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Change in biventricular function after cone reconstruction of Ebstein’s anomaly: an echocardiographic study

Change in biventricular function after cone reconstruction of Ebstein’s anomaly: an... Abstract Aims The Cone reconstruction in Ebstein’s anomaly (EA) aims to reduce tricuspid valve regurgitation (TR) and reposition the valve to the anatomic annulus, but post-operative progress of ventricular function is poorly understood. This study evaluated biventricular function after Cone reconstruction using echocardiographic techniques. Methods and results A retrospective study assessing longitudinal change was conducted from 2009 to 2014. All symptomatic patients with EA and severe TR undergoing surgery were included. Transthoracic advanced echocardiography was performed pre- and post-operatively (at short-term (<30 days) and mid-term). Conventional and longitudinal 2D strain parameters were measured for left ventricle (LV) and right ventricle (RV). Paired analyses were compared using Wilcoxon Matched-pairs signed rank test. From the 38 patients operated for EA, the echocardiographic data of 17 patients, aged 15 (1–57 years) at operation could be analysed. Median follow up was 6 months (8 days–54 months). The tricuspid annular plane systolic excursion (26.42 ± 5.79 mm vs. 8.75 ± 3.18 mm, P < 0.001), RV fractional area change (FAC) (45.00 ± 8.13% vs. 35.46 ± 5.76%, P = 0.038) and LV 2D peak systolic strain were significantly reduced post-operatively (−20.49 ± 2.79 vs. −17.73 ± 2.76, P = 0.041), with a trend to later recovery for LV 2D strain. There was no evidence of systolic mechanical dys-synchrony before or after operation. Conclusion Although clinical outcome of Cone reconstruction for EA remains excellent, acute post-operative changes leads to reduction of myocardial function of both ventricles, with a trend to later recovery for LV. Continuing impairment of RV function is multifactorial but may reflect intrinsic myocardial deficiency. Ebstein’s anomaly, cone reconstruction, myocardial performance, mechanical synchrony Introduction Ebstein’s anomaly (EA) is a rare congenital heart disease occurring in 1 per 200 000 live births and accounting for approximately 1% of all congenital cardiac abnormalities. It is characterized by adherence of the septal and posterior leaflets to the underlying myocardium, which is responsible for downward (apical) displacement of the functional annulus, dilation of the right atrioventricular junction (true tricuspid annulus) and dilation of the ‘atrialized’ portion of the right ventricle, with various degrees of hypertrophy or hypoplasia and thinning of the right ventricle (RV) wall, and dilation of the right atrioventricular junction (true tricuspid annulus). Because of tricuspid valve regurgitation (TR), both parts of the RV (i.e. atrialized and functional components) are exposed to abnormal physiology with high pre-load. The latest surgical reconstruction (Cone reconstruction), involves delamination and rotation of the detached TV anterosuperior leaflet and use of the remnant of the septal and inferior leaflets to create a Cone-shaped valve.1 This reconstruction involves haemodynamic changes as demonstrated by a recent study2 with reduction in TR and increase in forward flow through the pulmonary outflow tract and left ventricle (LV). Post-operative RV function, visually assessed and measured by tricuspid annular plane systolic excursion (TAPSE), has been shown to be poor after Cone reconstruction. The aim of the study was to investigate biventricular function after Cone reconstruction using conventional and advanced echocardiographic techniques. Methods Study design This is a retrospective observational study, using longitudinally acquired pre-operative and short- to mid-term post-operative data from study subjects. Ethics approval for data collection was granted following local ethics review. Patient selection All patients with EA referred for Cone reconstruction at Great Ormond Street Hospital and the Heart Hospital between 2009 and 2014 were included in the study. Indication for operation was based on our institutional criteria for offering surgery: symptoms (cyanosis, arrhythmia, heart failure with EA and tricuspid regurgitation), or asymptomatic patients with severe tricuspid regurgitation and severe right heart dilatation. All operations were performed by the same surgeon (VT). Echocardiography assessment in pre-operative, short- and mid-term post-operative periods was performed. For all patients, clinical status, presence of arrhythmias, operative characteristics and post-operative follow-up were collected. Electrocardiographic analysis Pre- and post-operative ECG’s were collected to detect right bundle branch, Wolff–Parkinson–White anomaly, atrio-ventricular block and measure PR and QRS durations. Transthoracic echocardiography Transthoracic echocardiographic studies were performed using Vivid e9 machines (GE, Milwaukee, WI, USA). All images were obtained according to prospective protocol to achieve optimal quality. Cine loops of two cardiac cycles triggered by the R wave of the QRS complex were digitally saved. Subcostal, apical four-chamber, and parasternal long- and short-axis views were used to obtain pictures of the morphology of the tricuspid valve (TV), atrial and ventricular chambers and ventricular outflow tracts. All echocardiographic recordings were stored on digital versatile discs for off-line analyses with EchoPac software (GE). All measurements were supervised by J.M. Early post-operative period was defined as the period between the day of surgery and the 30th day after the operation. Conventional echocardiographic parameters Conventional echocardiographic parameters were collected in pre- and post-operative periods, including the areas of the right and left atriums, atrialized right ventricle (aRV), functional RV, and LV to calculate GOSH score.3 The size of TV annulus and the grade of TR were measured. RV function was assessed by TAPSE and fractional area change (RV FAC) if functional ventricular shape was suitable for measurement. LV dimensions were measured from M-mode in standard parasternal long axis view. LV function was evaluated by fractional shortening and ejection fraction by Simpson method. All measured cardiac dimensions were expressed in z-scores, using Boston Children’s Hospital Heart Center reference. Diastolic and systolic eccentricity index were also measured in short axis view. 2D speckle tracking analysis Cine loops over three cardiac cycles with a frame rate from 40 to 100 fps were used for off-line analysis on Echopac®. The best apical four-chamber view to visualise the six myocardial segments of each ventricle was selected and the endocardium limit was traced by the operator (Figure 1). The software automatically generated a second line at the level of epicardium, delineating a region of interest. The measurement of systolic peak of longitudinal strain was automatic and the analysis was accepted if the software validated the measurement of each cardiac segment. Manual adjustment was applied in cases with inappropriate automated software tracking on visual observation. This analysis was done in pre- and post-operative periods. Figure 1 View largeDownload slide Example of 2D Strain analysis before and after Cone reconstruction. RA, right atrium; aRV, atrialized right ventricle; RV, right ventricle. Figure 1 View largeDownload slide Example of 2D Strain analysis before and after Cone reconstruction. RA, right atrium; aRV, atrialized right ventricle; RV, right ventricle. Synchronicity assessment by 2D speckle tracking Mechanical synchronicity assessment was also performed. Manual adjustment of aortic valve closure was done from parasternal long axis view using TM mode. Time-to-systolic peak was measured for each segment, corresponding to the time from the onset of QRS to longitudinal strain systolic peak corrected by the Bazett formula. Comparison to normal values Pre- and post-operative measurements of global LV 2D strain were compared with values of an aged- and sex-matched control group of healthy subjects, referred to cardiology clinic for a heart murmur, with structurally normal heart confirmed on standard comprehensive sequential echocardiographic assessment. Statistical analysis Continuous variables are presented as median (range) and denote the number of patients, unless otherwise stated. P < 0.05 was taken to be statistically significant. Paired analyses were performed using Wilcoxon Matched-pairs signed rank test. Intra- and interobserver assessment was done on 17 pre-operative studies for global LV 2D strain and global LV time-to-systolic peak. The intraobserver variability was assessed by one investigator performing off-line analysis on the same patients 6 months apart to reduce recall bias. The interobserver variability was assessed by a second investigator who was unaware of the previous results, performing the investigation on the same 17 patients. The intra- and interobserver agreement was assessed calculating the intra-class correlation coefficient (two-way mixed model and consistency type, average measurements). The statistical analysis was performed using SPSS, version 19 (SPSS, Chicago, IL, USA). Results Patients and operative characteristics Pre- and perioperative patient characteristics are presented in Table 1. Seventeen patients could be involved in the study. The median age at operation was 15 years-old (1–57). Four patients presented with WPW. None of the patients had evidence of LV non-compaction on echocardiogram. Table 1 Pre- and perioperative patient characteristics Number of patients 17 Sex (M/F) 8/9 Median of age at operation (years) 15 (1–57) Median of weight (kg) 48 (10–100) Symptoms Poor exercise tolerance 41% (7/17) Cyanosis 6% (1/17) Palpitation 12% (2/17) Growth retardation 6% (1/17) Asymptomatic 35% (6/17) NYHA (median) 3 (1–3) Previous procedure BT shunt 6% (1/17) Bidirectional Glenn 12% (2/17) RVPA conduit 6% (1/17) MV reconstruction 6% (1/17) Arrhythmia ablation 12% (2/17) CPB duration (min) 130.88 ± 16.45 Cross-clamp duration (min) 83.8 ± 21.07 Tricuspid annuloplasty 17 Maze procedure (pre-operative AF) 12% (2/17) Other valvular procedure 1 (pulmonary valve) Death 0/17 Median of follow-up length 6 months (8 days–54 months) Bidirectional cavo-pulmonary connection 0 Number of patients 17 Sex (M/F) 8/9 Median of age at operation (years) 15 (1–57) Median of weight (kg) 48 (10–100) Symptoms Poor exercise tolerance 41% (7/17) Cyanosis 6% (1/17) Palpitation 12% (2/17) Growth retardation 6% (1/17) Asymptomatic 35% (6/17) NYHA (median) 3 (1–3) Previous procedure BT shunt 6% (1/17) Bidirectional Glenn 12% (2/17) RVPA conduit 6% (1/17) MV reconstruction 6% (1/17) Arrhythmia ablation 12% (2/17) CPB duration (min) 130.88 ± 16.45 Cross-clamp duration (min) 83.8 ± 21.07 Tricuspid annuloplasty 17 Maze procedure (pre-operative AF) 12% (2/17) Other valvular procedure 1 (pulmonary valve) Death 0/17 Median of follow-up length 6 months (8 days–54 months) Bidirectional cavo-pulmonary connection 0 Table 1 Pre- and perioperative patient characteristics Number of patients 17 Sex (M/F) 8/9 Median of age at operation (years) 15 (1–57) Median of weight (kg) 48 (10–100) Symptoms Poor exercise tolerance 41% (7/17) Cyanosis 6% (1/17) Palpitation 12% (2/17) Growth retardation 6% (1/17) Asymptomatic 35% (6/17) NYHA (median) 3 (1–3) Previous procedure BT shunt 6% (1/17) Bidirectional Glenn 12% (2/17) RVPA conduit 6% (1/17) MV reconstruction 6% (1/17) Arrhythmia ablation 12% (2/17) CPB duration (min) 130.88 ± 16.45 Cross-clamp duration (min) 83.8 ± 21.07 Tricuspid annuloplasty 17 Maze procedure (pre-operative AF) 12% (2/17) Other valvular procedure 1 (pulmonary valve) Death 0/17 Median of follow-up length 6 months (8 days–54 months) Bidirectional cavo-pulmonary connection 0 Number of patients 17 Sex (M/F) 8/9 Median of age at operation (years) 15 (1–57) Median of weight (kg) 48 (10–100) Symptoms Poor exercise tolerance 41% (7/17) Cyanosis 6% (1/17) Palpitation 12% (2/17) Growth retardation 6% (1/17) Asymptomatic 35% (6/17) NYHA (median) 3 (1–3) Previous procedure BT shunt 6% (1/17) Bidirectional Glenn 12% (2/17) RVPA conduit 6% (1/17) MV reconstruction 6% (1/17) Arrhythmia ablation 12% (2/17) CPB duration (min) 130.88 ± 16.45 Cross-clamp duration (min) 83.8 ± 21.07 Tricuspid annuloplasty 17 Maze procedure (pre-operative AF) 12% (2/17) Other valvular procedure 1 (pulmonary valve) Death 0/17 Median of follow-up length 6 months (8 days–54 months) Bidirectional cavo-pulmonary connection 0 There was no death during the follow-up period. In this cohort, there was no re-operation necessary, neither for repair of the Cone apparatus, nor for haemodynamic failure. None of the patients required bidirectional cavo-pulmonary shunt at the time of Cone reconstruction or later after operation. Cardiopulmonary bypass and aortic cross-clamp times are given in Table 1. There was a significant improvement of NYHA status for all patients after Cone reconstruction (3 (1–3) vs. 1 (1–2), P = 0.010). The global median follow-up length was 6 months (8 days–54 months). Early post-operative period was defined as the period between the day of surgery and the 30th day after the operation. The median of early post-operative follow-up (<30 post-operative days) was 10 days (3–27). The median of mid-term post-operative period was 7 months (2–54). Electrocardiographic findings Right complete bundle branch was present in nine patients in pre-operative period and in all patients in post-operative period. Pre-excitation was found in four patients (two required pre-operative radiofrequency ablation of an accessory pathway and two surgical maze procedure for pre-operative atrial fibrillation). One patient had an ICD pacemaker implanted in 2011 because of documented ventricular tachycardia requiring cardioversion. There was no significant difference in PR duration after Cone reconstruction (157 ± 20 ms vs. 161 ± 16 ms, P = 0.500) but QRS was significantly longer after Cone reconstruction (113 ± 8 ms vs. 141 ± 8 ms, P = 0.027). Conventional echocardiographic parameters Results for conventional parameters are presented in Figure 2. Figure 2 View largeDownload slide Right ventricle (RV) and left ventricle (LV) parameters in pre- and post-operative periods. Figure 2 View largeDownload slide Right ventricle (RV) and left ventricle (LV) parameters in pre- and post-operative periods. Tricuspid annulus diameter was significantly reduced (45.23 ± 7.16 mm vs. 14.75 ± 4.02 mm, P < 0.001). After Cone repair, RA area was decreased (22.17 ± 5.52 cm2 vs. 12.93 ± 4.34 cm2, P = 0.004) whereas functional RV area (18.48 ± 5.49 cm2 vs. 24.20 ± 3.81cm2, P = 0.070 and −1.78 ± 1.89 vs. 0.69 ± 1.12, P = 0.018 for z-score) and LV area (15.05 ± 2.60 cm2 vs. 19.34 ± 4.96 cm2, P = 0.001 and −3.83 ± 0.78 vs. −2.57 ± 0.78, P = 0.003 for z-score) were increased. Therefore, GOSH score [(RA + aRV area)/(functional RV + LA + LV area) at end-diastole] was significantly reduced (1.07 ± 0.24 vs. 0.25 ± 0.06, P = 0.007) in post-operative period. LV diameters were increased after Cone reconstruction (32.18 ± 3.64 mm vs. 37.91 ± 4.44 mm, P = 0.002 for end-diastolic diameter and 18.81 ± 1.83 mm vs. 22.72 ± 3.00 mm, P < 0.001 for end-systolic diameter). RV function measured by TAPSE and RV FAC was significantly impaired after Cone reconstruction (TAPSE 26.42 ± 5.79 mm before vs. 8.75 ± 3.18 mm after operation, P < 0.001, RV FAC 45.00 ± 8.13% in pre-operative period vs. 35.46 ± 5.76% in post-operative period, P = 0.038). Myocardial performance assessed by 2D strain systolic peak ‘Feasibility’ and technical limitations for RV 2D strain The assessment of RV function by 2D strain was not feasible in pre- and post-operative periods. In both pre- and post-operative period, the aRV was grossly dilated with a thin wall, which prevented accurate measurement of RV myocardial function by 2D strain. Global and segmental LV longitudinal 2D strain Results are presented in Table 2. Global LV 2D strain was significantly lower after Cone reconstruction (−20.49 ± 2.79 vs. −17.73 ± 2.76, P = 0.041) whereas in segmental analysis, only the basal lateral segment of LV had a significantly impaired 2D strain after reconstruction (−21.27 ± 2.17 vs. −17.20 ± 4.35, P = 0.035). There was no significant impairment in the septum 2D strain after Cone reconstruction, notably the basal segment which was part of the aRV before surgery (−16.96 ± 2.74 vs. −14.44 ± 3.32, P = 0.097). In some patients, we could observe abnormal motion of the septum with contraction in systole followed by an abnormal movement of the septum towards the opening mitral valve in early diastole. Table 2 Segmental analysis of LV 2D strain and time-to-peak (TTP) synchronicity in pre- and post-operative periods LV 2D strain (%) Pre-operative Post-operative P-value Basal septal −16.96 ± 2.74 −14.44 ± 3.32 0.097 Mid-septal −19.07 ± 2.22 −16.80 ± 2.95 0.101 Apical septal −22.58 ± 3.12 −19.95 ± 4.37 0.164 Basal lateral −21.27 ± 2.17 −17.20 ± 4.35 0.035 Mid-lateral −21.26 ± 2.88 −18.24 ± 4.24 0.112 Apical lateral −23.14 ± 2.67 −19.74 ± 4.69 0.324 TTP (corrected by HR) (ms) Basal septal 428 ± 31 428 ± 30 0.421 Mid-septal 434 ± 29 429 ± 32 0.379 Apical septal 452 ± 37 425 ± 37 0.352 Basal lateral 438 ± 29 418 ± 29 0.298 Mid-lateral 435 ± 24 409 ± 24 0.170 Apical lateral 456 ± 40 424 ± 40 0.136 LV 2D strain (%) Pre-operative Post-operative P-value Basal septal −16.96 ± 2.74 −14.44 ± 3.32 0.097 Mid-septal −19.07 ± 2.22 −16.80 ± 2.95 0.101 Apical septal −22.58 ± 3.12 −19.95 ± 4.37 0.164 Basal lateral −21.27 ± 2.17 −17.20 ± 4.35 0.035 Mid-lateral −21.26 ± 2.88 −18.24 ± 4.24 0.112 Apical lateral −23.14 ± 2.67 −19.74 ± 4.69 0.324 TTP (corrected by HR) (ms) Basal septal 428 ± 31 428 ± 30 0.421 Mid-septal 434 ± 29 429 ± 32 0.379 Apical septal 452 ± 37 425 ± 37 0.352 Basal lateral 438 ± 29 418 ± 29 0.298 Mid-lateral 435 ± 24 409 ± 24 0.170 Apical lateral 456 ± 40 424 ± 40 0.136 Table 2 Segmental analysis of LV 2D strain and time-to-peak (TTP) synchronicity in pre- and post-operative periods LV 2D strain (%) Pre-operative Post-operative P-value Basal septal −16.96 ± 2.74 −14.44 ± 3.32 0.097 Mid-septal −19.07 ± 2.22 −16.80 ± 2.95 0.101 Apical septal −22.58 ± 3.12 −19.95 ± 4.37 0.164 Basal lateral −21.27 ± 2.17 −17.20 ± 4.35 0.035 Mid-lateral −21.26 ± 2.88 −18.24 ± 4.24 0.112 Apical lateral −23.14 ± 2.67 −19.74 ± 4.69 0.324 TTP (corrected by HR) (ms) Basal septal 428 ± 31 428 ± 30 0.421 Mid-septal 434 ± 29 429 ± 32 0.379 Apical septal 452 ± 37 425 ± 37 0.352 Basal lateral 438 ± 29 418 ± 29 0.298 Mid-lateral 435 ± 24 409 ± 24 0.170 Apical lateral 456 ± 40 424 ± 40 0.136 LV 2D strain (%) Pre-operative Post-operative P-value Basal septal −16.96 ± 2.74 −14.44 ± 3.32 0.097 Mid-septal −19.07 ± 2.22 −16.80 ± 2.95 0.101 Apical septal −22.58 ± 3.12 −19.95 ± 4.37 0.164 Basal lateral −21.27 ± 2.17 −17.20 ± 4.35 0.035 Mid-lateral −21.26 ± 2.88 −18.24 ± 4.24 0.112 Apical lateral −23.14 ± 2.67 −19.74 ± 4.69 0.324 TTP (corrected by HR) (ms) Basal septal 428 ± 31 428 ± 30 0.421 Mid-septal 434 ± 29 429 ± 32 0.379 Apical septal 452 ± 37 425 ± 37 0.352 Basal lateral 438 ± 29 418 ± 29 0.298 Mid-lateral 435 ± 24 409 ± 24 0.170 Apical lateral 456 ± 40 424 ± 40 0.136 Global and segmental longitudinal 2D strain comparing early- and mid-term post-operative periods The results are presented in Table 3.Global LV 2D strain measured in 10 patients in the early post-operative period was significantly altered after surgery (−19.45 ± 1.99 vs. −16.08 ± 2.26, P = 0.016). Global LV 2D strain measured in 12 patients in the mid-term post-operative period had improved and was not significantly different to the pre-operative measurement. (−20.71 ± 3.11 vs. −18.75 ± 2.37, P = 0.247). (Figure 3) Table 3 Segmental analysis of LV 2D strain and TTP in pre- and early/mid-term post-operative periods LV 2D strain (%) Pre-operative (N = 10) Early post-operative (N = 10) P-value Basal septal −16.64 ± 4.13 −13.27 ± 3.31 0.168 Mid-septal −18.67 ± 2.66 −15.73 ± 2.77 0.067 Apical septal −22.26 ± 2.64 −19.36 ± 3.94 0.065 Basal lateral −19.27 ± 2.17 −17.99 ± 4.96 0.592 Mid-lateral −19.63 ± 3.30 −15.00 ± 4.68 0.059 Apical lateral −22.16 ± 3.18 −16.91 ± 2.70 0.007 TTP (corrected by HR) (ms) Basal septal 450 ± 33 421 ± 38 0.074 Mid-septal 450 ± 29 409 ± 44 0.041 Apical septal 463 ± 39 432 ± 53 0.333 Basal lateral 459 ± 42 434 ± 58 0.508 Mid-lateral 452 ± 32 418 ± 48 0.173 Apical lateral 470 ± 42 428 ± 52 0.203 LV 2D strain (%) Pre-operative (N = 12) Mid-term post- operative (N = 12) P-value Basal septal −18.80 ± 2.63 −15.55 ± 2.29 0.074 Mid-septal −20.23 ± 2.65 −18.21 ± 1.88 0.371 Apical septal −23.08 ± 4.23 −22.23 ± 2.76 0.678 Basal lateral −22.12 ± 2.60 −16.59 ± 4.15 0.068 Mid-lateral −21.62 ± 3.82 −18.87 ± 3.93 0.327 Apical lateral −23.64 ± 3.60 −22.96 ± 3.61 0.919 TTP (corrected by HR) (ms) Basal septal 415 ± 35 439 ± 33 0.814 Mid-septal 429 ± 38 442 ± 29 0.859 Apical septal 459 ± 51 427 ± 25 0.374 Basal lateral 434 ± 31 416 ± 29 0.367 Mid-lateral 436 ± 33 414 ± 25 0.308 Apical lateral 465 ± 56 429 ± 27 0.136 LV 2D strain (%) Pre-operative (N = 10) Early post-operative (N = 10) P-value Basal septal −16.64 ± 4.13 −13.27 ± 3.31 0.168 Mid-septal −18.67 ± 2.66 −15.73 ± 2.77 0.067 Apical septal −22.26 ± 2.64 −19.36 ± 3.94 0.065 Basal lateral −19.27 ± 2.17 −17.99 ± 4.96 0.592 Mid-lateral −19.63 ± 3.30 −15.00 ± 4.68 0.059 Apical lateral −22.16 ± 3.18 −16.91 ± 2.70 0.007 TTP (corrected by HR) (ms) Basal septal 450 ± 33 421 ± 38 0.074 Mid-septal 450 ± 29 409 ± 44 0.041 Apical septal 463 ± 39 432 ± 53 0.333 Basal lateral 459 ± 42 434 ± 58 0.508 Mid-lateral 452 ± 32 418 ± 48 0.173 Apical lateral 470 ± 42 428 ± 52 0.203 LV 2D strain (%) Pre-operative (N = 12) Mid-term post- operative (N = 12) P-value Basal septal −18.80 ± 2.63 −15.55 ± 2.29 0.074 Mid-septal −20.23 ± 2.65 −18.21 ± 1.88 0.371 Apical septal −23.08 ± 4.23 −22.23 ± 2.76 0.678 Basal lateral −22.12 ± 2.60 −16.59 ± 4.15 0.068 Mid-lateral −21.62 ± 3.82 −18.87 ± 3.93 0.327 Apical lateral −23.64 ± 3.60 −22.96 ± 3.61 0.919 TTP (corrected by HR) (ms) Basal septal 415 ± 35 439 ± 33 0.814 Mid-septal 429 ± 38 442 ± 29 0.859 Apical septal 459 ± 51 427 ± 25 0.374 Basal lateral 434 ± 31 416 ± 29 0.367 Mid-lateral 436 ± 33 414 ± 25 0.308 Apical lateral 465 ± 56 429 ± 27 0.136 Table 3 Segmental analysis of LV 2D strain and TTP in pre- and early/mid-term post-operative periods LV 2D strain (%) Pre-operative (N = 10) Early post-operative (N = 10) P-value Basal septal −16.64 ± 4.13 −13.27 ± 3.31 0.168 Mid-septal −18.67 ± 2.66 −15.73 ± 2.77 0.067 Apical septal −22.26 ± 2.64 −19.36 ± 3.94 0.065 Basal lateral −19.27 ± 2.17 −17.99 ± 4.96 0.592 Mid-lateral −19.63 ± 3.30 −15.00 ± 4.68 0.059 Apical lateral −22.16 ± 3.18 −16.91 ± 2.70 0.007 TTP (corrected by HR) (ms) Basal septal 450 ± 33 421 ± 38 0.074 Mid-septal 450 ± 29 409 ± 44 0.041 Apical septal 463 ± 39 432 ± 53 0.333 Basal lateral 459 ± 42 434 ± 58 0.508 Mid-lateral 452 ± 32 418 ± 48 0.173 Apical lateral 470 ± 42 428 ± 52 0.203 LV 2D strain (%) Pre-operative (N = 12) Mid-term post- operative (N = 12) P-value Basal septal −18.80 ± 2.63 −15.55 ± 2.29 0.074 Mid-septal −20.23 ± 2.65 −18.21 ± 1.88 0.371 Apical septal −23.08 ± 4.23 −22.23 ± 2.76 0.678 Basal lateral −22.12 ± 2.60 −16.59 ± 4.15 0.068 Mid-lateral −21.62 ± 3.82 −18.87 ± 3.93 0.327 Apical lateral −23.64 ± 3.60 −22.96 ± 3.61 0.919 TTP (corrected by HR) (ms) Basal septal 415 ± 35 439 ± 33 0.814 Mid-septal 429 ± 38 442 ± 29 0.859 Apical septal 459 ± 51 427 ± 25 0.374 Basal lateral 434 ± 31 416 ± 29 0.367 Mid-lateral 436 ± 33 414 ± 25 0.308 Apical lateral 465 ± 56 429 ± 27 0.136 LV 2D strain (%) Pre-operative (N = 10) Early post-operative (N = 10) P-value Basal septal −16.64 ± 4.13 −13.27 ± 3.31 0.168 Mid-septal −18.67 ± 2.66 −15.73 ± 2.77 0.067 Apical septal −22.26 ± 2.64 −19.36 ± 3.94 0.065 Basal lateral −19.27 ± 2.17 −17.99 ± 4.96 0.592 Mid-lateral −19.63 ± 3.30 −15.00 ± 4.68 0.059 Apical lateral −22.16 ± 3.18 −16.91 ± 2.70 0.007 TTP (corrected by HR) (ms) Basal septal 450 ± 33 421 ± 38 0.074 Mid-septal 450 ± 29 409 ± 44 0.041 Apical septal 463 ± 39 432 ± 53 0.333 Basal lateral 459 ± 42 434 ± 58 0.508 Mid-lateral 452 ± 32 418 ± 48 0.173 Apical lateral 470 ± 42 428 ± 52 0.203 LV 2D strain (%) Pre-operative (N = 12) Mid-term post- operative (N = 12) P-value Basal septal −18.80 ± 2.63 −15.55 ± 2.29 0.074 Mid-septal −20.23 ± 2.65 −18.21 ± 1.88 0.371 Apical septal −23.08 ± 4.23 −22.23 ± 2.76 0.678 Basal lateral −22.12 ± 2.60 −16.59 ± 4.15 0.068 Mid-lateral −21.62 ± 3.82 −18.87 ± 3.93 0.327 Apical lateral −23.64 ± 3.60 −22.96 ± 3.61 0.919 TTP (corrected by HR) (ms) Basal septal 415 ± 35 439 ± 33 0.814 Mid-septal 429 ± 38 442 ± 29 0.859 Apical septal 459 ± 51 427 ± 25 0.374 Basal lateral 434 ± 31 416 ± 29 0.367 Mid-lateral 436 ± 33 414 ± 25 0.308 Apical lateral 465 ± 56 429 ± 27 0.136 Figure 3 View largeDownload slide Global LV 2D strain in pre- and early/mid-term post-operative periods. Figure 3 View largeDownload slide Global LV 2D strain in pre- and early/mid-term post-operative periods. Comparison to aged-matched control group The median age of the group of 17 EA patients was 15 years (1–57) vs. 13 years (1–55) for the 17 patients of control group (P = 0.061). Global LV 2D strain measurements in pre-operative period were not significantly different from the control group (−20.49 ± 1.91 for EA group vs. −21.72 ± 1.83 for control group, P = 0.568), whereas they were significantly decreased in post-operative period (−17.73 ± 1.89 for EA group vs. −21.72 ± 1.83 for control group, P = 0.004). Basal septum 2D strain was significantly lower at both periods in EA group (−16.96 ± 2.74 vs. −19.86 ± 2.00, P = 0.018 in pre-operative period and −14.44 ± 3.32 vs. −19.86 ± 2.00 in post-operative period, P = 0.002). Synchronicity assessment (LV time-to-systolic peak corrected by HR) before and after operation Global LV time-to-systolic peak corrected by HR was not significantly decreased after Cone reconstruction (441 ± 26 ms vs. 418 ± 24 ms, P = 0.121) and there was no regional difference when segmental analysis was performed (Table 2). Synchronicity assessment (time-to-systolic peak corrected by HR) in early- and mid-term post-operative periods Global LV time-to-systolic peak corrected by HR was not significantly decreased after Cone reconstruction (457 ± 25 ms vs. 417 ± 45 ms, P = 0.074 (comparison between pre-operative measurements and early post-operative data) and 440 ± 35 ms vs. 422 ± 17 ms, P = 0.286 (comparison between pre-operative measurements and mid-term post-operative data) (Figure 4) and there was no regional difference when segmental analysis was performed (Table 3), except for mid-septal segment in early post-operative period. Figure 4 View largeDownload slide Global time-to-systolic peak in pre- and early/mid-term post-operative periods. Figure 4 View largeDownload slide Global time-to-systolic peak in pre- and early/mid-term post-operative periods. Intra- and inter-variability assessment Intra-class correlation for pre-operative global LV 2D strain was respectively 0.887 (0.676–0.960) for interobserver reliability and 0.924 (0.773–0.974) for intraobserver reliability. Intra-class correlation for pre-operative global TTPc was respectively 0.839 (0.539–0.944) for interobserver reliability and 0.887 (0.677–0.961) for intraobserver reliability. Discussion The Cone reconstruction for EA has raised increasing interest after demonstrating major improvement of tricuspid regurgitation and TV annulus reduction. This operation, because of its technical success in vast majority of cases, leads to an important change in loading conditions; the RV is taken from a situation of high pre-load to a relatively high afterload (higher wall stress) and the underfilled LV is given increased filling. However, little is known about the adaptation of both ventricles to these acute changes. In our previous study, we confirmed that although right ventricular function appeared significantly impaired immediately after operation, clinical status improved due to elimination of tricuspid regurgitation, increased net pulmonary blood flow and increased left ventricular stroke volume. In this study, we suggested for the first time that despite evidence of biventricular impairment immediately after Cone reconstruction, there was a trend towards later improvement. Interestingly, we could not confirm significant left ventricular systolic mechanical dys-synchrony in our group using advanced echocardiographic techniques. Our surgical series suggested a high success rate of Cone reconstruction2 with no post-operative death and no concomitant additional bidirectional cavo-pulmonary anastomosis. This may be unexpected to some degree, considering that a minority of referred patients were not accepted for surgical reconstruction (two patients with complete lamination of all TV leaflets and one patient with LV myocardial non-compaction). Post-operative clinical outcome This cohort included patients with significant TR. Similarly to other published groups, poor exercise tolerance and dyspnea were the main pre-operative symptoms.4,5 Significant reduction of tricuspid regurgitation and subjective clinical improvement documented by a decrease in NYHA classification have been demonstrated across a wide range of valve morphology and age stages in our study2 and in similar studies from Mayo6,7 and Munich.8 Impact of Cone reconstruction on cardiac physiology Before Cone reconstruction, this histologically abnormal RV is under high pre-load condition because of significant TR. This mechanism of increase in RV pre-load improves myocardial contraction on the basis of Frank Starling mechanism but simultaneously reduces effective cardiac output by decreasing forward flow.9 After successful Cone reconstruction, with amelioration of TR and inclusion of the aRV into the functional RV, this RV is suddenly exposed to lower pre-load and relatively increased afterload, through increased wall stress. However, the forward flow from the RV is increased resulting in better LV filling and higher LV stroke volume, as demonstrated by conventional echocardiographic parameters and MRI.2,8 LV myocardial performance Conventional echocardiographic parameters indicated that LV filling was improved as shown by increased LV diameter and area. This is in agreement with our previous study2 and the study from Munich.2 Although LV function was not altered after Cone reconstruction, 2D strain measurements showed decreased LV function in the early post-operative period with a trend to later recovery. This finding may be explained by the impact of cardiopulmonary bypass and aortic cross-clamp on myocardial performance early after operation, as demonstrated in both human and animal models,10,11 rather than by direct impact of Cone reconstruction physiology. The maximal variation of strain values seems to occur in the early post-operative period12 and is linked to the ischaemia–reperfusion phenomenon, endothelial dysfunction, and general inflammation.13 The endocardial layer, mostly made of longitudinal fibres, is the first to suffer, explaining why longitudinal strain is altered while radial strain and left ventricular ejection fraction (LVEF) are preserved.14 Primary LV myocardial impairment could also be present, with EA. Structural abnormalities, such as LV non-compaction or associated mutations in MYH7 genes are present in 18% of EA patients.15,16 However, in our cohort, we could not confirm any significant intrinsic myocardial impairment suggestive of myocardial fibrosis or ischaemia of the LV prior Cone reconstruction. RV myocardial performance RV myocardial performance appears visually altered after Cone reconstruction, which is confirmed by conventional echocardiographic parameters. This decrease in myocardial performance is probably multifactorial. Histological findings on EA hearts may be a part of the answer. The aRV is functionally part of the right atrium before surgery. The wall is usually very thin, with aneurysmal dilation of the posterior wall. In rare extreme cases, the endocardium is smooth and often devoid of myocardial fibres17,18 replaced by extensive fibrous tissue.19 Fibrosis is more important in this part of the ventricle in adult hearts with EA, suggesting that this histological change may be acquired.20 This may be related to the increased volume loading with TR, as the RV appears more prone to developing fibrosis in this loading condition than LV.21 As for the functional RV, its dilation is associated with a thinner wall and less myocardial fibers compared with EA without RV dilation.17 Therefore, EA is a far more complex disease than a simple structural abnormality of the TV. The right bundle branch block is often present in patient with EA. QRS duration in our study was longer after Cone reconstruction and this could potentially cause RV electro-mechanical dys-synchrony similar to left bundle branch block in the failing LV. RV myocardial performance may also be altered because of the negative impact of surgery under bypass with long aortic cross-clamp times. In fact, the RV myocardium is more susceptible to oxidative stress with a decreased angiogenic response, and is more likely to activate all death pathways.22,23 Any coronary artery injury would exacerbate the risk of arrhythmia and ischaemic myocardial damage. In our cohort, early arrhythmic problem was not a burden of post-operative morbidity, possibly due to limited myocardial plication procedure at the time of Cone reconstruction. RV myocardial performance was assessed by TAPSE and FAC, both parameters being decreased after Cone reconstruction. These parameters however are load dependent and may not allow to correctly interpret true myocardial function. Before Cone reconstruction, TAPSE is higher (supranormal) than in normal physiology because of the high pre-load caused by tricuspid regurgitation. During Cone reconstruction, a tricuspid annuloplasty (semi-circular ring) reduces the effective tricuspid annulus. Both delamination of valvular leaflets, with removal of abnormal attachments of the anterior leaflet and aortic cross-clamp may contribute to RV impairment. Alteration of TAPSE measurement is therefore probably multifactorial. A decrease in TAPSE could reflect a true alteration of right ventricular myocardial longitudinal performance on one hand but could also reflect decreased annular displacement because of a less compliant prosthetic annular ring. This questions the reliability of TAPSE in this context. Cardiac surgery is also well known to reduce TAPSE with several hypotheses to explain this phenomenon: RV geometrical changes in association with interventricular septal paradoxical motion, poor RV protection during CPB with intraoperative ischaemia or extra-myocardial causes (pericardium, changes in fossa ovale, post-operative adherence of RV to the thoracic wall).23 The RV FAC has also limitations, especially in the pre-operative period, as the functional RV may be very small. The RV 2D strain was impossible to perform in most patients due to lack of a defined myocardial layer. Therefore, the speckle tracking curves more likely represent endo-pericardial motion and false interpretation of myocardial contraction. Similarly, in the post-operative period, the lateral wall was difficult to define. This is partly because of surgical alteration in some patients undergoing RV plication and partly because of intrinsically deficient myocardium affecting the lateral and postero-inferior wall. Ventricular interaction and basal septum When comparing basal septal 2D strain in pre- and post-operative periods to a control group, we showed that basal septal 2D strain was significantly lower in EA than normal subjects in both periods. In EA, this part of the septum belongs to the atrialized part of the RV, often subjected to fibrosis. With surgical delamination, this part of the septum may suffer from ischaemia and additional fibrosis, which may explain weak contraction. Under normal loading conditions, the septum is concave towards the LV in both systole and diastole.9 Before the Cone reconstruction, the volume overloaded RV is severely dilated, leading to paradoxical deviation of interventricular septum, which may alter LV function.9,24 In some patients after Cone reconstruction, a bulging of the septum into the LV in early diastole reflects prolonged septal shift that may be due to lengthening of the RV contractile period, which impacts on LV filling.21 Interestingly, in our study we did not find any difference in LV systolic synchronicity on echocardiographic tissue deformation imaging suggesting that paradoxical septal motion is pre-operatively not only caused by delayed RV contraction but also by abnormal right atrial (including aRV) and left ventricular diastolic interaction. These findings can be supported by recent MRI study25 suggesting that abnormal septal behaviour could be an artefact of anterior LV translation rather than intrinsic myocardial dyskinesia. Yet again, our explanation would be that abnormal ‘dyskinetic’ septal motion in unoperated EA is the result of delayed RV contraction and interaction of functional right atrial and left ventricular volume and pressure changes, when, at the diastole, pressure in the functional right atrium exceeds the LV diastolic pressure but with maintained, synchronised, function during systole. Limitations This is a retrospective study with a small sample population. However, our detailed analysis using longitudinal pre- and post-operative data from the same patients allowed individual comparison over a wide range of patient ages and across a range of clinical severity. It may be informative to compare our data between different age groups. However, we felt that age-stratified subgroups would be too small, and therefore not representative. Many post-operative patients were inaccessible for longitudinal data, because they lived a long distance from the study centres. The RV function and synchronicity assessment was incomplete due to technical limitations as discussed above, illustrating the difficulty to accurately assess RV function in patients before and after Cone reconstruction. Conclusion The Cone reconstruction of the TV offers an effective operation in patients with EA and severe regurgitation. Despite excellent surgical results in most patients with improved clinical outcome, increased pulmonary net flow and increased LV filling, the adaptation of the ventricles after Cone reconstruction needs to be assessed on a long-term basis. The significant RV impairment seen immediately after operation is of concern, and is likely caused by several mechanisms including intrinsic myocardial deficiency and fibrosis, myocardial injury following valve tissue delamination, aRV plication, right bundle branch block, impact of cardiopulmonary bypass and aortic cross clamp. Detailed assessment of right ventricular mechanics using a speckle tracking technique was technically difficult, particularly in those patients with intrinsic myocardial deficiency and/or fibrosis of the initially atrialized part of the ventricle. In our group, the LV function seems to be well preserved and likely only temporarily affected by cardiopulmonary bypass. Due to the nature of extensive RV myocardial surgery, only the time will tell whether the low incidence of significant early complications in our series can be translated into a reliable long-term management strategy for severe forms of EA. It remains to be seen, whether there is potential for post-operative myocardial cellular growth and intrinsic RV remodelling. Functional assessment and comprehensive cross sectional and microscopic imaging will help to learn more from this unique disease. Conflict of interest: None declared. References 1 da Silva JP , Baumgratz JF , da Fonseca L , Afiune JY , Franchi SM , Lopes LM et al. Ebstein’s anomaly: results of the conic reconstruction of the tricuspid valve . Arq Bras Cardiol 2004 ; 82 : 217 – 20 . 2 Ibrahim M , Tsang VT , Caruana M , Hughes ML , Jenkyns S , Perdreau E et al. Cone reconstruction for Ebstein’s anomaly: patient outcomes, biventricular function and cardiopulmonary exercise capacity . J Thorac Cardiovasc Surg 2015 ; 149 : 1144 – 50 . Google Scholar CrossRef Search ADS PubMed 3 Celermajer DS , Cullen S , Sullivan ID , Spiegelhalter D , Wyse RK , Deanfield JE. Outcome in neonates with Ebstein’s anomaly . J Am Coll Cardiol 1992 ; 19 : 1041 – 6 . Google Scholar CrossRef Search ADS PubMed 4 Danielson GK , Fuster V. Surgical reconstruction of Ebstein’s anomaly . Ann Surg 1982 ; 196 : 499 – 503 . Google Scholar CrossRef Search ADS PubMed 5 Sirivella S , Gielchinsky I. Surgery of the Ebstein’s anomaly: early and late outcomes . J Card Surg 2011 ; 26 : 227 – 33 . Google Scholar CrossRef Search ADS PubMed 6 da Silva JP , Baumgratz JF , da Fonseca L , Franchi SM , Lopes LM , Tavares GM et al. The cone reconstruction of the tricuspid valve in Ebstein’s anomaly. The operation: early and midterm results . J Thorac Cardiovasc Surg 2007 ; 133 : 215 – 23 . Google Scholar CrossRef Search ADS PubMed 7 Anderson HN , Dearani JA , Said SM , Norris MD , Pundi KN , Miller AR et al. Cone reconstruction in children with Ebstein anomaly: the Mayo clinic experience . Congenit Heart Dis 2014 ; 9 : 266 – 71 . Google Scholar CrossRef Search ADS PubMed 8 Lange R , Burri M , Eschenbach LK , Badiu CC , Da Silva JP , Nagdyman N et al. Da Silva's cone repair for Ebstein's anomaly: effect on right ventricular size and function . Eur J Cardiothorac Surg 2015 ; 48 : 316 – 20 . Google Scholar CrossRef Search ADS PubMed 9 Haddad F , Hunt SA , Rosenthal DN , Murphy DJ. Right ventricular function in cardiovascular disease, part 1: anatomy, physiology aging, and functional assessment of the right ventricle . Circulation 2008 ; 117 : 1436 – 48 . Google Scholar CrossRef Search ADS PubMed 10 Matsuwaka R , Matsuda H , Shirakura R , Kaneko M , Fukushima N , Taniguchi K et al. Changes in left ventricular performance after global ischemia: assessing LV pressure-volume relationship . Ann Thorac Surg 1994 ; 57 : 151 – 6 . Google Scholar CrossRef Search ADS PubMed 11 Furukawa S , Kreiner G , Bavaria JE , Bavaria JE , Streicher JT , Edmunds LH. Recovery of oxygen utilization efficiency after global myocardial ischemia . Ann Thorac Surg 1991 ; 52 : 1063 – 8 . Google Scholar CrossRef Search ADS PubMed 12 Gorcsan JIII , Gasior TA , Mandarino WA , Deneault LG , Hattler BG , Pinsky MR. Assessment of the immediate effects of cardiopulmonary bypass on left ventricular performance by on-line pressure-area relations . Circulation 1994 ; 89 : 180 – 90 . Google Scholar CrossRef Search ADS PubMed 13 Wu ZK , Tarkka MR , Eloranta J , Pehkonen E , Laurikka J , Kaukinen L et al. Effect of ischaemic preconditioning, cardiopulmonary bypass and myocardial ischaemic/reperfusion on free radical generation in CABG patients . Cardiovasc Surg 2001 ; 9 : 362 – 8 . Google Scholar CrossRef Search ADS PubMed 14 Gjesdal O , Hopp E , Vartdal T , Lunde K , Helle-Valle T , Aakhus S et al. Global longitudinal strain measured by two-dimensional speckle tracking echocardiography is closely related to myocardial infarct size in chronic ischaemic heart disease . Clin Sci 2007 ; 113 : 287 – 96 . Google Scholar CrossRef Search ADS PubMed 15 Attenhofer Jost CH , Connolly HM , O’leary PW , Warnes CA , Tajik AJ , Seward JB. Left heart lesions in patients with Ebstein anomaly . Mayo Clin Proc 2005 ; 80 : 361 – 8 . Google Scholar CrossRef Search ADS PubMed 16 Postma AV , van Engelen K , Van de Meerakker J , Rahman T , Probst S , Baars MJ et al. Mutations in the sarcomere gene MYH7 in Ebstein anomaly . Circ Cardiovasc Genet 2011 ; 4 : 43 – 50 . Google Scholar CrossRef Search ADS PubMed 17 Anderson KR , Lie JT. The right ventricular myocardium in Ebstein’s anomaly. A morphometric histopathologic study . Mayo Clin Proc 1979 ; 54 : 181 – 4 . Google Scholar PubMed 18 Anderson KR , Lie JT. Pathologic anatomy of Ebstein’s anomaly of the heart revisited . Am J Cardiol 1978 ; 41 : 739 – 45 . Google Scholar CrossRef Search ADS PubMed 19 Egidy Assenza G , Valente AM , Geva T , Graham D , Pluchinotta FR , Sanders SP et al. QRS duration and QRS fractionation on surface electrocardiogram are markers of right ventricular dysfunction and atrialization in patients with Ebstein’s anomaly . Eur Heart J 2013 ; 34 : 191 – 200 . Google Scholar CrossRef Search ADS PubMed 20 Lee AH , Moore IE , Fagg NL , Cook AC , Kakadekar AP , Allan LD et al. Histological changes in the left and right ventricle in hearts with Ebstein’s malformation and tricuspid valvar dysplasia: a morphometric study of patients dying in fetal and perinatal periods . Cardiovasc Pathol 1995 ; 4 : 19 – 24 . Google Scholar CrossRef Search ADS PubMed 21 Friedberg MK , Redington AN. Right versus left ventricular failure: differences, similarities, and interactions . Circulation 2014 ; 129 : 1033 – 44 . Google Scholar CrossRef Search ADS PubMed 22 Reddy S , Bernstein D. Molecular mechanisms of right ventricular failure . Circulation 2015 ; 132 : 1734 – 42 . Google Scholar CrossRef Search ADS PubMed 23 Tamborini G , Muratori M , Brusoni D , Celeste F , Maffessanti F , Caiani EG et al. Is right ventricular systolic function reduced after cardiac surgery? A two- and three-dimensional echocardiographic study . Eur J Echocardiogr 2009 ; 10 : 630 – 4 . Google Scholar CrossRef Search ADS PubMed 24 Yacoub MH. Two hearts that beat as one . Circulation 1995 ; 92 : 156 – 7 . Google Scholar CrossRef Search ADS PubMed 25 Goleski PJ , Sheehan FH , Chen SS , Kilner PJ , Gatzoulis MA. The shape and function of the left ventricle in Ebstein’s anomaly . Int J Cardiol 2014 ; 171 : 404 – 12 . Google Scholar CrossRef Search ADS PubMed Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: [email protected]. 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Change in biventricular function after cone reconstruction of Ebstein’s anomaly: an echocardiographic study

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Oxford University Press
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: [email protected].
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2047-2404
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10.1093/ehjci/jex186
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Abstract

Abstract Aims The Cone reconstruction in Ebstein’s anomaly (EA) aims to reduce tricuspid valve regurgitation (TR) and reposition the valve to the anatomic annulus, but post-operative progress of ventricular function is poorly understood. This study evaluated biventricular function after Cone reconstruction using echocardiographic techniques. Methods and results A retrospective study assessing longitudinal change was conducted from 2009 to 2014. All symptomatic patients with EA and severe TR undergoing surgery were included. Transthoracic advanced echocardiography was performed pre- and post-operatively (at short-term (<30 days) and mid-term). Conventional and longitudinal 2D strain parameters were measured for left ventricle (LV) and right ventricle (RV). Paired analyses were compared using Wilcoxon Matched-pairs signed rank test. From the 38 patients operated for EA, the echocardiographic data of 17 patients, aged 15 (1–57 years) at operation could be analysed. Median follow up was 6 months (8 days–54 months). The tricuspid annular plane systolic excursion (26.42 ± 5.79 mm vs. 8.75 ± 3.18 mm, P < 0.001), RV fractional area change (FAC) (45.00 ± 8.13% vs. 35.46 ± 5.76%, P = 0.038) and LV 2D peak systolic strain were significantly reduced post-operatively (−20.49 ± 2.79 vs. −17.73 ± 2.76, P = 0.041), with a trend to later recovery for LV 2D strain. There was no evidence of systolic mechanical dys-synchrony before or after operation. Conclusion Although clinical outcome of Cone reconstruction for EA remains excellent, acute post-operative changes leads to reduction of myocardial function of both ventricles, with a trend to later recovery for LV. Continuing impairment of RV function is multifactorial but may reflect intrinsic myocardial deficiency. Ebstein’s anomaly, cone reconstruction, myocardial performance, mechanical synchrony Introduction Ebstein’s anomaly (EA) is a rare congenital heart disease occurring in 1 per 200 000 live births and accounting for approximately 1% of all congenital cardiac abnormalities. It is characterized by adherence of the septal and posterior leaflets to the underlying myocardium, which is responsible for downward (apical) displacement of the functional annulus, dilation of the right atrioventricular junction (true tricuspid annulus) and dilation of the ‘atrialized’ portion of the right ventricle, with various degrees of hypertrophy or hypoplasia and thinning of the right ventricle (RV) wall, and dilation of the right atrioventricular junction (true tricuspid annulus). Because of tricuspid valve regurgitation (TR), both parts of the RV (i.e. atrialized and functional components) are exposed to abnormal physiology with high pre-load. The latest surgical reconstruction (Cone reconstruction), involves delamination and rotation of the detached TV anterosuperior leaflet and use of the remnant of the septal and inferior leaflets to create a Cone-shaped valve.1 This reconstruction involves haemodynamic changes as demonstrated by a recent study2 with reduction in TR and increase in forward flow through the pulmonary outflow tract and left ventricle (LV). Post-operative RV function, visually assessed and measured by tricuspid annular plane systolic excursion (TAPSE), has been shown to be poor after Cone reconstruction. The aim of the study was to investigate biventricular function after Cone reconstruction using conventional and advanced echocardiographic techniques. Methods Study design This is a retrospective observational study, using longitudinally acquired pre-operative and short- to mid-term post-operative data from study subjects. Ethics approval for data collection was granted following local ethics review. Patient selection All patients with EA referred for Cone reconstruction at Great Ormond Street Hospital and the Heart Hospital between 2009 and 2014 were included in the study. Indication for operation was based on our institutional criteria for offering surgery: symptoms (cyanosis, arrhythmia, heart failure with EA and tricuspid regurgitation), or asymptomatic patients with severe tricuspid regurgitation and severe right heart dilatation. All operations were performed by the same surgeon (VT). Echocardiography assessment in pre-operative, short- and mid-term post-operative periods was performed. For all patients, clinical status, presence of arrhythmias, operative characteristics and post-operative follow-up were collected. Electrocardiographic analysis Pre- and post-operative ECG’s were collected to detect right bundle branch, Wolff–Parkinson–White anomaly, atrio-ventricular block and measure PR and QRS durations. Transthoracic echocardiography Transthoracic echocardiographic studies were performed using Vivid e9 machines (GE, Milwaukee, WI, USA). All images were obtained according to prospective protocol to achieve optimal quality. Cine loops of two cardiac cycles triggered by the R wave of the QRS complex were digitally saved. Subcostal, apical four-chamber, and parasternal long- and short-axis views were used to obtain pictures of the morphology of the tricuspid valve (TV), atrial and ventricular chambers and ventricular outflow tracts. All echocardiographic recordings were stored on digital versatile discs for off-line analyses with EchoPac software (GE). All measurements were supervised by J.M. Early post-operative period was defined as the period between the day of surgery and the 30th day after the operation. Conventional echocardiographic parameters Conventional echocardiographic parameters were collected in pre- and post-operative periods, including the areas of the right and left atriums, atrialized right ventricle (aRV), functional RV, and LV to calculate GOSH score.3 The size of TV annulus and the grade of TR were measured. RV function was assessed by TAPSE and fractional area change (RV FAC) if functional ventricular shape was suitable for measurement. LV dimensions were measured from M-mode in standard parasternal long axis view. LV function was evaluated by fractional shortening and ejection fraction by Simpson method. All measured cardiac dimensions were expressed in z-scores, using Boston Children’s Hospital Heart Center reference. Diastolic and systolic eccentricity index were also measured in short axis view. 2D speckle tracking analysis Cine loops over three cardiac cycles with a frame rate from 40 to 100 fps were used for off-line analysis on Echopac®. The best apical four-chamber view to visualise the six myocardial segments of each ventricle was selected and the endocardium limit was traced by the operator (Figure 1). The software automatically generated a second line at the level of epicardium, delineating a region of interest. The measurement of systolic peak of longitudinal strain was automatic and the analysis was accepted if the software validated the measurement of each cardiac segment. Manual adjustment was applied in cases with inappropriate automated software tracking on visual observation. This analysis was done in pre- and post-operative periods. Figure 1 View largeDownload slide Example of 2D Strain analysis before and after Cone reconstruction. RA, right atrium; aRV, atrialized right ventricle; RV, right ventricle. Figure 1 View largeDownload slide Example of 2D Strain analysis before and after Cone reconstruction. RA, right atrium; aRV, atrialized right ventricle; RV, right ventricle. Synchronicity assessment by 2D speckle tracking Mechanical synchronicity assessment was also performed. Manual adjustment of aortic valve closure was done from parasternal long axis view using TM mode. Time-to-systolic peak was measured for each segment, corresponding to the time from the onset of QRS to longitudinal strain systolic peak corrected by the Bazett formula. Comparison to normal values Pre- and post-operative measurements of global LV 2D strain were compared with values of an aged- and sex-matched control group of healthy subjects, referred to cardiology clinic for a heart murmur, with structurally normal heart confirmed on standard comprehensive sequential echocardiographic assessment. Statistical analysis Continuous variables are presented as median (range) and denote the number of patients, unless otherwise stated. P < 0.05 was taken to be statistically significant. Paired analyses were performed using Wilcoxon Matched-pairs signed rank test. Intra- and interobserver assessment was done on 17 pre-operative studies for global LV 2D strain and global LV time-to-systolic peak. The intraobserver variability was assessed by one investigator performing off-line analysis on the same patients 6 months apart to reduce recall bias. The interobserver variability was assessed by a second investigator who was unaware of the previous results, performing the investigation on the same 17 patients. The intra- and interobserver agreement was assessed calculating the intra-class correlation coefficient (two-way mixed model and consistency type, average measurements). The statistical analysis was performed using SPSS, version 19 (SPSS, Chicago, IL, USA). Results Patients and operative characteristics Pre- and perioperative patient characteristics are presented in Table 1. Seventeen patients could be involved in the study. The median age at operation was 15 years-old (1–57). Four patients presented with WPW. None of the patients had evidence of LV non-compaction on echocardiogram. Table 1 Pre- and perioperative patient characteristics Number of patients 17 Sex (M/F) 8/9 Median of age at operation (years) 15 (1–57) Median of weight (kg) 48 (10–100) Symptoms Poor exercise tolerance 41% (7/17) Cyanosis 6% (1/17) Palpitation 12% (2/17) Growth retardation 6% (1/17) Asymptomatic 35% (6/17) NYHA (median) 3 (1–3) Previous procedure BT shunt 6% (1/17) Bidirectional Glenn 12% (2/17) RVPA conduit 6% (1/17) MV reconstruction 6% (1/17) Arrhythmia ablation 12% (2/17) CPB duration (min) 130.88 ± 16.45 Cross-clamp duration (min) 83.8 ± 21.07 Tricuspid annuloplasty 17 Maze procedure (pre-operative AF) 12% (2/17) Other valvular procedure 1 (pulmonary valve) Death 0/17 Median of follow-up length 6 months (8 days–54 months) Bidirectional cavo-pulmonary connection 0 Number of patients 17 Sex (M/F) 8/9 Median of age at operation (years) 15 (1–57) Median of weight (kg) 48 (10–100) Symptoms Poor exercise tolerance 41% (7/17) Cyanosis 6% (1/17) Palpitation 12% (2/17) Growth retardation 6% (1/17) Asymptomatic 35% (6/17) NYHA (median) 3 (1–3) Previous procedure BT shunt 6% (1/17) Bidirectional Glenn 12% (2/17) RVPA conduit 6% (1/17) MV reconstruction 6% (1/17) Arrhythmia ablation 12% (2/17) CPB duration (min) 130.88 ± 16.45 Cross-clamp duration (min) 83.8 ± 21.07 Tricuspid annuloplasty 17 Maze procedure (pre-operative AF) 12% (2/17) Other valvular procedure 1 (pulmonary valve) Death 0/17 Median of follow-up length 6 months (8 days–54 months) Bidirectional cavo-pulmonary connection 0 Table 1 Pre- and perioperative patient characteristics Number of patients 17 Sex (M/F) 8/9 Median of age at operation (years) 15 (1–57) Median of weight (kg) 48 (10–100) Symptoms Poor exercise tolerance 41% (7/17) Cyanosis 6% (1/17) Palpitation 12% (2/17) Growth retardation 6% (1/17) Asymptomatic 35% (6/17) NYHA (median) 3 (1–3) Previous procedure BT shunt 6% (1/17) Bidirectional Glenn 12% (2/17) RVPA conduit 6% (1/17) MV reconstruction 6% (1/17) Arrhythmia ablation 12% (2/17) CPB duration (min) 130.88 ± 16.45 Cross-clamp duration (min) 83.8 ± 21.07 Tricuspid annuloplasty 17 Maze procedure (pre-operative AF) 12% (2/17) Other valvular procedure 1 (pulmonary valve) Death 0/17 Median of follow-up length 6 months (8 days–54 months) Bidirectional cavo-pulmonary connection 0 Number of patients 17 Sex (M/F) 8/9 Median of age at operation (years) 15 (1–57) Median of weight (kg) 48 (10–100) Symptoms Poor exercise tolerance 41% (7/17) Cyanosis 6% (1/17) Palpitation 12% (2/17) Growth retardation 6% (1/17) Asymptomatic 35% (6/17) NYHA (median) 3 (1–3) Previous procedure BT shunt 6% (1/17) Bidirectional Glenn 12% (2/17) RVPA conduit 6% (1/17) MV reconstruction 6% (1/17) Arrhythmia ablation 12% (2/17) CPB duration (min) 130.88 ± 16.45 Cross-clamp duration (min) 83.8 ± 21.07 Tricuspid annuloplasty 17 Maze procedure (pre-operative AF) 12% (2/17) Other valvular procedure 1 (pulmonary valve) Death 0/17 Median of follow-up length 6 months (8 days–54 months) Bidirectional cavo-pulmonary connection 0 There was no death during the follow-up period. In this cohort, there was no re-operation necessary, neither for repair of the Cone apparatus, nor for haemodynamic failure. None of the patients required bidirectional cavo-pulmonary shunt at the time of Cone reconstruction or later after operation. Cardiopulmonary bypass and aortic cross-clamp times are given in Table 1. There was a significant improvement of NYHA status for all patients after Cone reconstruction (3 (1–3) vs. 1 (1–2), P = 0.010). The global median follow-up length was 6 months (8 days–54 months). Early post-operative period was defined as the period between the day of surgery and the 30th day after the operation. The median of early post-operative follow-up (<30 post-operative days) was 10 days (3–27). The median of mid-term post-operative period was 7 months (2–54). Electrocardiographic findings Right complete bundle branch was present in nine patients in pre-operative period and in all patients in post-operative period. Pre-excitation was found in four patients (two required pre-operative radiofrequency ablation of an accessory pathway and two surgical maze procedure for pre-operative atrial fibrillation). One patient had an ICD pacemaker implanted in 2011 because of documented ventricular tachycardia requiring cardioversion. There was no significant difference in PR duration after Cone reconstruction (157 ± 20 ms vs. 161 ± 16 ms, P = 0.500) but QRS was significantly longer after Cone reconstruction (113 ± 8 ms vs. 141 ± 8 ms, P = 0.027). Conventional echocardiographic parameters Results for conventional parameters are presented in Figure 2. Figure 2 View largeDownload slide Right ventricle (RV) and left ventricle (LV) parameters in pre- and post-operative periods. Figure 2 View largeDownload slide Right ventricle (RV) and left ventricle (LV) parameters in pre- and post-operative periods. Tricuspid annulus diameter was significantly reduced (45.23 ± 7.16 mm vs. 14.75 ± 4.02 mm, P < 0.001). After Cone repair, RA area was decreased (22.17 ± 5.52 cm2 vs. 12.93 ± 4.34 cm2, P = 0.004) whereas functional RV area (18.48 ± 5.49 cm2 vs. 24.20 ± 3.81cm2, P = 0.070 and −1.78 ± 1.89 vs. 0.69 ± 1.12, P = 0.018 for z-score) and LV area (15.05 ± 2.60 cm2 vs. 19.34 ± 4.96 cm2, P = 0.001 and −3.83 ± 0.78 vs. −2.57 ± 0.78, P = 0.003 for z-score) were increased. Therefore, GOSH score [(RA + aRV area)/(functional RV + LA + LV area) at end-diastole] was significantly reduced (1.07 ± 0.24 vs. 0.25 ± 0.06, P = 0.007) in post-operative period. LV diameters were increased after Cone reconstruction (32.18 ± 3.64 mm vs. 37.91 ± 4.44 mm, P = 0.002 for end-diastolic diameter and 18.81 ± 1.83 mm vs. 22.72 ± 3.00 mm, P < 0.001 for end-systolic diameter). RV function measured by TAPSE and RV FAC was significantly impaired after Cone reconstruction (TAPSE 26.42 ± 5.79 mm before vs. 8.75 ± 3.18 mm after operation, P < 0.001, RV FAC 45.00 ± 8.13% in pre-operative period vs. 35.46 ± 5.76% in post-operative period, P = 0.038). Myocardial performance assessed by 2D strain systolic peak ‘Feasibility’ and technical limitations for RV 2D strain The assessment of RV function by 2D strain was not feasible in pre- and post-operative periods. In both pre- and post-operative period, the aRV was grossly dilated with a thin wall, which prevented accurate measurement of RV myocardial function by 2D strain. Global and segmental LV longitudinal 2D strain Results are presented in Table 2. Global LV 2D strain was significantly lower after Cone reconstruction (−20.49 ± 2.79 vs. −17.73 ± 2.76, P = 0.041) whereas in segmental analysis, only the basal lateral segment of LV had a significantly impaired 2D strain after reconstruction (−21.27 ± 2.17 vs. −17.20 ± 4.35, P = 0.035). There was no significant impairment in the septum 2D strain after Cone reconstruction, notably the basal segment which was part of the aRV before surgery (−16.96 ± 2.74 vs. −14.44 ± 3.32, P = 0.097). In some patients, we could observe abnormal motion of the septum with contraction in systole followed by an abnormal movement of the septum towards the opening mitral valve in early diastole. Table 2 Segmental analysis of LV 2D strain and time-to-peak (TTP) synchronicity in pre- and post-operative periods LV 2D strain (%) Pre-operative Post-operative P-value Basal septal −16.96 ± 2.74 −14.44 ± 3.32 0.097 Mid-septal −19.07 ± 2.22 −16.80 ± 2.95 0.101 Apical septal −22.58 ± 3.12 −19.95 ± 4.37 0.164 Basal lateral −21.27 ± 2.17 −17.20 ± 4.35 0.035 Mid-lateral −21.26 ± 2.88 −18.24 ± 4.24 0.112 Apical lateral −23.14 ± 2.67 −19.74 ± 4.69 0.324 TTP (corrected by HR) (ms) Basal septal 428 ± 31 428 ± 30 0.421 Mid-septal 434 ± 29 429 ± 32 0.379 Apical septal 452 ± 37 425 ± 37 0.352 Basal lateral 438 ± 29 418 ± 29 0.298 Mid-lateral 435 ± 24 409 ± 24 0.170 Apical lateral 456 ± 40 424 ± 40 0.136 LV 2D strain (%) Pre-operative Post-operative P-value Basal septal −16.96 ± 2.74 −14.44 ± 3.32 0.097 Mid-septal −19.07 ± 2.22 −16.80 ± 2.95 0.101 Apical septal −22.58 ± 3.12 −19.95 ± 4.37 0.164 Basal lateral −21.27 ± 2.17 −17.20 ± 4.35 0.035 Mid-lateral −21.26 ± 2.88 −18.24 ± 4.24 0.112 Apical lateral −23.14 ± 2.67 −19.74 ± 4.69 0.324 TTP (corrected by HR) (ms) Basal septal 428 ± 31 428 ± 30 0.421 Mid-septal 434 ± 29 429 ± 32 0.379 Apical septal 452 ± 37 425 ± 37 0.352 Basal lateral 438 ± 29 418 ± 29 0.298 Mid-lateral 435 ± 24 409 ± 24 0.170 Apical lateral 456 ± 40 424 ± 40 0.136 Table 2 Segmental analysis of LV 2D strain and time-to-peak (TTP) synchronicity in pre- and post-operative periods LV 2D strain (%) Pre-operative Post-operative P-value Basal septal −16.96 ± 2.74 −14.44 ± 3.32 0.097 Mid-septal −19.07 ± 2.22 −16.80 ± 2.95 0.101 Apical septal −22.58 ± 3.12 −19.95 ± 4.37 0.164 Basal lateral −21.27 ± 2.17 −17.20 ± 4.35 0.035 Mid-lateral −21.26 ± 2.88 −18.24 ± 4.24 0.112 Apical lateral −23.14 ± 2.67 −19.74 ± 4.69 0.324 TTP (corrected by HR) (ms) Basal septal 428 ± 31 428 ± 30 0.421 Mid-septal 434 ± 29 429 ± 32 0.379 Apical septal 452 ± 37 425 ± 37 0.352 Basal lateral 438 ± 29 418 ± 29 0.298 Mid-lateral 435 ± 24 409 ± 24 0.170 Apical lateral 456 ± 40 424 ± 40 0.136 LV 2D strain (%) Pre-operative Post-operative P-value Basal septal −16.96 ± 2.74 −14.44 ± 3.32 0.097 Mid-septal −19.07 ± 2.22 −16.80 ± 2.95 0.101 Apical septal −22.58 ± 3.12 −19.95 ± 4.37 0.164 Basal lateral −21.27 ± 2.17 −17.20 ± 4.35 0.035 Mid-lateral −21.26 ± 2.88 −18.24 ± 4.24 0.112 Apical lateral −23.14 ± 2.67 −19.74 ± 4.69 0.324 TTP (corrected by HR) (ms) Basal septal 428 ± 31 428 ± 30 0.421 Mid-septal 434 ± 29 429 ± 32 0.379 Apical septal 452 ± 37 425 ± 37 0.352 Basal lateral 438 ± 29 418 ± 29 0.298 Mid-lateral 435 ± 24 409 ± 24 0.170 Apical lateral 456 ± 40 424 ± 40 0.136 Global and segmental longitudinal 2D strain comparing early- and mid-term post-operative periods The results are presented in Table 3.Global LV 2D strain measured in 10 patients in the early post-operative period was significantly altered after surgery (−19.45 ± 1.99 vs. −16.08 ± 2.26, P = 0.016). Global LV 2D strain measured in 12 patients in the mid-term post-operative period had improved and was not significantly different to the pre-operative measurement. (−20.71 ± 3.11 vs. −18.75 ± 2.37, P = 0.247). (Figure 3) Table 3 Segmental analysis of LV 2D strain and TTP in pre- and early/mid-term post-operative periods LV 2D strain (%) Pre-operative (N = 10) Early post-operative (N = 10) P-value Basal septal −16.64 ± 4.13 −13.27 ± 3.31 0.168 Mid-septal −18.67 ± 2.66 −15.73 ± 2.77 0.067 Apical septal −22.26 ± 2.64 −19.36 ± 3.94 0.065 Basal lateral −19.27 ± 2.17 −17.99 ± 4.96 0.592 Mid-lateral −19.63 ± 3.30 −15.00 ± 4.68 0.059 Apical lateral −22.16 ± 3.18 −16.91 ± 2.70 0.007 TTP (corrected by HR) (ms) Basal septal 450 ± 33 421 ± 38 0.074 Mid-septal 450 ± 29 409 ± 44 0.041 Apical septal 463 ± 39 432 ± 53 0.333 Basal lateral 459 ± 42 434 ± 58 0.508 Mid-lateral 452 ± 32 418 ± 48 0.173 Apical lateral 470 ± 42 428 ± 52 0.203 LV 2D strain (%) Pre-operative (N = 12) Mid-term post- operative (N = 12) P-value Basal septal −18.80 ± 2.63 −15.55 ± 2.29 0.074 Mid-septal −20.23 ± 2.65 −18.21 ± 1.88 0.371 Apical septal −23.08 ± 4.23 −22.23 ± 2.76 0.678 Basal lateral −22.12 ± 2.60 −16.59 ± 4.15 0.068 Mid-lateral −21.62 ± 3.82 −18.87 ± 3.93 0.327 Apical lateral −23.64 ± 3.60 −22.96 ± 3.61 0.919 TTP (corrected by HR) (ms) Basal septal 415 ± 35 439 ± 33 0.814 Mid-septal 429 ± 38 442 ± 29 0.859 Apical septal 459 ± 51 427 ± 25 0.374 Basal lateral 434 ± 31 416 ± 29 0.367 Mid-lateral 436 ± 33 414 ± 25 0.308 Apical lateral 465 ± 56 429 ± 27 0.136 LV 2D strain (%) Pre-operative (N = 10) Early post-operative (N = 10) P-value Basal septal −16.64 ± 4.13 −13.27 ± 3.31 0.168 Mid-septal −18.67 ± 2.66 −15.73 ± 2.77 0.067 Apical septal −22.26 ± 2.64 −19.36 ± 3.94 0.065 Basal lateral −19.27 ± 2.17 −17.99 ± 4.96 0.592 Mid-lateral −19.63 ± 3.30 −15.00 ± 4.68 0.059 Apical lateral −22.16 ± 3.18 −16.91 ± 2.70 0.007 TTP (corrected by HR) (ms) Basal septal 450 ± 33 421 ± 38 0.074 Mid-septal 450 ± 29 409 ± 44 0.041 Apical septal 463 ± 39 432 ± 53 0.333 Basal lateral 459 ± 42 434 ± 58 0.508 Mid-lateral 452 ± 32 418 ± 48 0.173 Apical lateral 470 ± 42 428 ± 52 0.203 LV 2D strain (%) Pre-operative (N = 12) Mid-term post- operative (N = 12) P-value Basal septal −18.80 ± 2.63 −15.55 ± 2.29 0.074 Mid-septal −20.23 ± 2.65 −18.21 ± 1.88 0.371 Apical septal −23.08 ± 4.23 −22.23 ± 2.76 0.678 Basal lateral −22.12 ± 2.60 −16.59 ± 4.15 0.068 Mid-lateral −21.62 ± 3.82 −18.87 ± 3.93 0.327 Apical lateral −23.64 ± 3.60 −22.96 ± 3.61 0.919 TTP (corrected by HR) (ms) Basal septal 415 ± 35 439 ± 33 0.814 Mid-septal 429 ± 38 442 ± 29 0.859 Apical septal 459 ± 51 427 ± 25 0.374 Basal lateral 434 ± 31 416 ± 29 0.367 Mid-lateral 436 ± 33 414 ± 25 0.308 Apical lateral 465 ± 56 429 ± 27 0.136 Table 3 Segmental analysis of LV 2D strain and TTP in pre- and early/mid-term post-operative periods LV 2D strain (%) Pre-operative (N = 10) Early post-operative (N = 10) P-value Basal septal −16.64 ± 4.13 −13.27 ± 3.31 0.168 Mid-septal −18.67 ± 2.66 −15.73 ± 2.77 0.067 Apical septal −22.26 ± 2.64 −19.36 ± 3.94 0.065 Basal lateral −19.27 ± 2.17 −17.99 ± 4.96 0.592 Mid-lateral −19.63 ± 3.30 −15.00 ± 4.68 0.059 Apical lateral −22.16 ± 3.18 −16.91 ± 2.70 0.007 TTP (corrected by HR) (ms) Basal septal 450 ± 33 421 ± 38 0.074 Mid-septal 450 ± 29 409 ± 44 0.041 Apical septal 463 ± 39 432 ± 53 0.333 Basal lateral 459 ± 42 434 ± 58 0.508 Mid-lateral 452 ± 32 418 ± 48 0.173 Apical lateral 470 ± 42 428 ± 52 0.203 LV 2D strain (%) Pre-operative (N = 12) Mid-term post- operative (N = 12) P-value Basal septal −18.80 ± 2.63 −15.55 ± 2.29 0.074 Mid-septal −20.23 ± 2.65 −18.21 ± 1.88 0.371 Apical septal −23.08 ± 4.23 −22.23 ± 2.76 0.678 Basal lateral −22.12 ± 2.60 −16.59 ± 4.15 0.068 Mid-lateral −21.62 ± 3.82 −18.87 ± 3.93 0.327 Apical lateral −23.64 ± 3.60 −22.96 ± 3.61 0.919 TTP (corrected by HR) (ms) Basal septal 415 ± 35 439 ± 33 0.814 Mid-septal 429 ± 38 442 ± 29 0.859 Apical septal 459 ± 51 427 ± 25 0.374 Basal lateral 434 ± 31 416 ± 29 0.367 Mid-lateral 436 ± 33 414 ± 25 0.308 Apical lateral 465 ± 56 429 ± 27 0.136 LV 2D strain (%) Pre-operative (N = 10) Early post-operative (N = 10) P-value Basal septal −16.64 ± 4.13 −13.27 ± 3.31 0.168 Mid-septal −18.67 ± 2.66 −15.73 ± 2.77 0.067 Apical septal −22.26 ± 2.64 −19.36 ± 3.94 0.065 Basal lateral −19.27 ± 2.17 −17.99 ± 4.96 0.592 Mid-lateral −19.63 ± 3.30 −15.00 ± 4.68 0.059 Apical lateral −22.16 ± 3.18 −16.91 ± 2.70 0.007 TTP (corrected by HR) (ms) Basal septal 450 ± 33 421 ± 38 0.074 Mid-septal 450 ± 29 409 ± 44 0.041 Apical septal 463 ± 39 432 ± 53 0.333 Basal lateral 459 ± 42 434 ± 58 0.508 Mid-lateral 452 ± 32 418 ± 48 0.173 Apical lateral 470 ± 42 428 ± 52 0.203 LV 2D strain (%) Pre-operative (N = 12) Mid-term post- operative (N = 12) P-value Basal septal −18.80 ± 2.63 −15.55 ± 2.29 0.074 Mid-septal −20.23 ± 2.65 −18.21 ± 1.88 0.371 Apical septal −23.08 ± 4.23 −22.23 ± 2.76 0.678 Basal lateral −22.12 ± 2.60 −16.59 ± 4.15 0.068 Mid-lateral −21.62 ± 3.82 −18.87 ± 3.93 0.327 Apical lateral −23.64 ± 3.60 −22.96 ± 3.61 0.919 TTP (corrected by HR) (ms) Basal septal 415 ± 35 439 ± 33 0.814 Mid-septal 429 ± 38 442 ± 29 0.859 Apical septal 459 ± 51 427 ± 25 0.374 Basal lateral 434 ± 31 416 ± 29 0.367 Mid-lateral 436 ± 33 414 ± 25 0.308 Apical lateral 465 ± 56 429 ± 27 0.136 Figure 3 View largeDownload slide Global LV 2D strain in pre- and early/mid-term post-operative periods. Figure 3 View largeDownload slide Global LV 2D strain in pre- and early/mid-term post-operative periods. Comparison to aged-matched control group The median age of the group of 17 EA patients was 15 years (1–57) vs. 13 years (1–55) for the 17 patients of control group (P = 0.061). Global LV 2D strain measurements in pre-operative period were not significantly different from the control group (−20.49 ± 1.91 for EA group vs. −21.72 ± 1.83 for control group, P = 0.568), whereas they were significantly decreased in post-operative period (−17.73 ± 1.89 for EA group vs. −21.72 ± 1.83 for control group, P = 0.004). Basal septum 2D strain was significantly lower at both periods in EA group (−16.96 ± 2.74 vs. −19.86 ± 2.00, P = 0.018 in pre-operative period and −14.44 ± 3.32 vs. −19.86 ± 2.00 in post-operative period, P = 0.002). Synchronicity assessment (LV time-to-systolic peak corrected by HR) before and after operation Global LV time-to-systolic peak corrected by HR was not significantly decreased after Cone reconstruction (441 ± 26 ms vs. 418 ± 24 ms, P = 0.121) and there was no regional difference when segmental analysis was performed (Table 2). Synchronicity assessment (time-to-systolic peak corrected by HR) in early- and mid-term post-operative periods Global LV time-to-systolic peak corrected by HR was not significantly decreased after Cone reconstruction (457 ± 25 ms vs. 417 ± 45 ms, P = 0.074 (comparison between pre-operative measurements and early post-operative data) and 440 ± 35 ms vs. 422 ± 17 ms, P = 0.286 (comparison between pre-operative measurements and mid-term post-operative data) (Figure 4) and there was no regional difference when segmental analysis was performed (Table 3), except for mid-septal segment in early post-operative period. Figure 4 View largeDownload slide Global time-to-systolic peak in pre- and early/mid-term post-operative periods. Figure 4 View largeDownload slide Global time-to-systolic peak in pre- and early/mid-term post-operative periods. Intra- and inter-variability assessment Intra-class correlation for pre-operative global LV 2D strain was respectively 0.887 (0.676–0.960) for interobserver reliability and 0.924 (0.773–0.974) for intraobserver reliability. Intra-class correlation for pre-operative global TTPc was respectively 0.839 (0.539–0.944) for interobserver reliability and 0.887 (0.677–0.961) for intraobserver reliability. Discussion The Cone reconstruction for EA has raised increasing interest after demonstrating major improvement of tricuspid regurgitation and TV annulus reduction. This operation, because of its technical success in vast majority of cases, leads to an important change in loading conditions; the RV is taken from a situation of high pre-load to a relatively high afterload (higher wall stress) and the underfilled LV is given increased filling. However, little is known about the adaptation of both ventricles to these acute changes. In our previous study, we confirmed that although right ventricular function appeared significantly impaired immediately after operation, clinical status improved due to elimination of tricuspid regurgitation, increased net pulmonary blood flow and increased left ventricular stroke volume. In this study, we suggested for the first time that despite evidence of biventricular impairment immediately after Cone reconstruction, there was a trend towards later improvement. Interestingly, we could not confirm significant left ventricular systolic mechanical dys-synchrony in our group using advanced echocardiographic techniques. Our surgical series suggested a high success rate of Cone reconstruction2 with no post-operative death and no concomitant additional bidirectional cavo-pulmonary anastomosis. This may be unexpected to some degree, considering that a minority of referred patients were not accepted for surgical reconstruction (two patients with complete lamination of all TV leaflets and one patient with LV myocardial non-compaction). Post-operative clinical outcome This cohort included patients with significant TR. Similarly to other published groups, poor exercise tolerance and dyspnea were the main pre-operative symptoms.4,5 Significant reduction of tricuspid regurgitation and subjective clinical improvement documented by a decrease in NYHA classification have been demonstrated across a wide range of valve morphology and age stages in our study2 and in similar studies from Mayo6,7 and Munich.8 Impact of Cone reconstruction on cardiac physiology Before Cone reconstruction, this histologically abnormal RV is under high pre-load condition because of significant TR. This mechanism of increase in RV pre-load improves myocardial contraction on the basis of Frank Starling mechanism but simultaneously reduces effective cardiac output by decreasing forward flow.9 After successful Cone reconstruction, with amelioration of TR and inclusion of the aRV into the functional RV, this RV is suddenly exposed to lower pre-load and relatively increased afterload, through increased wall stress. However, the forward flow from the RV is increased resulting in better LV filling and higher LV stroke volume, as demonstrated by conventional echocardiographic parameters and MRI.2,8 LV myocardial performance Conventional echocardiographic parameters indicated that LV filling was improved as shown by increased LV diameter and area. This is in agreement with our previous study2 and the study from Munich.2 Although LV function was not altered after Cone reconstruction, 2D strain measurements showed decreased LV function in the early post-operative period with a trend to later recovery. This finding may be explained by the impact of cardiopulmonary bypass and aortic cross-clamp on myocardial performance early after operation, as demonstrated in both human and animal models,10,11 rather than by direct impact of Cone reconstruction physiology. The maximal variation of strain values seems to occur in the early post-operative period12 and is linked to the ischaemia–reperfusion phenomenon, endothelial dysfunction, and general inflammation.13 The endocardial layer, mostly made of longitudinal fibres, is the first to suffer, explaining why longitudinal strain is altered while radial strain and left ventricular ejection fraction (LVEF) are preserved.14 Primary LV myocardial impairment could also be present, with EA. Structural abnormalities, such as LV non-compaction or associated mutations in MYH7 genes are present in 18% of EA patients.15,16 However, in our cohort, we could not confirm any significant intrinsic myocardial impairment suggestive of myocardial fibrosis or ischaemia of the LV prior Cone reconstruction. RV myocardial performance RV myocardial performance appears visually altered after Cone reconstruction, which is confirmed by conventional echocardiographic parameters. This decrease in myocardial performance is probably multifactorial. Histological findings on EA hearts may be a part of the answer. The aRV is functionally part of the right atrium before surgery. The wall is usually very thin, with aneurysmal dilation of the posterior wall. In rare extreme cases, the endocardium is smooth and often devoid of myocardial fibres17,18 replaced by extensive fibrous tissue.19 Fibrosis is more important in this part of the ventricle in adult hearts with EA, suggesting that this histological change may be acquired.20 This may be related to the increased volume loading with TR, as the RV appears more prone to developing fibrosis in this loading condition than LV.21 As for the functional RV, its dilation is associated with a thinner wall and less myocardial fibers compared with EA without RV dilation.17 Therefore, EA is a far more complex disease than a simple structural abnormality of the TV. The right bundle branch block is often present in patient with EA. QRS duration in our study was longer after Cone reconstruction and this could potentially cause RV electro-mechanical dys-synchrony similar to left bundle branch block in the failing LV. RV myocardial performance may also be altered because of the negative impact of surgery under bypass with long aortic cross-clamp times. In fact, the RV myocardium is more susceptible to oxidative stress with a decreased angiogenic response, and is more likely to activate all death pathways.22,23 Any coronary artery injury would exacerbate the risk of arrhythmia and ischaemic myocardial damage. In our cohort, early arrhythmic problem was not a burden of post-operative morbidity, possibly due to limited myocardial plication procedure at the time of Cone reconstruction. RV myocardial performance was assessed by TAPSE and FAC, both parameters being decreased after Cone reconstruction. These parameters however are load dependent and may not allow to correctly interpret true myocardial function. Before Cone reconstruction, TAPSE is higher (supranormal) than in normal physiology because of the high pre-load caused by tricuspid regurgitation. During Cone reconstruction, a tricuspid annuloplasty (semi-circular ring) reduces the effective tricuspid annulus. Both delamination of valvular leaflets, with removal of abnormal attachments of the anterior leaflet and aortic cross-clamp may contribute to RV impairment. Alteration of TAPSE measurement is therefore probably multifactorial. A decrease in TAPSE could reflect a true alteration of right ventricular myocardial longitudinal performance on one hand but could also reflect decreased annular displacement because of a less compliant prosthetic annular ring. This questions the reliability of TAPSE in this context. Cardiac surgery is also well known to reduce TAPSE with several hypotheses to explain this phenomenon: RV geometrical changes in association with interventricular septal paradoxical motion, poor RV protection during CPB with intraoperative ischaemia or extra-myocardial causes (pericardium, changes in fossa ovale, post-operative adherence of RV to the thoracic wall).23 The RV FAC has also limitations, especially in the pre-operative period, as the functional RV may be very small. The RV 2D strain was impossible to perform in most patients due to lack of a defined myocardial layer. Therefore, the speckle tracking curves more likely represent endo-pericardial motion and false interpretation of myocardial contraction. Similarly, in the post-operative period, the lateral wall was difficult to define. This is partly because of surgical alteration in some patients undergoing RV plication and partly because of intrinsically deficient myocardium affecting the lateral and postero-inferior wall. Ventricular interaction and basal septum When comparing basal septal 2D strain in pre- and post-operative periods to a control group, we showed that basal septal 2D strain was significantly lower in EA than normal subjects in both periods. In EA, this part of the septum belongs to the atrialized part of the RV, often subjected to fibrosis. With surgical delamination, this part of the septum may suffer from ischaemia and additional fibrosis, which may explain weak contraction. Under normal loading conditions, the septum is concave towards the LV in both systole and diastole.9 Before the Cone reconstruction, the volume overloaded RV is severely dilated, leading to paradoxical deviation of interventricular septum, which may alter LV function.9,24 In some patients after Cone reconstruction, a bulging of the septum into the LV in early diastole reflects prolonged septal shift that may be due to lengthening of the RV contractile period, which impacts on LV filling.21 Interestingly, in our study we did not find any difference in LV systolic synchronicity on echocardiographic tissue deformation imaging suggesting that paradoxical septal motion is pre-operatively not only caused by delayed RV contraction but also by abnormal right atrial (including aRV) and left ventricular diastolic interaction. These findings can be supported by recent MRI study25 suggesting that abnormal septal behaviour could be an artefact of anterior LV translation rather than intrinsic myocardial dyskinesia. Yet again, our explanation would be that abnormal ‘dyskinetic’ septal motion in unoperated EA is the result of delayed RV contraction and interaction of functional right atrial and left ventricular volume and pressure changes, when, at the diastole, pressure in the functional right atrium exceeds the LV diastolic pressure but with maintained, synchronised, function during systole. Limitations This is a retrospective study with a small sample population. However, our detailed analysis using longitudinal pre- and post-operative data from the same patients allowed individual comparison over a wide range of patient ages and across a range of clinical severity. It may be informative to compare our data between different age groups. However, we felt that age-stratified subgroups would be too small, and therefore not representative. Many post-operative patients were inaccessible for longitudinal data, because they lived a long distance from the study centres. The RV function and synchronicity assessment was incomplete due to technical limitations as discussed above, illustrating the difficulty to accurately assess RV function in patients before and after Cone reconstruction. Conclusion The Cone reconstruction of the TV offers an effective operation in patients with EA and severe regurgitation. Despite excellent surgical results in most patients with improved clinical outcome, increased pulmonary net flow and increased LV filling, the adaptation of the ventricles after Cone reconstruction needs to be assessed on a long-term basis. The significant RV impairment seen immediately after operation is of concern, and is likely caused by several mechanisms including intrinsic myocardial deficiency and fibrosis, myocardial injury following valve tissue delamination, aRV plication, right bundle branch block, impact of cardiopulmonary bypass and aortic cross clamp. Detailed assessment of right ventricular mechanics using a speckle tracking technique was technically difficult, particularly in those patients with intrinsic myocardial deficiency and/or fibrosis of the initially atrialized part of the ventricle. In our group, the LV function seems to be well preserved and likely only temporarily affected by cardiopulmonary bypass. Due to the nature of extensive RV myocardial surgery, only the time will tell whether the low incidence of significant early complications in our series can be translated into a reliable long-term management strategy for severe forms of EA. 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Journal

European Heart Journal – Cardiovascular Imaging – Oxford University Press

Published: Jul 31, 2017

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