Clinical Utility of Echocardiography in Former Preterm Infants with Bronchopulmonary Dysplasia

doi:10.1016/j.echo.2019.10.012

Journal of the American Society of Echocardiography

Volume 33, Issue 3, March 2020, Pages 378-388.e1

https://doi.org/10.1016/j.echo.2019.10.012 Get rights and content

Highlights

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Study of utility of echo in detecting pulmonary vascular resistance (PVRi) ≥3WU.
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Study includes infants with bronchopulmonary dysplasia (BPD) only.
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Doppler velocities or systolic septal flattening screen well for PVRi ≥3WU.
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Positive predictive value of echo is best in absence of post tricuspid valve shunt.
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Cardiac catheterization is still needed to measure the degree of PVRi elevation.

Background

The clinical utility of echocardiography for the diagnosis of pulmonary vascular disease (PVD) in former preterm infants with bronchopulmonary dysplasia (BPD) is not established. Elevated pulmonary vascular resistance (PVR) rather than pulmonary artery pressure (PAP) is the hallmark of PVD. We evaluated the utility of echocardiography in infants with BPD in diagnosing pulmonary hypertension and PVD (PVR >3 Wood units × m²) assessed by cardiac catheterization.

Methods

A retrospective single center study of 29 infants born ≤29 weeks of gestational age with BPD who underwent cardiac catheterization and echocardiography was performed. PVD was considered present by echocardiography if the tricuspid valve regurgitation jet peak velocity was >2.9 m/sec, post-tricuspid valve shunt systolic flow velocity estimated a right ventricular systolic pressure >35 mm Hg, or systolic septal flattening was present. The utility (accuracy, sensitivity, and positive predictive value [PPV]) of echocardiography in the diagnosis of PVD was tested. Subgroup analysis in patients without post-tricuspid valve shunts was performed. Echocardiographic estimations of right ventricular pressure, dimensions, function, and pulmonary flow measurements were evaluated for correlation with PVR.

Results

The duration between echocardiography and cardiac catheterization was a median of 1 day (interquartile range, 1-4 days). Accuracy, sensitivity, and PPV of echocardiography in diagnosing PVD were 72%, 90.5%, and 76%, respectively. Accuracy, sensitivity, and PPV increased to 93%, 91.7%, and 100%, respectively, when infants with post-tricuspid valve shunts were excluded. Echocardiography had poor accuracy in estimating the degree of PAP elevation by cardiac catheterization. In infants without post-tricuspid valve shunts, there was moderate to good correlation between indexed PVR and right ventricular myocardial performance index (rho = 0.89, P = .005), systolic to diastolic time index (0.84, P < .001), right to left ventricular diameter ratio at end systole (0.66, P = .003), and pulmonary artery acceleration time (0.48, P = .05).

Conclusions

Echocardiography performs well in screening for PVD in infants with BPD and may be diagnostic in the absence of a post-tricuspid valve shunt. However, cardiac catheterization is needed to assess the degree of PAP elevation and PVR. The diagnostic utility of echocardiographic measurements that correlate with PVR should be evaluated prospectively in this patient population.

Section snippets

Subject Enrollment

At the University of California, San Francisco, Benioff Children's Hospital, our practice is to screen premature infants with BPD for evidence of PH by serial echocardiograms. If an echocardiogram shows evidence of PH despite optimization of the patient's respiratory support, the patient undergoes cardiac catheterization prior to starting pulmonary vasodilator medications. Pulmonary vasodilator therapy is started prior to cardiac catheterization only in cases where it is deemed lifesaving or in

Results

The indication for cardiac catheterization in 25 (86%) patients was to assess for PVD, of which five patients were also suspected of having pulmonary vein stenosis. Three patients underwent catheterization for closure of their PDA, and one patient for closure of an ASD. The baseline demographic characteristics of the cohort are shown in Table 1. Median duration between the echocardiogram and cardiac catheterization was 1 day (IQR, 1, 4 days). All infants received the same pulmonary vasodilator

Discussion

In this study we found only fair to moderate agreement between an assessment of elevated PAP using multiple echocardiographic variables and classification of PH from catheter-based calculation of PVRi in former preterm infants with BPD. Further, we could not identify any substantial correlation between PVRi and multiple echocardiographic measurements of right heart and pulmonary vascular structure and function except after exclusion of data from patients with post-tricuspid valve shunts or

Conclusion

Echocardiography can be a useful screening tool for PVD in former preterm infants with BPD. Utility of echocardiography is limited for the presence or severity of PVD, however, when a post-tricuspid valve shunt is present. Our data suggest that cardiac catheterization remains an important diagnostic test to assess the severity of both PVD and PH using pressure criteria. Future studies should address the potential value of specific echocardiographic measurements for noninvasive assessment of

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Cited by (17)

Pulmonary Hypertension in Established Bronchopulmonary Dysplasia: Physiologic Approaches to Clinical Care
2024, Clinics in Perinatology
Bronchopulmonary dysplasia – associated pulmonary hypertension: An updated review
2023, Seminars in Perinatology
Bronchopulmonary dysplasia (BPD) is the leading cause of chronic lung disease in infants and the commonest complication of prematurity. Advances in respiratory and overall neonatal care have increased the survival of extremely low gestational age newborns, leading to the continued high incidence of BPD. Pulmonary hypertension (PH) represents the severe form of the pulmonary vascular disease associated with BPD, and affects almost one-third of infants with moderate to severe BPD. PH responds suboptimally to pulmonary vasodilators and increases morbidity and mortality in BPD infants. An up-to-date knowledge of the pathogenesis, pathophysiology, diagnosis, treatment, and outcomes of BPD-PH can be helpful to develop meaningful and novel strategies to improve the outcomes of infants with this disorder. Therefore, our multidisciplinary team has attempted to thoroughly review and summarize the latest advances in BPD-PH in preventing and managing this morbid lung disorder of preterm infants.
Pulmonary Vascular Phenotypes of Prematurity: The Path to Precision Medicine
2023, Journal of Pediatrics
Pulmonary hypertension (PH) is associated with significant morbidities and high mortality in preterm infants, yet mechanisms contributing to the pathogenesis of PH, the impact of early pulmonary vascular disease (PVD) on the risk for BPD, the role for PH-targeted drug therapies, and long-term pulmonary vascular sequelae remain poorly understood. PVD is not a homogeneous disease, rather, PVD in the setting of prematurity includes various phenotypes as based on underlying pathophysiology, the severity of associated PH, the timing of disease onset, its contribution to hemodynamic and respiratory status, late outcomes, and other features. As with term newborns, severe hypoxemia with acute respiratory failure (HRF) in preterm infants can be due to marked elevation of pulmonary artery pressure with extrapulmonary shunt, traditionally referred to as persistent pulmonary hypertension of the newborn (PPHN). Transient and less severe levels of PH can also be observed during the early transition after birth without evidence of severe HRF, representing physiologic PH or delayed pulmonary vascular transition in preterm infants. Importantly, echocardiographic evidence of early PH has been strongly associated with the subsequent development of bronchopulmonary dysplasia (BPD), late PH, and chronic respiratory disease during infancy and early childhood. Late PH beyond the first postnatal months in preterm in neonates with established BPD is further associated with poor outcomes, especially as related to BPD severity. In addition, echocardiographic signs of PVD can further persist throughout childhood and may lead to chronic PH of variable severity and cardiac maldevelopment in prematurely born young adults. This review discusses the importance of characterizing diverse pulmonary vascular phenotypes in preterm infants to better guide clinical care and research, and to enhance the development of more precise therapeutic strategies to optimize early and late outcomes of preterm infants.
Chronic Neonatal Respiratory Disorders
2023, Avery's Diseases of the Newborn
Chronic neonatal respiratory illness is marked by the intermediate outcome of bronchopulmonary dysplasia (BPD) and progresses through stages of elevated respiratory resource utilization and wheezing illness in infancy and early childhood, to chronic obstructive lung disease and wheeze and asthma in adolescence. Risk factors for BPD reflect impaired lung development at birth, including immaturity due to low gestational age and the consequences of an adverse fetal environment, associated with impaired placental function and fetal growth. Postnatal lung development in preterm newborns born with these vulnerabilities may be further impeded by exposure to supplemental oxygen and invasive mechanical ventilation, yet application of strategies to limit these exposures in the neonatal period have not translated broadly to later term benefit with respect to respiratory morbidity and carry some adverse consequences. Patterns of respiratory resource utilization and elevated prevalence of persistent wheezing illness in infancy in former preterm newborns portend later persistence of obstructive lung disease. Immune deficits related to degree of prematurity, infant lung dysfunction at hospital discharge, and well-known risks following discharge from environmental exposures such as tobacco smoke and pollutants likely confer susceptibility to lower respiratory tract infection and chronic obstructive airway disease in former premature newborns. Those infants and children born at extremely low gestational age and with more severe neonatal respiratory illness are at greatest risk for both near-term (BPD) and long-term consequences of dysplastic lung and airway development.
A Measurement-Based Protocol Improves Interrater Agreement and Accuracy of Right Ventricular Systolic Pressure Assessment by Echocardiography in Children: A Call for Quality Improvement
2022, Journal of the American Society of Echocardiography
Citation Excerpt :
This improvement in IR agreement was also accompanied by improvement in the agreement of RV systolic pressure estimates with RV systolic pressure measured invasively during cardiac catheterization. Therefore, there was improvement in bias as well as an improvement in IR agreement, which could be key to improving the well-documented misclassification of RV pressure by echocardiography in children.2,12,13 Our study supports the finding of fair IR agreement with subjective assessments of the RV noted by Smith et al.2 and improvements in the accuracy and IR agreement of the RV assessments reported in adult patients by Ling et al.3 after implementing measurement-based reporting.
Echocardiographic measurements carry the promise of improving interrater (IR) agreement over subjective assessment. The aim of this study was to assess the effect of implementing a measurement-based protocol on IR agreement and accuracy in reporting of right ventricular (RV) systolic pressure in children. The effect of this reporting protocol on IR agreement in reporting RV dilation, hypertrophy, and systolic function was also evaluated.
Five echocardiography readers reported their assessment of RV systolic pressure, dilation, hypertrophy, and systolic function on 40 deidentified echocardiograms using their individual accustomed methods and then using an agreed-upon protocol based solely on RV measurements. IR agreement was assessed using κ statistics. Accuracy of RV systolic pressure ratings was assessed using the McNemar test in comparison with hemodynamic data obtained by cardiac catheterization. The reliability of the RV measurements was assessed using intraclass correlation coefficient (ICC) and coefficient of variation.
IR agreement and accuracy of RV systolic pressure assessment improved after using the measurement-based protocol (agreement from 0.39 [95% CI, 0.27-0.5] to 0.62 [95% CI, 0.48-0.76] and accuracy from 18 of 40 to 29 of 40 [P = .03]). IR agreement of RV dilation improved (from 0.36 [95% CI, 0.25-0.48] to 0.63 [95% CI, 0.48-0.79]), while IR agreement of RV hypertrophy (from 0.29 [95% CI, 0.17-0.42] to 0.35 [95% CI, 0.15-0.55]) and RV systolic function (from 0.57 [95% CI, 0.45-0.69] to 0.53 [95% CI, 0.41-0.66]) did not improve. The reliability of the measurements was good (ICC > 0.8), except for RV free wall thickness (ICC = 0.62, coefficient of variation = 24%) and RV fractional area change (ICC = 0.47, coefficient of variation = 22%), suggesting a possible reason for the lack of improvement in IR agreement of RV hypertrophy and RV systolic function. Heteroscedasticity was observed in the reliability of RV measurements, with the ICC being significantly lower at larger magnitudes for all RV measurements.
Standardization of reporting protocols using RV measurements in place of subjective assessment improved IR agreement and accuracy of RV systolic pressure assessment. Reliable measurements (RV systolic pressure and dilation) resulted in improvement in IR agreement while unreliable measurements (RV hypertrophy and systolic function) did not. Special attention to measurements’ reliability and heteroscedasticity of reliability is required when designing clinical protocols to decrease IR disagreement as a source of error.
The Clinical and Cost Utility of Cardiac Catheterizations in Infants with Bronchopulmonary Dysplasia
2022, Journal of Pediatrics
Citation Excerpt :
The decision to initiate pulmonary hypertension-specific therapy in preterm infants with pulmonary hypertension associated with BPD has historically been gated by the acquisition of invasive hemodynamic data by cardiac catheterization. Because the echocardiographic assessment of pulmonary hypertension in this patient population has improved,2,8,12,44 and monotherapy sildenafil use in pediatrics has become more common,7,10 centers have now begun to initiate pulmonary hypertension-specific therapy based on echocardiography alone. However, controversy remains as consensus statements advocate for the clinical utility of invasive catheterization data.3,4,6
To evaluate the cost-utility of catheterization-obligate treatment in preterm infants with pulmonary hypertension, as compared with empiric initiation of sildenafil based on echocardiographic findings alone.
A Markov state transition model was constructed to simulate the clinical scenario of a preterm infant with echocardiographic evidence of pulmonary hypertension associated with bronchopulmonary dysplasia (BPD) and without congenital heart disease under consideration for the initiation of pulmonary vasodilator therapy via one of two modeled treatment strategies—empiric or catheterization-obligate. Transitional probabilities, costs and utilities were extracted from the literature. Forecast quality-adjusted life-years was the metric for strategy effectiveness. Sensitivity analyses for each variable were performed. A 1000-patient Monte Carlo microsimulation was used to test the durability of our findings.
The catheterization-obligate strategy resulted in an increased cost of $10 778 and 0.02 fewer quality-adjusted life-years compared with the empiric treatment strategy. Empiric treatment remained the more cost-effective paradigm across all scenarios modeled through one-way sensitivity analyses and the Monte Carlo microsimulation (cost-effective in 98% of cases).
Empiric treatment with sildenafil in infants with pulmonary hypertension associated with BPD is a superior strategy with both decreased costs and increased effectiveness when compared with catheterization-obligate treatment. These findings suggest that foregoing catheterization before the initiation of sildenafil is a reasonable strategy in preterm infants with uncomplicated pulmonary hypertension associated with BPD.

View all citing articles on Scopus

: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

: Conflicts of Interest: None.

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2019 by the American Society of Echocardiography.

Clinical InvestigationEchocardiography in ChildrenClinical Utility of Echocardiography in Former Preterm Infants with Bronchopulmonary Dysplasia

Highlights

Background

Methods

Results

Conclusions

Section snippets

Subject Enrollment

Results

Discussion

Conclusion

Am Heart J

Int J Cardiol

J Am Soc Echocardiogr

J Am Soc Echocardiogr

J Am Soc Echocardiogr

J Am Soc Echocardiogr

J Am Coll Cardiol

Am J Cardiol

J Am Soc Echocardiogr

Pediatric pulmonary hypertension: Guidelines from the American Heart Association and American Thoracic Society

Circulation

Pulmonary artery hypertension in formerly premature infants with bronchopulmonary dysplasia: clinical features and outcomes in the surfactant era

Pediatrics

Clinical Investigation
Echocardiography in Children
Clinical Utility of Echocardiography in Former Preterm Infants with Bronchopulmonary Dysplasia