Modeling of multiple atrial septal defects with inferior vena cava rim deficiency: Three-dimensional visualization of the rim based on transthoracic echocardiographic imaging.

The morphologic features of the multiple atrial septal defects assessed by TTE-based 3D imaging were similar to those by 3D-TEE. TTE-based 3D model had excellent visibility, allowing observation of 3D structure of the rims of the defects. It may be useful method for assessment of the multiple atrial septal defects.

Prenatal diagnosis and perinatal clinical course of isolated left-sided innominate artery.

Isolated left-sided innominate artery, a rare congenital anomaly in which the left-sided innominate artery arises from the main pulmonary trunk, is usually diagnosed incidentally in children and adults. Limited reports exist on its prenatal diagnosis, with none comprehensively describing the associated perinatal haemodynamic changes. We report a case of prenatally diagnosed isolated left-sided innominate artery, describing the postnatal clinical course.

Complex congenital cardiovascular anomaly in a patient with AGO1-associated disorder.

Pathogenic AGO1 variants have been associated with neurodevelopmental disorders, including autism spectrum disorder, developmental delay, intellectual disability, and dysmorphic facial appearance. In mammalian models, defects in microRNA (miRNA) biogenesis are associated with congenital heart disease and dilated cardiomyopathy. We describe the case of a patient with partial anomalous pulmonary venous return, hypoplastic left lung, bilateral pulmonary sequestration, and dilated myocardiopathy. We identified a de novo pathogenic variant of AGO1, which encodes an Argonaute protein forming a gene-silencing complex with microRNAs. The patient was diagnosed with dilated cardiomyopathy with no apparent cause at 3 years of age. She was started on enalapril and carvedilol, and her heart failure was well controlled. We expanded the AGO1-associated phenotype to include complex congenital cardiovascular anomaly and dilated cardiomyopathy in humans.

Intra-atrial re-entrant tachycardia after percutaneous atrial septal defect closure: a case report.

We report a case of a 6-year-old boy who developed intra-atrial re-entrant tachycardia after percutaneous atrial septal defect closure. Ablation was performed, and the circuit of tachycardia was identified. This was a rare complication caused by right atrial enlargement due to an atrial septal defect closure device.

Replacement of pulmonary venous stent during Fontan operation.

Post-operative pulmonary venous stenosis is a poor prognostic factor in single-ventricle haemodynamics. Implantation of a drug-eluting stent is a therapeutic option. However, due to their small size, they inevitably become inadequate as the patient grows. We present the first case, to the best of our knowledge, of the replacement of a small-diameter stent with a large-diameter stent during Fontan surgery.

Cardiac features of Noonan syndrome in Japanese patients.

BACKGROUND: Cardiovascular disease is one of the most important problems in long-term follow-up for Noonan syndrome. We examined cardiovascular issues and clinical manifestations, with a focus on the cardiovascular disease and prognosis of patients with Noonan syndrome. METHODS: This single-centre study evaluated patients who were clinically and genetically diagnosed with Noonan syndrome. RESULTS: Forty-three patients diagnosed with Noonan syndrome were analysed. The most prevalent responsible mutation was found in PTPN11 (25/43). The second and third most prevalent causative genes were SOS1 (6/43) and RIT1 (5/43), respectively, and 67.4% of genetically diagnosed patients with Noonan syndrome had structural cardiovascular abnormalities. Pulmonary valve stenosis was prevalent in patients with mutations in PTPN11 (8/25), SOS1 (4/6), and RIT1 (4/5). Hypertrophic cardiomyopathy was found in two of three patients with mutations in RAF1. There was no difference in the cardiovascular events or cardiovascular disease prevalence in patients with or without PTPN11 mutations. The proportion of RIT1 mutation-positive patients who underwent intervention due to cardiovascular disease was significantly higher than that of patients with PTPN11 mutations. Patients who underwent any intervention for pulmonary valve stenosis exhibited significantly higher pulmonary flow velocity than patients who did not undergo intervention, when they visited our hospital for the first time. All patients who underwent intervention for pulmonary valve stenosis had a pulmonary flow velocity of more than 3.0 m/s at first visit. CONCLUSIONS: These findings suggest that genetic information can provide a clinical prognosis for cardiovascular disease and may be part of genotype-based follow-up in Noonan syndrome.

Control of Heart Rate in Infant and Child Tachyarrhythmia With Reduced Cardiac Function Using Landiolol (HEARTFUL)　- Results of a Prospective, Multicenter, Uncontrolled Clinical Study.

BACKGROUND: The prospective Control of HEART rate in inFant and child tachyarrhythmia with reduced cardiac function Using Landiolol (HEARTFUL) study investigated the effectiveness and safety of landiolol, a short-acting ß1 selective blocker, in children.Methods and Results: Twenty-five inpatients aged ≥3 months to <15 years who developed supraventricular tachyarrhythmias (atrial fibrillation, atrial flutter, supraventricular tachycardia, and inappropriate sinus tachycardia) were treated with landiolol. The primary endpoint, the percent of patients with a reduction in heart rate ≥20% from the initial rate of tachycardia, or termination of tachycardia at 2 h after starting landiolol, was achieved in 12/25 patients (48.0%; 95% CI 28.4-67.6), which exceeded the predetermined threshold (38.0%). At 2 h after starting landiolol administration, heart rate had decreased by ≥20% in 45.8% (11/24) and recovery to sinus rhythm was achieved in 40.0% (6/15) of the patients. Adverse reactions (ARs) occurred in 24.0% (6/25) of patients, and the study was discontinued in 4.0% (1/25) of the patients; however, none of these ARs were considered serious. The most common AR was hypotension (20.0% [5/25] of patients). CONCLUSIONS: The HEARTFUL study has demonstrated the efficacy of landiolol, by reducing heart rate or terminating tachycardia, in pediatric patients with supraventricular tachyarrhythmias. Although serious ARs and concerns were not identified in this study, physicians should be always cautious of circulatory collapse due to hypotension.

Assessment of the left ventricular volume of tetralogy of Fallot by electrocardiogram.

BACKGROUND: Sufficient left ventricular volume is required for patients with tetralogy of Fallot (TOF) who are going to have biventricular repair. In this study, we investigated the utility of the electrocardiogram to evaluate left ventricular volume in patients with TOF. METHOD: Patients whose left ventricular (LV) end-diastolic volume was lower than 80% of normal were defined as having a small LV. Seven patients with TOF who had to undergo Blalock-Taussig shunt surgery because of a small LV were assigned to group S. Twenty patients with TOF who had sufficient LV volume were assigned to group G. The amplitudes of the Q wave of V5-7 leads (QV5-QV7), the S wave of V1 lead, and the R wave of the II, III, aVf, and V5-7 leads of the electrocardiogram were evaluated. RESULTS: The amplitude of QV5 was 0 mV in all cases in group S, which was significantly smaller than that in group G (0 vs 0.01 mV, P = 0.028). The frequency of absent QV5 was significantly higher in group S than in group G (100% vs 50%, P = 0.026). Absent QV5 showed 100% sensitivity, 50% specificity, and a negative predictive value of 100% for a small LV. CONCLUSIONS: In TOF, the amplitude of the septal Q wave reflects LV volume. In particular, the absence of QV5 suggests a small LV end-diastolic volume, which is lower than 80% of normal.

Takotsubo cardiomyopathy in a child with single-ventricle disease.

Takotsubo cardiomyopathy, a disease that causes transient contractile abnormalities mainly in the left ventricular apex, is rarely reported in children, especially in those with single-ventricle disease. A 4-year-old boy with a single right ventricle was transferred to our hospital following a severe seizure and was diagnosed with takotsubo cardiomyopathy by echocardiography. His cardiac function improved; however, he developed hypoxic-ischemic encephalopathy.

Transient phrenic nerve palsy induced by cardiac catheterisation in an infant.

We report on a 7-month-old male with transient phrenic nerve palsy induced by diagnostic cardiac catheterisation. The phrenic nerve palsy, which is a rare complication, was due to extravascular bleeding from a branch of the internal mammary artery.

Emery-Dreifuss muscular dystrophy with dilated cardiomyopathy preceding skeletal muscle symptoms.

Emery-Dreifuss muscular dystrophy is a slowly progressive skeletal muscle and joint disorder associated with cardiac complications. Dilated cardiomyopathy was the initial manifestation of Emery-Dreifuss muscular dystrophy in an 8-year-old girl. Despite normal muscle and myocardial biopsies, genetic testing revealed LMNA mutations. As Emery-Dreifuss muscular dystrophy is associated with minimal skeletal muscle weakness, cardiac complications can facilitate its diagnosis.

Cardiac features in a patient with erythrokeratodermia cardiomyopathy syndrome.

Patients with erythrokeratodermia cardiomyopathy syndrome exhibit congenital, generalised erythrokeratoderma and dilated cardiomyopathy during early childhood. We report a case of erythrokeratodermia cardiomyopathy syndrome in a 15-year-old male patient and focus this report on cardiac features that were present.

A retrospective study of perioperative clinical seizures and epilepsy in children after operation for CHD.

This study investigated the incidence and risk factors of perioperative clinical seizure and epilepsy in children after operation for CHD. We included 777 consecutive children who underwent operation from January 2013 to December 2016 at Kanagawa Children's Medical Center, Kanagawa, Japan. Perinatal, perioperative, and follow-up medical data were collected. Elastic net regression and mediation analysis were performed to investigate risk factors of perioperative clinical seizure and epilepsy. Anatomic CHD classification was performed based on the preoperative echocardiograms; cardiac surgery was evaluated using Risk Adjustment in Congenital Heart Surgery 1. Twenty-three (3.0%) and 15 (1.9%) patients experienced perioperative clinical seizure and epilepsy, respectively. Partial regression coefficient with epilepsy as the objective variable for anatomical CHD classification, Risk Adjustment in Congenital Heart Surgery 1, and the number of surgeries was 0.367, 0.014, and 0.142, respectively. The proportion of indirect effects on epilepsy via perioperative clinical seizure was 22.0, 21.0, and 33.0%, respectively. The 15 patients with epilepsy included eight cases with cerebral infarction, two cases with cerebral haemorrhage, and three cases with hypoxic-ischaemic encephalopathy; white matter integrity was not found. Anatomical complexity of CHD, high-risk cardiac surgery, and multiple cardiac surgeries were identified as potential risk factors for developing epilepsy, with a low rate of indirect involvement via perioperative clinical seizure and a high rate of direct involvement independently of perioperative clinical seizure. Unlike white matter integrity, stroke and hypoxic-ischaemic encephalopathy were identified as potential factors for developing epilepsy.

Clinical trial of the CP stent for pulmonary artery stenosis: the first investigator-initiated clinical trial for pediatric interventional cardiology in Japan.

Stenting is an important treatment option for pulmonary artery stenosis (PS) associated with congenital heart disease (CHD). However, no stent has been approved for this indication in Japan, despite negotiation between academia and the regulatory bodies for longer than 20 years. To evaluate efficacy and safety of the CP stent, we performed the first investigator-initiated clinical trial for pediatric interventional cardiology in Japan. This trial was designed as a single-arm, prospective, clinical trial. Patients who had postoperative PS associated with CHD were included. Stenting was attempted in 24 cases and succeeded in 22 cases. The median age of the patients was 11 years (3-36 years) and weight was 38 kg (12-69 kg), while follow-up for 12 months was completed. In all 22 cases, stenting was successful, with a 50% increase in the minimum lumen diameter (MLD) in 86.4% of patients (90% confidence interval, 68.4-96.2%). The mean percent change in MLD was 119.3 ± 52.5%. In two-ventricle repair, the mean percent change in systolic right ventricular/aortic pressure was - 8.5 ± 16.1%, while that of pressure gradient was - 55.9 ± 41.7%. In single-ventricle repair, the percent change in the mean pressure gradient was - 100.0 ± 0%, while that of SaO2 was 1.4 ± 1.7%. No serious adverse events or significant restenosis was reported. The CP stent is highly effective and safe for PS associated with CHD. This study has significant importance in not only scientific but also social considerations.

Correlation of exercise-induced peripheral venous hypertension with exercise intolerance in patients with Fontan circulation.

Owing to the absence of a sub-pulmonary ventricle, the central venous pressure rises in patients with Fontan circulation. During exercise, central venous pressure may rise further to increase the systemic ventricular preload and cardiac output. We performed a single-centre prospective trial of cardiopulmonary exercise test while monitoring peripheral venous pressure which strongly correlates with central venous pressure. The objective of this study was to test the hypothesis that peripheral venous pressure at peak exercise inversely correlates with exercise capacity in patients with Fontan circulation. Seventeen patients following Fontan operation performed cardiopulmonary exercise test while monitoring peripheral venous pressure. Peak oxygen uptake, heart rate reserve, peak oxygen pulse (divided by body surface area), and peripheral venous pressure at peak exercise were measured. Correlations of peripheral venous pressure at peak exercise with the peak oxygen uptake, heart rate reserve, and peak oxygen pulse were evaluated. The peripheral venous pressure at peak exercise inversely correlated with the peak oxygen uptake (R = -0.66, p < 0.01), heart rate reserve (R = -0.6, p < 0.05), and peak oxygen pulse (R = -0.48, p < 0.05). Exercise-induced peripheral venous hypertension correlates with exercise intolerance in patients with Fontan circulation. Peak oxygen uptake is a useful index for evaluating the status of congestion in the daily life of patients with Fontan circulation.

Fetal case of right atrial isomerism with infracardiac total anomalous pulmonary venous connection and agenesis of the ductus venosus.

After birth, the ductus venosus becomes an important route connecting the pulmonary and systemic venous systems for survival in infracardiac total anomalous pulmonary venous connection. We encountered a fetal case of right atrial isomerism with infracardiac total anomalous pulmonary venous connection and agenesis of ductus venosus. Prenatal echocardiography suggested that the fetus had severe pulmonary venous obstruction; however, no obstructive lesions were detected at the level of the vertical vein that drained into the portal veins. Therefore, we concluded that emergency surgical pulmonary venous obstruction release was the only way for the fetus to survive. However, the saturation level was maintained above 70% due to the abundant communications via the hepatic sinusoid over 1 week after birth. In conclusion, hepatic sinusoids can be a sufficient route for pulmonary venous return and may not cause severe pulmonary venous obstruction in infracardiac total anomalous pulmonary venous connection with agenesis of ductus venosus.

Physical and biological impacts of collimator-scattered protons in spot-scanning proton therapy.

To improve the penumbra of low-energy beams used in spot-scanning proton therapy, various collimation systems have been proposed and used in clinics. In this paper, focused on patient-specific brass collimators, the collimator-scattered protons' physical and biological effects were investigated. The Geant4 Monte Carlo code was used to model the collimators mounted on the scanning nozzle of the Hokkaido University Hospital. A systematic survey was performed in water phantom with various-sized rectangular targets; range (5-20 cm), spread-out Bragg peak (SOBP) (5-10 cm), and field size (2 × 2-16 × 16 cm2 ). It revealed that both the range and SOBP dependences of the physical dose increase had similar trends to passive scattering methods, that is, it increased largely with the range and slightly with the SOBP. The physical impact was maximized at the surface (3%-22% for the tested geometries) and decreased with depth. In contrast, the field size (FS) dependence differed from that observed in passive scattering: the increase was high for both small and large FSs. This may be attributed to the different phase-space shapes at the target boundary between the two dose delivery methods. Next, the biological impact was estimated based on the increase in dose-averaged linear energy transfer (LETd ) and relative biological effectiveness (RBE). The LETd of the collimator-scattered protons were several keV/µm higher than that of unscattered ones; however, since this large increase was observed only at the positions receiving a small scattered dose, the overall LETd increase was negligible. As a consequence, the RBE increase did not exceed 0.05. Finally, the effects on patient geometries were estimated by testing two patient plans, and a negligible RBE increase (0.9% at most in the critical organs at surface) was observed in both cases. Therefore, the impact of collimator-scattered protons is almost entirely attributed to the physical dose increase, while the RBE increase is negligible.

Familial total anomalous pulmonary venous return with 15q11.2 (BP1-BP2) microdeletion.

A 15q11.2 microdeletion (BP1-BP2) is associated with congenital heart diseases (CHDs), developmental delay, and epilepsy. This deletion co-occurs with CHD in 20-30% patients, but a familial case of CHD and a 15q11.2 deletion has not been identified. Here we report the first familial (three siblings) case of total anomalous pulmonary venous return associated with 15q11.2 deletion. Array comparative genomic hybridization identified a ~395 kb deletion at 15q11.2 in patient 1. This deletion was confirmed by fluorescence in situ hybridization in patients 1 and 3 and their asymptomatic father. No deleterious mutation was identified by proband-only exome sequencing of patient 1. One healthy sibling and their mother did not carry the deletion. This deletion is often inherited from asymptomatic parents with an estimated low penetrance of 10.4%. Conversely, we observed high penetrance of this deletion, but secondary copy-number variants or pathogenic variants were not detected in this family.