Role of Three-Dimensional Speckle Tracking Echocardiography in the Quantification of Myocardial Iron Overload in Patients with Beta-Thalassemia Major.

BACKGROUND: The new three-dimensional speckle tracking echocardiography (3DSTE) may enable comprehensive quantification of global left ventricular (LV) myocardial mechanics. METHODS: Twenty-four patients aged 29.3 ± 5.2 years and 22 controls were studied. 3DSTE was performed to assess LV 3D global strain, twist and torsion, ejection fraction, and systolic dyssynchrony index (SDI). The LV SDI was calculated as % of SD of times-to-peak strain of 16 segments/RR interval. The global performance index (GPI) was calculated as (global 3D strain·torsion)/SDI. Area under the receiver operating characteristic curve (AUC) was calculated to determine the capability of 3DSTE parameters to discriminate between patients with (cardiac magnetic resonance T2* <20 ms) and those without myocardial iron overload. RESULTS: Compared with controls, patients had significantly lower LV global 3D strain (P < 0.001), twist (P = 0.01), torsion (P = 0.04), and ejection fraction (P < 0.001) and greater SDI (P < 0.001). The GPI was lower in patients than controls (P < 0.001). T2* value correlated positively with global 3D strain (r = 0.74, P < 0.001) and GPI (r = 0.63, P = 0.001), and negatively with SDI (r = -0.44, P = 0.03). The AUCs of GPI, global 3D strain, ejection fraction, torsion, and 1/SDI were 0.94, 0.90, 0.87, 0.82, and 0.70, respectively. The GPI cutoff of 2.7°/cm had a sensitivity of 94.9% and a specificity of 88.9% of differentiating patients with from those without myocardial iron overload. CONCLUSIONS: The LV composite index of strain, torsion, and dyssynchrony derived from 3DSTE enables sensitive detection of myocardial iron overload in patients with thalassemia.

Pulmonary valve replacement and quality-of-life assessment.

BACKGROUND: Chronic pulmonary regurgitation is common after repair of tetralogy of Fallot. Despite the deleterious effects of chronic pulmonary regurgitation on right ventricular function, many patients with repaired tetralogy of Fallot remain asymptomatic. Health is defined not only by the absence of disease but also by physical, mental, and social wellbeing. We sought to examine the impact of pulmonary valve replacement on quality of life in asymptomatic patients with repaired tetralogy of Fallot and chronic pulmonary regurgitation. METHODS: From January 2009 to December 2012, 25 (18 male) asymptomatic patients (mean age 23.4 ± 7.4 years) who underwent pulmonary valve replacement for significant pulmonary regurgitation were recruited. Cardiac magnetic resonance was performed pre- and postoperatively. Quality of life was assessed using the Chinese version of the SF-36v2 evaluation tool. Demographics, clinical data, magnetic resonance findings, and quality-of-life scores were collected and calculated for comparison. RESULTS: After surgery, the indexed right ventricular end-diastolic volume (193 ± 47.3 vs. 105.6 ± 29.6 mL m(-2), p < 0.001) and indexed right ventricular end-systolic volume (108.5 ± 32.9 vs. 61.1 ± 23 mL m(-2), p < 0.001) decreased significantly. The response rates for pre- and postoperative quality-of-life assessments were 100%. Patients demonstrated improvements in all 8 domains of the SF-36v2 assessment. The physical (46.5 ± 6.6 vs. 49.9 ± 6.4, p = 0.012) and mental (43.7 ± 7.8 vs. 51.9 ± 7.6, p < 0.001) component summary scores increased after surgery. CONCLUSION: Pulmonary valve replacement can improve the quality of life in patients with chronic asymptomatic pulmonary regurgitation.

Right Atrial Mechanics Long-Term after Biventricular Repair of Pulmonary Atresia or Stenosis with Intact Ventricular Septum.

BACKGROUND: This study tested the hypothesis that right atrial (RA) mechanics are altered in patients after repair of pulmonary atresia with intact ventricular septum (PAIVS) and pulmonary stenosis (PS) and to explore their relationships with right ventricular (RV) diastolic function and P-wave indices. METHODS: Thirty-six adult patients, 16 with PAIVS and 20 with PS patients, and 20 age-matched healthy subjects were studied. Right atrial mechanics were assessed using speckle tracking echocardiography (STE) with quantification of positive, negative, and total strain, and strain rates at ventricular systole (aSRs ), early diastole (aSRed ), and atrial contraction (aSRac ). Right ventricular diastolic function was assessed by Doppler interrogation and STE. Maximum P-wave duration and P-wave dispersion were measured. RESULTS: Compared with controls, PAIVS and PS patients had significantly lower RA positive and total strain, aSRs and aSRed (all P < 0.05). Parameters of RV diastolic function including transtricuspid early (E) and late (A) diastolic inflow velocities, E/A ratio, early diastolic tricuspid annular velocity (e), early to late diastolic annular velocity ratio, E/e ratio, and RV early diastolic strain rate were found to correlate significantly with RA positive and total strain and aSRed (all P < 0.05). Maximum P-wave duration and P-wave dispersion increased progressively across control, PS, and PAIVS groups (P for trend <0.001). Both P-wave indices correlated negatively with RA positive strain, total strain, and aSRed (all P < 0.05). CONCLUSION: Impairment of RA mechanics occurs in patients long term after repair of PAIVS and PS and is associated with RV diastolic dysfunction, longer P-wave duration, and greater P-wave dispersion.

Plasma Levels of High Sensitivity Cardiac Troponin T in Adults with Repaired Tetralogy of Fallot.

Detectable low circulating level of cardiac troponin T (cTnT) may reflect subclinical myocardial injury. We tested the hypothesis that circulating levels of hs-cTnT are altered in adults with repaired tetralogy of Fallot (TOF) and associated with ventricular volume load and function. Eighty-eight TOF patients and 48 controls were studied. Plasma hs-cTnT levels were determined using a highly sensitive assay (hs-cTnT). The right (RV) and left ventricular (LV) volumes and ejection fraction (EF) were measured using 3D echocardiography and, in 52 patients, cardiac magnetic resonance (CMR). The median (interquartile range) for male and female patients were 4.87 (3.83-6.62) ng/L and 3.11 (1.00-3.87) ng/L, respectively. Thirty percent of female but none of the male patients had increased hs-cTnT levels. Female patients with elevated hs-cTnT levels, compared to those without, had greater RV end-diastolic and end-systolic volumes and LV systolic dyssynchrony index (all p < 0.05). For patient cohort only, hs-cTnT levels correlated positively with CMR-derived RV end-diastolic volume and negatively with echocardiography-derived LV and RV EF (all p < 0.05). Multiple linear regression identified sex and RV EF as significant correlates of log-transformed hs-cTnT levels. Increased hs-cTnT levels occur in 30% of female patients after TOF repair, and are associated with greater RV volumes and worse RV EF.

Atrial mechanics after surgical repair of tetralogy of Fallot.

BACKGROUND: Ventricular diastolic dysfunction in patients with repaired tetralogy of Fallot (TOF) may affect atrial mechanics. This study aimed to explore right atrial (RA) and left atrial (LA) mechanics in repaired TOF patients and their relationship with ventricular diastolic function. METHODS: Fifty-four patients (36 males), aged 17.8 ± 8.3 years, who had undergone TOF repair at 3.9 ± 3.3 years and 40 healthy subjects aged 16.9 ± 6.3 years (P = 0.57) were studied. Right and LA peak positive, peak negative, and total strain, strain rate at ventricular systole (SRs ), early diastole (SRed ), and atrial contraction (SRac ), and electromechanical delay were determined using speckle tracking echocardiography (STE). Ventricular diastolic function was assessed by tissue Doppler imaging and STE. Ventricular volumes and pulmonary regurgitant volume were derived from 3D echocardiography. RESULTS: Compared with controls, patients had significantly lower RA and LA peak positive and total strain, SRs , SRed , and SRac (all P < 0.001). The timing of RA (178 ± 33 msec vs. 152 ± 17 msec, P < 0.001) and LA (170 ± 32 msec vs. 152 ± 24 msec, P = 0.006) electromechanical coupling (EMC) was significantly longer in patients than in controls. The RA total strain, SRs , SRed , SRac , and EMC correlated positively with corresponding LA parameters (all P < 0.001). The RA and LA total strain and SRed were associated positively with diastolic annular velocities and strain rates of respective ventricles (all P < 0.05). The LA SRed correlated negatively with pulmonary regurgitant volume (r = -0.33, P = 0.016) and RV end-diastolic volume (r = -0.33, P = 0.015). CONCLUSION: Mechanics of both atria are impaired in patients after repair of TOF and are associated with diastolic performance of the respective ventricles.

Left ventricular mechanics in adolescents and young adults with a history of kawasaki disease: analysis by three-dimensional speckle tracking echocardiography.

BACKGROUND: Myocardial fibrosis and perfusion abnormalities can occur in patients with Kawasaki disease (KD). We explored using the new three-dimensional speckle tracking echocardiography (3DSTE) the left ventricular (LV) mechanics in adolescents and young adults with a history of KD. METHODS: Twenty-five KD patients (18 males) aged 17.0 ± 5.2 years, 14 with (group I) and 11 without (group II) coronary aneurysms, were studied. The 3D volume datasets were acquired for quantification of LV global 3D strain, global and regional area strain, systolic dyssynchrony index (SDI), twist, twist gradient (twist/LV length), and ejection fraction. RESULTS: The results were compared with those of 14 age-matched controls. Of the 14 group I patients, 6 had left, 2 had right, and 6 had both left and right coronary aneurysms. Compared with controls, group I patients had significantly lower LV systolic global 3D strain (43.7 ± 7.3% vs. 50.4 ± 6.6%, P = 0.02), twist (8.7 ± 1.3° vs. 11.4 ± 2.0°, P < 0.001), and twist gradient (1.5 ± 0.3°/cm vs. 1.9 ± 0.4°/cm, P = 0.01), greater SDI (6.8 ± 1.9% vs. 4.7 ± 1.9%, P < 0.001), and similar ejection fractions. Six patients in group I had perfusion defects, who had global 3DSTE parameters similar to those of the 8 patients without perfusion abnormalities (all P > 0.05). For group II patients, only the global area strain was significantly lower than that of controls (37.6 ± 3.5% vs. 40.7 ± 3.6%, P = 0.038). CONCLUSION: In adolescents and young adults with a history of KD, impairment of LV mechanics occurs and is worse in patients with than those without coronary complications.

Right and left ventricular mechanics and interaction late after balloon valvoplasty for pulmonary stenosis.

AIMS: This study sought to explore right (RV) and left ventricular (LV) mechanics and ventricular-ventricular interaction in adolescents and young adults late after percutaneous balloon pulmonary valvoplasty (PBPV) for valvar pulmonary stenosis (PS). METHODS AND RESULTS: Potential late effects of PS despite PBPV on cardiac mechanics have not been well defined. Thirty-one patients aged 20.2 ± 7.6 years were studied at 18 ± 6 years after PBPV. Ventricular myocardial deformation was determined using speckle tracking echocardiography, while RV and LV volumes and ejection fraction as well as LV systolic dyssynchrony index were assessed by three-dimensional echocardiography. The results were compared with those of 30 controls. Pulmonary regurgitation, mostly trivial to mild, was present in 90% (28/31) of patients. Compared with controls, patients had significantly greater RV end-diastolic (P < 0.001), RV end-systolic (P < 0.001), and LV end-systolic (P = 0.04) volumes as well as lower LV ejection fraction (P < 0.001). For deformation, patients had significantly reduced RV longitudinal systolic strain (P = 0.004), decreased LV circumferential systolic strain (P < 0.001), and strain rate (P = 0.001) as well as greater LV mechanical dyssynchrony (P < 0.001). In patients, RV end-diastolic and end-systolic volumes correlated with LV circumferential strain (r = -0.47, P = 0.008 and r = -0.36, P = 0.049, respectively) and dyssynchrony (r = 0.53, P = 0.002 and r = 0.49, P = 0.005, respectively). Patients who had PBPV at age ≤1 year had ventricular deformation indices similar to those who had interventions beyond 1 year. CONCLUSION: Impaired RV and LV mechanics and adverse ventricular-ventricular interaction occur in adolescents and young adults late after balloon valvoplasty for isolated valvar PS.

Atrial and ventricular mechanics in patients after Fontan-type procedures: atriopulmonary connection versus extracardiac conduit.

BACKGROUND: Differences in systemic venous flow dynamics and energy losses exist in various Fontan-type procedures, which may affect atrial and ventricular filling. The aim of this study was to test the hypothesis that atrial and ventricular mechanics differ between two types of Fontan procedures, atriopulmonary connection (APC) and extracardiac conduit, which have distinctly different systemic venous hemodynamics. METHODS: This was a cross-sectional, case-control study of 28 Fontan patients (13 with APC, 15 with extracardiac conduit) aged 19.8 ± 6.5 years and 26 healthy controls. Atrial and systemic ventricular myocardial deformation was determined using speckle-tracking echocardiography, while ventricular volumes and systolic dyssynchrony index were assessed using three-dimensional echocardiography. RESULTS: Compared with controls, patients had significantly lower values of global ventricular longitudinal, circumferential, and radial systolic strain in all three directions, reduced systolic and early diastolic strain rates (SRs) in more than one dimension, lower ejection fractions, and worse ventricular dyssynchrony. For atrial deformation, patients had lower global and positive strain and conduit and reservoir SRs and delayed electromechanical coupling. Among patients, those with APC had significantly lower ventricular longitudinal strain and early diastolic SRs, worse ventricular dyssynchrony, and reduced atrial positive and negative strain and conduit and active contractile SRs. Atrial global strain (r = 0.60, P = .001) and conduit SR (r = 0.49, P = .008) correlated positively with systemic ventricular early diastolic SR. CONCLUSIONS: Atrial and ventricular mechanics are impaired in patients after Fontan-type operation, which is worse with APC than extracardiac conduit.

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 (ß = 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.

Arterial mechanics at rest and during exercise in adolescents and young adults after arterial switch operation for complete transposition of the great arteries.

We sought to determine the arterial mechanics at rest and during exercise in adolescents and young adults with complete transposition of the great arteries after arterial switch operation and their relations with neoaortic complications. Thirty patients (22 men) aged 16.2 ± 2.1 years and 22 controls (15 men) were studied. Central and peripheral arterial pulse wave velocities, carotid and radial augmentation indices, and central systolic blood pressure (cSBP) were determined by oscillometry and applanation tonometry, whereas arterial dimensions were measured by 2-dimensional echocardiography. Arterial strain, distensibility, and stiffness were determined at rest and during supine bicycle exercise testing. At rest, patients had significantly higher heart-carotid pulse wave velocity, carotid and radial augmentation indices, and cSBP than controls. At rest and during submaximal exercise, patients had significantly lower aortic strain and distensibility, greater aortic and carotid stiffness, and higher SBP than controls. Dilated aortic sinus found in 23 (76.7%) patients was associated with lower aortic distensibility, greater aortic stiffness, and higher cSBP at rest and lower aortic distensibility and strain at submaximal exercise. Significant aortic regurgitation found in 20% (6 of 30) of patients was associated with significantly higher neoaortic z scores. Multivariate analysis identified aortic stiffness at rest (ß = 0.46, p = 0.003) and age at operation (ß = 0.44, p = 0.004) as significant determinants of aortic sinus z scores. In conclusion, altered mechanics of the central arteries are present at rest and during exercise in adolescents and young adults after arterial switch operation. These findings may have important implications on progression of neoaortic root dilation, exercise recommendations, and medical therapy.

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.

New three-dimensional speckle-tracking echocardiography identifies global impairment of left ventricular mechanics with a high sensitivity in childhood cancer survivors.

BACKGROUND: The aim of this case-control study was to assess the usefulness of three-dimensional (3D) speckle-tracking echocardiography in the evaluation of global left ventricular (LV) myocardial performance in adolescent and adult survivors of childhood cancers. METHODS: Fifty-three anthracycline-treated survivors of childhood cancers (mean age, 18.6 ± 5.1 years) and 38 controls were studied. Three-dimensional speckle-tracking echocardiography was performed to assess LV 3D global and segmental strain, time to peak segmental 3D strain, LV torsion, and ejection fraction. LV systolic dyssynchrony index (SDI) was calculated as the percentage of the standard deviation of times to peak strain of the 16 segments divided by the RR interval. A global performance index (GPI) was calculated as (global 3D strain × torsion)/SDI. The area under the receiver operating characteristic curve was calculated to determine the capability of various echocardiographic indices to discriminate between patients and controls. RESULTS: Compared with controls, patients had significantly reduced LV global 3D strain (P < .001), torsion (P < .001), and GPI (P < .001) and greater SDI (P < .001). All except the basal anteroseptal segment in patients had reduced regional 3D strain compared with controls (P < .05 for all). Global 3D strain (P = .018), SDI (P = .003), and GPI (P = .02) were correlated with cumulative anthracycline dose. The areas under the curves for GPI, global 3D strain, 1/SDI, torsion, and ejection fraction were 0.92, 0.79, 0.79, 0.79, and 0.78, respectively. A GPI cutoff of 10.6°/cm had sensitivity of 84.9% and specificity of 81.6% of differentiating patients from controls. CONCLUSIONS: Three-dimensional speckle-tracking echocardiography enables the derivation of an index of LV global performance that incorporates LV 3D strain, dyssynchrony, and torsion for the sensitive detection of altered LV mechanics in childhood cancer survivors.

Left ventricular contractile reserve after arterial switch operation for complete transposition of the great arteries: an exercise echocardiographic study.

AIMS: This study tested the hypothesis that left ventricular (LV) contractile reserve is altered in patients after arterial switch operation (ASO) for complete transposition of the great arteries (TGA) by non-invasive determination of LV force-frequency relationship (FFR). METHODS AND RESULTS: Thirty-two patients aged 16.2 ± 2.1 years and 22 healthy controls were studied. M-mode parameters, transmitral early (E) and late (A) diastolic velocities, and tissue Doppler-derived systolic (sm), early (em), and late (am) diastolic mitral annular velocities were determined at baseline and during submaximal exercise testing. The LV myocardial isovolumic acceleration (IVA) was measured at different heart rates during exercise for derivation of LV FFR and the average slope of IVA increment with heart rate. At baseline, patients had significantly greater E velocity, E/A and E/em ratios, shorter E deceleration time, and reduced mitral annular sm, em, and am velocities (all P < 0.05), but similar IVA (P = 0.29) compared with controls. During exercise, sm and em remained significantly reduced (P < 0.001), and LV IVA became lower (P < 0.001) in patients. The average FFR slope was significantly lower in patients (0.039 ± 0.019 vs. 0.070 ± 0.024 m/s(2) bpm, P < 0.001). The weighted average FFR curve of patients was flattened compared with the reported positive FFR reference curve based on a healthy paediatric cohort (P < 0.0001). Patients with variant compared with those with usual coronary arterial anatomy had significant flattening of FFR (P < 0.001) and a reduced FFR slope (P = 0.007). CONCLUSION: In adolescents and young adults after ASO, exercise stress revealed reduced LV contractile reserve, which is worse in those having variant coronary arterial anatomy.

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.

Dynamic dyssynchrony and impaired contractile reserve of the left ventricle in beta-thalassaemia major: an exercise echocardiographic study.

BACKGROUND: Performance of the left ventricle during exercise stress in thalassaemia patients is uncertain. We aimed to explore the phenomenon of dynamic dyssynchrony and assess contractile reserve in patients with beta-thalassaemia major and determine their relationships with myocardial iron load. METHODS AND RESULTS: Thirty-two thalassaemia patients (16 males), aged 26.8 ± 6.9 years, without heart failure and 17 healthy controls were studied. Their left ventricular (LV) volumes, ejection fraction, systolic dyssynchrony index (SDI), and myocardial acceleration during isovolumic LV contraction (IVA) were determined at rest and during submaximal bicycle exercise testing using 3-dimensional and tissue Doppler echocardiography. Myocardial iron load as assessed by T2* cardiac magnetic resonance in patients were further related to indices of LV dyssynchrony and contractile reserve. At rest, patients had significantly greater LV SDI (p<0.001) but similar IVA (p = 0.22) compared with controls. With exercise stress, the prevalence of mechanical dyssynchrony (SDI>4.6%, control+2SD) increased from baseline 25% to 84% in patients. Δ SDI(exercise-baseline) correlated with exercise-baseline differences in LV ejection fraction (p<0.001) and stroke volume (p = 0.006). Compared with controls, patients had significantly less exercise-induced increase in LV ejection fraction, cardiac index, and IVA (interaction, all p<0.05) and had impaired contractile reserve as reflected by the gentler IVA-heart rate slope (p = 0.018). Cardiac T2* in patients correlated with baseline LV SDI (r = -0.44, p = 0.011) and IVA-heart rate slope (r = 0.36, p = 0.044). CONCLUSIONS: Resting LV dyssynchrony is associated with myocardial iron load. Exercise stress further unveils LV dynamic dyssynchrony and impaired contractile reserve in patients with beta-thalassaemia major.

Three-dimensional mechanical dyssynchrony and myocardial deformation of the left ventricle in patients with tricuspid atresia after Fontan procedure.

BACKGROUND: The aim of this study was to test the hypothesis that dyssynchronous contraction of functional single ventricles occurs in Fontan patients and is related to indices of myocardial deformation and global ventricular function. METHODS: Twenty patients with tricuspid atresia (mean age, 23.5 ± 7.1 years) were studied 17.8 ± 3.8 years after undergoing the Fontan procedure. Three-dimensional echocardiographic data were acquired for determination of left ventricular (LV) volumes and systolic dyssynchrony indices. LV myocardial deformation was determined using speckle-tracking echocardiography. Calibrated integrated backscatter intensity was measured as an index of myocardial fibrosis. The results were compared with those in 20 controls. RESULTS: Compared with controls, patients had significantly greater systolic dyssynchrony indices (6.13 ± 1.32% vs 4.06 ± 0.84%, P < .001). The prevalence of LV mechanical dyssynchrony (systolic dyssynchrony index > 5.74%) in patients was 55% (95% confidence interval, 32%-77%). LV global systolic longitudinal, radial, and circumferential strain (P < .001 for all), longitudinal systolic (P < .001) and early diastolic (P < .001) strain rate, and circumferential systolic (P < .001) and early diastolic (P = .009) strain rate were significantly lower in patients than in controls, while the average calibrated integrated backscatter was higher (P < .001). Patients with LV dyssynchrony (n = 11) had lower global LV longitudinal strain (P = .02), reduced LV ejection fractions (P = .002), and higher average calibrated integrated backscatter (P = .03) compared with those without LV dyssynchrony (n = 9). CONCLUSIONS: A high proportion of patients with tricuspid atresia after the Fontan operation exhibit LV mechanical dyssynchrony, which may in part be related to myocardial fibrosis and has implications for myocardial deformation and global ventricular function.

Circulating annexin A5 levels after atrial switch for transposition of the great arteries: relationship with ventricular deformation and geometry.

BACKGROUND: Inflammatory cytokines, cardiomyocyte apoptosis, and altered collagen turnover may contribute to unfavourable ventricular remodeling. This unfavourable ventricular remodelling is well documented in patients after atrial switch operation for complete transposition of the great arteries. We therefore tested if levels of circulating markers of inflammation, apoptosis, collagen synthesis, and extracellular matrix degradation are altered in patients after atrial switch operation for transposition of the great arteries. METHODS AND RESULTS: Circulating tumour necrosis factor (TNF)-α, annexin A5 (AnxA5), carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP), matrix metalloproteinase-1 (MMP-1), and tissue inhibitor of metalloproteinase-1 (TIMP-1) levels were determined in 27 patients aged 25.2±3.1 years and 20 controls. Ventricular myocardial deformation and left ventricular eccentricity index (EI) were determined by speckle tracking and two-dimensional echocardiography, respectively. Compared with controls, patients had significantly higher circulating AnxA5 (p<0.001) and TNF-α (p = 0.018) levels, but similar PICP, PIIINP, MMP-1 and TIMP-1 levels. For the whole cohort, plasma AnxA5 correlated with serum TNF-α (p = 0.002), systemic ventricular global longitudinal strain (GLS) and systolic and early diastolic strain rate (all p<0.001), and subpulmonary ventricular GLS and early diastolic strain rate (both p<0.001). In patients, plasma AnxA5 level correlated positively with subpulmonary ventricular EI (p = 0.027). Multiple linear regression analysis identified systemic ventricular GLS (ß = -0.50, p<0.001) and serum TNF-α (ß = 0.29, p = 0.022) as significant correlates of plasma AnxA5. CONCLUSIONS: Elevated plasma AnxA5 level in patients after atrial switch operation is associated with impaired systemic myocardial deformation, increased subpulmonary ventricular eccentricity, and increased serum TNF-α level.

Circulating CD133(+)VEGFR2 (+) and CD34 (+)VEGFR2 (+) cells and arterial function in patients with beta-thalassaemia major.

Arterial dysfunction has been documented in patients with beta-thalassaemia major. This study aimed to determine the quantity and proliferative capacity of circulating CD133(+)VEGFR2(+) and CD34(+)VEGFR2(+) cells in patients with beta-thalassaemia major and those after haematopoietic stem cell transplantation (HSCT), and their relationships with arterial function. Brachial arterial flow-mediated dilation (FMD), carotid arterial stiffness, the quantity of these circulating cells and their number of colony-forming units (CFUs) were determined in 17 transfusion-dependent thalassaemia patients, 14 patients after HSCT and 11 controls. Compared with controls, both patient groups had significantly lower FMD and greater arterial stiffness. Despite having increased CD133(+)VEGFR2(+) and CD34(+)VEGFR2(+) cells, transfusion-dependent patients had significantly reduced CFUs compared with controls (p = 0.002). There was a trend of increasing CFUs across the three groups with decreasing iron load (p = 0.011). The CFUs correlated with brachial FMD (p = 0.029) and arterial stiffness (p = 0.02), but not with serum ferritin level. Multiple linear regression showed that CFU was a significant determinant of FMD (p = 0.043) and arterial stiffness (p = 0.02) after adjustment of age, sex, body mass index, blood pressure and serum ferritin level. In conclusion, arterial dysfunction found in patients with beta-thalassaemia major before and after HSCT may be related to impaired proliferation of CD133(+)VEGFR2(+) and CD34(+)VEGFR2(+) cells.

Circulating levels of biomarkers of collagen synthesis and ventricular function and dyssynchrony in adolescents and young adults after repair of tetralogy of Fallot.

BACKGROUND: Circulating carboxy-terminal propeptide of type I procollagen (PICP) and amino-terminal propeptide of type III procollagen (PIIINP) are biomarkers of collagen synthesis. We tested the hypothesis that circulating PICP and PIIINP are altered and may correlate with ventricular volume load and function in patients with repaired tetralogy of Fallot (TOF). METHODS AND RESULTS: Serum PICP and plasma PIIINP levels were determined in 39 patients with repaired TOF aged 17.7 ± 4.1 years and 25 healthy controls and correlated with right ventricular (RV) and left ventricular (LV) volumes, functional indices, and mechanical dyssynchrony as assessed by 3-dimensional and tissue Doppler echocardiography. Compared with controls, patients had significantly higher circulating PICP (P = .016) and PIIINP (P = .008) levels, worse RV function with intra-RV mechanical delay (all P < .001), impaired LV systolic functional indices (all P < .05), and greater LV systolic dyssynchrony index (SDI) (P < .001). For the whole cohort, circulating PICP and PIIINP levels correlated with age (P = .001 and P < .001, respectively), body mass index (P = .033 and P = .012, respectively), LV eccentricity (P = .035 and P = .046, respectively), RV end-diastolic volume (P = .029 and P = .047, respectively), and LV SDI (both P < .001). In addition, PICP levels correlated negatively with RV and LV isovolumic acceleration and RV ejection fraction. Multiple linear regression analysis identified LV SDI as a significant independent correlate of circulating levels of PICP (ß = .31, P = .045) and PIIINP (ß = .37, P = .004). CONCLUSION: Circulating levels of PICP and PIIINP correlate positively with LV mechanical dyssynchrony in patients after TOF repair, implicating a possible role of increased collagen synthesis in its pathogenesis.

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.