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According to current short-term evidence, ventricular septal defect (VSD) closure should be performed as early as possible after aortic regurgitation (AR) diagnosis in pediatric patients to prevent AR progression. However, long-term follow-up data are lacking. Therefore, our aim was to evaluate the long-term follow-up (≥ 10 years) of patients who underwent VSD closure as early as possible after AR diagnosis and to evaluate whether early VSD closure prevents progression of AR. This was a retrospective cohort study of 42 patients with VSD and AR who had undergone VSD closure at a median age of 2.9 years, with a median waiting period from AR diagnosis to VSD closure of 3.4 months and follow-up of a median 13.1 years (interquartile range 10.0-15.8 years). The preoperative degree of AR was trivial in 25 patients, mild in 15, and moderate in 2. Of the 33 patients followed up for ≥ 10 years, none required aortic valve replacement and there was no incidence of mortality. The degree of AR improved or did not change, except in 1 patient. The size of the VSD (odds ratio [OR] 0.85; 95% confidence interval [CI] 0.62-1.18; p = 0.33), time from diagnosis to surgery (OR 1.00; 95% CI 1.000-1.001; p = 0.657), and age at the time of surgery (OR 1.00; 95% CI 0.998-1.004; p = 0.452) were not predictive of persistent postoperative AR. Therefore, VSD closure performed as early as possible after AR diagnosis could successfully prevent AR progression in patients with less than moderate preoperative AR, eliminating the need for aortic valve replacement and valvuloplasty.

Background Mutations in GNAO1 typically result in neurodevelopmental disorders, including involuntary movements. They may be improved using calcium-channel modulators. Case The patient visited our hospital at age 2 years because of moderate global developmental delay. Her intermittent, generalized involuntary movements started at age 8 years. A de novo GNAO1 mutation, NM_020988.2:c.626G > A, (p.Arg209Cys), was identified by whole exome sequencing. At age 9 years, she experienced severe, intermittent involuntary movements, which led to rhabdomyolysis. She needed intensive care with administration of midazolam, dantrolene sodium hydrate, and plasma exchange. We started treating her with gabapentin (GBP), after which she recovered completely. At age 11 years, she developed continuous, generalized involuntary movements. This prompted us to increase the GBP dose, which again resolved the involuntary movements completely. Conclusion In the case of movement disorders associated with GNAO1 mutations, GBP treatment may be attempted before more invasive procedures are performed.

The patient was a 28-year-old woman who was misdiagnosed with tetralogy of Fallot and straddling mitral valve after birth. She underwent a left modified Blalock-Taussig shunt at the age of 1 year. At age 28, she presented with fatigue and progressive cyanosis. Finally, she was diagnosed with tetralogy of Fallot and complete atrioventricular septal defect. To measure the exact biventricular volumes, we performed cardiac magnetic resonance imaging in addition to cardiac angiography and ensured adequate volume capacity. We eventually decided to perform biventricular repair. Her postoperative course was uneventful, and she returned to full-time work.

Introduction A late aortic aneurysm at the site of previous open surgery for coarctation of the aorta (CoA) is a life threatening complication. Several strategies have been reported, however, these strategies have issues. This is the report of a case involving successful ascending to descending aortic bypass concomitant with endovascular embolisation for a pseudoaneurysm. Report The patient was a 23 year old man with a history of patch aortoplasty for coarctation of the aorta (CoA) via a left thoracotomy and patch closure of a ventricular septal defect. Enhanced computed tomography (CT) angiography performed in 2014 revealed a pseudoaneurysm at the site of the previous patch aortoplasty. CT also revealed a hypoplastic and severely kinked aortic arch that made it difficult to perform conventional thoracic endovascular aortic repair for this aneurysm. Therefore in order to prevent rupture, a combination of ascending to descending aortic bypass and endovascular embolisation using Amplatzer vascular plugs and coils was employed. Transection of the aortic arch and transposition of the left subclavian artery were performed to prevent antegrade flow into the aneurysm. Discussion The aneurysm was successfully excluded without complications. CT performed three years after the operation showed that the pseudoaneurysm had shrunk completely. Extra-anatomic bypass concomitant with endovascular embolisation for a late coarctation patched site aneurysm might be an alternative strategy that should be carefully considered in specific cases., Highlights • A case of late coarctation patched site pseudoaneurysm is presented. • Ascending to descending aortic bypass was performed successfully. • The aneurysm was treated successfully by endovascular embolisation. • Follow up computed tomography showed that the pseudoaneurysm had shrunk completely. • This approach might be an alternative strategy that should be carefully considered.

The predictive ability of neonatal illness severity scores for mortality or morbidity in extremely premature infants has not been extensively studied. We aimed to evaluate the ability of neonatal illness severity scores [Clinical Risk Index for Babies II (CRIB II), Score for Neonatal Acute Physiology II (SNAP-II), and SNAP-Perinatal Extension II (SNAPPE-II)] in predicting mortality and short-term morbidity of extremely premature infants.This retrospective study involved 171 infants with gestational age (GA) between 22 and 27 weeks who were admitted to the NICU during 2010-2017. Predictive ability of neonatal illness severity scores for mortality and short-term morbidity (bronchopulmonary dysplasia, retinopathy of prematurity, intraventricular hemorrhage, necrotizing enterocolitis, and gastrointestinal perforation) was assessed by comparing their area under the receiver operating characteristic curve.The overall mortality rate was 11.1%. Mortality at 23 weeks' gestation was higher than that at 24-27 weeks' gestation (The neonatal illness severity scores were excellent predictors of early death in extremely premature infants and might be useful for selecting extremely preterm infants who need intervention.

Background and Aim Anti‐tumor necrosis factor alpha (TNF‐α) therapy is an effective therapy for Crohn's disease (CD). We investigated FoxP3+ and CD127− regulatory T cells (Tregs) before and after administration of anti‐TNF‐α therapy in CD. Methods Eight patients with active CD who had received anti‐TNF‐α antibodies were enrolled. Treatment responses were followed by physical examination and Crohn's disease activity index (CDAI) scoring before and 2 weeks after the initial administration of anti‐TNF‐α antibodies. Peripheral blood samples were collected before and 2 weeks after treatment. White blood cell count and serum levels of C‐reactive protein (CRP) and albumin were measured. FoxP3+ expression and CD127− Tregs were measured by fluorescence activated cell sorting (FACS) analysis of whole blood samples. Results Median values of CDAI decreased significantly after treatment. The proportion of FoxP3+ Tregs increased significantly after treatment. There was a significant negative correlation between ΔCD127− Tregs and Δlymphocyte. Conclusions Anti‐TNF‐α therapy would enhance Tregs, which may account for the mechanism underlying the positive effect of the anti‐TNF‐α treatment in CD patients., We investigated regulatory T cells before and after administration of anti‐TNF‐a therapy in Crohn's disease. The proportion of FoxP3+ Tregs increased significantly after treatment. There was a significant negative correlation between ΔCD127− Tregs and Δlymphocyte.

Background Overnight catheter drainage (OCD) is introduced to avoid overdistention of the bladder at night-time when clean intermittent catheterization proves ineffective for daytime management of neurogenic bladder. We adopted OCD using disposable silicone no-balloon (DSnB) catheters, with the distal end outside the body opening into diapers. OCD using DSnB catheter, however, had risks of retrograde bacterial contamination. Therefore, in this study, the validity of equipping DSnB catheters with check valves to prevent retrograde bacterial contamination was examined. Methods For the in vitro study, excised saline-filled swine bladders were drained using DSnB catheters with or without check valves, and the time required for intravesical pressure to reach 5 cmH2 O was measured. For the in vivo study, in cross-over experiments comparing DSnB catheters with and without check valves, OCD using DSnB catheters for 10 h was performed in rabbits under analgesia. Bacterial growth from urine samples before and after OCD and residual urine volume were examined. Results For the in vitro experiment, the median drainage time was 368.2 s (range, 88-1,085 s) and 344.7 s (range, 28-840 s) with and without check valves, respectively (n = 6), which was not significantly different. For the in vivo experiment, in cross-over experiments (n = 8) new bacterial growth rates after OCD did not differ, and median residual urine volume was 17.1 mL (range, 0-75 mL) and 1.2 mL (range, 0-5 mL) with and without check valves, respectively (P = 0.055). Conclusions Installing a check valve in the DSnB catheter did not decrease new bacterial growth, while tending to increase residual urine volume. DSnB catheters without check valves appear to be better for continuous drainage of urine from bladder.

We describe a seven-month-old boy with tetralogy of Fallot and an absent left pulmonary artery. Due to the diminutive size of the left pulmonary artery, we performed a native tissue left pulmonary artery reconstruction and intrapulmonary artery septation procedure with a left modified Blalock-Taussig shunt. After confirming left pulmonary artery growth, the patient underwent tetralogy of Fallot repair, removal of septation patch, and division of the Blalock-Taussig shunt. Nine months post-surgery, we confirmed his balanced lung perfusion (R/L ratio 6:4). The intrapulmonary artery septation procedure would be suitable for both the resuscitation and reconstruction of the hypoplastic absent pulmonary artery.

Objective: To compare left ventricular (LV) and right ventricular (RV) volume, function, and image quality of a respiratory-triggered two-dimensional (2D)-cine k-adaptive-t-autocalibrating reconstruction for Cartesian sampling (2D kat-ARC) with those of the standard reference, namely, breath-hold 2D balanced steady-state free precession (2D SSFP), in patients with repaired tetralogy of Fallot (TOF). Methods: 30 patients (14 males, mean age 32.2 ± 13.9 years) underwent cardiac magnetic resonance, and 2D kat-ARC and 2D SSFP images were acquired on short-axis view. Biventricular end-diastolic volume (EDV) and end-systolic volume (ESV), stroke volume (SV), ejection fraction (EF), and LV mass (LVM) were analysed. Results: The 2D kat-ARC had significantly shorter scan time (35.2 ± 9.1 s vs 80.4 ± 16.7 s; p < 0.0001). Despite an analysis of image quality showed significant impairment using 2D kat-ARC compared to 2D SSFP cine (p < 0.0001), the two sequences demonstrated no significant difference in terms of biventricular EDV, LVESV, LVSV, LVEF, and LVM. However, the RVESV was overestimated for 2D kat-ARC compared with that for 2D SSFP (73.8 ± 43.2 ml vs 70.3 ± 44.5 ml, p = 0.0002) and the RVSV and RVEF were underestimated (RVSV = 46.2±20.5 ml vs 49.4 ± 20.4 ml, p = 0.0024; RVEF = 40.2±12.7% vs. 43.5±14.0%, p = 0.0002). Conclusion: Respiratory-triggered 2D kat-ARC cine is a reliable technique that could be used in the evaluation of LV volumes and function. Advances in knowledge: 2D cine kat-ARC is a reliable technique for the assessment LV volume and function in patients with repaired TOF.

Turner syndrome (TS) is the most frequent sex abnormality in women. The physical features include short stature, webbing of the neck, and gonadal dysgenesis. Typically, patients with Turner syndrome exhibit no intellectual disability, and a few cases of TS have been associated with epilepsy. Herein, we present a case of TS with intractable epilepsy. The patient presented with global developmental delay at the age of two and karyotyping revealed mosaicism [45, X/46, X del (X) (q21.1)]. At the age of seven, she had generalized tonic epilepsy as well as several focal-onset seizures. She developed daily seizures, which were refractory to several antiepileptic drugs. Interictal electroencephalography (EEG) revealed multifocal spikes, and ictal EEG revealed shifting foci. She visited our hospital at the age of 13. Her peripheral white blood cells G-band and fluorescence in situ hybridization (FISH) method chromosome with cheek swab examinations revealed 45, X. Her peripheral white blood cell mosaic pattern may have disappeared over time or become indetectable. We treated her with clobazam, and then lamotrigine and valproic acid combination therapy, which resulted in a reduction in the frequency of seizures by approximately 50%. Epilepsy and intellectual disability in this case may be due to the mosaic deletion at Xq21.1. Further analysis of similar cases may provide valuable information for effective therapeutic strategies.

Background: Left ventricular noncompaction (LVNC) is a hereditary type of cardiomyopathy. Although it is associated with high morbidity and mortality, the related ion channel gene variants in children have not been fully investigated. This study aimed to elucidate the ion channel genetic landscape of LVNC and identify genotype-phenotype correlations in a large Japanese cohort. Methods: We enrolled 206 children with LVNC from 2002 to 2017 in Japan. LVNC was classified as follows: LVNC with congenital heart defects, arrhythmia, dilated phenotype, or normal function. In the enrolled patients, 182 genes associated with cardiomyopathy were screened using next-generation sequencing. Results: We identified 99 pathogenic variants in 40 genes in 87 patients. Of the pathogenic variants, 8.8% were in genes associated with channelopathies, 27% were in sarcomere genes, and 11.5% were in mitochondrial genes. Ion channel gene variants were mostly associated with the arrhythmia classification, whereas sarcomere and mitochondrial gene variants were associated with the dilated phenotype. Echocardiography revealed that the group with ion channel gene variants had almost normal LV ejection fraction and LV diastolic diameter Z scores. Fragmented QRS, old age, and an arrhythmia phenotype were the most significant risk factors for ventricular tachycardia ( P =0.165, 0.0428, and 0.0074, respectively). Moreover, the group with ion channel variants exhibited a greater risk of a higher prevalence of arrhythmias such as ventricular tachycardia, rather than congestive heart failure. Conclusions: This is the first study that focused on genotype-phenotype correlations in a large pediatric LVNC patient cohort with ion channel gene variants that were determined using next-generation sequencing. Ion channel gene variants were strongly correlated with arrhythmia phenotypes. Genetic testing and phenotype specification allow for appropriate medical management of specific LVNC targets.

Aims Critical congenital heart disease (CCHD) requires surgery or catheter intervention within the first year of life; delayed diagnoses result in worsened outcomes. In Japan, there are few reports of delayed CCHD diagnosis. We investigated the diagnoses and factors associated with the late detection of CCHD. Methods This retrospective cohort study evaluated 88 CCHD infants admitted to a level IV facility. We compared the late detection rates across facility levels of neonatal care and CCHD characteristics. Results Critical congenital heart disease was identified prenatally in 46 (52%) infants: early (≤3 days postnatally) in 29 (33%) and late (≥4 days postnatally) in 13 (15%). The oxygen saturation of 27 of 29 infants with early detection and 7 of 13 infants with late detection was measured using pulse oximetry within 3 days postnatally. Factors associated with the late detection of CCHD were lack of clinical recognition of symptoms in five infants, referral to higher-level facilities after discharge in four infants, and definitive diagnosis not confirmed using echocardiography in four infants. The most common factors associated with late detection were referral to higher-level facilities after discharge in level I facilities and definitive diagnosis not confirmed using echocardiography in level II facilities. Conclusion Critical congenital heart disease may require advanced knowledge and echocardiographic techniques for diagnosis. Pulse oximetry and telemedicine should also be incorporated in the diagnostic algorithm. Improvement in these factors might contribute to reducing the late detection of CCHD.

Vitamin K deficiency in pregnant women causes intracranial hemorrhage (ICH) in fetuses. Fetal ICH frequently causes life-threatening and persistent neurological damage. However, indicators for preventing fetal ICH are not established. Two pregnant women developed long-term eating disorders caused by psychosis. They were administered intravenous fluid and vitamin supplementation, excluding vitamin K. The intracranial low-hypoechoic area on fetal ultrasound was suggestive of fetal ICH due to vitamin K deficiency. Their neonates showed severe developmental delay. Laboratory analysis revealed a normal prothrombin time, but elevated protein induced by vitamin K absence II. Pregnant women who have eating disorders more than 3 weeks could develop fetal ICH due to maternal subclinical vitamin K deficiency. Illness duration and protein induced by vitamin K absence II of pregnant woman may be indicators for vitamin K administration to prevent fetal intracranial hemorrhage.

The case of a 16-year-old male patient with left renal artery stenosis due to fibromuscular dysplasia (FMD) and an atrophic kidney due to a right multicystic dysplastic kidney (MCDK) who presented with refractory hypertension is reported. On continuous Doppler imaging, the peak systolic velocity (PSV) at the stenotic site of the left renal artery was 404 cm/s. The FMD formed a "string-of-beads" appearance on computed tomographic angiography (CTA) and renal artery angiography. Percutaneous transluminal renal angioplasty (PTRA) with a balloon catheter was performed, after which the left renal artery returned to near normal, and his blood pressure decreased to within the normal range. In this case, the main cause of refractory hypertension was considered to have been renal artery stenosis due to left FMD.

The case of a patient in whom hemodynamic and electrocardiographic studies using the occlusion test for coronary artery fistulas (CAF) were safely performed prior to catheter embolization is reported. A 1-year-old girl had a separate right coronary artery arising from a left single coronary artery that formed a significant coronary artery fistula to the right ventricle. Coronary steal by the large coronary artery fistula narrowed the left coronary artery. The right coronary artery branches could not be clearly identified due to an overlap with the fistula. Due to the long porous CAF, embolic procedures could cause serious complications. We confirmed the safety by performing an occlusion test of the CAF’s proximal blood vessels. Following total occlusion of the CAF for 10 minutes, pulmonary arterial pressure and aortic blood pressure were not significantly changed. No bradycardia, atrioventricular block, or ST changes were observed. Coil embolization treatment was performed safely. For patients with long distal CAF complicated with a single coronary artery, myocardial ischemia and conduction system disorders can be identified by performing the occlusion test before embolization.

Severe pulmonary arterial hypertension (PAH) rarely develops in children with an atrial septal defect (ASD), even those with a large defect. We herein report the case of a 27-year-old man with a moderate-sized secundum ASD and right ventricular failure due to severe PAH, which developed in his early teens. He was diagnosed as having a genetic mutation of the bone morphogenetic protein receptor-2 (BMPR2) gene and was successfully treated with bilateral lung transplantation with ASD path closure. In patients with congenital heart disease, a genetic analysis may provide information about the lifetime risk of developing PAH.

Background/ Aims: Owing to practical and technical developments, continuous renal replacement therapy (CRRT) has been administered even in critically ill neonates. In this study, the complications in CRRT for neonates were examined to establish a safe CRRT. Methods: This retrospective study reviewed the clinical records of neonates who underwent CRRT at our neonatal intensive care unit between 2009 and 2017. Results: Eight neonates with a body weight of 1,462–3,288 g were treated by 70 CRRT sessions with blood priming. Intradialytic hypotension (IDH) was observed in 39 sessions (55.7%), most of which occurred soon after the start of the CRRT. Body temperature decreased in 48 sessions (70.5%), and thrombocytopenia during CRRT occurred 30 times (42.9%). Conclusion: Complications during CRRT in neonates comprised IDH at the start of the CRRT, body temperature decline, and thrombocytopenia. These complications need to be analyzed for a safe neonatal CRRT.

Background Recent technical and experimental advances in extracorporeal blood purification therapy (eBPT) can be applied in paediatric patients, including neonates. However, there are several specific issues in performing eBPT in paediatric patients in regard to the safety and effectiveness of treatments. The aim of this review is to explore the technical aspects of acute paediatric eBPT, especially regarding renal replacement therapy and the present situation in Japan. Summary In children requiring eBPT, especially small children and neonates, it is difficult to secure sufficient blood flow to obtain optimal treatment effects for various diseases and critical illnesses. In such conditions, it should be considered which modalities of eBPT and anticoagulants are used and how optimal blood flow and replacement fluid/dialysate flow rate should be chosen for the safety and effectiveness of treatments. Key Messages: In paediatric patients requiring eBPT, frequent complications are observed; therefore, we should apply optimal eBPT depending on the pathophysiological conditions of paediatric patients, develop a deep understanding about paediatric eBPT, and collect evidence on treatment outcomes. In addition, the eBPT systems and devices specifically for small children are expected to be developed in Japan to improve the safety and efficacy of eBPT.

Background: Left ventricular wall motion is depressed in patients with dilated cardiomyopathy (DCM). However, whether or not the depressed left ventricular wall motion is caused by impairment of sarcomere dynamics remains to be fully clarified. Methods and Results: We analyzed the mechanical properties of single sarcomere dynamics during sarcomeric auto-oscillations (calcium spontaneous oscillatory contractions [Ca-SPOC]) that occurred at partial activation under the isometric condition in myofibrils from donor hearts and from patients with severe DCM (New York Heart Association classification III-IV). Ca-SPOC reproducibly occurred in the presence of 1 μmol/L free Ca 2+ in both nonfailing and DCM myofibrils, and sarcomeres exhibited a saw-tooth waveform along single myofibrils composed of quick lengthening and slow shortening. The period of Ca-SPOC was longer in DCM myofibrils than in nonfailing myofibrils, in association with prolonged shortening time. Lengthening time was similar in both groups. Then, we performed Tn (troponin) exchange in myofibrils with a DCM-causing homozygous mutation (K36Q) in cTnI (cardiac TnI). On exchange with the Tn complex from healthy porcine ventricles, period, shortening time, and shortening velocity in cTnI-K36Q myofibrils became similar to those in Tn-reconstituted nonfailing myofibrils. Protein kinase A abbreviated period in both Tn-reconstituted nonfailing and cTnI-K36Q myofibrils, demonstrating acceleration of cross-bridge kinetics. Conclusions: Sarcomere dynamics was found to be depressed under loaded conditions in DCM myofibrils because of impairment of thick-thin filament sliding. Thus, microscopic analysis of Ca-SPOC in human cardiac myofibrils is beneficial to systematically unveil the kinetic properties of single sarcomeres in various types of heart disease.

Living cells sense absolute temperature and temporal changes in temperature using biological thermosensors such as ion channels. Here, we reveal, to our knowledge, a novel mechanism of sensing spatial temperature gradients within single cells. Spherical mitotic cells form directional membrane extensions (polar blebs) under sharp temperature gradients (≥∼0.065°C μm−1; 1.3°C temperature difference within a cell), which are created by local heating with a focused 1455-nm laser beam under an optical microscope. On the other hand, multiple nondirectional blebs are formed under gradual temperature gradients or uniform heating. During heating, the distribution of actomyosin complexes becomes inhomogeneous due to a break in the symmetry of its contractile force, highlighting the role of the actomyosin complex as a sensor of local temperature gradients.

Background: In small children, conduits for right ventricular out ow tract reconstruction are limited because of patient size and conduit resources, particularly in Japan. Methods: Since 2007, we have performed the Rastelli-type procedure using 16-mm hand-made trilea et expanded polytetra uoroethylene (ePTFE) conduits in nine approximately 1-year-old children. e median age and body weight at surgery was 17.3 months (range: 10~22 months) and 8.9 kg (range: 6.8~11 kg), respectively. e patient diagnoses were double-outlet right ventricle (DORV) with pulmonary stenosis (PS) in four, pulmonary atresia with ventricular septal defect (PA/VSD) and major aortopulmonary collateral arteries (MAPCA) in four, and PA/VSD in one patient. All patients had undergone previous surgical procedures, including modi ed Blalock shunt in ve and unifocalization of MAPCA and modi ed Blalock shunt in four patients. Conduit function, re-intervention, and right ventricular function were retrospectively investigated. Results: ere was no early or late mortality. During the median follow-up of 45 months (range: 18~79 months), balloon dilation for conduit stenosis was performed in two patients at 47 and 51 months post surgery, respectively. One of these patients required conduit replacement 27 months a er balloon dilation. Excluding this patient, the most recent echocardiographic pressure gradients of the conduits were 0~20 mmHg in four, 21~40 mmHg in four, and no patient had conduit stenosis with the pressure gradients over 41 mmHg. Conduit regurgitation was trivial in four, mild in two, and moderate in two patients. Conclusion: e Rastelli-type procedure using 16-mm hand-made trilea et ePTFE conduits in approximately 1-year-old infants showed acceptable mid-term results. Conduit stenosis gradually developed over 5~6 years. Balloon dilation for conduit stenosis has the potential to delay conduit replacement without increasing conduit regurgitation.

Objective: Anti-TNF-α therapy is an effective therapy for Crohn’s disease (CD). Thus anti-TNF-α therapy may alter CD64 expression, one of the Fc receptors for IgG, in CD. We investigated CD64 expression on neutrophils before and after treatment with anti-TNF-α therapy in CD. Methods: A total of 11 patients with active CD treated with anti-TNFα antibodies were enrolled. The severity of CD was assessed with the CD activity index (CDAI). Peripheral venous blood was obtained before and 2 weeks after the initial administration of anti-TNF-α antibody. CD64 expression on neutrophils was measured by FACS analysis of whole blood samples. Results: CDAI, C-reactive protein value and CD64 expression decreased significantly after anti-TNF-α therapy. Both prior to and after anti-TNF treatment, there was a significant and positive correlation between CD64 expression and CDAI or CRP. Similarly, there was a significant and negative correlation between CD64 and albumin value. Conclusion: Anti-TNF-α therapy suppresses CD64 expression of neutrophils, which may account for the mechanism underlying the efficacy of the medication in CD.

Background: The genetic background of catecholaminergic polymorphic ventricular tachycardia (CPVT) has been extensively investigated for the last decade in Western countries, but it remains unstudied in the Asian population. Methods and Results: In 50 Japanese probands from unrelated families who satisfied clinical criteria for CPVT, genetic testing was conducted in all exons on 3 CPVT-related genes: cardiac ryanodine receptor 2 (RYR2), calsequestrin 2 (CASQ2) and inward rectifier potassium channel 2 (KCNJ2), and the clinical features between RYR2-genotyped and -non-genotyped patient groups were compared. Genetic and clinical evaluation was also done in 46 family members. In the genetic screening, 28 (18 novel) RYR2 (56.0%), 1 compound heterozygous CASQ2 (2.0%) and 1 KCNJ2 (2.0%) mutation carriers were identified. In the RYR2 mutation-positive group, the frequency of bidirectional ventricular tachycardia and the use of β-blockers were significantly higher than in the mutation-negative group. In contrast, there was no significant difference in supraventricular arrhythmias between the 2 groups. With regard to disease penetrance, the number of family members of RYR2-genotyped probands with a clinical diagnosis of CPVT was high. Conclusions: Thirty gene mutation carriers were found for 3 genes in 50 probands clinically diagnosed as having CPVT. The penetrance of CPVT phenotype was significantly higher in RYR2 mutation carriers, thus RYR2 gene screening in CPVT patients would be indispensable to prevent unexpected cardiac sudden death of young family members. (Circ J 2013; 77: 1705–1713)

A 3-year-old girl presented with muscle weakness of her limbs and trunk 6 days after developing symptoms of common cold. Two days later, she experienced respiratory arrest with a Glasgow Coma Scale score of 3, necessitating endotracheal intubation. Therefore, she was transferred to our hospital with suspected acute encephalopathy. Although no abnormalities were observed on brain and spinal magnetic resonance imaging and electroencephalography, peripheral nerve conduction velocity tests failed to evoke motor and sensory nerve action potentials. Thus, we gave a diagnosis of fulminant Guillain-Barre syndrome and initiated immunoglobulin therapy. On day 3 of admission, she developed sinus tachycardia that induced circulatory failure and oliguria, which was successfully treated with landiolol. Subsequently, we performed plasmapheresis followed by immunoglobulin and steroid pulse therapies. She was weaned off the mechanical ventilator by day 20 of admission, was ambulatory by day 44, and had completely recovered without any adverse sequelae by day 55. In conclusion, landiolol was effective for treating acute sinus tachycardia-induced circulatory failure and played a key role in saving the life of this patient.

In this clinical report, following computer-guided (3D Procera Software Planning Program, Nobel Biocare, Yorba Linda, CA) placement and immediate provisionalization of 12 dental implants (NobelSpeedy™ Replace, Nobel Biocare), misfits of the prefabricated screw-retained interim prostheses were noted at several implant-abutment junctions. Nevertheless, adaptation of the misfits was observed 10 days later, after the loosened screws were tightened. While a high mean marginal bone loss of 2.1 mm (range: 1.4 to 3.5 mm) was noted, all implants remained osseointegrated at 3-year follow-up.

症例は13歳，女児．くり返す運動後の失神を認めたため，当センターに紹介された．経胸壁心エコー検査で心機能に異常は認めなかったものの，24時間ホルター心電図で心拍の上昇に伴う ST 低下，およびトレッドミル負荷心筋シンチで同様の ST 低下を伴う心電図異常とともに左室前壁に虚血所見を認めた．冠動脈 CT 検査では左冠動脈主幹部低形成が認められたため，心筋虚血に伴う心原性失神と診断された．手術は非体外循環下で左内胸動脈-前下行枝の1枝バイパスを施行した．術後のストレスシンチでは心電図異常および心筋虚血の所見も認められず，冠動脈 CT 検査においてもグラフトの開存は良好であった．現在運動後の失神発作などは全く認められていない．学童期に失神を契機に発見された左冠動脈主幹部低形成の1手術例を報告した．冠動脈の形態異常に伴う心原性失神は非常に希であるが，放置すれば突然死などの原因となり，失神の鑑別診断として注意しておくべきである．また本症例のように，虚血が関与するくり返す失神に関しては積極的な冠動脈バイパス術が考慮されるべきであると考えられた．

Background Arrhythmia is a major late complication in adults with repaired tetralogy of Fallot, although a large-scale study has not been carried out in Japan. Methods and Results A nationwide multicenter study with 512 operative survivors was performed. Actuarial survival rate at 30 years (maximum follow-up) was 98.4%. Fifty-four patients (10.5%) had clinically important arrhythmias, including 23 patients with bradycardia caused by sick sinus syndrome or atrioventricular block (AVB). A patient with complete AVB (CAVB) without pacemaker implantation (PMI) died later. Two patients had sustained ventricular tachycardia (VT) and syncope was reported in 18 patients with ventricular arrhythmias (VA). Atrial tachyarrhythmias were observed in 13 patients. Older age at operation was a risk factor for atrial fibrillation/flutter, longer postoperative survival duration for VA, and QRS duration >120 ms for VT. Perimembranous ventricular septal defect was related to CAVB. Right ventricular outflow patch was not a risk factor. Importantly, 60% of the subjects had QRS duration

The management of congenitally corrected transposition of the great arteries and associated lesions is frequently challenging. Restrictive ventricular septal defect and mild pulmonary stenosis are contraindications to the double switch procedure, including the atrial-Rastelli switch procedure, due to the production of postoperative left ventricular outflow tract obstruction. We describe a case of aortic translocation using the hemi-Mustard procedure after left ventricular training in order to prevent postoperative left ventricular outflow obstruction.

Quantitative evaluation of right ventricular myocardial performance in preterm infants remains a challenge because of the limitations of conventional echocardiographic measurement and the complex geometry of the right ventricle (RV). Serial assessment of peak longitudinal systolic strain on the right and left sides of the ventricular septum (VS), RV, and left ventricle (LV) during the transitional period in preterm infants using two-dimensional speckle-tracking echocardiography is reported. In 21 preterm infants (33 ± 2 gestational weeks, 1,913 ± 218 g birth weight) without mechanical ventilation, inotropic agents, or symptomatic patent ductus arteriosus (PDA), longitudinal strain (LS) was measured on both sides of the VS, RV free wall, and LV, along with conventional echocardiography at 1, 3, 6, 9, 12, 24, 48, and 72 h after birth. Correlations and factors associated with echocardiographic measurements were analyzed. LS was maintained on the four analyzed regions during the first 72 h of life despite significant hemodynamic changes, including a decrease in pulmonary artery pressure and PDA closure. LS was significantly larger on the left side of the VS than on the right side of the VS at 1, 48, and 72 h after birth. Preterm infants showed stable LS on both sides of the VS, the RV free wall, and the LV despite significant hemodynamic changes during the first 72 h of life. These results suggest that the right and left sides of the VS respond differently to the complex cardiopulmonary transitions from fetal to neonatal life in preterm infants.

We report a case of aortic regurgitation (AR), coronary artery–to–pulmonary artery (CAPA) fistula, pulmonary atresia with ventricular septal defect (PA/VSD), and major aortopulmonary collateral arteries (MAPCAS). As a result of coronary steal and AR, myocardial ischemia and ventricular dysfunction occurred. When the patient was 2 months old with a body weight of 2.7 kg, we performed fistula ligation, aortic valvuloplasty, unifocalization of the MAPCAS, and right ventricle–to–pulmonary artery shunting. After the operation, the AR volume reduced, and the patient was scheduled for repair.

Background The beneficial effect of inhaled nitric oxide (NO) on pulmonary hypertension is well known. However, the indications for NO inhalation therapy for pulmonary hypertension associated with congenital heart lesions are still unclear. The aim of the current study was to seek a measure that would predict the effectiveness of inhaled NO in infants undergoing cardiac surgery. Methods Forty-six infants with pulmonary hypertension were studied. Pulmonary vascular resistance (PVR) measured at the time of cardiac catheterization was used as an indicator and compared with pulmonary arterial pressure/systemic blood pressure ratio (Pp/Ps) at the time of weaning from cardiopulmonary bypass. The effect of 40 ppm of inhaled NO for 15 min was evaluated in patients whose Pp exceeded systemic values. Results Preoperative PVR correlated positively with Pp/Ps at the time of weaning from cardiopulmonary bypass (r2 = 0.86; P < 0.05; n = 46). A Pp/Ps greater than or equal to 1 was not observed in any cases in which the preoperative PVR values were less than 7 Wood units m2; Pp/Ps ratio greater than or equal to 1 occurred in four patients. Each of these had PVR values greater than 7 Wood units m2. Three of these patients who had PVR values in the 7-12 Wood units m2 range were responsive to inhaled NO. The fourth patient, whose PVR value was greater than 15 Wood units m2, was unresponsive. Lung biopsy specimens were obtained in two patients whose preoperative PVR values were greater than 10 Wood units m2. Conclusion Preoperative PVR correlates reasonably well with postbypass Pp/Ps.

Coronary artery stenosis is seen in 10-45% of patients with Takayasu's arteritis (TA) and coronary ostia are most frequently involved. It may cause angina pectoris and sudden death during the early course of the disease. We describe a 14-year-old girl who first presented with exertional angina and syncope and was diagnosed as having left coronary artery ostial stenosis from TA by using transthoracic echocardiography. This is the first report showing the important role of color flow and pulsed Doppler echocardiography to detect coronary artery stenosis caused by TA.

Background Several coronary artery Z score models have been developed. However, a Z score model derived by the lambda-mu-sigma (LMS) method has not been established. Methods Echocardiographic measurements of the proximal right coronary artery, left main coronary artery, proximal left anterior descending coronary artery, and proximal left circumflex artery were prospectively collected in 3,851 healthy children ≤18 years of age and divided into developmental and validation data sets. In the developmental data set, smooth curves were fitted for each coronary artery using linear, logarithmic, square-root, and LMS methods for both sexes. The relative goodness of fit of these models was compared using the Bayesian information criterion. The best-fitting model was tested for reproducibility using the validation data set. The goodness of fit of the selected model was visually compared with that of the previously reported regression models using a Q-Q plot. Results Because the internal diameter of each coronary artery was not similar between sexes, sex-specific Z score models were developed. The LMS model with body surface area as the independent variable showed the best goodness of fit; therefore, the internal diameter of each coronary artery was transformed into a sex-specific Z score on the basis of body surface area using the LMS method. In the validation data set, a Q-Q plot of each model indicated that the distribution of Z scores in the LMS models was closer to the normal distribution compared with previously reported regression models. Finally, the final models for each coronary artery in both sexes were developed using the developmental and validation data sets. A Microsoft Excel–based Z score calculator was also created, which is freely available online (http://raise.umin.jp/zsp/calculator/). Conclusions Novel LMS models with which to estimate the sex-specific Z score of each internal coronary artery diameter were generated and validated using a large pediatric population.

The afterload to the left ventricle increases following valve replacement in chronic mitral regurgitation (MR), yet there has been no study taking into account left ventricular (LV) afterload. In 43 patients with isolated chronic MR undergoing mitral valve replacement (MVR), we calculated LV wall stress using preoperative LV end-diastolic dimensions and diastolic aortic pressure (predictive LV wall stress = pWS). This value would represent LV wall stress at the instant of aortic valve opening immediately after MVR, assuming that LV end-diastolic dimensions and the aortic pressure did not change after operation. We also calculated end-systolic wall stress/volume index (ESS/ESVI) ratio, an index of myocardial function. None of 15 patients with the ESS/ESVI ratio1.6 had postoperative mortality or morbidity, whereas among the 26 patients with the ESS/ESVI ratio1.6, 12 patients had mortality (3 patients) and/or morbidity requiring intraaortic balloon pumping or prolonged catecholamine support. Three patients who died had pWS200 kdynes/cm2. Including these 3, all 5 patients whose pWS200 had mortality or severe morbidity immediately after surgery. In contrast, among the 38 patients with lower pWS, none died and only 7 patients (18%) had morbidity. Thus, patients who had a low contractility index and a high predictive afterload value had high mortality and morbidity. We conclude that the prediction of postoperative mortality and morbidity is improved by combined assessment of myocardial function and the hypothetical postoperative LV afterload.

Aortopulmonary window (APW) is a rare malformation. We recently operated on a child with APW, ventricular septal defect, right aortic arch, and anomalous right coronary artery from the APW. This patient also had a chromosomal abnormality. He underwent the repair of this complex lesion in a staged operation.

A 4-month-old boy with ventricular septal defect was found to have accessory mitral valve tissue attached to the anterior leaflet of the mitral valve. Operation was successfully performed to excise the accessory mitral tissue in the left ventricular outflow tract and close the ventricular septal defect. Most previously reported cases with accessory mitral valve tissue were associated with left ventricular outflow tract obstruction. This boy had no pressure gradient across the left ventricular outflow tract. The indications for prophylactic excision of nonobstructing accessory mitral valve tissue in a patient with other forms of congenital cardiac disease are discussed.

The first autopsy case of dilated cardiomyopathy associated with Noonan's syndrome is described. A 9-month-old girl with Noonan's syndrome died from cardiac failure. Autopsy showed biatrial and biventricular enlargement of the heart. The posterior half of the ventricular septum and right ventricular wall were remarkably thin. Other parts of the wall were nearly normal in thickness, but both ventricular cavities were dilated. Microscopically, the myocardium of both ventricles consisted of mainly abnormally thinned, elongated, and loosely arranged myocardial fibers lacking immunoreactivity to anti-dystrophin antibody. Myocardial disarray was not found except for where it normally existed. The abnormal changes of the myocardial fibers were considered to be primary. Common cardiomyopathy associated with Noonan's syndrome is a hypertrophic type. Various types of cardiovascular abnormality associated with Noonan's syndrome, including dilated cardiomyopathy, might be disclosed by further investigation and precise diagnosis of Noonan's syndrome.

Left ventricular (LV) afterload increases after mitral valve replacement, thus it would be useful to estimate postoperative LV afterload before surgery. We tested the usefulness of an index, wall stress, obtained from preoperative end-diastolic LV dimensions and diastolic blood pressure which would represent LV afterload after surgery. The data were compared with surgical mortality and morbidity. The wall stress ranged from 98 to 220 kdynes/cm2 and was 202 or higher in 3 patients who died. Five patients had wall stress above 200 kdynes/cm2. Among these, intra-aortic balloon pumping (IABP) was used in 4, and 3 died. Prolonged catecholamine support for greater than 10 days was given to all of the 4 patients, including two who died 14 and 23 days after surgery. Among 38 patients who had wall stress less than 200 kdynes/cm2, none died, IABP was performed in 3 patients, and prolonged catecholamine infusion was required in 5 patients. The incidence of mortality and morbidity were significantly higher in the high stress than in the low stress group (Chi-square analysis). Left ventricular end-diastolic index was larger in the high stress than in the low stress group (p less than 0.05). The mass/end-diastolic volume ratio was smaller in the high stress group than in the low stress group (P less than 0.05). In conclusion, this new index, predictive wall stress, is useful in selecting patients who would have high mortality and morbidity.