Pak-cheong Chow

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.

Oxidative stress in children late after Kawasaki disease: relationship with carotid atherosclerosis and stiffness

BackgroundPersistent arterial dysfunction in patients with a history of Kawasaki disease (KD) and an integral role of oxidative stress in the development of cardiovascular disease are increasingly recognized. We sought to test the hypothesis that oxidative stress is increased in KD patients and related to carotid atherosclerotic changes and stiffness.MethodsWe compared the serum levels of oxidative stress biomarkers, carotid intima-media thickness (IMT), and carotid stiffness index among KD patients with coronary aneurysms (n = 32), those without coronary complications (n = 19), and controls (n = 32).ResultsCompared with controls, patients with coronary aneurysms had significantly higher serum levels of malonaldehyde (2.62 ± 0.12 μM vs 2.22 ± 0.07 μM, p = 0.014) and hydroperoxides (26.50 ± 1.13 μM vs 22.50 ± 0.62 μM, p = 0.008). A linear trend of the magnitude of oxidative stress in relation to inflammatory damage was observed for malonaldehyde (p = 0.018) and hydroperoxides (p = 0.014) levels. Serum malonaldehyde and hydroperoxide levels correlated positively with carotid IMT (p < 0.001 and p = 0.034, respectively) and stiffness index (p = 0.001 and p = 0.021, respectively). Multiple linear regression analysis identified serum malonaldehyde level as a significant determinant of carotid IMT (β = 0.31, p = 0.006) and stiffness (β = 0.27, p = 0.008).ConclusionOur findings suggest oxidative stress is increased in KD patients with coronary aneurysms and is associated with carotid intima-media thickening and stiffening.

Circulating microRNA expression profile and systemic right ventricular function in adults after atrial switch operation for complete transposition of the great arteries

BackgroundData 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.MethodsCirculating 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.ResultsCompared 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.ConclusionsA 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.

Under-recognition of 22q11.2 deletion in adult Chinese patients with conotruncal anomalies: implications in transitional care.

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.

Diastolic ventricular interaction in patients after atrial switch for transposition of the great arteries: A speckle tracking echocardiographic study

BACKGROUND We tested the hypothesis that diastolic ventricular interaction occurs after atrial switch operation for transposition of the great arteries (TGA) and that subpulmonary LV diastolic function is influenced by septal geometry. METHODS Twenty-nine patients (male 19) after atrial switch operation for TGA aged 20.8 ± 4.1 years and 27 healthy controls were studied. Two-dimensional longitudinal systolic strain, systolic (SRs), early diastolic (SRe), and late diastolic (SRa) strain rates of both ventricles were determined using speckle tracking echocardiography. Early diastolic trans-atrioventricular velocity (E) and myocardial early diastolic myocardial velocity (e) at the ventricular free wall-annular junction were measured. Geometry of the morphologic left ventricle was quantified by the diastolic eccentricity index (EI). RESULTS In both systemic and subpulmonary ventricles, SRe and SRa were significantly lower and trans-atrioventricular E/e ratios higher in patients than controls (all p<0.001). In patients, RV SRe correlated with left ventricular (LV) SRe (r=0.49, p=0.008), and RV SRa correlated with LV SRa (r=0.46, p=0.01). Significant leftward shifting of the septum in patients was reflected by the greater LV EI (p<0.001). In patients, LV EI correlated with age- and sex-adjusted z score of LV end-diastolic volume. As a group, LV EI correlated negatively with LV SRe (r=-0.62, p<0.001) and LV SRa (r=-0.51, p<0.001), and positively with mitral E/e ratio (r=0.33, p=0.02). CONCLUSIONS Systemic RV diastolic dysfunction occurs after atrial switch operation and correlates with subpulmonary LV diastolic dysfunction. The observed diastolic ventricular interaction may potentially be mediated through alteration of septal geometry.

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 (β = .31, P = .045) and PIIINP (β = .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.

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 (β = −0.50, p<0.001) and serum TNF-α (β = 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.

Apoptosis of cardiomyocytes in children with right ventricular pressure overload with and without hypoxemia.

Cardiomyocyte apoptosis has been implicated in ventricular remodeling and initiation of cardiac failure. We sought to determine the severity of right ventricular (RV) cardiomyocyte apoptosis in cyanotic and acyanotic children with RV pressure overload.

Circulating MicroRNA in Patients with Repaired Tetralogy of Fallot

Emerging data suggest that heart‐related microRNAs (miRs) may serve as circulating biomarkers of myocardial injury. We aimed to determine the circulating profile of miRs in patients with volume‐overloaded right ventricles after repair of tetralogy (TOF).