A Noonan-like pediatric patient with a de novo CBL pathogenic variant and an RNF213 polymorphism p.R4810K presenting with cardiopulmonary arrest due to left main coronary artery ostial atresia.

Left main coronary artery ostial atresia (LMCAOA) is an extremely rare condition. Here, we report the case of a 14-year-old boy with Noonan syndrome-like disorder in whom LMCAOA was detected following cardiopulmonary arrest. The patient had been diagnosed with Noonan syndrome-like disorder with a pathogenic splice site variant of CBL c.1228-2 A > G. He suddenly collapsed when he was running. After administering two electric shocks using an automated external defibrillator, the patient's heartbeat resumed. Cardiac catheterization confirmed the diagnosis of LMCAOA. Left main coronary artery angioplasty was performed. The patient was discharged without neurological sequelae. Brain magnetic resonance imaging revealed asymptomatic Moyamoya disease. In addition, RNF213 c.14429 G > A p.R4810K was identified. There are no reports on congenital coronary malformations of compound variations of RNF213 and CBL. In contrast, the RNF213 p.R4810K polymorphism has been established as a risk factor for angina pectoris and myocardial infarction in adults, and several congenital coronary malformations due to genetic abnormalities within the RAS/MAPK signaling pathway have been reported. This report aims to highlight the risk of sudden death in patients with RASopathy and RNF213 p.R4810K polymorphism and emphasize the significance of actively searching for coronary artery morphological abnormalities in these patients.

Changes in Cerebral Hemodynamics During Systemic Pulmonary Shunt and Pulmonary Artery Banding in Infants with Congenital Heart Disease.

Palliative surgery is often performed in the treatment of congenital heart disease. Two representative palliative procedures are the systemic pulmonary shunt and pulmonary artery banding. Dramatic changes in cerebral hemodynamics may occur in these operations due to changes in the pulmonary-to-systemic blood flow ratio and systemic oxygenation. However, there seem to be almost no studies evaluating them. Accordingly, we evaluated cerebral perfusion by transcranial Doppler ultrasonography and cerebral oxygenation by near infrared spectroscopy during these procedures. In the post hoc analysis of a previous prospective observational study, cerebral blood flow velocities of the middle cerebral artery measured by transcranial Doppler were compared between the start and end of surgery as were the pulsatility index and resistance index. The cerebral oxygenation values were also compared between the start and end of surgery. Twenty-two infants with systemic pulmonary shunt and 20 infants with pulmonary artery banding were evaluated. There were no significant differences of the flow velocities between the start and end of surgery in either procedure. The pulsatility index significantly increased after pulmonary artery banding, which may compete with the increase in cerebral perfusion due to the increase in systemic blood flow. The cerebral oxygenation decreased in both procedures, possibly due to an increase in body temperature. Arterial oxygen saturation was almost the same before and after both procedures. Contrary to our expectation, the changes in cerebral hemodynamics in the palliative operations were small if the management of physiological indices such as arterial oxygen saturation was properly performed during the procedures.

Perioperative junctional ectopic tachycardia associated with congenital heart disease: risk factors and appropriate interventions.

The risk factors and the appropriate interventions for perioperative junctional ectopic tachycardia (JET) in congenital heart disease (CHD) surgery have not been sufficiently investigated despite the severity of this complication. This study aimed to examine the risk factors and interventions for perioperative JET. From 2013 to 2020, 1062 surgeries for CHD (median patient age: 4.3 years, range 0.0-53.0) with or without a cardiopulmonary bypass (CPB) were performed at Hokkaido University, Japan. We investigated the correlation between perioperative JET morbidity factors, such as age, genetic background, CPB/aortic cross-clamp (ACC) time, use of inotropes and dexmedetomidine, STAT score, and laboratory indices. The efficacy of JET therapies was also evaluated. Of the 1062 patients, 86 (8.1%) developed JET. The 30-day mortality was significantly high in JET groups (7% vs. 0.8%). The independent risk factors for JET included heterotaxy syndrome [odds ratio (OR) 4.83; 95% confidence interval (CI) 2.18-10.07], ACC time exceeding 90 min (OR 1.90; CI 1.27-2.39), and the use of 3 or more inotropes (OR 4.11; CI 3.02-5.60). The combination of anti-arrhythmic drugs and a temporary pacemaker was the most effective therapy for intractable JET. Perioperative JET after CHD surgery remains a common cause of mortality. Inotrope use was a risk factor for developing JET overall surgery risk. In short ACC surgeries, heterotaxy syndrome could increase the risk of JET, which could develop even without inotrope use in long ACC surgeries. It is crucial not to delay the treatment in cases with unstable hemodynamics caused by this arrhythmia. It is recommended to reduce numbers not dose of inotropes.

Left ventricular inflow obstruction due to a coronary arteriovenous fistula: a paediatric case report.

BACKGROUND: We report a rare case of left ventricular inflow obstruction from a branch of the left circumflex coronary artery to the right atrium caused by a coronary arteriovenous fistula (CAVF) in a young Japanese male child. CASE PRESENTATION: The patient was diagnosed with CAVF following a heart murmur shortly after birth. The left-to-right shunt caused right ventricular volume overload and pulmonary congestion. An emergency surgical intervention was performed for the CAVF on day 6 after birth. However, by 5 years of age, his left ventricular inflow obstruction worsened. We found an abnormal blood vessel originating from the proximal part of a branch of the left circumflex coronary artery, circling the outside of the mitral valve annulus along the medial side of the coronary sinus. As the child gets older, the blood inflow into the left ventricle might get restricted further, resulting in left-sided heart failure. CONCLUSION: Our findings suggest that even after CAVF closure surgery, it is essential to monitor for complications caused by progressive dilatation of a persistent CAVF.

Forns Index is a predictor of cardiopulmonary bypass time and outcomes in Fontan conversion.

Recent reports suggested that cardiopulmonary bypass (CPB) time is one of the risk factors for postoperative complications after Fontan conversion. Although Fontan conversion may be performed for the patients with hepatic fibrosis after initial Fontan procedure, there is no predictive indicator regarding the liver function associated with hemostasis which can affects CPB time. Thirty-one patients who underwent Fontan conversion using the same surgical procedure (extracardiac conduit conversion with right atrium exclusion) were enrolled. In multivariate analyses including age at Fontan conversion, interval from initial Fontan to conversion, hemodynamic data such as right atrial pressure, ventricular end-diastolic pressure, and cardiac index, hepatic data such as platelet count, prothrombin time international normalized ratios, serum total bilirubin, hyaluronic acid levels, five known indices for hepatic fibrosis (Forns Index, APRI, FIB4, FibroIndex, and MELD-XI), and liver stiffness measured by ultrasound elastography, only the Forns Index remained independently associated with the CPB time (P < 0.01) and blood transfusions (plasma transfusions and platelet concentrations: P < 0.01 for both). The cutoff level for Forns Index to predict the prolonged CPB time (exceeding 240 min) was 4.85 by receiver-operating characteristic curve (area under the curve 0.823, sensitivity 76.9%, and specificity 72.2%). Three patients with Forns Index > 7.0 had poor outcomes with long CPB time and massive blood transfusions in contrast with the other 28 patients. In conclusion, Forns Index could serve as a practical predictor of CPB time and is associated with blood transfusion volume in Fontan conversion.

Reconstruction of right ventricular outflow tract with severe calcification: lantern procedure.

Right ventricular outflow tract reconstruction is repeatedly required after the Rastelli procedure. However, standard right ventricular outflow tract reconstruction using direct anastomosis on the posterior right ventricular outflow tract wall is unfeasible in cases with severe calcification. Herein, we present a novel technique called the "lantern procedure," which can fix the prosthetic pulmonary valve without anastomosis to the calcified right ventricular outflow tract wall.

Revisiting the supramolecular organization of photosystem II in Chlamydomonas reinhardtii.

Photosystem II (PSII) is a multiprotein complex that splits water and initiates electron transfer in photosynthesis. The central part of PSII, the PSII core, is surrounded by light-harvesting complex II proteins (LHCIIs). In higher plants, two or three LHCII trimers are seen on each side of the PSII core whereas only one is seen in the corresponding positions in Chlamydomonas reinhardtii, probably due to the absence of CP24, a minor monomeric LHCII. Here, we re-examined the supramolecular organization of the C. reinhardtii PSII-LHCII supercomplex by determining the effect of different solubilizing detergents. When we solubilized the thylakoid membranes with n-dodecyl-ß-D-maltoside (ß-DM) or n-dodecyl-α-D-maltoside (α-DM) and subjected them to gel filtration, we observed a clear difference in molecular mass. The α-DM-solubilized PSII-LHCII supercomplex bound twice more LHCII than the ß-DM-solubilized supercomplex and retained higher oxygen-evolving activity. Single-particle image analysis from electron micrographs of the α-DM-solubilized and negatively stained supercomplex revealed that the PSII-LHCII supercomplex had a novel supramolecular organization, with three LHCII trimers attached to each side of the core.

Bronchial artery hypertrophy-associated perioperative pulmonary hemorrhage in cardiovascular surgery: a case report.

BACKGROUND: Pulmonary hemorrhage is a life-threatening complication of cardiovascular surgery. Bronchial artery hypertrophy, a rare pathology associated with inflammatory and ischemic respiratory diseases, increases the risk of pulmonary hemorrhage; however, its involvement in cardiovascular surgery is not well known. We present two cardiovascular surgical cases in which embolization of the hypertrophied bronchial artery was effective in controlling perioperative pulmonary hemorrhage. CASE PRESENTATION: The first case was a 51-year-old man with chronic obstructive pulmonary disease who developed acute type A aortic dissection. After emergent surgery, his blood pressure suddenly dropped in the intensive care unit; computed tomography revealed a right hemothorax. Because a 4-mm dilated bronchial artery was identified on preoperative computed tomography, the hemothorax was suspected to be associated with bronchial artery hypertrophy. Selective bronchial arteriography was emergently performed and revealed a right pulmonary parenchymal blush. After subsequent coil embolization of the bronchial artery, the parenchymal blush disappeared, and his hemodynamic condition stabilized. The second case was a 66-year-old man with bronchiectasis who was referred for redo aortic valve replacement due to structural valve deterioration. A bioprosthesis was previously implanted to avoid permanent anticoagulation because the patient had repeated episodes of hemoptysis; however, he still had persistent hemosputum during admission for the redo aortic valve replacement. A dilated bronchial artery 3.7 mm in size was incidentally identified on preoperative computed tomography, and hence, the repeated hemosputum was suspected to be associated with bronchial artery hypertrophy. Bronchial arteriography revealed a right pulmonary parenchymal blush, and prophylactic embolization of the bronchial artery was performed. The hemosputum disappeared after the procedure, and redo aortic valve replacement was performed uneventfully 8 days later. CONCLUSION: In cardiovascular surgery, the risk of pulmonary hemorrhage associated with bronchial artery hypertrophy should be considered, especially in patients with inflammatory and ischemic respiratory diseases.

Usefulness of Prolonged PR Interval to Predict Atrial Tachyarrhythmia Development Following Surgical Repair of Tetralogy of Fallot.

Atrial tachyarrhythmias (ATAs), which may occur after tetralogy of Fallot (TOF) surgery, can cause sudden cardiac death. However, ATAs may also develop in response to electrical substrates. This study aims to examine the predictive factors for ATAs by identifying electrical substrates in the atrium obtained from 12-lead electrocardiogram in patients who underwent TOF repair. A total of 144 patients aged >15 years (median, 31.6 years) who underwent TOF repair at Hokkaido University were enrolled. We investigated the correlation between the development of ATAs with age, time interval after initial corrective surgery, brain natriuretic peptide levels, cardiac magnetic resonance parameters (right ventricular end-diastolic volume index, right ventricular end-systolic volume index, right ventricular ejection fraction, right atrial volume index, left ventricular end-diastolic volume index, left ventricular ejection fraction), and 12-lead electrocardiogram parameters (P wave maximum voltage, PR interval, QRS width, number of fragmented QRS). Of the 144 patients, 44 patients (30.6%) developed ATAs. Multivariate analysis revealed time interval after initial corrective surgery (odds ratio 6.7, 95% confidence interval 1.78 to 12.6) and PR interval (odds ratio 2.7, 95% confidence interval: 1.17 to 4.20) as independent risk factors for the development of ATAs. The receiver operating characteristic curve revealed a PR interval cut-off value of >200 milliseconds as predictive of the development of ATAs in patients more than 15 years after initial corrective surgery (area under the curve, 0.658; sensitivity, 71.4%; specificity, 66.4%). The present study demonstrated that a prolonged PR interval is a simple and convenient predictor for the development of ATAs in patients who underwent TOF repair.

Intralobar pulmonary sequestration associated with left main coronary artery obstruction and mitral regurgitation.

A 4-year-old boy with left intralobar pulmonary sequestration associated with left main coronary artery obstruction (LMCAO) and severe mitral regurgitation (MR) was admitted to our hospital. Since the patient presented with dyskinesia of the cardiac apex and increased left ventricular end-diastolic volume (LVEDV), left main coronary artery reconstruction and mitral annuloplasty were performed. The enlargement of the left ventricle was improved after sequential surgeries. There was a risk of deterioration of MR and regrowth of LVEDV due to shunt blood flow; therefore, left lower lobectomy and aberrant artery division were performed. This is a very rare case of a patient with pulmonary sequestration associated with LMCAO and severe MR.

Total Anomalous Pulmonary Venous Connection with Lethal Pulmonary Venous Obstruction Managed by Multidisciplinary Cooperation.

BACKGROUND: Total anomalous pulmonary venous connection (TAPVC) is a critical congenital heart disease for which emergency surgery is required after birth. In cases of no intervention, TAPVC is associated with a high mortality rate in the first year of life. Although foetal echocardiographic techniques for diagnosing TAPVC have improved, TAPVC remains one of the most difficult congenital heart diseases to diagnose via foetal echocardiography. Here, we report a case of TAPVC with pulmonary venous obstruction (PVO), which was diagnosed via foetal echocardiography. Case Presentation. On foetal echocardiography at 32 weeks' gestation, a large atrial septal defect, enlarged superior vena cava, and continuous flow pattern in the vertical vein from the common chamber were observed in the foetus. Paediatric cardiologists and cardiac surgeons, neonatologists, and obstetricians planned to perform a caesarean section and emergency heart surgery. The male infant was born at 37 weeks' gestation via caesarean section, and postnatal echocardiography revealed PVO at the confluence of the superior vena cava and common chamber. Similarly, chest computed tomography confirmed the foetal diagnosis. The postnatal diagnoses were TAPVC type Ib, PVO, atrial septal defect, and patent ductus arteriosus. Surgical repair of the TAPVC was initiated within the first 3 hours of life. Screening brain echocardiography and head computed tomography revealed intracranial haemorrhage and hydrocephalus. Therefore, the patient underwent emergency bilateral external drainage on day 13. On day 48, a ventriculoperitoneal shunt was inserted owing to progressive brain ventricular dilatation. The patient was discharged home on postoperative day 68. CONCLUSIONS: Although the prognosis of TAPVC with PVO remains poor, continuous observation through foetal echocardiography and early interdepartmental collaboration can result in good outcomes.

Persistent Fifth Aortic Arch With Left Ventricular Dysfunction and Left Bronchial Obstruction.

Persistent fifth aortic arch (AA) is a rare anomaly in congenital heart disease, which is often associated with aortic obstructive diseases. We report a 7-month-old infant diagnosed with persistent fifth AA with left ventricular dysfunction along with left bronchial malacia due to compression from their own heart. Surgical repair was performed, including AA reconstruction using the fifth AA as an in situ flap to enlarge the fourth AA with end-to-end anastomosis, and external stenting for the left bronchial malacia. Postoperative courses were uneventful. On computed tomography, a reconstructed AA without obstruction and an expanded left bronchus were seen.

Effects of blood flow dynamics on autologous pericardial degeneration in reconstructed pulmonary arteries.

OBJECTIVES: To clarify the risk factors for abnormal degeneration of autologous pericardium, the mechanical stress on the endothelial tissue caused by turbulent blood flow in the pulmonary artery (PA) reconstructed with autologous pericardium and major aortopulmonary collateral arteries was assumed in pulmonary atresia and ventricular septal defect. METHODS: Patient-specific PA models were created for 6 patients based on their past computed tomography images taken after unifocalization of major aortopulmonary collateral arteries. Computational fluid dynamics models were created to simulate the physiological pulsatile flow including the peripheral reflection wave, characteristic impedance and autonomous regulation system. Flow streamline, wall shear stress (WSS) and the oscillatory shear index (OSI) were calculated from the simulated result. PA degeneration was evaluated with the computed tomography images before the intracardiac repair. RESULTS: Regions with physiological high WSS had fewer abnormal changes. Excessively high WSS was often detected at the anastomosis site of the reconstructed PA, and intimal thickening was found in these regions during intracardiac repair. Regions with high OSI and low WSS had dilated change within several months. In 1 patient, in particular, detached vortex flow occurred at the rectangular angle anastomosis site of the right PA in flow streamline, resulting in high OSI and low WSS with abnormal enlargement in the pericardium. CONCLUSIONS: Endothelial stress caused by blood flow would affect the degeneration of autologous pericardium and major aortopulmonary collateral arteries in the reconstructed PA. High OSI and low WSS might induce enlargement or dilatation, and excessively high WSS in the anastomosis site might induce intimal thickening.

A Novel Surgical Technique for Right-Sided Interrupted Aortic Arch by Interposition of a Pulmonary Autograft Tube.

Right-sided interrupted aortic arch (IAA) is a rare cardiac anomaly. In general, the right bronchus sits higher than the left bronchus, so aortic arch reconstruction with a direct anastomosis has a risk of tracheal and bronchial obstruction. This report describes the successful definitive repair of a right-sided IAA in a 2.5-kg neonate by aortic arch reconstruction with a pulmonary autograft tube (PA tube). Postoperative three-dimensional multidetector computed tomography showed the reconstructed aortic arch without airway obstruction or aortic stenosis. The use of a PA tube is a simple and useful technique for aortic arch reconstruction in patients with a high risk of tracheal andbronchial obstruction, such as right-sided IAA.

First Successful Clinical Application of the In Vivo Tissue-Engineered Autologous Vascular Graft.

PURPOSE: The ideal material for pediatric pulmonary artery (PA) augmentation is autologous pericardium. However, its utility for multistaged operations is limited. In this study, we applied an in vivo tissue-engineered autologous Biotube graft to a patient with congenital heart disease for the first time. DESCRIPTION: For molds of the Biotubes, two silicone 19F drain tubes were embedded in the subcutaneous spaces of a 2-year-old girl with a diagnosis of pulmonary atresia and ventricular septal defect with major aortopulmonary collateral arteries during palliative surgical procedures. When definitive repair was performed after 8 months, the implants were removed to prepare Biotubes, one of which was cut open and autologously implanted into the PA for patch augmentation. EVALUATION: Seven months after implantation, the Biotube patch-augmented PA tolerated balloon angioplasty (BAP) for residual stenosis of the peripheral PA. Computed tomography images after BAP showed the well-preserved shape of the Biotube patch-augmented PA. Neither aneurysm formation nor stenosis was observed. CONCLUSIONS: The safety and feasibility of Biotubes for pediatric PA patch augmentation are described. Because Biotubes are completely autologous, they may be ideal material for pediatric PA augmentation.

Smaller-Sized Expanded Polytetrafluoroethylene Conduits With a Fan-Shaped Valve and Bulging Sinuses for Right Ventricular Outflow Tract Reconstruction.

BACKGROUND: One of the critical factors limiting conduit longevity in right ventricular outflow tract (RVOT) reconstruction with homografts and xenografts is the small size of the conduit. The aim of our study was to assess the outcome of using smaller-sized expanded polytetrafluoroethylene (ePTFE) conduits with a fan-shaped valve and bulging sinuses for RVOT reconstruction. METHODS: This retrospective review examined 303 patients who underwent RVOT reconstruction with ePTFE conduits at 63 Japanese hospitals between 2003 and 2014. Inclusion criteria were a conduit size less than or equal to 16 mm and the use of operative treatment as the primary correction for underlying heart disease. Patients undergoing palliative procedures were excluded. RESULTS: Median follow-up was 1.7 years. Freedom from conduit replacement and freedom from conduit reintervention were 90.1% ± 4.8% and 77.2% ± 5.6%, respectively. The most common indication for conduit reintervention was pulmonary artery (PA) bifurcation stenosis (82%). Modeling z-scores as a dichotomous variable revealed that freedom from conduit reintervention for PA bifurcation stenosis was significantly decreased for conduits with a z-score greater than or equal to 1.4 compared with z-scores less than 1.4 (p = 0.036). There were 30 patients (9.9%) who experienced at least moderate conduit stenosis and 21 patients (6.9%) with at least moderate conduit insufficiency. Univariate Cox regression analysis showed that conduit size was a significant factor for conduit stenosis (p = 0.006). CONCLUSIONS: Excellent midterm outcomes were achieved with ePTFE valved conduits, even when using smaller sizes. Conduit z-scores around 1.4 were optimal for RVOT reconstruction in younger patients.

Distinct physiological responses to a high light and low CO2 environment revealed by fluorescence quenching in photoautotrophically grown Chlamydomonas reinhardtii.

Mechanisms for countering environmental stress are essential to photosynthetic organisms. Alteration of the photosynthetic apparatus, a mechanism for balancing the flux of light energy and carbon fixation, can be characterized by fluorescence properties. In this study, we have established a simple protocol to determine the extent of energy-dependent quenching (qE) and quenching by state transition (qT) in Chlamydomonas cells by examining their fluorescence properties under light fluctuations. We identified qE as the uncoupler-sensitive NPQ component that was rapidly relaxed upon transition to dark conditions. We characterized the qT component by determining low-temperature fluorescence spectra and analyzing a state-transition-less mutant. By these methods, we observed that similar abiotic stresses-high light conditions (where excess energy is supplied) and low CO2 conditions (where energy utilization is limited)-induced different types of NPQ. High light conditions induced mainly qE-quenching that increased gradually while low CO2 conditions induced mainly qT-quenching that peaked in 20 min and then decreased gradually. That high light and low carbon signals induced different physiological responses suggests that they triggered different genetic responses, which altered protein expression under each of the conditions.