AbstractBackgroundEarly diastolic relaxation creates an intraventricular pressure difference (IVPD) and resulting diastolic suction. Non-invasive estimation by echocardiographic techniques would allow to clinically evaluate this IVPD as an important component of ventricular filling. Recently, Blood Speckle Tracking (BST) echocardiography was introduced, allowing two-dimensional assessment of ventricular flow dynamics. Mitral inflow BST data can be used to estimate IVPD. The aims of the current study were to evaluate the accuracy of BST-based IVPD estimation compared to invasive pressure measurements in an in vivo animal model, and to clinically apply the method by comparing IVPD in children with univentricular hearts (UVH) and healthy controls.MethodsThe accuracy of BST-based IVPD-estimates was assessed in an open-chest porcine model, comparing BST-based IVPD with simultaneous repeated invasive pressure measurements in six pigs using micromanometer catheters. BST-based IVPD assessment was performed in 120 healthy controls and 44 patients with UVH < 18 years of age. Total IVPD (from base to apex) and apical IVPD (from the apical 2/3 of the ventricle) during early diastolic filling of the systemic ventricle was compared between patients with UVH and healthy controls.ResultsThe validation in pigs included 103 measurements, demonstrating a mean difference of - 0.01mmHg (p=0.33) and high correlation (r = 0.95, p-value < 0.001) between IVPD from BST (-1.31 ± 0.28 mmHg) and invasive measurements (-1.30 ± 0.31 mmHg). In the pediatric patients, age range 2 days-17.76 years, feasibility was 96% in controls and 88.6% in UVH patients. Total and apical IVPD were significantly higher in controls compared to UVH (-1.82 vs -0.88 mmHg and -0.63 vs -0.33 mmHg, p < 0.001).Variability was low with intraclass correlation coefficients of 0.99/0.96 (interobserver) and 0.98/0.99 (intraobserver) for total and apical IVPD respectively.ConclusionsBST echocardiography provides accurate estimation of early diastolic IVPD. When clinically applied in children, we found high feasibility and reproducibility. IVPD was significantly lower in children with UVH compared to controls suggesting lower diastolic suction which can impact overall filling dynamics.Clinical perspectiveWhat is newBlood speckle tracking echocardiography provides non-invasive estimation of intraventricular pressure difference in early diastole using two-dimensional blood flow velocitiesIntraventricular pressure difference based on blood speckle tracking is highly feasible, accurate and reproducibleBlood speckle tracking demonstrates significantly reduced intraventricular pressure difference in early diastole in children with univentricular hearts indicating impaired relaxation and suction in these patientsWhat are the clinical implicationsIntraventricular pressure difference based on blood speckle tracking is a novel and potential sensitive echocardiographic parameter to describe early diastolic ventricular relaxation and diastolic function in children with univentricular heartsBlood speckle tracking could improve assessment of diastolic function in children with congenital heart diseaseNon-invasive estimation of intraventricular pressure difference based on blood speckle tracking could improve assessment of diastolic function both in children and adults with heart disease

Background: The lack of reliable echocardiographic techniques to assess diastolic function in children is a ma-jor clinical limitation. Our aim was to develop and validate the intraventricular pressure difference (IVPD) calcu-lation using blood speckle-tracking (BST) and investigate the method's potential role in the assessment of diastolic function in children. Methods: Blood speckle-tracking allows two-dimensional angle-independent blood flow velocity estimation. Blood speckle-tracking images of left ventricular (LV) inflow from the apical 4-chamber view in 138 controls, 10 patients with dilated cardiomyopathies (DCMs), and 21 patients with hypertrophic cardiomyopathies (HCMs) <18 years of age were analyzed to study LV IVPD during early diastole. Reproducibility of the IVPD analysis was assessed, IVPD estimates from BST and color M mode were compared, and the validity of the BST-based IVPD calculations was tested in a computer flow model. Results: Mean IVPD was significantly higher in controls (-2.28 +/- 0.62 mm Hg) compared with in DCM (-1.21 +/- 0.39 mm Hg, P < .001) and HCM (-1.57 +/- 0.47 mm Hg, P < .001) patients. Feasibility was 88.3% in controls, 80% in DCM patients, and 90.4% in HCM patients. The peak relative negative pressure occurred earlier at the apex than at the base and preceded the peak E-wave LV filling velocity, indicating that it repre-sents diastolic suction. Intraclass correlation coefficients for intra-and interobserver variability were 0.908 and 0.702, respectively. There was a nonsignificant mean difference of 0.15 mm Hg between IVPD from BST and color M mode. Estimation from two-dimensional velocities revealed a difference in peak IVPD of 0.12 mm Hg (6.6%) when simulated in a three-dimensional fluid mechanics model. Conclusions: Intraventricular pressure difference calculation from BST is highly feasible and provides informa-tion on diastolic suction and early filling in children with heart disease. Intraventricular pressure difference was significantly reduced in children with DCM and HCM compared with controls, indicating reduced early dia-stolic suction in these patient groups. (J Am Soc Echocardiogr 2023;36:523-32.)

Background:There is conflicting literature regarding the long-term effect of anthracycline treatment on arterial stiffness. This study assessed local arterial stiffness using ultrafast ultrasound imaging (UUI) in anthracycline treated childhood cancer survivors, at rest and during exercise.Methods:20 childhood cancer survivors (mean age 21.02 ± 9.45 years) treated with anthracyclines (mean cumulative dose 200.7 ± 126.80 mg/m2) and 21 healthy controls (mean age 26.00 ± 8.91 years) were included. Participants completed a demographic survey, fasting bloodwork for cardiovascular biomarkers, and performed a submaximal exercise test on a semi-supine bicycle. Pulse wave velocity (PWV) was measured in the left common carotid artery by direct pulse wave imaging using UUI at rest and submaximal exercise. Both PWV at the systolic foot (PWV-SF) and dicrotic notch (PWV-DN) were measured. Central (carotid-femoral) PWV was obtained by applanation tonometry. Carotid measurements were taken by conventional ultrasound. Measures were compared using two-tailed Students t-test or Chi-squared test, as appropriate.Results:There was no statistically significant difference (p > 0.05) between childhood cancer survivors and healthy controls in demographic parameters (age, sex, weight, height, BMI), blood biomarkers (total cholesterol, triglycerides, LDL-c, HDL-c, hs-CRP, fasting glucose, insulin, Hb A1c), cardiovascular parameters (intima media thickness, systolic and diastolic blood pressure, heart rate, carotid diameters, distensibility) or PWV measured by UUI at rest or at exercise. There was also no difference in the cardiovascular adaptation between rest and exercise in the two groups (p > 0.05). Multivariate analysis revealed age (p = 0.024) and LDL-c (p = 0.019) to be significant correlates of PWV-SF in childhood cancer survivors, in line with previously published data.Conclusion:We did not identify a significant impact of anthracycline treatment in young survivors of childhood cancer on local arterial stiffness in the left common carotid artery as measured by UUI.

Type of funding sources: Foundation. Main funding source(s): Labatt Family Heart Centre Bicuspid aortic valves (BAV) are the most common form of congenital heart disease with a prevalence of up to 2%. Fusion of the aortic cusps result in complex flow patterns in the aortic root which may contribute to the risk of progressive dilation. Imaging these patterns with conventional echocardiography is challenging due to the angle dependency of colour Doppler. Blood speckle tracking (BST) is a novel method based on high-frame rate ultrasound that is less angle-independent and developed to evaluate complex flow. The aims of this study were to 1) describe and quantify flow patterns in the aortic root using blood speckle tracking and 2) quantitatively compare flow parameters (energy loss, vorticity, kinetic energy) between paediatric patients with BAVs and those with normal aortic valves. Clinical and routine echocardiographic parameters were collected for children with normal and BAVs.  Children were imaged using a commercially available clinical scanner with research software enabling the acquisition of high-frame rate imaging and blood speckle tracking. Aortic root energy loss, vorticity and kinetic energy were measured in the parasternal long axis view. Data from 46 patients were analyzed (31 normal aortic valves, 15 BAVs) with no significant difference in age, height, weight or BSA between groups. Nine patients (60%) had right-left fusion; 6 (40%) had right-non fusion. Qualitative flow assessment in aortic root demonstrated disturbed flow in the BAV group (see figure) generally directed towards the non-fused cusp (i.e non coronary cusp in right-left fusion). Patients with a BAV had higher aortic valve peak velocity (2.1 m/s vs 0.9 m/s, p< 0.001);  aortic root systolic energy loss (4.29 mW/m vs 1.79 mW/m, p< 0. 001), vorticity (38.7 1/s vs 31.1 1/s, p< 0.01) and kinetic energy (34.5  mJ/m vs 24.5 mJ/m, p = 0.04) compared to those with normal aortic valves. Conclusion(s) Blood speckle tracking can demonstrate altered flow patterns in the aortic root in patients with BAV. These patients have increased energy losses, vorticity and kinetic energy when compared to age matched patients with normal aortic valves however the relationship of theses parameters to aortic root dilation remains to be demonstrated. Abstract Figure. Flow patterns (A-C) and analysis (D-F)

Abstract Funding Acknowledgements Type of funding sources: None. Background The arterial switch operation (ASO) has improved outcomes for patients with transposition of the great arteries (TGA) however the long-term impact on myocardial function and functional reserve during exercise remains poorly described. The aim of this study was to evaluate left (LV), and right ventricular (RV) myocardial response to exercise in children post ASO using semi-supine cycle ergometry stress echocardiography (SSCE). Methods This is a single-center cross-sectional study. Participants prospectively underwent exercise stress echocardiography using a semi-supine bicycle and a stepwise exercise protocol. Systolic (s’) and diastolic (e’) tissue Doppler velocities, as well as myocardial acceleration during isovolumic contraction (IVA) were measured at rest and during exercise at incremental heart rates (HR) in the basal segments of the RV lateral wall, IVS and LV lateral wall. Systolic and diastolic reserve were evaluated by plotting s’ and e’ against HR while contractile reserve was assessed by plotting IVA values against HR which represents the force-frequency relationship (FFR). Results A total of 40 patients with TGA and 29 controls were included. There were no differences between groups in age (14.6 ± 2.9 vs 14.3 ± 3.1 years, p= 0.75), sex (male= 30/40 vs 20/29 p= 0.58), and resting HR (67 ± 12 vs. 71 ± 12 bpm, p = 0.31). Peak HR was lower in the ASO group (142.2 ±12.4 vs 157 ± 12.3 bpm, p< 0.01). At rest, the ASO group showed lower s’ in the RV and IVS (RV s’: 5.7 ± 1.4 vs. 10.2 ± 2.1 cm/s, p <0.001; IVS s’: 4.2 ± 1.3 vs. 6.2 ± 1.8 cm/s, p< 0.001); lower IVA in the IVS and LV (IVS: 1.01 ± 0.37 vs. 1.23 ± 0.4 m/s2, p= 0.03; LV: 0.86 ± 0.32 vs. 1.1 ± 0.4 m/s2, p =0.02), and reduced e’ in all segments. At peak exercise the ASO group showed reduced s’, e’, and IVA in all segments (table1). When plotted against HR, there was blunting of the s’ slope in RV and septal segments while the LV s’ slope was similar between groups. There were no differences in e’ slope when compared to controls (figure 1). The ASO group showed a blunted IVA response to HR in all measured segments compared to controls. Conclusion(s): Our data demonstrate patients post ASO have reduced RV and LV contractile reserve in response to exercise. The etiology and long-term implications of these abnormalities however remains to be described. Abstract Figure. Doppler velocities at baseline and peak Abstract Figure. Dynamic response to exercise

Background:Paediatric pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance resulting in increased pulmonary artery (PA) and right ventricular pressure (RV). This is associated with disturbed flow dynamics in the PA and RV that are not well characterized. We aimed to compare flow dynamics in children with PAH compared with healthy controls using blood speckle tracking echocardiography. Methods:Patients <10 years of age with PAH and healthy controls were included. We examined flow dynamics in the main PA (MPA) and right ventricle based on acquisition blood speckle tracking images obtained from the RV and PA. Qualitative and quantitative analyses were performed. Results:Eighteen subjects were included in each group. A diastolic vortex in the MPA was identified in 16 of the patients with PAH, but not in controls. Significantly higher MPA systolic (4.84 vs 2.42 mW/m; P = 0.01) and diastolic (0.69 vs 0.14 mW/m; P = 0.01) energy loss, as well as increased vector complexity (systole: 0.21 vs 0.04, P = 0.003; diastole: 0.13 vs 0.05, P = 0.04) and diastolic vorticity (15.2 vs 4.4 Hz; P = 0.001), were noted in PAH compared with controls. Conclusion:This study demonstrates the presence of abnormal flow patterns in the MPA with diastolic vortex formation in most patients with PAH. This diastolic vortex likely results from reflected waves from the distal pulmonary bed. Our data indicate that the diastolic vortex could potentially be used in the diagnosis of PAH. The clinical significance of the energy loss findings warrants further investigation in a larger cohort of patients with PAH.

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): CIHR Background Anthracyclines, which are commonly used in cancer treatment can induce myocardial damage, result in heart failure during treatment and have cardiac effects even decades after treatment. Monitoring of cardiotoxicity during treatment is largely based on the use of echocardiographic functional markers like ejection fraction and more recently myocardial strain imaging. Some studies have also looked at the utility of biomarkers like troponin and BNP. The utility of this surveillance strategy remains controversial as larger prospective studies are lacking. Purpose The aim of this study was to prospectively describe the impact of anthracycline treatment on echocardiographic functional parameters and cardiac biomarkers (high sensitivity troponin T and NT-Pro BNP) during the treatment period and twelve months after completion of treatment. In the current study we wanted to look at whether monitoring parameters during treatment were predictive of left ventricular function 12 months after treatment. Methods This was a prospective multi-centre nested case-control study of 256 children diagnosed with cancer requiring anthracycline therapy. Baseline functional echocardiographic parameters and cardiac biomarkers were obtained prior to starting anthracycline therapy, during the treatment protocol, and 12 months after treatment completion. Patients were assigned to one of two comparison groups based on the fractional shortening at the12-month echocardiogram: patients in group 1 had normal fractional shortening, (FS ³ 28%) while patients in group 2 had reduced fractional shortening (FS < 28%). Results A total of 917 echoes were performed, 376 of these occurred during the treatment period. FS was reduced in 27 (7%) of echoes obtained during the treatment period with 22 patients developing new onset dysfunction. Twelve months after treatment completion 232 patients had normal FS (Group 1), while 24 patients showed reduced FS (Group 2). Both groups had normal systolic function and cardiac biomarkers at baseline, however patients in group 2 were older at diagnosis (13.2 years (11.8-16) vs 6.5 years (3.4-13.2), p = 0.003) and received a higher cumulative anthracycline dose (200 mg/m2 (143-318) vs 125 mg/m2 (75-200), p= 0.005). One third (8/24) of patients in group 2 had at least 1 abnormal echo during the treatment period compared to 7% (16/232) in the normal group P < 0.001. The proportion of patients with at least one abnormal biomarker during this period however, was similar between groups. Conclusion(s) Patients receiving higher accumulative anthracycline doses and those with abnormal FS during the treatment period are at higher risk of having reduced cardiac function 12 months after treatment. High sensitivity troponin and NT-Pro BNP levels during the treatment period fail to discriminate patients at risk of developing early reduced systolic function. The relationship of these early results to long term cardiac function remains to be demonstrated.

OBJECTIVES:Having an anomalous right subclavian artery has been quoted to be a risk factor for early and late adverse events. We wanted to determine the rate of adverse outcomes in patients who have undergone arch repair with an associated anomalous right subclavian artery. METHODS:The follow-up of 76 patients, with an anomalous right subclavian artery, who underwent arch repair at a single institution for various indications between 1981 and 2017 was reviewed. RESULTS:There were 12 patient deaths. Twenty-three patients required an aortic arch reintervention (17 surgeries, 2 of which were indicated for bronchial obstruction). At last follow-up, 8 of 54 surviving patients (15%) had arch reobstruction (peak gradient >25 mmHg or reintervention). Freedom from aortic arch obstruction at 10 and 15 years was 51% [95% confidence interval (CI) 36-65%] and 35% (95% CI 19-51%), respectively. Neither the complete resection of the adjacent ridge nor the detachment and reimplantation of the anomalous subclavian vessel seemed to have an impact on the rate of reobstruction [hazard ratio (HR) 1.6, 95% CI 0.77-3.5; P = 0.2 and HR 0.61, 95% CI 0.083-4.5; P = 0.6, respectively]. CONCLUSIONS:Patients with an anomalous right subclavian artery are at risk of arch reobstruction necessitating reintervention but long-term follow-up was unable to demonstrate the mechanism of this obstruction in patients with this anomaly.