The Valsalva maneuver, the most sensitive test for patent foramen ovale (PFO) detection, is difficult during transesophageal echocardiography (TEE), especially after sedation. The aim of this study ...was to compare PFO detection effectiveness between inferior vena cava (IVC) compression and the Valsalva maneuver.
A total of 293 patients with paroxysmal atrial fibrillation undergoing TEE before initial atrial fibrillation ablation were prospectively enrolled. Agitated saline was injected in 290 patients under three conditions: Valsalva maneuver under conscious sedation, at rest, and IVC compression under deep sedation. Three patients with newly diagnosed atrial septal defects on TEE were excluded. The IVC compression maneuver consisted of manual compression 5 cm to the right of the epigastric region and depressed the abdominal wall by 5 cm for 30 sec and compression release immediately before right atrial opacification with microbubbles by agitated intravenous saline.
The overall PFO detection rate was better with IVC compression (57 PFOs 19.7%) than at rest (15 patients 5.2%) (P < .0001) or with the Valsalva maneuver (37 patients 12.8%) (P = .024). There were no significant differences in PFO detection between IVC compression and the Valsalva maneuver (IVC compression, 43 patients 22.5%; Valsalva maneuver, 35 patients 18.3%; P = .31), even in patients who could perform the Valsalva maneuver effectively (n = 191).
IVC compression is feasible and effective for detecting PFO and is not inferior to the Valsalva maneuver. In particular, IVC compression could be an alternative diagnostic method for PFO using TEE when the Valsalva maneuver cannot be performed under deep sedation.
Patients with inflammatory bowel disease (IBD) have an increased risk of developing colitis‐associated colorectal cancer (CAC). CAC cells often develop chemoresistance, resulting in a poorer ...prognosis than that of sporadic colorectal cancer (CRC). The mechanism by which CAC enhances malignant potential remains unknown. We have previously reported that the proteasomal degradation of the transcription factor Atonal homolog 1 (Atoh1) protein results in the non‐mucinous form of CRC. It also remains unknown whether Atoh1 protein is expressed in CAC. Therefore, in the present study, we investigated whether Atoh1 protein stabilizes in CAC. Consequently, the treatment with TNF‐α stabilized Atoh1 protein through the inactivation of GSK‐3β via Akt, resulting in the mucinous form of CRC cell lines. Atoh1 protein also enriched cancer stem cells with upregulated Lgr5 expression and cells in G0/G1 cell cycle phase, resulting in both the chemoresistance to 5‐fluorouracil and oxaliplatin and the promotion of cell migration. Immunofluorescence of the human mucinous CAC specimens showed the accumulation of NF‐κB p65 at nuclei with the expression of Atoh1 in mucinous cancer. In conclusion, the inflammation associated with carcinogenesis may preserve the differentiation system of intestinal epithelial cell (IEC), resulting in the acquisition of both the mucinous phenotype and high malignant potential associated with the enrichment of cancer stem cell.
Inflammation associated with carcinogenesis may preserve the differentiation system of IEC by stabilizing Atoh1 protein via TNF‐Akt axis, resulting in the acquisition of both the mucinous phenotype and high malignant potential, including the enrichment of cancer stem cells.
Background: The pre-procedural prediction of atrial fibrillation (AF) termination by catheter ablation in patients with persistent AF has not been evaluated fully. The aim of this study was to ...evaluate the pre-procedural predictors of persistent AF termination by ablation associated with the possibility of reverse remodeling of the left atrium (LA). Methods and Results: Seventy consecutive patients (mean age, 62±8 years) with persistent or long-standing persistent AF underwent ablation. They were divided into 2 groups: those with AF terminated by ablation (n=14; group 1) and those with AF terminated by cardioversion after ablation (n=56; group 2). The left atrial appendage (LAA) contraction velocity determined on transesophageal echocardiography was significantly decreased in group 2 as compared to group 1 (P<0.001). Kaplan-Meier analysis showed that the group 1 patients had a higher AF-free survival rate than those in group 2 during 12±4.1 months of follow-up (P=0.048). The LA reverse remodeling ratio, given as the volume difference between before and 3 months after ablation in group 1, was significantly greater after ablation than that in group 2 (25.8±13% vs. 15.0±15%, P=0.015). Multivariate logistic regression analysis indicated that the LAA contraction velocity was an independent predictor of persistent AF termination by ablation (P=0.018). Conclusions: The LAA contraction velocity was the only non-invasive pre-procedural predictor of persistent AF termination by ablation, indicating the possibility of reverse remodeling of the LA. (Circ J 2013; 77: 1416–1423)
Retinol (ROL), the alcohol form of vitamin A, is known to control cell fate decision of various types of stem cells in the form of its active metabolite, retinoic acid (RA). However, little is known ...about whether ROL has regulatory effects on colonic stem cells. We examined in this study the effect of ROL on the growth of murine normal colonic cells cultured as organoids. As genes involved in RA synthesis from ROL were differentially expressed along the length of the colon, we tested the effect of ROL on proximal and distal colon organoids separately. We found that organoid forming efficiency and the expression level of Lgr5, a marker gene for colonic stem cells were significantly enhanced by ROL in the proximal colon organoids, but not in the distal ones. Interestingly, neither retinaldehyde (RAL), an intermediate product of the ROL-RA pathway, nor RA exhibited growth promoting effects on the proximal colon organoids, suggesting that ROL-dependent growth enhancement in organoids involves an RA-independent mechanism. This was confirmed by the observation that an inhibitor for RA-mediated gene transcription did not abrogate the effect of ROL on organoids. This novel role of ROL in stem cell maintenance in the proximal colon provides insights into the mechanism of region-specific regulation for colonic stem cell maintenance.
Background
This study aimed to evaluate the atrial substrate in the left atrium (LA) by low‐voltage areas (LVAs) and high‐dominant frequencies (DFs) after circumferential pulmonary vein isolation ...(PVI) in nonparoxysmal atrial fibrillation (AF).
Methods
In 70 patients with nonparoxysmal AF patients (41 persistent AF), LA voltage maps were created during sinus rhythm by external cardioversion after PVI and DF mapping. The patients were divided into AF‐free and AF‐recurrent groups.
Results
The AF freedom rate without antiarrhythmic drugs was 69.0% after PVI after 1 procedure during a 12‐month follow‐up. There was a significant difference in the LVA (<0.5 mV)/LA surface area after PVI between the AF‐free and AF‐recurrent groups (15% vs 23%, P = .033). AF freedom was significantly greater in those with LVAs of ≤24% than in those with LVAs of >24% during 12 months of follow‐up (78.6% vs 53.8%, Log‐rank test P = .020). Fifty‐six (72%) of the 78 high‐DF sites (≥8 Hz) overlapped with LVAs. Thirty‐one (55%) of 56 high‐DF sites overlapped with LVAs that existed at LVA border zones. There were no significant differences in number of high‐DF sites that overlapped with LVAs in the LA between the two groups. However, in persistent AF patients, the max‐DF value in the LA exhibited a significant difference between the two groups (P = .008).
Conclusions
LVAs were associated with AF recurrences after PVI in nonparoxysmal AF patients and overlapped with many high‐DF sites. PVI alone may be enough to treat patients with mild‐to‐moderate extent (≤24%) of LVAs.
Background: The prevalence, gender- and age-related differences, ablation success rate and inter-relationship between the origins of the idiopathic ventricular arrhythmias (I-VA) have not been ...clarified. Methods and Results: A total of 625 consecutive patients with symptomatic, drug resistant I-VA (315 males and 310 females; mean age, 54±17 years; 218 ventricular tachycardias, 407 premature ventricular contractions) who underwent catheter ablation were studied. The patients were divided into 5 groups based on the VA origin: (1) outflow tract (OT)-VA, consisting of right ventricular (RV) OT-VA and left ventricular (LV) OT-VA; (2) inflow tract (IT)-VA, consisting of tricuspid annulus (TA)-free wall (FW)-VA, IT-septum-VA, and mitral (MA)-FW-VA; (3) LV-inferoseptum-VA; (4) LV-other-VA; and (5) RV-other-VA. RVOT-VA in women were 1.5 times more frequent than in men, while LVOT-VA were more frequent in men. The prevalence of LVOT origin I-VA increased with age compared to that for the RVOT. The mean age of MA-FW-VA patients (62±14 years) was higher than that of TA-FW-VA patients (51±18 years; P=0.03). The ablation success rate for RVOT-VA (88%) was higher than that for LVOT-VA (58%; P<0.0001). A multivariate analysis revealed that the patient age was one of the valuable predictors of a successful ablation (odds ratio=0.97; 95% confidence interval: 0.95-0.99; P=0.007). Conclusions: Distinct gender and age differences were found in the incidence of I-VA according to their site of origin. (Circ J 2011; 75: 1585-1591)
Beta-blockers are associated with several clinical benefits in patients with reduced left ventricular ejection fraction (REF) after acute myocardial infarction (AMI), such as lower rates of ...mortality, recurrence of myocardial infarction, and heart failure. However, the long-term prognosis of beta-blockers has rarely been investigated in patients with non-REF after AMI. This study aimed to investigate the clinical benefits of beta-blockers in these patients.
A total of 3281 consecutive patients who were hospitalized within 48 h after AMI were registered in the J-MINUET study. Patients who underwent primary percutaneous coronary intervention (PCI) and had a left ventricular ejection fraction ≥40 % were enrolled, and patients who died during admission were excluded. Included patients were divided into two groups according to the prescription of beta-blockers at discharge. Their characteristics and clinical outcomes were compared.
The number of AMI patients treated with beta-blockers was 1353 (70.4 %). Patients who received beta-blockers were younger and had a higher incidence of hypertension, dyslipidemia, and ST-segment elevation myocardial infarction than those who did not receive beta-blockers. The peak creatine kinase level after primary PCI was significantly higher in patients who received beta-blockers. These patients also had a lower incidence of a composite of all-cause death, myocardial infarction, and stroke compared to those that did not receive beta-blockers (7.3 % vs. 11.9 %, p = 0.001). Multivariate analysis showed that beta-blocker use was an independent factor for better clinical outcomes.
The J-MINUET study revealed the clinical benefit of beta-blockers in AMI patients with non-REF after primary PCI.
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•The J-MINUET trial is a prognostic study of patients diagnosed with acute myocardial infarction (AMI) based on the new definition.•Beta-blockers improved the composite endpoint in AMI patients without reduced left ventricular (LV) dysfunction.•Beta-blockers did not affect the incidence of heart failure in patients without LV dysfunction.
Notch signaling is activated in the intestinal epithelial cells (IECs) of patients with inflammatory bowel disease (IBD), and contributes to mucosal regeneration. Our previous study indicated that ...TNF-α and Notch signaling may synergistically promote the expression of the intestinal stem cell (ISC) marker OLFM4 in human IECs. In the present study, we investigated the gene regulation and function of OLFM4 in human IEC lines. We confirmed that TNF-α and Notch synergistically upregulate the mRNA expression of OLFM4. Luciferase reporter assay showed that OLFM4 transcription is regulated by the synergy of TNF-α and Notch. At the protein level, synergy between TNF-α and Notch promoted cytoplasmic accumulation of OLFM4, which has potential anti-apoptotic properties in human IECs. Analysis of patient-derived tissues and organoids consistently showed cytoplasmic accumulation of OLFM4 in response to NF-κB and Notch activation. Cytoplasmic accumulation of OLFM4 in human IECs is tightly regulated by Notch and TNF-α in synergy. Such cytoplasmic accumulation of OLFM4 may have a cell-protective role in the inflamed mucosa of patients with IBD.
•Notch and TNF-α signaling is important in IECs of patients with IBD.•Notch and TNF-α signaling promotes the cytoplasmic accumulation of OLFM4.•OLFM4 accumulation may have anti-apoptotic properties.•OLFM4 could protect against mucosal inflammation in IBD.
Patients with ulcerative colitis (UC) are at an increased risk of developing colitis-associated cancer (CAC), suggesting that continuous inflammation in the colon promotes the transformation of ...colonic epithelial cells. However, the mechanisms underlying cell transformation in UC remain unknown. We therefore aimed to investigate the effect of long-term inflammation on intestinal epithelial cells (IECs) using organoid culture.
IECs were isolated from mice colon, and were cultured according to a method for a three-dimensional (3D) organoid culture. To mimic chronic inflammation, a mixture of cytokines and bacterial components were added to the medium for over a year. Cell signal intensity was assessed by 3D immunofluorescence. Cell transformation was assessed by microarray with gene set enrichment analysis.
Stimulation with cytokines resulted in a significant induction of target genes for the nuclear factor (NF)-κB pathway in colonic organoids. Following 60 weeks of continuous stimulation, cell differentiation was suppressed. Continuous stimulation also resulted in significant amplification of NF-κB signalling. Amplified NF-κB signalling by long-term stimulation remained in colonic organoids even 11 weeks after the removal of all cytokines. Some genes were specifically upregulated only in colonic organoids after the removal all cytokines following long-term stimulation.
Colonic organoids stimulated with cytokines for a prolonged period were established as in vitro model to assess long-term epithelial responses to inflammatory cytokines. Chronic inflammation led to sustained NF-κB signalling activation in colonic organoids, resulting in cell transformation that might be related to the carcinogenesis of CAC in UC.
Abstract Background The endpoint of ablation procedures is suggested to be non-inducibility of paroxysmal atrial fibrillation (PAF). However, the prognosis of induced AF/atrial tachycardia (AT) after ...pulmonary vein isolation (PVI) in PAF patients remains unclear. Methods A total of 122 PAF patients were divided into the following 3 groups: Group 1, 79 without AF/AT induced after PVI; Group 2, 21 with AF/AT induced or sustained after PVI, and followed by a high-dominant frequency (DF) and continuous complex fractionated atrial electrogram (CFAE) site ablation and, if necessary, linear ablation; and Group 3, 22 with external cardioversion of AF/AT induced or sustained after PVI. High-DF (DF≥8 Hz) and continuous CFAE (fractionated intervals≤50 ms) sites were targeted. The ablation endpoint was non-inducibility of PAF. Results In Group 2, AF terminated in 2 patients with a high-DF and continuous CFAE site ablation. In 4 patients, AF induced after cardioversion did not terminate with left atrium linear ablation, and required additional cardioversion. Common atrial flutter in 2 patients terminated with cavotricuspid isthmus ablation. An AT terminated with a roofline ablation. Finally, no AF/AT could be induced in any of the patients in Group 2 after all the procedures. The cumulative freedom from AF/AT recurrence without antiarrhythmic drugs in Groups 1 and 2 was significantly greater than that in Group 3 after 1 procedure during 12 months of follow-up (90% and 91% vs. 64%, Log-rank test P =0.001 and P =0.033, respectively). Conclusions Atrial substrate ablation may improve the clinical outcome after ablation in patients after PVI with residual arrhythmia inducibility.
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