Lung sound analysis for predicting recurrent wheezing in preschool children.

Background: In young healthy children, assessing airflow limitation may be difficult because of narrowing of the airways, which is a pathology of asthma, and responsiveness to bronchodilators. Objective: We investigated whether lung sound analysis could predict the development of recurrent wheezing (RW), which is one of the signs of asthma. Methods: In healthy children aged 3 to 24 months, we recorded and analyzed lung sounds before and after inhalation of bronchodilators and conducted a questionnaire survey. The children were followed up and assessed for the development of RW at age 3 years. Results: Of the 62 patients analyzed, 19 (30.6%) developed RW. The parameters ratio of power and frequency at 50% of the highest frequency of the dB power spectrum (RPF50) and ratio of power and frequency at 75% of the highest frequency of the dB power spectrum (RPF75), calculated by lung sound analysis, were lower in the RW group, with odds ratios of 0.77 (95% CI = 0.61-0.98) and 0.81 (95% CI = 0.66-0.99), respectively. The rate of change of lung sound analysis parameters after bronchodilator inhalation did not differ among the participants as a group; however, in the subgroup of children with a history of atopic dermatitis, the fourth area under the curve (B4) divided by the total area under the curve of 100 Hz to the highest frequency of the dB power spectrum (AT) and difference between the values of the ratio of power and frequency at 50% of the highest frequency of the dB power spectrum (ΔRPF50) were elevated in the RW group (P = .015 and P = .041, respectively). In the subgroup of children with total a IgE level greater than 20 kUA/L, the sensitivities and specificities for predicting the development of RW were 85.7% (95% CI = 48.7-99.3) and 68.8% (95% CI = 44.4-85.8), respectively, when the cutoff value of ΔRPF50 was set at 10.5%. Conclusion: The method of lung sound analysis allows noninvasive assessment of the airway, including airway hypersensitivity, in young children and may predict the risk of development of RW.

Non-missense variants of KCNH2 show better outcomes in type 2 long QT syndrome.

AIMS: More than one-third of type 2 long QT syndrome (LQT2) patients carry KCNH2 non-missense variants that can result in haploinsufficiency (HI), leading to mechanistic loss-of-function. However, their clinical phenotypes have not been fully investigated. The remaining two-thirds of patients harbour missense variants, and past studies uncovered that most of these variants cause trafficking deficiency, resulting in different functional changes: either HI or dominant-negative (DN) effects. In this study, we examined the impact of altered molecular mechanisms on clinical outcomes in LQT2 patients. METHODS AND RESULTS: We included 429 LQT2 patients (234 probands) carrying a rare KCNH2 variant from our patient cohort undergoing genetic testing. Non-missense variants showed shorter corrected QT (QTc) and less arrhythmic events (AEs) than missense variants. We found that 40% of missense variants in this study were previously reported as HI or DN. Non-missense and HI-groups had similar phenotypes, while both exhibited shorter QTc and less AEs than the DN-group. Based on previous work, we predicted the functional change of the unreported variants-whether they cause HI or DN via altered functional domains-and stratified them as predicted HI (pHI)- or pDN-group. The pHI-group including non-missense variants exhibited milder phenotypes compared to the pDN-group. Multivariable Cox model showed that the functional change was an independent risk of AEs (P = 0.005). CONCLUSION: Stratification based on molecular biological studies enables us to better predict clinical outcomes in the patients with LQT2.

Novel Calmodulin Variant p.E46K Associated With Severe Catecholaminergic Polymorphic Ventricular Tachycardia Produces Robust Arrhythmogenicity in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes.

BACKGROUND: CaM (calmodulin) is a ubiquitously expressed, multifunctional Ca2+ sensor protein that regulates numerous proteins. Recently, CaM missense variants have been identified in patients with malignant inherited arrhythmias, such as long QT syndrome and catecholaminergic polymorphic ventricular tachycardia (CPVT). However, the exact mechanism of CaM-related CPVT in human cardiomyocytes remains unclear. In this study, we sought to investigate the arrhythmogenic mechanism of CPVT caused by a novel variant using human induced pluripotent stem cell (iPSC) models and biochemical assays. METHODS: We generated iPSCs from a patient with CPVT bearing CALM2 p.E46K. As comparisons, we used 2 control lines including an isogenic line, and another iPSC line from a patient with long QT syndrome bearing CALM2 p.N98S (also reported in CPVT). Electrophysiological properties were investigated using iPSC-cardiomyocytes. We further examined the RyR2 (ryanodine receptor 2) and Ca2+ affinities of CaM using recombinant proteins. RESULTS: We identified a novel de novo heterozygous variant, CALM2 p.E46K, in 2 unrelated patients with CPVT accompanied by neurodevelopmental disorders. The E46K-cardiomyocytes exhibited more frequent abnormal electrical excitations and Ca2+ waves than the other lines in association with increased Ca2+ leakage from the sarcoplasmic reticulum via RyR2. Furthermore, the [3H]ryanodine binding assay revealed that E46K-CaM facilitated RyR2 function especially by activating at low [Ca2+] levels. The real-time CaM-RyR2 binding analysis demonstrated that E46K-CaM had a 10-fold increased RyR2 binding affinity compared with wild-type CaM which may account for the dominant effect of the mutant CaM. Additionally, the E46K-CaM did not affect CaM-Ca2+ binding or L-type calcium channel function. Finally, antiarrhythmic agents, nadolol and flecainide, suppressed abnormal Ca2+ waves in E46K-cardiomyocytes. CONCLUSIONS: We, for the first time, established a CaM-related CPVT iPSC-CM model which recapitulated severe arrhythmogenic features resulting from E46K-CaM dominantly binding and facilitating RyR2. In addition, the findings in iPSC-based drug testing will contribute to precision medicine.

Efficacy of SubcutAneous implantable cardioVErter-defibrillators in ≤18 year-old CHILDREN: SAVE-CHILDREN registry.

BACKGROUND: In adult patients, subcutaneous implantable cardioverter defibrillators (S-ICDs) have been reported to be non-inferior to transvenous ICDs with respect to the incidence of device-related complications and inappropriate shocks. Only a few reports have investigated the efficacy of S-ICDs in the pediatric field. This study aimed to investigate the utility and safety of S-ICDs in patients ≤18 years old. METHODS: This study was a multicenter, observational, retrospective study on S-ICD implantations. Patients <18 years old who underwent S-ICD implantations were enrolled. The detailed data on the device implantations and eligibility tests, incidence of appropriate- and inappropriate shocks, and follow-up data were assessed. RESULTS: A total of 62 patients were enrolled from 30 centers. The patients ranged in age from 3 to 18 (median 14 years old [IQR 11.0-16.0 years]). During a median follow up of 27 months (13.3-35.8), a total of 16 patients (26.2%) received appropriate shocks and 13 (21.3%) received inappropriate shocks. The common causes of the inappropriate shocks were sinus tachycardia (n = 4, 30.8%) and T-wave oversensing (n = 4, 30.8%). In spite of the physical growth, the number of suitable sensing vectors did not change during the follow up. No one had any lead fractures or device infections in the chronic phase. CONCLUSIONS: Our study suggested that S-ICDs can prevent sudden cardiac death in the pediatric population with a low incidence of lead complications or device infections. The number of suitable sensing vectors did not change during the patients' growth.

Disrupted CaV1.2 selectivity causes overlapping long QT and Brugada syndrome phenotypes in the CACNA1C-E1115K iPS cell model.

BACKGROUND: A missense mutation in the α1c subunit of voltage-gated L-type Ca2+ channel-coding CACNA1C-E1115K, located in the Ca2+ selectivity site, causes a variety of arrhythmogenic phenotypes. OBJECTIVE: We aimed to investigate the electrophysiological features and pathophysiological mechanisms of CACNA1C-E1115K in patient-specific induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs). METHODS: We generated iPSCs from a patient carrying heterozygous CACNA1C-E1115K with overlapping phenotypes of long QT syndrome, Brugada syndrome, and mild cardiac dysfunction. Electrophysiological properties were investigated using iPSC-CMs. We used iPSCs from a healthy individual and an isogenic iPSC line corrected using CRISPR-Cas9-mediated gene editing as controls. A mathematical E1115K-CM model was developed using a human ventricular cell model. RESULTS: Patch-clamp analysis revealed that E1115K-iPSC-CMs exhibited reduced peak Ca2+ current density and impaired Ca2+ selectivity with an increased permeability to monovalent cations. Consequently, E1115K-iPSC-CMs showed decreased action potential plateau amplitude, longer action potential duration (APD), and a higher frequency of early afterdepolarization compared with controls. In optical recordings examining the antiarrhythmic drug effect, late Na+ channel current (INaL) inhibitors (mexiletine and GS-458967) shortened APDs specifically in E1115K-iPSC-CMs. The AP-clamp using a voltage command obtained from E1115K-iPSC-CMs with lower action potential plateau amplitude and longer APD confirmed the upregulation of INaL. An in silico study recapitulated the in vitro electrophysiological properties. CONCLUSION: Our iPSC-based analysis in CACNA1C-E1115K with disrupted CaV1.2 selectivity demonstrated that the aberrant currents through the mutant channels carried by monovalent cations resulted in specific action potential changes, which increased endogenous INaL, thereby synergistically contributing to the arrhythmogenic phenotype.

Characteristics of Breath Sounds During Methacholine-induced Bronchoconstriction in Children with Asthma.

OBJECTIVE: The utility of an analysis of breath sounds as a non-invasive lung function test in children and adults has been studied. Analyzing specific breath sounds during methacholine inhalation challenge is useful for evaluating airway constriction in asthmatic patients. PATIENTS AND METHODS: The study population included 57 children with atopic asthma (male: female = 38: 19; median age, 10 years [range, 5-16 years]). The breath sound spectrum was measured before a methacholine inhalation test, just after the methacholine inhalation challenge and after ß2 agonist inhalation. The values of breath sound parameters were analyzed and the direct changes of the sound spectrum during methacholine inhalation challenge were evaluated. RESULTS: The values of breath sound parameters, RPF75 and RPF50, were significantly decreased after methacholine inhalation (P < 0.001, p < 0.001, respectively), indicationg bronchoconstriction, and increased after ß2 agonist inhalation (P < 0.001, p < 0.001, respectively), indicating bronchodilation. The high-pitch area of the sound spectrum curve around 1,500 Hz was significantly increased after methacholine inhalation (P < 0.001). The values returned to the baseline level after ß2 agonist inhalation. CONCLUSIONS: Bronchoconstriction by methacholine inhalation induced a reversible high-pitch sound. The assessment of changes in the high-pitch area of the breath sound spectrum may be useful for the detection of airway narrowing in asthmatic patients.

Association Between Deleterious SCN5A Variants and Ventricular Septal Defect in Young Patients With Brugada Syndrome.

OBJECTIVES: This study aimed to investigate the clinical characteristics of young patients with Brugada syndrome (BrS) with ventricular septal defect (VSD) and explore their genetic backgrounds. BACKGROUND: VSD is the most frequently occurring congenital heart disease among children. In contrast, BrS is a rare hereditary disease that is responsible for ventricular fibrillation and sudden cardiac death. Owing to their low incidence, the genetic background and clinical characteristics of patients with BrS with VSD have not been elucidated yet. METHODS: This study enrolled 36 individuals who were diagnosed with BrS when they were <20 years of age and performed genetic screening for SCN5A. The functional alteration in mutant Na+ channels was confirmed by patch clamp technique. RESULTS: Among the 36 patients with BrS, 5 had been diagnosed with VSD. This study found 14 heterozygous SCN5A variants in 15 unrelated patients. The 5 patients with VSD carried SCN5A variants, including R367S, R535∗, R893C, W1345C, and G1743R. The 3 missense variants (R893C, W1345C, and G1743R) have been proved to reduce peak Na+ current to <10%. A functional analysis of SCN5A R367S was performed and the variant was found to be nonfunctional. CONCLUSIONS: This study identified 5 loss-of-function SCN5A variants in 5 young patients with BrS with VSD. The study hypothesizes that altered blood flow in the right ventricular outflow tract leads to fibrosis and electrophysiological changes, predisposing the patients to earlier clinical presentation of BrS. In patients with VSD and ST-segment elevation in the right precordial leads, BrS should be considered and appropriate screening should be pursued accordingly.

Lung sound analysis in infants with risk factors for asthma development.

BACKGROUND AND OBJECTIVES: Using a lung sound analysis, the prognosis of asthma was investigated in infants with risk factors for asthma development by a long-term observation. METHODS: A total of 268 infants were included (median age: 8 months old). The lung sound parameters (the ratio of the third and fourth area to the total area under the curve [A3/AT and B4/AT], and the ratio of power and frequency at 50% and 75% of the highest frequency [RPF50 and RPF75]) were evaluated at the first visit. At 3 years old, using a questionnaire, we examined the relationship between the lung sound parameters and risk factors of asthma development. RESULTS: Among the 268 infants, 175 infants were in good health and 93 had a history of acute respiratory infection (ARI) within 7 days at the first visit. Among the 3- to 12-month-old infants with an ARI, the A3/AT, B4/AT values in those with a history of asthma/asthmatic bronchitis, atopic dermatitis, and atopy were smaller than in the infants without such histories. Among the 13- to 24-month-old infants with an ARI, the A3/AT and B4/AT values in those with a wheezing history were larger than in the infants without such a history. CONCLUSIONS: The characteristics of the lung sounds in infants with risk factors for asthma development were demonstrated over long-term follow-up. Lung sound analyses may be useful for assessing the airway condition of infants.

Late recovery of the cardiopulmonary exercise capacity after transcatheter amplatzer device closures for atrial septal defects in adults.

Transcatheter atrial septal defect (ASD) closures using an Amplatzer Septal Occluder (ASO) have been widely performed. Compared to children, we sometimes experience late recovery of exercise performance in adult patients. Our study aimed to evaluate the change in the cardiopulmonary exercise capacity in asymptomatic or mildly symptomatic adult patients after a transcatheter ASD closure using an ASO. The subjects consisted of 29 patients (age 39.5 ± 13.6 years) that underwent cardiopulmonary exercise testing (CPX) before, 3, 6, and 12 months after a transcatheter secundum ASD closure using an ASO. The peak oxygen consumption (peak VO2), anaerobic threshold (AT), and slope of the correlation between the ventilation and carbon dioxide production (VE/VCO2 slope) were evaluated. We also evaluated the left-ventricular end-diastolic diameter (LVEDD), right-ventricular end-diastolic dimension (RVEDD) by echocardiography, and hemodynamic values by cardiac catheterization before the ASO procedure. The peak VO2 did not show any improvement 3 months after the ASO procedure; however, a significant improvement was displayed 6 and 12 months (baseline: 23.4 ± 6.3, 3 months: 23.6 ± 6.4, 6 months: 25.1 ± 5.6, 12 months: 26.4 ± 5.3 mL/kg/min; p < 0.001) after the ASO. The LVEDD (before: 38.1 ± 3.6, 3 months: 43.4 ± 3.4 mm; p < 0.001) and RVEDD (before: 33.6 ± 5.3, 3 months: 26.3 ± 2.6 mm; p < 0.001) on echocardiography quickly improved 3 months after the ASO. Although the LVEDD and RVEDD normalized 3 months after the ASO, the peak VO2 still decreased; however, the peak VO2 improved to almost a normal range 6 months after the ASO.

Diagnostic value of P-waves in children with idiopathic restrictive cardiomyopathy.

Restrictive cardiomyopathy (RCM) is a rare myocardial disease with an impaired diastolic function and poor prognosis. Almost all RCM patients are reported to have abnormal P-waves due to atrial overloading. This study aimed to reveal the characteristics of the P-waves in RCM patients and to suggest the diagnostic index of RCM in children with a 12-lead electrocardiogram (ECG). We retrospectively investigated 17 ECGs of children with idiopathic RCM during the initial visit at 15 institutes in Japan between 1979 and 2013. The RCM group was divided into four groups based on the age (elementary school [ES] and junior high school [JHS] students) and inception of the diagnosis (abnormal ECG on school-heart-screening [e-RCM] and some cardiovascular symptoms [s-RCM]), the ES/e-RCM (n = 5), ES/s-RCM (n = 4), JHS/e-RCM (n = 4), and JHS/s-RCM (n = 4) groups. As an aged-match control group, school-heart-screening ECGs of 1st-grade ES students (16,770 students) and 1st-grade JHS students (18,126 students) from Kagoshima in 2016 were adopted. For a comparison between the groups, we used the effect size "Hedge's g" by calculating the mean and standard deviation of the two groups. An effect size of 0.8 (or above) had an overlap of 53% (or less). The effect sizes of the sum of the absolute values of the forward and backward amplitudes in lead V1 (P1 + P2 V1) was the largest, and the ES/e-RCM, ES/s-RCM, JHS/e-RCM, and JHS/s-RCM were 15.8, 22.1, 9.4, and 10.3, respectively. A P1 + P2 V1 > 200 µV was able to rule in all RCM patients, thus, we proposed 200 µV as the cutoff value for screening purposes. In conclusion, the P1 + P2 V1 in the school-heart-screening may be useful for detecting asymptomatic or early-stage RCM in school-age children.

Impact of the T-wave characteristics on distinguishing arrhythmogenic right ventricular cardiomyopathy from healthy children.

BACKGROUND: T-wave inversion (TWI) is not considered useful for diagnosing pediatric arrhythmogenic right ventricular cardiomyopathy (ARVC), because right precordial TWI in ARVC resembles a normal juvenile pattern. OBJECTIVES: The aims of this study were to clarify the electrocardiographic (ECG) characteristics of pediatric ARVC to distinguish those patients from healthy children. METHODS: Between 1979 and 2017, 11 ARVC patients under 18 years old were registered and compared with school screening ECGs from 48,401 healthy children. RESULTS: The mean age at the first arrhythmic event or diagnosis was 13.3 ± 4.7 years. Nine patients were asymptomatic initially and were found by ECG screening, but 6 developed severe symptoms during the follow-up. Healthy children had a normal juvenile pattern, while ARVC children, especially symptomatic patients, had a significant tendency to have inferior and anterior TWI. The phenomenon of T-wave discontinuity (TWD) in which the TWI became deeper from V1 to V3 and suddenly turned positive in V5 was significantly more frequent in ARVC (60%) than healthy children (0.55%). Anterior TWI and TWD were also significantly more frequent in those who developed severe symptoms. The sensitivity and specificity of TWD were 60% (95% CI, 31-83%), and 99% (95% CI, 99-99%) to distinguish ARVC from healthy children, as well as 100% (95% CI, 71-100%) and 80% (95% CI, 51-80%), respectively, to predict severe symptoms in the future. CONCLUSIONS: The ECG is useful to distinguish ARVC children, even in the early phase. Anterior TWI and TWD could detect ARVC children and to predict the possible serious conditions.

New Technique to Analyze the Breath Sound Spectrum in Children with Asthma.

OBJECTIVE: Breath sound parameters have been reported as useful biomarkers for evaluating the airway condition. METHODS: The reliability of breath sound analysis using an improved method was investigated. Eighty-three asthmatic children were included in the present study. After adjusting the 0 level based on the background noises of the breath sound spectrum, the total area under the curve of the dBm (AT), the roll-off from 600-1200 Hz (Slope), the ratio of the third and fourth area to the AT (A3/AT and B4/AT), and the ratio of power and frequency at 50% and 75% of the highest frequency (RPF75 and RPF50), were evaluated before and after ß2 agonist inhalation. Spirography and the forced oscillation technique were also used to evaluate all subjects. RESULTS: Using the new method, A3/AT, B4/AT, RPF75 and RPF50, were significantly increased after ß2 agonist inhalation. The increase in A3/AT and B4/AT were significantly correlated with the increase in FEV1 and FEE25-75, and the increase in RPF75 was reversibly correlated with that in R5-R20. CONCLUSIONS: The spectrum curve indices using the adjusted 0 level can indicate bronchial dilation with ß2 agonist inhalation. These parameters may be useful for the assessment of bronchial reversibility in asthmatic children.

[EFFECT OF INSPIRATORY FLOW ON BREATH SOUND ANALYSIS IN CHILDREN WITH ASTHMA].

BACKGROUND: In order to determine the optimal breathing method for childhood lung sound analyses, it is important to study the effect of airflow on the parameters of lung sounds. METHODS: Sixty-one well-controlled children with atopic asthma (median; 12 years) participated. After confirming that there was no wheezing or respiratory symptoms, the lung sound spectrums of the inspiratory flow before and after inhalation of a ß2 stimulant were analyzed. At the same time, their lung function was measured by a spirogram and the forced oscillation technique. RESULTS: Before ß2 agonist inhalation, the area under the entire curve (AT) and 99% frequency (F99) in the lung sound of inspiratory flow around 2.0L/s due to slightly strong breathing were significantly higher than the lung sound of inspiratory flow around 1.0L/s due to rest breathing. However, no marked differences were observed in the lung sound parameters based on the lung sound spectrum. The improvement in the lung sound parameters after ß2 agonist inhalation was clearer at an inspiratory flow around 1.0L/s than that around 2.0L/s. CONCLUSION: The present study showed that changes after ß2 agonist inhalation and the correlation with the lung function parameters were clear during resting breathing. This method may be used for the long-term montoring of children with asthma.

Changes in the Breath Sound Spectrum with Bronchodilator Inhalation in Asthmatic Children with Long-term Management.

OBJECTIVE: Using a commercially available breath sound analyzer, the airway reversibility in asthmatic children during healthy periods was investigated. METHODS: Fifty samples of 34 children with asthma (median age, 11 years; range, 6-16 years) who visited our hospital and whose lung function was normal were included. The breath sound parameters, the frequency limiting 99% of the power spectrum (F99) and spectrum curve indices, the total area under the curve of the dBm data (A3/AT and B4/AT) and the ratio of power and frequency at 50% and 75% of the highest frequency of the power spectrum (RPF75 and RPF50) were evaluated before and after ß2 agonist inhalation. RESULTS: The values of spectrum curve indices were significantly increased after ß2 agonist inhalation. The changes in these parameters were more marked than the changes in the FOT parameters. The changes in A3/AT and B4/AT were significantly related to two FOT parameters: R5-R20 and X5. CONCLUSIONS: Our study suggested that significant changes in breath sound parameters were present in asthmatic children during the period of good control. A breath sound analysis may be useful for assessing the airway condition of asthmatic children during long-term management.

Successful Ablation of Atrial Tachycardia Originating from Inside the Single Atrium and Conduit After a Fontan Operation.

An 18-year-old male who had a past medical history of an intracardiac total cavopulmonary connection (TCPC) operation was referred to our hospital for radiofrequency catheter ablation (RFCA) of supraventricular tachycardia (SVT). Two types of SVTs were induced, and 3-dimensional (3D) maps were created using an ultra-high-density 3-dimensional mapping system (Rhythmia). The earliest atrial activation site (EAAS) of SVT1 was at the superior part of the conduit, and the EAAS of SVT2 was at the inferior part of the single atrium (SA). The SVTs were terminated by energy deliveries to the EAAS from the conduit in SVT1 and from inside the single atrium in SVT2. Detailed maps of the SVTs were important to understand the mechanisms of the SVTs. The Rhythmia system was useful for the detailed mapping of complex arrhythmias. The use of Rhythmia in patients after a TCPC is difficult, because puncturing the TCPC conduit and proceeding and manipulating the Orion catheter via a narrow puncture hole are difficult. We were the first to succeed in ablating two atrial tachycardias (ATs) originating from the inside and outside of the conduit after a TCPC operation by using an ultra-high-density 3-dimensional mapping system.

Anomalous origin of the coronary artery coursing between the great vessels presenting with a cardiovascular event (J-CONOMALY Registry).

AIMS: Anomalous origin of the coronary artery (AOCA) with an inter-arterial course (IAC) between the great vessels poses a risk for a life-threatening cardiovascular event. We assessed, in a registry-based study, the clinical features, treatment strategies, and prognoses of life-threatening cardiovascular events ensuant to AOCA. METHODS AND RESULTS: Included were 65 AOCA patients (48 men/17 women, aged 41 ± 23 years) from 40 clinical centres who had experienced sudden cardiac arrest (SCA) (n = 30), acute myocardial infarction (AMI) (n = 5), angina (n = 23), or syncope (n = 7). The anomalous vessel was the right coronary artery in 72% of patients and left coronary artery in 28%; the ostium was slit-like in 42%. Coronary luminal narrowing ≥75% was absent in patients with SCA or syncope (86% and 57%, respectively), but occlusion or narrowing was seen in those with AMI (100%) or angina (52%). Age ≤40 years, male sex, sporting activity, absence of prodromal symptoms, acutely angled (≤30°) take-off from the aorta, and absence of luminal narrowing of the IAC segment were associated with SCA in this patient group. Coronary vasospasm was inducible in 12 of 17 patients without coronary narrowing. Management included surgical revascularization (n = 26) percutaneous coronary intervention (n = 9), and medical treatment (n = 26). Four SCA patients died while hospitalized; no others died during the median 5.0 (range, 1.8-7.0)-year follow-up period. CONCLUSIONS: In patients with AOCA, age ≤40 years, male sex, sporting activity, and an acute take-off angle appear to be risk factors for SCA. Appropriate management can be beneficial. Confirmation in a large-scale study is warranted.

Cardiopulmonary failure as a result of brainstem encephalitis caused by enterovirus D68.

Enterovirus D68 (EV-D68) causes respiratory illnesses such as pneumonia, and has been reported to cause acute flaccid myelitis. Enterovirus A71 (EV-A71) is known to cause cardiopulmonary failure due to brainstem encephalitis, but there have been few reports of these conditions being associated with EV-D68. Outbreaks of EV-D68 infection have occurred in the USA, Canada, Europe and Asia. Clinical management is largely supportive and there are no specific antivirals available. The case patient, a 4-year-old girl, had cardiopulmonary failure due to brainstem encephalitis. EV-D68 was isolated from a throat swab. On admission, she had cardiopulmonary failure, which required intensive care using a ventilator and inotropic agents. Her cardiac function improved, but she had residual bulbar paralysis and limb weakness, which resolved over a 6-month period. This case confirms that EV-D68, may cause severe illness due to brainstem encephalitis, similar to that caused by EV-A71.

Improvement in Dyssynchrony with Pharmacological Ablation of Right-Sided Accessory Pathway-Induced Cardiomyopathy in Infants.

Right-sided accessary pathways in patients with Wolff-Parkinson-White (WPW) syndrome may cause cardiac dyssynchrony and dilated cardiomyopathy, with a characteristic septal shape, irrespective of any supraventricular tachycardia episodes. We report on two infants (13 and 5 months), whose right-sided accessary pathway-induced dilated cardiomyopathy was successfully treated by flecainide for the first time. After the flecainide administration, an abnormal aneurysmal dilation of the basal interventricular septum was almost restored to normal, and the decreased ejection fraction recovered. Flecainide use may be an important therapeutic option for this entity to avoid catheter ablation during infancy.

Usefulness of Red Blood Cell Distribution Width in the Assessment of Hemodynamics After Tetralogy of Fallot Repair.

BACKGROUND: There are no reports on the effect of red blood cell distribution width (RDW) in surgical repair of tetralogy of Fallot (ToF). Methods and Results: A total of 50 patients who underwent cardiac catheterization after surgical repair of ToF were retrospectively assessed. RDW was positively correlated with the ratio of right ventricular pressure to left ventricular pressure (RVP/LVP; P<0.0001, r2=0.57). Patients with elevated RDW had a higher RVP/LVP than those with a normal RDW (P<0.0001). Also, elevated RDW was related to elevated central venous pressure (P<0.0001), decreased mixed venous oxygen saturation (P<0.0001), greater pulmonary stenosis (P=0.003) and severe pulmonary regurgitation on echocardiography (P<0.0001), a higher rate of residual ventricular septal defect leak (P=0.004) and higher reoperation rate (P=0.009). Of the 7 patients who underwent reoperation, 6 had decrease in RDW after reoperation (P=0.012). On multivariable regression analysis, RDW was the strongest indicator of higher RVP/LVP. CONCLUSIONS: For the first time, RDW has been shown to be a strong indicator for assessing the hemodynamics and risk of later reoperation after surgical repair of ToF.