Yiu-Fai Cheung

Queen Mary Hospital, Hong Kong, Hong Kong

Are you Yiu-Fai Cheung?

Claim your profile

Publications (74)236.15 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: We assessed the left ventricular (LV) contractile reserve in young adults with repaired coarctation of the aorta and interrupted aortic arch by determination of LV force-frequency relation (FFR). Eighteen (7 men) patients aged 24.2 ± 5.4 years and 20 (9 men) healthy controls were studied. Blood pressures in the right arm were measured by oscillometry. Transmitral early (E) and late (A) diastolic velocities, tissue Doppler-derived mitral annular systolic (sm), early diastolic (em) and late diastolic (am) velocities, and myocardial isovolumic acceleration (IVA) were measured. The LV FFR and average slope were derived from the IVA measured at different heart rates during supine bicycle exercise. Blood pressures at rest were similar between patients and controls (all p >0.05). At baseline, patients compared with controls had significantly greater E velocity, E/A and E/em ratios, and lower sm and em velocities (all p <0.05) but similar IVA (p = 0.18). At submaximal exercise, diastolic (p = 0.001) and mean (p = 0.003) blood pressures became significantly higher in patients than controls, sm (p = 0.001) and em (p <0.001) velocities remained reduced, whereas the IVA became lower (p <0.001). The weighted average FFR was flattened (p <0.001), and average FFR slope was lower (p <0.001) in patients compared with controls. The average FFR slope correlated negatively with the magnitude of exercise-induced increase in systolic (r = -0.32, p = 0.050), mean (r = -0.41, p = 0.011), and diastolic (r = -0.40, p = 0.013) blood pressures. In conclusion, young adults after coarctation of the aorta and interrupted aortic arch repair exhibit reduced LV contractile reserve, which is related to the blood pressure response during exercise stress. Copyright © 2014 Elsevier Inc. All rights reserved.
    The American journal of cardiology. 11/2014;
  • Yiu-Fai Cheung
    [Show abstract] [Hide abstract]
    ABSTRACT: This review aims to provide an overview of conventional and novel indices used in clinical and research arenas for evaluation of right ventricular (RV) function in congenital heart diseases with a dual-chambered circulation.
    Chinese medical journal. 11/2014; 127(21):3789-97.
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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). 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. Impaired RV and LV mechanics and adverse ventricular-ventricular interaction occur in adolescents and young adults late after balloon valvoplasty for isolated valvar PS.
    European heart journal cardiovascular Imaging. 04/2014;
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Iron may damage sarcomeric proteins through oxidative stress. We explored the left ventricular (LV) torsional mechanics in patients with beta-thalassaemia major and its relationship to myocardial iron load. Using HL-1 cell and B6D2F1 mouse models, we further determined the impact of iron load on proteolysis of the giant sarcomeric protein titin.Methods and results: In 44 thalassaemia patients aged 25 +/- 7 years and 38 healthy subjects, LV torsion and twisting velocities were determined at rest using speckle tracking echocardiography. Changes in LV torsional parameters during submaximal exercise testing were further assessed in 32 patients and 17 controls. Compared with controls, patients had significantly reduced LV apical rotation, torsion, systolic twisting velocity, and diastolic untwisting velocity. T2* cardiac magnetic resonance findings correlated with resting diastolic untwisting velocity. The increments from baseline and resultant LV torsion and systolic and diastolic untwisting velocities during exercise were significantly lower in patients than controls. Significant correlations existed between LV systolic torsion and diastolic untwisting velocities in patients and controls, both at rest and during exercise. In HL-1 cells and ventricular myocardium of B6D2F1 mice overloaded with iron, the titin-stained pattern of sarcomeric structure became disrupted. Gel electrophoresis of iron-overloaded mouse myocardial tissue further showed significant decrease in the amount of titin isoforms and increase in titin degradation products. Resting and dynamic LV torsional mechanics is impaired in patients with beta-thalassaemia major. Cell and animal models suggest a potential role of titin degradation in iron overload-induced alteration of LV torsional mechanics.
    BMC Cardiovascular Disorders 04/2014; 14(1):49. · 1.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 22q11.2 deletion syndrome (22q11.2DS) is a multi-systemic disorder with high phenotypic variability. Under-diagnosis in adults is common and recognition of facial dysmorphic features can be affected by age and ethnicity. This study aims to determine the prevalence of undiagnosed 22q11.2DS in adult Chinese patients with conotruncal anomalies and to delineate their facial dysmorphisms and extra-cardiac manifestations. We recruited consecutively 156 patients with conotruncal anomalies in an adult congenital heart disease (CHD) clinic in Hong Kong and screened for 22q11.2DS using fluorescence-PCR and fluorescence in-situ hybridization. Assessment for dysmorphic features was performed by a cardiologist at initial screening and then by a clinical geneticist upon result disclosure. Clinical photographs were taken and childhood photographs collected. Eighteen patients (11.5%) were diagnosed with 22q11.2DS, translating into 1 previously unrecognized diagnosis of 22q11.2DS in every 10 adult patients with conotruncal anomalies. While dysmorphic features were detected by our clinical geneticist in all patients, only two-thirds were considered dysmorphic by our cardiologist upon first assessment. Evolution of facial dysmorphic features was noted with age. Extra-cardiac manifestations included velopharyngeal incompetence or cleft palate (44%), hypocalcemia (39%), neurodevelopmental anomalies (33%), thrombocytopenia (28%), psychiatric disorders (17%), epilepsy (17%) and hearing loss (17%). We conclude that under-diagnosis of 22q11.2DS in Chinese adults with conotruncal defects is common and facial dysmorphic features may not be reliably recognized in the setting of adult CHD clinic, referral for genetic evaluation and molecular testing for 22q11.2DS should be offered to patients with conotruncal defects.
    European journal of medical genetics 04/2014; · 1.57 Impact Factor
  • Jia Hou, Hong-Kui Yu, Sophia J Wong, Yiu-Fai Cheung
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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. 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). Mechanics of both atria are impaired in patients after repair of TOF and are associated with diastolic performance of the respective ventricles.
    Echocardiography 04/2014; · 1.26 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Increased circulating endothelial microparticles (EMPs) have been shown to associate with endothelial dysfunction. We explored the effect of iron on EMP generation by human umbilical vein endothelial cells (HUVECs) and the potential protective effect of carvedilol. Methods: FeCl3 was added to HUVEC culture. Iron entry into cells was monitored using fluorescent microscopic imaging, while the quantity of EMPs that was released was determined by flow cytometry. The apoptosis of HUVECs was assessed by annexin V/propidium iodide assay and caspase-3 expression. Membrane bleb formation was visualized using electron microscopy. Intracellular production of reactive oxygen species (ROS) was also monitored. The effects of beta-blockers, carvedilol and propranolol on these processes were determined by co-incubation in a dose-dependent manner. Iron entry into HUVECs was not blocked by either beta-blocker. Iron induced the generation of EMPs, the formation of membrane blebs, the apoptosis of HUVECs and the production of ROS, each in a dose-dependent manner. Carvedilol, but not propranolol, ameliorated all of these processes. Results: Our result indicates that iron induces EMP generation and apoptosis of endothelial cells in association with increased oxidative stress. Conclusion: The protective effects of carvedilol, via its antioxidant effect, may have therapeutic potential in patients with iron overload. © 2014 S. Karger AG, Basel.
    Acta Haematologica 03/2014; 132(2):200-210. · 0.89 Impact Factor
  • Shu-juan Li, Sophia J. Wong, Yiu-fai Cheung
    [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 01/2014; · 2.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Iron overload cardiomyopathy that prevails in some forms of hemosiderosis is caused by excessive deposition of iron into the heart tissue and ensuing damage caused by a raise in labile cell iron. The underlying mechanisms of iron uptake into cardiomyocytes in iron overload condition are still under investigation. Both L-type calcium channels (LTCC) and T-type calcium channels (TTCC) have been proposed to be the main portals of non-transferrinic iron into heart cells, but controversies remain. Here, we investigated the roles of LTCC and TTCC as mediators of cardiac iron overload and cellular damage by using specific Calcium channel blockers as potential suppressors of labile Fe(II) and Fe(III) ingress in cultured cardiomyocytes and ensuing apoptosis.
    PLoS ONE 01/2014; 9(11):e112915. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 01/2014; · 2.98 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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 (β = 0.46, p = 0.003) and age at operation (β = 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.
    The American journal of cardiology 11/2013; · 3.58 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: We sought to quantify plasma high sensitivity cardiac troponin (hs-cTnT) levels, their determinants, and their associations with left ventricular (LV) myocardial deformation in adult survivors of childhood acute leukaemias. One hundred adult survivors (57 males) of childhood acute leukaemias, aged 24.1±4.2 years, and 42 age-matched controls (26 males) were studied. Plasma cTnT was determined using a highly sensitive assay. Genotyping of NAD(P)H oxidase and multidrug resistance protein polymorphisms was performed. Left ventricular function was assessed by conventional, three-dimensional, and speckle tracking echocardiography. The medians (interquartile range) of hs-cTnT in male and female survivors were 4.9 (4.2 to 7.2) ng/L and 1.0 (1.0 to 3.5) ng/L, respectively. Nineteen survivors (13 males, 6 females) (19%) had elevated hs-cTnT (>95(th) centile of controls). Compared to those without elevated hs-TnT levels, these subjects had received larger cumulative anthracycline dose and were more likely to have leukaemic relapse, stem cell transplant, and cardiac irradiation. Their LV systolic and early diastolic myocardial velocities, isovolumic acceleration, and systolic longitudinal strain rate were significantly lower. Survivors having CT/TT at CYBA rs4673 had higher hs-cTnT levels than those with CC genotype. Functionally, increased hs-cTnT levels were associated with worse LV longitudinal systolic strain and systolic and diastolic strain rates. Increased hs-cTnT levels occur in a significant proportion of adult survivors of childhood acute leukaemias and are associated with larger cumulative anthracycline dose received, history of leukaemic relapse, stem cell transplant, and cardiac irradiation, genetic variants in free radical metabolism, and worse LV myocardial deformation.
    PLoS ONE 10/2013; 8(10):e77063. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Data on the use of circulating microRNAs (miRNAs) as biomarkers of cardiovascular diseases are emerging. Little, however, is known on the expression profile of circulating of microRNAs in congenital heart malformations with a systemic right ventricle that is prone to functional impairment. We aimed to test the hypothesis that circulating miRNA profile is altered in patients late after atrial switch operation for complete transposition of the great arteries (TGA) and further explored possible relationships between alteration of circulating miRNAs and systemic ventricular contractility. Circulating miRNA expression profiling of serum samples from 5 patients and 5 healthy controls was performed. The results were validated in 26 patients and 20 controls using real-time quantitative reverse-transcription polymerase chain reaction for candidate miRNAs with fold changes >3 by expression profiling. Systemic ventricular myocardial acceleration during isovolumic contraction (IVA) was determined by colour tissue Doppler echocardiography. Compared with controls, patients had significantly lower systemic ventricular IVA (p = 0.002). Of the 23 upregulated miRNAs identified by profiling, 11 were validated to be increased in patients compared with controls: miR-16, miR-106a, miR-144*, miR-18a, miR-25, miR-451, miR-486-3p, miR-486-5p, miR-505*, let-7e and miR-93. Among the validated 11 miRNAs, miR-18a (r = -0.45, p = 0.002) and miR-486-5p (r = -0.35, p = 0.018) correlated negatively with systemic ventricular IVA for the whole cohort. A distinct serum miRNA expression signature exists in adults with complete TGA after atrial switch operation, with serum miR-18a and miR-486-5p being associated with systemic ventricular contractility.
    BMC Cardiovascular Disorders 09/2013; 13(1):73. · 1.46 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 05/2013; · 2.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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). 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.
    PLoS ONE 01/2013; 8(11):e78826. · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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 (s(m)), early (e(m)), and late (a(m)) 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/e(m) ratios, shorter E deceleration time, and reduced mitral annular s(m), e(m), and a(m) velocities (all P < 0.05), but similar IVA (P = 0.29) compared with controls. During exercise, s(m) and e(m) 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.
    European heart journal cardiovascular Imaging. 10/2012;
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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.
    European heart journal cardiovascular Imaging. 07/2012;
  • [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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. 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). 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.
    Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 01/2012; 25(4):393-400. · 2.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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). 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.
    PLoS ONE 01/2012; 7(9):e45265. · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: 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. 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 (β = -0.50, p<0.001) and serum TNF-α (β = 0.29, p = 0.022) as significant correlates of plasma AnxA5. 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.
    PLoS ONE 01/2012; 7(12):e52125. · 3.53 Impact Factor