Novel insights into presenilin 1 mutation associated with a distinctive dementia phenotype and cotton wool plaques.

BACKGROUND: The mutations in the presenilin 1 gene (PSEN1) are the main cause of familial Alzheimer's disease. PSEN1 mutations affect amyloid-beta peptide production, which accumulates in the brain as senile plaque and cotton wool plaques (CWPs) and relates to other neurodegenerative disorders. Here we report the second case of the PSEN1 G266S mutation, which showed distinctive neuropathological features, including abundant CWPs. Lewy body pathology, and altered amyloid-beta production. METHOD: Using the proband's samples, we performed genetic analysis of the PSEN1, APP, MAPT, and APOE genes, histopathological and immunohistochemical analysis of the brain tissue, and biochemical analysis of Aß production in COS cells transfected with wild-type or mutant PSEN1. RESULTS: The patient presented with memory loss, abnormal behavior, and visual hallucinations. Brain scans showed reduced blood flow, mild atrophy, and white matter lesions. Genetic analysis revealed a heterozygous mutation at codon 266 (G266S) of PSEN1 and polymorphism of MAPT (Q230R). The brain had many CWPs, severe cerebral amyloid angiopathy (CAA), senile plaque, Lewy bodies, and neurites. Electron microscopy displayed myelinated fiber degeneration, mitochondrial damage, and amyloid fibrils in the white matter. The production level of Aß42 in PSEN1 G266S-transfected cells significantly increased. CONCLUSION: Our findings suggest that the PSEN1 G266S mutation may cause a heterogeneous clinical and pathological phenotype, influenced by other genetic or environmental factors.

Evaluating Emotional Outcomes of Medical Students in Pediatric Emergency Medicine Telesimulation.

The coronavirus disease 2019 (COVID-19) pandemic has challenged the feasibility of traditional in-person simulation-based clinical training due to the public health recommendation on social distancing. During the pandemic, telesimulation training was implemented to avoid multiple students and faculties gathering in confined spaces. While medical trainees' perceived emotions have been acknowledged as a critical outcome of the in-person simulation-based training, the impact of telesimulation on trainees' emotions has been unexamined. We conducted an educational team-based simulation study with a pediatric case of septic shock. Seventeen and twenty-four medical students participated in the telesimulation training and in-person simulation training, respectively. The institutional pandemic social restrictions at the time of each training session determined the participant assignment to either the telesimulation training or in-person simulation training. All participants responded to the Japanese version of the Medical Emotion Scale, which includes 20 items rated on a five-point Likert-type scale before, during, and after the simulation sessions. The measured emotions were categized into four emotion groups according to two dimensions: positive or negative and activating or deactivating emotions. The one-way analysis of variance between the telesimulation and in-person simulation training revealed no significant differences in the emotions perceived by the participants before, during, and after the simulation training sessions. The perceived emotions of medical students were comparable between the telesimulation and in-person simulation training. Further longitudinal studies with larger samples and multiple variables are needed to generalize the effectiveness of telesimulation.

A prospective observational study of video laryngoscopy-guided coaching in the pediatric intensive care unit.

BACKGROUND: There are limited data on the use of video laryngoscopy for pediatric patients outside of the operating room. AIM: Our primary aim was to evaluate whether implementation of video laryngoscopy-guided coaching for tracheal intubation is feasible with a high level of compliance and associated with a reduction in adverse tracheal intubation-associated events. METHODS: This is a pre-post observational study of video laryngoscopy implementation with standardized coaching language for tracheal intubation in a single-center, pediatric intensive care unit. The use of video laryngoscopy as a coaching device with standardized coaching language was implemented as a part of practice improvement. All patients in the pediatric intensive care unit were included between January 2016 and December 2017 who underwent primary tracheal intubation with either video laryngoscopy or direct laryngoscopy. The uptake of the implementation, sustained compliance, tracheal intubation outcomes including all adverse tracheal intubation-associated events, oxygen desaturations (<80% SpO2), and first attempt success were measured. RESULTS: Among 580 tracheal intubations, 284 (49%) were performed during the preimplementation phase, and 296 (51%) postimplementation. Compliance for the use of video laryngoscopy with standardized coaching language was high (74% postimplementation) and sustained. There were no statistically significant differences in adverse tracheal intubation-associated events between the two phases (pre- 9% vs. post- 5%, absolute difference -3%, CI95 : -8% to 1%, p = .11), oxygen desaturations <80% (pre- 13% vs. post- 13%, absolute difference 1%, CI95 : -6% to 5%, p = .75), or first attempt success (pre- 73% vs. post- 76%, absolute difference 4%, CI95 : -3% to 11%, p = .29). Supervisors were more likely to use the standardized coaching language when video laryngoscopy was used for tracheal intubation than with standard direct laryngoscopy (80% vs. 43%, absolute difference 37%, CI95 : 23% to 51%, p < .001). CONCLUSIONS: Implementation of video laryngoscopy as a supervising device with standardized coaching language was feasible with high level of adherence, yet not associated with an increased occurrence of any adverse tracheal intubation-associated events and oxygen desaturation.

[A Case of Diffuse Large B Cell Lymphoma of the Extrahepatic Bile Duct Cholangiocarcinoma].

The patient was an 81-year-old man who was hospitalized with poor appetite and obstructive jaundice. An abdominal CT scan showed remarkable thickening of the wall from the cystic duct to extrahepatic bile duct. Endoscopic retrograde cholangiopancreatography( ERCP)revealed stricture at the extrahepatic bile duct. Cholangiocarcinoma was diagnosed and pancreaticoduodenectomy was performed. The histopathological diagnosis was diffuse large B cell lymphoma (DLBCL). The patient was stable after the operation. We present a case report describing the resection of DLBCL of the extrahepatic bile duct along with a review of the literature.

Novel anti-GARP antibody DS-1055a augments anti-tumor immunity by depleting highly suppressive GARP+ regulatory T cells.

Regulatory T (Treg) cells, which are essential for maintaining self-tolerance, inhibit anti-tumor immunity, consequently hindering protective cancer immunosurveillance, and hampering effective anti-tumor immune responses in tumor-bearing hosts. Here, we show that depletion of Treg cells via targeting glycoprotein A repetitions predominant (GARP) induces effective anti-tumor immune responses. GARP was specifically expressed by highly suppressive Treg cells in the tumor microenvironment (TME) of multiple cancer types in humans. In the periphery, GARP was selectively induced in Treg cells, but not in effector T cells, by polyclonal stimulation. DS-1055a, a novel afucosylated anti-human GARP monoclonal antibody, efficiently depleted GARP+ Treg cells, leading to the activation of effector T cells. Moreover, DS-1055a decreased FoxP3+CD4+ T cells in the TME and exhibited remarkable anti-tumor activity in humanized mice bearing HT-29 tumors. We propose that DS-1055a is a new Treg-cell-targeted cancer immunotherapy agent with augmentation of anti-tumor immunity.

Acute Subdural Hematoma in High School Rugby Players in Japan: The Importance of Playing Experience for Injury Prevention.

OBJECTIVES: Acute subdural hematoma (ASDH) is known to be devasting sport-related head injury but it is relatively rare in rugby compared with other contact sports. Certain cases of ASDH have happened in high school rugby players in Japan. To prevent them from the injury we report a background of the players. METHODS: Data of high school rugby players who suffered ASDH were extracted from injury reports in the Japan Rugby Football Union between April 2004 and March 2020. The number of injured players, diagnosis on the report, school year, phase of play where the injury occurred, and playing career were analyzed. RESULTS: There were 30 cases of ASDH including 16 cases in the first year, 9 in the second year, and 5 in the third year of playing. Phase of play was mainly being tackled in 11 (37%), and tackling in 13 (43%). Novice players, defined as a player having less playing experience of rugby during junior high school, accounted for 77% of phase of tackling, 82% of being tackled. First year novice players accounted for 100% of phase of being tackled. Outcome within 6 months after injury was recovery in 14, morbidity in 6, mortality in 2, and unknown in 8. CONCLUSIONS: Playing experience in high school rugby players should be considered as an important factor for prevention of ASDH-in particular, phase of being tackled is riskier than that of tackling for first year novice players.

[A Case of Disseminated Myelocarcinoma with Bone Metastasis 15 Years after Mastectomy and Relatively Long-Term Survival through Multidisciplinary Treatment].

The patient was a 62-year-old woman who had undergone mastectomy in August 2003 for cancer of the right breast. In addition to radiation therapy in the remaining breast, chemotherapy and endocrine therapy were subsequently performed. The patient had a 10-year recurrence-free postoperative course followed by annual surveillance. Beginning in 2016, an elevation in the serum level of tumor markers was detected; however, no accumulations were found in PET-CT over 2 consecutive years(2016 and 2017). Thereafter, serum levels of tumor markers continued to rise, and a PET-CT in 2018 revealed costal accumulations leading to a diagnosis of late-stage bone metastasis in postoperative year 15. Although hormone therapy was resumed, a continuing rise in the serum level of tumor markers led to a diagnosis of diffuse bone metastasis by MRI in 2019. Treatment with abemaciclib was initiated, and with effective radiotherapy, the PS was maintained at 0-1, serum levels of tumor markers decreased, and the lesions themselves continued at SD. However, in June 2020, multiple liver metastases appeared in an abdominothoracic CT scan. The patient refused chemotherapy; this, a BSC policy was adopted. Acute hemolytic anemia occurred immediately thereafter, and the PS gradually deteriorated. The patient died in September 2020, 17 years and 1 month after surgery.

[A Case of Gastric Endocrine Carcinoma].

The patient was an 80-year-old man, hospitalized with poor appetite, light-headedness, and black stool. Esophagogastroduodenoscopy showed an ulcerative lesion in cardia, and the tumor was diagnosed as gastric cancer using the biopsy specimens. The patient underwent a gastrectomy with D1-node dissection. Pathologically, the small tumor cells infiltrated the muscularis propria of the gastric wall, and these tumor cells immunohistochemically showed a positive reaction for synaptophysin. Therefore, the tumor was diagnosed as small cell-neuroendocrine carcinoma of the stomach. Metastasis was not observed in regional lymph nodes, and the TNM classification was defined as pStage ⅠB. After surgery, adjuvant chemotherapy was not performed. The patient is well without recurrence for more than 7 months after the surgery. We experienced and report a case of gastric endocrine cell carcinoma that underwent resection and provide a review of the literature.

Clarifying the structure of serious head and spine injury in youth Rugby Union players.

This study aimed to clarify the cause of rugby head and spinal cord injuries through a network centrality analysis of 14-year (2004-2018) longitudinal data in Japan. The study hypothesis is that understanding the causal relationship among the occurrence of serious injuries, the quality of player experience and play situation as a network structure could be possible to obtain practical knowledge on injury prevention. In this study, bipartite graphs are used to make it easier to understand the situation of players and injuries. This would also help to elucidate more characteristic subgroup. A network bipartite graph and subgroup (cluster) analyses were performed to clarify the injured players' experience and the cause of injury. We used the algorithm of R program, IGRAPH, clustering edge betweenness. For subgroup extraction, the modularity Q value was used to determine which step to cut. The Japanese rugby population was 93,873 (2014-2018 average), and 27% were high school students. The data showed that careful attention would be particularly needed for groups of inexperienced Japanese high school players. Our study suggests that we should consider introducing rules that prohibit "head-on collisions" in youth rugby.

Analysis of CPR quality by individual providers in the pediatric emergency department.

OBJECTIVES: To describe chest compression (CC) quality by individual providers in two pediatric emergency departments (EDs) using video review and compression monitor output during pediatric cardiac arrests. METHODS: Prospective observational study. Patients <18 yo receiving CC for >1 min were eligible. Data was collected from video review and CC monitor device in a synchronized fashion and reported in 'segments' by individual providers. Univariate comparison by age (<1 yo, 1-8 yo, >8 yo) was performed by chi-square testing for dichotomous variables ('high-quality' CPR) and nonparametric testing for continuous variables (CC rate and depth). Univariate comparison of ventilation rate (V) was made between segments with an advanced airway versus without. RESULTS: 524 segments had data available; 42/524 (8%) met criteria for 'high-quality CC'. Patients >8 yo had more segments meeting criteria (18% vs. 2% and 0.5%; p < 0.001). Segments compliant for rate were less frequent in <1 yo (17% vs. 24% vs. 27%; p = 0.03). Segments compliant for depth were less frequent in <1 year olds and 1-8 year olds (5% and 9% vs. 20%, p < 0.001.) Mean V for segments with an advanced airway was higher than with a natural airway (24 ±â€¯18 vs. 14 ±â€¯10 bpm, p < 0.001). Hyperventilation was more prevalent in CPR segments with an advanced airway (66% vs. 32%, p < 0.001). CONCLUSIONS: CC depth is rarely guideline compliant in infants. Hyperventilation is more prevalent during CPR periods with an advanced airway in place. Measuring individual provider CPR quality is feasible, allowing future studies to evaluate the impact of CPR training.

Benefit of Rate Response with Closed-Loop Stimulation in Patients with Difficult Hemodialysis.

Rate-responsive pacing is known to improve quality of life (QOL) in patients with sick sinus syndrome and chronotropic incompetence. However, the sensors for rate response include accelerometers, closed-loop stimulation (CLS), and minute ventilation sensors (MV sensors), each of which has a different mode of action. For this reason, it is important to select appropriate sensors that match the daily habits and behavioral patterns of the patient. For example, young and active patients are expected to have a rate increase when an accelerometer is used, while elderly patients and patients with a physical disability who are only able to move slowly often have a poor response to the accelerometer. MV sensors are therefore better suited to these patients. Furthermore, CLS is considered effective for patients who require an increase in heart rate when at rest, for example, patients undergoing maintenance dialysis.We describe a representative case, demonstrating the effectiveness of closed-loop stimulation in a patient with hypotension during dialysis.

Standardising communication to improve in-hospital cardiopulmonary resuscitation.

AIM: Recommendations for standardised communication to reduce chest compression (CC) pauses are lacking. We aimed to achieve consensus and evaluate feasibility and efficacy using standardised communication during cardiopulmonary resuscitation (CPR) events. METHODS: Modified Delphi consensus process to design standardised communication elements. Feasibility was pilot tested in 16 simulated CPR scenarios (8 scenarios with physician team leaders and 8 with chest compressors) randomized (1:1) to standardised [INTERVENTION] vs. closed-loop communication [CONTROL]. Adherence and efficacy (duration of CC pauses for defibrillation, intubation, rhythm check) was assessed by audiovisual recording. Mental demand and frustration were assessed by NASA task load index subscales. RESULTS: Consensus elements for standardised communication included: 1) team preparation 15-30 s before CC interruption, 2) pre-interruption countdown synchronized with last 5 CCs, 3) specific action words for defibrillation, intubation, and interrupting/resuming CCs. Median (Q1,Q3) adherence to standardised phrases was 98% (80%,100%). Efficacy analysis showed a median [Q1,Q3] peri-shock pause of 5.1 s. [4.4; 5.8] vs. 7.5 s. [6.3; 8.8] seconds, p < 0.001, intubation pause of 3.8 s. [3.6; 5.0] vs. 6.9 s. [4.8; 10.1] seconds, p = 0.03, rhythm check pause of 4.2 [3.2,5.7] vs. 8.6 [5.0,10.5] seconds, p < 0.001, median frustration index of 10/100 [5,20] vs. 35/100 [25,50], p < 0.001, and median mental demand load of 55/100 [30,70] vs. 65/100 [50,85], p = 0.41 for standardised vs. closed loop communication. CONCLUSION: This pilot study demonstrated feasibility of using consensus-based standardised communication that was associated with shorter CC pauses for defibrillation, intubation, and rhythm checks without increasing frustration index or mental demand compared to current best practice, closed loop communication.

Anomalous origin of the coronary artery coursing between the great vessels presenting with a cardiovascular event (J-CONOMALY Registry).

AIMS: Anomalous origin of the coronary artery (AOCA) with an inter-arterial course (IAC) between the great vessels poses a risk for a life-threatening cardiovascular event. We assessed, in a registry-based study, the clinical features, treatment strategies, and prognoses of life-threatening cardiovascular events ensuant to AOCA. METHODS AND RESULTS: Included were 65 AOCA patients (48 men/17 women, aged 41 ± 23 years) from 40 clinical centres who had experienced sudden cardiac arrest (SCA) (n = 30), acute myocardial infarction (AMI) (n = 5), angina (n = 23), or syncope (n = 7). The anomalous vessel was the right coronary artery in 72% of patients and left coronary artery in 28%; the ostium was slit-like in 42%. Coronary luminal narrowing ≥75% was absent in patients with SCA or syncope (86% and 57%, respectively), but occlusion or narrowing was seen in those with AMI (100%) or angina (52%). Age ≤40 years, male sex, sporting activity, absence of prodromal symptoms, acutely angled (≤30°) take-off from the aorta, and absence of luminal narrowing of the IAC segment were associated with SCA in this patient group. Coronary vasospasm was inducible in 12 of 17 patients without coronary narrowing. Management included surgical revascularization (n = 26) percutaneous coronary intervention (n = 9), and medical treatment (n = 26). Four SCA patients died while hospitalized; no others died during the median 5.0 (range, 1.8-7.0)-year follow-up period. CONCLUSIONS: In patients with AOCA, age ≤40 years, male sex, sporting activity, and an acute take-off angle appear to be risk factors for SCA. Appropriate management can be beneficial. Confirmation in a large-scale study is warranted.

Narrower QRS may be enough to respond to cardiac resynchronization therapy in lightweight patients.

A prolonged QRS duration (QRSd) is promising for a response to cardiac resynchronization therapy (CRT). The variation in human body sizes may affect the QRSd. We hypothesized that conduction disturbances may exist in Japanese even with a narrow (< 130 ms)-QRS complex; such patients could be CRT candidates. We investigated the relationships between QRSd and sex and body size in Japanese. We retrospectively analyzed the values of 338 patients without heart failure (HF) (controls) and 199 CRT patients: 12-lead electrocardiographically determined QRSd, left ventricular diastolic and systolic diameters (LVDd and LVDs), body surface area (BSA), body mass index (BMI), and LVEF. We investigated the relationships between the QRSd and BSA, BMI, and LVD. The men's and women's BSA values were 1.74 m2 and 1.48 m2 in the controls (p < 0.0001), and 1.70 m2 and 1.41 m2 in the CRT patients (p < 0.0001). The men's and women's QRSd values were 96.1 ms and 87.4 ms in the controls (p < 0.0001), and 147.8 ms and 143.9 ms in the CRT group (p = 0.4633). In the controls, all body size and LVD variables were positively associated with QRSd. The CRT response rate did not differ significantly among narrow-, mid-, and wide-QRS groups (83.6%, 91.3%, 92.4%). An analysis of the ROC curve provided a QRS cutoff value of 114 ms for CRT responder. The QRSd appears to depend somewhat on body size in patients without HF. The CRT response rate was better than reported values even in patients with a narrow QRSd (< 130 ms). When patients are considered for CRT, a QRSd > 130 ms may not be necessary, and the current JCS guidelines appear to be appropriate.

Is Vagal Response During Left Atrial Ganglionated Plexi Stimulation a Normal Phenomenon?: Comparison Between Patients With and Without Atrial Fibrillation.

BACKGROUND: Ganglionated plexi (GPs) play an important role in both the initiation and maintenance of atrial fibrillation (AF). GPs can be located by using continuous high-frequency stimulation (HFS) to elicit a vagal response, but whether the vagal response phenomenon is common to patients without AF is unknown. METHODS: HFS of the left atrial GPs was performed in 42 patients (aged 58.0±10.2 years) undergoing ablation for AF and 21 patients (aged 53.2±12.8 years) undergoing ablation for a left-sided accessory pathway. The HFS (20 Hz, 25 mA, 10-ms pulse duration) was applied for 5 seconds at 3 sites within the presumed anatomic area of each of the 5 major left atrial GPs (for a total of 15 sites per patient). We defined vagal response to HFS as prolongation of the R-R interval by >50% in comparison to the mean pre-HFS R-R interval averaged over 10 beats and active-GP areas as areas in which a vagal response was elicited. RESULTS: Overall, more active-GP areas were found in the AF group patients than in the non-AF group patients, and at all 5 major GPs, the maximum R-R interval during HFS was significantly prolonged in the AF patients. After multivariate adjustment, association was established between the total number of vagal response sites and the presence of AF. Conclusions The significant increase in vagal responses elicited in patients with AF compared with responses in non-AF patients suggests that vagal responses to HFS reflect abnormally increased GP activity specific to AF substrates.

Adverse Clinical Events during Long-Term Follow-Up After Catheter Ablation of Atrial Fibrillation.

Pulmonary vein isolation (PVI) of atrial fibrillation (AF) can reduce the AF burden and, potentially, reduce the long-term risk of strokes and death. However, it remains unclear whether anticoagulants can be stopped after PVI because of post-ablation AF recurrence in some patients. This study aimed to investigate the discontinuation rate of anticoagulants and long-term incidence of strokes after PVI.We enrolled 512 consecutive Japanese patients with AF (mean age, 63.4 ± 10.4 years; 123 women; 234 with non-paroxysmal AF; CHADS2 score/CHA2DS2-VASC score, 1.32 ± 1.12/2.21 ± 1.54) who underwent PVI between 2012 and 2015. During a 28.0 ± 17.1 -month follow-up, anticoagulants were terminated in 230 (44.9%) of the 512 patients, AF recurred in 200 (39.1%), and 10 (1.95%) suffered from a stroke. Death occurred in 5 (0.98%) patients. Although the incidence of strokes, by a Kaplan-Meier analysis, was similar, the incidence of death was lower (Hazard ratio 0.37, 95% confidence interval 0.12-0.93, P = 0.041) in the AF ablation group than the control group without ablation after 1:1 propensity score matching (the control data was derived from 2,986 patients in the SAKURA AF Registry, a large-cohort AF registry).Anticoagulants were discontinued in nearly half the patients who underwent AF ablation; of these, 39.1% experienced AF recurrences, 1.95% suffered from strokes, and 0.98% died, but the risk of death after AF ablation appeared to be lower than that in a propensity score-matched control group without ablation during long-term follow-up.

Preclinical Development of U3-1784, a Novel FGFR4 Antibody Against Cancer, and Avoidance of Its On-target Toxicity.

The FGFR4/FGF19 signaling axis is overactivated in 20% of liver tumors and currently represents a promising targetable signaling mechanism in this cancer type. However, blocking FGFR4 or FGF19 has proven challenging due to its physiological role in suppressing bile acid synthesis which leads to increased toxic bile acid plasma levels upon FGFR4 inhibition. An FGFR4-targeting antibody, U3-1784, was generated in order to investigate its suitability as a cancer treatment without major side effects.U3-1784 is a high-affinity fully human antibody that was obtained by phage display technology and specifically binds to FGFR4. The antibody inhibits cell signaling by competing with various FGFs for their FGFR4 binding site thereby inhibiting receptor activation and downstream signaling via FRS2 and Erk. The inhibitory effect on tumor growth was investigated in 10 different liver cancer models in vivo The antibody specifically slowed tumor growth of models overexpressing FGF19 by up to 90% whereas tumor growth of models not expressing FGF19 was unaffected. In cynomolgus monkeys, intravenous injection of U3-1784 caused elevated serum bile acid and liver enzyme levels indicating potential liver damage. These effects could be completely prevented by the concomitant oral treatment with the bile acid sequestrant colestyramine, which binds and eliminates bile acids in the gut. These results offer a new biomarker-driven treatment modality in liver cancer without toxicity and they suggest a general strategy for avoiding adverse events with FGFR4 inhibitors.

The modified ablation index: a novel determinant of acute pulmonary vein reconnections after pulmonary vein isolation.

BACKGROUND: Although pulmonary vein isolation (PVI) guided by the ablation index (AI) has been well-developed, acute PV reconnections (PVRs) still occur. This study aimed to compare the prognostic performance of the modified AI and its optimal cut-off value for the prediction of acute PVRs to ensure durable PVI. METHODS: Three-dimensional left atrium (LA) voltage maps created before an extensive encircling PVI in 64 patients with atrial fibrillation (AF) (45 men, 62 ± 10 years) were examined for an association between electrogram voltage amplitude recorded from the PV-LA junction and acute post-PVI PVRs (spontaneous PVRs and/or ATP-provoked dormant PV conduction). RESULTS: Acute PVRs were observed in 22 patients (34%) and 33 (3%) of the 1012 PV segments. Acute PVRs were significantly associated with segments with higher bipolar voltage zones (3.23 ± 1.17 vs. 1.97 ± 1.20 mV, P < 0.0001), lower mean AI values (449 [428-450] vs. 460 [437-486], P = 0.05), and radiofrequency lesion gaps ≥ 6 mm (48 vs. 32%, P = 0.04), but not with contact force, force-time integral, or power. We created the modified AI calculated as AI/LA bipolar voltage, and found it to be significantly lower in areas with acute PVRs than in those without (152 [109-185] vs. 256 [176-413] AU/mV, P < 0.0001). Univariate analysis showed the prognostic performance of the modified AI, with an area under the curve of 0.801 (0.775-0.825), to be the highest of all the significant parameters. CONCLUSIONS: Low values of the novel modified AI on the PV-encircling ablation line were strongly associated with acute PVRs.

Effect of epicardial fat and metabolic syndrome on reverse atrial remodeling after ablation for atrial fibrillation.

BACKGROUND: Metabolic syndrome/epicardial adipose tissue (EAT) plays an important role in atrial fibrillation (AF). Although reverse atrial remodeling (RAR) often occurs after AF ablation, the effects of EAT on RAR remain unknown. METHODS: Study subjects were 104 patients in whom transthoracic echocardiography (TTE) was performed before AF ablation and 3, 6, and 12 months afterward. EAT was assessed in terms of its thickness adjacent to the right ventricular anterior wall in the TTE parasternal view. RAR was defined as >10% reduction in the left atrial volume (LAV) index by the 3-month follow-up examination. RESULTS: Postablation RAR occurred in 57/104 (55%) patients. RAR absence was associated with a relatively thick EAT (4.92 ± 1.65 vs. 3.92 ± 1.17 mm, P = 0.0005), small LAV index (24.6 ± 7.5 vs. 28.8 ± 10.6 mL/m2, P = 0.0233), and metabolic syndrome (62% vs. 28%, P = 0.0006). Metabolic syndrome and EAT were shown to be independent predictors of RAR absence. Thick EAT was significantly associated with AF recurrence after ablation (5.05 ± 2.19 mm vs. 4.17 ± 1.16 mm for no AF recurrence group, P = 0.0116), but metabolic syndrome was not (48% vs. 42%, P = 0.6189). Despite no change in body weight, EAT thickness decreased significantly by 12 months in patients without AF recurrence (4.17 ± 1.16 vs. 3.65 ± 1.16 mm, P < 0.0001). CONCLUSIONS: EAT and metabolic syndrome appear to be strongly associated with RAR absence, but only the thick EAT was significantly associated with the postablation AF recurrence. Our findings, especially the thinning of EAT, suggest that thick EAT lead to AF vulnerability but that EAT reduction favorably affects ablation outcome.

Influence of balloon temperature and time to pulmonary vein isolation on acute pulmonary vein reconnection and clinical outcomes after cryoballoon ablation of atrial fibrillation.

BACKGROUND: Limited data exist on indicators of durable pulmonary vein isolation (PVI) undergoing cryoballoon ablation (CBA) for atrial fibrillation (AF). We investigated whether balloon temperature and time to PVI can be used to predict early PV reconduction (EPVR), including residual PV conduction and adenosine triphosphate-induced dormant conduction and the relation between touch-up ablation of EPVR sites and mid-term recurrence of AF. METHODS: We obtained procedural and outcome data from the records of 130 consecutive patients who underwent CBA and followed up for 13.4 months. RESULTS: EPVR was identified in 86 (17%) PVs of 61 (47%) patients. Balloon temperatures during 30 seconds (-27 ± 5.7°C vs -31 ± 5.5°C), 60 seconds (-36 ± 5.6°C vs -41 ± 5.4°C), and at the nadir point (-41 ± 7.4°C vs -49 ± 7.0°C) were significantly higher, and the time to PVI was longer (90 ± 50 seconds vs 52 ± 29 seconds) in PVs with EPVR than in those without (P < 0.0001 for all). Among PVs without EPVR, the time to PVI was longer and balloon temperature was lower for the left superior pulmonary vein/ right inferior pulmonary vein (LSPV/RIPV) than for the right superior pulmonary vein/left inferior pulmonary vein (RSPV/LIPV) (time: 60 ± 25/73 ± 37 seconds vs 41 ± 31/45 ± 20 seconds, P < 0.0001) (temp: -39.2 ± 11.3/-39.4 ± 8.3°C vs -33.8 ± 10.6/-33.6 ± 6.8°C, P = 0.0023). AF recurrence rates were equivalent between patients with and without EPVR (13% [8/69] vs 15% [9/61], P = 0.845). CONCLUSIONS: Cryoballoon temperature and time to PVI appear to be useful in predicting durable PVI, that is, prevention of EPVR, but the balloon temperature and time required for PVI differ between PVs. Although EPVR does not predict AF recurrence, high success rates can be expected when touch-up ablation of EPVR sites is performed.