Browsing by Author "Hamvas, Aaron"

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    Maturational Patterns of Systolic Ventricular Deformation Mechanics by Two-Dimensional Speckle Tracking Echocardiography in Preterm Infants over the First Year of Age
    (Elsevier, 2017-07) Levy, Philip T.; EL-Khuffash, Afif; Patel, Meghna D.; Breatnach, Colm R.; James, Adam T.; Sanchez, Aura A.; Abuchabe, Cristina; Rogal, Sarah R.; Holland, Mark R.; McNamara, Patrick J.; Jain, Amish; Franklin, Orla; Mertens, Luc; Hamvas, Aaron; Singh, Gautam K.; Radiology and Imaging Sciences, School of Medicine
    BACKGROUND: The aim of this study was to determine the maturational changes in systolic ventricular strain mechanics by two-dimensional speckle-tracking echocardiography in extremely preterm neonates from birth to 1 year of age and discern the impact of common cardiopulmonary abnormalities on the deformation measures. METHODS: In a prospective multicenter study of 239 extremely preterm infants (<29 weeks gestation at birth), left ventricular (LV) global longitudinal strain (GLS) and global longitudinal systolic strain rate (GLSRs), interventricular septal wall (IVS) GLS and GLSRs, right ventricular (RV) free wall longitudinal strain and strain rate, and segmental longitudinal strain in the RV free wall, LV free wall, and IVS were serially measured on days 1, 2, and 5 to 7, at 32 and 36 weeks postmenstrual age, and at 1 year corrected age (CA). Premature infants who developed bronchopulmonary dysplasia or had echocardiographic findings of pulmonary hypertension were analyzed separately. RESULTS: In uncomplicated preterm infants (n = 103 [48%]), LV GLS and GLSRs remained unchanged from days 5 to 7 to 1 year CA (P = .60 and P = .59). RV free wall longitudinal strain, RV free wall longitudinal strain rate, and IVS GLS and GLSRs significantly increased over the same time period (P < .01 for all measures). A significant base-to-apex (highest to lowest) segmental longitudinal strain gradient (P < .01) was seen in the RV free wall and a reverse apex-to-base gradient (P < .01) in the LV free wall. In infants with bronchopulmonary dysplasia and/or pulmonary hypertension (n = 119 [51%]), RV free wall longitudinal strain and IVS GLS were significantly lower (P < .01), LV GLS and GLSRs were similar (P = .56), and IVS segmental longitudinal strain persisted as an RV-dominant base-to-apex gradient from 32 weeks postmenstrual age to 1 year CA. CONCLUSIONS: This study tracks the maturational patterns of global and regional deformation by two-dimensional speckle-tracking echocardiography in extremely preterm infants from birth to 1 year CA. The maturational patterns are ventricular specific. Bronchopulmonary dysplasia and pulmonary hypertension leave a negative impact on RV and IVS strain, while LV strain remains stable.
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    Prematurity and respiratory outcomes program (PROP): study protocol of a prospective multicenter study of respiratory outcomes of preterm infants in the United States
    (BioMed Central, 2015-04) Pryhuber, Gloria S.; Maitre, Nathalie L.; Ballard, Roberta A.; Cifelli, Denise; Davis, Stephanie D.; Ellenberg, Jonas H.; Greenberg, James M.; Kemp, James; Mariani, Thomas J.; Panitch, Howard; Ren, Clement; Shaw, Pamela; Taussig, Lynn M.; Hamvas, Aaron; Department of Pediatrics, Indiana University School of Medicine
    Background With improved survival rates, short- and long-term respiratory complications of premature birth are increasing, adding significantly to financial and health burdens in the United States. In response, in May 2010, the National Institutes of Health (NIH) and the National Heart, Lung, and Blood Institute (NHLBI) funded a 5-year $18.5 million research initiative to ultimately improve strategies for managing the respiratory complications of preterm and low birth weight infants. Using a collaborative, multi-disciplinary structure, the resulting Prematurity and Respiratory Outcomes Program (PROP) seeks to understand factors that correlate with future risk for respiratory morbidity. Methods/Design The PROP is an observational prospective cohort study performed by a consortium of six clinical centers (incorporating tertiary neonatal intensive care units [NICU] at 13 sites) and a data-coordinating center working in collaboration with the NHLBI. Each clinical center contributes subjects to the study, enrolling infants with gestational ages 23 0/7 to 28 6/7 weeks with an anticipated target of 750 survivors at 36 weeks post-menstrual age. In addition, each center brings specific areas of scientific focus to the Program. The primary study hypothesis is that in survivors of extreme prematurity specific biologic, physiologic and clinical data predicts respiratory morbidity between discharge and 1 year corrected age. Analytic statistical methodology includes model-based and non-model-based analyses, descriptive analyses and generalized linear mixed models. Discussion PROP incorporates aspects of NICU care to develop objective biomarkers and outcome measures of respiratory morbidity in the <29 week gestation population beyond just the NICU hospitalization, thereby leading to novel understanding of the nature and natural history of neonatal lung disease and of potential mechanistic and therapeutic targets in at-risk subjects.
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    Pulmonary Artery Acceleration Time Provides a Reliable Estimate of Invasive Pulmonary Hemodynamics in Children
    (Elsevier, 2016-11) Levy, Philip T; Patel, Meghna D; Groh, Georgeann; Choudhry, Swati; Murphy, Joshua; Holland, Mark R; Hamvas, Aaron; Grady, Mark R.; Singh, Gautam K; Radiology and Imaging Sciences, School of Medicine
    Background Pulmonary artery acceleration time (PAAT) is a non-invasive method to assess pulmonary hemodynamics, but lacks validity in children. This study sought to evaluate the accuracy of Doppler echocardiography (DE) derived PAAT in predicting right heart catheterization (RHC) derived pulmonary arterial pressure (PAP), pulmonary vascular resistance (PVR) and compliance in children. Methods Prospectively acquired and retrospectively measured DE derived PAAT and RHC derived systolic PAP (sPAP), mean PAP (mPAP), index PVR (PVRi) and compliance were compared by regression analysis in a derivation cohort of 75 children (median age, 5.3 years; 1.3–12.6) with wide ranges of pulmonary hemodynamics. To account for heart rate variability, PAAT was adjusted for right ventricle ejection time (RVET) and corrected by the RR interval. Regression equations incorporating PAAT and PAAT:RVET from the derivation cohort were then evaluated for the accuracy of its predictive values for invasive pulmonary hemodynamics in a validation cohort of 50 age- and weight- matched children with elevated PAP and PVR. Results There were significant inverse correlations between PAAT and RHC derived mPAP (r = −0.82) and PVRi (r= −0.78) and direct correlation (r= 0.78) between PAAT and pulmonary compliance in the derivation cohort. For detection of pulmonary hypertension (PRVi > 3 WU x m2 and mPAP > 25 mmHg), PAAT < 90 msec and PAAT:RVET < 0.31 resulted in a sensitivity of 97% and a specificity of 95%. In the derivation cohort, the regression equations relating PAAT with mPAP and PVRi were: mPAP = 48 – 0.28 x PAAT and PVRi = 9 –0.07 x PAAT. These PAAT integrated equations predicted RHC measured pulmonary hemodynamics in the validation cohort with good correlations (r = 0.88, 0.83 respectively), small biases (<10%), and minimal coefficient of variation (<8%). Conclusions PAAT inversely correlates with RHC measured pulmonary hemodynamics and directly correlates with pulmonary arterial compliance in children. The study established PAAT based regression equations in children to accurately predict RHC derived PAP and PVR.
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    Reference Ranges of Left Ventricular Strain Measures by Two-Dimensional Speckle-Tracking Echocardiography in Children: A Systematic Review and Meta-Analysis
    (Elsevier, 2016-03) Levy, Philip T.; Machefsky, Aliza; Sanchez, Aura A.; Patel, Meghna D.; Rogal, Sarah; Fowler, Susan; Yaeger, Lauren; Hardi, Angela; Holland, Mark R.; Hamvas, Aaron; Singh, Gautam K.; Department of Radiology and Imaging Sciences, IU School of Medicine
    BACKGROUND: Establishment of the range of reference values and associated variations of two-dimensional speckle-tracking echocardiography (2DSTE)-derived left ventricular (LV) strain is a prerequisite for its routine clinical adoption in pediatrics. The aims of this study were to perform a meta-analysis of normal ranges of LV global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) measurements derived by 2DSTE in children and to identify confounding factors that may contribute to variance in reported measures. METHODS: A systematic review was launched in MEDLINE, Embase, Scopus, the Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Library. Search hedges were created to cover the concepts of pediatrics, STE, and left-heart ventricle. Two investigators independently identified and included studies if they reported 2DSTE-derived LV GLS, GCS, or GRS. The weighted mean was estimated by using random effects models with 95% CIs, heterogeneity was assessed using the Cochran Q statistic and the inconsistency index (I(2)), and publication bias was evaluated using the Egger test. Effects of demographic (age), clinical, and vendor variables were assessed in a metaregression. RESULTS: The search identified 2,325 children from 43 data sets. The reported normal mean values of GLS among the studies varied from -16.7% to -23.6% (mean, -20.2%; 95% CI, -19.5% to -20.8%), GCS varied from -12.9% to -31.4% (mean, -22.3%; 95% CI, -19.9% to -24.6%), and GRS varied from 33.9% to 54.5% (mean, 45.2%; 95% CI, 38.3% to 51.7%). Twenty-six studies reported longitudinal strain only from the apical four-chamber view, with a mean of -20.4% (95% CI, -19.8% to -21.7%). Twenty-three studies reported circumferential strain (mean, -20.3%; 95% CI, -19.4% to -21.2%) and radial strain (mean, 46.7%; 95% CI, 42.3% to 51.1%) from the short-axis view at the midventricular level. A significant apex-to-base segmental longitudinal strain gradient (P < .01) was observed in the LV free wall. There was significant between-study heterogeneity and inconsistency (I(2) > 94% and P < .001 for each strain measure), which was not explained by age, gender, body surface area, blood pressure, heart rate, frame rate, frame rate/heart rate ratio, tissue-tracking methodology, location of reported strain value along the strain curve, ultrasound equipment, or software. The metaregression showed that these effects were not significant determinants of variations among normal ranges of strain values. There was no evidence of publication bias (P = .40). CONCLUSIONS: This study defines reference values of 2DSTE-derived LV strain in children on the basis of a meta-analysis. In healthy children, mean LV GLS was -20.2% (95% CI, -19.5% to -20.8%), mean GCS was -22.3% (95% CI, -19.9% to -24.6%), and mean GRS was 45.2% (95% CI, 38.3% to 51.7%). LV segmental longitudinal strain has a stable apex-to-base gradient that is preserved throughout maturation. Although variations among different reference ranges in this meta-analysis were not dependent on differences in demographic, clinical, or vendor parameters, age- and vendor-specific referenced ranges were established as well.
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    Urine Gastrin Releasing Peptide in the First Week Correlates with BPD and Post-Prematurity Respiratory Disease
    (Wiley, 2020-04) Voynow, Judith A.; Fisher, Kimberley; Sunday, Mary E.; Cotton, C. Michael; Hamvas, Aaron; Hendricks-Muñoz, Karen D.; Poindexter, Brenda B.; Pryhuber, Gloria S.; Ren, Clement L.; Ryan, Rita M.; Sharp, Jack K.; Young, Sarah P.; Zhang, Haoyue; Greenberg, Rachel G.; Herring, Amy H.; Davis, Stephanie D.; Pediatrics, School of Medicine
    Rationale: Bronchopulmonary dysplasia (BPD) is associated with post-prematurity respiratory disease (PRD) in survivors of extreme preterm birth. Identifying early biomarkers that correlate with later development of BPD and PRD may provide insights for intervention. In a preterm baboon model, elevated gastrin-releasing peptide (GRP) is associated with BPD, and GRP inhibition mitigates BPD occurrence. Objective: We performed a prospective cohort study to investigate whether urine GRP levels obtained in the first postnatal week were associated with BPD, PRD, and other urinary biomarkers of oxidative stress. Methods: Extremely low gestational age infants (23-28 completed weeks) were enrolled in a US multicenter observational study, The Prematurity and Respiratory Outcomes Program (http://clinicaltrials.gov/ct2/show/NCT01435187). We used multivariable logistic regression to examine the association between urine GRP in the first postnatal week and multiple respiratory outcomes: BPD, defined as supplemental oxygen use at 36 + 0 weeks postmenstrual age, and post-PRD, defined by positive quarterly surveys for increased medical utilization over the first year (PRD score). Results: A total of 109 of 257 (42%) infants had BPD, and 120 of 217 (55%) had PRD. On adjusted analysis, GRP level more than 80 was associated with BPD (adjusted odds ratio [aOR], 1.83; 95% confidence interval [CI], 1.03-3.25) and positive PRD score (aOR, 2.46; 95% CI, 1.35-4.48). Urine GRP levels correlated with duration of NICU ventilatory and oxygen support and with biomarkers of oxidative stress: allantoin and 8-hydroxydeoxyguanosine. Conclusions: Urine GRP in the first postnatal week was associated with concurrent urine biomarkers of oxidative stress and with later diagnoses of BPD and PRD.