Early Clinical Results From the Japanese Prospective Multicenter Study to Evaluate Zenith Alpha Abdominal Stent Graft for Abdominal Aortic Aneurysm (JUSTICE) Registry Demonstrate Acceptable Limb Patency at 12 Months.

PURPOSE: Recent reports of the Zenith Alpha abdominal endovascular graft (Zenith Alpha AAA, Cook, Inc., Bloomington, Indiana) have demonstrated an unexpectedly high incidence of limb graft occlusion (LGO). The purpose of this study was to prospectively evaluate the performance of the Zenith AAA in Japan, with a specific focus on LGO. MATERIALS AND METHODS: All endovascular aneurysm repairs (EVARs) for abdominal aortic aneurysms performed using the Zenith Alpha AAA from July 2020 to October 2021 in 23 Japanese hospitals were prospectively evaluated. All computed tomographic images were analyzed in the core laboratory. Late complications were defined as any aneurysm-related events occurring >30 days after EVAR, including aneurysm sac enlargement of >5 mm and any reinterventions performed. Endoleaks without sac enlargement or reintervention were excluded as late complications. RESULTS: During the study period, 147 EVARs were performed using the Zenith Alpha AAA. The mean patient age was 76.5±7.7 years, 84.4% of patients were male, and the mean aneurysm diameter was 52.4±9.2 mm. Instruction-for-use violations were observed in 76 patients (51.7%), primarily associated with a severely angulated proximal neck (>60°). There were six intraoperative complications and 62 additional intraoperative treatments reported, most of which involved preemptive coil embolization of the inferior mesenteric artery (37 cases). Technical success, defined as the absence of type 1 or 3 endoleaks on final angiography, was achieved in 99.3% of patients. At 12 months, there was only one case of type 1/3 endoleak (0.8%) and one aneurysm sac enlargement exceeding 5 mm (0.8%); however, a high incidence of type 2 endoleaks was observed in 35.2% of patients, and aneurysm sac regression exceeding 5 mm was achieved in 30.1% of patients. Nine late complications were observed, and the rate of freedom from late complications at 12 months was 93.5%, encompassing four LGOs and one limb graft stenosis (3.4%). CONCLUSIONS: In contrast to recent reports, our Japanese multicenter prospective study demonstrated satisfactory early clinical results, including an acceptable LGO rate, for the low-profile Zenith Alpha AAA. Long-term follow-ups will be performed to confirm the persistence of these outcomes. CLINICAL IMPACT: This study prospectively evaluated the performance of 147 Zenith Alpha AAAs used for endovascular aneurysm repair with core-lab adjudication focusing especially on limb graft occlusion (LGO). At 12 months, aneurysm sac regression exceeding 5 mm was achieved in 30.1% of patients, and there was only one type 1/3 endoleak, one aneurysm sac enlargement (>5 mm), and nine late complications including five LGOs (3.4%), resulting in rate of freedom from late complications at 93.5%. Satisfactory early clinical results, including an acceptable rate of LGO can be achieved, particularly with cautious usage of the Zenith Alpha Spiral-Z Endovascular Leg." 5mm), and nine late complications including five LGOs (3.4%), resulting in rate of freedom from late complications at 93.5%. Satisfactory early clinical results, including an acceptable rate of LGO can be achieved, particularly with cautious usage of the Zenith Alpha Spiral-Z Endovascular Leg.

Modification of pulmonary endarterectomy to prevent neurologic adverse events.

PURPOSE: Neurologic adverse events (NAEs) are a major complication after pulmonary endarterectomy (PEA) performed under periods of deep hypothermic circulatory arrest (HCA) for chronic thromboembolic pulmonary hypertension. We modified the PEA strategy to prevent NAEs and evaluated the effectiveness of these modifications. METHODS: We reviewed the surgical outcomes of 87 patients divided into the following three groups based on the surgical strategy used: group S (n = 49), periods of deep HCA with alpha-stat strategy; group M1 (n = 19), deep HCA with modifications of slower cooling and rewarming rates and the pH-stat strategy for cooling: and group M2 (n = 13), multiple short periods of moderate HCA. RESULTS: PEA provided significant improvement of pulmonary hemodynamics in each group. Sixteen (29%) of the 49 group S patients suffered NAEs, associated with total circulatory arrest time (cutoff, 57 min) and Jamieson type I disease. The Group M1 and M2 patients did not suffer NAEs, although the group M1 patients had prolonged cardiopulmonary bypass (CPB) and more frequent respiratory failure. CONCLUSIONS: NAEs were common after PEA performed under periods of deep HCA. The modified surgical strategy could decrease the risk of NAEs but increase the risk of respiratory failure. Multiple short periods of moderate HCA may be useful for patients at risk of NAEs.

Stent-Graft Placement for Radiation-Induced Abdominal Aortic Stenosis after Renal Autotransplantation.

Renovascular hypertension (RVH) is a common cause of secondary hypertension. However, there have been no reports on RVH due to radiation-induced abdominal aorta stenosis after renal autotransplantation. A 27-year-old woman with a history of neuroblastoma treated by radiation therapy and RVH treated with renal autotransplantation presented with hypertension and dyspnea. At age 19, she had experienced hypertensive heart failure due to RVH from radiation-induced left renal artery stenosis and had undergone renal autotransplantation involving the extraction of her left kidney. Her systolic blood pressure (BP) was well-controlled but had increased progressively. She was diagnosed with hypertensive heart failure and admitted to hospital. Although her dyspnea soon subsided after treatment, her BP remained high. Renal artery ultrasound revealed no obvious stenosis. The ankle brachial pressure index (ABI) showed a significant bilateral decrease to 0.71/0.71 (right/left) from 0.94/0.95 eight years before. Magnetic resonance angiography and aortic angiography revealed severe stenosis in the abdominal aorta, and the systolic pressure gradient of intra-aortic blood flow, distal and proximal to a stenotic lesion, was 58 mmHg. These arterial stenoses in the irradiated area were highly suggestive of radiation-induced vasculopathy. She finally underwent an endovascular VIABAHN VBX balloon-expandable stent-graft placement for this radiation-induced abdominal aorta stenosis, which resolved the pressure gradient. After the procedure, her ABI improved to 0.91/0.88 and her BP was well-controlled. This is the first case of successful stent-graft placement for RVH after renal autotransplantation due to radiation-induced abdominal aorta stenosis as a consequence of neuroblastoma.

Differential immunostaining patterns of transient receptor potential (TRP) ion channels in the rat nodose ganglion.

Vagal afferents regulate numerous physiological functions including arterial blood pressure, heart rate, breathing, and nociception. Cell bodies of vagal afferents reside in the inferior vagal (nodose) ganglia and their stimulation by various means is being considered as a way to regulate cardiorespiratory responses and control pain sensations. Stimulation of the nodose by exposure to infrared light is recently being considered as a precise way to elicit responses. These responses would likely involve the activity of temperature-sensitive membrane-bound channels. While papers have been published to track the expression of these transient receptor potential ion channels (TRPs), further studies are warranted to determine the in situ expression of the endogenous TRP proteins in the nodose ganglia to fully understand their pattern of expression, subcellular locations, and functions in this animal model. TRP ion channels are a superfamily of Na+ /Ca2+ -channels whose members are temperature- and/or mechano-sensitive and therefore represent a potential set of proteins that will be activated directly or indirectly by infrared light. Here, we report the spatial localization of six TRP channels, TRPV1, TRPV4, TRPM3, TRPM8, TRPA1, and TRPC1, from nodose ganglia taken from juvenile male Sprague-Dawley rats. The channels were detected using immunohistology with fluorescent tags on cryosections and imaged using confocal microscopy. All six TRP channels were detected with different levels of intensity in neuronal cell bodies and some were also detected in axonal fibers and blood vessels. The TRP receptors differed in their prevalence, in their patterns of expression, and in subcellular expression/localization. More specifically, TRPV1, TRPV4, TRPA1, TRPM8, TRPC1, and TRPM3 were found in vagal afferent cell bodies with a wide range of immunostaining intensity from neuron to neuron. Immunostaining for TRPV1, TRPV4, and TRPA1 appeared as fine particles scattered throughout the cytoplasm of the cell body. Intense TRPV1 immunostaining was also evident in a subset of axonal fibers. TRPM8 and TRPC1 were expressed in courser particles suggesting different subcellular compartments than for TRPV1. The localization of TRPM3 differed markedly from the other TRP channels with an immunostaining pattern that was localized to the periphery of a subset of cell bodies, whereas a scattering or no immunostaining was detected within the bulk of the cytoplasm. TRPV4 and TRPC1 were also expressed on the walls of blood vessels. The finding that all six TRP channels (representing four subfamilies) were present in the nodose ganglia provides the basis for studies designed to understand the roles of these channels in sensory transmission within vagal afferent fibers and in the responses elicited by exposure of nodose ganglia to infrared light and other stimuli. Depending on the location and functionality of the TRP channels, they may regulate the flux of Na+ /Ca2+ -across the membranes of cell bodies and axons of sensory afferents, efferent (motor) fibers coursing through the ganglia, and in vascular smooth muscle.

Do Community Social Capital and Built Environment Associate With Homebound in Older Adults? The JAGES Niigata Study.

BACKGROUND: Homebound status is one of the most important risk factors associated with functional decline and long-term care in older adults. Studies show that neighborhood built environment and community social capital may be related to homebound status. This study aimed to clarify the association between homebound status for community-dwelling older adults and community environment-including social capital and neighborhood built environment-in rural and urban areas. METHODS: We surveyed people aged 65 years and older residing in three municipalities of Niigata Prefecture, Japan, who were not certified as requiring long-term care. The dependent variable was homebound status; explanatory variables were community-level social capital and neighborhood built environment. Covariates were age, sex, household, marital status, socioeconomic status, instrumental activities of daily living, the Geriatric Depression Scale-15, self-rated health, number of diseases under care, and individual social capital. The association between community social capital or neighborhood built environment and homebound status, stratified by rural/urban areas, was investigated using multilevel logistic regression analysis. RESULTS: Among older adults (n = 18,099), the homebound status prevalence rate was 6.9% in rural areas and 4.2% in urban areas. The multilevel analysis showed that, in rural areas, fewer older adults were homebound in communities with higher civic participation and with suitable parks or pavements for walking and exercising. However, no significant association was found between community social capital or neighborhood built environment and homebound status for urban older adults. CONCLUSION: Community social capital and neighborhood built environment were significantly associated with homebound status in older adults in rural areas.

Assessment of coding-based frailty algorithms for long-term outcome prediction among older people in community settings: a cohort study from the Shizuoka Kokuho Database.

OBJECTIVES: To assess the applicability of Electronic Frailty Index (eFI) and Hospital Frailty Risk Score (HFRS) algorithms to Japanese administrative claims data and to evaluate their association with long-term outcomes. STUDY DESIGN AND SETTING: A cohort study using a regional government administrative healthcare and long-term care (LTC) claims database in Japan 2014-18. PARTICIPANTS: Plan enrollees aged ≥50 years. METHODS: We applied the two algorithms to the cohort and assessed the scores' distributions alongside enrollees' 4-year mortality and initiation of government-supported LTC. Using Cox regression and Fine-Gray models, we evaluated the association between frailty scores and outcomes as well as the models' discriminatory ability. RESULTS: Among 827,744 enrollees, 42.8% were categorised by eFI as fit, 31.2% mild, 17.5% moderate and 8.5% severe. For HFRS, 73.0% were low, 24.3% intermediate and 2.7% high risk; 35 of 36 predictors for eFI, and 92 of 109 codes originally used for HFRS were available in the Japanese system. Relative to the lowest frailty group, the highest frailty group had hazard ratios [95% confidence interval (CI)] of 2.09 (1.98-2.21) for mortality and 2.45 (2.28-2.63) for LTC for eFI; those for HFRS were 3.79 (3.56-4.03) and 3.31 (2.87-3.82), respectively. The area under the receiver operating characteristics curves for the unadjusted model at 48 months was 0.68 for death and 0.68 for LTC for eFI, and 0.73 and 0.70, respectively, for HFRS. CONCLUSIONS: The frailty algorithms were applicable to the Japanese system and could contribute to the identifications of enrollees at risk of long-term mortality or LTC use.

Determinant analysis and developing evaluation indicators of grade of execution score of double axel jump in figure skating.

A figure skating jump score is determined by the sum of the base value based on the difficulty and grade of execution (GOE) that indicates the performance quality. Therefore, performing a high-quality jump to obtain a high GOE is essential to win a competition. However, the relationship between the GOE and kinematic parameters remains unclear. We analysed the horizontal distance, vertical height, and landing speed of double axel jumps in the Ladies' Short Program at the 2019 World Championships. The highest GOE group had significantly larger horizontal distances than the middle and lower groups, while the landing speed and vertical height were not significantly different. A principal component regression analysis was conducted to clarify the contrast between the three variables affecting the GOE. The results showed that greater horizontal distance and landing speed compared to vertical height (component 1) and greater horizontal distance compared to landing speed (component 3) contributed to higher GOE. We divided skaters into four clusters using these two components and provided general GOE acquisition strategies for each cluster. Finally, to apply our results to the industry, we proposed two new evaluation indicators which are highly correlated with the two components and easy to interpret.

Prenatal ethanol exposure impairs the conduction delay at the atrioventricular junction in the looping heart.

The etiology of ethanol-related congenital heart defects has been the focus of much study, but most research has concentrated on cellular and molecular mechanisms. We have shown with optical coherence tomography (OCT) that ethanol exposure led to increased retrograde flow and smaller atrioventricular (AV) cushions compared with controls. Since AV cushions play a role in patterning the conduction delay at the atrioventricular junction (AVJ), this study aims to investigate whether ethanol exposure alters the AVJ conduction in early looping hearts and whether this alteration is related to the decreased cushion size. Quail embryos were exposed to a single dose of ethanol at gastrulation, and Hamburger-Hamilton stage 19-20 hearts were dissected for imaging. Cardiac conduction was measured using an optical mapping microscope and we imaged the endocardial cushions using OCT. Our results showed that, compared with controls, ethanol-exposed embryos exhibited abnormally fast AVJ conduction and reduced cushion size. However, this increased conduction velocity (CV) did not strictly correlate with decreased cushion volume and thickness. By matching the CV map to the cushion-size map along the inflow heart tube, we found that the slowest conduction location was consistently at the atrial side of the AVJ, which had the thinner cushions, not at the thickest cushion location at the ventricular side as expected. Our findings reveal regional differences in the AVJ myocardium even at this early stage in heart development. These findings reveal the early steps leading to the heterogeneity and complexity of conduction at the mature AVJ, a site where arrhythmias can be initiated.NEW & NOTEWORTHY To the best of our knowledge, this is the first study investigating the impact of ethanol exposure on the early cardiac conduction system. Our results showed that ethanol-exposed embryos exhibited abnormally fast atrioventricular conduction. In addition, our findings, in CV measurements and endocardial cushion thickness, reveal regional differences in the AVJ myocardium even at this early stage in heart development, suggesting that the differentiation and maturation at this site are complex and warrant further studies.

Glutathione Protects the Developing Heart from Defects and Global DNA Hypomethylation Induced by Prenatal Alcohol Exposure.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is caused by prenatal alcohol exposure (PAE), the intake of ethanol (C2 H5 OH) during pregnancy. Features of FASD cover a range of structural and functional defects including congenital heart defects (CHDs). Folic acid and choline, contributors of methyl groups to one-carbon metabolism (OCM), prevent CHDs in humans. Using our avian model of FASD, we have previously reported that betaine, another methyl donor downstream of choline, prevents CHDs. The CHD preventions are substantial but incomplete. Ethanol causes oxidative stress as well as depleting methyl groups for OCM to support DNA methylation and other epigenetic alterations. To identify more compounds that can safely and effectively prevent CHDs and other effects of PAE, we tested glutathione (GSH), a compound that regulates OCM and is known as a "master antioxidant." METHODS/RESULTS: Quail embryos injected with a single dose of ethanol at gastrulation exhibited congenital defects including CHDs similar to those identified in FASD individuals. GSH injected simultaneously with ethanol not only prevented CHDs, but also improved survival and prevented other PAE-induced defects. Assays of hearts at 8 days (HH stage 34) of quail development, when the heart normally has developed 4-chambers, showed that this single dose of PAE reduced global DNA methylation. GSH supplementation concurrent with PAE normalized global DNA methylation levels. The same assays performed on quail hearts at 3 days (HH stage 19-20) of development, showed no difference in global DNA methylation between controls, ethanol-treated, GSH alone, and GSH plus ethanol-treated cohorts. CONCLUSIONS: GSH supplementation shows promise to inhibit effects of PAE by improving survival, reducing the incidence of morphological defects including CHDs, and preventing global hypomethylation of DNA in heart tissues.

Application of cytochrome P450 reactivity on the characterization of chemical compounds and its association with repeated-dose toxicity.

Repeated-dose toxicity (RDT) studies are one of the critical studies to assess chemical safety. There have been some studies attempting to predict RDT endpoints based on chemical substructures, but it remains very difficult to establish such a method, and a more detailed characterization of chemical compounds seems necessary. Cytochrome P450s (P450s) comprise multiple forms with different substrate specificities and play important roles in both the detoxification and metabolic activation of xenobiotics. In this study, we investigated possible use of P450 reactivity of chemical compounds to classify the compounds. A total of 148 compounds with available rat RDT test data were used as test compounds and subjected to inhibition assays against 18 human and rat P450s. Among the tested compounds, 82 compounds inhibited at least one P450 form. Hierarchical clustering analyses using the P450 inhibitory profiles divided the 82 compounds into nine groups, some of which showed characteristic chemical and biological properties. Principal component analyses of the P450 inhibition data in combination with the calculated chemical descriptors demonstrated that P450 inhibition data were plotted differently than most chemical descriptors in the loading plots. Finally, association analyses between P450 inhibition and RDT endpoints showed that some endpoints related to the liver, kidney and hematology were significantly associated with the inhibition of some P450s. Our present results suggest that the P450 reactivity profiles can be used as novel descriptors for characterizing chemical compounds for the investigation of the toxicity mechanism and/or the establishment of a toxicity prediction model.

Adverse event reports in patients taking psychiatric medication during pregnancy from spontaneous reports in Japan and the United States: an approach using latent class analysis.

BACKGROUND: Little is known regarding the association between adverse events (AEs) and psychiatric medications administered to pregnant women in clinical trials during the pre-marketing period. This study analyzes reports of AE association with psychiatric medication administrated during pregnancy using post-marketing spontaneous reports of AE from the Japanese Adverse Drug Event Report (JADER) database and Food and Drug Administration Adverse Event Reporting System in the United States (FAERS-US). METHODS: We summarized AE reports of psychiatric medication administrated during pregnancy by comparing data obtained from JADER and FAERS-US databases with medication patterns determined as classes via latent class analysis. The odds ratios (ORs) of AE reports categorized into system organ classes in which each class was compared with those without psychiatric medications. RESULTS: The proportions of AE reports under psychiatric medication in pregnancy among all AE reports were 22.0% and 16.6% in JADER and FAERS-US, respectively. The 10,389 reports of psychiatric medication during pregnancy were classified into 11 classes. The proportion of patients receiving four or more psychiatric drugs in JADER was larger than that in FAERS-US. The maximum number of reports in combinations of AE and medication pattern in JADER was 169, for 'general disorders and administration site conditions' from the class of four or more medications (OR = 9.1), while that in FAERS-US was 1,654, for 'injury, poisoning, and procedural complications' from the class of single psychiatric medication (OR = 2.8). CONCLUSIONS: The main AE reports and associated AE differed depending on medication patterns in pregnant women taking psychiatric medication. This study may provide a prediction of AEs that are likely to be reported with each medication pattern. Our findings of the association between AE reports and medication patterns could help improve the administration of psychiatric medications during pregnancy, though further research on additional datasets is needed to clarify these results.

A case of left ventricular assist device application for chemotherapy-related cardiomyopathy caused by trastuzumab and anthracycline.

Left ventricular assist device (LVAD) is an established therapy for patients with severe heart failure. Because the incidence of cardiotoxicity owing to anticancer agents is low, it is difficult to predict the recovery prospects when the cause of heart failure is due to anticancer agents. In this context, cancer patients who present with severe symptoms of heart failure and who fail medical therapy for heart failure may pose a dilemma, especially in countries such as Japan where implantable LVADs are not approved for purposes other than bridging to transplant. Recently, we encountered a 32-year-old woman with chemotherapy-related cardiomyopathy that developed after anticancer treatment using trastuzumab and anthracycline. LVAD therapy was the only option to save the young woman. The patient received an extracorporeal LVAD, her cardiac function gradually recovered while on support, and the device was successfully removed.

Adverse reaction reports of neuroleptic malignant syndrome induced by atypical antipsychotic agents in the Japanese Adverse Drug Event Report (JADER) database.

AIM: This study evaluates reports on neuroleptic malignant syndrome (NMS) as an adverse event associated with the use of atypical antipsychotic agents (AAA) in Japan. We examined NMS occurrence following monotherapy and combination therapy with AAA in real clinical practice using the Japanese Adverse Drug Event Report database. METHODS: Adverse drug reaction reports associated with the use of one or more AAA or haloperidol were analyzed. The odds ratios of NMS occurrence after monotherapy and combination therapy with AAA without typical antipsychotic agents (TAA) relative to those after haloperidol monotherapy were estimated using multiple logistic regression. RESULTS: Associated with the use of one or more AAA without TAA were 721 events of NMS in 11 071 cases. NMS occurrence after monotherapy with most AAA and their combinations had lower odds ratios than that after haloperidol use. However, the odds ratios after blonanserin monotherapy and combination therapies with quetiapine and zotepine, and risperidone and zotepine were estimated higher than 1. CONCLUSION: Monotherapy or combination therapy with most AAA without TAA was not likely to cause NMS as an adverse reaction compared to haloperidol monotherapy. However, blonanserin monotherapy and combination therapies with quetiapine and zotepine, and risperidone and zotepine, possibly increase the report of NMS. Our results may provide useful information for medications such as AAA that are clinically used to treat mental disorders, though further research with more data are needed to clarify this.

Does the presence of coronary artery disease affect the outcome of aortic valve replacement?

The purpose of this study is to compare the late outcome of aortic valve replacement with or without preoperative coronary artery disease, and with or without coronary artery bypass. Between 2014 and 2015, 291 patients underwent aortic valve replacement. Average follow-up term was 2.5 ± 2.2 years. The retrospective comparative study was performed between the patients with (n = 115) or without (n = 176) preoperative coronary artery disease (Study 1) and with (n = 93) or without (n = 198) coronary artery bypass grafting (Study 2). Study 1: male patients were more, and diabetes was more in the patients with coronary artery disease. Long-term survival rate was significantly low in the patients with coronary artery disease (p = 0.0002 by log rank test). Freedom from repeat coronary revascularization rate was lower in the patients with coronary artery disease (p = 0.02 by log rank test). Study 2: operation time (419 ± 130 vs 290 ± 101; p = 0.0001) was longer in the patients with coronary artery bypass grafting. Improvement of ejection fraction at follow-up was more in the patients with coronary artery bypass(114 ± 43 vs 104 ± 26%; p = 0.03). Long-term survival rate and freedom from major adverse cardiac event rater were not different with or without coronary artery bypass grafting (p = 0.26 and p = 0.59, respectively, by log rank test). Although prevalence of coronary artery disease inversely affected the long-term outcome of the aortic valve replacement, simultaneous coronary artery bypass did not. Aggressive simultaneous coronary revascularization would be important to improve the long-term outcome of aortic valve replacement.

Left ventricular assist device implantation after plasma exchange for heparin-induced thrombocytopenia.

Treating a patient with heparin-induced thrombocytopenia can be challenging particularly when the patient requires urgent cardiac surgery that uses heparin for anticoagulation. We herein report a case of a 61-year-old man with idiopathic dilated cardiomyopathy associated with heparin-induced thrombocytopenia and who underwent plasma exchange to remove heparin-induced thrombocytopenia antibodies before undergoing left ventricular assist device implantation. The surgery was performed using cardiopulmonary bypass and unfractionated heparin.

Is ganglionated plexus ablation effective for treating atrial fibrillation?

PURPOSE: Very few studies have investigated the efficacy of ganglionated plexus ablation during the conventional maze procedure. In this study, we sought to evaluate its additive effect in reducing recurrent atrial fibrillation after concomitant maze surgery. METHODS: A retrospective study was conducted of 79 patients who underwent Cox maze IV concomitantly with open-heart surgery with (GP group) or without (Maze group) ganglionated plexus mapping. All active ganglionated plexuses were ablated. The two groups were compared and their follow-up data were analyzed. RESULTS: Active ganglionated plexuses were found in 81% of patients who underwent ganglionated plexus mapping. The rates of freedom from atrial fibrillation at 1 year in the GP and Maze groups were 77 and 75%, respectively. The cumulative freedom from atrial fibrillation at follow-up (27.7 ± 17.3 months) was comparable in the two groups (p = 0.427). A multivariate analysis revealed that persistent atrial fibrillation for more than 90 months was an independent predictor of recurrent atrial fibrillation. CONCLUSION: Ganglionated plexus ablation with Cox maze IV did not reduce the incidence of recurrent atrial fibrillation in comparison to Maze alone.

Supplementation with the Methyl Donor Betaine Prevents Congenital Defects Induced by Prenatal Alcohol Exposure.

BACKGROUND: Despite decades of public education about dire consequences of prenatal alcohol exposure (PAE), drinking alcohol during pregnancy remains prevalent. As high as 40% of live-born infants exposed to alcohol during gestation and diagnosed with fetal alcohol syndrome have congenital heart defects that can be life-threatening. In animal models, the methyl donor betaine, found in foods such as wheat bran, quinoa, beets, and spinach, ameliorated neurobehavioral deficits associated with PAE, but effects on heart development are unknown. METHODS: Previously, we modeled a binge drinking episode during the first trimester in avian embryos. Here, we investigated whether betaine could prevent adverse effects of alcohol on heart development. Embryos exposed to ethanol (EtOH) with and without an optimal dose of betaine (5 µM) were analyzed at late developmental stages. Cardiac morphology parameters were rapidly analyzed and quantified using optical coherence tomography. DNA methylation at early stages was detected by immunofluorescent staining for 5-methylcytosine in sections of embryos treated with EtOH or cotreated with betaine. RESULTS: Compared to EtOH-exposed embryos, betaine-supplemented embryos had higher late-stage survival rates and fewer gross head and body defects than seen after alcohol exposure alone. Betaine also reduced the incidence of late-stage cardiac defects such as absent vessels, abnormal atrioventricular (AV) valves, and hypertrophic ventricles. Furthermore, betaine cotreatment brought measurements of great vessel diameters, interventricular septum thickness, and AV leaflet volumes in betaine-supplemented embryos close to control values. Early-stage 5-methycytosine staining revealed that DNA methylation levels were reduced by EtOH exposure and normalized by co-administration with betaine. CONCLUSIONS: This is the first study demonstrating efficacy of the methyl donor betaine in alleviating cardiac defects associated with PAE. These findings highlight the therapeutic potential of low-concentration betaine doses in mitigating PAE-induced birth defects and have implications for prenatal nutrition policies, especially for women who may not be responsive to folate supplementation.

Cardiac neural crest ablation results in early endocardial cushion and hemodynamic flow abnormalities.

Cardiac neural crest cell (CNCC) ablation creates congenital heart defects (CHDs) that resemble those observed in many syndromes with craniofacial and cardiac consequences. The loss of CNCCs causes a variety of great vessel defects, including persistent truncus arteriosus and double-outlet right ventricle. However, because of the lack of quantitative volumetric measurements, less severe defects, such as great vessel size changes and valve defects, have not been assessed. Also poorly understood is the role of abnormal cardiac function in the progression of CNCC-related CHDs. CNCC ablation was previously reported to cause abnormal cardiac function in early cardiogenesis, before the CNCCs arrive in the outflow region of the heart. However, the affected functional parameters and how they correlate with the structural abnormalities were not fully characterized. In this study, using a CNCC-ablated quail model, we contribute quantitative phenotyping of CNCC ablation-related CHDs and investigate abnormal early cardiac function, which potentially contributes to late-stage CHDs. Optical coherence tomography was used to assay early- and late-stage embryos and hearts. In CNCC-ablated embryos at four-chambered heart stages, great vessel diameter and left atrioventricular valve leaflet volumes are reduced. Earlier, at cardiac looping stages, CNCC-ablated embryos exhibit abnormally twisted bodies, abnormal blood flow waveforms, increased retrograde flow percentage, and abnormal cardiac cushions. The phenotypes observed in this CNCC-ablation model were also strikingly similar to those found in an established avian fetal alcohol syndrome model, supporting the contribution of CNCC dysfunction to the development of alcohol-induced CHDs.

Endovascular Treatment for Proximal Anastomotic Pseudoaneurysm after Total Arch Replacement in Behcet's Disease.

A 17-year-old patient underwent total arch replacement for aortic arch aneurysm due to vascular Behcet's disease (BD). Follow-up computed tomography, performed 6 months after the operation, demonstrated pseudoaneurysm formation at the proximal anastomotic site. We performed endovascular treatment and used a short stent graft that was originally designed for abdominal aortic aneurysm. To avoid the occlusion of the coronary or brachiocephalic artery (BCA) due to stent graft migration, we used right ventricular rapid pacing and BCA ballooning. Thus, we believe that endovascular treatment can be used for anastomotic complications in the ascending aorta after open surgery for connective tissue disorders including BD.

Analysis of anatomical risk factors for persistent type II endoleaks following endovascular abdominal aortic aneurysm repair using CT angiography.

PURPOSE: To predict persistent type II endoleaks (pT2Es) following endovascular aneurysm repair (EVAR) of abdominal aortic aneurysms, we examined factors related to post-EVAR pT2Es. METHODS: Eighty-four cases of EVAR were analyzed. T2Es that persisted for ≥6 months were defined as pT2Es. pT2Es flowing from an inferior mesenteric artery (IMA) and lumbar artery (LA) were termed pIMA-T2Es and pLA-T2Es, respectively. The anatomical factors concerning the aneurysm, IMA and LAs were assessed in the preoperative CT angiography images. A statistical analysis was performed on the factors associated with pT2Es. RESULTS: The incidence of pT2Es was 25 %. pT2Es were associated with postoperative changes in the aneurysm diameter. A univariate analysis showed that a sac thrombus and the number of patent side branches arising from an aneurysm were significant factors associated with pT2Es. The IMA diameters were significantly larger in cases of pIMA-T2Es. The significant factors associated with pLA-T2Es were a circumferential thrombus, the number of patent LAs and the mean LA diameter. Multivariate analyses indicated that a circumferential thrombus was a protective factor for pT2Es, whereas an IMA ≥2.6 mm and each additional LA branch ≥1.9 mm were powerful risk factors for a pT2E. CONCLUSION: Significant anatomical factors associated with pT2E were found in this study. These factors may be useful in selecting patients for perioperative intervention.