© 2014, Wiley Periodicals, Inc. DOI: 10.1111/echo.12797
Echocardiography
ORIGINAL INVESTIGATION
Tricuspid Annular Plane Systolic Excursion Is Reduced in Infants with Pulmonary Hypertension Dala Zakaria, M.D.,* Ritu Sachdeva, M.D.,* Jeffrey M. Gossett, M.S.,† Xinyu Tang, Ph.D.,† and Matthew J. O’Connor, M.D.* *Division of Pediatric Cardiology, University of Arkansas for Medical Sciences, Arkansas Children’s Hospital, Little Rock, Arkansas; and †Biostatistics Program, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas
Background: Right ventricular (RV) function is reduced in infants with pulmonary hypertension (PH) but echocardiographic assessment can be challenging. We sought to determine the role of tricuspid annular plane systolic excursion (TAPSE) in infants with PH and compared it with other markers such as tricuspid annular S’ and RV fractional area change (RVFAC). Methods: Retrospective review of medical records of 30 infants treated for PH and 69 healthy controls from January 2012 to November 2012 was performed. Patients with significant congenital heart disease were excluded. Offline analysis of echocardiograms was performed to obtain TAPSE, tricuspid annular S’, and RVFAC. TAPSE was indexed to body surface area (TAPSE/BSA). Logistic regression analysis was performed to evaluate the relation between echocardiographic markers and PH. Results: TAPSE and TAPSE/BSA were significantly lower in PH patients. PH patients were younger than controls; however, TAPSE was significantly lower in PH patients after matching with controls by age. Tricuspid annular S’ was decreased in PH patients, but RVFAC was similar. On multivariate analysis, tricuspid S’ did not have a significant effect on the probability of PH (P = 0.067). The odds of PH significantly increased with each 1 mm decrease in TAPSE (OR 1.78, 95% CI 1.26–2.45). Inter-observer agreement for TAPSE showed concordance correlation coefficient of 0.89. Conclusions: TAPSE is a feasible and reproducible marker of RV systolic function in infants with PH and is superior to tricuspid annular S’ and RVFAC. Longitudinal studies are needed to evaluate the role of TAPSE in serial evaluation of PH. (Echocardiography 2014;00:1–5) Key words: pulmonary hypertension, children, echocardiography, TAPSE
Pulmonary hypertension (PH) is a common cause of morbidity and mortality in infants. Two common causes of PH in infants include persistent PH of the newborn (PPHN) and bronchopulmonary dysplasia in premature infants.1,2 The incidence of PPHN is approximately 1 in 500 live births and has a mortality of up to 10%.1 The clinical syndrome of PH in infants has multiple etiologies, such as vasoconstriction, pulmonary vascular hypoplasia, pulmonary venous obstruction, and pulmonary parenchymal disease, all of which share an abnormal elevation of pulmonary vascular resistance.1,3 Severe PH results in impaired oxygenation, right ventricular (RV) failure, and pulmonary-to-systemic shunting, all of which result in cyanosis. Secondarily, severe PH causes low cardiac output due to decreased left heart preload on account of decreased pulmonary venous return and the mechanical effects of Address for correspondence and reprint requests: Dala Zakaria, M.D., University of Arkansas for Medical Sciences, Arkansas Children’s Hospital, Little Rock, AR. Fax: 501-364-3667; E-mail: [email protected]
the hypertensive RV on left heart filling. Advances in neonatal intensive care, including high-frequency ventilation, surfactant instillation, extracorporeal membrane oxygenation (ECMO), and inhaled nitric oxide (iNO), have reduced PPHNrelated mortality.4–6 PH is ideally evaluated by cardiac catheterization since pulmonary vascular resistance and right heart hemodynamics can be directly measured.7 However, it is an invasive technique with significant risks in patients with PH. Transthoracic echocardiography (TTE) is routinely used for assessment of RV systolic pressure in neonates with PH. However, RV functional assessment in PH is typically qualitative in nature, which leads to inter-observer variability and limits the ability to follow RV function over time. Studies in adult patients with PH have used several markers to quantitate RV systolic function and have reported their prognostic relevance as well. These markers include tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RVFAC), and Doppler tissue 1
Zakaria, et al.
imaging-(DTI) derived systolic (S’) velocities.8,9 The utility of TAPSE in assessing RV systolic function in infants with PH has not been well studied. We hypothesized that TAPSE would be reduced in infants with PH. The purpose of this study was to evaluate TAPSE in infants with PH and compare it with previously used measures of RV systolic function such as tricuspid annular S’ and RVFAC. Material and Methods: A retrospective review of medical records of infants (less than 12 months) with PH cared for in the neonatal intensive care unit at our institution who had an echocardiogram that included TAPSE and DTI was performed. Infants referred for an echocardiogram for murmur whose study was normal served as controls. The study period was January 2012 to November 2012. Infants with congenital heart disease (except those with trivial lesions such as small atrial septal defect, patent foramen ovale, small ventricular septal defect [VSD], small patent ductus arteriosus [PDA], and nonobstructive bicuspid aortic valve) were excluded. PH was defined based on quantification of pulmonary arterial pressure using tricuspid regurgitation (TR) or pulmonary regurgitation (PR) velocities, and gradients across VSD and/or PDA, when present. Clinical evidence of PH was defined as either the use of iNO and/or ECMO. Intentional exclusion of patients who were not treated with iNO or ECMO was performed to exclude questionable cases of PH that may confound the results. For the purpose of this study, therefore, only patients with both clinical and echocardiographic evidence of PH were considered in the PH group. This study was approved by the Institutional Review Board at the University of Arkansas for Medical Sciences. Data abstracted for each patient included demographic variables: age, weight, body surface area (BSA), gestational age, and age at TTE. Offline analysis of echocardiographic images stored on the Syngo PACS system (Siemens, Mountain View, CA, USA) was performed to obtain TAPSE, tricuspid annular S’, and RVFAC. All images were analyzed by a pediatric cardiologist (D. Z.). In addition, for inter-observer reliability, TAPSE was measured by another cardiologist (M. O.) in all PH patients. TAPSE was acquired by placing an M-mode cursor through the tricuspid annulus in the apical four-chamber view and measuring the amount of longitudinal (base to apex) motion, measured in centimeters, of the tricuspid annulus at peak systole. TAPSE was determined by the total excursion of the tricuspid lateral annulus from its highest position to the lowest point of descent 2
during ventricular systole (Fig. 1). TAPSE values were indexed to BSA. To minimize the effect of respiration on variability, TAPSE and tricuspid annular S’ averaged over 3 consecutive beats were recorded. To calculate RVFAC, RV was traced along the endocardium at the end of diastole and at the end of systole in apical four-chamber view as recommended by the American Society of Echocardiography.9 Peak TR velocities were recorded from the window giving maximal velocity by continuouswave Doppler. Care was taken to measure the peak velocity using a distinct peak and avoid overestimation from feathering or underestimating due to incomplete signal. RV systolic pressure was estimated using the simplified Bernoulli equation and adding a mean central venous pressure of 5 mmHg. Infants were considered to have PH by echocardiographic criteria if estimated RV systolic pressure was 2/3 or greater compared to the systemic systolic blood pressure recorded at the time of the echocardiogram. In patients without adequate TR Doppler signals, RV pressure was determined using the PDA gradient or PR velocity. The peak PDA gradient estimated by continuous-wave Doppler was subtracted from systemic BP to estimate RV pressure. Statistical Analysis: With a sample size of 30 PH and 69 control patients, this study had at least 80% power to detect a standardized effect size of 0.62 differences between 2 groups. All the data were analyzed using R software v3.0.1 (R Foundation for Statistical Computing, Vienna, Austria). Summary
Figure 1. Apical four-chamber view. White broken line indicates M-mode cursor to measure TAPSE. Yellow lines indicate absolute longitudinal displacement of tricuspid annulus; red arrow marks upper and lower points for TAPSE measurement. TAPSE = tricuspid annular plane systolic excursion; RA = right atrium; LA = left atrium; RV = right ventricle; LV = left ventricle; TV = tricuspid valve.
TAPSE Is Reduced in Infants with Pulmonary Hypertension
statistics were expressed as median and interquartile range (IQR: 25th percentile, 75th percentile) for continuous variables. The distributions of continuous variables were compared between patients with PH and controls using the Mann–Whitney U-tests. A logistic regression model was fitted for the probability of PH as a function of age, TAPSE, and tissue Doppler. This model specification was designated to evaluate the effect of TAPSE on the probability of PH after adjusting for the confounding effects of age and tissue Doppler. A similar model was fitted by replacing the TAPSE with the TAPSE/BSA. To validate our findings, we matched our case and control patients by age using the Matching package in R software (Little Rock, AR, USA). We used oneto-one matching without replacement, in which only one control patient was matched to each case patient with a similar age, and each control patient was matched only once. The distributions of continuous variables were compared between matched PH and control patients using the Wilcoxon signed-rank tests. Inter-observer agreement was evaluated using Lin’s concordance correlation coefficient analysis. P-values
Echocardiography
ORIGINAL INVESTIGATION
Tricuspid Annular Plane Systolic Excursion Is Reduced in Infants with Pulmonary Hypertension Dala Zakaria, M.D.,* Ritu Sachdeva, M.D.,* Jeffrey M. Gossett, M.S.,† Xinyu Tang, Ph.D.,† and Matthew J. O’Connor, M.D.* *Division of Pediatric Cardiology, University of Arkansas for Medical Sciences, Arkansas Children’s Hospital, Little Rock, Arkansas; and †Biostatistics Program, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas
Background: Right ventricular (RV) function is reduced in infants with pulmonary hypertension (PH) but echocardiographic assessment can be challenging. We sought to determine the role of tricuspid annular plane systolic excursion (TAPSE) in infants with PH and compared it with other markers such as tricuspid annular S’ and RV fractional area change (RVFAC). Methods: Retrospective review of medical records of 30 infants treated for PH and 69 healthy controls from January 2012 to November 2012 was performed. Patients with significant congenital heart disease were excluded. Offline analysis of echocardiograms was performed to obtain TAPSE, tricuspid annular S’, and RVFAC. TAPSE was indexed to body surface area (TAPSE/BSA). Logistic regression analysis was performed to evaluate the relation between echocardiographic markers and PH. Results: TAPSE and TAPSE/BSA were significantly lower in PH patients. PH patients were younger than controls; however, TAPSE was significantly lower in PH patients after matching with controls by age. Tricuspid annular S’ was decreased in PH patients, but RVFAC was similar. On multivariate analysis, tricuspid S’ did not have a significant effect on the probability of PH (P = 0.067). The odds of PH significantly increased with each 1 mm decrease in TAPSE (OR 1.78, 95% CI 1.26–2.45). Inter-observer agreement for TAPSE showed concordance correlation coefficient of 0.89. Conclusions: TAPSE is a feasible and reproducible marker of RV systolic function in infants with PH and is superior to tricuspid annular S’ and RVFAC. Longitudinal studies are needed to evaluate the role of TAPSE in serial evaluation of PH. (Echocardiography 2014;00:1–5) Key words: pulmonary hypertension, children, echocardiography, TAPSE
Pulmonary hypertension (PH) is a common cause of morbidity and mortality in infants. Two common causes of PH in infants include persistent PH of the newborn (PPHN) and bronchopulmonary dysplasia in premature infants.1,2 The incidence of PPHN is approximately 1 in 500 live births and has a mortality of up to 10%.1 The clinical syndrome of PH in infants has multiple etiologies, such as vasoconstriction, pulmonary vascular hypoplasia, pulmonary venous obstruction, and pulmonary parenchymal disease, all of which share an abnormal elevation of pulmonary vascular resistance.1,3 Severe PH results in impaired oxygenation, right ventricular (RV) failure, and pulmonary-to-systemic shunting, all of which result in cyanosis. Secondarily, severe PH causes low cardiac output due to decreased left heart preload on account of decreased pulmonary venous return and the mechanical effects of Address for correspondence and reprint requests: Dala Zakaria, M.D., University of Arkansas for Medical Sciences, Arkansas Children’s Hospital, Little Rock, AR. Fax: 501-364-3667; E-mail: [email protected]
the hypertensive RV on left heart filling. Advances in neonatal intensive care, including high-frequency ventilation, surfactant instillation, extracorporeal membrane oxygenation (ECMO), and inhaled nitric oxide (iNO), have reduced PPHNrelated mortality.4–6 PH is ideally evaluated by cardiac catheterization since pulmonary vascular resistance and right heart hemodynamics can be directly measured.7 However, it is an invasive technique with significant risks in patients with PH. Transthoracic echocardiography (TTE) is routinely used for assessment of RV systolic pressure in neonates with PH. However, RV functional assessment in PH is typically qualitative in nature, which leads to inter-observer variability and limits the ability to follow RV function over time. Studies in adult patients with PH have used several markers to quantitate RV systolic function and have reported their prognostic relevance as well. These markers include tricuspid annular plane systolic excursion (TAPSE), RV fractional area change (RVFAC), and Doppler tissue 1
Zakaria, et al.
imaging-(DTI) derived systolic (S’) velocities.8,9 The utility of TAPSE in assessing RV systolic function in infants with PH has not been well studied. We hypothesized that TAPSE would be reduced in infants with PH. The purpose of this study was to evaluate TAPSE in infants with PH and compare it with previously used measures of RV systolic function such as tricuspid annular S’ and RVFAC. Material and Methods: A retrospective review of medical records of infants (less than 12 months) with PH cared for in the neonatal intensive care unit at our institution who had an echocardiogram that included TAPSE and DTI was performed. Infants referred for an echocardiogram for murmur whose study was normal served as controls. The study period was January 2012 to November 2012. Infants with congenital heart disease (except those with trivial lesions such as small atrial septal defect, patent foramen ovale, small ventricular septal defect [VSD], small patent ductus arteriosus [PDA], and nonobstructive bicuspid aortic valve) were excluded. PH was defined based on quantification of pulmonary arterial pressure using tricuspid regurgitation (TR) or pulmonary regurgitation (PR) velocities, and gradients across VSD and/or PDA, when present. Clinical evidence of PH was defined as either the use of iNO and/or ECMO. Intentional exclusion of patients who were not treated with iNO or ECMO was performed to exclude questionable cases of PH that may confound the results. For the purpose of this study, therefore, only patients with both clinical and echocardiographic evidence of PH were considered in the PH group. This study was approved by the Institutional Review Board at the University of Arkansas for Medical Sciences. Data abstracted for each patient included demographic variables: age, weight, body surface area (BSA), gestational age, and age at TTE. Offline analysis of echocardiographic images stored on the Syngo PACS system (Siemens, Mountain View, CA, USA) was performed to obtain TAPSE, tricuspid annular S’, and RVFAC. All images were analyzed by a pediatric cardiologist (D. Z.). In addition, for inter-observer reliability, TAPSE was measured by another cardiologist (M. O.) in all PH patients. TAPSE was acquired by placing an M-mode cursor through the tricuspid annulus in the apical four-chamber view and measuring the amount of longitudinal (base to apex) motion, measured in centimeters, of the tricuspid annulus at peak systole. TAPSE was determined by the total excursion of the tricuspid lateral annulus from its highest position to the lowest point of descent 2
during ventricular systole (Fig. 1). TAPSE values were indexed to BSA. To minimize the effect of respiration on variability, TAPSE and tricuspid annular S’ averaged over 3 consecutive beats were recorded. To calculate RVFAC, RV was traced along the endocardium at the end of diastole and at the end of systole in apical four-chamber view as recommended by the American Society of Echocardiography.9 Peak TR velocities were recorded from the window giving maximal velocity by continuouswave Doppler. Care was taken to measure the peak velocity using a distinct peak and avoid overestimation from feathering or underestimating due to incomplete signal. RV systolic pressure was estimated using the simplified Bernoulli equation and adding a mean central venous pressure of 5 mmHg. Infants were considered to have PH by echocardiographic criteria if estimated RV systolic pressure was 2/3 or greater compared to the systemic systolic blood pressure recorded at the time of the echocardiogram. In patients without adequate TR Doppler signals, RV pressure was determined using the PDA gradient or PR velocity. The peak PDA gradient estimated by continuous-wave Doppler was subtracted from systemic BP to estimate RV pressure. Statistical Analysis: With a sample size of 30 PH and 69 control patients, this study had at least 80% power to detect a standardized effect size of 0.62 differences between 2 groups. All the data were analyzed using R software v3.0.1 (R Foundation for Statistical Computing, Vienna, Austria). Summary
Figure 1. Apical four-chamber view. White broken line indicates M-mode cursor to measure TAPSE. Yellow lines indicate absolute longitudinal displacement of tricuspid annulus; red arrow marks upper and lower points for TAPSE measurement. TAPSE = tricuspid annular plane systolic excursion; RA = right atrium; LA = left atrium; RV = right ventricle; LV = left ventricle; TV = tricuspid valve.
TAPSE Is Reduced in Infants with Pulmonary Hypertension
statistics were expressed as median and interquartile range (IQR: 25th percentile, 75th percentile) for continuous variables. The distributions of continuous variables were compared between patients with PH and controls using the Mann–Whitney U-tests. A logistic regression model was fitted for the probability of PH as a function of age, TAPSE, and tissue Doppler. This model specification was designated to evaluate the effect of TAPSE on the probability of PH after adjusting for the confounding effects of age and tissue Doppler. A similar model was fitted by replacing the TAPSE with the TAPSE/BSA. To validate our findings, we matched our case and control patients by age using the Matching package in R software (Little Rock, AR, USA). We used oneto-one matching without replacement, in which only one control patient was matched to each case patient with a similar age, and each control patient was matched only once. The distributions of continuous variables were compared between matched PH and control patients using the Wilcoxon signed-rank tests. Inter-observer agreement was evaluated using Lin’s concordance correlation coefficient analysis. P-values
