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.

Milrinone effects on cardiac mitochondria, hemodynamics, and death in catecholamine-infused rats.

BACKGROUND: Catecholamine-storm is considered the major cause of enterovirus 71-associated cardiopulmonary death. To elucidate the effect of milrinone on cardiac mitochondria and death, a rat model of catecholamine-induced heart failure was investigated. METHODS: Young male Spray-Dawley rats received a continuous intravenous infusion of norepinephrine then followed by co-treatment with and without milrinone or esmolol. Vital signs were monitored and echocardiography was performed at indicated time points. At the end of experiments, hearts were extracted to study mitochondrial function, biogenesis, and DNA copy numbers. RESULTS: Hypernorepinephrinemia induced persistent tachycardia, hypertension, and high mortality and significantly impaired the activities of the electron transport chain and suppressed mitochondrial DNA copy number, mitochondrial transcription factor A and peroxisome proliferator-activated receptor-gamma coactivator 1-α. Norepinephrine-induced hypertension could be significantly suppressed by milrinone and esmolol. Milrinone improved but esmolol deteriorated the survival rate. The left ventricle was significantly enlarged shortly after norepinephrine infusion but later gradually reduced in size by milrinone. The impairment and suppression of mitochondrial function could be significantly reversed by milrinone but not by esmolol. CONCLUSIONS: Milrinone may protect the heart via maintaining mitochondrial function from hypernorepinephrinemia. This study warrants the importance of milrinone and the preservation of mitochondrial function in the treatment of catecholamine-induced death. IMPACT: Milrinone may protect the heart from hypernorepinephrinemia-induced death via maintaining myocardial mitochondrial activity, function, and copy number. Maintenance of cardiac mitochondrial function may be a potential therapeutic strategy in such catecholamine-induced heart failure.

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.

Antibody Profiling of Kawasaki Disease Using Escherichia coli Proteome Microarrays.

Kawasaki disease (KD) is a form of systemic vasculitis that generally occurs in children under 5 years old. Currently, KD is still diagnosed according to its clinical symptoms, including prolonged fever, skin rash, conjunctivitis, neck lymphadenopathy, palm erythema, and oral mucosa changes. Because KD is a type of inflammation without specific marker for diagnosis, we plan to profile the plasma antibodies by using E. coli proteome microarray and analyze the differences between KD and healthy subjects. Plasmas were collected from KD patient before intravenous immunoglobulin treatment (KD1), at least 3 weeks after treatment (KD3), nonfever control (NC), and fever control (FC) children. The initial screening, which consisted of 20 KD1, 20 KD3, 20 NC, and 20 FC, were explored using E. coli proteome microarrays (∼4200 unique proteins). About ∼70 proteins were shown to have high accuracy, e.g. 0.78∼0.92, with regard to separating KD1, KD3, NC, and FC. Those proteins were then purified to fabricate KD focus arrays for training (n = 20 each) and blind-testing (n = 20 each). It only took 125 pl of plasma, less than a drop of blood, in the focus array assays. The AUC scores for blind tests of KD1 versus NC (17 protein markers), KD1 versus FC (20 protein markers), KD3 versus NC (9 protein markers), and KD1 versus KD3 (6 protein markers) were 0.84, 0.75, 0.99 and 0.98, respectively. This study is the first to profile plasma antibodies in KD and demonstrate that an E. coli proteome microarray can screen differences among patients with KD, nonfever controls, and fever controls.

Prognostic nutrition index as a predictor of coronary artery aneurysm in Kawasaki Disease.

BACKGROUND: Kawasaki Disease (KD) is considered a major acquired heart disease in children under the age of 5. Coronary artery aneurysm (CAA) can occur in serious cases despite extreme therapy efforts. Previous studies have reported low serum albumin level was associated with disease outcome, but no further investigation was addressed yet. METHOD: This retrospective (case-control) study randomly included children with KD who were admitted and underwent laboratory tests before undergoing IVIG treatment in this institution, the largest tertiary medical center in southern Taiwan from 2012 to 2016. Prognostic nutrition index (PNI), an albumin-based formula product, was evaluated as a predictor of CAA the first time. The progression of CAA was monitored using serial echocardiography for six months. We performed multivariable logistic regression analysis on the laboratory test and PNI with the disease outcome of the KD patients. RESULT: Of the 275 children, 149 had CAA, including transient dilatation, while the other 126 did not develop CAA during the 6-month follow-up period. A multivariate logistic regression model revealed that PNI, gender, IVIG non-responder, and platelet count are significant predictors of CAA with a 95% confidence interval estimator of 1.999, 3.058, 3.864 and 1.004, respectively. Using PNI to predict CAA presence gave an area under the receiver-operating-characteristics (ROC) curve of 0.596. For a cutoff of 0.5 in the logistic regression model and the PNI cut-off point is taken as 55 together with IVIG non-responder, boy gender, and platelet count take into account, sensitivity and specificity were 65.7 and 70.4%. CONCLUSION: PNI could be a candidate of adjunctive predictor of coronary artery aneurysm in addition to IVIG non-responder. Together with low PNI, IVIG non-responder, male gender and platelet count will give high odds to predict coronary artery aneurysm within 6 months of illness.

Evaluation of endothelial dysfunction, endothelial plasma markers, and traditional metabolic parameters in children with adiposity.

BACKGROUND/PURPOSE: To investigate the correlations among endothelial function assessment parameters, asymmetric dimethylarginine (ADMA)-related biomarkers, and traditional risk factors in adipose children. METHODS: We enrolled adipose children aged 7-18 years between July 2014 and August 2016 as well as normal-weight controls from the outpatient clinic. Vascular measurements including echocardiography, carotid intima media thickness, pulse wave velocity (PWV), and flow-mediated dilation (FMD) were measured. Venous blood samples including traditional metabolic and endothelial dysfunction parameters were analyzed. Participants were grouped as adipose vs. normal-weight and as adipose with hypertension vs. adipose without hypertension. Clinical presentations, laboratory data, and cardiovascular measurement were compared. RESULTS: Of the 105 enrolled children, 85 were adipose. Adipose children had higher systolic blood pressure, larger left ventricular (LV) mass, and adverse traditional metabolic biomarkers. FMD was significantly reduced (8.25 (5.32-12.06) % vs. 12.49 (7.18-16.58) %, p = 0.018) in the adipose group. PWV was markedly increased (4.65 (4.2-5.5) m/sec vs. 3.95 (3.38-4.35) m/sec, p < 0.001) in the hypertensive adipose children. Endothelial dysfunction parameters were not significantly changed in this study. CONCLUSION: Adipose children were at higher risk of hypertension and LV hypertrophy. FMD, PWV and traditional cardiovascular biomarkers can detect subtle vascular changes. Hypertension is an important sign of arterial involvement in adipose children. Although ADMA-related biomarkers were not statistically significant, future studies are needed to confirm its correlation with adiposity and hypertension in children. The early detection and prevention of endothelial dysfunction may decrease the rate of progression to cardiovascular consequences in later life.

Prenatal dexamethasone and postnatal high-fat diet have a synergistic effect of elevating blood pressure through a distinct programming mechanism of systemic and adipose renin-angiotensin systems.

BACKGROUND: Hypertension may result from high-fat (HF) diet induced-obesity and overexposure to glucocorticoids in utero. Recent studies demonstrated the potent contribution of adipose tissue's renin-angiotensin system (RAS) to systemic RAS, which plays a key role in regulating blood pressure (BP). In this study, we investigated the effects of prenatal dexamethasone (DEX) exposure and postnatal HF diet on RAS of adipose tissue. METHODS: RAS and BP of 6-month old rats exposed to prenatal DEX and/or postnatal HF diet were examined. RESULTS: Prenatal DEX plus postnatal HF exerted a synergistic effect on systolic BP. Prenatal DEX exposure suppressed plasma angiotensin (ANG) I and ANG II, whereas postnatal HF suppressed plasma ANG-(1-7) level. Prenatal DEX increased prorenin receptor and renin levels, but suppressed angiotensinogen (AGT) and angiotensin-converting-enzyme 1 (ACE1) mRNA expressions in adipose tissue. Postnatal HF increased AGT mRNA expression, but suppressed prorenin receptor, renin, ACE2, ANG II type 2 receptor (AT2R), and Mas receptor (MasR) mRNA expression levels. CONCLUSIONS: Prenatal GC exposure altered the ACE1/ANG II/ANG II type 1 receptor (AT1R) axis, whereas postnatal HF negatively impacted the ACE2/ANG-(1-7)/MasR axis. Prenatal DEX exposure and postnatal HF synergistically elevated BP through a distinct programming mechanism of systemic and adipose RAS. Adipose RAS might be a target for precise hypertension treatment.

Effectiveness of intravenous immunoglobulin alone and intravenous immunoglobulin combined with high-dose aspirin in the acute stage of Kawasaki disease: study protocol for a randomized controlled trial.

BACKGROUND: Kawasaki disease (KD) is an acute febrile systemic vasculitis most commonly seen in children under 5 years old. High-dose aspirin is often administered, but the duration of such treatment varies. Many centers reduce the aspirin dose once the patient is afebrile, even before treating said patient with intravenous immunoglobulin (IVIG). However, a randomized controlled trial regarding high-dose aspirin in the acute stage of KD has not previously been carried out. METHODS/DESIGN: This trial has been designed as a multi-center, prospective, randomized controlled, evaluator-blinded trial with two parallel groups to determine whether IVIG alone as the primary therapy in acute-stage KD is as effective as IVIG combined with high-dose aspirin therapy. The primary endpoint is defined as coronary artery lesion (CAL) formation at 6-8 weeks. Patients meeting the eligibility criteria are randomly assigned (1:1) to a test group (that receives only IVIG) or a standard group (that receives IVIG plus high-dose aspirin). This clinical trial is conducted at three medical centers in Taiwan. DISCUSSION: Since high-dose aspirin has significant anti-inflammatory and anti-platelet functions, it does not appear to affect disease outcomes. Furthermore, it can decrease hemoglobin levels. Therefore, we have initiated this randomized controlled trial to evaluate the necessity of high-dose aspirin in the acute stage of KD. TRIAL REGISTRATION: Kawasaki Disease Center, Kaohsiung Chang Gung Memorial Hospital, Taiwan. ClinicalTrials.gov Identifier: NCT02951234. Release Date: November 3, 2016.

Clinical utility and diagnostic accuracy of palm-held, mini-sized ultrasonocardiographic scanner in congenital heart disease.

BACKGROUND/PURPOSE: To investigate whether a palm-held ultrasonocardiographic scanner would be useful for screening and follow-up in congenital heart disease (CHD). METHODS: We retrospectively reviewed the echocardiographic images from June 1, 2014 to November 1, 2014. All patients underwent two ultrasonographic examinations including palm-held scanner examination and standard echocardiography. To compare the quality of the two instruments, we developed a diagnostic scoring system ranging from 1 point to 10 points, with 10 points indicating the best quality. Two experienced echocardiographers retrospectively reviewed all recorded images blindedly and gave each examination a score. Comparisons of diagnostic score between two equipments were performed. RESULTS: A total of 262 patients' images were reviewed. All cardiac lesions could be detected with both instruments. The mean diagnostic score of palm-held scanner and standard echocardiography were 8.20±0.53 versus 9.64±0.37 (p<0.05) in color image and 7.00±1.05 versus 8.56±1.14 (p<0.05) in gray-scale two-dimensional image, respectively. When we compared the score between the two instruments in individual CHDs, we found standard echocardiography had better quality except for detecting muscular ventricular septal defect and pulmonary regurgitation. CONCLUSION: The diagnostic sensitivity of palm-held scanner in detecting CHD was very good. Despite both instruments having a high diagnostic score in detecting CHD, standard echocardiography had better quality. Traditional echocardiography is still the standard tool for CHD evaluation. However, the palm-held scanner can support physical examination for initial screening and follow-up, and offer cardiologists an opportunity to visualize and listen to the heart at any time.

Age-Dependent Effects of Prenatal Dexamethasone Exposure on Immune Responses in Male Rats.

Prenatal glucocorticoid therapy is indicated in preterm delivery to prevent respiratory distress. This study was designed to evaluate the age-dependent effects of prenatal dexamethasone (DEX) therapy on the immune system using a rat model. Pregnant Sprague-Dawley rats received an intraperitoneal injection of DEX (0.1 mg/kg/day) or saline (VEH) over gestational days 14-20. Male offspring were sacrificed at postnatal day 7 (D7; infant stage), D120 (young adult stage), and D180 (adult stage) for evaluation of leukocyte subsets and isolation of splenocytes. The production of innate and adaptive immune cytokines was assessed from the culture supernatants of splenocytes, stimulated with lipopolysaccharide and concanavalin A, respectively. For innate cytokines, the levels of interferon gamma inducible protein 10 were significantly higher, but those of tumor necrosis factor-α were significantly lower, in the culture medium of splenocytes prepared from the DEX group at D120 than those in the VEH group. For adaptive cytokines, the levels of interleukin-4 (IL-4) were significantly higher at D7 and those of IL-10 were significantly higher at D120 after prenatal exposure to DEX. We also showed that the expression level of IL-4 mRNA was significantly higher in splenocytes prepared from the DEX group at D7, compared with the VEH group. Importantly, the mRNA expression level of T-bet, a key transcription factor for immune cells, was greatly decreased in the spleen of the DEX group at D7, compared with the VEH group. In conclusion, prenatal dexamethasone exposure shows the greater impact on immune responses of their male offspring in early life.

Application of desaturation index in post-surgery follow-up in children with obstructive sleep apnea syndrome.

Adenotonsillectomy is recommended for children who need surgery for obstructive sleep apnea syndrome (OSAS). Overnight, polysomnography (PSG) is suggested for post-surgery follow-up, but this diagnostic technique is time consuming and inconvenient. Desaturation index (DI) has been reported as a good tool for predicting both the presence and severity of OSAS in children. The purpose of this study was to determine the usefulness of the DI for post-surgery follow-up of children with OSAS. This retrospective study enrolled 42 children, aged 3-12 years, who were snorers diagnosed with OSAS by overnight PSG and who underwent an adenotonsillectomy. Pre- and postoperative PSG parameters, nocturnal pulse oximetry data, and modified Epworth sleepiness scale scores were assessed. Previously determined cut-off DI values (2.05, 3.50, and 4.15 for mild, moderate, and severe OSAS, respectively) were used to predict residual OSAS. Of the 42 children, obvious improvements were observed in apnea-hypopnea index (AHI, decreased 45.5 %), arousal index (decreased 30.5 %), DI (decreased 40.4 %), and snore index (decreased 100.3 %) compared with the preoperative measurements. Among these objective PSG measures, DI had the strongest correlation with AHI both pre- and post-surgeries (r = 0.947 and r = 0.954, respectively; p all <0.001). The DI change, before and after surgery, also had the strongest positive correlation to the AHI change (r = 0.482 and p = 0.001). Using the previously determined DI cut-off values to predict postoperative residual OSAS, there was a good positive predictive value (92.6 %) for mild residual OSAS and a good negative predictive value for moderate and severe residual OSAS (85.2 and 89.7 %, respectively). These findings suggest that DI, as determined using a nocturnal pulse oximeter, may be an alternative tool for postoperative evaluation and follow-up of children with OSAS.

Platelet Endothelial Cell Adhesion Molecule-1 Gene Polymorphisms are Associated with Coronary Artery Lesions in the Chronic Stage of Kawasaki Disease.

BACKGROUND: Kawasaki disease is the most common cause of pediatric acquired heart disease. The role of platelet endothelial cell adhesion molecule-1 in the inflammatory process has been documented. To date, no report has investigated the relationship between coronary artery lesions of Kawasaki disease and platelet endothelial cell adhesion molecule-1 polymorphisms. METHODS: A total of 114 Kawasaki disease children with coronary artery lesions and 185 Kawasaki disease children without coronary artery lesions were recruited in this study. The TaqMan assay was conducted to identify the genotype in this case-control study. RESULTS: In three single nucleotide polymorphisms (Leu125Val, Ser563Asn, and Arg670Gly) of platelet endothelial cell adhesion molecule-1, we found that the Leu-Ser-Arg haplotype was associated with a significantly increased risk for coronary artery lesions in the chronic stage (odds ratio 3.05, 95% confidence interval 1.06-8.80, p = 0.039), but not for coronary artery lesions in the acute stage. Analysis based on the diplotypes of platelet endothelial cell adhesion molecule-1 also showed that Kawasaki disease with one or two alleles of Leu-Ser-Arg had a significantly increased risk of chronic coronary artery lesions (odds ratio 3.38, 95% confidence interval 1.11-10.28, p = 0.032) and had increased platelet counts after Kawasaki disease was diagnosed, as compared to those with other diplotypes. CONCLUSIONS: The haplotype of platelet endothelial cell adhesion molecule-1 Leu-Ser-Arg might be associated with the increased platelet counts and the following risk of chronic coronary artery lesions in a dominant manner in Kawasaki disease.

An Acoustic Tracking Approach for Medical Ultrasound Image Simulator.

Ultrasound examinations are a standard procedure in the clinical diagnosis of many diseases. However, the efficacy of an ultrasound examination is highly dependent on the skill and experience of the operator, which has prompted proposals for ultrasound simulation systems to facilitate training and education in hospitals and medical schools. The key technology of the medical ultrasound simulation system is the probe tracking method that is used to determine the position and inclination angle of the sham probe, since this information is used to display the ultrasound images in real time. This study investigated a novel acoustic tracking approach for an ultrasound simulation system that exhibits high sensitivity and is cost-effective. Five air-coupled ultrasound elements are arranged as a 1D array in front of a sham probe for transmitting the acoustic signals, and a 5 × 5 2D array of receiving elements is used to receive the acoustic signals from the moving transmitting elements. Since the patterns of the received signals can differ for different positions and angles of the moving probe, the probe can be tracked precisely by the acoustic tracking approach. After the probe position has been determined by the system, the corresponding ultrasound image is immediately displayed on the screen. The system performance was verified by scanning three different subjects as image databases: a simple commercial phantom, a complicated self-made phantom, and a porcine heart. The experimental results indicated that the tracking and angle accuracies of the presented acoustic tracking approach were 0.7 mm and 0.5°, respectively. The performance of the acoustic tracking approach is compared with those of other tracking technologies.

Efficacy and Safety of Transthoracic Echocardiography Alone in Transcatheter Closure of Secundum-Type Atrial Septal Defects in Adults.

BACKGROUND: On-site transthoracic echocardiography (TTE) to guide the transcutaneous closure of secundum-type atrial septal defects (ASDs) in the catheterization laboratory remains unclear, especially in adults. METHODS: Between 2005 and 2012, a total of 82 adults underwent transcutaneous closure of ASDs. The initial 15 cases underwent the procedure with both on-site transesophageal echocardiography (TEE) and TTE monitoring. Since January 2008, a total of 67 patients underwent on-site TTE alone to guide the procedure. RESULTS: Among the 82 adult patients who underwent a transcutaneous closure of the secundum-type ASD procedure, all had successful closure of the defects, and no periprocedural adverse complications occurred. No statistical significance was observed in the successful complete shunt closure rate between the TEE plus TTE and TTE groups during sequential follow-up (postprocedure 24 hour [87% vs. 92%],1 month [93% vs. 95%], 3 month [93% vs. 97%], and 12 month [93% vs. 97%], P > 0.05, respectively) nor was a significant difference observed between the two groups, including decreased right ventricular dimension (29.5 ± 3.3 vs. 32.0 ± 4.9 mm, 26.5 ± 3.0 vs. 28.7 ± 4.6 mm, 26.2 ± 3.1 vs. 28.2 ± 4.8 mm, and 25.6 ± 2.8 vs. 27.7 ± 4.7 mm, P > 0.05, respectively) or increased left ventricular end-diastolic dimension (41.1 ± 2.0 vs. 42.6 ± 3.0 mm, 44.3 ± 2.7 vs. 45.5 ± 3.1 mm, 44.2 ± 2.8 vs. 45.4 ± 3.1 mm, 44.9 ± 2.7 vs. 45.8 ± 2.6 mm, P > 0.05, respectively) before the procedure, and at the 3-, 6-, and 12-month follow-up evaluations. CONCLUSION: This study showed that TTE guidance alone may be considered efficacious and safe as TEE during a transcutaneous ASD occlusion procedure in select adults.

Mid- to long-term follow-up of pediatric patients with coronary artery fistula.

BACKGROUND/PURPOSE: To investigate mid- to long-term outcomes in children with coronary artery fistula (CAF). METHODS: We retrospectively reviewed the medical records of patients seen between September 1996 and August 2011. We enrolled those diagnosed with CAF via echocardiography (Philips SONOS 7500 system and Philips IE33) or angiography. The mean follow time was 42.58 ± 3.4 months (range, 1-166 months). For comparative purposes, participants were grouped as acquired versus congenital, and symptomatic versus asymptomatic. We also measured the size of the coronary artery (CA) in patients with CA dilatation (CAD). RESULTS: Out of 122 CAF patients, spontaneous closure was detected in 37 patients at 21.59 ± 3.45 months after diagnosis. This timeframe did not differ between the acquired and congenital groups (21.64 ± 6.26 months vs. 21.57 ± 4.15 months; p = 0.991). Ninety patients were asymptomatic and remained so; their spontaneous closure rate was 28.89%. Moreover, 24 patients had CAD, including 17 with Kawasaki disease and seven with congenital CAF. The CAs of all congenital-CAF-plus-CAD patients were initially > 5 mm; these patients underwent percutaneous transcatheter intervention, and their CA sizes decreased significantly (6.11 ± 0.79 mm vs. 3.76 ± 0.36 mm; p = 0.002). CONCLUSION: With the advanced sensitivity of echocardiography, CAF can be detected more easily than ever before. Most patients with small CAFs are asymptomatic and may experience spontaneous closure. Therefore, management of CAF depends on symptoms; if patients are asymptomatic and have small CAFs, intervention may not be necessary, especially in acquired cases. However, if patients present with symptoms or persistent dilatation of the proximal CA, surgical or percutaneous closure should be performed.

Prenatal Dexamethasone and Postnatal High-Fat Diet Decrease Interferon Gamma Production through an Age-Dependent Histone Modification in Male Sprague-Dawley Rats.

Overexposure to prenatal glucocorticoid (GC) disturbs hypothalamic-pituitary-adrenocortical axis-associated neuroendocrine metabolism and susceptibility to metabolic syndrome. A high-fat (HF) diet is a major environmental factor that can cause metabolic syndrome. We aimed to investigate whether prenatal GC plus a postnatal HF diet could alter immune programming in rat offspring. Pregnant Sprague-Dawley rats were given intraperitoneal injections of dexamethasone or saline at 14-21 days of gestation. Male offspring were then divided into four groups: vehicle, prenatal dexamethasone exposure, postnatal HF diet (VHF), and prenatal dexamethasone exposure plus a postnatal HF diet (DHF). The rats were sacrificed and adaptive immune function was evaluated. Compared to the vehicle, the DHF group had lower interferon gamma (IFN-γ) production by splenocytes at postnatal day 120. Decreases in H3K9 acetylation and H3K36me3 levels at the IFN-γ promoter correlated with decreased IFN-γ production. The impaired IFN-γ production and aberrant site-specific histone modification at the IFN-γ promoter by prenatal dexamethasone treatment plus a postnatal HF diet resulted in resilience at postnatal day 180. Prenatal dexamethasone and a postnatal HF diet decreased IFN-γ production through a site-specific and an age-dependent histone modification. These findings suggest a mechanism by which prenatal exposure to GC and a postnatal environment exert effects on fetal immunity programming.

Hepcidin-Induced Iron Deficiency Is Related to Transient Anemia and Hypoferremia in Kawasaki Disease Patients.

Kawasaki disease (KD) is a type of systemic vasculitis that primarily affects children under the age of five years old. For sufferers of KD, intravenous immunoglobulin (IVIG) has been found to successfully diminish the occurrence of coronary artery lesions. Anemia is commonly found in KD patients, and we have shown that in appropriately elevated hepcidin levels are related to decreased hemoglobin levels in these patients. In this study, we investigated the time period of anemia and iron metabolism during different stages of KD. A total of 100 patients with KD and 20 control subjects were enrolled in this study for red blood cell and hemoglobin analysis. Furthermore, plasma, urine hepcidin, and plasma IL-6 levels were evaluated using enzyme-linked immunosorbent assay in 20 KD patients and controls. Changes in hemoglobin, plasma iron levels, and total iron binding capacity (TIBC) were also measured in patients with KD. Hemoglobin, iron levels, and TIBC were lower (p < 0.001, p = 0.009, and p < 0.001, respectively) while plasma IL-6 and hepcidin levels (both p < 0.001) were higher in patients with KD than in the controls prior to IVIG administration. Moreover, plasma hepcidin levels were positively and significantly correlated with urine hepcidin levels (p < 0.001) prior to IVIG administration. After IVIG treatment, plasma hepcidin and hemoglobin levels significantly decreased (both p < 0.001). Of particular note was a subsequent gradual increase in hemoglobin levels during the three weeks after IVIG treatment; nevertheless, the hemoglobin levels stayed lower in KD patients than in the controls (p = 0.045). These findings provide a longitudinal study of hemoglobin changes and among the first evidence that hepcidin induces transient anemia and hypoferremia during KD's acute inflammatory phase.

FCGR2A Promoter Methylation and Risks for Intravenous Immunoglobulin Treatment Responses in Kawasaki Disease.

Kawasaki disease (KD) is characterized by pediatric systemic vasculitis of an unknown cause. The low affinity immunoglobulin gamma Fc region receptor II-a (FCGR2A) gene was reported to be involved in the susceptibility of KD. DNA methylation is one of the epigenetic mechanisms that control gene expression; thus, we hypothesized that methylation status of CpG islands in FCGR2A promoter associates with the susceptibility and therapeutic outcomes of Kawasaki disease. In this study, 36 KD patients and 24 healthy subjects from out-patient clinic were recruited. Eleven potential methylation sites within the targeted promoter region of FCGR2A were selected for investigation. We marked the eleven methylation sites from A to K. Our results indicated that methylation at the CpG sites G, H, and J associated with the risk of KD. CpG sites B, C, E, F, H, J, and K were found to associate with the outcomes of IVIG treatment. In addition, CpG sites G, J, and K were predicted as transcription factors binding sites for NF-kB, Myc-Max, and SP2, respectively. Our study reported a significant association among the promoter methylation of FCGR2A, susceptibility of KD, and the therapeutic outcomes of IVIG treatment. The methylation levels of CpG sites of FCGR2A gene promoter should be an important marker for optimizing IVIG therapy.

Rapid spontaneous closure and remodelling of a medium-sized symptomatic congenital coronary artery fistula in an infant before the age of 3 months.

It is controversial to observe or close symptomatic congenital coronary artery fistula in infants. We herein describe a medium-sized symptomatic congenital coronary artery fistula that underwent rapid spontaneous closure in an infant aged <3 months.

Virtual-Reality Simulator System for Double Interventional Cardiac Catheterization Using Fractional-Order Vascular Access Tracker and Haptic Force Producer.

This study proposes virtual-reality (VR) simulator system for double interventional cardiac catheterization (ICC) using fractional-order vascular access tracker and haptic force producer. An endoscope or a catheter for diagnosis and surgery of cardiovascular disease has been commonly used in minimally invasive surgery. It needs specific skills and experiences for young surgeons or postgraduate year (PGY) students to operate a Berman catheter and a pigtail catheter in the inside of the human body and requires avoiding damaging vessels. To improve the training in inserting catheters, a double-catheter mechanism is designed for the ICC procedures. A fractional-order vascular access tracker is used to trace the senior surgeons' consoled trajectories and transmit the frictional feedback and visual feedback during the insertion of catheters. Based on the clinical feeling through the aortic arch, vein into the ventricle, or tortuous blood vessels, haptic force producer is used to mock the elasticity of the vessel wall using voice coil motors (VCMs). The VR establishment with surgeons' consoled vessel trajectories and hand feeling is achieved, and the experimental results show the effectiveness for the double ICC procedures.