Yiu-fai Cheung

The possible role of hydrogen sulfide as a smooth muscle cell proliferation inhibitor in rat cultured cells

Hydrogen sulfide (H2S) was recently suggested to be a possible endogenous gasotransmitter in physiological concentration. For the purpose of understanding its possible role in the regulation of the cardiovascular system, we explored the potential effect of H2S on the proliferation of cultured aortic vascular smooth muscle cells (VSMCs) of rats and mitrogen-activated protein kinase (MAPK) as a signaling transduction pathway. Vascular smooth muscle cells were cultured in vitro and the cells were divided into six groups: (1) control group, (2) serum group, (3) endothelin group, (4) NaHS group, (5) serum + NaHS group, and (6) endothelin + NaHS group. VSMC proliferation was measured by [3H]thymidine ([3H]TdR) incorporation and MAPK activity in the VSMCs was determined by radioactivity assay. The results showed that endothelin-1 increased VSMC [3H]TdR incorporation 2.39-fold (P ≪ 0.01) and MAPK activity 1.62-fold (P ≪ 0.01), as compared with controls. Hydrogen sulfide at 5 × 10−5 mol/l, 1 × 10−4 mol/l, and 5 × 10−4 mol/l decreased VSMC [3H]TdR incorporation by 16.8%, 26.60%, and 37.40%, respectively, and reduced MAPK activity by 7.37% (P ≫ 0.05), 23.39%, and 33.57%, respectively (P ≪ 0.01). The results demonstrated that H2S could dose-dependently suppress the proliferation of VSMCs through the MAPK pathway.

Arterial stiffness and endothelial function in patients with β-thalassemia major

BACKGROUND Increased iron store has been linked to risk of cardiovascular disease. Structural alterations of arteries in beta-thalassemia major patients and in vitro functional disturbance of vascular endothelial cells by thalassemic serum have been described. We sought to determine whether arterial stiffness and endothelial function are altered in vivo. METHODS AND RESULTS Thirty thalassemia patients (16 male) aged 22.2+/-7.4 years were recruited. Left ventricular (LV) mass and function were assessed echocardiographically. Carotid and brachioradial artery stiffness was assessed by stiffness index and pulse-wave velocity (PWV), respectively. Brachial artery endothelial function was assessed by vascular response to reactive hyperemia (flow-mediated dilation [FMD]) and sublingual glyceryl trinitrate. These indexes were compared with those of 30 age- and sex-matched controls. None of the patients had LV systolic or diastolic dysfunction. When compared with controls, patients had greater absolute (113.8+/-38.0 versus 109.0+/- 32.6 g, P=0.04) and indexed (82.4+/-17.5 versus 66.7+/-12.7 g/m(2), P<0.001) LV mass, carotid artery stiffness index (8.1+/-3.5 versus 5.5+/-1.6, P<0.001), and brachioradial PWV (8.9+/-2.4 versus 7.9+/-1.7 m/s, P= 0.03). Their FMD was impaired (3.5+/-3.3% versus 8.8+/-3.9%, P<0.001), whereas glyceryl trinitrate- mediated dilation was preserved (17.9+/-7.6% versus 16.3+/-6.1%, P=0.40). Both stiffness index and PWV correlated inversely with magnitude of FMD (r=-0.40, P=0.03; r=-0.41, P=0.03) and positively with indexed LV mass (r=0.50, P=0.005; r=0.40, P=0.027). Nonetheless, no significant correlation existed between ferritin level and carotid stiffness, PWV, or FMD. CONCLUSIONS Increased arterial stiffness, endothelial dysfunction, and LV hypertrophy occur in patients with beta-thalassemia major, which may result in reduction of mechanical efficiency of the heart.

Fetal origins of reduced arterial distensibility in the donor twin in twin-twin transfusion syndrome

Twin-twin transfusion syndrome permits investigation of vascular programming independent of genetic influence. Arterial distensibiity was lower in the donor twin during infancy, implying the intrauterine vascular remodelling might result in raised cardiac afterload and could influence later cardiovascular health.

New two-dimensional global longitudinal strain and strain rate imaging for assessment of systemic right ventricular function

Objectives: To determine the usefulness of new two-dimensional strain indices, based on speckle tracking imaging, for assessment of systemic right ventricular (RV) function after an atrial switch operation for transposition of the great arteries. Design: Cross-sectional study. Setting: Tertiary paediatric cardiac centre. Methods: 26 patients, mean (SD) age 21.0 (3.6) years at 19.9 (3.2) years after an atrial switch operation, and 27 age-matched controls were studied. Two-dimensional imaging at the four-chamber view was obtained with tracing of the entire RV endocardial border. The RV global longitudinal strain (GLS) and GLS rate were derived using automated software (EchoPAC, GE Medical) and correlated with tissue Doppler-derived RV isovolumic acceleration (IVA), and, in the patient cohort, with cardiac magnetic resonance-derived RV ejection fraction. Results: Intra- and interobserver variability for measurement of GLS, as determined from the mean (SD) of differences in two consecutive results from 20 studies, were 0.06 (1.39)% and 0.24 (1.77)%, respectively. Compared with controls, patients had lower RV GLS (17.1 (1.9)% vs 26.3 (2.9)%, p<0.001), a reduced GLS rate (0.78 (0.11)/s vs 1.33 (0.23)/s, p<0.001), lower RV IVA (1.10 (0.36) m/s2 vs 1.56 (0.53) m/s2, p<0.001) and increased RV myocardial performance index (0.52 (0.09) vs 0.38 (0.09), p<0.001). Both RV GLS and GLS rate correlated positively with RV IVA (r = 0.43, p = 0.001 and r = 0.46, p<0.001, respectively), and negatively with RV myocardial performance index (r = −0.65, p<0.001 and r = −0.57, p<0.001, respectively). In patients, the GLS rate correlated positively with RV ejection fraction (r = 0.62, p = 0.001). Conclusions: Two-dimensional RV GLS and GLS rate are new, potentially useful indices for assessment of systemic RV function.

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

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

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

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

Meta-Analysis of Pulmonary Valve Replacement After Operative Repair of Tetralogy of Fallot

The present meta-analysis aimed to determine the outcomes and effect on right ventricular (RV) function of surgical pulmonary valve replacement (PVR) in patients after repair of tetralogy of Fallot. The reported outcomes of surgical PVR in children and adults after tetralogy of Fallot repair were from relatively small observational studies. The PubMed database was searched from its inception to April 2009. Observational studies reporting on the following outcomes measures after surgical PVR were reviewed: early and late all-cause mortalities, the redo-PVR rate, and changes in the indexed RV volumes, ejection fraction, and QRS duration after PVR. Of the 305 citations screened, 15 met the criteria and were analyzed. The pooled early mortality rate (n = 595) was 2.1% (95% confidence interval [CI] 1.1% to 4.0%). The late mortality rate was 0.5%/patient-year (95% CI 0.2% to 0.8%/patient-year), and the redo-PVR rate was 1.9%/patient-year (95% CI 1.3% to 2.5%/patient-year). Data on RV volumes and ejection fractions were available from 5 studies (n = 141). The pooled mean difference in the indexed RV end-diastolic and end-systolic volume was -63 ml/m(2) (95% CI -55 to -72) and -37 ml/m(2) (95% CI -30 to -45), respectively. No significant changes in the pooled mean difference of the RV ejection fraction (95% CI -1% to 3%) or QRS duration (95% CI -10 to 1 ms) were observed. In conclusion, surgical PVR in patients after tetralogy of Fallot repair has been associated with low early and late mortality and significant decreases in RV volumes but no changes in the RV ejection fraction or QRS duration.

Arterial distensibility in children and teenagers: normal evolution and the effect of childhood vasculitis

Background: Polyarteritis nodosa is a necrotising vasculitis of the medium sized and small muscular arteries. The inflammatory and subsequent reparative processes may alter the arterial mechanical properties. The effect of vasculitic damage on arterial distensibility has never been explored however. Aim: To determine the normal values and the effect of childhood vasculitis on arterial distensibility in children and teenagers. Methods: Distensibility of the brachioradial arterial segment was studied using pulse wave velocity (PWV ∝1/√distensibility), in 13 children with polyarteritis nodosa at a median age of 11.8 (range 4.9–16) years. As a control group, 155 healthy schoolchildren (6–18 years, 81 boys) were studied. PWV was assessed using a photoplethysmographic technique; blood pressure was measured by an automatic sphygmomanometer (Dinamap). Data from patients were expressed as z scores adjusted for age and compared to a population mean of 0 by a single sample t test. Determinants of PWV in normal children were assessed by univariate and multivariate linear regression analyses. Results: Age, height, weight, and systolic blood pressure correlated individually with the brachioradial PWV. Multivariate analysis identified age as the only independent determinant. Ten of the patients were in clinical remission, while three had evidence of disease activity at the time of study. The PWV in the patient group as a whole was significantly greater than those in healthy children (mean z score +0.99). Raised C reactive protein concentration (>2 mg/dl) in the three patients with active disease was associated with a higher PWV when compared to those in remission (z score +2.78 v +0.45). The diastolic blood pressure of the patients was higher than those of the controls (z score +1.04) while the systolic pressure was similar (z score −0.36). Conclusions: PWV in the brachioradial arterial segment increases gradually during childhood independent of body weight, height, mass, and blood pressure. Increased PWV, and hence decreased distensibility, in this peripheral arterial segment occurs in polyarteritis nodosa and is amplified during acute inflammatory exacerbation.

Peritoneal dialysis after surgery for congenital heart disease in infants and young children

BACKGROUND We determined the risk factors for peritoneal dialysis (PD) in young children undergoing open heart surgery and, in those patients requiring PD, factors associated with prolonged PD and mortality. METHODS The clinical records of 182 children, aged 3 years or younger, who had undergone open heart surgery during a 2-year period were reviewed. Demographic data, preoperative risk factors, intraoperative variables, and postoperative complications were compared between patients requiring PD and those who did not, and between survivors and nonsurvivors of PD. RESULTS Of the 182 patients, 31 (17%) required PD. Patients requiring PD were lighter and more likely to have required preoperative ventilation; had undergone more complex surgery requiring longer bypass and circulatory arrest; and had experienced a pulmonary hypertensive crisis (p < 0.01). Logistic regression identified circulatory arrest (relative risk, 9.4; p = 0.002), cardiopulmonary bypass duration (relative risk, 1.02; p = 0.028), and low cardiac output syndrome (relative risk, 12.9; p < 0.0001) as significant determinants. Peritoneal dialysis was effective in achieving negative fluid balance, although serum urea and creatinine levels remained static. Prolonged PD was associated with younger age, higher preoperative serum creatinine, higher postoperative oxygen requirement, postoperative pulmonary hypertensive crisis, and low cardiac output syndrome (p < 0.05). When compared with survivors (n = 22), nonsurvivors (n = 9) were more likely to have had syndrome disorders and required preoperative ventilation and higher postoperative ventilatory settings (p < 0.05). CONCLUSIONS Risk factors for PD in young children undergoing open heart surgery are circulatory arrest, cardiopulmonary bypass duration, and low cardiac output syndrome. The preoperative and postoperative cardiopulmonary status has a significant bearing on PD duration and patient survival.

Impact of Right Ventricular Dilation on Left Ventricular Myocardial Deformation in Patients After Surgical Repair of Tetralogy of Fallot

Left ventricular (LV) dysfunction is 1 of the major determinants of late adverse clinical outcomes in patients after surgical repair of tetralogy of Fallot (TOF). The aim of this study was to test the hypothesis that LV myocardial deformation is impaired in patients after TOF repair and related to right ventricular (RV) dilation and exercise capacity. Longitudinal, radial, and circumferential LV myocardial deformation was determined using speckle-tracking echocardiography in 23 postoperative patients with TOF and compared to that of 23 age-matched controls. Relations between LV strain and strain rate (SR) and RV volumes and exercise parameters were determined in patients. Compared to controls, patients had reduced global LV longitudinal, radial, and circumferential strain (all p values <0.05). Patients with significantly increased RV end-systolic volume (>2 SDs higher than normal; n = 17) had reduced global LV circumferential strain (p = 0.048) and SR (p = 0.038), but similar longitudinal and radial speckle-tracking echocardiographic parameters, compared to those without (n = 6). RV end-systolic volume was correlated inversely with global LV circumferential strain and SR (r = -0.58, p = 0.004, and r = -0.58, p = 0.005, respectively), while RV end-diastolic volume was correlated only with global LV circumferential strain (r = -0.43, p = 0.047). In patients, the LV ejection fraction was correlated with global LV circumferential strain (r = 0.54, p = 0.01) and SR (r = 0.66, p = 0.001) but not with longitudinal or radial speckle-tracking echocardiographic parameters. Using multivariate analysis, global LV circumferential SR (beta = 0.66, p = 0.001) and male gender (beta = 0.46, p = 0.012) were identified as independent predictors of peak oxygen consumption. In conclusion, the negative impact of RV dilation on LV function relates to its influence on LV circumferential strain and SR in patients after TOF repair.