Electrocardiographic Diagnosis of Hypertrophic Cardiomyopathy in the Pre- and Post-Diagnostic Phases in Children and Adolescents.

BACKGROUND: The usefulness of electrocardiographic (ECG) voltage criteria for diagnosing hypertrophic cardiomyopathy (HCM) in pediatric patients is poorly defined.Methods and Results:ECGs at the 1st grade (mean [±SD] age 6.6±0.3 years) were available for 11 patients diagnosed with HCM at around the 7th grade (13.2±0.3 years). ECGs were available for another 64 patients diagnosed with HCM in the 1st (n=15), 7th (n=32), and 10th (n=17) grades. Fifty-one voltage criteria were developed by grade and sex using 62,841 ECGs from the general population. Voltage criteria were set at the 99.95th percentile (1/2,000) point based on the estimated prevalence of childhood HCM (2.9 per 100,000 [1/34,483]) to decrease false negatives. Conventional criteria were from guidelines for school-aged children in Japan. Of 11 patients before diagnosis, 2 satisfied conventional criteria in 1st grade; 5 (56%) of the remaining 9 patients fulfilled 2 voltage criteria (R wave in limb-lead I [RI]+S wave in lead V3 [SV3] and R wave in lead V3 [RV3]+SV3). Robustness analysis for sensitivity showed RV3+SV3 was superior to RI+SV3. For all patients after diagnosis, RI+SV4 was the main candidate. However, conventional criteria were more useful than voltage criteria. CONCLUSIONS: Early HCM prediction was possible using RV3+SV3 in >50% of patients in 1st grade. Voltage criteria may help diagnose prediagnostic or early HCM, and prevent tragic accidents, although further prospective studies are required.

Decreased Stroke Volume and Venous Return in School Children with Postural Tachycardia Syndrome.

In postural tachycardia syndrome (POTS), a subtype of orthostatic intolerance, the changes in hemodynamics due to postural changes are poorly understood. We speculated that inappropriate venous return, which may occur in the upright position in patients with school-aged POTS, could be detected by echocardiography. Our prospective study was conducted with 100 POTS patients (45 boys and 55 girls), aged 13.1 ± 1.5 years and 52 age- and sex-matched healthy subjects (control). Echocardiography was performed in the supine and sitting positions. Cardiac parameters [stroke volume index, cardiac index, heart rate, and the maximum inferior vena cava diameter (max IVC)] were evaluated in addition to pulse pressure. Unlike the control subjects, POTS patients demonstrated decreased stroke volume index (P = 0.02) and max IVC (P < 0.01) irrespective of posture. The rates of max IVC change did not differ between control and POTS groups. The enrolled POTS patients were divided into two subgroups [dilatation (n = 57) and contraction (n = 43)] based on whether the change rate of max IVC was less than zero or not. The contraction group showed a significantly higher heart rate than the dilatation group with respect to posture (P = 0.03), indicating the poor response of peripheral vessels in the lower limbs only in the contraction group. In conclusion, echocardiographic assessment detected decreased stroke volume and venous return in POTS. The changes in max IVC in response to postural changes may indicate an underlying pathophysiology in POTS.

Normal reference values for left atrial strains and strain rates in school children assessed using two-dimensional speckle-tracking echocardiography.

Left atrium (LA) function is a known predictive marker of heart failure in adults. Few reports of LA function analyses using LA strain (ɛ) and strain rate (SR) measurements in children exist. Thus, this study aimed to determine normal reference values for LA ɛ and SR in healthy school children and to investigate methods of interpreting LA function data based on maturational changes using two-dimensional speckle-tracking echocardiography (2DSTE). We recruited 112 healthy school children (median age 12.0 years; range 6-16 years). LA ɛ and SR were investigated using 2DSTE multi-vendor analysis software (TomTec Imaging Systems, Germany) and compared to Doppler parameters and LA volumes measured by the conventional method. The onset of the P wave was selected as the reference point for the LA ɛ analysis. Normal ranges of LA ɛ [reservoir (ɛRS), conduit (ɛCD), or contractile (ɛCT)] and positive SR (SRPOS), early negative SR (SREN), and late negative SR (SRLN) were obtained using Z-score models via the lambda-mu-sigma method. According to the Z-score curves, all ɛ showed slight falling or continuous flat lines against age, body surface area (BSA), or heart rate (HR); however, ɛ CT showed modestly positive associations with HR. As for SR, the Z-score curves showed falling lines against age and BSA. In contrast, Z-score curves for SREN and SRLN showed rising lines against HR. SREN was independent of E/e' and was negatively correlated with LA volume indexed against BSA. This study demonstrated the normal reference values for LA ɛ and SR using 2DSTE in school children. The present results recommended that LA ɛ should be evaluated together with changes in LA SR for accurate assessment, considering maturational changes including age, BSA, and HR in school children.

Safety and accuracy of the Rhythmia mapping system in pediatric patients.

BACKGROUND: A new mapping system (Rhythmia) using a 64 mini-electrode small basket array (Orion) was developed that enables rapid high-density mapping in a short time. However, there are few reports about the usefulness of this system in pediatric cases. OBJECTIVE: The purpose of this study was to investigate the safety and accuracy of the Rhythmia system and Orion catheter in children. METHODS: Catheter ablation was performed using the Rhythmia system and Orion catheter in 23 patients younger than 20 years (body weight >20 kg) without a past medical history of cardiac disease. Mapping time, number of mapping beats, and number of mapping electrodes were compared for left atrium, right atrium and right ventricular outflow tract. RESULTS: Twenty-three maps of the right atrium were acquired in 12.6 minutes (range 8.9-15.1), consisting of 709 beats (range 492-1163) and 7132 electrograms (range 4618-10,533). Twelve maps of the left atrium were acquired in 12.1 minutes (range 9.8-14.6), consisting of 565 beats (range 446-881) and 6412 electrograms (range 4912-11,402). There were no significant difference in mapping time, accepted beats, and electrograms between the 2 chambers. Manual annotation was needed in 53 of 293,185 electrograms (0.01%) due to far-field ventricular electrogram sensing and artifact. No adverse events occurred in any of the cases. CONCLUSION: The Orion catheter and Rhythmia mapping system were safe and accurate for mapping various arrhythmias in pediatric patients. Detailed geometry and high-resolution activation mapping were acquired without the need for manual reannotation.

Appropriate use of a beta-blocker in paediatric coronary CT angiography.

BACKGROUND: There is no standard dose or protocol for beta-blocker administration as preconditioning in children undergoing coronary CT angiography. METHODS: A total of 63 consecutive patients, with a mean age of 10.0±3.1 years, who underwent coronary CT angiography to assess possible coronary complications were enrolled in a single-centre, retrospective study. All patients were given an oral beta-blocker 1 hour before coronary CT angiography. Additional oral beta-blocker or intravenous beta-blocker was given to those with a high heart rate. We compared image quality, radiation exposure, and adverse events among the patients without additional beta-blocker, with additional oral beta-blocker, and with additional intravenous beta-blocker. RESULTS: There were no significant differences in image quality or radiation exposure among the groups. The heart rate just before scanning was significantly correlated with image quality (p<0.001, r=-0.533) but was not correlated with radiation exposure (p=0.45, r=0.096). There were no adverse events related to any allergic reaction, thereby showing the effectiveness of the beta-blocker. CONCLUSION: Initial oral beta-blocker administration (0.8 mg/kg/dose) should be administered to all children undergoing coronary CT angiography. Additional intravenous beta-blocker should be given to those with poor heart rate control to improve image quality without increasing radiation exposure or allowing adverse events.

Recent updates on echocardiography and ultrasound for Kawasaki disease: beyond the coronary artery.

Kawasaki disease (KD) is a systemic vasculitis with a predilection for damage to the coronary arteries. In the acute phase, clinical decision making for KD relies on the measurements of the coronary z-score obtained by 2-dimensional echocardiography (2DE). In the convalescent phase, KD patients with coronary artery abnormalities (CAAs) eventually show arteriosclerotic vascular remodeling characterized by marked intimal proliferation and neoangiogenesis after KD vasculitis, which often induces myocardial ischemia. To date, several well-established surrogate markers including dobutamine stress echocardiography (DSE), the carotid intima-media thickness (CIMT) and flow-mediated dilatation (FMD), have been made available for risk assessment and the prediction of cardiovascular disease (CVD) in KD patients. Additionally, the use of carotid contrast-enhanced ultrasonography (CEUS), has enabled the visualization and quantification of the adventitial vasa vasorum (VV) network, assessing active vascular remodeling at remote arterial sites in KD patients with CAAs. However, there was no evidence of major vascular structural changes in KD patients in whom CAAs had never been detected. Thus, assessment of multiple modalities using 2DE may provide direct information not only on the vascular health but also on the stratification of the risk of CVD in KD patients with CAAs.

Association of Severity of Coronary Artery Aneurysms in Patients With Kawasaki Disease and Risk of Later Coronary Events.

Importance: Few studies with sufficient statistical power have shown the association of the z score of the coronary arterial internal diameter with coronary events (CE) in patients with Kawasaki disease (KD) with coronary artery aneurysms (CAA). Objective: To clarify the association of the z score with time-dependent CE occurrence in patients with KD with CAA. Design, Setting, and Participants: This multicenter, collaborative retrospective cohort study of 44 participating institutions included 1006 patients with KD younger than 19 years who received a coronary angiography between 1992 and 2011. Main Outcomes and Measures: The time-dependent occurrence of CE, including thrombosis, stenosis, obstruction, acute ischemic events, and coronary interventions, was analyzed for small (z score, <5), medium (z score, ≥5 to <10; actual internal diameter, <8 mm), and large (z score, ≥10 or ≥8 mm) CAA by the Kaplan-Meier method. The Cox proportional hazard regression model was used to identify risk factors for CE after adjusting for age, sex, size, morphology, number of CAA, resistance to initial intravenous immunoglobulin (IVIG) therapy, and antithrombotic medications. Results: Of 1006 patients, 714 (71%) were male, 341 (34%) received a diagnosis before age 1 year, 501 (50%) received a diagnosis between age 1 and 5 years, and 157 (16%) received a diagnosis at age 5 years or older. The 10-year event-free survival rate for CE was 100%, 94%, and 52% in men (P < .001) and 100%, 100%, and 75% in women (P < .001) for small, medium, and large CAA, respectively. The CE-free rate was 100%, 96%, and 79% in patients who were not resistant to IVIG therapy (P < .001) and 100%, 96%, and 51% in patients who were resistant to IVIG therapy (P < .001), respectively. Cox regression analysis revealed that large CAA (hazard ratio, 8.9; 95% CI, 5.1-15.4), male sex (hazard ratio, 2.8; 95% CI, 1.7-4.8), and resistance to IVIG therapy (hazard ratio, 2.2; 95% CI, 1.4-3.6) were significantly associated with CE. Conclusions and Relevance: Classification using the internal diameter z score is useful for assessing the severity of CAA in relation to the time-dependent occurrence of CE and associated factors in patients with KD. Careful management of CE is necessary for all patients with KD with CAA, especially men and IVIG-resistant patients with a large CAA.

Cardiac function on 3-D speckle tracking imaging and cytokines in Kawasaki disease.

BACKGROUND: Serum N-terminal pro-brain natriuretic peptide (NT-proBNP) tends to rise in acute phase Kawasaki disease (KD), but the cause of NT-proBNP elevation has not been clarified. In a previous study, cardiac function evaluated on 2-D echocardiography (2D-E) such as ejection fraction was normal, but this does not reflect subtle changes in cardiac dysfunction, and hence the association between cardiac function and NT-proBNP elevation is still controversial. The aim of this study was therefore to elucidate the influence of cardiac function on NT-proBNP elevation, by evaluating cardiac function via strain on 3-D speckle tracking imaging (3D-STI), in acute and subacute KD patients. Given that cytokines are also thought to induce NT-proBNP in acute phase KD, serum cytokines and cytokine receptors were measured at the same time. METHODS: Laboratory data and echocardiography in 52 KD patients in the acute and subacute phases were reviewed. RESULTS: Median NT-proBNP was significantly elevated in the acute phase compared with the subacute phase (356.5 pg/mL; IQR, 145-904 pg/mL vs 103.5 pg/mL; IQR, 59-150 pg/mL, P < 0.01). All cytokines were also significantly elevated in the acute phase compared with the subacute phase. Tumor necrosis factor (TNF)-α, soluble TNF receptor (sTNFR)1, and sTNFR2 concentration were all significantly higher in the acute phase. Indices of cardiac function were not significant different between phases. NT-proBNP in the acute and subacute phases correlated with sTNFR1 (r = 0.63/0.43, P < 0.01), sTNFR2 (r = 0.50/0.31, P < 0.05), and interleukin-6 (r = 0.58/0.43, P < 0.01). NT-proBNP did not correlate with global longitudinal strain (GLS) on 3D-STI. CONCLUSION: Although no correlation was seen between NT-proBNP and GLS on 3D-STI, correlations between NT-proBNP and cytokines were clear. NT-proBNP might be a marker of inflammation in KD, but is not a marker of cardiac function.

A Combination Therapy for Kawasaki Disease with Severe Complications: a Case Report.

Kawasaki disease (KD) is a form of acute multisystem vasculitis that presents with various complications, including coronary artery aneurysm. Heart failure and brain damage are rare, but life-threatening complications are associated with KD. Here, we describe a 4-year-old girl who developed intravenous immunoglobulin-resistant KD with both left ventricular failure and acute encephalopathy. On day 8 of the illness, the low left ventricular ejection fraction, mitral regurgitation, and low blood pressure, which required continuous administration of dobutamine, were observed during the treatments for KD, including intravenous immunoglobulin. She also appeared unconscious, where the electroencephalogram showed slow waves of activity in all regions of the brain. The cardiac performance improved after she received plasma exchange for three days. However, her unconsciousness with slow waves of activity on electroencephalogram and fever continued after the plasma exchange. Therefore, she was treated with methylprednisolone pulse, followed by prednisolone, as well as intravenous immunoglobulin. Finally, she recovered without any cardiac or neurological sequelae not only at the time she was discharged, but also throughout the follow-up period. The combination therapy using plasma exchange and methylprednisolone pulse may be a treatment option for severe KD with left ventricular failure and acute encephalopathy complications.

Factors affecting N-terminal pro-brain natriuretic peptide elevation in the acute phase of Kawasaki disease.

BACKGROUND: The aim of this study was to investigate the clinical significance and factors that affect N-terminal pro-brain natriuretic peptide (NT-proBNP) elevation in the acute phase of Kawasaki disease (KD) despite the absence of apparent cardiac complications. METHODS: The laboratory and echocardiography results of 44 KD patients in the acute and subacute phases were reviewed. RESULTS: With preserved cardiac function, median NT-proBNP was significantly elevated in the acute phase compared with the subacute phase (343 pg/mL, IQR, 162-1182 pg/mL vs 98 pg/mL, IQR, 61-205 pg/mL, respectively; P < 0.0001). The respective levels of tumor necrosis factor (TNF)-α, soluble TNF receptor (sTNFR)1, and sTNFR2 were also significantly elevated in the acute phase compared with the subacute phase: TNF-α, 3.3 pg/mL (IQR, 2.6-4.8 pg/mL) versus 2.4 pg/mL (IQR 1.9-4.0 pg/mL; P < 0.01), sTNFR1, 2741 pg/mL (IQR, 2080-3183 pg/mL) versus 976 pg/mL (IQR, 814-1247 pg/mL; P < 0.0001), sTNFR2, 5644 pg/mL (IQR, 4693-7520 pg/mL) versus 3169 pg/mL (IQR, 2132-3878 pg/mL; P < 0.0001). Log-transformed NT-proBNP was correlated with TNF-α (r = 0.29, P = 0.056), sTNFR1 (r = 0.60, P < 0.0001), and sTNFR2 (r = 0.65, P < 0.0001). TNF-α was correlated with sTNFR1 (r = 0.35, P = 0.02) and sTNFR2 (r = 0.51, P < 0.001). CONCLUSION: Tumor necrosis factor-α may cause NT-proBNP elevation in the acute phase of KD, and NT-proBNP level may be an indicator of TNF-α activity.

Idiopathic pulmonary hemosiderosis complicated by Down syndrome.

We report the case of a 9-year-old girl with Down syndrome (DS) diagnosed with idiopathic pulmonary hemosiderosis (IPH). Although acute pneumonia complicated by hemolytic anemia was suspected, IPH was finally diagnosed on bronchoscopy. Treatment with prednisolone achieved good clinical response. An association between IPH and DS was not able to be identified, but immunological issues in DS may contribute to the onset of IPH. Recurrent and intractable respiratory symptoms with marked infiltrative shadows in the bilateral lungs and complicated by severe anemia in patients with DS should suggest IPH.

Efficacy of hemodynamic-based management of tachyarrhythmia after repair of tetralogy of Fallot.

BACKGROUND: Supraventricular and ventricular tachyarrhythmias (SVT, VT) are major concerns after repair of tetralogy of Fallot (TOF). This study evaluated the impact of comprehensive treatment, including hemodynamic interventions such as surgery, catheter-based intervention and pacemaker implantation (PMI), on tachyarrhythmia in repaired TOF patients. METHODS AND RESULTS: Of 66 repaired TOF patients with tachyarrhythmia (age at onset, 23±11 years), 29 patients had sustained SVT, 21 had sustained or non-sustained VT, and 16 had both (SVT+VT). Successful treatment with catheter-directed ablation and/or anti-arrhythmic drugs (AADs) alone was achieved in 31 (69%) and partially achieved in 6 (13%) of 45 patients. Surgery, catheter-based intervention, and/or PMI were performed in 21 (32%) of 66 patients and resulted in complete control of the arrhythmia in 8 (38%) and partial control in 7 (33%) of these 21 patients, 20 (95%) of whom were receiving AADs. Patients with successfully controlled tachyarrhythmia in response to catheter ablation and/or AADs without hemodynamic intervention had a significantly higher probability of absence of sinus node dysfunction (odds ratio [OR], 23.2; 95% confidence interval [CI], 1.8-845.2; P=0.02) and lone intra-atrial reentrant tachycardia (OR, 12.4; 95% CI: 1.3-278.7; P=0.03). CONCLUSIONS: Hemodynamic interventions resulted in an improvement in outcomes in repaired TOF patients with tachyarrhythmia. To effectively manage intractable tachyarrhythmia with hemodynamic abnormalities, it is essential to understand hemodynamics and consider hemodynamic intervention.

The follow-up evaluation of electrocardiogram and arrhythmias in children with fulminant myocarditis.

BACKGROUND: Fulminant myocarditis involves various serious arrhythmias that sometimes have lethal consequences. The purpose of the present study was to investigate the electrocardiogram findings, arrhythmogenicity and abnormalities of the cardiac conduction system in children with fulminant myocarditis. METHODS AND RESULTS: Between 1999 and 2008, 7 consecutive patients (mean age: 7 years) who suffered from fulminant myocarditis were included in the study. A 12-lead electrocardiogram, Holter monitoring and signal-averaged electrocardiograms were performed and compared between the acute, convalescent, and recovery phases in the 4 surviving patients. Also, electrophysiologic assessment was carried out during the convalescent phase. Five out of 7 patients developed complete atrioventricular block, 3 developed ventricular tachycardia, 2 had cardiac arrest, 2 developed sinus tachycardia, 1 developed ventricular fibrillation, 1 had advanced atrioventricular block, and 1 developed sick sinus syndrome. Among the surviving patients, all arrhythmias resolved during the convalescent and remote phases. No atrial or ventricular arrhythmias were induced in any patients during the programmed stimulation study. In the convalescent phase, no arrhythmias could be induced and there were no signs of any conduction abnormalities on electrophysiological assessment. CONCLUSIONS: Close follow-up should be performed to observe for the occurrence of any new arrhythmias and/or a decrease in cardiac function in children with fulminant myocarditis.

Effects of miglitol, an alpha-glucosidase inhibitor, on glycaemic status and histopathological changes in islets in non-obese, non-insulin-dependent diabetic Goto-Kakizaki rats.

Miglitol, a 1-deoxynojirimycin derivative, is an alpha-glucosidase inhibitor. In the present study, the effects of acute (single-dose) and chronic (8-week) oral administration of miglitol in Goto-Kakizaki (GK) rats, an animal model of type 2 diabetes, were investigated. Dose-dependent decreases in incremental blood glucose concentrations integrated over a period of 2 h (deltaAUC0-2 h) for values of blood glucose after sucrose-loading in miglitol-treated GK rats were observed following an acute oral administration of miglitol (1, 3 or 10 mg/kg body weight). At 10 mg/kg, the deltaAUC0-2 h of blood glucose was decreased by 45 % compared with the control group. Following the oral administration of miglitol in a dietary mixture (10 mg, 20 mg or 40 mg miglitol/100 g control diet) for 8 weeks, the ratio of HbA1c at 8 weeks compared with 0 weeks in GK rats treated with 40 mg miglitol/100 g control diet miglitol was significantly decreased compared with control GK rats without changes in body weight. In oral glucose tolerance testing, miglitol caused a slight decrease in the deltaAUC0-2 h of plasma glucose concentration. In addition, miglitol treatment slightly inhibited the reduction in beta-cell mass, and lessened the irregular contours and fibrosis of the islets in GK rats. These results indicate that miglitol ameliorates the hyperglycaemic state of GK rats and the impaired function of the pancreatic islets, as well as preventing the degeneration of islets in GK rats.