In this study, we investigated the clinical utility of Doppler echocardiography to estimate sPAP and to determine the presence and severity of PH in young children with neonatal CLD. We found that estimation of sPAP with echocardiography on the basis of the presence of adequate TRJV measurements was possible for 61% of infants with CLD. As used in typical clinical practice, however, echocardiographic estimates of sPAP correlated poorly with measurements of sPAP obtained with subsequent cardiac catheterization. Estimates of sPAP diagnosed the presence or absence of PH correctly in 79% of the studies in which a TRJV was detected. However, echocardiography was able to determine the severity of PH correctly in only 47% of those studies. Estimations of presence of adequate TRJV measurements was possible for 61% of infants with CLD. As used in typical clinical practice, however, echocardiographic estimates of sPAP correlated poorly with measurements of sPAP obtained with subsequent cardiac catheterization. Estimates of sPAP diagnosed the presence or absence of PH correctly in 79% of the studies in which a TRJV was detected. However, echocardiography was able to determine the severity of PH correctly in only 47% of those studies. Estimations of sPAP with echocardiography produced errors in both directions, failing to diagnose PH in 11% of studies in which PH was diagnosed with cardiac catheterization and inaccurately diagnosing PH in 11% of studies in which no PH was determined with cardiac catheterization. In the absence of a measurable TRJV, qualitative echocardiographic findings, including right atrial enlargement, right ventricular hypertrophy, right ventricular dilation, PA dilation, and septal flattening, either alone or in combination, have relatively poor predictive value. We found that, when the TRJV can be measured, echocardiography may be a useful screening tool for PH detection, but assessments of PH severity are unreliable in young children with CLD.
As applied in clinical practice, echocardiography is used to determine the presence and severity of PH or to monitor patients with known PH. For older patients with PH, serial determinations of functional class and exercise capacity and routine right heart catheterization are recommended to guide therapy.14
The inability to assess functional class and exercise capacity in young children and the reluctance of many physicians to perform right heart catheterizations in these children further complicate decision-making regarding the management of PH in CLD. Therefore, practitioners have relied more on echocardiographic findings in this population, not only to screen and to diagnose PH but also to monitor disease progression and to assess responses to therapy. Confusing this issue further is the lack of a data-derived definition of PH and a known basal level of PA pressure above which predictable consequences occur. Therefore, defining the levels of PA pressure to identify the presence and severity of PH and to guide therapy remains uncertain.14
We chose to use the commonly accepted cutoff value of mPAP of >25 mm Hg, as determined with cardiac catheterization, to define PH.15
Although echocardiography-estimated sPAP of >35 mm Hg has been used to define PH, we used the more-conservative cutoff value of >40 mm Hg to eliminate possible false-positive results.16
Estimated sPAP derived from the TRJV has become one of the most often used echocardiographic findings for evaluation of PH in adults with heart disease or idiopathic PA hypertension.5–8
Those studies showed excellent correlation coefficients (r
= 0.93–0.97), in comparison with the standard cardiac catheterization measurements. Such studies are extremely limited for children <2 years of age and have been performed only in patients with congenital heart disease.7, 12
Those studies evaluated echocardiography and cardiac catheterization performed simultaneously under the same hemodynamic conditions, eliminating differences in sedation level, oxygenation, and ventilator support and significant time intervals between studies. Although previous studies of children with PH showed better correlation between echocardiography-estimated sPAP and the cardiac catheterization measurement, previous studies represent the best possible performance of echocardiography under ideal conditions, not as applied in routine clinical practice as in the present study.
Although the time interval between echocardiography and cardiac catheterization can be considered a limitation of this study, a strength of the current study is evaluation of these tests as actually applied in clinical practice. Patients included in this study received similar levels of support and treatment at the times of echocardiography and cardiac catheterization. There were no detectable differences in medications or fluid status between the studies. In comparison with echocardiography, however, patients were treated longer by the time cardiac catheterization was performed. Whether the additional treatment time could alter hemodynamic factors to a significant degree is unclear. Although the time interval between studies ranged from 0 days to 57 days, when the data were reanalyzed to reduce the interval between echocardiography and cardiac catheterization to ≤10 days, the correlation and accuracy between the measurements did not improve. Another factor that might have contributed to the differing results is that fact that most patients who did not require mechanical ventilatory support at baseline were evaluated with cardiac catheterization under general anesthesia. Although an effort was made to maintain the preexisting goals for oxygenation and ventilation, subtle changes in gas exchange during anesthesia with mechanical ventilation and differing levels of oxygen supplementation could have led to changes in the assessed hemodynamic variables. Differences in the sedation levels of patients undergoing echocardiography and cardiac catheterization might further limit the comparability of the assessed hemodynamic values. In clinical decision-making, however, echocardiography and cardiac catheterization are generally interpreted with little regard to the level of sedation and its subsequent effect on hemodynamic factors. We chose to define the severity of PH on the basis of the pulmonary/systemic pressure ratio, rather than absolute PA pressure, to limit the potential impact of sedation on hemodynamic factors.
A few studies specifically evaluated echocardiography-estimated sPAP in adults with CLD, most with chronic obstructive pulmonary disease.17–19
Those studies reported smaller proportions of patients in whom a TRJV could be measured and lower correlation coefficients between echocardiography-estimated sPAP and cardiac catheterization measurements, compared with adults with primary PH or heart disease. Echocardiography-estimated sPAP in that population also had poor accuracy.18,20
Echocardiography was able to detect a measurable TRJV in 61% of our patients, but estimates of sPAP had both poor correlation and poor accuracy for determining PH severity, compared with values measured with subsequent cardiac catheterization. The ability to estimate sPAP in this study was greater than that reported in a study of premature infants with established CLD (31%), in which 79% of studies revealed PH.21
It has been postulated that factors associated with CLD, specifically marked pulmonary hyperinflation, expansion of the thoracic cage, and alteration of the position of the heart, adversely affect the ability to detect and to measure TRJV.18
These mechanisms may also apply to children with CLD, especially infants with BPD and those requiring mechanical ventilation. It was also reported that tricuspid regurgitation is not always present, even in neonates with systemic pressure-level PA pressures,22
which was confirmed in this study.
The ability to estimate sPAP accurately through echocardiography depends on the quality of the tricuspid regurgitant jet. Doppler recording of the frequency spectrum of a tricuspid regurgitation jet optimally shows a smooth, sharply demarcated envelope. In some patients, however, this frequency spectrum is incomplete and its envelope is poorly demarcated. Such inadequate signals may not allow reliable measurement of the spectrum's peak velocity, yielding imprecise estimates of sPAP. Clinical documentation of the quality of the envelope from which the TRJV is measured may be lacking or may not be well understood by noncardiologists, limiting proper interpretation of the estimated sPAP. We recommend close communication with the consulting cardiologist to determine the reliability of the tricuspid regurgitant jet envelope and the subsequently estimated sPAP.
Because the tricuspid regurgitant jet is not always present or measurable, qualitative echocardiographic measures of PH, such as right atrial enlargement, right ventricular hypertrophy, right ventricular dilation, PA dilation, and septal flattening, have been used as non-invasive screening tools. These measurements, with the exception of PA dilation, seem to have good sensitivity and positive predictive value for diagnosing PH in children with CLD, but specificity and negative predictive value are poor. Furthermore, for patients in whom a tricuspid regurgitant jet was not measurable, qualitative measures were less reliable, which suggests that the ability to estimate sPAP may influence the subjective assessment of these parameters. Several studies have used right ventricular outflow patterns or time intervals obtained with echocardiography to estimate PA pressures and to diagnose PH in children,11,23–28
with limited success, especially in children with CLD.26,28
Interestingly, 68% of children in this study had a history of a shunt lesion, and shunt lesions, primarily atrial shunts, were detected in 58% of the patients. Whether the presence of shunt lesions contributed to the decision to evaluate these patients with cardiac catheterization, accelerated changes of pulmonary vascular disease, or both, is unclear. Although there is limited evidence to describe accurately the prevalence of shunt lesions in neonatal patients with CLD,29
the observations of this study raise the possibility that patients with CLD who have shunt lesions may be at increased risk for pulmonary vascular disease and PH. Additional studies on the impact of left-to-right shunt lesions in children with CLD, as well as early treatment for pulmonary overcirculation, should be evaluated.
There are several other limitations to this study. First, the patients described in this study clearly represent a group of children with severe lung disease, with more than two thirds of patients being hospitalized and more than one half of the patients requiring mechanical ventilation at the time of study. Echocardiographic findings may be more accurate in young children with less-severe lung disease but, because many such children do not undergo cardiac catheterization, it is difficult to make that assessment. The high prevalence of PH in this study also makes it difficult to assess the negative predictive value of echocardiography as used in clinical practice, where the prevalence is assumed to be lower. Because patients with normal or mildly abnormal echocardiographic findings rarely are referred for cardiac catheterization, it is difficult to evaluate the false-negative rate of echocardiography in this group.