Background
The purpose of this study was to investigate changes in right ventricular (RV) function and deformation parameters before and at steady state after the Norwood operation in neonates with hypoplastic left heart syndrome. A further aim was to delineate factors that affected these changes.
Methods
On echocardiograms before and 21 days (range, 10–35 days) after the Norwood operation, the two-dimensional speckle-tracking parameters global and regional peak systolic longitudinal strain and strain rate were retrospectively compared in 33 patients with hypoplastic left heart syndrome. In addition, RV functional assessment included RV fractional area change and tricuspid annular plane systolic excursion. The associations between postoperative echocardiographic findings and preoperative or postoperative complications, prenatal diagnosis, postoperative heart rate, oxygen saturation, and medication use as well as cardiopulmonary bypass and aortic cross-clamp times were tested.
Results
Global strain (−18.3 ± 3.6% vs −16.8 ± 3.8%, P = .02) and global strain rate (−1.6 ± 0.3 vs −1.2 ± 0.3 sec −1 , P < .0001) decreased significantly. Regional strain decreased significantly in the apical and mid lateral segments, while regional strain rate decreased significantly in all but the basal septal segments. Tricuspid annular plane systolic excursion of the lateral annulus decreased significantly, while RV fractional area change remained the same. No significant associations were found between postoperative RV function and potential impact factors.
Conclusions
Two-dimensional global and regional longitudinal strain and strain rate as well as tricuspid annular plane systolic excursion were reduced in patients with hypoplastic left heart syndrome after the Norwood operation. None of the examined preoperative and postoperative patient or surgical factors was found to explain this decrease.
Two-dimensional (2D) deformation imaging techniques such as 2D speckle tracking are gaining more and more acceptance as useful tools to assess global and regional myocardial deformation in adults and children. Two-dimensional speckle tracking may be particularly well suited when imaging right and single ventricles, because it is independent of the angle of insonation and the geometry of the ventricle. Thus, the technique lends itself especially well to the investigation of systemic right ventricular (RV) deformation in children with hypoplastic left heart syndrome (HLHS). However, a potential drawback of the method is its inherent sensitivity to loading conditions. The negative impact of cardiopulmonary bypass surgery on ventricular function has been well documented, even in children with simple congenital heart defects, and it has been shown that children with HLHS after the Norwood operation show decreases in RV systolic myocardial velocities.
Using the new technique of 2D speckle tracking as well as the traditional parameters for RV function assessment, tricuspid annular plane systolic excursion (TAPSE) and RV fractional area change (RVFAC), the purposes of this study were to (1) investigate changes in global and regional RV function in neonates with HLHS before and at steady state after the Norwood operation and (2) delineate factors influencing these changes.
Methods
Patients
A retrospective database search identified 45 children with HLHS who underwent modified Norwood operations at our institution from February 2008 to September 2010. Of these, 33 fulfilled our inclusion criteria of (1) having echocardiographic data suitable for speckle-tracking analysis of the right ventricle available before and after surgery and (2) being hemodynamically stable at the time of preoperative and postoperative echocardiography, without the need for mechanical ventilation or intravenous inotropic support.
All 33 patients were treated according to a standardized preoperative protocol with low-dose prostaglandin, furosemide, and afterload reduction either with sodium nitroprusside or phentolamine, oral feeding and avoidance of mechanical ventilation or inotropic support, as previously described, and then had underwent modified Norwood operations with Blalock-Taussig shunts performed by a single surgeon (J.S.). Medications at the time of postoperative echocardiography included furosemide, spironolactone, aspirin or warfarin, and digoxin in the earlier study period. Because of a change in medical management, metoprolol was used instead of digoxin in patients in the later part of the study period. Two patients additionally received amiodarone. Informed consent for anonymized data analysis was obtained for every patient.
HLHS
HLHS is a spectrum of cardiac malformations with variable hypoplasia of the left ventricle. Both the mitral and aortic valves can be either stenotic or atretic, and thus four anatomic subtypes are possible: mitral atresia (MA) and aortic atresia (AA), mitral stenosis (MS) and AA, MS and aortic stenosis (AS), and MA and AS (typically associated with a ventricular septal defect). Because of the left-sided hypoplasia, systemic blood flow depends on a patent ductus arteriosus that is kept open after birth with prostaglandin infusions in all patients until surgery. Because both systemic (Qs) and pulmonary (Qp) blood flow is provided by the right ventricle, the ratio of Qp to Qs becomes a critical issue and depends on pulmonary and systemic vascular resistance. Thus, the clinical picture can range from cyanosis (low Qp) to heart failure (high Qp).
Modified Norwood Operation
Our routine modified Norwood procedure is typically performed in the first week of life. The pulmonary artery is transected at the bifurcation, and the proximal end is connected side by side to the diminutive ascending aorta, which is incised longitudinally along the inner curvature from the distal aortic arch into the aortic root. The extension of the longitudinal incision into the aortic root results in a short precoronary segment. The aortic arch and the ascending aorta are patch augmented and connected with the circumference of the transected pulmonary artery to construct the neoaorta. In the majority of patients, bovine pericardium xenografts were used as patch material.
In all 33 patients, a modified Blalock-Taussig shunt (Gore-Tex; W. L. Gore & Associates, Newark, DE) 3.0 or 3.5 mm in diameter was inserted between the innominate artery and the reconstructed pulmonary bifurcation to provide pulmonary blood flow. All patients were operated on with low-flow antegrade selective cerebral perfusion during the reconstruction of the aortic arch. The pH-stat method was used for cooling to a temperature of 18°C and continued during bypass with an intermittent low-flow strategy. Hemofiltration was routinely used in all patients. Primary chest closure was achieved in all patients.
Echocardiography
All echocardiograms were obtained using a Vivid 7 scanner (GE Healthcare, Wauwatosa, WI) by trained physicians and stored digitally for offline analysis. Preoperative echocardiograms were obtained in all patients during stable conditions without mechanical ventilation or inotropic support. Postoperative echocardiograms were performed a median of 21 days after surgery, when patients had recovered from surgery clinically. All patients were extubated and without intravenous inotropic medication at the time of the postoperative study.
From the preoperative and postoperative echocardiograms, the following data were acquired: (1) RV area in end-diastole and end-systole from the apical four-chamber view at the level of the tricuspid valve annulus; (2) RVFAC, calculated as (end-diastolic area − end-systolic area)/end-diastolic area; (3) M-mode measurement of TAPSE at the RV free wall and interventricular septum or remnant thereof ( Figure 1 ); (4) severity of tricuspid valve regurgitation, graded subjectively (0 = none, 1 = trivial, 2 = mild, 3 = moderate, or 4 = severe), taking into account the vena contracta width and area of the color Doppler jet in relation to size of the right ventricle and atrium; and (5) the diameter of the ascending aorta, obtained from the preoperative echocardiographic study in the parasternal long-axis imaging plane. Measurements were made in systole using the inner edge–to–inner edge technique.
In addition to the routine echocardiographic study, the following data were collected. Grayscale images (73–113 frames/sec) optimized for speckle-tracking echocardiographic analysis were acquired from the apical four-chamber view ( Figure 2 A). The data were retrospectively analyzed offline using dedicated software (EchoPAC PC 2008; GE Healthcare). Manual tracing of the endocardial border started from the septal tricuspid valve annular hinge point and commenced along the apex to the lateral tricuspid valve annular hinge point. The region of interest was adjusted according to myocardial thickness. The software then divided the right ventricle automatically into six segments: basal septal, mid septal, apical septal, apical lateral, mid lateral, and basal lateral ( Figure 2 B). Of note, the software was originally designed for left ventricular analysis, and therefore segmental allocation in the right ventricle did not always correlate to the anatomy. For instance, in the absence of a left ventricle, there may not have been a true apical septal segment, because there was no septum per se. Segments were excluded if the myocardium was not visualized well enough to allow speckle tracking. Aortic valve closure and opening were determined from aortic (pre) and neoaortic (post) outflow spectral Doppler tracings. Peak systolic longitudinal strain (ϵ; percentage change in segment length from end-diastole) and peak systolic longitudinal strain rate (SR; representing the rate of deformation) were recorded for each segment. The ϵ and SR curves for the individual segments were reviewed, and if the automatically placed peak ϵ and peak SR values by the software were incorrect, these were adjusted manually. From the regional segmental data, global ϵ and SR were calculated by the software.
Additional Data
We also recorded heart rate and arterial oxygen saturation at the time of the preoperative and postoperative echocardiographic studies.
The incidence of preoperative and postoperative complications, such as shock, need for intubation, need for intravenous inotropic support, or cerebrovascular accidents, and prenatal diagnosis, as well as the cardiopulmonary bypass and aortic cross clamp-times, were recorded.
Intraobserver and Interobserver Variability
To assess intraobserver variability, the same observer made two measurements of the same 2D loop at different points in time, ≥4 weeks apart, in 20 randomly selected studies. Duplicate measurements were made for global longitudinal ϵ and SR as well as regional ϵ and SR in the six segments, and the coefficient of variation was calculated. Interobserver variability was assessed by having a second observer measure the same 2D loop used by the first observer, and the coefficient of variation was calculated. For both intraobserver and interobserver variability, the coefficient of variation for duplicate measurements was calculated as
coefficient of variation ( % ) = ( SD / mean ) × 1 0 0 ,
SD = ∑ ( X 1 − X 2 ) 2 2 n
, and <SPAN role=presentation tabIndex=0 id=MathJax-Element-3-Frame class=MathJax style="POSITION: relative" data-mathml='mean=(X1−X2)2n’>mean=(X1−X2)2n−−−−−−√mean=(X1−X2)2n
mean = ( X 1 − X 2 ) 2 n
.
Statistical Methods
Data analysis was performed using SPSS version 15.0 for Windows (SPSS, Inc., Chicago, IL).
Data are expressed as mean ± SD or as medians with ranges. Testing for normality was performed using the Kolmogorov-Smirnov test. For the comparison of preoperative and postoperative data, paired Wilcoxon’s signed-rank tests or paired two-sample Student’s t tests were used as appropriate. Comparisons between independent groups were performed using Mann-Whitney U tests or t tests for independent samples. Correlations were calculated using Pearson’s correlation coefficient for normally distributed data and Spearman’s rank correlation coefficient for not normally distributed data. To assess differences among anatomic subtypes with regard to postoperative RV function, the Kruskal-Wallis test was used. For all calculations, P values < .05 were considered statistically significant.
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