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Background and Objective: Ectopic beats originating from the pulmonary vein (PV) trigger atrial fibrillation (AF). The purpose of this study was to clarify the electrophysiological determinant of AF initiation from the PVs. Methods: Pacing studies were performed with a single extra stimulus mimicking an ectopic beat in the left superior pulmonary veins (LSPVs) in 62 patients undergoing AF ablation. Inducibility of AF, effective refractory period (ERP) and conduction properties within the PVs were analyzed. Results: A single extra stimulus in LSPV induced AF in 20 patients (32% of all patients) at the mean coupling interval (CI) of 172 ms. A CI-dependent anisotropic conduction at the AF onset was visualized in a 3D-mapping. Onset of AF was site-specific with reproducibility in each individual. Mean ERP in LSPV in the AF inducible group was shorter than that in the AF non-inducible group (182 ± 55 ms vs 254 ± 51 ms, P

Aims It has been reported that congestive heart failure (CHF) readmission has not decreased in the last decade. It is also reported that CHF readmission is likely to occur shortly after discharge. We investigated whether an early follow‐up at outpatient care within 2 weeks after discharge affects the long‐term readmission rate and prognosis. Methods and results We reviewed consecutive 1002 patients admitted to our hospital due to CHF. Two‐hundred and fifty‐nine patients who died in‐hospital or were transferred to another hospital or readmitted within 2 weeks were excluded and 743 of discharged patients were analysed. We extracted contributing variables associated with heart failure (HF) readmission and the composite adverse outcome (all cause death or HF readmissions) by univariate and multivariate analysis. Multivariate analysis showed that the early follow‐up was independently associated with freedom from HF readmission and the composite outcome. We divided these patients into two groups, with/without early follow‐up and performed a propensity score‐matching analysis (n = 259 each). HF readmission during 2 year follow‐up was significantly less in the early follow‐up group [P = 0.02, hazard ratio (HR) = 0.647, 95% confidence interval (CI) = 0.447–0.935] as well as the composite outcome was less in the early follow‐up group (P = 0.01, HR = 0.643, 95% CI = 0.456–0.908). Medication adjustments were done in only 33.2% of the patients. Rates of HF readmissions were comparable regardless of whether or not medication adjustment was done at the early follow‐up (P = 0.505, HR = 1.208, 95% CI = 0.692–2.106). Conclusions The present study demonstrates that an early follow‐up approach after discharge in CHF patients may improve the long‐term prognosis. These results may not depend on medication adjustment but rather on modifying patient factors early after discharge.

Background The pulmonary veins (PVs) have unique electrophysiological properties triggering and maintaining atrial fibrillation (AF). Bigeminal PV electrical activity (PV bigeminy) during sinus rhythm has been reported; however, its mechanisms and clinical implication remain unclear. We hypothesized that PV bigeminy indicates arrhythmogenic activities and influences clinical outcome. Methods and Results We retrospectively analyzed electrophysiological studies in 465 patients with AF who underwent first session PV isolation (PVI). PV bigeminy was observed in 30 PVs of 23 patients (4.9% of patients). PV bigeminy was observed in left inferior PV (LIPV) in 15 patients, which was the most prevalent, followed by left superior in seven and right superior in seven and right inferior in one. In response to atrial extra stimulus, the second PV potentials (PV2) showed decremental conduction properties, suggesting reentrant mechanisms involved (n = 5). Interestingly, AF was initiated from the 23 PVs with bigeminy in 21 patients (76.7% of 30 PVs with bigeminy), spontaneously or in response to drugs, which was significantly more prevalent from the AF initiation rate from each PV in the control 442 patients (182 firings in 1290 PVs, 14.1%, P, PV bigeminy is relatively rare but a unique electrophysiological finding that indicates arrhythmogenic PV triggering AF.

BackgroundCongenital scoliosis (CS) is a common vertebral malformation. Spondylocostal dysostosis (SCD) is a rare skeletal dysplasia characterised by multiple vertebral malformations and rib anomalies. In a previous study, a compound heterozygosity for a null mutation and a risk haplotype composed by three single-nucleotide polymorphisms inTBX6have been reported as a disease-causing model of CS. Another study identified bi-allelic missense variants in a SCD patient. The purpose of our study is to identifyTBX6variants in CS and SCD and examine their pathogenicity.MethodsWe recruited 200 patients with CS or SCD and investigatedTBX6variants. We evaluated the pathogenicity of the variants by in silico prediction and in vitro experiments.ResultsWe identified five 16p11.2 deletions, one splice-site variant and five missense variants in 10 patients. In vitro functional assays for missense variants identified in the previous and present studies demonstrated that most of the variants caused abnormal localisation of TBX6 proteins. We confirmed mislocalisation of TBX6 proteins in presomitic mesoderm cells induced from SCD patient-derived iPS cells. In induced cells, we found decreased mRNA expressions ofTBX6and its downstream genes were involved in somite formation. All CS patients with missense variants had the risk haplotype in the opposite allele, while a SCD patient with bi-allelic missense variants did not have the haplotype.ConclusionsOur study suggests that bi-allelic loss of function variants ofTBX6cause a spectrum of phenotypes including CS and SCD, depending on the severity of the loss ofTBX6function.

Patients with pancreatic ductal adenocarcinoma (PDAC) that have a history of other primary malignancies are not well documented. The current study therefore aimed to evaluate the clinicopathological characteristics of patients with PDAC with or without a history of other primary malignancies. A total of 102 patients with surgically treated PDAC that presented with or without a history of other primary malignancies were retrospectively analyzed. A total of 25 patients (24.5%) had a history of other primary malignancies (age, with history of other primary malignancy vs. without, 74.2 vs. 68.9 years; P=0.005) and the reason for consultation (P

Background Induction of atrial fibrillation (AF)/atrial tachycardia (AT) by atrial burst pacing following ablation procedure may reflect the presence of residual substrates in the atria that maintain AF. However, the relation between the inducibility and left atrial low voltage area (LVA) has not been established. Methods Fifty-nine patients (65 years old, 43 males) with persistent AF who underwent pulmonary vein isolation (PVI)-based ablation were studied. All patients underwent left atrial voltage mapping during sinus rhythm and atrial burst pacing after PVI. Atrial burst pacing was performed with 30-beat at an amplitude of 10V from the ostium of the coronary sinus; increasing from 240 to 320 ppm in steps of 20 ppm or failure to 1:1 atrial capture. Inducibility was defined as AF/AT lasting more than 5 minutes following burst pacing. Left atrial LVA and other co-variates were analyzed with regard to burst pacing positivity. Results AF/AT was induced by burst pacing in 23 patients (39%). Univariate analysis revealed that past history of stroke, CHADS2 score and presence of left atrial LVA were significantly associated with the inducibility of AF/AT. Multivariate analysis revealed that only the presence of LVA was associated with the inducibility (OR 1.5: per 10% increase; p=0.04). We focused on the relationship between the extent of LVA and burst positivity. AF/AT inducibility increased as low voltage area increased, and it was as high as 72.7% when low voltage area was more than 20% (P Conclusions Presence of left atrial LVA is an independent predictor of atrial tachyarrhythmia inducibility after PVI in patients with persistent AF. A large amount of low voltage area is related to AT inducibility rather than AF. Extent of LVA and burst positivity Funding Acknowledgement Type of funding source: None

Background/Introduction It has been reported that heart failure (HF) readmission has not declined even with current cardiology practice in the last 10 years. It has been also reported that HF readmission tends to occur shortly after discharge. This may be due to overwork and excessive salt intake after discharge. In other words, it is conceivable that patient factors are largely attributable, which should be intervene for better clinical outcomes. Purpose We hypothesized and investigated whether an early follow-up visit at outpatient care within 2 weeks after discharge affects the re-admission rate and prognosis in patients with decompensated HF. Methods We retrospectively investigated consecutive 407 hospitalized patients due to decompensated HF. After exclusion of 99 patients with in-hospital death, transfer to another hospital and readmission within 2 weeks after discharge, consecutive 308 out of 407 patients were investigated. Two-year clinical outcomes after discharge were collected and analyzed. An early follow-up was defined as an outpatient care visit within 2 weeks after discharge with the adjustment of drugs and/or the lifestyle guidance, if necessary. A setting of early follow-up in each patient was according to a physician's discretion. Results One hundred-twenty eight patients underwent early follow-up visits and other 180 patients were without it. An univariate analysis showed that the early follow-up was significantly associated with a lower HF readmission rate during 2 years (17.1% in the early follow-up group, 34.4% in the control group, p≤0.001, OR=0.397, 95% CI=0.230–0.685, Figure) and a 2-year composite adverse outcome (all cause death and HF readmission; 18.7% vs. 40.5%, p Conclusions The present study suggests that an early follow-up approach after discharge in decompensated HF patients may improve the long-term prognosis. These results were not dependent on whether a medication adjustment was performed or not. An early follow-up may help improve patient factors of HF worsening. Main results Funding Acknowledgement Type of funding source: None

Background Fibrodysplasia ossificans progressiva (FOP) is a rare autosomal-dominant disease characterized by heterotopic ossification (HO) in soft tissues and caused by a mutation of the ACVR1A/ALK2 gene. Activin-A is a key molecule for initiating the process of HO via the activation of mTOR, while rapamycin, an mTOR inhibitor, effectively inhibits the Activin-A-induced HO. However, few reports have verified the effect of rapamycin on FOP in clinical perspectives. Methods We investigated the effect of rapamycin for different clinical situations by using mice conditionally expressing human mutant ACVR1A/ALK2 gene. We also compared the effect of rapamycin between early and episode-initiated treatments for each situation. Results Continuous, episode-independent administration of rapamycin reduced the incidence and severity of HO in the natural course of FOP mice. Pinch-injury induced HO not only at the injured sites, but also in the contralateral limbs and provoked a prolonged production of Activin-A in inflammatory cells. Although both early and injury-initiated treatment of rapamycin suppressed HO in the injured sites, the former was more effective at preventing HO in the contralateral limbs. Rapamycin was also effective at reducing the volume of recurrent HO after the surgical resection of injury-induced HO, for which the early treatment was more effective. Conclusion Our study suggested that prophylactic treatment will be a choice of method for the clinical application of rapamycin for FOP.

Background Induction test of atrial fibrillation (AF) is one of endpoint measures in catheter ablation (CA). However, its predictive value in long‐term outcome remains controversial. Methods Ninety‐eight patients (61 years, 77 males) with persistent AF who underwent pulmonary vein antrum isolation‐based CA were retrospectively analyzed. We determined whether inducibility of AF/atrial tachyarrhythmias (AT) by atrial burst pacing at the end of CA and other characteristics were associated with the recurrence of AF/AT. Atrial burst pacing was performed with 30‐beat from the coronary sinus; increasing from 240 to 320 ppm. Inducibility was defined as AF/AT lasting ≥5 minutes following atrial burst pacing. Results AF/AT was induced in 50 patients (51%). During 1 year of follow‐up, 71 patients (72.4%) had no recurrence of AF/AT. A logistic regression analysis showed that female gender (OR 3.8; P = 0.02), multiple sessions (OR 3.5; P = 0.02), and early recurrence of AF/AT (OR 5.3; P = 0.004) were associated with clinical recurrence. AF/AT Inducibility was not associated with clinical recurrence (P = 0.65). A subanalysis in patients with enlarged LA (LA diameter ≥45 mm, n = 40) showed that AF/AT inducibility was associated with recurrence (OR 8.1; P = 0.04). The positive and negative predictive values of AF/AT inducibility for AF/AT recurrence were 41 and 89%, respectively. Negative predictive value was increased to 92.3% when the inducibility was defined as AF/AT of ≥30 seconds following atrial burst pacing. Conclusions AF/AT inducibility cannot predict long‐term clinical recurrence in patients with persistent AF. However, it may have a prognostic value especially in patients with enlarged LA.

Summary Background Postoperative pancreatic fistula (POPF) after pancreatoduodenectomy greatly influences patients' postoperative course. Several evaluation methods have been used to assess the risk of clinically relevant POPF (CR-POPF) after pancreatoduodenectomy namely, the original, alternative, and updated alternative fistula risk scores (o-FRS, a-FRS, and ua-FRS, respectively). Methods We enrolled 106/179 patients who underwent pancreatoduodenectomy in our institution between April 2013 and Mar 2018. CR-POPF was defined as grade B and C POPF according to the 2016 definitions of the International Study Group on Pancreatic Surgery. Results Pancreatic gland texture was the only significant risk factor for CR-POPF (p = 0.007). The CR-POPF incidence increased significantly according to the risk groups defined by both o-FRS (p = 0.004) and a-FRS (p = 0.004). The area under the curve for o-FRS, a-FRS, and ua-FRS was 0.693, 0.693, and 0.671, respectively. Conclusion o-FRS, a-FRS, and ua-FRS were almost equally useful for risk evaluation for CR-POPF after pancreatoduodenectomy. Further studies, especially for preoperative objective evaluation of pancreatic gland texture, are needed for more useful and accurate risk evaluation.

Pathophysiological functions of chloride intracellular channel protein 3 (CLIC3) in human gastric cancer have been unclear. In the tissue microarray analysis using 107 gastric cancer specimens, CLIC3 expression was negatively correlated with pathological tumor depth, and the patients with lower expression of CLIC3 exhibited poorer prognosis. CLIC3 was expressed in the plasma membrane of cancer cells in the tissue. CLIC3 expression was also found in a human gastric cancer cell line (MKN7). In whole-cell patch-clamp recordings of the cells expressing CLIC3, NPPB-sensitive outwardly rectifying Cl− currents were observed. Cell proliferation was significantly accelerated by knockdown of CLIC3 in MKN7 cells. On the other hand, the proliferation was attenuated by exogenous CLIC3 expression in human gastric cancer cells (KATOIII and NUGC-4) in which endogenous CLIC3 expression is negligible. Our results suggest that CLIC3 functions as a Cl− channel in the plasma membrane of gastric cancer cells and that decreased expression of CLIC3 results in unfavorable prognosis of gastric cancer patients.

Background Atrial functional mitral regurgitation (AFMR) occurs in patients with atrial fibrillation. However, morphological mechanisms of AFMR are poorly understood. Purpose The purpose of this study was to examine the morphological characteristics in patients with AFMR. Methods Among consecutive 795 patients undergoing initial radiofrequency catheter ablation (RFCA) at our hospital, twenty-five patients with persistent AF accompanied by AFMR (≥ moderate) before RFCA (AFMR group) were studied. Age-matched 25 patients with persistent AF without MR were defined as a control group. Results Left ventricular ejection fraction (LVEF) was lower and left atrium volume index was larger in the AFMR group (Table). Mitral valve annulus diameter and length of anterior mitral leaflet (AML) were similar between groups, whereas length of posterior mitral leaflet (PML) was significantly shorter in the AFMR group. Smaller tethering angle of AML (γ in the figure) and shorter tethering height were significantly associated with the occurrence of AFMR, which were different from morphology of functional mitral regurgitation in patients with dilated LV. Multiple regression analysis revealed that less tenting height (p Echocardiographic parameters AFMR (n=25) Control (n=25) P value Age, y 69±8 66±10 NS Male, n (%) 9 (36) 20 (80) P=0.001 LVEF,% 60±9 67±6 P=0.004 LAD, mm 44±5 41±7 NS LAVI, ml/m2 56±17 41±13 P Conclusions AFMR occurs in patients with unique morphological features, such as less tethering height and LA dilatation toward the posterior.

Background Catheter ablation (CA) of atrial fibrillation (AF) improves left ventricular ejection fraction (LVEF) and clinical outcomes in patients with left ventricular systolic dysfunction (LVSD). However, predictors of the improvement of LV function and clinical outcomes by CA were poorly understood. Purpose We examined the efficacy of CA in AF patients with LVSD and predictive factors associated with clinical outcomes. Method Among consecutive 795 patients undergone initial RFCA at our hospital, we studied 51 patients with LVSD (LVEF ≤50%). Improved LVEF more then 5% at 1-year after CA was classified as “responder” to CA. We analyzed clinical variables and echocardiographic parameters before and after the CAs. Results In the responder group, LVEF was significantly improved 1-year after catheter ablation compared with the non-responder group. (ΔLVEF 22±12% vs. −1±4%, p Baseline characteristics Responder (N=35) Non-Responder (N=16) P value Age, y 62±11 69±8 p Conclusion Younger age, absence of LV dilatation, lower plasma BNP, or absence of LGE may well predict favorable clinical outcomes after CA in patients with LVSD.

The pathophysiology of non-pulmonary vein (PV) triggers of atrial fibrillation (AF) is unclear. We hypothesized that left atrial non-PV (LANPV) triggers are associated with atrial tissue degeneration. This study analyzed 431 patients that underwent catheter ablation (mean age 62 yrs, 303 men, 255 paroxysmal AF [pAF] patients). Clinical and electrophysiological characteristics of non-PV trigger were analyzed. Fifty non-PV triggers in 40 patients (9.3%) were documented; LANPV triggers were the most prevalent (n = 19, 38%). LANPV triggers were correlated with non-paroxysmal AF (non-pAF) (OR 3.31, p = 0.04) whereas right atrial non-PV (RANPV) triggers (n = 14) and SVC triggers (n = 17) were not. The voltage at the LANPV sites during SR was 0.3 ± 0.16 mV (p

Purpose: Circumferential pulmonary vein ablation (CPVA) has been widely applied to atrial fibrillation (AF), however the effectiveness for chronic AF (CAF) is limited. Methods and Results: In order to improve success rate of CAF, we attempted to extend ablation line from left pulmonary vein to atrial septum passing through coronary sinus (EXAS method). In consecutive 77 CAF cases, latest 53 patients were treated with EXAS method, and initial 24 cases were treated with conventional CPVA method. During the procedure, CAF was terminated in 60% patients of EXAS group, whereas 27% in CPVA group (p=0.02). Freedom from recurrence of AF at 6 months was 8% in EXAS group, and 46% in CPVA group (p=0.0006). Conclusion: Stepwise additional ablation into atrial septum is effective method of CAF.