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In pulmonary valve replacement (PVR) after tetralogy of Fallot (TOF) repair, it is recommended that PVR be performed before the right ventricular end-diastolic volume index (RVEDVI) reaches 170 ml/m2 on cardiac magnetic resonance imaging (cMRI) to normalize the RV volume after PVR. We examined the utility of QRS duration, cardiothoracic ratio (CTR), and plasma brain natriuretic peptide (BNP) as markers of an enlarged RV volume to perform PVR at the optimal timing. We assessed the correlation of QRS duration, CTR, and BNP with RVEDVI and RVESVI on cMRI in 26 patients after TOF repair. Fifteen patients underwent PVR (age, 45.2 ± 11.4 years). The RV volume changes from before to after PVR were investigated. Twelve patients underwent post-PVR cMRI. QRS duration, BNP, and CTR were positively correlated with RVEDVI and RVESVI after TOF repair. The post-PVR QRS duration was also positively correlated with post-PVR RVEDVI (p = 0.017) and RVESVI (p = 0.001). From before to after PVR, in cases with QRS duration ≤ 160 ms, the QRS duration decreased from 110.4 ± 28.9 to 101.8 ± 30.5 ms (p = 0.063). Both RVEDVI and RVESVI decreased to the normal range in 4 of 5 cases. In contrast, in cases with QRS duration > 160 ms, the QRS duration decreased from 183.0 ± 17.4 to 160.3 ± 23.8 ms (p = 0.013); however, RVESVI did not normalize in 6 of 7 cases. A prolonged QRS duration is a useful marker of RVEDVI and RVESVI enlargement after TOF repair. A QRS duration of 160 ms is a sensitive cutoff value for predicting RV volume normalization after PVR.

Minimally invasive cardiac surgery( MICS) has emerged in 1990s. Nowadays, MICS via mini thoracotomy became popular for valvular heart disease. Robot-assisted cardiac surgery was introduced with extension to MICS. Robot-assisted cardiac surgery for valvular heart disease has been covered by health insurance since 2018. So far, the number of authorized facilities for robot-assisted cardiac surgery is only 25. Currently available da Vinci surgical system is a burden to not only the surgical team but also the facility. There are a lot of problems to overcome for applying robot-assisted cardiac surgery as a standardized procedure. An educational institution like a university hospital needs to expand systematic human resource development and technological innovation for continuing and developing the robot-assisted cardiac surgery. The most important thing for the surgeon is to keep in mind for true minimally invasive surgery for the patients not for minimally incisional surgery for the cosmetic reason.

The characterization of aortic valve interstitial cells (VICs) cultured under optimal conditions is essential for understanding the molecular mechanisms underlying aortic valve stenosis. Here, we propose 2% hypoxia as an optimum VIC culture condition. Leaflets harvested from patients with aortic valve regurgitation were digested using collagenase and VICs were cultured under the 2% hypoxic condition. A significant increase in VIC growth was observed in 2% hypoxia (hypo-VICs), compared to normoxia (normo-VICs). RNA-sequencing revealed that downregulation of oxidative stress-marker genes (such as superoxide dismutase) and upregulation of cell cycle accelerators (such as cyclins) occurred in hypo-VICs. Accumulation of reactive oxygen species was observed in normo-VICs, indicating that low oxygen tension can avoid oxidative stress with cell-cycle arrest. Further mRNA quantifications revealed significant upregulation of several mesenchymal and hematopoietic progenitor markers, including CD34, in hypo-VICs. The stemness of hypo-VICs was confirmed using osteoblast differentiation assays, indicating that hypoxic culture is beneficial for maintaining growth and stemness, as well as for avoiding senescence via oxidative stress. The availability of hypoxic culture was also demonstrated in the molecular screening using proteomics. Therefore, hypoxic culture can be helpful for the identification of therapeutic targets and the evaluation of VIC molecular functions in vitro.

The Impella (Abiomed, Danvers, MA, USA) is a novel percutaneous heart pump device for left ventricular (LV) assistance; however, LV thrombus is a notable contraindication for this device. Contrast computed tomography assessment is useful for detecting LV thrombus and preventing thromboembolism in patients recommended for Impella use.

ObjectivesThe molecular mechanisms underlying post-operative pericardial adhesions remain poorly understood. We aimed to unveil the temporal molecular and cellular mechanisms underlying tissue dynamics during adhesion formation, including inflammation, angiogenesis, and fibrosis.Methods and ResultsWe visualized cell-based tissue dynamics during pericardial adhesion using histological evaluations. To determine the molecular mechanism, RNA-seq was performed. Chemical inhibitors were administered to confirm the molecular mechanism underlying adhesion formation. A high degree of adhesion formation was observed during the stages in which collagen production was promoted. Histological analyses showed that arterioles excessively sprouted from pericardial tissues after the accumulation of neutrophils on the heart surface in mice as well as humans. The combination of RNA-seq and histological analyses revealed that hyperproliferative endothelial and smooth muscle cells with dedifferentiation appeared in cytokine-exposed sprouting vessels and adhesion tissue but not in quiescent vessels in the heart. SMAD2/3 and ERK activation was observed in sprouting vessels. The simultaneous abrogation of PI3K/ERK or TGF-β/MMP9 signaling significantly decreased angiogenic sprouting, followed by inhibition of adhesion formation. Depleting MMP9-positive neutrophils shortened mice survival and decreased angiogenic sprouting and fibrosis in the adhesion. Our data suggest that TGF-β/matrix metalloproteinase-dependent tissue remodeling and PI3K/ERK signaling activation might contribute to unique angiogenesis with dedifferentiation of vascular smooth muscle cells from the contractile to the synthetic phenotype for fibrosis in the pericardial cavity.ConclusionsOur findings provide new insights in developing prevention strategies for pericardial adhesions by targeting the recruitment of vascular cells from heart tissues.

Introduction A dumbbell-shaped mediastinal granular cell tumor has never been reported, and there have been no reports of dumbbell-shaped tumors resected with a combination of uniportal video-assisted thoracic surgery and the posterior approach. Presentation of case An 18-year-old woman was diagnosed with a mediastinal dumbbell-shaped granular cell tumor by computed tomography. Complete resection was achieved via a posterior approach combined with the uniportal video-assisted thoracic surgery. First, a T3 left hemilaminectomy was performed in the prone position and the tumor located inside the intervertebral foramen was removed as far as possible. Next, the patient was repositioned to the right lateral decubitus position, a 2.5-cm skin incision was made on the 4th intercostal posterior axillary line, and resection of the residual tumor was performed. Pathological diagnosis of the resected tumor revealed a benign granular cell tumor. The patient recovered post-surgery and no tumor was reported in the 4-month follow-up magnetic resonance imaging. Discussion This is the first reported case of a mediastinal dumbbell-shaped granular cell tumor and its successful resection using a combined posterior and uniportal video-assisted thoracic surgery approach. Conclusion This is a potentially safe and effective procedure for mediastinal granular cell tumors, with outstanding cosmetic advantages., Highlights • Our case presented with a rare mediastinal dumbbell-shaped granular cell tumor. • The tumor was resected using a combined posterior and uniportal VATS approach. • This is a safe and effective procedure for mediastinal dumbbell-shaped tumors.

Background The relationship between shot-to-shot sampling rates for dynamic myocardial computed tomography perfusion (CTP) and robustness of CTP-derived myocardial blood flow (CT-MBF) is debatable. We retrospectively investigated the influence of a reduced sampling rate for dynamic CTP on CT-MBF computation and diagnostic performance for detecting myocardial perfusion abnormalities. Methods Pharmacological stress dynamic whole-heart CTP was performed in 120 patients suspected with coronary artery disease. Dynamic CTP data were obtained for 30 continuous heartbeats during the R-peak to R-peak (1RR) interval on electrocardiography. Three additional datasets were created with sub-sampling acquisitions every 2, 3, and 4 heartbeats from the original dataset as interval times of 2RR, 3RR, and 4RR, respectively. CT-MBF was calculated using deconvolution analysis and determined as the mean value of the whole heart (global CT-MBF) and using the 16-segment model (segmental CT-MBF). The diagnostic performance of segmental CT-MBF for detecting perfusion abnormalities was compared to that of cardiac magnetic resonance imaging as the gold standard in 32 of 120 patients. These results were compared among the four CTP datasets. Results Global CT-MBFs for 1RR, 2RR, 3RR, and 4RR sampling were 1.57 ± 0.34, 1.54 ± 0.36, 1.51 ± 0.37, and 1.41 ± 0.33 mL/g/min, respectively. Areas under the receiver operating characteristic curves of segmental CT-MBF for 1RR, 2RR, 3RR, and 4RR sampling were 0.84, 0.83, 0.79, and 0.76, respectively (1RR versus [vs.] 2RR, non-significant; 1RR vs. 3RR or 4RR, p Conclusion CT-MBF with 2RR sampling has similar performance with regard to quantification and detecting myocardial perfusion abnormalities as that with 1RR sampling.

OBJECTIVES: Infective endocarditis (IE) is a critical infection with a high mortality rate, and it usually causes sepsis. Though disseminated intravascular coagulation (DIC) sometimes occurs in IE patients, no definitive treatment strategy for IE patients with DIC as a complication exists. Therefore, we evaluated the prevalence, surgical results and treatment strategy for IE complicated with DIC. METHODS: Between 2009 and 2017, a total of 585 patients undergoing valve surgery for active IE were enrolled at 14 institutions, of whom 116 (20%) had DIC as a complication. For further evaluation, we divided DIC patients into medical treatment-first (n = 45, group M) and valve surgery-first (n = 51, group S) groups after excluding 20 patients with intracranial haemorrhage. RESULTS: The overall survival rates at 1 and 5 years were 91% and 85% in the non-DIC group and 65% and 55% in the DIC group, respectively (P CONCLUSIONS: Mortality and IE recurrence were statistically significantly higher in DIC patients. Valve surgery should not be delayed because most patients proceeding with medical treatment eventually require emergency surgery and their clinical outcomes are worse than those of patients undergoing early surgery.

The effect of uniportal video-assisted thoracoscopic surgery (uni-VATS) versus that of conventional VATS on postoperative quality of life (QOL) is unclear. This prospective randomized controlled study compared uni-VATS and conventional 3-port VATS in terms of QOL and patient satisfaction. The subjects of this study were 84 patients with pulmonary nodules or bullous formation, randomized to undergo uniportal or conventional 3-port video-assisted thoracoscopic partial lung resection. The primary endpoint was postoperative pain, assessed using a numeric rating scale on postoperative day (POD) 1. No differences were found in the numeric rating scale on POD 1 after uni-VATS and conventional 3-port VATS. There were also no differences in blood loss, operative time, complication rate, surgical margin, analgesic requirement, vital capacity (VC), forced expiratory volume in 1 s (FEV1), the 6-min walk test (6MWT), C-reactive protein (CRP) levels, white blood cell count (WBC), or duration of chest tube drainage and hospital stay. Differences were found in the numeric rating scale on days 2, 3, 5, and 10 and in the patient satisfaction score on PODs 5 and 10. Uni-VATS is associated with less chest pain and better patient satisfaction in the short term but without differences in complication rates or surgical margins from the lesions. University Hospital Medical Information Network Clinical Trial Registry (UMIN000015340 http://www.umin.ac.jp/english/ ).

OBJECTIVES Although primary repair in early infancy has for decades been the prevalent strategy for management of truncus arteriosus (TA), recent concerns about the levels of morbidity and mortality have led to consideration of a staged surgical approach. Our goal was to describe recent patterns of management, to characterize patients who underwent primary or staged repair and to evaluate risk factors associated with operative mortality in a contemporary multicentre cohort. METHODS In the Japanese Cardiovascular Surgery Database, we identified all cases of TA undergoing an initial surgical procedure from 2008 to 2018. Operative mortality was defined as death within 30 days of an operation or in-hospital death regardless of the length of hospital stay. The hospital volume was defined by the average volume of TA repairs per year. RESULTS The total number of patients undergoing initial surgery for TA was 286. Sixty-eight (24%, 68/286) underwent primary repair (primary repair group). The remaining 218 (76%, 218/286) underwent initial bilateral pulmonary artery banding as part of a planned staged approach (staged repair group). One hundred sixty-two patients out of 218 initially banded patients underwent the repair of TA during this study period. Concomitant diagnoses in the entire cohort included interrupted aortic arch repair in 36 patients and truncal valve regurgitation in 32. No centres handling an average of ≥2 truncus cases/year of the repair of TA were identified in this cohort. A total of 30% (85/286) of the cases were performed at centres that handled an average of ≥1 and CONCLUSIONS The staged repair of TA has emerged as the preferred option for surgical timing at most of the centres participating in the Japanese Cardiovascular Surgery Database. The management outcomes of the patients with TA were favourable, even for the patients at low-volume centres.

Minimally invasive cardiac surgery (MICS) through partial sternotomy or parastenal incision was introduced for valvular heart disease in 1990s, it has gradually faded because it was somehow challenging without standardized manner or positive merits for the patients. Conversely, MICS via mini-thoracotomy has been started for mostly the patients undergoing mitral valve repair in 2000s, the number of MICS through mini-thoracotomy cases has increased progressively with the supports by academic societies and a national registry database system. Some enthusiasm for less invasiveness fashion oriented smaller skin incision and endoscopic procedures. Recently, robotically-assisted mitral valve surgery has taken place under strict regulation. Performing MICS requires not only surgeon's skills but also heart team strength including anesthesiologists and perfusionists. MICS should give cosmetic benefit and patient satisfaction, and credibility for cardiologists and society. Past and current status of MICS in Japan is described based on over 20-year author's experience from partial sternotomy MICS to robotically-assisted surgery for valvular heart disease.

A 47-year-old woman with a history of mitral valve replacement (MVR) through a median sternotomy was admitted to our hospital due to dyspnea on exertion. Echocardiography showed bioprosthetic valve dysfunction with mitral stenosis. Right heart catheter examination revealed severe pulmonary hypertension and right ventricular dysfunction. We considered that she could not tolerate the hemodynamic changes during induction of general anesthesia without any cardiopulmonary support. Therefore, the percutaneous cardiopulmonary support was started before induction of anesthesia. To avoid the risk of injury to cardiac structures, we performed redo mitral valve replacement via right mini-horacotomy in the 4th intercostal space. Severe calcification was found in the leaflets of the prosthetic valve. She was discharged home on postoperative day 42.

Background Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is an essential device in the field of emergency and intensive-care medicine. However, long-term use of VA-ECMO has various severe complications, including thrombosis. Case presentation A 60-year-old man underwent his third aortic root replacement using a homograft because of infectious endocarditis. Although the operation was difficult because of severe adhesion caused by the two previous interventions, aortic root replacement using a homograft was performed. At the time of withdrawal from cardiopulmonary bypass, the maintenance of hemodynamics was difficult because of bleeding from the surgical site, leading to hypovolemic shock. Cardiac function subsequently deteriorated; therefore, VA-ECMO was established and the operation was finished. Three days later, thrombus was formed inside the homograft and completely occluded ascending aorta. Evacuation of hematoma was performed, however, cardiac function was not ameliorated. Eventually, the patient had brain infarction and died. To prevent thrombus formation in very severe low cardiac output cases under VA-ECMO management after surgery, to prevent the stagnation of the blood flow from VA-ECMO will be necessary because anticoagulant therapy will be difficult. Impella ventricular assist device which is recently used widely generates anterograde blood flow and effectively prevents stagnation. Conclusions To prevent thrombus formation in cases of very severe low cardiac output, Impella® should be combinatorially introduced from the beginning of VA-ECMO establishment to prevent thrombosis.

Objectives Radical surgery with systematic upper mediastinal node dissection for primary lung cancer can cause recurrent laryngeal nerve (RLN) paralysis, but this is poorly reported. Methods We retrospectively reviewed the clinical data for consecutive patients who underwent radical surgery for primary lung cancer with an observation period of at least 12 months. During follow-up, hoarseness and vocal fold movement were assessed clinically and laryngoscopically, respectively. Results Of the 365 patients included in this study, 22 (6.0%) experienced hoarseness as a complication. All 22 patients who experienced hoarseness had undergone upper mediastinal node dissection. Although 1 of the 22 patients refused to undergo laryngoscopy, we assessed the vocal fold movement in the remaining patients (95.5%). Among these, 5 patients (23.8%) had right RLN paralysis, and 15 (71.4%) had left RLN paralysis and showed no sign of RLN paralysis. Over 1-24 months, vocal cord movement improved in 61.1% (11/18); and over 1-28 months, hoarseness improved in 72.7% (16/22). All patients with right RLN paralysis improved without further treatment. Conclusions We conclude that extensive follow-up is necessary to discern whether hoarseness is a temporary or permanent complication of radical surgery in patients with primary lung cancer who have undergone systematic lymph node dissection.

Background Lung injury is a life-threatening complication in patients with liver dysfunction. We recently provided an experimental lung injury model in mouse with common bile duct ligation. In this study, we aimed to characterize the pathologic and biochemical features of lung tissues in common bile duct ligation mice using a proteomic approach. Methods Common bile ducts of BALB/c mice, 8 weeks of age, were ligated operatively. CD31-expressing pulmonary cells were sorted with immunomagnetic microbeads, and protein profiles were examined by 2-dimensional gel electrophoresis. Based on the results of protein identification, immunohistochemistry and quantitative reverse transcription polymerase chain reaction were carried out in pulmonary and hepatic tissues. Results Two-dimensional gel electrophoresis revealed 3 major inflammation-associated proteins exhibiting considerable increases in the number of CD31-positive pulmonary cells after common bile duct ligation. Mass spectrometry analysis identified these proteins as SerpinB1a (48 kDa), ANXA1 (46 kDa), and S100A9 (16 kDa). Furthermore, the 3 proteins were more highly expressed in dilated pulmonary blood vessels of common bile duct ligation mice, in which neutrophils and monocytes were prominent, as shown by immunohistochemistry. More importantly, SerpinB1a mRNA and protein were significantly upregulated in the liver, whereas S100A9 and ANXA1 mRNA and protein were upregulated in the lungs, as shown by quantitative reverse transcription polymerase chain reaction and Western blotting. Conclusion We identified 3 proteins that were highly expressed in the lung after common bile duct ligation using a proteomics-based approach.

OBJECTIVES Bidirectional cavopulmonary shunt (BCPS) has played an important role in the staged Fontan approach; however, the timing remains controversial, especially in younger patients. Therefore, we examined the outcomes of BCPS in infants younger than 3 months of age. METHODS From 2004 to 2018, 120 patients underwent BCPS at RESULTS The median age and body weight at the time of the BCPS were 102 days and 4.2 kg for the younger group versus 196 days and 6.3 kg for the older group, respectively. Forty-eight patients (14.8%, 48 of 324; 16 in the younger group, 32 in the older group) had primary BCPS; the remaining 276 (104 in younger group, 172 in older group) had various forms of single-ventricle palliation before the BCPS procedure. Although preoperatively, 7 patients required extracorporeal membrane oxygenation (ECMO) support due to haemodynamic instability, they were successfully weaned from ECMO through haemodynamic benefits after BCPS. The 10-year actual survival rate (Kaplan–Meier) was 89% in the younger group and 86% in the older group (P = 0.55). Atrioventricular valve regurgitation (AVVR) was identified as a factor associated with hospital deaths in the younger group (P = 0.009), and much older age at BCPS was associated with late deaths in the older group (P = 0.027). CONCLUSIONS In this study population, early performance of BCPS is applicable for patients who have undergone prior palliation and for those in whom primary BCPS is the first surgical intervention, even for patients with haemodynamic instabilities.

Background The molecular mechanisms underlying aortic valve calcification are poorly understood. Here, we aimed to identify the master regulators of calcification by comparison of genes in valve interstitial cells (VICs) with calcified and noncalcified aortic valves. Methods Calcified aortic valves were surgically excised from patients with aortic valve stenosis who required aortic valve replacements. Noncalcified and calcified sections were obtained from aortic valve leaflets. Collagenase-digested tissues were seeded into dishes, and VICs adhering to the dishes were cultured for 3 weeks, followed by comprehensive gene expression analysis. Functional analyses of identified proteins were performed by in vitro calcification assays. Tissue localization was determined by immunohistochemical staining for normal (n = 11) and stenotic valves (n = 30). Results We found 87 genes showing greater than a twofold change in calcified tissues. Among these genes, 68 were downregulated and 19 were upregulated. Cyclooxygenase-1 (COX1) messenger RNA and protein levels were upregulated in VICs from calcified tissues. The COX1 messenger RNA and protein levels in VICs were also strongly increased by stimulation with osteoblast differentiation medium. These were VIC-specific phenotypes and were not observed in other cell types. Immunohistochemical staining revealed that COX1-positive VICs were specifically localized in the calcified area of aortic valve tissues. Conclusions The VIC-specific COX1 overexpression played a crucial role in calcification by promoting osteoblast differentiation in aortic valve tissues.

Posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities, and sternal malformations' (PHACES) syndrome comprises various defects that require a concrete therapeutic plan. Herein, we report a case of a very low birth weight infant with PHACES syndrome presenting complete sternal cleft, interrupted aortic arch with ventricular septal defect, and absence of communicating cerebral arteries. Due to the infant's very low birth weight, we planned staged surgery for this complex disease. First, bilateral pulmonary artery banding was performed to improve unstable hemodynamics. Then, after sufficient body weight was obtained, aortic arch and intracardiac repair was done. However, when the tracheal tube was removed 2 weeks after surgery, the patient could not breathe well due to paradoxical chest movement related to complete sternal cleft. Consequently, to improve chest wall compliance, the upper sternum was constructed with dislocated ribs. After these treatments, the patient gained adequate weight and was in stable condition. Staged surgical treatment of sternal cleft and congenital heart defects is a potential therapeutic option for PHACES syndrome, particularly in very low birth weight infants with complex cardiovascular disease.

Calcification of bioprosthetic valves (BVs) implanted in aortic position can result in gradual deterioration and necessitate aortic valve replacement. The molecular mechanism of calcium deposition on BV leaflets has been investigated, but remains to be fully elucidated. The present study aimed to identify explanted bioprosthetic valve (eBV)-specific proteins using a proteomics approach and to unveil their biochemical and histological involvements in calcium deposition on BV leaflets. Calcification, fibrosis, and glycosylation of the valves were histologically assessed using Von Kossa, Masson's Trichrome and Alcian Blue staining, as well as immunostaining. Protein expression in the explanted biological valves was analysed using proteomics and western blotting. In a histological evaluation, αSMA-positive myofibroblasts were not observed in eBV, whereas severe fibrosis occurred around calcified areas. SDS-PAGE revealed three major bands with considerably increased intensity in BV leaflets that were identified as plasminogen and fibrinogen gamma chain (100 kDa), and fibrinogen beta chain (50 and 37 kDa) by mass analysis. Immunohistochemistry showed that fibrinogen β-chain was distributed throughout the valve tissue. On the contrary, plasminogen was strongly stained in CD68-positive macrophages, as evidenced by immunofluorescence. The results suggest that two important blood coagulation-related proteins, plasminogen and fibrinogen, might affect the progression of BV degeneration., Summary: Fibrinogen was specifically deposited on whole deteriorated tissue valve leaflets, and plasminogen-positive macrophages strongly invaded the areas around calcified bioprosthetic and native tissues.

Vascular endothelial cell growth factor receptor 2 (VEGFR2) is an essential receptor for the homeostasis of endothelial cells. In this study, we showed that NEDD8-conjugated Cullin3 (CUL3)-based ubiquitin E3 (UbE3) ligase plays a crucial role in VEGFR2 mRNA expression. Human umbilical vein endothelial cells treated with MLN4924, an inhibitor of NEDD8-activating enzyme, or with CUL3 siRNA drastically lost their response to VEGF due to the intense decrease in VEGFR2 expression. Moreover, speckle-type POZ protein (SPOP) and death-domain associated protein (DAXX) were involved in the CUL3 UbE3 ligase complex as a substrate adaptor and a substrate, respectively. Knockdown of SPOP and CUL3 led to the upregulation of DAXX protein and downregulation of VEGFR2 levels. These levels were inversely correlated with one another. In addition, simultaneous knockdown of SPOP and DAXX completely reversed the downregulation of VEGFR2 levels. Moreover, the CUL3-SPOP-DAXX axis had the same effects on NOTCH1, DLL4 and NRP1 expression. Taken together, these findings suggest that the CUL3-SPOP-DAXX axis plays a very important role in endothelial cell function by targeting key angiogenic regulators.

Background Congenital long QT syndrome (LQTS) can cause ventricular arrhythmic events with syncope and sudden death resulting from malignant torsades de pointes (TdP) followed by ventricular fibrillations (VFs). However, the syndrome is often overlooked prior to the development of arrhythmic events in patients with congenital heart diseases demonstrating right bundle branch block on electrocardiogram (ECG). We present a case of an adult patient with congenital heart disease who developed VFs postoperatively, potentially due to his mutation in a LQTS related gene, which was not identified on preoperative assessment due to incomplete evaluation of his family history. Case presentation A 64-year-old man was diagnosed as having multiple atrial septal defects. He presented with no symptoms of heart failure. His preoperative ECG showed complete right bundle branch block (CRBBB) with a corrected QT interval time of 478 ms. He underwent open-heart surgery to close the defects through median sternotomy access. Three hours after the operation, he developed multiple events of TdP and VFs in the intensive care unit. Cardiopulmonary resuscitation and multiple cardioversions were attempted for his repetitive TdP and VFs. He eventually reverted to sinus rhythm, and intravenous beta-blocker was administered to maintain the sinus rhythm. After this event, his family history was reviewed, and it was confirmed that his daughter and grandson had a medical history of arrhythmia. A genetic test confirmed that he had a missense mutation in CACNA1C, p.K1580 T, which is the cause for type 8. Conclusions This case highlights the importance of paying attention to other ECG findings in patients with CRBBB, which can mask prolonged QT intervals.

Aortic coarctation rarely occurs after an arterial switch operation for D-transposition of the great arteries with intact ventricular septum. We report the case of a neonate patient in whom aortic coarctation developed 28 days after an uncomplicated arterial switch operation. Preoperatively, the aorta was noted to have an irregular shape, but there was no pressure gradient across the lesion. The patient underwent successful reoperation to correct the coarctation. We hope that our report raises awareness of a rare early complication after arterial switch operation with intact ventricular septum, and the need to carefully monitor the aortic isthmus in patients who have aortic irregularities, even in the absence of a pressure gradient.

Aortic prosthetic graft infection detected by F-fluorodeoxyglucose positron emission tomography/computed tomography Tamami Kono ⁎, Akiyoshi Ogimoto , Chiharuko Iio , Kaori Fujimoto , Akira Fujii , Teruyoshi Uetani , Takayuki Nagai , Kazuhisa Nishimura , Katsuji Inoue , Jun Suzuki , Go Hiasa , Hideki Okayama , Takafumi Okura , Masao Miyagawa , Teruhito Mochizuki , Hironori Izutani , Jitsuo Higaki a

Vascular endothelial cell growth factor receptor 2 (VEGFR2) is an essential receptor for the homeostasis of endothelial cells. In this study, we showed that NEDD8-conjugated Cullin3 (CUL3)-based ubiquitin E3 (UbE3) ligase plays a crucial role in VEGFR2 mRNA expression. Human umbilical vein endothelial cells treated with MLN4924, an inhibitor of NEDD8-activating enzyme, or with CUL3 siRNA drastically lost their response to VEGF due to the intense decrease in VEGFR2 expression. Moreover, speckle-type POZ protein (SPOP) and death-domain associated protein (DAXX) were involved in the CUL3 UbE3 ligase complex as a substrate adaptor and a substrate, respectively. Knockdown of SPOP and CUL3 led to the upregulation of DAXX protein and downregulation of VEGFR2 levels. These levels were inversely correlated with one another. In addition, simultaneous knockdown of SPOP and DAXX completely reversed the downregulation of VEGFR2 levels. Moreover, the CUL3-SPOP-DAXX axis had the same effects on NOTCH1, DLL4 and NRP1 expression. Taken together, these findings suggest that the CUL3-SPOP-DAXX axis plays a very important role in endothelial cell function by targeting key angiogenic regulators.

Purpose: This study clarified the features of a hemoconcentrator-based, alternative hemodialysis (ALTHD) method that improves the speed of serum potassium (K+) concentration adjustments, compared with dilutional ultrafiltration (DUF), during cardiopulmonary bypasses. Methods: Standardized bovine blood was recirculated (300 ml/min) through an in vitro hemoconcentrator circuit; hematocrit, K+ and glucose levels were measured at 5–20 min after DUF or ALTHD. We evaluated DUF at dialysis speeds of 50–250 ml/min and ALTHD at speeds of 50–1000 ml/min. Results: ALTHD rapidly corrected K+ and glucose concentrations at speeds up to 800 ml/min. ALTHD took 8.9 min to reach a K+ level of 4.5 mmol/L, faster than DUF (12.8 min). The ALTHD efficiency curves plateaued at 600 ml/min. Conclusion: ALTHD allowed faster adjustment of electrolyte levels, with peak efficiency at 600 ml/min. ALTHD has possible clinical application if available for potential use during all cardiopulmonary bypass surgeries involving extracorporeal circulation.

Objective: Cardioplegic solutions often cause high blood concentrations of potassium. The conventional hemoconcentration circuit was improved to correct electrolyte imbalances through a method involving dilutional ultrafiltration (DUF) and an alternative hemodialysis (ALTHD) method. This study aimed to determine the effectiveness of this ALTHD method. Methods: Bovine blood was used, in conjunction with a hemoconcentrator, in an experimental hemodialysis (HD) circuit to evaluate an ALTHD method. The effectiveness of the method was determined by electrolyte and hematocrit measurements following the procedure. Results: The ALTHD method corrected electrolyte levels as effectively as DUF and was less affected by dilution than DUF. Conclusion: The ALTHD method may provide faster electrolyte adjustments than DUF because its efficiency depends on both the blood and dialysate flow rates. In addition, the ALTHD method is expected to provide increased efficiency. Thus, our DUF/ALTHD circuit-switching method may be clinically useful when rapid electrolyte correction is required.

Vascular endothelial (VE)-cadherin, a major endothelial adhesion molecule, regulates vascular permeability, and increased vascular permeability has been observed in several cancers. The aim of this study was to elucidate the role of the NEDD8-Cullin E3 ligase, in maintaining barrier permeability. To this end, we investigated the effects of the inhibition of Cullin E3 ligases, by using inhibitors and knockdown techniques in HUVECs. Furthermore, we analyzed the mRNA and protein levels of the ligases by quantitative RT-PCR and Western blotting, respectively. The results revealed that NEDD8-conjugated Cullin 3 is required for VE-cadherin-mediated endothelial barrier functions. Treatment of HUVECs with MLN4924, a chemical inhibitor of the NEDD8-activating enzyme, led to high vascular permeability due to impaired cell-cell contact. Similar results were obtained when HUVECs were treated with siRNA directed against Cullin 3, one of the target substrates of NEDD8. Immunocytochemical staining showed that both treatments equally depleted VE-cadherin protein localized at the cell-cell borders. However, quantitative RT-PCR showed that there was no significant difference in the VE-cadherin mRNA levels between the treatment and control groups. In addition, cycloheximide chase assay revealed that the half-life of VE-cadherin protein was dramatically reduced by Cullin 3 depletion. Together, these findings suggest that neddylated Cullin 3 plays a crucial role in endothelial cell barrier function by regulating VE-cadherin.

An 83-year-old woman presented with a rapidly progressing dyspnoea and generalized oedema that had developed over a few days. On admission, her blood pressure was 88/68 mmHg and her heart rate was 94 beats per minute. Echocardiography revealed an ellipsoidal mass measuring 20 × 28 mm, which occupied most of the …