Agreement of an echocardiogram-based diagnosis of pulmonary hypertension in infants at risk for bronchopulmonary dysplasia among masked reviewers

McCrary, Andrew W.; Barker, Piers; Török, Rachel D.; Spears, Tracy; Li, Jennifer S.; Hornik, Christoph P.; Laughon, Matthew M.

doi:10.1038/s41372-018-0277-6

Cited by 17 publications

(15 citation statements)

References 29 publications

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“…Tricuspid regurgitant jet velocity is used as a surrogate measure of pulmonary artery pressure, but if it is not sufficient to measure on echocardiogram, more qualitative measures, such as the position of the intraventricular septum or evaluation of right ventricular function are often interpreted. Scoring systems based on several qualitative and quantitative measures have been investigated with good intra-observer agreement, but results based on echocardiogram were not compared to the gold standard in PH diagnosis [9]. The gold standard for diagnosis of PH is cardiac catheterization, but it is often reserved for very severe cases or nonresponders.…”

Section: Pulmonary Hypertensionmentioning

confidence: 99%

Bronchopulmonary Dysplasia: a Multidisciplinary Approach to Management

Connors

Gibbs

2019

Curr Pediatr Rep

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Purpose of Review We aim to present the challenges in defining bronchopulmonary dysplasia (BPD) and summarize optimized management of established BPD in a multidisciplinary fashion. Recent Findings In the last few years, several meta-analyses assessing the treatment of BPD have been updated to assist in guiding clinical management. In addition, a new severity grading system was proposed at the National Institute of Child Health and Human Development (NICHD) BPD workshop with more objective criteria including commonly used modes of noninvasive respiratory support. Summary Although survival of infants born prematurely has improved over the last several decades, the incidence of BPD has remained unchanged. Defining BPD and stratifying its severity continue to be challenging for clinicians. Successful BPD management requires a multidisciplinary approach to optimize ventilator strategies, provide adequate nutrition, utilize pharmacotherapeutics in an evidence-based fashion, and screen for comorbidities.

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Section: Pulmonary Hypertensionmentioning

confidence: 99%

Bronchopulmonary Dysplasia: a Multidisciplinary Approach to Management

Connors

Gibbs

2019

Curr Pediatr Rep

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“…Recognizing this concern, the American Heart Association recommends screening echocardiography to monitor for PH in infants with BPD [5]. However, echocardiographic parameters are limited by subjective, varied, or missing measures, as well as modest correlation with pulmonary arterial pressure measured via cardiac catheterization [6][7][8][9]. Further, screening for PH often varies from center to center.…”

Section: Introductionmentioning

confidence: 99%

Utility of echocardiography in predicting mortality in infants with severe bronchopulmonary dysplasia

et al. 2019

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Objective To determine the relationship between interventricular septal position (SP) and right ventricular systolic pressure (RVSP) and mortality in infants with severe BPD (sBPD). Study design Infants with sBPD in the Children's Hospitals Neonatal Database who had echocardiograms 34-44 weeks' postmenstrual age (PMA) were included. SP and RVSP were categorized normal, abnormal (flattened/bowed SP or RVSP > 40 mmHg) or missing. Results Of 1157 infants, 115 infants (10%) died. Abnormal SP or RVSP increased mortality (SP 19% vs. 8% normal/ missing, RVSP 20% vs. 9% normal/missing, both p < 0.01) in unadjusted and multivariable models, adjusted for significant covariates (SP OR 1.9, 95% CI 1.2-3.0; RVSP OR 2.2, 95% CI 1.1-4.7). Abnormal parameters had high specificity (SP 82%; RVSP 94%), and negative predictive value (SP 94%, NPV 91%) for mortality. Conclusions Abnormal SP or RVSP is independently associated with mortality in sBPD infants. Negative predictive values distinguish infants most likely to survive.

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“…We have immediate plans to replicate this study in a larger and independent BPD cohort. Another major limitation has been the difficulty of diagnosing PH in neonates and infants, however bedside echocardiography is now the standard of care and serves as a useful and less-invasive tool to reliably diagnose neonatal PH (39).…”

Section: Discussionmentioning

confidence: 99%

Dual-specificity phosphatase (DUSP) genetic variants predict pulmonary hypertension in patients with bronchopulmonary dysplasia

et al. 2019

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Background Bronchopulmonary dysplasia (BPD) is a pediatric chronic lung disease. Pulmonary hypertension (PH) can develop in BPD, greatly increasing morbidity and mortality. PH is the result of decreased pulmonary vascular lumen diameter from vasoconstriction and/or vascular remodeling. Vasoconstriction and vascular remodeling result from activation of abnormal signal transduction cascades including the mitogen‐activated protein kinases (MAPK). MAPK deactivation is regulated by a family of phosphatases called the dual specificity phosphatases (DUSPs). In the present study, we hypothesized that (1) single nucleotide polymorphisms (SNPs) within the DUSP gene family are differentially expressed in a cohort of BPD patients with and without PH and that (2) DUSP SNPs, when combined with clinical data, could be useful as a biomarker for PH development in BPD patients. Methods BPD patients (n=188) who were born at <35 weeks gestation and enrolled at Nationwide Children's Hospital were studied. PH was defined by established echocardiographic criteria. DNA from patient blood samples was assayed for 31 SNPs in DUSP genes by Agena Massarray. DUSP SNPs were selected from NCBI database for their putative functionality. Clinical characteristics and minor allele frequencies (MAF) were compared between BPD‐PH (cases) and BPD alone (control) groups using t‐test or chi‐square as appropriate with p‐value <0.05 as significant. Biomarker models were analyzed by calculating area under the curve (AUC) for clinical and SNP data separately and together. Results In a cohort of 188 patients with BPD, 61 (32%) showed echocardiographic evidence of PH. Patients with BPD‐PH had a lower birthweight (806g ± 343g vs. 972g ± 414g, p=0.004), gestational age (262 ± 24 vs. 270 ± 25, p=0.041), and were more often small for gestational age (20% vs. 7%, p=0.010) than BPD alone patients. Patients with BPD‐PH received less surfactant (48% vs. 63%, p=0.044), more post‐natal pre‐admit steroids (33% vs. 12%, p=0.001), and more mechanical ventilation (92% vs. 73%, p=0.003) than BPD alone patients. Of the 31 DUSP SNPs evaluated, DUSP‐1 SNP rs322351 was less common in cases than controls (MAF; 0.32 vs. 0.44, p=0.021), and DUSP‐5 SNPs rs1042606 (MAF; 0.44 vs. 0.34, p=0.042) and rs3793892 (MAF; 0.42 vs. 0.32, p=0.049) were more common in cases than in controls. The best fit biomarker model combines clinical (birthweight<700g + post‐natal, preadmission steroids + mechanical ventilation + no surfactant) and SNP data (DUSP1 rs322351 + DUSP5 rs1042606) with AUC 0.76. Conclusions In the present study, we identified several potential clinical and genetic biomarkers for BPD‐PH patients including birthweight, gestational age, small for gestational age, surfactant, post‐natal pre‐admit steroids, mechanical ventilation, DUSP‐1 SNP rs322351, and DUSP‐5 SNPs rs1042606 and rs3793892. Combining clinical and DUSP‐1 SNP data yields the most robust biomarker for PH in BPD. Support or Funding Information This research was funded by the National Heart, Lung, and Blood Institute (Gran...

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Agreement of an echocardiogram-based diagnosis of pulmonary hypertension in infants at risk for bronchopulmonary dysplasia among masked reviewers

Cited by 17 publications

References 29 publications

Bronchopulmonary Dysplasia: a Multidisciplinary Approach to Management

Bronchopulmonary Dysplasia: a Multidisciplinary Approach to Management

Utility of echocardiography in predicting mortality in infants with severe bronchopulmonary dysplasia

Dual-specificity phosphatase (DUSP) genetic variants predict pulmonary hypertension in patients with bronchopulmonary dysplasia

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