Two-Dimensional Echocardiography

Two-dimensional echocardiograms were retrospectively reviewed. We analyzed the last complete study before each surgical stage. Anatomic subtype was noted as mitral atresia, mitral stenosis with aortic atresia, mitral stenosis with aortic stenosis, or mitral atresia with aortic atresia. TR severity was determined by two echocardiographers’ review of the echocardiogram, taking into account the vena contracta width (summation of jets if more than one), as per the clinical routine in our laboratory, and classified as none or trivial, mild, moderate, or severe. For the purpose of this study, a vena contracta width ≤ 2.5 mm indicated mild TR and a vena contract width > 2.5 mm indicated moderate or severe TR, taking into consideration the TV annulus. Ventricular function was subjectively assessed as normal or mildly, moderately, or severely depressed and quantitatively by RV fractional area change (FAC; [end-diastolic area − end-systolic area]/end-diastolic area) from the apical four-chamber view. To determine if structural abnormalities of the TV were primarily responsible for TR, TV structural abnormalities were determined from the echocardiogram. These included leaflet prolapse (leaflet free edge overriding the annular plane during systole), chordal shortening or leaflet tethering restricting leaflet motion, leaflet dysplasia (thickening, nodular irregularity, or extra zone of apposition), or papillary muscle abnormality. We also noted the presence of annular dilatation, which was defined as a TV annular Z score > 2, using institutional Z scores.

QRS duration was measured from a 12-lead electrocardiogram.

RV Dyssynchrony

Asymmetric RV contraction between the septal and RV lateral walls was assessed by measuring the difference in peak strain and the difference in time to peak strain between septum and RV lateral wall. Longitudinal strain was measured using Digital Imaging and Communications in Medicine–format apical four-chamber view–equivalent grayscale images by vector velocity imaging (TomTec Imaging Systems GmBH, Munich, Germany) ( Figure 1 ). The endocardium was manually traced, and adequate tracking was ensured throughout the cardiac cycle. The right ventricle is a complex shape, and therefore analysis concentrated on segments adjacent to the TV annulus and papillary muscles: the basal and middle segments of the RV free wall and septum (if the septum was very short and not divisible into two segments, it was counted as a basal segment only) or the left-sided RV free wall, depending on the individual anatomy (whether a discernible left ventricle was present). These segments are those that have the most influence over TV configuration. Difference in peak strain was calculated as the difference in the average RV free wall basal and middle segments strain and the average of the basal and middle septum or left-sided RV free wall strain. Difference in time to peak strain was calculated as the difference in the average of the time to peak strain in the RV free wall basal and middle segments and average of the time to peak strain in septal or left-sided RV free wall basal and middle segments. Additional analysis was performed to calculate the difference in time to peak strain as a percentage of the RR interval, to correct for heart rate.

(A) Apical four-chamber view equivalent with a superimposed endocardial border tracing. (B) Resulting longitudinal strain curve. The basal septal segment is represented in green , the middle septal segment (in this example, this is adjacent to the left ventricular apex) is in pale pink , the apical segments (not included in the analysis) are in cyan and dark pink , the middle RV free wall segment is in yellow , and the basal RV free wall is in dark blue . In this example, both the basal and mid septal segments and the basal and mid right segments reach their peak strain at different times. The basal and mid septal segments have low peak strain values and reach their peak before the right.

Differences in loading conditions occur with different stages of palliation. Therefore, a separate analysis was carried out of the difference in peak strain and the difference in time to peak longitudinal strain according to patients’ surgical stage, with patients divided into groups of no surgery and status post stage 1, stage 2, or stage 3 palliation.

Because normal RV synchrony in patients with HLHS has not been defined, and we therefore could not categorize patients as having “normal” or “abnormal” strain, we carried out comparisons within the cohort by dividing the patients into two groups above (group A) and below (group B) the median difference in time to peak longitudinal strain between the RV free wall and the septum or left-sided RV wall.

The institutional ethics board approved this study.

Statistical Analysis

Because TV interventions are rarely performed in patients with less than moderate TR, we compared patients with no or trivial or mild TR with those with moderate or severe TR.

Data are displayed as mean ± SD for normally distributed variables, or as medians with interquartile ranges, and were analyzed using Fisher’s exact tests or Mann-Whitney tests, respectively (InStat; GraphPad Software, Inc., La Jolla, CA). Multiple groups were compared using analysis of variance. P values < .05 were considered statistically significant.

Interobserver and intraobserver reproducibility of strain measurements was assessed using intraclass correlation coefficients of variation in 10 random patients. For interobserver variability, using the same cardiac cycle, two independent observers drew new regions of interest. For the assessment of intraobserver variability, regions of interest were redrawn ≥1 month following the original measurements.

Patient Characteristics

Sixty echocardiograms from 54 patients were identified (25 female), with a median age of 0.54 years (interquartile range, 0.04–1.63 years) and a median weight of 6.40 kg (interquartile range, 3.70–10.45 kg). Six patients were included who had echocardiograms analyzed at two different stages of palliation each. Each of these six had a grade of TR that differed by at least one grade at the time of the second analysis. Patient characteristics are shown in Table 1 and anatomic subtypes in Table 2 . TR was absent or trivial in 25 (42%), mild in 20 (33%), moderate in five (8%), and severe in 10 (17%) patients.

Twenty patients (33%) were taking medications; these were prostaglandin infusion in nine patients (15%), angiotensin-converting enzyme inhibitors in seven (12%), diuretics in seven (12%), antiplatelet or anticoagulation agents in eight (13%), antireflux medications in six (10%), and other medications in four (7%).

Two-Dimensional Echocardiography

TV structural abnormalities were found in 24 of 60 echocardiograms (19 with no or trivial or mild TR and five with moderate or severe TR; Table 3 ). There was no significant difference in the frequency of TV structural abnormalities on the basis of TR severity.

On subjective assessment, RV function was not depressed in 48 echocardiograms (23 with no or trivial TR, 16 with mild TR, four with moderate TR, and five with severe TR), mildly depressed in seven (two with no or trivial TR, two with mild TR, one with moderate TR, and two with severe TR), moderately depressed in one subject with mild TR, and severely depressed in three subjects, all with severe TR. RV FAC was not different between subjects with no, trivial, or mild TR and those with moderate or severe TR (37.6 ± 13.4% vs 35.4 ± 14.7%, P = .28).

Patients with moderate or severe TR had significantly larger TV annular Z scores compared with those with no, trivial, or mild TR (mean, 2.6 ± 2.0 vs 1.3 ± 2.1, P = .02).

Electrocardiography

The mean heart rate of all patients was 124 beats/min (148 beats/min for patients before any surgical intervention, 138 beats/min after stage 1, 118 beats/min after stage 2, and 93 beats/min after stage 3).

The mean QRS duration was 82.7 ± 20.5 msec. The mean interval between electrocardiography and echocardiography was 5.7 days; the majority of electrocardiographic assessments were performed within 24 hours of echocardiography. QRS duration was not significantly different between patients with no, trivial, or mild TR and those with moderate or severe TR (82.4 ± 22.1 vs 83.6 ± 15.2 msec).

Deformation Imaging

Digital Imaging and Communications in Medicine images stored at a default setting of 30 frames/sec were analyzed.

Peak longitudinal strain and time to peak longitudinal strain values are presented in Table 4 . Peak longitudinal strain was low in all segments, particularly in the septum or left-sided RV wall. The difference in peak longitudinal strain between RV free wall and septum or left-sided RV wall was significantly higher in patients with moderate or severe TR compared with those with no, trivial, or mild TR (2.93 ± 6.03% vs 0.16 ± 6.6%, P = .04). The difference in time to peak longitudinal strain between the two walls was significantly longer in those with moderate or severe TR compared with those with no, trivial, or mild TR (57.4 ± 145.1 vs 15.8 ± 75.9 msec, P = .04). Corrected for heart rate, time to peak longitudinal strain remained significantly longer in those with moderate or severe TR (13.8 ± 18.8% vs 7.5 ± 6.2% of the RR interval, P = .03).

Proportions of anatomic subtype differed significantly between groups A and B ( P = .05; Table 5 ). However, there was no difference in the frequency of TV structural abnormalities between the groups. There was no significant difference in RV FAC (36.2 ± 14.4% vs 41.4 ± 9.2%, P = .10) or QRS duration (82.6 ± 21.0 vs 82.9 ± 20.3 msec, P = .84) between groups A and B. Patients at different stages of palliation were spread evenly between groups A and B as follows: group A: unoperated n = 5, stage 1 palliation n = 10, stage 2 palliation n = 10, and stage 3 palliation n = 5; group B: unoperated n = 6, stage 1 palliation n = 7, stage 2 palliation n = 9, and stage 3 palliation n = 8. There was no difference in either peak longitudinal strain ( P = .05) or time to peak longitudinal strain between opposing walls ( P = .86) if patients were grouped according to surgical stage.

Table 5

Anatomic subtype and difference in time to peak longitudinal strain

Anatomic subtype	TR	Group A ∗	Group B †	Total
Mitral atresia	None/trivial/mild	0	3	3
	Moderate/severe	0	1	1
Mitral stenosis and aortic atresia	None/trivial/mild	8	10	18
	Moderate/severe	2	5	7
Mitral stenosis and aortic stenosis	None/trivial/mild	11	5	16
	Moderate/severe	0	1	1
Mitral atresia and aortic atresia	None/trivial/mild	5	3	8
	Moderate/severe	4	2	6

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