Cameron Slorach

Comparison between Different Speckle Tracking and Color Tissue Doppler Techniques to Measure Global and Regional Myocardial Deformation in Children

BACKGROUND Myocardial deformation parameters obtained by speckle-tracking echocardiography (STE) and color Doppler tissue imaging (CDTI) using two different ultrasound systems and three different software packages were compared. METHODS Apical four-chamber, short-axis grayscale, and color Doppler tissue images were prospectively acquired using Vivid 7 and iE33 ultrasound systems in 34 children and then analyzed using EchoPAC and QLAB (STE) and SPEQLE (CDTI). RESULTS Measurement of myocardial deformation was feasible for all three modalities. Longitudinal strain (epsilon) measurements showed the lowest intraobserver and interobserver variability (intraobserver and interobserver coefficients of variation, 9% and 8% for EchoPAC, 5% and 6% for QLAB, and 14% and 16% for SPEQLE). In addition, longitudinal epsilon had a small bias and narrow limits of agreement when comparing different techniques. The coefficients of variation of circumferential epsilon by EchoPAC and QLAB were 12% and 11% (intraobserver) and 9% and 13% (interobserver), respectively. Circumferential epsilon by STE had a small systematic bias but relatively narrow limits of agreement. The reproducibility of radial epsilon measurements using STE was low, while CDTI epsilon provided better performance (intraobserver and interobserver coefficients of variation for radial posterior epsilon, 12% and 24% for EchoPAC, 39% and 56% for QLAB, and 12% and 14% for SPEQLE). Radial epsilon was on average 50% lower using QLAB compared with EchoPAC and SPEQLE. Systolic strain rate values obtained by STE were lower compared with CDTI-derived values. The limits of agreement for strain rate values among the three modalities were wide, and intraobserver and interobserver variability was poor for all three modalities. CONCLUSIONS Some deformation measurements (e.g., longitudinal and circumferential epsilon) are comparable among different ultrasound machines and software packages, whereas others are significantly different (e.g., radial epsilon and strain rate). This study stresses the need for an industry standard for these techniques.

The Effect of Cyclooxygenase-2 Inhibition on Renal Hemodynamic Function in Humans With Type 1 Diabetes

OBJECTIVE—Studies in animal models suggest that cyclooxygenase-2 (COX2) plays a role in the regulation of the renal microcirculation in diabetes. Accordingly, we examined the role of COX2 in the control of renal hemodynamic function and in the renal response to hyperglycemia in humans with uncomplicated type 1 diabetes. We hypothesized that COX2 inhibition would alleviate the hyperfiltration state and would abrogate the hyperglycemia-mediated rise in glomerular filtration rate (GFR). RESEARCH DESIGN AND METHODS—Renal function was assessed during clamped euglycemia and hyperglycemia on 2 consecutive days before and then again after 14 days of COX2 inhibition using 200 mg celecoxib once daily by mouth. For analysis, the cohort was then divided into two groups based on the baseline GFR: 9 subjects exhibited hyperfiltration (GFR ≥135 ml/min per 1.73 m2), and 12 subjects exhibited normofiltration (GFR <135 ml/min per 1.73 m2). RESULTS—Under euglycemic conditions, COX2 inhibition resulted in a significant decline in GFR in the hyperfiltration group (150 ± 5 to 139 ± 5 ml/min per 1.73 m2) but increased GFR in the normofiltration group (118 ± 5 to 138 ± 5 ml/min per 1.73 m2). COX2 inhibition did not blunt the hyperglycemia-associated rise in GFR in the normofiltration group and was instead associated with an augmented rise in GFR. CONCLUSIONS—In summary, our results support the hypothesis that COX2 is an important determinant of renal hemodynamic function in subjects with type 1 diabetes. The renal response to COX2 inhibition emphasizes that hyperfiltration and normofiltration are distinct physiological states.

Effect of Transcatheter Pulmonary Valve Implantation on Short-Term Right Ventricular Function as Determined by Two-Dimensional Speckle Tracking Strain and Strain Rate Imaging

Transcatheter pulmonary valve implantation (PVI) is an emerging therapy for right ventricular (RV) outflow dysfunction in congenital heart disease. We investigated, for the first time in children after surgery for congenital heart disease, the short-term effects of PVI on RV and left ventricular (LV) function using 2-dimensional speckle tracking echocardiography and tissue Doppler imaging. We hypothesized that the short-term RV and LV function would improve. Two-dimensional speckle tracking echocardiograms and pulsed tissue Doppler images were obtained before and 1 to 2 days after PVI (18-mm Melody valve). The catheter right heart hemodynamics were recorded. The strain and strain rate of the basal lateral left ventricle, lateral right ventricle, and interventricular septum were measured by 2-dimensional speckle tracking echo, and the pre- and postprocedure values were compared. Of the 16 eligible patients (age 16 +/- 2 years), the scans of 10 had correct image format and adequate quality. PVI was performed for volume (n = 4) or combined pressure-volume (n = 6) loading. After PVI, the RV to pulmonary artery pressure gradient (33 +/- 22 to 12 +/- 4 mm Hg, p = 0.02), pulmonary regurgitation, and RV end-diastolic volume (3.2 +/- 0.8 to 2.8 +/- 0.6 cm, p = 0.02) decreased, and the septal systolic velocities (3.5 +/- 1.1 to 4.7 +/- 1.1 cm/s, p = 0.04), strain (-7.6 +/- 9.3% to -15.6% +/- 6.7%, p = 0.01) and strain rate (-0.3 +/- 1.1 to -1.1 +/- 0.5 1/s, p = 0.04) and RV free wall strain increased (-17.4 +/- 8.6% to -23.4% +/- 6.2%, p = 0.03). The LV tissue velocities, strain, and strain rate were unchanged. In conclusion, PVI leads to RV unloading and acutely improves RV and septal function.

Renal Hyperfiltration is a Determinant of Endothelial Function Responses to Cyclooxygenase 2 Inhibition in Type 1 Diabetes

OBJECTIVE Our aim was to examine the effect of cyclooxygenase 2 (COX2) inhibition on endothelial function in subjects with type 1 diabetes analyzed on the basis of renal filtration status. RESEARCH DESIGN AND METHODS Flow-mediated dilation (FMD) was determined in type 1 diabetic subjects and hyperfiltration (glomerular filtration rate ≥135 ml/min/1.73 m2, n = 13) or normofiltration (glomerular filtration rate ≥135 ml/min/1.73 m2, n = 11). Studies were performed before and after celecoxib (200 mg daily for 14 days) during euglycemia and hyperglycemia. RESULTS Baseline parameters were similar in the two groups. Pretreatment, FMD was augmented in normofiltering versus hyperfiltering subjects during clamped euglycemia (10.2 ± 5.3% vs. 5.9 ± 2.3%, P = 0.003). COX2 inhibition suppressed FMD in normofiltering (10.2 ± 5.3% to 5.8 ± 3.4%, P = 0.006) versus hyperfiltering subjects (ANOVA interaction, P = 0.003). CONCLUSIONS Systemic hemodynamic function, including the response to COX2 inhibition, is related to filtration status in diabetic subjects and may reflect general endothelial dysfunction.

Exercise induces biventricular mechanical dyssynchrony in children with repaired tetralogy of Fallot

Objective The mechanisms underlying adverse electro-mechanical interaction after tetralogy of Fallot (TOF) repair remain unclear. This study investigated biventricular dyssynchrony in children with TOF and its relationship to exercise, QRS duration (QRSd) and ventricular mechanics. Methods 29 asymptomatic children (5–18 years) with repaired TOF were prospectively evaluated by MRI, cardiopulmonary exercise testing and echocardiography at rest and during bicycle exertion. Their dyssynchrony results were compared with those of 44 resting and 27 exercising, age- and sex-matched controls. An intraventricular dyssynchrony index was calculated from the SD of regional time intervals in 12 left ventricular (LV) ‘Ts LV-12SD’ and eight right ventricular (RV) ‘Ts RV-8SD’ segments. Ventricular size, volumes, ejection fractions, pulmonary regurgitant volumes and peak oxygen consumption and N-terminal BNP levels were quantified in the patients. Results Despite moderate RV dilatation (median indexed RV end-diastolic volume 145.2 ml/m2) and right bundle branch block (median QRSd 130 ms) compared with controls, children with TOF demonstrated neither RV nor LV dyssynchrony at rest (Ts RV-8SD, 37.9±10.2 vs 44.3±10.3, 95% CI −11.8 to −0.99, p=0.02; Ts LV-12SD, 38.6±16.8 vs 34.0±10.8, 95% CI −1.8 to 11.0, p=0.16). Exercise stress induced biventricular dyssynchrony in patients with TOF but not in controls (Ts RV-8SD, 59.9±34.4 vs 28.2±10.4, p<0.0001, 95% CI 17.2 to 46.3; Ts LV-12SD, 48.0±18.6 vs 31.9±10.7, 95% CI 7.9 to 24.4, p=0.002). This was unrelated to QRSd, ventricular volumes and function, or peak oxygen consumption. Conclusion Exercise induces biventricular mechanical dyssynchrony in children with TOF.

Isovolumic Acceleration at Rest and During Exercise in Children: Normal Values for the Left Ventricle and First Noninvasive Demonstration of Exercise-Induced Force-Frequency Relationships

OBJECTIVES This study aimed to determine the normal variation of left ventricular (LV) isovolumic acceleration (IVA) in healthy children and to assess the feasibility of an entirely noninvasive method for demonstration of the LV force-frequency relationship (FFR). BACKGROUND Pediatric cardiologists continue to seek noninvasive, load-independent indexes for the assessment of LV contractility and myocardial reserve. METHODS Resting LV IVA was measured by echocardiogram in 236 healthy children and compared with their clinical characteristics. Further measurements were made in 51 children at incremental heart rates during semi-recumbent exercise. For these, FFRs were constructed by plotting LV IVA against heart rate. To assess potential clinical applications, pilot FFR data were collected from 16 children previously treated with anthracyclines. RESULTS In healthy children, median resting LV IVA was 1.2 m/s(2), interquartile range 0.9 to 1.6 m/s(2). Resting LV IVA was unaffected by age, sex, weight, height, and body surface area but associated with baseline heart rate (r = 0.18, p = 0.0006). Noninvasive evaluation of the LV FFR was possible in 98% of subjects. Positive FFRs were confirmed in all the healthy children. By comparison, several of the children with anthracycline exposure demonstrated flattened force-frequency curves that were largely independent of resting LV ejection fraction and suggest reduced contractile reserve. CONCLUSIONS In children over 7 years, it is possible to demonstrate the LV FFR by interval measurement of IVA during exercise. The availability of pediatric normal values for both this relation and resting LV IVA might facilitate future investigation of LV contractility and myocardial contractile reserve during childhood.

Relation Between Left Ventricular Regional Radial Function and Radial Wall Motion Abnormalities Using Two-Dimensional Speckle Tracking in Children With Idiopathic Dilated Cardiomyopathy

Left ventricular (LV) regional radial function and its relation to radial wall motion abnormalities have not been investigated in children with idiopathic dilated cardiomyopathy (IDC). Radial strain was measured using 2-dimensional speckle tracking to evaluate regional radial function and wall motion in 6 LV segments in 24 children (0 to 18 years old) with IDC and 16 healthy controls. Patients and controls were similar in age. Patients with IDC had higher heart rates (97 +/- 28 vs 77 +/- 19, p <0.05) and decreased ejection fraction (34 +/- 12% vs 66 +/- 7%, p <0.0001) compared with controls. Radial strain in all segments was significantly lower in patients with IDC. In IDC, average radial strain correlated well with ejection fraction (r = 0.8, p <0.0001). The SD of time to peak radial strain among 6 LV segments was significantly higher in patients with IDC than in controls (56 +/- 38 vs 15 +/- 12 ms, p <0.0001). Segmental peak radial strain correlated closely to time to peak radial strain in controls (r = 0.98, p = 0.0008), but less in patients with IDC (r = 0.76, p = 0.07). In conclusion, LV regional radial function is impaired in pediatric IDC, in association with increased radial dyssynchrony, revealing a possible important mechanism for LV dysfunction in these children.

Renal hemodynamic effect of cyclooxygenase 2 inhibition in young men and women with uncomplicated type 1 diabetes mellitus

In experimental studies, cyclooxygenase 2 (COX2)-derived vasodilatory prostaglandins play a more prominent role in arterial vasoregulation in females. The gender-dependent effect of COX2 modulation in humans with type 1 diabetes mellitus (DM) is unknown. Accordingly, we examined the renal hemodynamic role of prostaglandins by assessing the response to COX2 inhibition in young men and women with type 1 DM. We also used a graded ANG II infusion to determine whether gender-based differences were mediated by effects of COX2 inhibition on the renin angiotensin system (RAS). We hypothesized that COX2 inhibition would be associated with preferential vasoconstriction in women and would augment their response to ANG II. Baseline renal function and the response to an ANG II infusion were assessed during clamped euglycemia, and again after COX2 inhibition (200 mg celecoxib daily for 14 days) in 12 men and 9 women after 1 wk on a controlled protein and sodium diet. COX2 inhibition was associated with increases in filtration fraction (P = 0.045) and renal vascular resistance and a decline in renal blood flow (P = 0.04) in women compared with men. Before COX2 inhibition, women exhibited a decline in glomerular filtration rate in response to ANG II. COX2 inhibition abolished this effect, whereas the response was not altered in men. In summary, COX2 inhibition was associated with hemodynamic effects that differed based on gender. The ANG II response suggests that with uncomplicated type 1 DM, prostaglandins may contribute to RAS-mediated gender differences. Our results are consistent with experimental data suggesting augmented female prostanoid dependence.

Myocardial Tissue Doppler Velocity Imaging in Children: Comparative Study between Two Ultrasound Systems

BACKGROUND The investigators compared pulsed-wave tissue Doppler (PWTD) and color tissue Doppler (CTD) ventricular tissue velocities obtained using Vivid 7 (GE) and iE33 (Philips) ultrasound systems within a 30-minute time frame and examined interobserver and intraobserver variability. METHODS Longitudinal PWTD and CTD images were prospectively acquired in 49 children from the base of the right and left ventricular free wall and septum and stored for offline analysis. RESULTS Intraobserver and interobserver coefficients of variation for PWTD velocities ranged from 4% to 6% and 5% to 10% for GE and from 1% to 10% and 2% to 14% for Philips, respectively. Intraobserver and interobserver coefficients of variation for CTD velocities ranged from 4% to 15% and 6% to 24% for GE and from 6% to 19% and 7% to 25% for Philips, respectively. Mean biases between the two systems for PWTD velocities, expressed as percentage differences, were around 0%, with the narrowest limits of agreement for systolic velocities at the septal annulus and the widest limits of agreement for early diastolic velocities at the lateral tricuspid valve annulus, respectively. Peak CTD-derived velocities were significantly and consistently lower for Philips compared with GE. CONCLUSIONS Agreement between GE-derived and Philips-derived PWTD velocities was reasonable, whereas CTD-derived velocities differed substantially.

Relation of right ventricular mechanics to exercise tolerance in children after tetralogy of Fallot repair

BACKGROUND Progressive right ventricular (RV) dysfunction and exercise intolerance are common problems after tetralogy of Fallot (TOF) repair. We investigated RV myocardial deformation and dyssynchrony in children after TOF repair and their association with exercise capacity. METHODS Asymptomatic children after TOF repair were investigated by 2-dimensional speckle tracking echocardiography, magnetic resonance, and metabolic exercise study. Patients with RV outflow obstruction were excluded. Peak RV longitudinal strain and strain rate (SR) and dyssynchrony (RV intraventricular delay) were compared with healthy controls. Associations between RV strain, dyssynchrony, and exercise capacity were analyzed. RESULTS Thirty-nine (81%) of 48 TOF patients and 40 healthy controls had adequate RV strain imaging. The TOF patients had moderately dilated RVs and normal RV ejection fraction. Right ventricular peak systolic strain (-23.2% ± 5.1% vs -28.5% ± 8.5%, P < .001) and SR (-1.46 ± 0.68 vs -2.1 ± 0.8, P < .001) were reduced in TOF patients compared with controls. Right ventricular intraventricular delay was higher in TOF patients (146.0 ± 159 vs 71.0 ± 92 milliseconds, P = .008). Decreased RV strain and SR were associated with increased RV dyssynchrony (strain parameter estimate [PE] 6.31 [2.30], P = .007; SR [PE] 11.32 [3.84], P = .004). Increased RV-left ventricular delay was associated with prolonged QRS duration (PE 0.13 [0.058], P = .03) and reduced RV ejection fraction (PE -2.95 [1.275], P = .02). Reduced RV peak SR was associated with decreased exercise peak oxygen uptake (PE 0.14 [0.07], P = .04). CONCLUSIONS After repair of TOF, asymptomatic children have reduced RV deformation in association with RV dyssynchrony and reduced exercise tolerance.