Differential Adaptation of Biventricular Myocardial Kinetic Energy in Patients With Repaired Tetralogy of Fallot Assessed by MR Tissue Phase Mapping.

BACKGROUND: The myocardial kinetic energy (KE) and its association with pulmonary regurgitation (PR) have yet to be investigated in repaired tetralogy of Fallot (rTOF) patients. PURPOSE: To evaluate the adaptation of myocardial KE in rTOF patients by tissue phase mapping (TPM). STUDY TYPE: Prospective. POPULATION: A total of 49 rTOF patients (23 ± 5 years old; male = 32), 47 normal controls (22 ± 1 year old; male = 29). FIELD STRENGTH/SEQUENCE: 3-T/2D dark-blood three-directional velocity-encoded gradient-echo sequence. ASSESSMENT: Left and right ventricle (LV, RV) myocardial KE in radial (KEr ), circumferential (KEø ), longitudinal (KEz ) directions. The proportions of KE in each direction to the sum of all KE (KErøz ): %KEr , %KEø , %KEz . PR fraction. STATISTICAL TEST: Student's t test, multivariable regression. Statistical significance: P < 0.05. RESULTS: In rTOF group, LV KEz remained normal in systole (P = 0.565) and diastole (P = 0.210), whereas diastolic LV %KEz (62% ± 14% vs. 72% ± 7%) and systolic LV %KEø (9% ± 6% vs. 20% ± 7%) were significantly decreased. The KEr and %KEr of both ventricles significantly increased in the rTOF group (RV in diastole: 6 ± 3 vs. 3 ± 1 µJ and 54% ± 13% vs. 27% ± 7%). The rTOF group exhibited significantly higher RV/LV ratios of %KEr (systole: 1.3 ± 0.3 vs. 1.0 ± 0.3) and %KEø (systole: 1.6 ± 0.8 vs. 1.0 ± 0.3) and significantly lower ratios of %KEz in systole (0.7 ± 0.2 vs. 1.0 ± 0.1) and diastole (0.5 ± 0.2 vs. 0.9 ± 0.1). In multivariable regression analysis, the RV peak systolic KErøz , RV systolic KEz , and LV diastolic %KEø were independently associated with PR fraction in the rTOF group (adjusted R2  = 0.479). DATA CONCLUSION: In rTOF patients, the adaptation of the KE proportion occurred earlier than that of the KE amplitude, and the biventricular balance of %KE was disrupted. PR may cause differential KE adaptation in RV and LV. TPM-derived KE may be useful in investigation of myocardial adaptation in rTOF patients. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 3.

The Potential Biomarker of Di(2-ethylhexyl) Phthalate Exposure during Catheterization.

Background: Di(2-ethylhexyl) phthalate (DEHP) may produce toxicity, posing a risk to human health. Medical devices composed of DEHP are frequently used in catheterization, but few studies have investigated DEHP exposure during catheterization. The aim of this prospective series was to characterize the exposure pattern of DEHP during catheterization. Methods: We enrolled 16 patients with congenital heart disease undergoing catheterization. Collection of urine was done to measure DEHP metabolites on hospitalization, before catheterization, after catheterization, and at discharge. The following DEHP metabolites were measured: mono-(2-ethylhexyl) phthalate (MEHP), mono (2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono-(2-ethyl-5-oxohexyl) phthalate (MEOHP), and the ratio of MEHP to overall metabolites (MEHP%) was determined. DEHP exposure from polyvinyl chloride (PVC)-containing catheter and infusion systems were recorded in detail. Differences in DEHP levels before and after catheterization were analyzed. Results: Urinary levels of MEHP, MEHHP, and MEOHP significantly decreased from before catheterization to after catheterization (all p < 0.01), but did not change significantly from initial hospitalization to before catheterization. Urinary MEHP% significantly decreased from initial hospitalization to before catheterization (p < 0.001), then increased after catheterization (p < 0.001), and decreased gradually at discharge (p = 0.03). Urinary MEHP% after catheterization and at discharge was significantly positively related to the duration of using PVC-containing catheter systems. There was a significant positive correlation between urinary MEHP% and the duration of using PVC-containing infusion system before catheterization, and a borderline significant correlation at both post-catheterization time slots. Conclusions: Our results demonstrated that urinary MEHP% may be a potential biomarker of DEHP contamination from the use of PVC-containing catheters or infusion systems.

iTRAQ Proteomics Identified the Potential Biomarkers of Coronary Artery Lesion in Kawasaki Disease and In Vitro Studies Demonstrated That S100A4 Treatment Made HCAECs More Susceptible to Neutrophil Infiltration.

Coronary artery lesions (CAL) are a major complication of Kawasaki disease (KD). The early prediction of CAL enables the medical personnel to apply adequate medical intervention. We collected the serum samples from the KD patients with CAL (n = 32) and those without CAL (n = 31), followed by a global screening with isobaric tagging for relative and absolute quantification (iTRAQ) technology and specific validation with an enzyme-linked immunosorbent assay (ELISA). iTRAQ identified 846 proteins in total in the serum samples, and four candidate proteins related to CAL were selected for ELISA validation as follows: Protein S100-A4 (S100A4), Catalase (CAT), Folate receptor gamma (FOLR3), and Galectin 10 (CLC). ELISA validation showed that the S100A4 level was significantly higher in KD patients with CAL than in those without CAL (225.2 ± 209.5 vs. 143.3 ± 83 pg/mL, p < 0.05). In addition, KD patients with CAL had a significantly lower CAT level than those without CAL (1.6 ± 1.5 vs. 2.7 ± 2.3 ng/mL, p < 0.05). Next, we found that S100A4 treatment on human coronary artery endothelial cells (HCAECs) reduced the abundance of cell junction proteins, which promoted the migration of HCAECs. Further assays also demonstrated that S100A4 treatment enhanced the permeability of the endothelial layer. These results concluded that S100A4 treatment resulted in an incompact endothelial layer and made HCAECs more susceptible to in vitro neutrophil infiltration. In addition, both upregulated S100A4 and downregulated CAT increased the risk of CAL in KD. Further in vitro study implied that S100A4 could be a potential therapeutic target for CAL in KD.

Reappraisal of VEGF in the Pathogenesis of Kawasaki Disease.

Vascular endothelial growth factor (VEGF) is an important factor in mediating the inflammation of Kawasaki disease (KD). The literature regarding the relationship between VEGF and KD is sparse. The purpose of this study was to investigate the correlation of VEGF and KD. In a prospective study of 42 Taiwanese KD patients (18.9 ± 12.2 months, M/F 22/20) treated with intravenous immunoglobulin (IVIG), a series of VEGF levels was measured from the acute to convalescent phases. KD patients were classified into two subgroups with (n =20) and without (n = 22) acute coronary artery lesions (CALs). Control samples were obtained from 30 febrile controls (19.1 ± 13.7 months, M/F 13/17). In KD patients, VEGF levels in the pre-IVIG acute phase were significantly higher than those in the subacute and convalescent phases (both p < 0.001). In KD patients with CALs, VEGF levels significantly increased immediately in the post-IVIG phase (p = 0.039), and then significantly decreased in the subacute phase (p = 0.002). KD patients with acute CALs had higher median VEGF levels than those without acute CALs from acute to convalescent phases. In the subacute phase, KD patients with acute CALs had significantly higher VEGF levels (p = 0.022) than those without acute CALs. Our data show that VEGF did not decrease after IVIG treatment, and increased significantly after IVIG treatment in KD patients with acute CALs in acute phase. VEGF might be related to the complications of CALs in KD patients.

Prediction Model for Diagnosis of Kawasaki Disease Using iTRAQ-Based Analysis.

A quick prediction method may help confirm the diagnosis of Kawasaki disease (KD), and reduce the risk of coronary artery lesions. The purpose of this study was to evaluate potential candidate diagnostic serum proteins in KD using isobaric tagging for relative and absolute quantification (iTRAQ) gel-free proteomics. Ninety two subjects, including 68 KD patients (1.6 ± 1.2 years, M/F 36/32) and 24 fever controls with evident respiratory tract infection (2.1 ± 1.2 years, M/F 13/11) were enrolled. Medical records were reviewed for demographic and laboratory data. The iTRAQ gel-free proteomics was used to screen serum proteins completely and compare the difference between two groups followed by specific validation with ELISA. The candidate proteins and conventional laboratory items were selected for the prediction model of KD diagnosis by support vector machine. Five selected candidate proteins, including protein S100-A8, protein S100-A9, protein S100-A12, neutrophil defensin 1, and alpha-1-acid glycoprotein 1 were identified for developing the prediction model of KD diagnosis. They were used to develop an efficient KD prediction model with an area under receiver operating characteristic (auROC) value of 0.92 (95% confidence interval: 0.84, 0.98). These protein biomarkers were significantly correlated with the conventional laboratory items as follows: C-reactive protein, glutamic pyruvic transaminase, white blood count, platelet, segment and hemoglobin. These conventional laboratory items were used to develop a prediction model of KD diagnosis with an auROC value of 0.88 (95% confidence interval: 0.80, 0.96). Our result demonstrated that the prediction model with combined five selected candidate protein levels may be a good diagnostic tool of KD. Further prediction model with combined six conventional laboratory data is also an acceptable alternative method for KD diagnosis.

Identifying Circulating MicroRNA in Kawasaki Disease by Next-Generation Sequencing Approach.

Kawasaki disease (KD) typically occurs in children aged under 5 years and can cause coronary artery lesions (CALs). Early diagnosis and treatment with intravenous immunoglobulin can reduce the occurrence of CALs; therefore, identifying a good biomarker for diagnosing KD is essential. Here, using next-generation sequencing in patients with recurrent KD, those with viral infection, and healthy controls, we identified dysregulated circulating microRNAs as diagnostic biomarkers for KD. Pathway enrichment analysis illustrated the putative role of these miRNAs in KD progression. Their expression levels were validated using real-time polymerase chain reaction (qPCR). Fifteen dysregulated circulating miRNAs (fold changes >2 and <0.5) were differentially expressed in the recurrent KD group compared with the viral infection and control groups. These miRNAs were significantly involved in the transforming growth factor-ß, epithelial-mesenchymal transition, and cell apoptosis signaling pathways. Notably, their expression levels were frequently restored after intravenous immunoglobulin treatment. Among the candidates, miR-24-3p expression level was significantly higher in patients with recurrent KD compared with healthy controls or viral infection controls (p < 0.001). Receiver operating characteristic analysis revealed that high miR-24-3p expression levels may be a potential biomarker for KD diagnosis. In conclusion, we identified miR-24-3p significantly higher in KD patients, which may be a potential diagnostic biomarker for KD.

Serum proteins may facilitate the identification of Kawasaki disease and promote in vitro neutrophil infiltration.

Kawasaki disease (KD) usually affects the children younger than 5 years of age and subsequently causes coronary artery lesions (CALs) without timely identification and treatment. Developing a robust and fast prediction method may facilitate the timely diagnosis of KD, significantly reducing the risk of CALs in KD patients. The levels of inflammatory serum proteins dramatically vary during the onsets of many immune diseases, including in KD. However, our understanding of their pathogenic roles in KD is behind satisfaction. The purpose of this study was to evaluate candidate diagnostic serum proteins and the potential mechanism in KD using iTRAQ gel-free proteomics. We enrolled subjects and conducted iTRAQ gel-free proteomics to globally screen serum proteins followed by specific validation with ELISA. Further in vitro leukocyte trans-endothelial model was also applied to investigate the pathogenesis roles of inflammatory serum proteins. We identified six KD protein biomarkers, including Protein S100-A8 (S100A8), Protein S100-A9 (S100A9), Protein S100-A12 (S100A12), Peroxiredoxin-2 (PRDX2), Neutrophil defensin 1 (DEFA1) and Alpha-1-acid glycoprotein 1 (ORM1). They enabled us to develop a high-performance KD prediction model with an auROC value of 0.94, facilitating the timely identification of KD. Further assays concluded that recombinant S100A12 protein treatment activated neutrophil surface adhesion molecules responsible for adhesion to endothelial cells. Therefore, S100A12 promoted both freshly clinically isolated neutrophils and neutrophil-like cells to infiltrate through the endothelial layer in vitro. Finally, the antibody against S100A12 may attenuate the infiltration promoted by S100A12. Our result demonstrated that evaluating S100A8, S100A9, S100A12, PRDX2, DEFA1 and ORM1 levels may be a good diagnostic tool of KD. Further in vitro study implied that S100A12 could be a potential therapeutic target for KD.

Arterial stiffness late after Kawasaki disease in children: Assessment by performing brachial-ankle pulse wave velocity.

BACKGROUND: Whether low-risk Kawasaki disease (KD) patients are at increased risk of cardiovascular disease later in life remains controversial. The purpose of this study is to examine the arterial stiffness and exercise performance of KD patients in chronic stage. METHODS: This study included 158 subjects. They were divided into three groups: 37 KD patients with regressed coronary artery lesions (CALs) (M/F 23/14, 13.6 ± 6.5 years) (group I), 43 KD patients without CALs (M/F 26/17, 13.9 ± 6.2 years) (group II), and 78 age- and gender-matched normal controls (M/F 44/34, 13.2 ± 6.9 years) (group III). They all underwent brachial-ankle pulse wave velocity (baPWV), an exercise test, and blood sampling to measure the levels of high-sensitivity C-reactive protein (hs-CRP), triglycerides (TG), high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, and total cholesterol (TC). The differences among the groups were compared. RESULTS: There were significant differences among the three groups in terms of right and left baPWV (p < 0.01 respectively), HDL level (p < 0.05), TC/HDL ratio (p < 0.05), and oxygen consumption (VO2) peak (p < 0.05). Moreover, group I subjects had significantly higher right and left baPWV (p < 0.05 respectively), lower HDL level (p < 0.05), and lower VO2 peak (p < 0.05) than group II subjects. Furthermore, baPWV was significantly correlated with TG level (r = 0.326, p < 0.05), TC/HDL ratio (r = 0.483, p < 0.01), LDL level (r = 0.386, p < 0.01), and VO2 peak (r = -0.385, p < 0.05) in group I subjects. Only the TC/HDL ratio was found to be a significant correlating factor for an increase of baPWV (beta = 0.68, p < 0.05) in KD patients after multiple linear regression. CONCLUSION: Our results suggest that arterial stiffness is present late after KD and may adversely affect exercise performance, especially in patients with regressed CALs. Regular measurement of baPWV may be indicated in the long-term follow-up of KD patients.

Biventricular myocardial adaptation in patients with repaired tetralogy of Fallot: Mechanistic insights from magnetic resonance imaging tissue phase mapping.

BACKGROUND: The myocardial adaptive mechanism in patients with repaired tetralogy of Fallot (rTOF) is less understood. We aimed to investigate biventricular myocardial adaptive remodeling in rTOF patients. METHODS: We recruited 32 rTOF patients and 38 age- and sex-matched normal controls. The pulmonary stenosis of rTOF patients was measured using catheterized pressure gradient between right ventricle (RV) and pulmonary artery (PGRVPA). rTOF patients with PGRVPA < 15 mmHg and ≥15 mmHg were classified as low pulmonary stenosis (rTOFlow, n = 19) and high pulmonary stenosis (rTOFhigh, n = 13) subgroups, respectively. Magnetic resonance imaging tissue phase mapping was employed to evaluate the voxelwise biventricular myocardial motion in longitudinal (Vz), radial (Vr), and circumferential (Vφ) directions. RESULTS: The rTOFlow subgroup presented higher pulmonary regurgitation fraction than rTOFhigh subgroup (p < 0.001). Compared with the normal group, only rTOFlow subgroup presented a decreased RV ejection fraction (RVEF) (p < 0.05). The rTOFlow subgroup showed decreased systolic and diastolic Vz in RV and LV, whereas rTOFhigh subgroup showed such change only in RV. In rTOFlow subgroup, RVEF significantly correlated with RV systolic Vr (r = 0.56, p < 0.05), whereas LVEF correlated with LV systolic Vz (r = 0.51, p = 0.02). Prolonged QRS correlated with RV systolic Vr (r = -0.58, p < 0.01) and LV diastolic Vr (r = 0.81, p < 0.001). No such correlations occurred in rTOFhigh subgroup. CONCLUSIONS: The avoidance of unfavorable functional interaction in RV and LV in rTOFhigh subgroup suggested that adequate pulmonary stenosis (PGRVPA ≥ 15 mmHg in this sereis) has a protective effect against pulmonary regurgitation.

Adenovirus infection and subsequent risk of Kawasaki disease: A population-based cohort study.

BACKGROUND: The relationship between adenovirus infection and Kawasaki disease (KD) is unclear. The purpose of this study was to determine the relationship between adenovirus infection and KD using a cohort study in Taiwan. METHODS: We used Taiwan National Health Insurance data (from 2000 to 2008) to conduct a population-based cohort study, analyzing children that was under 18 years of age. In total, 5280 children had adenovirus infection, and 5280 children without adenovirus infection were matched and followed up. Subsequent KD was the major outcome event. The Cox proportional hazards model was used to estimate the hazard ratio (HR) with 95% confidence intervals (CIs) of developing KD associated with adenovirus infection. RESULTS: There was a significantly higher cumulative incidence of KD in the adenovirus-infected cohort than that in the control cohort (log-rank test, p < 0.001). In the adenovirus-infected cohort, overall incidence of KD was 5.29 times higher than that of the control cohort (adjusted HR 5.29, 95% CI: 2.48-11.3). Increased KD risk was associated with previous adenovirus infection in children aged 3-5 years, in female patients, in those with a low urbanization level, and in those with allergies. CONCLUSION: An association between previous adenovirus infection and KD was identified in Taiwanese children, but other potential risk factors were not fully analyzed. The relationship between infection and KD requires further study.

Hepatic pathology in patients after Fontan operation: A computed tomography imaging study.

BACKGROUND: Hepatic dysfunction is an important long-term complication in Fontan patients. The purpose of this study was to evaluate the hepatic computed tomography (CT) findings after Fontan surgery and identify their association with clinical parameters. METHODS: This study recruited 43 patients (23 male and 20 female patients aged 15.3 ± 6.8 years), who underwent Fontan surgery. Medical records were reviewed to collect their age, sex, congenital heart disease type, date of Fontan surgery, laboratory data, and hepatic CT findings. The relationship between hepatic findings and clinical parameters was analyzed. RESULTS: The follow-up duration was 6.8 ± 4.1 years. Abnormal hepatic parenchymal enhancement was observed in 77% of the patients, with mild degree in 18, moderate degree in 10, and severe degree in 5 patients. According to the univariate analysis, risk factors for hepatic parenchymal enhancement were follow-up duration (odds ratio [OR]: 1.354 [95% confidence interval (CI): 1.024-2.078]; p = 0.042), hypoplastic left heart syndrome (HLHS) (OR: 3.262 [95% CI: 1.145-5.628]; p = 0.002), mean pulmonary artery pressure (OR: 1.598 [95% CI: 1.089-2.132]; p = 0.026), pulmonary vascular resistance index (OR: 1.263 [95% CI: 1.068-1.245]; p = 0.032), and brain natriuretic peptide (OR: 1.956 [95% CI: 1.085-2.673]; p = 0.045). According to the multivariate analysis, only HLHS (OR: 3.856 [95% CI: 1.389-5.863]; p = 0.001), mean pulmonary artery pressure (OR: 1.846 [95% CI: 1.362-2.549]; p = 0.015), and pulmonary vascular resistance index (OR: 1.185 [95% CI: 1.042-1.736]; p = 0.047) were significant risk factors for abnormal parenchymal enhancement. CONCLUSION: Abnormal hepatic parenchymal enhancement detected through CT is common in Fontan patients. Regular liver function test in conjunction with imaging studies may be considered when following up Fontan patients.

MiR-182-5p enhances in vitro neutrophil infiltration in Kawasaki disease.

BACKGROUND: Kawasaki disease (KD) patients could develop coronary artery lesion (CAL) which threatens children's life. A previous study identified KD biomarker miRNAs that could discriminate KD patients from febrile non-KD patients. We wonder whether these KD prediction biomarkers could be further applied to predict CAL formation in KD patients. METHODS: To examine this hypothesis, we conducted a meta-analysis, miRNA mimic transfection, in vitro cell model and microarray assays. RESULTS: We first showed that miR-182-5p and miR-183-5p kept higher levels in the KD patients with CAL than those without CAL (p < .05). Further machine learning alignment confirmed that CAL formation could be predicted, with an auROC value of 0.86. We further treated neutrophil cells with miR-182-5p mimic, followed by in vitro transendotherial migration assay. As a result, miR-182-5p overexpression significantly (p < .05) enhanced neutrophil cells to infiltrate the endothelial layer composed of human coronary artery endothelium cells. Further microarray assay and pathway enrichment analysis showed that the genes activated with miR-182-5p overexpression were significantly enriched in the leukocyte transendothelial migration pathway (kegg_pathway_194, p < .05). CONCLUSION: Therefore, our study suggested that miR-182-5p enhanced in vitro leukocyte infiltration by activating the leukocyte transendothelial migration pathway in CAL formation in KD.

Update on association between Kawasaki disease and infection.

The relationship between infection and Kawasaki disease (KD) remains unclear. Infection has long been considered a key predisposing factor for KD. Bacterial and viral agents may be related to the onset of KD because of superantigen and cytokine production. Various bacterial and viral infections have been reported to be associated with KD, but the actual mechanism remains unknown. The higher association between KD and enterovirus has been well documented by using Taiwan National Health Insurance Research Database. However, no evidence has been obtained that various bacterial and viral infections induce KD. Comprehensive research, including infectious agents, should be conducted to elucidate the pathogenesis of KD.

Safrole induced cytotoxicity, DNA damage, and apoptosis in macrophages via reactive oxygen species generation and Akt phosphorylation.

Safrole is a natural compound categorized as a group 2B carcinogen extracted from betel quid chewing, which is a common practice of psychoactive habits integrated into social and cultural ceremonies among serveral million people, especially in Southern or Southeastern Asia. Safrole is one of the major risk compunds for development of oral squamous cell carcinoma and hepatocellular carcinoma via DNA adduction. In innate immunity, macrophages are the predominant cells for non-specific first line defense against pathogens in oral tissue. Up to now, there is no evidence to implicate the potential toxicological effect of safrole on macrophages. In this study, we found safrole induced the generation of reactive oxygen species (ROS) and myeloperoxidase (MPO) in RAW264.7 macrophages in a concentration-dependent manner. Furthermore, cytotoxicity, DNA damage, and apoptosis were caused by safrole in a concentration-dependent manner. While the activation of antioxidative enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) was reduced, the phosphorylation of Akt was induced by safrole in a concentration-dependent manner. These results indicated that the induction of cytotoxicity, DNA damage, and apoptosis in macrophages by safrole was through generation of ROS and inhibition of antioxidative enzymes possibly via Akt phosphorylation.

Enterovirus Infection and Subsequent Risk of Kawasaki Disease: A Population-based Cohort Study.

BACKGROUND: The relationship of enterovirus (EV) infection and Kawasaki disease (KD) is still unclear. The purpose of this study was to conduct a population-based cohort study to determine the relationship between KD and EV infection in Taiwan. METHODS: A population-based cohort study was conducted to analyze the children file (age < 18 years) of the Taiwan National Health Insurance program between 2000 and 2008. In total, 285,636 children with EV infection and 285,636 children without EV infection were included and followed up. The subsequent KD was the major outcome event. RESULTS: The cumulative incidence of KD was significantly higher in the EV-infected cohort than in the non-EV-infected cohort (log-rank test, P < 0.001). The overall incidence of KD was 56% higher in the EV-infected cohort than in the non-EV-infected cohort, with an adjusted hazard ratio of 1.56 (95% confidence interval: 1.44-1.69). Stratified analysis showed higher KD risk associated with previous EV infection in children 3-5 years old, in girls, in children living in less urbanization levels, in children with parental low-income occupation, and in children with allergic diseases. CONCLUSIONS: There is a higher association between KD and previous EV infection in Taiwanese children, especially in those 3-5 years old, with female sex, with less urbanization level, with low-income parental occupation, and with allergy.

Abnormal biventricular performance in asymptomatic adolescents late after repaired Tetralogy of Fallot: Combined two-dimensional speckle tracking and three-dimensional echocardiography study.

BACKGROUND: The aim of this prospective study was to assess biventricular performance in asymptomatic adolescents with repaired tetralogy of Fallot (TOF) using 2D speckle tracking and real time 3D echocardiography simultaneously. METHODS: We studied 31 patients with repaired TOF (M/F: 22/9, age: 16.1 ± 6.1 yrs) who had history of cardiac surgery with mean follow-up duration of 12.8 years, and 32 age- and sex-matched normal individuals (M/F: 23/9, age: 16.6 ± 5.1 yrs). All subjects underwent speckle tracking and 3D echocardiography, electrocardiogram, treadmill, and blood sampling for measurement of brain natriuretic peptide (BNP). RESULTS: Compared to the control group, the TOF group had higher BNP level (31.8 ± 21.4 vs 14.1 ± 12.4 pg/ml, p < 0.01), lower peak oxygen consumption (8.4 ± 1.7 vs 9.9 ± 1.6 ml/kg/min, p < 0.05), and longer QRS duration (126 ± 30 vs 82 ± 9 ms, p < 0.01). Patients with repaired TOF had significantly impaired right ventricle (RV) global and all six regional longitudinal strain and strain rate than normal controls. Left ventricle (LV) global and mainly apical regional longitudinal strain and strain rate were reduced in patients with repaired TOF. There was a significant correlation of global longitudinal strain (r = 0.456, p = 0.01) and global time to peak longitudinal strain (r = 0.484, p < 0.01) between LV and RV in patients with repaired TOF. In terms of 3D echo cardiographic volume data, patients with repaired TOF had lower LV stroke volume index (p < 0.05), but higher RV end diastolic volume index (p < 0.01), RV end systolic volume index (p < 0.01), RV stroke volume index (p < 0.01), and pulmonary regurgitation fraction (p < 0.01) than normal controls. CONCLUSION: Our results suggest asymptomatic adolescents with repaired TOF had abnormal biventricular myocardial performance, as demonstrated by combined 2D speckle-tracking and 3D echocardiography. The implications of these findings for management of adolescents late after repaired TOF remain to be determined.