ORIGINAL ARTICLE. Heiner Latus*, Pauline Hachmann, Kerstin Gummel, Markus Khalil, Can Yerebakan, Juergen Bauer, Dietmar Schranz and Christian Apitz

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1 European Journal of Cardio-Thoracic Surgery 48 (2015) doi: /ejcts/ezu396 Advance Access publication 5 November 2014 ORIGINAL ARTICLE Cite this article as: Latus H, Hachmann P, Gummel K, Khalil M, Yerebakan C, Bauer J et al. Impact of residual right ventricular outflow tract obstruction on biventricular strain and synchrony in patients after repair of tetralogy of Fallot: a cardiac magnetic resonance feature tracking study. Eur J Cardiothorac Surg 2015;48: Impact of residual right ventricular outflow tract obstruction on biventricular strain and synchrony in patients after repair of tetralogy of Fallot: a cardiac magnetic resonance feature tracking study Heiner Latus*, Pauline Hachmann, Kerstin Gummel, Markus Khalil, Can Yerebakan, Juergen Bauer, Dietmar Schranz and Christian Apitz Pediatric Heart Centre, University Children s Hospital, Giessen, Germany * Corresponding author. Justus Liebig University of Giessen, Pediatric Heart Centre, Feulgenstr. 12, Giessen, Germany. Tel: ; fax: ; heiner.latus@googl .com (H. Latus). Received 7 June 2014; received in revised form 27 August 2014; accepted 2 September 2014 Abstract OBJECTIVES: Residual right ventricular outflow tract (RVOT) obstruction () is considered beneficial in patients after repair of tetralogy of Fallot (TOF) although underlying mechanisms are unknown. We sought to elucidate differences in myocardial strain and dyssynchrony parameters in patients after TOF repair with and without residual using cardiovascular magnetic resonance (CMR) feature-tracking (CMR-FT) analysis. METHODS: Fifty-four patients (mean age 16.4 ± 8.4 years) were assessed by CMR 14.2 ± 7.3 years after repair of TOF. Residual on echocardiography was defined as a peak systolic RVOT gradient >25 mmhg and was present in 27 patients (no in n = 27 patients). Right ventricular (RV) and left ventricular (LV) strain measurements were performed using CMR-FT software. RESULTS: The two groups were well matched for age at CMR scan, time and type of surgical repair. There was no difference in the degree of pulmonary regurgitation (PR) and RV end-diastolic volume. Patients with showed significant higher RV circumferential strain (CS) (P = 0.02) and RV radial strain (RS) (P = 0.02) values, whereas RV longitudinal strain (LS) did not differ between the two groups (P =0.39).The degree of showed a significant correlation with RV-CS (r =0.37;P = 0.006) and RV-RS (r = 0.30; P = 0.03) while RV-LS was unrelated to (r = 0.06; P = 0.68). Significant relationships between RV and LV strain parameters were only found in the group. Interventricular dyssynchrony was significantly higher in the group without (P = 0.03) while LV-LS (P = 0.03) and LV intraventricular synchrony (P = 0.05) were impaired in the group. CONCLUSIONS: In patients after TOF repair, residual seems to preserve RV strain and results in stronger RV LV interactions and less interventricular dyssynchrony and may therefore possess an early protective effect on RV remodelling. However, the potential negative impact of residual pulmonary stenosis on LV strain and intraventricular synchrony needs further investigation. Keywords: Tetralogy of Fallot Residual pulmonary stenosis CMR feature tracking INTRODUCTION Patients after repair of tetralogy of Fallot (TOF) are frequently affected by the adverse effects of pulmonary regurgitation and subsequently evolve dilatation of the right ventricle (RV) in the long-term follow-up, which may lead to progressive RV failure. Therefore, the current surgical technique in TOF repair tends to preserve the integrity of the pulmonary valve to avoid the deleterious long-term effects of pulmonary valve incompetence. This strategy usually results in a certain degree of residual pressure gradient across the right ventricular outflow tract (RVOT). Recent studies confirmed that residual RVOT obstruction () leads to smaller RV volumes [1 4] and therefore may protect from pulmonary valve replacement (PVR) [5, 6]. These data suggest that residual represents a benign lesion. However, underlying mechanisms behind these findings and the definition of an acceptable degree of have so far remained unclear. These concerns were confirmed by a recent study by Valente et al. who found elevated RV pressure and RV hypertrophy as independent risk factors for poor outcome in TOF patients [7]. In addition, appears to be associated with decreased exercise performance, despite smaller RV volumes [8]. These results highlight that the phenomenon of residual pressure load after TOF repair is more complex than expected and requires further studies. As reported in patients with RV volume overload [9, 10], residual might also have an impact on both ventricles and ventricular interaction. CONGENITAL The Author Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.

2 84 H. Latus et al. / European Journal of Cardio-Thoracic Surgery Therefore, the aim of our study was to compare myocardial functional data of both ventricles and to focus on ventricular interactions in TOF patients with and without using cardiovascular magnetic resonance (CMR) feature tracking (CMR-FT), a new technique that allows assessment of ventricular strain and dyssynchrony derived from standard CMR cine images [11 13], thereby revealing differences in biventricular myocardial strain and synchrony parameters. MATERIALS AND METHODS Study population We included 54 patients with repaired TOF and echocardiographic evidence of PR who subsequently underwent CMR examination between August 2008 and November 2013 at our institution. Patients were excluded if (i) echocardiographic or CMR studies were incomplete or of poor image quality, (ii) residual intracardiac or extracardiac shunt lesions were seen, (iii) significant (>15 mmhg) branch or peripheral pulmonary artery stenosis was present, (iv) at the supravalvular level was present, (v) regurgitation at a valve other than the pulmonary valve was more than mild on echocardiography and/or (vi) a valved conduit had been implanted at corrective surgery. Clinical data were retrospectively obtained from hospital medical records including date of birth, gender, anatomical diagnoses, age and type of each surgical procedure and age at CMR evaluation. The study protocol was approved by the local ethics committee and consent for use of anonymized CMR and clinical data for research purposes was obtained from all patients or parents of the patients. Echocardiography Transthoracic echocardiographic data within 1 year of the CMR study were analysed. Continuous wave Doppler was used to determine the maximal velocity across the RVOT. Residual was defined as a peak RVOT gradient >25 mmhg [1, 3]. All patients were reviewed for the presence of residual septal defect (ventricular septal defect) and/or significant regurgitation at a valve other than the pulmonary valve. Cardiovascular magnetic resonance imaging All CMR studies were performed on a 3-T system (Verio, Siemens, Erlangen, Germany). Images were acquired with two 16-element phased array coils. The CMR protocol included a stack of short-axis slices from the base of the heart to the apex using cine steady-state free precession (SSFP) with breath-hold that were assessed with the following sequence parameters: TR 48 ms, TE 1.5 ms, flip angle 60, slice thickness 6 mm, in plane image resolution 1.3 mm 1.3 mm 6.0 mm, temporal resolution phases. End-diastolic (maximal) and end-systolic (minimal) volumes, stroke volumes (SV) and ejection fractions (EF) for the RV and left ventricle (LV) were calculated by dedicated software (ARGUS, Siemens, Erlangen, Germany) after the RV and LV endocardial borders were traced manually at end-systole and end-diastole. All parameters were adjusted to body surface area (BSA). Phase contrast analysis of forward and reverse flow in the main pulmonary artery was achieved using a retrospectively gated gradient echo sequence during free breathing using the following parameters: TR 34 ms, TE 2.9 ms, flip angle 25, slice thickness 5 mm, in plane image resolution 1.3 mm 1.3 mm 5.0 mm. Imaging plane was located at the midpoint of main pulmonary artery or conduit and prescribed perpendicular to the vessel by the double oblique technique. In all cases, encoding velocity was adjusted to avoid aliasing. The pulmonary regurgitant fraction was calculated as a percentage of the pulmonary regurgitant volume (PRV) divided by the pulmonary forward volume. PRV was defined as a total reverse flow indexed for BSA and expressed in ml/m 2. Cardiovascular magnetic resonance feature tracking for the assessment of myocardial strain and synchrony Strain is a dimensionless quantity and is produced by application of stress. It represents the percentage change from the original or unstressed dimension. Myocardial strain is a measure of regional deformation and represents an intrinsic mechanism of the myocardium to augment the effects of a given degree of myocyte shortening in the different orthogonal planes. By definition, negative strain means compression or shortening while positive strain means lengthening/ expansion. As the myocardial wall is a 3D object, deformation may occur along three planes, corresponding to three types of strain: longitudinal (LS), circumferential (CS) and radial strain (RS) [14]. CMR-FT is a novel method that allows quantitative assessment of myocardial strain derived from standard cine CMR images. FT is a simple technique analogous to echocardiographic speckle tracking and is based on a software algorithm previously published [15]. After manually placing points along the ventricular endocardium in a single frame, the software algorithm then follows this border throughout the cardiac cycle automatically (Fig. 1A). SSFP images were analysed using dedicated CMR-FT software (TomTec Imaging Systems, Unterschleissheim, Germany). Eight to ten points along the endocardial border were manually placed in the short-axis (at midpapillary level) and the 4-chamber view separately for the RV and LV. These points were used by the FT software to calculate biventricular LS, CS and RS. Strain versus time was calculated for each of six segments. The values of peak strain and time to peak strain were recorded for each segment and global strain was calculated as the average of the six segments. Intraventricular synchrony measurements were performed as previously described [12, 13]. Briefly, from the time-to-peak analysis, the maximum wall delay between the six segments as well as the standard deviation of the six segments was calculated serving as a parameter of intraventricular synchrony. The time delay between the RV and the LV free wall longitudinal time to peak served as an indicator of interventricular dyssynchrony (Fig. 1B) [16]. Statistical analysis All continuous variables were tested for normality using the Kolmogorov Smirnov test and are presented as mean with standard deviation. Comparisons between groups with and without were made with Student s t-test, the Mann Whitney U-test or the Fisher s exact test, as appropriate. Box-and-whiskers plot was used to display variation in myocardial strain in the two groups. Regression analysis was used to analyse simple linear relationships between different variables. Analysis was performed using GraphPad statistical software package (San Diego, CA, USA). A P-value 0.05 was considered statistically significant.

3 H. Latus et al. / European Journal of Cardio-Thoracic Surgery 85 CONGENITAL Figure 1: Representative images of CMR feature-tracking analysis. (A) CMR feature-tracking analysis of the left and right ventricle in the midpapillary short-axis view (for the assessment of circumferential and radial strain; upper panel) and in the 4-chamber view (for the assessment of longitudinal strain; lower panel). The green line represents the endocardial border that has been manually drawn in a single frame. The software algorithm then follows this border throughout the cardiac cycle automatically. (B) Resulting longitudinal strain versus time for the LV (top) and the RV (bottom) free wall (three segments included). Assessment of interventricular dyssynchrony using the time delay (red arrow) between the LV (262 ms) and the RV free wall (303 ms) time to peak strain. CMR: cardiovascular magnetic resonance; LV: left ventricle; RV: right ventricle.

4 86 H. Latus et al. / European Journal of Cardio-Thoracic Surgery Table 1: Baseline characteristics and clinical data of the study population Table 2: CMR findings and results of the CMR featuretracking analysis RESULTS Group 1 Group 2 No Patient characteristics and clinical findings Significance (P) Patients, n Male/female 11/16 14/13 BSA (m 2 ) 1.46 ± ± Age at study (years) 16.2 ± ± Age at repair (years) 1.7 ± ± Follow-up (years) 14.3 ± ± Palliative procedures, n (%) 6 (22) 5 (18) 1.0 Type of RVOT surgery 0.64 TAP, n (%) 13 (48) 15 (56) RVOT patch, n (%) 9 (33) 9 (33) Transatrial/ 5 (19) 3 (11) transpulmonary, n (%) RVOT gradient (mmhg) 40.5 ± ± 5.0 <0.001 NYHA Class I/II/III, n 19/8/0 19/7/ QRS duration (ms) 132 ± ± Data are presented as mean ± 1 standard deviation. RVOT(O): right ventricular outflow tract (obstruction); BSA: body surface area; TAP: transannular patch; NYHA: New York Heart Association. A total of 54 patients (29 females) with repaired TOF fulfilled the entry criteria and were enrolled in the study. Twenty-seven patients (mean age 16.2 ± 6.9 years) had echocardiographic evidence of residual with a mean gradient of 40.5 ± 12.4 mmhg whereas the other 27 patients (mean age 16.6 ± 9.8 years; P =0.6) had isolated PR with a mean gradient across the RVOT of 15.6 ± 4.9 mmhg (P < ). Patients with residual were assigned to Group 1, those presenting without a relevant RVOT stenosis were assigned to Group 2 (Table 1). Age at and type of repair, as well as follow-up (time interval between corrective surgery and present CMR study), did not differ significantly between the two groups. There was no difference in the spectrum of clinical symptoms or heart rate, and QRS duration was similar in the two groups (Table 1). Cardiovascular magnetic resonance findings and feature-tracking analysis The two groups did not differ significantly in PR fraction (25.8 ± 9.9 vs 29.6 ± 8.2%; P = 0.12) and RV end-diastolic volume (97.1 ± vs ± 17.8 ml/m 2 ; P = 0.39) whereas there was a significant difference in RV end-systolic volume (44.9 ± 21.9 vs 50.0 ± 12.6 ml/m 2 ; P = 0.05). RVEF was similar in the two groups (54.9 ± 9.7 vs 52.6 ± 6.7%; P = 0.31). LV parameters showed no significant difference between the two groups (Table 2). Patients with showed significant higher RV CS ( 15.7 ± 4.0 vs 12.3 ± 5.8%; P = 0.02) and RS (15.0 ± 4.8 vs 11.8 ± 5.3%; P = 0.02) values, whereas RV LS did not differ between the two groups ( 9.9 ± 5.4 vs 11.5 ± 5.9%; P = 0.39) (Fig. 2). The magnitude of showed a significant correlation with RV-CS (r = 0.37; P = 0.006) and RV-RS (r = 0.30; P = 0.03) while RV-LS was unrelated to (r = 0.06; P = 0.68) (Fig. 3). RV strain parameters were not related to PR and indexed end-diastolic RV Variable Group 1 (n = 27) volume whereas a significant correlation was found between RV-RS and indexed end-systolic RV volume (RVESVi) (r = 0.33; P = 0.01) (Fig. 4). Significant relationships between corresponding RV and LV strain parameters were only found in the group (Fig. 5): LV-CS and LV-RS did not differ between the groups, but LV-LS was found to be significantly lower in the group with ( 9.2 ± 5.2 vs 12.4 ± 5.0%; P = 0.03). Age at and time since repair (follow-up), as well as age at study were not related to the measured RV and LV strain and synchrony values. Synchrony measurements No difference in RV intraventricular synchrony was found between the two groups although there was a tendency towards better radial synchrony in the group, which did not reach statistical significance(79 ± 65 vs 110 ± 81 ms; P = 0.07) (Table 3). LV longitudinal synchrony tended to be lower in the group (385 ± 201 vs 286 ± 161 ms; P = 0.05) whereas circumferential and radial LV synchrony showed no statistical significance. Interventricular dyssynchrony was significantly higher in the group with free PR (87 ± 114 vs 126 ± 101 ms; P = 0.03). No significant relationships were found between QRS duration and synchrony measurements, but there was a tendency towards better RV-RS intraventricular synchrony with increasing RVOT gradient (r = 0.22;P = 0.09). DISCUSSION Group 2 No (n = 27) CMR RVEDVi (ml/m 2 ) 97.1 ± ± RVESVi (ml/m 2 ) 44.9 ± ± RVSVi (ml/m 2 ) 52.2 ± ± RVEF (%) 54.9 ± ± PRF (%) 25.8 ± ± PRV (ml/m 2 ) 14.4 ± ± LVEDVi (ml/m 2 ) 64.0 ± ± LVESVi (ml/m 2 ) 23.7 ± ± LVSVi (ml/m 2 ) 40.3 ± ± LVEF (%) 63.0 ± ± CMR-FT RV-LS (%) 9.9 ± ± RV-CS (%) 15.7 ± ± RV-RS (%) 15.1 ± ± LV-LS (%) 9.2 ± ± LV-CS (%) 20.9 ± ± LV-RS (%) 19.6 ± ± Significance (P) Data are presented as mean ± 1 standard deviation. CMR: cardiac magnetic resonance; FT: feature tracking; : right outflow tract obstruction; RV: right ventricle; LV: left ventricle; EDV: end-diastolic volume; ESV: end-systolic volume; SV: stroke volume; EF: ejection fraction; PRF: pulmonary regurgitant fraction; PRV: pulmonary regurgitant volume; LS: longitudinal strain; CS: circumferential strain; RS: radial strain; RVEF: right ventricular ejection fraction; LVEF: left ventricular ejection fraction. Our study shows for the first time that residual after repair of TOF preserves RV myocardial strain. Furthermore, we were able

5 H. Latus et al. / European Journal of Cardio-Thoracic Surgery 87 Figure 2: Box-and-whiskers plot of RV radial (RV-RS), circumferential (RV-CS) and longitudinal strain (RV-LS) in the two groups. The central line represents the median with the boxes representing the 5th and 95th percentiles. A significant difference in RV-RS and RV-CS was found between the two groups while RV-LS was not affected by. LV: left ventricle; RV: right ventricle; : right ventricular outflow tract obstruction. Figure 3: Significant relationships between RV-CS and RV-RS and the degree of were found whereas RV-LS showed no correlation with the residual pressure load. RV-RS: RV radial strain; RV-CS: RV circumferential strain: RV-LS: longitudinal strain; : right ventricular outflow tract obstruction. Figure 4: Correlation between RVESVi and RV-RS. RVESVi: indexed end-systolic volume of the RV; RV-RS: RV radial strain. to demonstrate a strong relation between RV and LV strain parameters and a less impaired interventricular synchrony in the group, which suggests a beneficial effect of on ventricular ventricular interaction. However, the finding of reduced LV strain and higher LV intraventricular dyssynchrony suggests a potential negative effect of an LV performance and needs further investigation. Impact of residual right ventricular outflow tract obstruction on right ventricular myocardial function The rationale behind our study was based on the findings by Kuehne et al. who demonstrated that additional pressure overload enhanced RV contractility and promoted compensatory hypertrophy compared with a group with free PR in an experimental swine model of pulmonary valve incompetence [17]. Bove et al. demonstrated that in growing juvenile swine pressure load before RVOT surgery increased contractile systolic but decreased load-independent diastolic function and concluded that RV hypertrophy prior to surgical correction might have a protective effect on RV remodelling when RV volume overload occurs due to pulmonary valve insufficiency [18]. In the present study, we were able to support these observations in TOF patients late after repair as the group with residual showed higher values of RV-CS and RV-RS, whereas RV-LS was unaffected by additional pressure load. These results suggest an early protective effect of residual RVOT stenosis on RV remodelling by preserving RV myocardial strain while global pump function (i.e. EF) was not yet different between the two groups. Furthermore, RV-CS and RV-RS parameters were significantly related to the degree of whereas RV-LS showed no relationship with residual obstruction. These findings are mainly explained by the physiological rise in RV contractility when its afterload increases, the so-called Anrep effect [19]. Although usually known as an acute phenomenon, it has previously been shown in a preclinical model that RV function can be also improved by chronic RV afterload [20]. Using echocardiographic speckle tracking, van der Hulst et al. found a significant relationship of with RV-LS but not with RV-CS and RV-RS [21], and Yoo et al. demonstrated a weak relationship between the gradient and RVEF [1]. Harrild et al. assessed the impact of transcatheter PVR on biventricular strain and synchrony in patients with dysfunctional RVOT by CMR-FT analysis [12]. A significant increase in RV strain was only found in the group with predominant, whereas LV strain improved in both groups, findings that highlight the importance of on overall biventricular performance. Although we included all patients independent of severity of, we were not able to determine a cut-off value for that impairs RV contractility. Therefore, a threshold for that is optimal or still acceptable needs to be determined in future studies. CONGENITAL

6 88 H. Latus et al. / European Journal of Cardio-Thoracic Surgery Figure 5: Significant relationships between corresponding RV and LV strain parameters were only found in the group. LV: left ventricle; RV: right ventricle; : right ventricular outflow tract obstruction. Table 3: Results of synchrony measurements using CMR feature tracking Variable Group 1 (n = 27) Group 2 No (n = 27) LV-LS Maximum wall delay (ms) 385 ± ± SD (time to peak) (ms) 153 ± ± LV-CS Maximum wall delay (ms) 130 ± ± SD (time to peak) (ms) 50 ± ± LV-RS Maximum wall delay (ms) 210 ± ± SD (time to peak) (ms) 80 ± ± RV-LS Maximum wall delay (ms) 380 ± ± SD (time to peak) (ms) 148 ± ± RV-CS Maximum wall delay (ms) 152 ± ± SD (time to peak) (ms) 60 ± ± RV-RS Maximum wall delay (ms) 211 ± ± SD (time to peak) (ms) 79 ± ± Interventricular delay (ms) 87 ± ± Significance (P) Data are presented as mean ± 1 standard deviation (SD). : right outflow tract obstruction; RV: right ventricle; LV: left ventricle; CMR: cardiac magnetic resonance; LS: longitudinal strain; CS: circumferential strain; RS: radial strain. Our results also highlight the importance of the assessment of less load-dependent measures of systolic function such as the strain parameters compared with the load-dependent EF. While EF was unchanged between both groups, RV myocardial strain was improved in the group. Interestingly, RVESVi correlated significantly with RV radial strain, which suggests that endsystolic RV volume may also reflect RV function better than EF does in TOF patients. These data are in agreement with a previous study from Uebing et al. who found similar results using invasive conductance catheter assessment for RV contractility [22]. As indexed endsystolic volume (ESV) may also reflect RVOT-patch dysfunction after repair, we suggest that ESV appears to be a parameter of great importance and its role in RV remodelling after TOF repair needs further investigation [23]. Impact of residual pressure load on right ventricular left ventricular interaction, intraventricular synchrony and left ventricular mechanics This is, to our knowledge, the first study investigating the impact of residual pressure load on intra- and interventricular dyssynchrony in patients affected by PR. Significant relationships between all RV and LV strain parameters were only found in the group and interventricular dyssynchrony was significantly reduced in patients with. Given the results of previous studies that assessed ventricular dyssynchrony in patients after TOF repair and found clinically relevant relationships with RV dimensions, function and exercise

7 H. Latus et al. / European Journal of Cardio-Thoracic Surgery 89 capacity [10, 16], our results suggest that favourable mechanical ventricular ventricular interactions may also play an important role in remodelling of the pressure and volume loaded RV. However, we can only speculate about the reason for the observed difference, but altered position and motion of the interventricular septum, as well as preserved RVOT geometry, may play a role. LV LS was significantly lower and LV longitudinal dyssynchrony was more pronounced in the group. These findings, while surprising regarding the described preserved RV LV interaction in the group, may suggest a certain negative impact of on LV performance and needs further investigation, particularly because impaired LV LS and dyssynchrony has been found to be associated with arrhythmia [13] and adverse longterm outcomes [24]. Study limitations As the surgical strategy for repairing TOF has changed markedly during recent decades, our study included patients who underwent surgery by former generations of surgeons at a time when the surgical strategy for TOF was quite different, as well as patients who were operated with a contemporary surgical approach. While this has resulted in some heterogeneity of patient cohorts regarding surgical strategy, the bias in a monoinstitutional study regarding different surgeons and varying strategies appears to be limited. Surgical repair of TOF includes reconstruction of the RVOT frequently followed by scar formation and pulmonary valve incompetence that evolves over time and subsequently causes RVOT dysfunction. As we derived RV strain from short-axis view at midpapillary level, our findings might underestimate the significance of infundibular disease in TOF patients [4, 25]. Normal values for biventricular strain values derived by feature-tracking analysis are currently not available in healthy children and adolescents. Therefore, the measured RV and LV strain measurements in our study population cannot be analysed in this context. The different approaches to measure intra- and interventricular dyssychrony by CMR-FT are not validated and may be hampered by the relatively low reproducibility of segmental strain values [12]. Furthermore, we did not investigate intra- and interobserver reproducibility of the strain measurements, which might be especially important for the assessment of radial strain. However, previous studies found acceptable reproducibility of global strain measurements for the LV and the RV [11]. So far, RV diastolic function cannot be reliably evaluated by CMR-FT; therefore, the potential negative impact on RV pressure load on diastolic function could not be assessed. CONCLUSIONS In patients after TOF repair, residual seems to preserve RV strain and results in stronger RV LV interactions and less interventricular dyssynchrony and may therefore contribute an early protective effect on RV remodelling. However, the potential negative impact of residual pulmonary stenosis on LV strain and intraventricular synchrony requires further investigation. Funding The study was supported by the Doris-Haag Stiftung, Frankfurt am Main, Germany and the Willy Robert Pitzer Stiftung, Bad Nauheim, Germany. Conflict of interest: none declared. REFERENCES [1] Yoo BW, Kim JO, Kim YJ, Choi JY, Park HK, Park YH et al. Impact of pressure load caused by right ventricular outflow tract obstruction on right ventricular volume overload in patients with repaired tetralogy of Fallot. J Thorac Cardiovasc Surg 2012;143: [2] Spiewak M, Biernacka EK, Malek LA, Petryka J, Kowalski M, Milosz B et al. 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