Sophia J. Wong

Relationship between carotid intima-media thickness and arterial stiffness in children after Kawasaki disease

Background: Evidence of premature atherosclerosis and systemic arterial stiffening in patients after Kawasaki disease is accumulating. Aim: To test the hypothesis that carotid intima-media thickness (IMT), a surrogate marker of atherosclerosis, is associated with systemic arterial stiffness in children after Kawasaki disease. Methods: A cohort of 72 patients was studied, comprising 26 patients with Kawasaki disease and coronary aneurysms (group I), 24 patients with Kawasaki disease and normal coronary arteries (group II) and 22 healthy age-matched children (group III). The carotid IMT, carotid artery stiffness index, brachioradial pulse wave velocity (PWV), fasting total cholesterol, high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol were determined and compared among the three groups. Results: The carotid IMT was related to indices of arterial stiffness, and significant determinants of carotid IMT were identified by multivariate analysis. The mean (standard deviation (SD)) carotid IMT of both group I (0.41 (0.04) mm) and group II (0.39 (0.04) mm) was significantly greater than that of group III (0.36 (0.04) mm; p<0.001 and p = 0.008, respectively). For the entire cohort, carotid IMT correlated positively with LDL cholesterol (r = 0.31, p = 0.009), carotid artery stiffness index (r = 0.40, p = 0.001) and brachioradial PWV (r = 0.28, p = 0.016), but not with age, body mass index, systemic blood pressure, and HDL and total cholesterol. Multiple linear regression analysis identified carotid artery stiffness index (β = 0.25, p = 0.028) and subject grouping (β = −0.39, p = 0.001; model R2 = 0.29) as significant correlates of carotid IMT. Conclusion: The increased carotid IMT in children after Kawasaki disease is associated with systemic arterial stiffening.

Left ventricular myocardial deformation and mechanical dyssynchrony in children with normal ventricular shortening fraction after anthracycline therapy

Objective The M-mode-derived left ventricular shortening fraction is incorporated into most of the paediatric oncology protocols for monitoring of cardiotoxicity. This study tested the hypothesis that alteration of left ventricular myocardial deformation and mechanical dyssynchrony may occur in asymptomatic children after anthracycline therapy despite having left ventricular shortening fractions within the limits of normal. Design Cross-sectional study. Setting Tertiary paediatric cardiac centre. Methods Left ventricular longitudinal, circumferential and radial myocardial deformation was determined using speckle tracking echocardiography in 45 patients aged 15.3±5.8 years. Real-time three-dimensional echocardiographic data were acquired for the measurement of left ventricular volumes and systolic dyssynchrony index (SDI), the latter derived from the dispersion of time-to-minimum regional volume using a 16-segment model. The results were compared with those of 44 controls. Results Compared with controls, patients had reduced left ventricular global systolic longitudinal strain (p=0.012), circumferential strain (p<0.001), radial strain (p=0.006) and circumferential strain rate (SR; p=0.002). The cumulative anthracycline dose correlated negatively with global longitudinal (r=−0.33, p=0.027) and circumferential (r=−0.32, p=0.035) SR. The left ventricular SDI was significantly greater in patients than controls (4.46±1.52% vs 3.80±0.58%, p=0.03). The prevalence of left ventricular mechanical dyssynchrony (SDI >4.96%) in patients was 16% (95% CI 6% to 29%). In patients, SDI correlated negatively with left ventricular ejection fraction (r=−0.52, p<0.001), radial strain (r=−0.35, p=0.021), circumferential strain (r=−0.37, p=0.015) and circumferential SR (r=−0.43, p=0.004), but not with the cumulative anthracycline dose (p=0.82). Conclusions Impaired left ventricular myocardial deformation and mechanical dyssynchrony may exist in children after anthracycline therapy despite having normal left ventricular shortening fractions.

Impact of Right Ventricular Volume Overload on Three-Dimensional Global Left Ventricular Mechanical Dyssynchrony After Surgical Repair of Tetralogy of Fallot

This study aimed to test the hypothesis that right ventricular (RV) volume overload may result in left ventricular (LV) systolic dysfunction through induction of LV systolic dyssynchrony after tetralogy of Fallot (TOF) repair. Sixty patients with TOF repair were studied at 14.3 +/- 7.2 years after TOF repair. Real-time 3-dimensional echocardiographic data sets were acquired for measurement of LV and RV volumes and derivation of ejection fractions and pulmonary regurgitant volume. The LV systolic dyssynchrony index (SDI) was derived from the dispersion of time to minimum regional volume using a 16-segment model. The results were compared with those of 29 healthy controls. LV SDI was significantly higher in patients than controls (7.4% +/- 2.0% vs 3.0% +/- 0.9%, p <0.001). The prevalence of LV mechanical dyssynchrony (SDI >4.7%) in patients was 93% (95% confidence interval 87% to 100%). The time to minimum regional volume was significantly longer in all of the 6 basal segments and the midposterior segment (all p <0.05) in patients than controls. Multivariate analysis identified RV end-diastolic volume (beta = 0.58, p <0.001), LV ejection fraction (beta = -0.38, p <0.001), and LV end-diastolic volume (beta = 0.26, p = 0.002) as significant correlates of LV SDI. In conclusion, in patients after TOF repair, RV volume overload has a negative effect on LV systolic function through induction of global LV mechanical dyssynchrony.

Central and peripheral arterial stiffness in patients after surgical repair of tetralogy of Fallot: implications for aortic root dilatation

Objectives: To test the hypotheses that (1) the central conduit arteries stiffen preferentially over the peripheral conduit arteries in patients with repaired tetralogy of Fallot (ToF); and (2) central arterial stiffening is related to aortic root dilatation. Design and patients: Heart–femoral pulse wave velocity (PWV), femoral–ankle PWV, carotid augmentation index and body surface area-adjusted aortic sinotubular dimension were determined in 31 children after ToF repair and compared with those in 31 age-matched controls after left-to-right shunt repair. In addition, the PWVs and augmentation index were related to the sinotubular junction dimension. Settings: Tertiary paediatric cardiac centre. Results: Compared with controls, patients had significantly greater heart–femoral PWV (mean 666 (SD 151) v 587 (81) cm/s, p  =  0.021) and carotid augmentation index (−14.1 (17.0)% v −25.2 (14.6)%, p  =  0.016), whereas the right (888 (202) v 845 (207) cm/s, p  =  0.42) and left (918 (227) v 851 (215) cm/s, p  =  0.25) femoral–ankle PWVs were similar between the two groups. The sinotubular junction z score of patients was significantly greater than that of controls (4.7 (1.5) v 1.1 (1.4), p < 0.001). Univariate analysis showed that the sinotubular junction z score correlated positively with heart–femoral PWV (r  =  0.43, p  =  0.001) and carotid augmentation index (r  =  0.46, p  =  0.001). Multiple linear regression similarly identified heart–femoral PWV (β  =  0.30, p  =  0.04) and carotid augmentation index (β  =  0.31, p  =  0.04) (model R2  =  0.26) as significant determinants of sinotubular junction z score. Conclusions: The aorta stiffens in patients with repaired ToF, which may contribute to progressive dilatation of the aortic root in the long term.

Left ventricular twisting and untwisting motion in childhood cancer survivors.

Background: Anthracycline has been shown to degrade titin that plays a role in myocardial twisting and untwisting. This study aimed to test the hypothesis that left ventricular (LV) twisting and untwisting motion may be altered in children after anthracycline therapy. Methods: Thirty‐six childhood leukemia survivors aged 15.6 ± 5.5 years and 20 healthy controls aged 16.8 ± 7.7 years (P = 0.54) were studied. LV twisting and untwisting motion was determined using speckle tracking imaging, whereas LV ejection fraction and systolic and diastolic mitral annular velocities were determined respectively by three‐dimensional and tissue‐Doppler echocardiography. Results: Compared with controls, patients had significantly lower LV ejection fraction (P = 0.01) but similar systolic and diastolic mitral annular velocities (all P > 0.05). Their peak LV torsion (P = 0.003), systolic twisting velocity (P < 0.001), and diastolic untwisting velocity (P = 0.04) were significantly lower than controls, which could be attributable to their reduced apical rotation (P = 0.03) and apical untwisting rate (P = 0.002). For the whole cohort, LV systolic torsion and twisting velocity correlated significantly with apical untwisting rate (P < 0.001) and LV diastolic untwisting velocity (P < 0.001). In patients, none of the twisting or untwisting parameters were found to correlate with cumulative anthracycline dose (all P > 0.05). Twenty‐eight (78%) patients had LV ejection fractions ≥50%. Although their systolic and diastolic mitral annular velocities were similar to those of controls, their peak LV torsion (P = 0.005), apical untwisting rate (P = 0.01), and LV systolic twisting velocity (P = 0.001) remained significantly lower. Conclusion: Impairment of LV twisting and untwisting motion is evident in children after anthracycline therapy, even in those with “normal” LV ejection fractions. (Echocardiography 2011;28:738‐745)

Transmural strain and rotation gradient in survivors of childhood cancers

AIMS Subendocardial layer of the ventricle has been shown to be sensitive to anthracycline damage. This study tested the hypothesis that anthracycline therapy for childhood malignancies has differential impact on deformation and rotation of left ventricular (LV) subendocardial and subepicardial layers and hence transmural myocardial strain and rotation gradients. METHODS AND RESULTS Thirty-two anthracycline-treated survivors of childhood malignancies aged 19.3 ± 5.4 years and 28 controls were studied. Apical four-chamber and parasternal LV short-axis acquisitions at base, papillary muscle level, and apex were analysed for layer-specific myocardial strain and apical and basal rotation and rotational velocities using two-dimensional speckle tracking echocardiography. Transmural strain and rotation gradients were calculated as differences between peak systolic strain and rotation between the inner and outer layers, respectively. Compared with controls, patients had significantly lower transmural circumferential, but not radial or longitudinal, strain gradients (P< 0.05), accounted by the reduced subendocardial circumferential strain, at all three ventricular levels (all P< 0.05). No significant difference in basal transmural rotation gradient was found between patients and controls (P= 0.32). On the other hand, apical rotation, systolic twisting velocity, and diastolic untwisting velocity were reduced preferentially at the subendocardial layer in patients (all P< 0.05), hence accounting for their significantly reduced transmural rotation gradient compared with controls (P< 0.001). The LV ejection fraction correlated inversely with apical transmural circumferential strain gradient (r= -0.39, P= 0.002) and rotation gradient (r= 0.33, P= 0.01). CONCLUSION Preferential impairment of subendocardial circumferential deformation and apical rotation with consequential reduction of transmural circumferential strain and rotation gradients occurs in anthracycline-treated survivors of childhood cancers.

Left ventricular mechanics in repaired tetralogy of Fallot with and without pulmonary valve replacement: analysis by three-dimensional speckle tracking echocardiography.

Background Altered septal curvature and left ventricular (LV) geometry secondary to right ventricular (RV) dilation render two-dimensional assessment of LV mechanics difficult in repaired tetralogy of Fallot (TOF) patients. The novel three-dimensional (3D) speckle tracking echocardiography enables comprehensive evaluation of true 3D LV mechanics. Methods and Results Seventy-six patients aged 23.6±8.3 years, 55 with isolated repair (group I) and 21 with subsequent pulmonary valve replacement (group II), and 34 healthy controls were studied. Three-dimensional volume datasets were acquired for assessment of LV global and regional 3D strain, systolic dyssynchrony index (SDI), twist, twist gradient (twist/LV length), and ejection fraction. A global performance index was calculated as (global 3D strain•twist gradient)/SDI. The septal curvature and LV eccentricity were determined from the mid-ventricular short-axis. Compared with controls, group I and II patients had significantly reduced LV global 3D strain, LV twist, twist gradient, septal curvature, and global performance index, and greater LV systolic and diastolic eccentricity and SDI (all p<0.05). All but the four apical LV segments in patients had reduced regional 3D strain compared with controls (all p<0.05). Septal curvature correlated with LV global 3D strain (r = 0.41, p<0.001), average septal strain (r = 0.38, p<0.001), twist (r = 0.32, p<0.001), twist gradient (r = 0.33, p<0.001), and global performance index (r = 0.43, p<0.001). Conclusions Adverse 3D LV mechanics as characterized by impaired global and regional 3D systolic strain, mechanical dyssynchrony, and reduced twist is related to reduced septal curvature in repaired TOF patients with and without pulmonary valve replacement.

Restrictive Right Ventricular Physiology and Right Ventricular Fibrosis as Assessed by Cardiac Magnetic Resonance and Exercise Capacity After Biventricular Repair of Pulmonary Atresia and Intact Ventricular Septum

The hypertrophic myocardium, myocardial fiber disarray, and endocardial fibroelastosis in pulmonary atresia and intact ventricular septum (PAIVS) may provide anatomic substrates for restrictive filling of the right ventricle.

Myocardial Deformation in Patients with Beta-Thalassemia Major: A Speckle Tracking Echocardiographic Study

Background: Increasing data suggest that parameters of myocardial deformation are strong indices of ventricular systolic and diastolic function. We sought to determine myocardial deformation of the left ventricle and assess relationship of deformation rates with myocardial iron load in patients with beta‐thalassemia major. Methods: The left ventricular longitudinal, circumferential, and radial myocardial deformation was determined using speckle tracking echocardiography in 42 thalassemia patients aged 24.4 ± 6.4 years. The results were compared with those of 38 age‐matched controls. The rates of longitudinal and circumferential deformation were correlated with cardiac T2* magnetic resonance findings. Results: Compared with controls, patients had significantly greater global systolic radial strain (P = 0.001), but similar global systolic longitudinal (P = 0.12) and circumferential strain (P = 0.84). On the other hand, patients had significantly lower longitudinal systolic strain rate (SR) (P = 0.019), longitudinal early diastolic SR (P = 0.036), and circumferential early diastolic SR (P = 0.04) than controls. The cardiac T2* findings correlated positively with longitudinal (r = 0.44, P = 0.004) and circumferential early diastolic SR (r = 0.37, P = 0.019), but not with the respective systolic SRs and left ventricular ejection fraction (all P > 0.05). Patients with iron overload (T2*< 20 msec), compared to those without, had significantly lower longitudinal (1.45 ± 0.33/sec vs. 1.76 ± 0.27/sec, P = 0.002) and circumferential (1.01 ± 0.31/sec vs. 1.22 ± 0.31/sec, P = 0.03) early diastolic SR. Conclusions: Patients with beta‐thalassemia major have reduced longitudinal systolic SR, longitudinal early diastolic SR, and circumferential early diastolic SR. The rates of diastolic deformation in the longitudinal and circumferential dimensions are inversely related to myocardial iron overload. (Echocardiography 2010;27:253‐259)

Right Ventricular Mechanics in Adults after Surgical Repair of Tetralogy of Fallot: Insights from Three-Dimensional Speckle-Tracking Echocardiography

BACKGROUND The clinical relevance of evaluating right ventricular (RV) myocardial deformation in congenital heart disease is increasingly recognized. The aim of this study was to explore, using three-dimensional (3D) speckle-tracking echocardiography, RV mechanics in terms of 3D global area strain and mechanical dyssynchrony in adults with repaired tetralogy of Fallot. METHODS Twenty patients (12 men) aged 24.7 ± 8.6 years and 22 age-matched controls (11 men) were studied. Global RV peak area strain and area strain-derived systolic dyssynchrony index (SDI) were determined using 3D speckle-tracking echocardiography. RV end-diastolic volume and end-systolic volume, ejection fraction (EF), and pulmonary regurgitation fraction were measured in patients using cardiac magnetic resonance. RESULTS Coefficients of variation for intraobserver and interobserver measurements of RV global area strain were 6.1% and 7.9%, respectively, and those for SDI were 7.6% and 10.1%, respectively. Compared with controls, patients had significantly lower global area strain (P = .005) and greater SDI (P = .008). The prevalence of RV mechanical dyssynchrony (SDI > control mean + 2 SDs) in patients was 30%. In patients, global area strain correlated inversely with SDI (r = -0.42, P = .04), RV end-diastolic volume (r = -0.48, P = .032), and RV end-systolic volume (r = -0.48, P = .031) and positively with EF (r = -0.51, P = .02), while RV SDI correlated positively with RV end-systolic volume (r = 0.55, P = .012), pulmonary regurgitation fraction (r = 0.54, P = .031), and QRS duration (r = 0.51, P = .022) and negatively with RV EF (r = -0.62, P = .004). Multivariate analysis showed that RV EF (β = 0.22, P = .048) was a significant correlate of global area strain in patients. CONCLUSIONS In adults after tetralogy of Fallot repair, 3D RV deformation is impaired in association with RV dyssynchrony, volume overloading, and reduced EF.