© 2014, Wiley Periodicals, Inc. DOI: 10.1111/echo.12581
Echocardiography
Impaired Right and Left Ventricular Function in Asymptomatic Children with Repaired Tetralogy of Fallot by Two-Dimensional Speckle Tracking Echocardiography Study Yuman Li, M.D., Ph.D., Mingxing Xie, M.D., Ph.D., Xinfang Wang, M.D., Ph.D., Qing Lu, M.D., Ph.D., Li Zhang, M.D., Ph.D., and Pingping Ren, M.D., Ph.D. Department of Ultrasonography, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Background: Early detection of right ventricular (RV) and left ventricular (LV) dysfunction in patients with repaired tetralogy of Fallot (TOF) is essential because dysfunction is correlated with a poor clinical outcome. The aim of this study was to assess RV and LV function in asymptomatic children with repaired TOF by two-dimensional ultrasound speckle tracking echocardiography (STE). Methods: Fifty-six asymptomatic children with a preserved biventricular ejection fraction (EF) after repair of TOF and 35 healthy control subjects were studied. RV and LV strain and strain rate were measured by STE. RVEF and pulmonary regurgitation (PR) were assessed using cardiac magnetic resonance imaging. Results: Compared with the control subjects, RV regional longitudinal strain and strain rate and global longitudinal strain (GLS) and strain rate (GLSR) were impaired in children with repaired TOF. Likewise, LV circumferential and radial strain and strain rate were reduced in patients with TOF. In contrast, longitudinal strain and strain rate did not differ between the groups. RV and LV GLSR were correlated with postoperative follow-up period (r1 = 0.44; r2 = 0.48). RV GLS and GLSR were associated with RVEF (r1 = 0.64; r2 = 0.60) and PR (r1 = 0.48; r2 = 0.49). LV circumferential strain rate was related to PR (r = 0.45). Conclusions: STE can identify abnormalities that may represent early impairment of RV and LV systolic function in postoperative TOF patients with a preserved EF. PR is associated with decreased biventricular performance in repaired patients. STE-derived strain and strain rate may be useful indices for detecting the early deterioration of biventricular performance in patients with TOF. (Echocardiography 2015;32:135–143) Key words: echocardiography, right ventricular function, left ventricular function, tetralogy of Fallot, strain–strain rate Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect.1 With the advent of intra-cardiac surgery, most patients with repaired TOF have a good long-term prognosis. However, many postoperative patients have pulmonary regurgitation (PR) that leads to right ventricular (RV) dilation, right heart failure, arrhythmias, or sudden cardiac death.2 RV systolic dysfunction in repaired patients has been described as the determinant of long-term survival and the independent predictor of poor clinical status.3 In addition, PR and RV dilation may have an impact on the shape and function of the Address for correspondence and reprint requests: Mingxing Xie, M.D., Ph.D., Department of Ultrasonography, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277# Jiefang Ave, Wuhan 430022, China. Fax: 86-27-85726386; E-mail: [email protected]
left ventricle (LV). A recent study suggests that LV longitudinal dysfunction is associated with a greater risk of sudden cardiac death/life-threatening ventricular arrhythmias.4 Although most patients with repaired TOF are asymptomatic in the clinical setting, RV and LV function in these patients may be impaired; therefore, RV and LV functional assessment in patients with repaired TOF has increased in clinical practice. Recently, two-dimensional speckle tracking echocardiography (STE) emerged as a promising tool for assessing myocardial performance. This technique does not depend on geometric assumptions and has no angle dependence; therefore, it can be widely used in the evaluation of RV and LV function in patients with a variety of heart diseases,5–8 including congenital heart disease.9,10 The purpose of this study was to use STE to evaluate RV and LV function in asymptomatic 135
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children with repaired TOF and to explore the correlations between the biventricular systolic function parameters and the degree of PR, postoperative follow-up period, and Q-, R-, and Swave duration. Methods: Study Population: From December 2008 to June 2011, 56 consecutive children (34 males, 22 females; 5.4 4.1 years, range 1.5–16 years) with TOF repaired in our hospital were enrolled in this study. The mean postoperative follow-up period was 2.8 years (median 2 years, range 1–11 years). The mean age at surgery was 2.5 years (median 1 year, range 0.5– 11.5 years). All patients were in New York Heart Association (NYHA) functional class I. The inclusion criteria were postoperative follow-up period >1 year and no residual intra-cardiac shunt or residual RV outflow tract (RVOT) obstructions. Patients with 1 or more of the following criteria were excluded: severe tricuspid regurgitation, significant RVOT obstructions (>30 mmHg), RV pacemaker, and RV – pulmonary arterial connection by conduit. The patients were divided according to surgery approach into infundibular patch and transannular patch subgroups. The infundibular patch was nontransannular. The transannular patch involved a more extensive incision made across the pulmonary valve annulus for placement of a large patch. The control group consisted of 35 age- and sex-matched normal subjects (5.7 4.9 years, range 1–18 years; 22 males) who had no evidence of cardiopulmonary disease as assessed by physical checkup, electrocardiogram (Cardimax Fx-7302, Beijing, China), chest x-ray, and echocardiography. All of the subjects were in sinus rhythm. The study was approved by the institutional review ethics board. Echocardiographic Equipment and Conventional Echocardiographic Parameters: Echocardiography was performed using a commercially available ultrasound transducer and equipment (M3S and M7S probes, Vivid 7; GE Medical Systems, Horten, Norway). During echocardiography, the subjects were at rest in the left lateral decubitus position. RV end-diastolic diameter (RVEDD) and right atrial diameter (RA) were determined from the apical four-chamber view.11 For conventional RV function assessment, tricuspid annular peak systolic velocity (Sm), early diastolic velocity (Em) and late diastolic velocity (Am) assessed by tissue Doppler imaging (TDI), and tricuspid annular peak systolic excursion (TAPSE) assessed by M-mode echocardiography were measured from the apical four-chamber 136
view at the RV free wall level.11 LV ejection fraction (EF) was calculated according to the biplane Simpson rule. Two-Dimensional STE Processing: Two-dimensional grayscale images were obtained for the subjects using the apical fourchamber view and the parasternal short-axis view at the mid-ventricular level at frame rates of 60– 90 frames/sec. RV and LV longitudinal strain and strain rates were measured from the apical fourchamber view; LV radial strain and strain rate and circumferential strain and strain rate were measured from mid-ventricular short-axis images. All of the images were digitally stored for offline analysis (EchoPAC, version BT06; GE-Vingmed, Horten, Norway). The RV and LV endocardial borders were manually traced in the end-systolic frame at the point in the cardiac cycle in which the endocardial border was the clearest. The region of interest (ROI) in each image was automatically generated. The position of the ROI and its width was adjusted manually when the speckle tracking appeared to be poor. The software automatically tracked and accepted segments of good tracking quality and rejected poorly tracked segments. When all segments of the RV or LV were accepted, the RV and LV longitudinal strain and strain rate curves and the LV radial and circumferential strain and strain rate curves were automatically generated. Representative examples of RV and LV strain and strain rate curves in patients with TOF are shown in Figure 1. CMR Imaging: A subset of 21 patients with TOF was also studied using cardiac magnetic resonance (CMR) imaging to assess RV volumes and RVEF, LVEF, and PR fractions within 1 month of echocardiography. A 1.5-T MRI scanner (Magnetom Avanto; Siemens Healthcare, Erlangen, Germany) was used, and consecutive single-slice acquisitions from the base to the apex of the RV and LV in the standard short-axis orientation were obtained using a retrospectively ECG-gated cine steady-state free precession (SSFP) sequence (TR 39.75 msec, TE 1.12 msec, slice thickness 6–8 mm, FOV 320– 400 mm2 [according to the individual’s size], matrix 156 9 192, bandwidth 930, flip angle 80°, average 1). Image datasets were transferred to a computer workstation and were analyzed with dedicated software (Argus, Erlangen, Germany) by a single experienced observer who was blinded to the echocardiographic results. End-diastolic and end-systolic contours were manually traced for each slice in the short-axis view. RV end-diastolic volume (RVEDV), RV endsystolic volume (RVESV), RVEF, and LVEF were automatically obtained from the analysis above.
Biventricular Function in Repaired TOF by STE
Figure 1. RV longitudinal strain and strain rate curves in a child with repaired TOF A, B. LV radial C, D. and circumferential E, F. strain and strain rate curves in a child with repaired TOF. RV = right ventricular; TOF = tetralogy of Fallot; LV = left ventricular.
Total pulmonary forward flow, pulmonary reverse flow, and PR fraction were calculated. PR fraction was defined as the diastolic reversed flow expressed as a percentage of the forward flow. Statistical Analysis: Statistical analysis was performed with an SPSS software package (SPSS for Windows 11.5, SPSS Inc., Chicago, IL, USA). Continuous data are
expressed as the mean value standard deviation (SD). Categorical data were analyzed by chisquare test. The TOF and control groups were compared using two-sample independent t tests. Further comparisons among the transannular patch, infundibular patch, and control groups were made using one-way analysis of variance with Bonferroni’s post hoc analysis. Correlations between the biventricular global systolic function 137
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TABLE I General Characteristics and Two-Dimensional Echocardiography and Tissue Doppler Imaging Variable Male/female Age (year) Heart rate (beats/min) LVEF (%) RA diameter (cm) RVEDD (cm) Sm (cm/sec) Em (cm/sec) Am (cm/sec) TAPSE (cm) QRS duration (msec)
Controls (n = 35)
Total – TOF (n = 56)
Infundibular Patch (n = 27)
Transannular Patch (n = 29)
22/13 5.7 4.9 88 18 67.27 5.12 2.76 0.66 2.59 0.63 9.23 1.12 9.15 1.53 8.45 2.87 1.73 0.38 97 23
34/22 5.4 4.1 81 17 65.98 6.56 3.26 0.74* 3.29 0.75* 6.15 1.42* 7.18 2.39* 4.75 1.85* 1.23 0.32* 126 18*
16/11 4.3 2.4 78 14 63.46 6.29 3.16 0.78* 3.17 0.79* 5.91 1.41* 7.37 2.28* 5.01 2.25* 1.19 0.35* 127 15*
18/11 6.1 4.9 85 20 62.39 7.38 3.35 0.71* 3.40 0.72* 6.37 1.43* 7.09 2.25* 4.52 1.41* 1.27 0.29* 124 21*
TOF = tetralogy of Fallot; LVEF = left ventricular ejection fraction; RA = right atrial; RVEDD = right ventricular end-diastolic diameter; Sm = tricuspid annular plane peak systolic velocity; Em = tricuspid annular plane early diastolic velocity; Am = tricuspid annular plane late diastolic velocity; TAPSE = tricuspid annular plane peak systolic excursion. *P < 0.05 compared with normal controls.
Results: Baseline Characteristics: The baseline characteristics of the study population are listed in Table I. Twenty-nine of the patients had received transannular patches, and 27 had infundibular patches. There was no significant difference in LVEF between the groups. Sm, Em, Am, and TAPSE were decreased in children with repaired TOF compared with the control subjects. The postoperative TOF group exhibited a dilated RA and RV and a longer QRS duration than the control group. In contrast, RA, RV, QRS duration, Sm, Em, Am, and TAPSE did not differ between the transannular and infundibular patch subgroups.
Figure 2. RV regional and global strain A. and strain rate B. in the control and postoperative TOF groups. Base = basal RV free wall; Mid = mid RV free wall; Apex = apical RV free wall; RV = right ventricular; TOF = tetralogy of Fallot. *P < 0.05 versus the control group.
and CMR parameters, postoperative follow-up period, and QRS duration were calculated as Pearson’s or Spearman’s correlation coefficients depending on the data distribution. Intra-observer and inter-observer variability was assessed in 15 randomly selected subjects (10 patients with repaired TOF and 5 normal control subjects). Inter-observer and intra-observer reproducibility was evaluated using the intraclass correlation coefficient (ICC). For all analyses, a value of P < 0.05 was considered statistically significant. 138
RV Global and Regional Function in Patients with Repaired TOF: The RV regional and global longitudinal strain (GLS) and strain rate (GLSR) for the control and postoperative TOF groups are shown in Figure 2. The longitudinal strain and strain rate of the RV free wall for all segments were significantly impaired in patients with repaired TOF compared with the control subjects (P < 0.05 for all segments). Likewise, RV GLS and GLSR were lower in patients than in normal control subjects. RV GLS and GLSR in the control subjects and repaired children with transannular and infundibular patches are summarized in Figure 3. Compared with the control group, postoperative patients with transannular and infundibular patches had significantly decreased RV GLS and GLSR. Furthermore, both GLS and GLSR were lower in postoperative children with transannular patches than in those with infundibular patches. There was no significant association between RV GLS or
Biventricular Function in Repaired TOF by STE
Figure 3. RV GLS A. and GLSR B. in the control subjects and patients with transannular and infundibular patches. RV = right ventricular; GLS = global longitudinal strain; GLSR = global longitudinal strain rate. *P < 0.05 versus the control group; #P < 0.05 versus patients with an infundibular patch.
Figure 4. Comparisons of LV regional and global systolic longitudinal A, B. circumferential C, D. and radial E, F. strain and strain rate between patients and control subjects. Base-L = basal LV lateral wall; Mid-L = mid LV lateral wall; Apex-L = apical LV lateral wall; Base-S = basal septum; Mid-S = mid septum; and Apex-S = apical septum; LV = left ventricular. *P < 0.05 versus control subjects.
GLSR and age at repair (r1 = r2 = 0.26, P = 0.19).
0.15, P = 0.46;
LV Global and Regional Function in Patients with Repaired TOF: LV longitudinal, circumferential, and radial strain and strain rate are shown in Figure 4. LV circum-
ferential and radial strain and strain rate were reduced in patients with TOF compared with control subjects. Longitudinal septal peak strain and strain rate were lower in patients with TOF than in control subjects, whereas LV lateral wall longitudinal strain and strain rate did not differ between the groups. The age at repair was not 139
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Figure 5. Correlations between biventricular GLSR and postoperative follow-up period A, C. and between RV GLSR and QRS duration B. The relationship between CMR-derived PR fraction and RV GLS D. RV GLSR E. and LV GCSR F. The association between CMR-derived RVEF and RV GLS G. and GLSR H. GLSR = global longitudinal strain rate; RV = right ventricular; CMR = cardiac magnetic resonance; PR = pulmonary regurgitation; GLS = global longitudinal strain; LV = left ventricular; GCSR = global circumferential strain rate; RVEF = right ventricular ejection fraction.
associated with LV longitudinal, radial, or circumferential strain and strain rate.
radial, or circumferential strain and strain rate and QRS duration.
Correlation between Postoperative Period or QRS Duration and LV and RV Global Systolic Function: RV GLSR was correlated inversely with postoperative follow-up period and QRS duration (r1 = 0.44, P < 0.05; r2 = 0.48, P < 0.05; Fig. 5A and B). In contrast, there was no correlation between RV GLS and QRS duration or postoperative follow-up period in this study (r1 = 0.30, P = 0.07; r2 = 0.05, P = 0.76). LV GLSR was related to postoperative follow-up period (r = 0.48, P < 0.05; Fig. 5C), whereas there was no association between LV circumferential or radial strain and strain rate and postoperative follow-up period. Likewise, we did not identify a significant association between LV longitudinal,
Association between Echocardiographic Biventricular Function and CMR Parameters: The CMR findings in 21 patients were as follows: RVEDV 145.4 56.8 mL, RVESV 54.6 32.5 mL, RVEF 52.5 11.5%, LVEF 60.7 8.4%, and PR fraction 37.1 13.8%. The RVEF values in 4 patients were below the published lower level for normal healthy volunteers.12 PR fraction was correlated inversely with RV GLS and GLSR (r1 = 0.48, P < 0.05; r2 = 0.49, P < 0.05; Fig. 5D and E). In contrast, we did not identify an association between PR fraction and RVEF in this study (r = 0.30, P = 0.19). We also found a significant association between LV global circumferential strain rate and PR fraction (r = 0.45, P < 0.05; Fig. 5F). However, LV longitudinal or
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radial strain and strain rate were not related to PR. RV GLS and GLSR were associated with CMRderived RVEF (r1 = 0.64, P < 0.05; r2 = 0.60, P < 0.05; Fig. 5G and H), whereas TAPSE and Sm were not associated with CMR-based RVEF. Intra-Observer and Inter-Observer Variability: The inter-observer ICC was 0.94 for RV GLS and 0.93 for RV GLSR. The intra-observer ICC was 0.95 and 0.94 for RV GLS and RV GLSR, respectively. Discussion: This study demonstrates that RV and LV strain and strain rate in asymptomatic children with preserved biventricular EF after TOF repair are decreased compared with those of control subjects. The reduction in the biventricular strain and strain rate in postoperative patients is correlated with PR. RV and LV strain rates are associated with the postoperative follow-up period, suggesting that STE may be a useful follow-up tool for the serial evaluation of biventricular myocardial performance in patients with repaired TOF. Impaired RV regional and global function in patients with repaired TOF is not unique and has also been identified in other studies.13–17 However, the majority of these studies observed older patients or all subsets of patients, including asymptomatic and symptomatic patients. This study focused on asymptomatic children with repaired TOF. In a previous RV strain and strain rate study, the parameters were obtained from TDI, which has an intrinsic limitation of angle dependence. In contrast, we quantified the RV regional and global function using a speckle tracking technique that has been shown to be superior to TDI. In this study, we found that RV regional and global strain and strain rate were significantly reduced in patients compared with control subjects despite normal or near normal RVEF in the majority of patients with repaired TOF. Furthermore, we also identified that RV GLS and GLSR are lower in patients with transannular patches than in those with infundibular patches. These results suggest that the type of RVOT reconstruction may have an effect on postoperative RV function. A previous study demonstrated that several unfavorable factors influence RV function in postoperative patients, including: (1) chronic PR, (2) a noncontractile RVOT patch, (3) a chronic dilated free wall, and (4) septum dysfunction.18 In addition, Babu-Narayan et al.19 showed that RV myocardial fibrosis was present extensively in patients with repaired TOF. These changes in myocardial architecture have contributed to RV function impairment.
Because LV dysfunction is a strong predictor of worsening prognosis in patients with repaired TOF, early detection of the LV dysfunction is crucial in these patients. In this study, LV circumferential and radial strain and strain rate were decreased despite a normal LVEF in patients after TOF repair, and these parameters may be early indicators of the deterioration of LV function. However, LV lateral longitudinal strain and strain rate were relatively maintained. These results are consistent with recent studies.20,21 Probable mechanisms for LV dysfunction in postoperative patients with TOF include preoperative hypoxemia, LV fibrosis, LV dyssynchrony, and RV dilatation and dysfunction.22 Our finding of significant differences in the longitudinal systolic strain/ strain rate of the LV free wall compared with the septum between patients and control subjects suggests that ventricular–ventricular interactions are most likely responsible. The mechanism of ventricular–ventricular interaction may be mediated through the ventricular septum. In addition, we found that a decreased LV global circumferential strain rate was associated with PR fraction, suggesting unfavorable left–right ventricular interactions.22 Unlike conventional RV function parameters, such as TAPSE, Sm, and RV fractional area change, STE-derived indices not only allow the global analysis of RV function but also allow the regional analysis of RV contractility.23 In this study, we found a significant association between RV STE indices and CMR-derived RVEF, whereas TAPSE and Sm were not associated with CMR-based RVEF. These results are in agreement with the findings of Mercer-Rosa et al.,24 who demonstrated that TAPSE is not associated with CMR-based RVEF or representative of global RV function in patients with TOF. Moreover, we showed that patients with transannular patches had a significantly lower RV GLS and GLSR than those with infundibular patches; however, Sm and TAPSE were not different between the groups. Sm and TAPSE failed to differentiate patients with transannular patches from those with infundibular patches. Therefore, we conclude that STE indices may be more accurate echocardiographic measurements of RV systolic performance than conventional echocardiographic parameters of RV function. In addition, although RVEF levels were normal or near normal in the majority of patients in this study, RV longitudinal strain, and strain rate were reduced in patients compared with control subjects. We also identified a decrease in LV circumferential and radial strain in patients with preserved LVEF after TOF repair. Moreover, we found that RV and LV longitudinal strain rates were associated significantly with postoperative 141
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follow-up duration. This finding is consistent with the study of Scherptong et al.,13 which showed during follow-up that CMR-derived RVEF remained unchanged but RV longitudinal peak strain decreased. Therefore, we conclude that STE-derived strain and strain rate may be more sensitive for detecting changes in biventricular performance and that STE may be a useful follow-up tool in the early detection of myocardial impairment. In this study, we attempted to analyze the impact of PR on RV function in asymptomatic children with repaired TOF. Our findings showed that PR was significantly correlated with RV strain and strain rate. Previous reports showing the effect of PR on regional RV function were discordant. Eyskens et al.25 and Kowalik et al.26 showed that PR was associated with TDI-derived RV strain and strain rate. In contrast, Frigiola et al.27 showed no correlation between TDIderived RV deformation and the severity of PR in patients with repaired TOF. The lack of association between RV deformation and the degree of PR in that study may be due to their semiquantitative, subjective assessment of PR using echocardiography. However, the correlation between the degree of PR and RV strain and strain rate by STE is unknown. To our knowledge, this study is the first to show a significant association between the severity of PR and RV deformation abnormalities as assessed by STE. Most importantly, PR was quantified objectively using CMR imaging in this study. We also examined the effect of PR on LV performance using STE and demonstrated a negative impact of PR on LV performance. This result was consistent with that of Fernandes et al.,20 who found that PR was correlated with decreased LV strain. Study Limitations: This study has potential limitations. First, this study included a small number of patients, and future studies with a larger sample size are needed to determine the utility of STE-derived strain and strain rate for the assessment of biventricular myocardial function. Second, not all patients underwent CMR imaging. Therefore, the relationship between echocardiographic biventricular function and CMR parameters must be assessed further. A third limitation of this study is that it is a single-center study. Surgical techniques may differ from center to center. Different surgical techniques may impact postoperative RV/LV function. A fourth limitation is the lack of longitudinal follow-up data in this study. Therefore, we cannot demonstrate whether the abnormalities in RV and LV function are reversible or irreversible.
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Finally, myocardial motion is a complicated three-dimensional motion, and STE based on two-dimensional images cannot fully reflect three-dimensional myocardial motion. Conclusions: Asymptomatic children with preserved biventricular EF after TOF repair exhibited impaired RV and LV myocardial function, suggesting subclinical myocardial damage. PR affects RV performance in asymptomatic children with repaired TOF. Reduced LV strain was associated with PR, which most likely indicates adverse ventricular interactions. STE may be a useful technique in the early detection of myocardial impairment in patients after TOF repair. References 1. Brickner ME, Hillis LD, Lange RA: Congenital heart disease in adults: Second of two parts. N Engl J Med 2000;342:334–342. 2. Gatzoulis MA, Balaji S, Webber SA, et al: Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: A multicenter study. Lancet 2000;356:975–981. 3. Geva T, Sandweiss BM, Gauvreau K, et al: Factors associated with impaired clinical status in long-term survivors of tetralogy of Fallot repair evaluated by magnetic resonance imaging. J Am Coll Cardiol 2004;43:1068–1074. 4. Diller GP, Kempny A, Liodakis E, et al: Left ventricular longitudinal function predicts life-threatening ventricular arrhythmia and death in adults with repaired tetralogy of Fallot. Circulation 2012;125:2440–2446. 5. Prinz C, van Buuren F, Faber L, et al: Myocardial fibrosis is associated with biventricular dysfunction in patients with hypertrophic cardiomyopathy. Echocardiography 2012;29:438–444. 6. Tanboga IH, Kurt M, Bilen E, et al: Assessment of right ventricular mechanics in patients with mitral stenosis by two-dimensional deformation imaging. Echocardiography 2012;29:956–961. 7. Delgado M, Ruiz M, Mesa D, et al: Early improvement of the regional and global ventricle function estimated by two-dimensional speckle tracking echocardiography after percutaneous aortic valve implantation speckle tracking after Core Valve implantation. Echocardiography 2013;30:37–44. 8. Platz E, Hassanein AH, Shah A, et al: Regional right ventricular strain pattern in patients with acute pulmonary embolism. Echocardiography 2012;29:464–470. 9. Forsey J, Friedberg MK, Mertens L: Speckle tracking echocardiography in pediatric and congenital heart disease. Echocardiography 2013;30:447–459. 10. Bussadori C, Oliveira P, Arcidiacono C, et al: Right and left ventricular strain and strain rate in young adults before and after percutaneous atrial septal defect closure. Echocardiography 2011;28:730–737. 11. Rudski LG, Lai WW, Afilalo J, et al: Guidelines for the echocardiographic assessment of the right heart in adults: A report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr 2010;23:685–713. 12. Fiechter M, Fuchs TA, Gebhard C, et al: Age-related normal structural and functional ventricular values in cardiac
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function assessed by magnetic resonance. BMC Med Imaging 2013;13:6. Scherptong RW, Mollema SA, Blom NA, et al: Right ventricular peak systolic longitudinal strain is a sensitive marker for right ventricular deterioration in adult patients with tetralogy of Fallot. Int J Cardiovasc Imaging 2009;25:669–676. D’Andrea A, Caso P, Sarubbi B, et al: Right ventricular myocardial dysfunction in adult patients late after repair of tetralogy of Fallot. Int J Cardiol 2004;94:213–220. Weidemann F, Eyskens B, Mertens L, et al: Quantification of regional right and left ventricular function by ultrasonic strain rate and strain indexes after surgical repair of tetralogy of Fallot. Am J Cardiol 2002;90:133– 138. Brili S, Alexopoulos N, Latsios G, et al: Tissue Doppler imaging and brain natriuretic peptide levels in adults with repaired tetralogy of Fallot. J Am Soc Echocardiogr 2005;18:1149–1154. Davlouros PA, Kilner PJ, Hornung TS, et al: Right ventricular function in adults with repaired tetralogy of Fallot assessed with cardiovascular magnetic resonance imaging: Detrimental role of right ventricular outflow aneurysms or akinesia and adverse right-to-left ventricular interaction. J Am Coll Cardiol 2002;40:2044–2052. Dexter L: Atrial septal defect. Br Heart J 1956;18:209– 225. Babu-Narayan SV, Kilner PJ, Li W, et al: Ventricular fibrosis suggested by cardiovascular magnetic resonance in adults with repaired tetralogy of Fallot and its relationship to adverse markers of clinical outcome. Circulation 2006;113:405–413. Fernandes FP, Manlhiot C, Roche SL, et al: Impaired left ventricular myocardial mechanics and their relation to
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pulmonary regurgitation, right ventricular enlargement and exercise capacity in asymptomatic children after repair of tetralogy of Fallot. J Am Soc Echocardiogr 2012;25:494–503. Takayasu H, Takahashi K, Takigiku K, et al: Left ventricular torsion and strain in patients with repaired tetralogy of Fallot assessed by speckle tracking imaging. Echocardiography 2011;28:720–729. Cheung EW, Liang XC, Lam WW, et al: Impact of right ventricular dilation on left ventricular myocardial deformation in patients after surgical repair of tetralogy of Fallot. Am J Cardiol 2009;104:1264–1270. Reisner SA, Lysyansky P, Agmon Y, et al: Global longitudinal strain: A novel index of left ventricular systolic function. J Am Soc Echocardiogr 2004;17:630–633. Mercer-Rosa L, Parnell A, Forfia PR, et al: Tricuspid annular plane systolic excursion in the assessment of right ventricular function in children and adolescents after repair of tetralogy of Fallot. J Am Soc Echocardiogr 2013;26:1322–1329. Eyskens B, Brown SC, Claus P, et al: The influence of pulmonary regurgitation on regional right ventricular function in children after surgical repair of tetralogy of Fallot. Eur J Echocardiogr 2010;11:341–345. ski J, et al: The impact of z_ an Kowalik E, Kowalski M, Ro pulmonary regurgitation on right ventricular regional myocardial function: An echocardiographic study in adults after total repair of tetralogy of Fallot. J Am Soc Echocardiogr 2011;24:1199–1204. Frigiola A, Redington AN, Cullen S, et al: Pulmonary regurgitation is an important determinant of right ventricular contractile dysfunction in patients with surgically repaired tetralogy of Fallot. Circulation 2004;110:II153– II157.
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Impaired Right and Left Ventricular Function in Asymptomatic Children with Repaired Tetralogy of Fallot by Two-Dimensional Speckle Tracking Echocardiography Study Yuman Li, M.D., Ph.D., Mingxing Xie, M.D., Ph.D., Xinfang Wang, M.D., Ph.D., Qing Lu, M.D., Ph.D., Li Zhang, M.D., Ph.D., and Pingping Ren, M.D., Ph.D. Department of Ultrasonography, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
Background: Early detection of right ventricular (RV) and left ventricular (LV) dysfunction in patients with repaired tetralogy of Fallot (TOF) is essential because dysfunction is correlated with a poor clinical outcome. The aim of this study was to assess RV and LV function in asymptomatic children with repaired TOF by two-dimensional ultrasound speckle tracking echocardiography (STE). Methods: Fifty-six asymptomatic children with a preserved biventricular ejection fraction (EF) after repair of TOF and 35 healthy control subjects were studied. RV and LV strain and strain rate were measured by STE. RVEF and pulmonary regurgitation (PR) were assessed using cardiac magnetic resonance imaging. Results: Compared with the control subjects, RV regional longitudinal strain and strain rate and global longitudinal strain (GLS) and strain rate (GLSR) were impaired in children with repaired TOF. Likewise, LV circumferential and radial strain and strain rate were reduced in patients with TOF. In contrast, longitudinal strain and strain rate did not differ between the groups. RV and LV GLSR were correlated with postoperative follow-up period (r1 = 0.44; r2 = 0.48). RV GLS and GLSR were associated with RVEF (r1 = 0.64; r2 = 0.60) and PR (r1 = 0.48; r2 = 0.49). LV circumferential strain rate was related to PR (r = 0.45). Conclusions: STE can identify abnormalities that may represent early impairment of RV and LV systolic function in postoperative TOF patients with a preserved EF. PR is associated with decreased biventricular performance in repaired patients. STE-derived strain and strain rate may be useful indices for detecting the early deterioration of biventricular performance in patients with TOF. (Echocardiography 2015;32:135–143) Key words: echocardiography, right ventricular function, left ventricular function, tetralogy of Fallot, strain–strain rate Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart defect.1 With the advent of intra-cardiac surgery, most patients with repaired TOF have a good long-term prognosis. However, many postoperative patients have pulmonary regurgitation (PR) that leads to right ventricular (RV) dilation, right heart failure, arrhythmias, or sudden cardiac death.2 RV systolic dysfunction in repaired patients has been described as the determinant of long-term survival and the independent predictor of poor clinical status.3 In addition, PR and RV dilation may have an impact on the shape and function of the Address for correspondence and reprint requests: Mingxing Xie, M.D., Ph.D., Department of Ultrasonography, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277# Jiefang Ave, Wuhan 430022, China. Fax: 86-27-85726386; E-mail: [email protected]
left ventricle (LV). A recent study suggests that LV longitudinal dysfunction is associated with a greater risk of sudden cardiac death/life-threatening ventricular arrhythmias.4 Although most patients with repaired TOF are asymptomatic in the clinical setting, RV and LV function in these patients may be impaired; therefore, RV and LV functional assessment in patients with repaired TOF has increased in clinical practice. Recently, two-dimensional speckle tracking echocardiography (STE) emerged as a promising tool for assessing myocardial performance. This technique does not depend on geometric assumptions and has no angle dependence; therefore, it can be widely used in the evaluation of RV and LV function in patients with a variety of heart diseases,5–8 including congenital heart disease.9,10 The purpose of this study was to use STE to evaluate RV and LV function in asymptomatic 135
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children with repaired TOF and to explore the correlations between the biventricular systolic function parameters and the degree of PR, postoperative follow-up period, and Q-, R-, and Swave duration. Methods: Study Population: From December 2008 to June 2011, 56 consecutive children (34 males, 22 females; 5.4 4.1 years, range 1.5–16 years) with TOF repaired in our hospital were enrolled in this study. The mean postoperative follow-up period was 2.8 years (median 2 years, range 1–11 years). The mean age at surgery was 2.5 years (median 1 year, range 0.5– 11.5 years). All patients were in New York Heart Association (NYHA) functional class I. The inclusion criteria were postoperative follow-up period >1 year and no residual intra-cardiac shunt or residual RV outflow tract (RVOT) obstructions. Patients with 1 or more of the following criteria were excluded: severe tricuspid regurgitation, significant RVOT obstructions (>30 mmHg), RV pacemaker, and RV – pulmonary arterial connection by conduit. The patients were divided according to surgery approach into infundibular patch and transannular patch subgroups. The infundibular patch was nontransannular. The transannular patch involved a more extensive incision made across the pulmonary valve annulus for placement of a large patch. The control group consisted of 35 age- and sex-matched normal subjects (5.7 4.9 years, range 1–18 years; 22 males) who had no evidence of cardiopulmonary disease as assessed by physical checkup, electrocardiogram (Cardimax Fx-7302, Beijing, China), chest x-ray, and echocardiography. All of the subjects were in sinus rhythm. The study was approved by the institutional review ethics board. Echocardiographic Equipment and Conventional Echocardiographic Parameters: Echocardiography was performed using a commercially available ultrasound transducer and equipment (M3S and M7S probes, Vivid 7; GE Medical Systems, Horten, Norway). During echocardiography, the subjects were at rest in the left lateral decubitus position. RV end-diastolic diameter (RVEDD) and right atrial diameter (RA) were determined from the apical four-chamber view.11 For conventional RV function assessment, tricuspid annular peak systolic velocity (Sm), early diastolic velocity (Em) and late diastolic velocity (Am) assessed by tissue Doppler imaging (TDI), and tricuspid annular peak systolic excursion (TAPSE) assessed by M-mode echocardiography were measured from the apical four-chamber 136
view at the RV free wall level.11 LV ejection fraction (EF) was calculated according to the biplane Simpson rule. Two-Dimensional STE Processing: Two-dimensional grayscale images were obtained for the subjects using the apical fourchamber view and the parasternal short-axis view at the mid-ventricular level at frame rates of 60– 90 frames/sec. RV and LV longitudinal strain and strain rates were measured from the apical fourchamber view; LV radial strain and strain rate and circumferential strain and strain rate were measured from mid-ventricular short-axis images. All of the images were digitally stored for offline analysis (EchoPAC, version BT06; GE-Vingmed, Horten, Norway). The RV and LV endocardial borders were manually traced in the end-systolic frame at the point in the cardiac cycle in which the endocardial border was the clearest. The region of interest (ROI) in each image was automatically generated. The position of the ROI and its width was adjusted manually when the speckle tracking appeared to be poor. The software automatically tracked and accepted segments of good tracking quality and rejected poorly tracked segments. When all segments of the RV or LV were accepted, the RV and LV longitudinal strain and strain rate curves and the LV radial and circumferential strain and strain rate curves were automatically generated. Representative examples of RV and LV strain and strain rate curves in patients with TOF are shown in Figure 1. CMR Imaging: A subset of 21 patients with TOF was also studied using cardiac magnetic resonance (CMR) imaging to assess RV volumes and RVEF, LVEF, and PR fractions within 1 month of echocardiography. A 1.5-T MRI scanner (Magnetom Avanto; Siemens Healthcare, Erlangen, Germany) was used, and consecutive single-slice acquisitions from the base to the apex of the RV and LV in the standard short-axis orientation were obtained using a retrospectively ECG-gated cine steady-state free precession (SSFP) sequence (TR 39.75 msec, TE 1.12 msec, slice thickness 6–8 mm, FOV 320– 400 mm2 [according to the individual’s size], matrix 156 9 192, bandwidth 930, flip angle 80°, average 1). Image datasets were transferred to a computer workstation and were analyzed with dedicated software (Argus, Erlangen, Germany) by a single experienced observer who was blinded to the echocardiographic results. End-diastolic and end-systolic contours were manually traced for each slice in the short-axis view. RV end-diastolic volume (RVEDV), RV endsystolic volume (RVESV), RVEF, and LVEF were automatically obtained from the analysis above.
Biventricular Function in Repaired TOF by STE
Figure 1. RV longitudinal strain and strain rate curves in a child with repaired TOF A, B. LV radial C, D. and circumferential E, F. strain and strain rate curves in a child with repaired TOF. RV = right ventricular; TOF = tetralogy of Fallot; LV = left ventricular.
Total pulmonary forward flow, pulmonary reverse flow, and PR fraction were calculated. PR fraction was defined as the diastolic reversed flow expressed as a percentage of the forward flow. Statistical Analysis: Statistical analysis was performed with an SPSS software package (SPSS for Windows 11.5, SPSS Inc., Chicago, IL, USA). Continuous data are
expressed as the mean value standard deviation (SD). Categorical data were analyzed by chisquare test. The TOF and control groups were compared using two-sample independent t tests. Further comparisons among the transannular patch, infundibular patch, and control groups were made using one-way analysis of variance with Bonferroni’s post hoc analysis. Correlations between the biventricular global systolic function 137
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TABLE I General Characteristics and Two-Dimensional Echocardiography and Tissue Doppler Imaging Variable Male/female Age (year) Heart rate (beats/min) LVEF (%) RA diameter (cm) RVEDD (cm) Sm (cm/sec) Em (cm/sec) Am (cm/sec) TAPSE (cm) QRS duration (msec)
Controls (n = 35)
Total – TOF (n = 56)
Infundibular Patch (n = 27)
Transannular Patch (n = 29)
22/13 5.7 4.9 88 18 67.27 5.12 2.76 0.66 2.59 0.63 9.23 1.12 9.15 1.53 8.45 2.87 1.73 0.38 97 23
34/22 5.4 4.1 81 17 65.98 6.56 3.26 0.74* 3.29 0.75* 6.15 1.42* 7.18 2.39* 4.75 1.85* 1.23 0.32* 126 18*
16/11 4.3 2.4 78 14 63.46 6.29 3.16 0.78* 3.17 0.79* 5.91 1.41* 7.37 2.28* 5.01 2.25* 1.19 0.35* 127 15*
18/11 6.1 4.9 85 20 62.39 7.38 3.35 0.71* 3.40 0.72* 6.37 1.43* 7.09 2.25* 4.52 1.41* 1.27 0.29* 124 21*
TOF = tetralogy of Fallot; LVEF = left ventricular ejection fraction; RA = right atrial; RVEDD = right ventricular end-diastolic diameter; Sm = tricuspid annular plane peak systolic velocity; Em = tricuspid annular plane early diastolic velocity; Am = tricuspid annular plane late diastolic velocity; TAPSE = tricuspid annular plane peak systolic excursion. *P < 0.05 compared with normal controls.
Results: Baseline Characteristics: The baseline characteristics of the study population are listed in Table I. Twenty-nine of the patients had received transannular patches, and 27 had infundibular patches. There was no significant difference in LVEF between the groups. Sm, Em, Am, and TAPSE were decreased in children with repaired TOF compared with the control subjects. The postoperative TOF group exhibited a dilated RA and RV and a longer QRS duration than the control group. In contrast, RA, RV, QRS duration, Sm, Em, Am, and TAPSE did not differ between the transannular and infundibular patch subgroups.
Figure 2. RV regional and global strain A. and strain rate B. in the control and postoperative TOF groups. Base = basal RV free wall; Mid = mid RV free wall; Apex = apical RV free wall; RV = right ventricular; TOF = tetralogy of Fallot. *P < 0.05 versus the control group.
and CMR parameters, postoperative follow-up period, and QRS duration were calculated as Pearson’s or Spearman’s correlation coefficients depending on the data distribution. Intra-observer and inter-observer variability was assessed in 15 randomly selected subjects (10 patients with repaired TOF and 5 normal control subjects). Inter-observer and intra-observer reproducibility was evaluated using the intraclass correlation coefficient (ICC). For all analyses, a value of P < 0.05 was considered statistically significant. 138
RV Global and Regional Function in Patients with Repaired TOF: The RV regional and global longitudinal strain (GLS) and strain rate (GLSR) for the control and postoperative TOF groups are shown in Figure 2. The longitudinal strain and strain rate of the RV free wall for all segments were significantly impaired in patients with repaired TOF compared with the control subjects (P < 0.05 for all segments). Likewise, RV GLS and GLSR were lower in patients than in normal control subjects. RV GLS and GLSR in the control subjects and repaired children with transannular and infundibular patches are summarized in Figure 3. Compared with the control group, postoperative patients with transannular and infundibular patches had significantly decreased RV GLS and GLSR. Furthermore, both GLS and GLSR were lower in postoperative children with transannular patches than in those with infundibular patches. There was no significant association between RV GLS or
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Figure 3. RV GLS A. and GLSR B. in the control subjects and patients with transannular and infundibular patches. RV = right ventricular; GLS = global longitudinal strain; GLSR = global longitudinal strain rate. *P < 0.05 versus the control group; #P < 0.05 versus patients with an infundibular patch.
Figure 4. Comparisons of LV regional and global systolic longitudinal A, B. circumferential C, D. and radial E, F. strain and strain rate between patients and control subjects. Base-L = basal LV lateral wall; Mid-L = mid LV lateral wall; Apex-L = apical LV lateral wall; Base-S = basal septum; Mid-S = mid septum; and Apex-S = apical septum; LV = left ventricular. *P < 0.05 versus control subjects.
GLSR and age at repair (r1 = r2 = 0.26, P = 0.19).
0.15, P = 0.46;
LV Global and Regional Function in Patients with Repaired TOF: LV longitudinal, circumferential, and radial strain and strain rate are shown in Figure 4. LV circum-
ferential and radial strain and strain rate were reduced in patients with TOF compared with control subjects. Longitudinal septal peak strain and strain rate were lower in patients with TOF than in control subjects, whereas LV lateral wall longitudinal strain and strain rate did not differ between the groups. The age at repair was not 139
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Figure 5. Correlations between biventricular GLSR and postoperative follow-up period A, C. and between RV GLSR and QRS duration B. The relationship between CMR-derived PR fraction and RV GLS D. RV GLSR E. and LV GCSR F. The association between CMR-derived RVEF and RV GLS G. and GLSR H. GLSR = global longitudinal strain rate; RV = right ventricular; CMR = cardiac magnetic resonance; PR = pulmonary regurgitation; GLS = global longitudinal strain; LV = left ventricular; GCSR = global circumferential strain rate; RVEF = right ventricular ejection fraction.
associated with LV longitudinal, radial, or circumferential strain and strain rate.
radial, or circumferential strain and strain rate and QRS duration.
Correlation between Postoperative Period or QRS Duration and LV and RV Global Systolic Function: RV GLSR was correlated inversely with postoperative follow-up period and QRS duration (r1 = 0.44, P < 0.05; r2 = 0.48, P < 0.05; Fig. 5A and B). In contrast, there was no correlation between RV GLS and QRS duration or postoperative follow-up period in this study (r1 = 0.30, P = 0.07; r2 = 0.05, P = 0.76). LV GLSR was related to postoperative follow-up period (r = 0.48, P < 0.05; Fig. 5C), whereas there was no association between LV circumferential or radial strain and strain rate and postoperative follow-up period. Likewise, we did not identify a significant association between LV longitudinal,
Association between Echocardiographic Biventricular Function and CMR Parameters: The CMR findings in 21 patients were as follows: RVEDV 145.4 56.8 mL, RVESV 54.6 32.5 mL, RVEF 52.5 11.5%, LVEF 60.7 8.4%, and PR fraction 37.1 13.8%. The RVEF values in 4 patients were below the published lower level for normal healthy volunteers.12 PR fraction was correlated inversely with RV GLS and GLSR (r1 = 0.48, P < 0.05; r2 = 0.49, P < 0.05; Fig. 5D and E). In contrast, we did not identify an association between PR fraction and RVEF in this study (r = 0.30, P = 0.19). We also found a significant association between LV global circumferential strain rate and PR fraction (r = 0.45, P < 0.05; Fig. 5F). However, LV longitudinal or
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radial strain and strain rate were not related to PR. RV GLS and GLSR were associated with CMRderived RVEF (r1 = 0.64, P < 0.05; r2 = 0.60, P < 0.05; Fig. 5G and H), whereas TAPSE and Sm were not associated with CMR-based RVEF. Intra-Observer and Inter-Observer Variability: The inter-observer ICC was 0.94 for RV GLS and 0.93 for RV GLSR. The intra-observer ICC was 0.95 and 0.94 for RV GLS and RV GLSR, respectively. Discussion: This study demonstrates that RV and LV strain and strain rate in asymptomatic children with preserved biventricular EF after TOF repair are decreased compared with those of control subjects. The reduction in the biventricular strain and strain rate in postoperative patients is correlated with PR. RV and LV strain rates are associated with the postoperative follow-up period, suggesting that STE may be a useful follow-up tool for the serial evaluation of biventricular myocardial performance in patients with repaired TOF. Impaired RV regional and global function in patients with repaired TOF is not unique and has also been identified in other studies.13–17 However, the majority of these studies observed older patients or all subsets of patients, including asymptomatic and symptomatic patients. This study focused on asymptomatic children with repaired TOF. In a previous RV strain and strain rate study, the parameters were obtained from TDI, which has an intrinsic limitation of angle dependence. In contrast, we quantified the RV regional and global function using a speckle tracking technique that has been shown to be superior to TDI. In this study, we found that RV regional and global strain and strain rate were significantly reduced in patients compared with control subjects despite normal or near normal RVEF in the majority of patients with repaired TOF. Furthermore, we also identified that RV GLS and GLSR are lower in patients with transannular patches than in those with infundibular patches. These results suggest that the type of RVOT reconstruction may have an effect on postoperative RV function. A previous study demonstrated that several unfavorable factors influence RV function in postoperative patients, including: (1) chronic PR, (2) a noncontractile RVOT patch, (3) a chronic dilated free wall, and (4) septum dysfunction.18 In addition, Babu-Narayan et al.19 showed that RV myocardial fibrosis was present extensively in patients with repaired TOF. These changes in myocardial architecture have contributed to RV function impairment.
Because LV dysfunction is a strong predictor of worsening prognosis in patients with repaired TOF, early detection of the LV dysfunction is crucial in these patients. In this study, LV circumferential and radial strain and strain rate were decreased despite a normal LVEF in patients after TOF repair, and these parameters may be early indicators of the deterioration of LV function. However, LV lateral longitudinal strain and strain rate were relatively maintained. These results are consistent with recent studies.20,21 Probable mechanisms for LV dysfunction in postoperative patients with TOF include preoperative hypoxemia, LV fibrosis, LV dyssynchrony, and RV dilatation and dysfunction.22 Our finding of significant differences in the longitudinal systolic strain/ strain rate of the LV free wall compared with the septum between patients and control subjects suggests that ventricular–ventricular interactions are most likely responsible. The mechanism of ventricular–ventricular interaction may be mediated through the ventricular septum. In addition, we found that a decreased LV global circumferential strain rate was associated with PR fraction, suggesting unfavorable left–right ventricular interactions.22 Unlike conventional RV function parameters, such as TAPSE, Sm, and RV fractional area change, STE-derived indices not only allow the global analysis of RV function but also allow the regional analysis of RV contractility.23 In this study, we found a significant association between RV STE indices and CMR-derived RVEF, whereas TAPSE and Sm were not associated with CMR-based RVEF. These results are in agreement with the findings of Mercer-Rosa et al.,24 who demonstrated that TAPSE is not associated with CMR-based RVEF or representative of global RV function in patients with TOF. Moreover, we showed that patients with transannular patches had a significantly lower RV GLS and GLSR than those with infundibular patches; however, Sm and TAPSE were not different between the groups. Sm and TAPSE failed to differentiate patients with transannular patches from those with infundibular patches. Therefore, we conclude that STE indices may be more accurate echocardiographic measurements of RV systolic performance than conventional echocardiographic parameters of RV function. In addition, although RVEF levels were normal or near normal in the majority of patients in this study, RV longitudinal strain, and strain rate were reduced in patients compared with control subjects. We also identified a decrease in LV circumferential and radial strain in patients with preserved LVEF after TOF repair. Moreover, we found that RV and LV longitudinal strain rates were associated significantly with postoperative 141
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follow-up duration. This finding is consistent with the study of Scherptong et al.,13 which showed during follow-up that CMR-derived RVEF remained unchanged but RV longitudinal peak strain decreased. Therefore, we conclude that STE-derived strain and strain rate may be more sensitive for detecting changes in biventricular performance and that STE may be a useful follow-up tool in the early detection of myocardial impairment. In this study, we attempted to analyze the impact of PR on RV function in asymptomatic children with repaired TOF. Our findings showed that PR was significantly correlated with RV strain and strain rate. Previous reports showing the effect of PR on regional RV function were discordant. Eyskens et al.25 and Kowalik et al.26 showed that PR was associated with TDI-derived RV strain and strain rate. In contrast, Frigiola et al.27 showed no correlation between TDIderived RV deformation and the severity of PR in patients with repaired TOF. The lack of association between RV deformation and the degree of PR in that study may be due to their semiquantitative, subjective assessment of PR using echocardiography. However, the correlation between the degree of PR and RV strain and strain rate by STE is unknown. To our knowledge, this study is the first to show a significant association between the severity of PR and RV deformation abnormalities as assessed by STE. Most importantly, PR was quantified objectively using CMR imaging in this study. We also examined the effect of PR on LV performance using STE and demonstrated a negative impact of PR on LV performance. This result was consistent with that of Fernandes et al.,20 who found that PR was correlated with decreased LV strain. Study Limitations: This study has potential limitations. First, this study included a small number of patients, and future studies with a larger sample size are needed to determine the utility of STE-derived strain and strain rate for the assessment of biventricular myocardial function. Second, not all patients underwent CMR imaging. Therefore, the relationship between echocardiographic biventricular function and CMR parameters must be assessed further. A third limitation of this study is that it is a single-center study. Surgical techniques may differ from center to center. Different surgical techniques may impact postoperative RV/LV function. A fourth limitation is the lack of longitudinal follow-up data in this study. Therefore, we cannot demonstrate whether the abnormalities in RV and LV function are reversible or irreversible.
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Finally, myocardial motion is a complicated three-dimensional motion, and STE based on two-dimensional images cannot fully reflect three-dimensional myocardial motion. Conclusions: Asymptomatic children with preserved biventricular EF after TOF repair exhibited impaired RV and LV myocardial function, suggesting subclinical myocardial damage. PR affects RV performance in asymptomatic children with repaired TOF. Reduced LV strain was associated with PR, which most likely indicates adverse ventricular interactions. STE may be a useful technique in the early detection of myocardial impairment in patients after TOF repair. References 1. Brickner ME, Hillis LD, Lange RA: Congenital heart disease in adults: Second of two parts. N Engl J Med 2000;342:334–342. 2. Gatzoulis MA, Balaji S, Webber SA, et al: Risk factors for arrhythmia and sudden cardiac death late after repair of tetralogy of Fallot: A multicenter study. Lancet 2000;356:975–981. 3. Geva T, Sandweiss BM, Gauvreau K, et al: Factors associated with impaired clinical status in long-term survivors of tetralogy of Fallot repair evaluated by magnetic resonance imaging. J Am Coll Cardiol 2004;43:1068–1074. 4. Diller GP, Kempny A, Liodakis E, et al: Left ventricular longitudinal function predicts life-threatening ventricular arrhythmia and death in adults with repaired tetralogy of Fallot. Circulation 2012;125:2440–2446. 5. Prinz C, van Buuren F, Faber L, et al: Myocardial fibrosis is associated with biventricular dysfunction in patients with hypertrophic cardiomyopathy. Echocardiography 2012;29:438–444. 6. Tanboga IH, Kurt M, Bilen E, et al: Assessment of right ventricular mechanics in patients with mitral stenosis by two-dimensional deformation imaging. Echocardiography 2012;29:956–961. 7. Delgado M, Ruiz M, Mesa D, et al: Early improvement of the regional and global ventricle function estimated by two-dimensional speckle tracking echocardiography after percutaneous aortic valve implantation speckle tracking after Core Valve implantation. Echocardiography 2013;30:37–44. 8. Platz E, Hassanein AH, Shah A, et al: Regional right ventricular strain pattern in patients with acute pulmonary embolism. Echocardiography 2012;29:464–470. 9. Forsey J, Friedberg MK, Mertens L: Speckle tracking echocardiography in pediatric and congenital heart disease. Echocardiography 2013;30:447–459. 10. Bussadori C, Oliveira P, Arcidiacono C, et al: Right and left ventricular strain and strain rate in young adults before and after percutaneous atrial septal defect closure. Echocardiography 2011;28:730–737. 11. Rudski LG, Lai WW, Afilalo J, et al: Guidelines for the echocardiographic assessment of the right heart in adults: A report from the American Society of Echocardiography endorsed by the European Association of Echocardiography, a registered branch of the European Society of Cardiology, and the Canadian Society of Echocardiography. J Am Soc Echocardiogr 2010;23:685–713. 12. Fiechter M, Fuchs TA, Gebhard C, et al: Age-related normal structural and functional ventricular values in cardiac
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