bhombal, S., Feinstein, J., Hopper, R. K., Tacy, T. A. 2019; 9 (3)
  • Targeted neonatal echocardiography in the United States of America: the contemporary perspective and challenges to implementation PEDIATRIC RESEARCH Giesinger, R. E., Stanford, A. H., Rios, D. R., Bhombal, S., Fraga, M. V., Levy, V. Y., McNamara, P. J., Ashrafi, A., Backes, C., Bhombal, S., Fraga, M., Giesinger, R. E., Groves, A., Katheria, A., Leone, T., Levy, P. T., Levy, V. Y., Noori, S., McNamara, P. J., Rios, D. R., Ruoss, J. W., Vargas, D., US Hemodynamics Collaborative 2019; 85 (7): 919–21
  • Death or resolution: the "natural history" of pulmonary hypertension in bronchopulmonary dysplasia JOURNAL OF PERINATOLOGY Altit, G., Bhombal, S., Hopper, R. K., Tacy, T. A., Feinstein, J. 2019; 39 (3): 415–25
  • Targeted neonatal echocardiography in the United States of America: the contemporary perspective and challenges to implementation. Letter to the Editor. Pediatric research Giesinger, R., Stanford, A., Rios, D., Bhombal, S., Fraga, M., Levy, V., McNamara, P., United States Hemodynamics Collaborative 2019

    View details for PubMedID 30776791

  • Death or resolution: the "natural history" of pulmonary hypertension in bronchopulmonary dysplasia. Journal of perinatology : official journal of the California Perinatal Association Altit, G., Bhombal, S., Hopper, R. K., Tacy, T. A., Feinstein, J. 2019


    OBJECTIVES: The primary objective was to describe the early "natural history" of pulmonary hypertension (PH) in the premature population. The secondary objective was to describe factors associated with poor outcomes in the premature population with PH at 36 weeks post-menstrual age (PMA).STUDY DESIGN: Retrospective chart review of patients followed at our institution from 2000 to 2017 with echocardiographic (ECHO) evidence of PH at 36 weeks PMA, and born≤32 weeks estimated gestational age (GA). Cox regression was used for survival analysis.RESULTS: Sixty-one patients with PH (26.5±1.5 weeks at birth) were included. All PH patients had bronchopulmonary dysplasia (BPD), with 89% considered severe; 38% were small for gestational age. Necrotizing enterocolitis requiring surgery was common (25%). Use of post-natal steroids (HR 11.02, p=0.01) and increased severity of PH (HR 1.05, p<0.001) were associated with mortality. Pulmonary vein stenosis (PVS) was documented in 26% of the PH cohort, but not associated with increased mortality. ECHO estimation of pulmonary artery pressure (PAP) was available in 84%. PAP was higher in those who died (sPAP/sBP ratio 1.09±27 vs 0.83±20 %, p=0.0002). At follow-up (mean 250±186 weeks PMA), 72% of the PH cohort was alive. Most survivors (66%) had resolution of their PH on their most recent ECHO; 31% remained on PH therapy.CONCLUSION: PH resolved in most survivors in this study population. Mortality in those with BPD-PH was associated with male sex, post-natal steroid use, and increased severity of PH, but not with PVS.

    View details for PubMedID 30617286

  • PDA: To treat or not to treat Sankar, M. N., Bhombal, S., Benitz, W. E. WILEY. 2019: 46–51

    View details for DOI 10.1111/chd.12708

    View details for Web of Science ID 000459811500009

  • 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


    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

  • Immediate Postnatal Ventricular Performance Is Associated with Mortality in Hypoplastic Left Heart Syndrome PEDIATRIC CARDIOLOGY Altit, G., Bhombal, S., Chock, V. Y., Tacy, T. A. 2019; 40 (1): 168–76
  • Hemodynamic management in chronically ventilated infants. Seminars in fetal & neonatal medicine Bhombal, S. n., Noori, S. n. 2019: 101038


    Positive pressure ventilation can significantly alter hemodynamics. The reduction in systemic venous return and increase in right ventricular afterload in response to an inappropriately high mean airway pressure can decrease pulmonary blood flow and compromise systemic perfusion as a result. In addition to ventilator parameters, the degree of hemodynamic effects depends on the baseline cardiac function and lung compliance. Furthermore, the chronically ventilated infants often have a multitude of comorbidities which may also impact hemodynamics. These include pulmonary and systemic hypertension which can lead to myocardial dysfunction as a result of the increase in the right and left ventricular afterload, respectively. In this section, we aim to outline the hemodynamic changes associated with chronic lung disease and mechanical ventilation and discuss management options.

    View details for DOI 10.1016/j.siny.2019.101038

    View details for PubMedID 31668736

  • PDA: To treat or not to treat. Congenital heart disease Sankar, M. N., Bhombal, S., Benitz, W. E. 2019; 14 (1): 46–51


    Management of patent ductus arteriosus in extremely preterm infants remains a topic of debate. Treatment to produce ductal closure was widely practiced until the past decade, despite lack of evidence that it decreases morbidities or mortality. Meta-analyses of trials using nonsteroidal anti-inflammatory drugs have shown effectiveness in accelerating ductal closure, but no reduction in neonatal morbidities, regardless of agent used, indication, timing, gestational age, or route of administration. Surgical ligation closes the ductus but is associated with adverse effects. Recent experience with conservative approaches to treatment suggest improved neonatal outcomes and a high rate of spontaneous ductal closure after discharge. Careful postdischarge follow-up is important, however, because potential adverse effects of long-standing aortopulmonary shunts may be an indication for catheter-based ductal closure. Identification of extremely preterm infants at greatest risk of potential harm from a persistently patent ductus, who may benefit most from treatment are urgently needed.

    View details for PubMedID 30811796

  • Immediate Postnatal Ventricular Performance Is Associated with Mortality in Hypoplastic Left Heart Syndrome. Pediatric cardiology Altit, G., Bhombal, S., Chock, V. Y., Tacy, T. A. 2018


    Right ventricular (RV) function as assessed by deformation has been evaluated prenatally and after palliation in hypoplastic left heart syndrome (HLHS). However, limited data exist about the immediate postnatal cardiac adaptation and RV function in HLHS. We compared echocardiographic measures of cardiac performance in HLHS versus controls in their first week of life. As a secondary objective, we evaluated if markers at the first echocardiogram were associated with mid- and long-term outcomes. Clinical and echocardiographic data of patients with HLHS between 2013 and 2016 were reviewed. The study population was matched with controls whose echocardiograms were obtained due to murmur or rule out coarctation. Speckle-tracking echocardiography was used to assess deformation. Thirty-four patients with HLHS and 28 controls were analyzed. Age at echocardiogram was similar between HLHS and controls. The RV of HLHS was compared to both RV and left ventricle (LV) of controls. HLHS deformation parameters [RV peak global longitudinal strain (GLS), global longitudinal strain rate (GLSR)] and tricuspid annular plane systolic excursion (TAPSE) were decreased compared to RV of controls. The LV-fractional area change, peak GLS, GLSR, circumferential strain, and strain rate of controls were higher than the RV of HLHS. Calculated cardiac output (CO) was higher in the HLHS group (592 vs. 183mL/kg/min, p=0.0001) but similar to the combined LV and RV output of controls. Later mortality or cardiac transplantation was associated with the RV CO and RV stroke distance at initial echocardiogram. Cox proportional hazard regression determined that restriction at atrial septum, decreased initial RV stroke distance and decreased TAPSE had a higher risk of death or cardiac transplantation. TAPSE and RV stroke distance by velocity time integral had adequate inter-reader variability by Bland-Altman plot and Pearson's correlation. Our study found that the HLHS RV deformation is decreased in the early postnatal period when compared to both LV and RV of controls, but deformation was not associated with mid- and long-term outcomes. Later mortality or cardiac transplantation was associated with decreased initial stroke distance and cardiac output. Early evaluation of patients with HLHS should include an assessment of stroke distance and future research should evaluate its implication in management strategies.

    View details for PubMedID 30178190

  • Diminished Cardiac Performance and Left Ventricular Dimensions in Neonates with Congenital Diaphragmatic Hernia PEDIATRIC CARDIOLOGY Altit, G., Bhombal, S., Van Meurs, K., Tacy, T. A. 2018; 39 (5): 993–1000


    Newborns with congenital diaphragmatic hernia (CDH) have varying degrees of pulmonary hypoplasia and pulmonary hypertension (PH), and there is limited evidence that cardiac dysfunction is present. We sought to study early neonatal biventricular function and performance in these patients by reviewing early post-natal echocardiography (ECHO) measurements and comparing them to normal term newborns.Retrospective case-control study reviewing clinical and ECHO data on term newborns with CDH and normal controls born between 2009 and 2016. Patients were excluded if major anomalies, genetic syndromes, or no ECHO available. PH was assessed by ductal shunting and tricuspid regurgitant jet velocity. Speckle-tracking echocardiography was used to assess myocardial deformation using velocity vector imaging.Forty-four patients with CDH and 18 age-matched controls were analyzed. Pulmonary pressures were significantly higher in the CDH cohort (systolic pulmonary arterial pressure to systolic blood pressure of 103 ± 13 vs. 78 ± 29%, p = 0.0001). CDH patients had decreased RV fractional area change (FAC - 28.6 ± 11.1 vs. 36.2 ± 9.6%, p = 0.02), tricuspid annular plane of systolic excursion (TAPSE-5.6 ± 1.6 vs. 8.6 ± 1.6 mm, p = 0.0001), and RV outflow tract stroke distance (8.6 ± 2.7 vs. 14.0 ± 4.5 cm, p = 0.0001) compared with controls. The left ventricular (LV) ejection fraction was similar in both groups, but CDH patients had a decreased LV end-diastolic volume by Simpson's rule (2.7 ± 1.0 vs. 5.0 ± 1.8 mL, p = 0.0001) and LVOT stroke distance (9.7 ± 3.4 vs. 12.6 ± 3.6 cm, p = 0.004). Biventricular global longitudinal strain (GLS) was markedly decreased in the CDH population compared to controls (RV-GLS: - 9.0 ± 5.3 vs. - 19.5 ± 1.4%, p = 0.0001; LV GLS: - 13.2 ± 5.8 vs. - 20.8 ± 3.5%, p = 0.0001).CDH newborns have evidence of biventricular dysfunction and decreased cardiac output. Abnormal function may be a factor in the non-response to pulmonary arterial vasodilators in CDH patients. A two-pronged management strategy aimed at improving cardiac function, as well as reducing pulmonary artery pressure in CDH newborns, may be warranted.

    View details for PubMedID 29523920

  • End-Organ Saturation Differences in Early Neonatal Transition for Left-versus Right-Sided Congenital Heart Disease NEONATOLOGY Altit, G., Bhombal, S., Tacy, T. A., Chock, V. Y. 2018; 114 (1): 53–61


    For neonates with congenital heart disease (CHD), left-sided (LL) and right-sided (RL) single ventricular physiologies (LL, hypoplastic left heart syndrome; RL, tricuspid atresia or pulmonary atresia with intact ventricular septum) may demonstrate distinct changes in tissue saturation in the first 72 h of life. Near-infrared spectroscopy (NIRS) can measure regional cerebral saturation (Csat) and renal saturation (Rsat) to clarify differences between LL and RL over time.Our primary objective was to measure changes in Csat and Rsat in the first 72 h of life using NIRS between CHD infants with LL compared to RL. The secondary objective was to correlate NIRS values to an echocardiographic marker of perfusion.Newborns with hypoplastic left heart syndrome, tricuspid atresia, and pulmonary atresia with intact ventricular septum from 2013 to 2016 underwent routine NIRS monitoring. Csat, Rsat, and systemic saturations (SpO2) in the first 72 h of life were retrospectively analyzed and the echocardiographic descending aorta velocity time integral (VTI) was measured. Mixed effects models compared differences over time between LL and RL.The final cohort included 13 LL, 12 RL, and 4 controls. Csat decreased for RL compared to LL (p = 0.005), while Rsat decreased for both (p = 0.008). Over time, SpO2 increased for LL but decreased for RL (p = 0.046). Compared to the controls, infants with CHD had lower Csat, lower Rsat, and lower SpO2. The descending aorta VTI was correlated with Rsat (R2 = 0.24, p = 0.02).NIRS Csat measures were better preserved in LL compared to RL. Rsat decreased in both groups through time. The correlation between the descending aorta VTI and Rsat suggests an association between NIRS measures of renal saturation and renal perfusion.

    View details for PubMedID 29649824

  • Ventricular Performance is Associated with Need for Extracorporeal Membrane Oxygenation in Newborns with Congenital Diaphragmatic Hernia JOURNAL OF PEDIATRICS Altit, G., Bhombal, S., Van Meurs, K., Tacy, T. A. 2017; 191: 28-+
  • Ventricular Performance is Associated with Need for Extracorporeal Membrane Oxygenation in Newborns with Congenital Diaphragmatic Hernia. The Journal of pediatrics Altit, G., Bhombal, S., Van Meurs, K., Tacy, T. A. 2017


    OBJECTIVE: To compare echocardiography (ECHO) findings of patients with congenital diaphragmatic hernia (CDH) who required extracorporeal membrane oxygenation (ECMO) to non-ECMO treated patients.STUDY DESIGN: We reviewed clinical and ECHO data of newborns with CDH born between 2009 and 2016. Exclusions included major anomalies, genetic syndromes, or no ECHO prior to ECMO. Pulmonary hypertension was assessed by ductal shunting and tricuspid regurgitant jet. Speckle tracking echocardiography (STE) assessed function by quantifying deformation.RESULTS: Patients with CDH (15 ECMO and 29 with no ECMO) were analyzed. Most patients had a left CDH (88.6%). Age at ECHO was similar between groups. Outborn status (P=.009) and liver position (P=.009) were associated with need for ECMO. Compared with non-ECMO patients, patients who required ECMO had significantly decreased left and right ventricular function by both conventional and STE measures, as well as decreased right and left ventricular output. The right ventricular eccentricity index was higher in ECMO vs non-ECMO patients (2.2 vs 1.8, P=.02). There was no difference in pulmonary hypertension between CDH groups.CONCLUSIONS: Need for ECMO was associated with decreased left and right ventricular function, as assessed by standard and STE measures. There was no difference in pulmonary hypertension between non ECMO and ECMO patients. Abnormal cardiac function may explain nonresponse to pulmonary vasodilators in patients with CDH. Management strategies to improve cardiac function may reduce the need for ECMO in newborns with CDH.

    View details for PubMedID 29037794

  • The use of non-steroidal anti-inflammatory drugs for patent ductus arteriosus closure in preterm infants SEMINARS IN FETAL & NEONATAL MEDICINE Benitz, W. E., Bhombal, S. 2017; 22 (5): 302–7


    Over the last four decades, non-steroidal anti-inflammatory drugs have been widely used to induce closure of the patent ductus arteriosus (PDA) in preterm infants. Evidence to support this practice is lacking, despite performance of >50 randomized trials. The credibility of those trials may have been compromised by high rates of open treatment in controls, era of study prior to advent of modern practices, or inclusion of insufficient numbers of very immature infants. Meta-analyses show little impact of those factors on main conclusions. Essentially all trials reporting important long-term outcomes (other than mortality) initiated treatment within five days after birth, so no evidence regarding later treatment is available. Accruing clinical experience suggests that long-term outcomes are not compromised, and may be improved, with non-interventional management strategies. Future studies to identify preterm infants at greatest risk of potential harm from a persistent PDA, particularly after the second postnatal week, are urgently needed.

    View details for PubMedID 28724506

  • Prophylactic Indomethacin-Is It Time to Reconsider? JOURNAL OF PEDIATRICS Bhombal, S., Benitz, W. E. 2017; 187: 8–10

    View details for PubMedID 28552451

  • Practices surrounding pulmonary hypertension and bronchopulmonary dysplasia amongst neonatologists caring for premature infants. Journal of perinatology : official journal of the California Perinatal Association Altit, G. n., Lee, H. C., Hintz, S. n., Tacy, T. A., Feinstein, J. A., Bhombal, S. n. 2017


    Pulmonary hypertension (PH) is associated with bronchopulmonary dysplasia (BPD). Screening strategies, a thorough investigation of co-morbidities, and multidisciplinary involvement prior to anti-PH medications have been advocated by recent guidelines. We sought to evaluate current practices of neonatologists caring for premature infants with PH.Electronic survey of American Academy of Pediatrics neonatology members.Among 306 neonatologist respondents, 38% had an institutional screening protocol for patients with BPD; 83% screened at 36 weeks for premature neonates on oxygen/mechanical ventilation. In those practicing more than 5 years, 54% noted increasing numbers of premature infants diagnosed with PH. Evaluation for PH in BPD patients included evaluations for micro-aspiration (41%), airways anomalies (29%), and catheterization (10%). Some degree of acquired pulmonary vein stenosis was encountered in 47%. A majority (90%) utilized anti-PH medications during the neonatal hospitalization.Screening for PH in BPD, and subsequent evaluation and management is highly variable.

    View details for PubMedID 29234146