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A 74 year-old man presented with complaints of dysuria and miction pain. Since the prostate volume was 43.5 ml, the patient was scheduled for surgical treatment of benign prostatic hyperplasia. However, prostate cancer was suspected from the magnetic resonance imaging findings and a prostate biopsy was performed. No malignant findings were observed in the pathological results, but numerous plasma cells stained positive for IgG4. Abdominal computed tomography showed pancreatic head enlargement with surrounding inflammatory changes and elevated serum IgG4 was also observed. The patient was diagnosed with IgG4-related disease (pancreatitis/prostatitis). Dysuria improved with induction of 30 mg prednisolone. The patient no longer needed to take the α1 blocker and 5α reductase inhibitor. The international prostate symptom score and urine flow measurement indicated that the patient remained in good condition at 18 months since the start of treatment.

Background: The electrophysiological characteristics of residual conduction gaps between the left atrium (LA) and pulmonary veins (PVs) after HotBalloon-based wide antral ablation (HBWA) of atrial fibrillation (AF) remain incompletely understood. This study aimed to characterize the residual gaps by means of ultra-high-resolution mapping.Methods and Results:A total of 55 AF patients underwent HBWA by a predetermined protocol (6-shot total-based antral approach). LA-PV maps were created using 64-electrode minibasket catheters. In total, 55 residual gaps were identified among 26 (47%) patients. Residual gaps included 33 left superior (LS: 60%), 10 left inferior (18%), 6 right superior (11%), and 6 right inferior (11%) PVs. Those gaps demonstrated both extremely lower bipolar amplitudes (0.11 [interquartile range: 0.06-0.27] mV) and conduction velocities (0.75±0.27 m/s); however, the length was confined (10.3±4.1 mm) except for the LSPV anterior carina (12.2±2.4 mm) region. Among the carina regions, all gaps had far-field potentials consistently added to the PV potentials. Left atrial appendage pacing to split the far-field activity identified confined gap regions (6.7±1.9 mm). Touch-up ablation eliminated the residual PV potentials in all cases., Conclusions: HBWA resulted in a certain degree of residual gap conduction in particular antral regions. These gaps exhibited narrow lengths with lower amplitudes, and often had far-field recordings from the left atrial appendage. Combined with pacing maneuvers, ultra-high-resolution activation maps could both visualize all confined gaps and ensure a bare minimum of touch-up ablations in all patients with gap conduction.

Background: CT-guided marking technique is rarely used in abdominal or urologic surgery. We developed and performed a marking technique for a small tumor, undetectable by ultrasound, using CT guidance before laparoscopic resection of the tumor. Case Presentation: A 73-year-old woman with a history of breast cancer underwent right colectomy with D3 lymph node dissection for ascending colon cancer. Five years after the operation, a solitary tumor was found in the right pararenal region of the retroperitoneal space on enhanced abdominal CT. The tumor was 20 mm in diameter and undetectable by ultrasound, so we performed a marking technique using CT guidance before the operation. Placing the patient in a prone position on the CT table, a 22-gauge needle was inserted into the Gerota's fascia percutaneously and a mixed fluid containing India ink and Iopamidol was injected para to the tumor by the radiologist. During the surgery, the marker was clearly identified and the cutting line was determined to ensure a sufficient surgical margin. The tumor was laparoscopically resected as planned. The histopathologic diagnosis was adenocarcinoma, compatible with metastasis of colon cancer. The postoperative course was uneventful and the patient remained free of disease at 10 months after surgery. Conclusion: When resecting small tumors or tumors with an irregular margin, a marking technique is conducted before the surgery. But, preoperative CT-guided marking has not been applied generally for resection of intraabdominal lesion yet. CT-guided marking can be effective when performing minimally invasive and curable surgery on small tumors. This is the first report of an effective CT-guided marking before retroperitoneal laparoscopic tumorectomy. We believe that this technique provides an important therapeutic option for small tumors that may be undetectable by ultrasound., Competing Interests: No competing financial interests exist.

Background: Current guidelines call for high-intensity statin therapy in patients with cardiovascular disease on the basis of several previous "more versus less statins" trials. However, no clear evidence for more versus less statins has been established in an Asian population., Methods: In this prospective, multicenter, randomized, open-label, blinded end point study, 13 054 Japanese patients with stable coronary artery disease who achieved low-density lipoprotein cholesterol (LDL-C) <120 mg/dL during a run-in period (pitavastatin 1 mg/d) were randomized in a 1-to-1 fashion to high-dose (pitavastatin 4 mg/d; n=6526) or low-dose (pitavastatin 1 mg/d; n=6528) statin therapy. The primary end point was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal ischemic stroke, or unstable angina requiring emergency hospitalization. The secondary composite end point was a composite of the primary end point and clinically indicated coronary revascularization excluding target-lesion revascularization at sites of prior percutaneous coronary intervention., Results: The mean age of the study population was 68 years, and 83% were male. The mean LDL-C level before enrollment was 93 mg/dL with 91% of patients taking statins. The baseline LDL-C level after the run-in period on pitavastatin 1 mg/d was 87.7 and 88.1 mg/dL in the high-dose and low-dose groups, respectively. During the entire course of follow-up, LDL-C in the high-dose group was lower by 14.7 mg/dL than in the low-dose group ( P <0.001). With a median follow-up of 3.9 years, high-dose as compared with low-dose pitavastatin significantly reduced the risk of the primary end point (266 patients [4.3%] and 334 patients [5.4%]; hazard ratio, 0.81; 95% confidence interval, 0.69-0.95; P =0.01) and the risk of the secondary composite end point (489 patients [7.9%] and 600 patients [9.7%]; hazard ratio, 0.83; 95% confidence interval, 0.73-0.93; P =0.002). High-dose pitavastatin also significantly reduced the risks of several other secondary end points such as all-cause death, myocardial infarction, and clinically indicated coronary revascularization. The results for the primary and the secondary composite end points were consistent across several prespecified subgroups, including the low (<95 mg/dL) baseline LDL-C subgroup. Serious adverse event rates were low in both groups., Conclusions: High-dose (4 mg/d) compared with low-dose (1 mg/d) pitavastatin therapy significantly reduced cardiovascular events in Japanese patients with stable coronary artery disease., Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01042730., (© 2018 The Authors.)

Background: Left ventricular outflow tract obstruction (LVOTO) occurs from not only obstructive hypertrophic cardiomyopathy but also other conditions such as sigmoid septum or post mitral valve repair. However, the changes of the LVOT pressure gradient (LVOT PG) in LVOTO with various conditions remain unclear., Methods: The clinical characteristics and echocardiographic parameters of 73 patients with LVOT PG ≥50 mmHg at rest on Doppler ultrasound were retrospectively investigated., Results: In these patients (age 69 ± 15 years, 38% male), high prevalences of hypertension (66%) and anemia (43%) were observed. The most frequent clinical disease causing LVOTO was hypertrophic obstructive cardiomyopathy (HOCM) (74%). There were other conditions, including hypertensive left ventricular hypertrophy (9%), post-open heart surgery (7%), sigmoid septum (4%), hyperkinetic LV (3%), takotsubo cardiomyopathy (1.5%), and discrete subaortic membrane (1.5%). Significant improvement or reduction of LVOTO was observed in 93% of cases at follow-up (mean 44 months) echocardiography compared with the initial one with the use of medications and transcatheter procedures., Conclusions: The causes of LVOTO are diverse. However, the occurrence of LVOTO might depend on the coexistence of primary morphological LV characteristics and hemodynamic LV status. Specific factors causing LVOTO need to be investigated, and efforts for improvement of each individual status by the appropriate approach are required.

Background: Bone marrow-derived progenitor cells likely contribute to both endothelial- and smooth muscle cell-dependent healing responses in stent-injured vessel sites. This study aimed to assess mobilization of progenitor cells and vessel healing after zotarolimus-eluting (ZES) and everolimus-eluting (EES) stents., Methods and Results: In 63 patients undergoing coronary stent implantation, we measured circulating CD34 + CD133 + CD45low cells and serum levels of biomarkers relevant to stem cell mobilization. In 31 patients of them, we assessed vessel healing within the stented segment using optical coherence tomography (OCT) imaging. The CD34 + CD133 + CD45low cells increased 68 ± 59% 7 days after bare metal stent (BMS), 10 ± 53% after ZES ( P  < 0.01 vs BMS), 3 ± 49% after EES ( P  < 0.001 vs BMS), compared with baseline. Percent change in CD34 + CD133 + CD45low cells was positively correlated with that in stromal cell-derived factor (SDF)-1α ( R  = 0.29, P  = 0.034). Percentage of uncovered struts was higher in the EES group (14.4 ± 17.3%), compared with the BMS (0.7 ± 1.3, P  < 0.01) and ZES (0.4 ± 0.5, P  < 0.01) groups. The change in CD34 + CD133 + CD45low cells showed positive correlation with OCT-quantified mean neointimal area ( R  = 0.48, P < 0.01). Finally, circulating mononuclear cells obtained from 5 healthy volunteers were isolated to determine the effect of sirolimus, zotarolimus and everolimus on vascular cell differentiation. The differentiation of mononuclear cells into endothelial-like cells was dose-dependently suppressed by sirolimus, zotarolimus, and everolimus., Conclusions: Mobilization of progenitor cells was suppressed, and differentiation of mononuclear cells into endothelial-like cells was inhibited, in association with increased number of uncovered stent struts, even after second generation drug-eluting stenting. These data suggest that new approaches are necessary to enhance stent healing.

Background: The alarmin family member myeloid-related protein (MRP)-14 (S100A9), which has been identified by platelet transcriptional profiling as an acute myocardial infarction gene, regulates vascular inflammation and thrombosis. Elevated plasma levels of MRP-8/14 (S100A8/A9) heterodimer predict first and recurrent cardiovascular events. The aim of this study was to elucidate pathophysiological roles of MRP-8/14 in acute coronary syndrome (ACS)., Methods and Results: In 38 consecutive ACS patients, the MRP-8/14 level in coronary artery blood obtained at thrombus aspiration was higher in 23 patients, in whom aspirated thrombus was confirmed, compared to the 15 patients, in whom it was absent [4.86 (1.95, 8.29) vs 2.94 (1.31, 4.44), P=0.017]. The MRP-8/14 level was correlated with myeloperoxidase (MPO) level (R 2 =0.52), but not with soluble P-selectin level (R 2 =0.0002) in the coronary artery blood. Immunohistochemistry of the aspirated thrombus exhibited that expression of MRP8/14 was co-localized with leukocytes positive for activated Mac-1. Finally, in cultured human umbilical vein endothelial cells, MRP-8/14 increased tissue factor expression., Conclusions: Our findings indicate that MRP-8/14 concentration increases in coronary artery blood in association with thrombus formation in ACS, co-localizes with leukocytes, and is associated with leukocyte activation. MRP-8/14 is positioned as a unique biomarker at the interface of inflammation and thrombosis in ACS., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Here, we report on a healthy 30-year-old man with no significant medical history, who tested negative for human immunodeficiency virus antigenemia but developed Aspergillus pancarditis. A case of this kind is extremely rare, and to the best of our knowledge, this is the first report of a patient with Aspergillus pancarditis, which generally leads to a very poor outcome, who had a long-term favorable clinical course. A biopsy from the right atrium of hypertrophied atrial septum was essential for obtaining the definitive diagnosis. Long-term administration of an effective antifungal oral agent might account for the patient's favorable outcome.

Background: Atrial low-voltage zones (LVZ) are suggested as important factors for maintaining persistent atrial fibrillation (PsAF). The relationship between LVZs and left atrial (LA) contact areas (CoAs) is still unclear., Objective: To assess whether CoA regions were involved in atrial substrate properties maintaining PsAF., Methods: A total of 50 patients with PsAF (36 long-lasting) were analyzed. Three representative CoA detection areas (ascending aorta-anterior-LA, descending aorta-left pulmonary vein antrum, and vertebrae-posterior-LA) were registered on the mapping geometry. Electrograms during AF and sinus rhythm (SR) were acquired, and the fractionated electrograms (CFE; < 80milliseconds) and voltages were analyzed regarding the CoAs., Results: After SR conversion, 76% (38/50) had a significant LVZ (>5% of the total LA surface area). Patients with long-lasting PsAF versus PsAF had larger CoA areas (7.7 ± 3.0 vs. 4.5 ± 2.5cm 2 , P < 0.05) and overlapped-LVZs (8.2 [3.2-11.0] vs. 2.1 [0.7-3.7] cm 2 , P = 0.0126) between the SR-LVZs (<0.5 mV) and AF-LVZs (<0.2 mV). Overlapped-LVZs were frequently observed in CoA regions (anterior 76.4%; LIPV antrum 78.8%, and vertebrae 39.2%), and those LVZs had smaller unipolar voltages than those distant from the CoA regions (0.64 ± 0.16 vs. 2.5 ± 1.5 mV, P < 0.0001). SR-LVZ targeted ablation, including of CoA regions, rendered AF termination (n = 8, 21%), and 88% of the sites were not located immediately above, but adjacent to, the overlapped-LVZs. Significant AF slowing (6.0 ± 0.6 to 5.6 ± 0.6 Hz; P < 0.05) accompanied by unintentional CFE elimination (9.8-1.8 cm 2 ; P < .0001) was achieved in patients without termination., Conclusion: Our data suggested that external structures in contact with the LA are involved in the creation of localized diseased myocardium necessary for PsAF maintenance., (© 2017 Wiley Periodicals, Inc.)

Although measurement of right ventricular ejection fraction (RVEF) may be relevant for evaluation of therapeutic efficacy and/or prognosis in patients with pulmonary hypertension, RVEF obtained by echocardiography has limited accuracy. In contrast, radionuclide and/or magnetic resonance imaging can measure RVEF more reliably. In this study, we investigated the relationship between RVEF measured by radionuclide angiography and the echocardiographic parameters that are recommended by the American Society of Echocardiography as representative of right heart function. There were 23 study participants with pulmonary hypertension who underwent radionuclide angiography and 2-dimensional and Doppler echocardiography (n = 30 measurements). RVEF measured by radionuclide angiography correlated with right ventricular Tei index (RV Tei index) measured by Doppler echocardiography (r = -0.601, P < 0.0005). Receiver operating characteristic curve analysis showed that an RV Tei index cut-off value of 0.371 was the best of predictor of RVEF ≤35% (area under the curve = 0.768, sensitivity = 0.857, selectivity = 0.667). Multiple regression analysis showed that RVEF was correlated with the RV Tei index, and this association was independent of other echocardiographic right ventricular function parameters (r = -0.644, P < 0.005). The RV Tei index measured by Doppler echocardiography may be an acceptable surrogate marker of RVEF in patients with pulmonary hypertension.

Herein, we report two cases of urethral clear cell carcinoma in two patients who had previously undergone radical hysterectomyfor utetine cancer. Case 1 presented with bloodyvaginal discharge and case 2 presented with acute urinaryretention. Magnetic resonance imaging revealed a periurethral tumor in both cases. Both cases were suspected to be recurrence at first. However, pathological findings of the transurethral resection-biopsyshowed clear cell adenocarcinoma in both cases. Subsequentlyradical cystourethrectomy and pelvic lymphadenectomy were performed in both cases. Surgical findings showed tumor invasion of the vaginal muscularis in case 1 and invasion of the anterior wall of the vagina and bladder neck in case 2. Although adjuvant postoperative therapywas not performed, there has been no evidence of recurrence to date.

Background: Type 2 diabetes mellitus (T2DM) is characterized by systemic metabolic abnormalities and the development of micro- and macrovascular complications, resulting in a shortened life expectancy. A recent cardiovascular (CV) safety trial, the EMPA-REG OUTCOME trial, showed that empagliflozin, a sodium glucose cotransporter 2 (SGLT2) inhibitor, markedly reduced CV death and all-cause mortality and hospitalization for heart failure in patients with T2DM and established CV disease (CVD). SGLT2 inhibitors are known to not only decrease plasma glucose levels, but also favorably modulate a wide range of metabolic and hemodynamic disorders related to CV pathways. Although some experimental studies revealed a beneficial effect of SGLT2 inhibitors on atherosclerosis, there is a paucity of clinical data showing that they can slow the progression of atherosclerosis in patients with T2DM. Therefore, the EMBLEM trial was designed to investigate whether empagliflozin treatment can improve endothelial function, which plays a pivotal role in the pathogenesis of atherosclerosis, in patients with T2DM and established CVD., Methods: The EMBLEM trial is an ongoing, prospective, multicenter, placebo-controlled double-blind randomized, investigator-initiated clinical trial in Japan. A total of 110 participants with T2DM (HbA1c range 6.0-10.0%) and with established CVD will be randomized (1:1) to receive either empagliflozin 10 mg once daily or a placebo. The primary endpoint of the trial is change in the reactive hyperemia (RH)-peripheral arterial tonometry-derived RH index at 24 weeks from baseline. For comparison of treatment effects between the treatment groups, the baseline-adjusted means and their 95% confidence intervals will be estimated by analysis of covariance adjusted for the following allocation factors: HbA1c (<7.0 or ≥7.0%), age (<65 or ≥65 years), systolic blood pressure (<140 or ≥140 mmHg), and current smoking status (nonsmoker or smoker). Key secondary endpoints include the change from baseline for other vascular-related markers such as arterial stiffness, sympathetic nervous activity, and parameters of cardiac and renal function. Importantly, serious adverse effects independently on the causal relationship to the trial drugs and protocol will be also evaluated throughout the trial period., Discussion: EMBLEM is the first trial to assess the effect of empagliflozin on endothelial function in patients with T2DM and established CVD. Additionally, mechanisms associating empagliflozin-mediated actions with endothelial function and other CV markers will be evaluated. Thus, the trial is designed to elucidate potential mechanisms by which empagliflozin protects CV systems and improves CV outcomes. Trial registration Unique Trial Number, UMIN000024502 ( https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000028197 ).

Purpose: The atrial conduction time measured by echocardiography using tissue Doppler imaging (TDI) has been reported as a predictive factor of left atrial (LA) remodeling. We investigated the P wave to LA appendage (LAA) conduction time defined by transthoracic echocardiography using TDI (P-LAA TDI), and directly compared the actual LA electrical conduction time determined by the electrophysiological data. Additionally, we confirmed the clinical utility of the P-LAA TDI by examining the relationship to the electroanatomical LA remodeling data., Methods: Sixty-three AF patients (22 paroxysmal AF, 41 persistent AF) underwent ablation and electroanatomical LA mapping. The P-LAA TDI was measured after the ablation and was compared with the electrophysiological data during sinus rhythm, including the actual electrical conduction time., Results: A strong linear correlation (r = 0.776, p < 0.001, y = 1.28x + 49) was observed between the P-LAA TDI (161 ± 24 ms) and electrophysiological P-LAA time (87 ± 15 ms). The P-LAA TDI was also strongly correlated with the LA volume (173 ± 52 ml, r = 0.632, p < 0.001) and LA conduction velocity index (1.07 ± 0.19 mm/ms, r = -0.735, p < 0.001), but less to the focal anterior-LVA region surface area (2.2 [0.4-5.0] cm 2 , r = 0.380, p = 0.002). Additionally, a stepwise multiple linear regression demonstrated that both the LA volume and LA conduction velocity index were strongly associated with the value of the P-LAA TDI (p < 0.001)., Conclusions: The P-LAA TDI was useful for estimating the actual electrophysiological conduction time and represented both electrical and anatomical LA remodeling.

A 45-year-old man complained of swelling of the left side of his neck and left upper limb. Ultrasonography and enhanced computed tomography (CT) revealed thrombosis of the left internal jugular, subclavian, and brachiocephalic vein. Based on various examinations, the patient was diagnosed with idiopathic venous thrombosis early in his clinical course. There were no findings to suggest malignancy or abnormal coagulability. However, two months after the start of treatment, the patient was diagnosed with gastric cancer. Despite the presence of Trousseau syndrome, treatment with edoxaban (an oral anticoagulant), reduced the swelling dramatically without any bleeding complications.

A 65-year-old man with non-ischemic cardiomyopathy, underwent an autopsy 2 months after the successful ablation of a sustained left ventricular (LV) summit ventricular tachycardia (VT). The patient died due to interstitial pneumonia from amiodarone use. The earliest activation sites of the VT were documented from both inside the anterior interventricular vein (AIV) and epicardial surface. The diameter of the AIV was 3-4 mm, and the radiofrequency (RF) lesion inside the AIV was a slight lesion due to high impedance with a high temperature. The lesion from the epicardial surface was also superficial and insufficient due to neighboring coronary arteries and the existence of epicardial fat. A successful application was performed from the LV endocardium, and diffuse myocardial fibrosis was observed in the mid-myocardium including inside the RF lesions. The actual relationship between the myocardial fibrosis and LV summit VT remains unclear, but this case showed the difficulty of achieving a successful ablation from the epicardial side, when the focus exists in the mid-myocardium around the LV summit.

A 20-year-old woman underwent an electrophysiological study for drug-resistant persistent inappropriate sinus tachycardia (IST). Use of a high-dose continuous intravenous administration of landiolol, a short-acting beta-adrenoreceptor blocker, made the patient׳s heart rate suddenly drop with a slight change in the P-wave morphology. Three-dimensional right atrial (RA) activation mapping revealed that the earliest activation site moved 8 mm to a lower anterior site around the high lateral RA. Radiofrequency energy applied to the earliest activation site during tachycardia was successful. A temporal sinus node modification with landiolol administration was useful for mapping and for safe catheter ablation of IST.

Background: A high catheter tip-tissue contact force (CF) with the myocardium may cause 3-dimensional (3D) map distortion, however, the influence of external structures surrounding the left atrium (LA) on that distortion remains unknown. This study characterized the impact of high CF mapping on the local LA geometry distortion., Methods: Thirty AF patients underwent 3D-ultrasound merged with CT images (3D-Merge-CT). The LA area in contact with external structures was identified by enhanced CT. Fast-electroanatomical-mapping (FAM) geometries were created by two methods, point-by-point mapping with high (>10g) CFs (high-CF guided-FAM), followed by that with multielectrode-mapping catheters (conventional-FAM). The resulting geometries were compared with the 3D-Merge-CT images., Results: Three representative anatomical contact areas (ascending aorta-vs.-anterior wall, descending aorta-vs.-left pulmonary vein [PV], and vertebrae-vs.-posterior wall) were identified. The PV antrum distorted distance on the 3D-Merge-CT was significantly longer for high-CF guided-FAMs than conventional-FAMs (1.7[0-3.6] vs. 0[0-1.8]mm, P<0.0001). In high-CF maps, the distorted distance significantly differed between regions with and without contact areas in both the PV antrum (0[0-0.17] vs. 1.7[0-3.9]mm, P=0.0201) and LA body region (0[0-1.5] vs. 1.7[0.7-2.2]mm, P<0.005). The catheter tip-tissue CF did not correlate with the distorted distance (r=0.08, P=0.46), and a multivariate analysis revealed that the absence of anatomical contact areas was strongly associated with significant local distortion, independent of the CF., Conclusions: High-CF guided mapping yields greater 3D-image anatomical distortion than conventional-FAM methods. That distortion was attenuated by regions with anatomical contact areas, suggesting that regional anatomic distortion is involved in the existence of external structures surrounding the LA., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Despite the low restenosis rates of drug-eluting stents (DES), several problems remain, including stent thrombosis, stent fracture, and neo-atherosclerosis. 'Stent-less' (balloon alone) percutaneous coronary intervention (PCI) is still being used, and several clinical trials have supported the efficacy of DCB. The aim of this study was to investigate the efficacy of a drug-coated balloon (DCB) in the treatment of de novo coronary artery disease., Methods: We enrolled 60 consecutive patients who had been given elective PCI between May 2014 and June 2015. They were randomly assigned to a 'stent-less' group (n=30) and a 'stent' group (n=30). Twenty-seven patients were treated with DCB alone and 33 with DES, and then evaluated for target lesion revascularization (TLR) rate and by quantitative coronary angiography (QCA) eight months later., Results: TLR rates were similar in the two groups (DCB; 0.0%, DES; 6.1%, P=0.169). In the QCA analysis, minimal lumen diameter (MLD) and acute gain were significantly smaller in the DCB group than in the DES group immediately after PCI (2.36±0.46 vs 2.64±0.37, P=0.011, and 1.63±0.41 vs 2.08±0.37, P<0.0001, respectively). Eight months after PCI, however, there was no significant difference in MLD or late lumen loss between the two groups., Conclusions: A 'stent-less' PCI using DCB could be useful even in the DES era. After 'stent-less' PCI, antiplatelet agents might be reduced or discontinued more safely than after DES implantation., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Type 2 diabetes mellitus is associated strongly with an increased risk of micro- and macro-vascular complications, leading to impaired quality of life and shortened life expectancy. In addition to appropriate glycemic control, multi-factorial intervention for a wide range of risk factors, such as hypertension and dyslipidemia, is crucial for management of diabetes. A recent cardiovascular outcome trial in diabetes patients with higher cardiovascular risk demonstrated that a SGLT2 inhibitor markedly reduced mortality, but not macro-vascular events. However, to date there is no clinical evidence regarding the therapeutic effects of SGLT2 inhibitors on arteriosclerosis. The ongoing PROTECT trial was designed to assess whether the SGLT2 inhibitors, ipragliflozin, prevented progression of carotid intima-media thickness in Japanese patients with type 2 diabetes mellitus., Methods: A total of 480 participants with type 2 diabetes mellitus with a HbA1c between 6 and 10 % despite receiving diet/exercise therapy and/or standard anti-diabetic agents for at least 3 months, will be randomized systematically (1:1) into either ipragliflozin or control (continuation of conventional therapy) groups. After randomization, ipragliflozin (50-100 mg once daily) will be added on to the background therapy in participants assigned to the ipragliflozin group. The primary endpoint of the study is the change in mean intima-media thickness of the common carotid artery from baseline to 24 months. Images of carotid intima-media thickness will be analyzed at a central core laboratory in a blinded manner. The key secondary endpoints include the change from baseline in other parameters of carotid intima-media thickness, various metabolic parameters, and renal function. Other cardiovascular functional tests are also planned for several sub-studies., Discussion: The PROTECT study is the first to assess the preventive effect of ipragliflozin on progression of carotid atherosclerosis using carotid intima-media thickness as a surrogate marker. The study has potential to clarify the protective effects of ipragliflozin on atherosclerosis. Trial registration Unique Trial Number, JPRN/UMIN000018440 ( https://upload.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000021348 ).

Overall stent performance should be characterized by geometric luminal gain acquisition, neointimal coverage of the stent struts, and stabilization of the underlying inflammatory neoatheroma. The aim of this study was to compare the performance of zotarolimus-eluting stent (ZES), everolimus-eluting stent (EES) and bare metal stent (BMS) using optical coherence tomography (OCT) and coronary angioscopy. For 36 stented coronary lesions (BMS, 12 lesions; ZES, 11 lesions; EES, 13 lesions) in 27 patients, we calculated neointimal area and uncovered stent strut rate based on OCT findings at 10 months after stent placement. The grades of neointimal coverage and yellow color, both of which were classified from 0 to 3, were also assessed by coronary angioscopy. The plaque area of the ZES lesions was larger than that of the EES lesions (P < 0.05) but smaller than that of the BMS lesions (P < 0.05). The OCT-based uncovered rate of the ZES lesions was less than that of the EES lesions (P < 0.01), but similar to that of the BMS lesions. The stent coverage grade by angioscopy was higher in the ZES lesions than in the EES lesions (P < 0.05), but similar to the BMS lesions. The yellow grade was less in the ZES lesions than in the EES lesions (P < 0.01), but similar to the BMS lesions. ZES might be better than BMS in terms of neointimal thickening, and better than EES in terms of neointimal coverage as well as prevention of neoatheroma formation. ZES may have superior performance compared with EES.

Background: Xanthine oxidase inhibitors are anti-hyperuricemic drugs that decrease serum uric acid levels by inhibiting its synthesis. Xanthine oxidase is also recognized as a pivotal enzyme in the production of oxidative stress. Excess oxidative stress induces endothelial dysfunction and inflammatory reactions in vascular systems, leading to atherosclerosis. Many experimental studies have suggested that xanthine oxidase inhibitors have anti-atherosclerotic effects by decreasing in vitro and in vivo oxidative stress. However, there is only limited evidence on the clinical implications of xanthine oxidase inhibitors on atherosclerotic cardiovascular disease in patients with hyperuricemia. We designed the PRIZE study to evaluate the effects of febuxostat on a surrogate marker of cardiovascular disease risk, ultrasonography-based intima-media thickness of the carotid artery in patients with hyperuricemia., Methods: The study is a multicenter, prospective, randomized, open-label and blinded-endpoint evaluation (PROBE) design. A total of 500 patients with asymptomatic hyperuricemia (uric acid >7.0 mg/dL) and carotid intima-media thickness ≥1.1 mm will be randomized centrally to receive either febuxostat (10-60 mg/day) or non-pharmacological treatment. Randomization is carried out using the dynamic allocation method stratified according to age (<65, ≥65 year), gender, presence or absence of diabetes mellitus, serum uric acid (<8.0, ≥8.0 mg/dL), and carotid intima-media thickness (<1.3, ≥1.3 mm). In addition to administering the study drug, we will also direct lifestyle modification in all participants, including advice on control of body weight, sleep, exercise and healthy diet. Carotid intima-media thickness will be evaluated using ultrasonography performed by skilled technicians at a central laboratory. Follow-up will be continued for 24 months. The primary endpoint is percentage change in mean intima-media thickness of the common carotid artery 24 months after baseline, measured by carotid ultrasound imaging., Conclusions: PRIZE will be the first study to provide important data on the effects of febuxostat on atherosclerosis in patients with asymptomatic hyperuricemia. Trial Registration Unique trial Number, UMIN000012911 ( https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=brows&action=brows&type=summary&recptno=R000015081&language=E ).

A 70-year-old man underwent stent implantation for right coronary artery (RCA) lesions with a bare metal stent (BMS) and two sirolimus-eluting stents (SES). However, as both the BMS and SES stented sites developed restenosis after 13 months, he underwent target lesion revascularization using directional coronary atherectomy (DCA). On histopathology, the restenosis lesion at the SES-deployed site showed greater inflammation and less re-endothelialization than that at the BMS-deployed site. Three months later, the SES-deployed site developed a second restenosis, in which paclitaxel-eluting stents (PES) were implanted (PES-in-SES), while the BMS-deployed site was restenosis free. Five years later, restenosis was absent in these RCA lesions. However, by optical coherence tomography and/or coronary angioscopy, the PES-in-SES site in the RCA showed poor neointimal coverage over the stent struts and yellowish neointima, suggesting lipid-rich neoatheroma formation, whereas at the BMS site appropriate white neointima formation was observed. Drug-eluting stents still have problems of persistent inflammation, inappropriate neointima formation, and neoatherosclerosis. Although we are now in the era of second generation DESs in which better stent performance would be promising, we should remember that we are obliged to continue to follow-up all patients in whom first generation DESs such as SES or PES have been placed.

Background and Aims: Heparin/protamine micro/nanoparticles (LH/P-MPs) were recently developed as low-molecular weight, biodegradable carriers for adipose-derived stromal cells (ADSCs). These particles can be used for a locally delivered stem cell therapy that promotes angiogenesis. LH/P-MPs bind to the cell surface of ADSCs and promote cell-to-cell interaction and aggregation of ADSCs. Cultured ADSC/LH/P-MP aggregates remain viable. Here, we examined the ability of these aggregates to rescue limb loss in a mouse model of hindlimb ischemia., Methods: Unilateral hindlimb ischemia was induced in adult male BALB/c mice by ligation of the iliac artery and hindlimb vein. For allotransplantation of ADSCs from the same inbred strain, we injected ADSC alone or ADSC/LH/P-MP aggregates or control medium (sham-treated) directly into the ischemic muscles. Ischemic limb blood perfusion, vessel density, and vessel area were recorded. The extent of ischemic limb necrosis or limb loss was assessed on postoperative days 2, 7, and 14., Results: Compared with the sham-treatment control, treatment with ADSCs alone showed modest effects on blood perfusion recovery and increased the number of α-SMA-positive vessels. Response to ADSC/LH/P-MP aggregates was significantly greater than ADSCs alone for every endpoint. ADSC/LH/P-MP aggregates more effectively prevented the loss of ischemic hindlimbs than ADSCs alone or the sham-treatment., Conclusion: The LH/P-MPs augmented the effects of ADSCs on angiogenesis and reversal of limb ischemia. Use of ADSC/LH/P-MP aggregates offers a novel and convenient treatment method and potentially represents a promising new therapeutic approach to inducing angiogenesis in ischemic diseases., (Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.)

Background: The aim of the present study was to elucidate the effect of teneligliptin on oxidative stress and endothelial function in Japanese patients with type 2 diabetes and chronic kidney disease (CKD)., Methods: Forty-five patients with type 2 diabetes and CKD who received sitagliptin for at least 12 months were randomized to either continue sitagliptin (n = 23) or switch to teneligliptin (n = 22) for 24 weeks. The following parameters were evaluated at baseline and after 24 weeks of treatment with continued sitagliptin or teneligliptin: blood pressure, haemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), urinary albumin excretion, endothelial function by reactive hyperaemia index (RHI; EndoPAT(®) system), reactive oxygen metabolites (ROMs) measured by the d-ROMS test, 8-hydroxy-2'-deoxyguanosine, urinary liver-type fatty acid binding protein (L-FABP), and urinary 8-isoprostane., Results: The two groups did not significantly differ with regard to age, male-to-female ratio, duration of diabetes, body mass index, HbA1c, eGFR, or urinary albumin excretion levels at baseline. We found no significant differences in changes of HbA1c, eGFR, or urinary albumin excretion levels between the two groups after 24 weeks of treatment. However, treatment with teneligliptin, but not sitagliptin, significantly improved RHI values and was correlated with the percent changes in RHI and d-ROMs., Conclusions: The present study demonstrated that teneligliptin, can improve endothelial function and reduce renal and vascular oxidative stress in patients with type 2 diabetes and CKD, independently of reducing albuminuria or improving glucose control. Trial registration UMIN000017180.

Background: The impact of obstructive sleep apnoea on heart failure with preserved ejection fraction is unknown., Methods: Fifty-eight patients who had heart failure with a left ventricular ejection fraction; ≥50% underwent a sleep study. Brain natriuretic peptide (BNP) levels were determined at enrolment and at one, six, 12 and 36 months after enrolment., Results: Obstructive sleep apnoea was found in 39 patients (67%), and they were all subsequently treated with continuous positive airway pressure. Echocardiography at admission showed that E/E' tended to be higher in the 39 patients with, than in the 19 patients without, obstructive sleep apnoea (15.0±3.6 vs 12.1±1.9, respectively, P=0.05). The median BNP levels at enrolment were similar in patients with and without obstructive sleep apnoea [median (interquartile range): 444 (233-752) vs 316 (218-703) pg/ml]. Although BNP levels decreased over time in both groups, the reduction was less pronounced in patients with obstructive sleep apnoea (P<0.05). Consequently, BNP levels were higher in patients with sleep apnoea at six months, [221 (137-324) vs 76 (38-96) pg/ml, P<0.05], 12 months [123 (98-197) vs 52 (38-76) pg/ml, P<0.05] and 36 months [115 (64-174) vs 56 (25-74) pg/ml, P<0.05]., Conclusion: Obstructive sleep apnoea, even when treated appropriately, may worsen long-term cardiac function and outcomes in patients who have heart failure with preserved ejection fraction., (Copyright © 2015 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Introduction: Atrial low-voltage zones (LVZs) may be related to maintenance of atrial fibrillation (AF). The influence of left atrial (LA) contact areas (CoAs) on reentrant or rotor-like sources maintaining AF has not been investigated., Methods and Results: Forty patients with persistent AF (PsAF) were analyzed. Three representative CoA regions in the LA (ascending aorta: anterior wall; descending aorta: left inferior pulmonary vein; and vertebrae: posterior wall) were visualized by enhanced CT. Using circular catheters, the LVZs (<0.5 mV) were assessed after restoration of SR, and local activation mapping and frequency domain analyses were performed after induction of AF. Circular activation during AF was visually defined as sites with ≥2 rotations by serial electrograms encompassing >80% of the mean AF cycle length. A pivot was defined as the core of the localized circular activation. Anterior (39/40 patients, 98%), left pulmonary vein antrum (27/40, 68%), and posterior (19/40, 48%) CoAs were identified, and 80% (68/85) of those sites were overlapped by or close (<3 mm) to LVZs. Thirty-six (90%) patients demonstrated circular activation (3.1±1.7 sites/patients) along with significantly higher organized dominant frequencies (6.3 ± 0.5 Hz, regularity-index: 0.26 [0.23-0.41]) within the LA, and the average electrogram amplitude of those pivots was 0.30 mV (0.18-0.52). Of those sites, 55% (66/120) were located at or close to CoA regions. Catheter ablation including of LVZs neighboring CoAs terminated AF in 9 (23%) patients., Conclusions: External anatomical structures contacting the LA may be related to unique conduction properties in diseased myocardium necessary for PsAF maintenance., (© 2016 Wiley Periodicals, Inc.)

Background: Because type 2 diabetes mellitus is associated strongly with an increased risk of cardiovascular diseases, the number of patients with diabetes with chronic heart failure is increasing steadily. However, clinical evidence of therapeutic strategies in such patients is still lacking. A recent randomized, placebo-controlled trial in patients with type 2 diabetes with high cardiovascular risk demonstrated that the SGLT2 inhibitor, empagliflozin, reduced the incidence of hospitalization for heart failure. Because SGLT2 inhibitors cause a reduction in body weight and blood pressure in addition to improving glycemic control, they have the potential to exert beneficial effects on the clinical pathophysiology of heart failure. The aim of the ongoing CANDLE trial is to test the safety and non-inferiority of canagliflozin, another SGLT2 inhibitor, compared with glimepiride, a sulfonylurea agent, in patients with type 2 diabetes mellitus and chronic heart failure., Methods: A total of 250 patients with type 2 diabetes who are drug-naïve or taking any anti-diabetic agents and suffering from chronic heart failure with a New York Heart Association classification I to III will be randomized centrally into either canagliflozin or glimepiride groups (1: 1) using the dynamic allocation method stratified by age (<65, ≥65 year), HbA1c level (<6.5, ≥6.5 %), and left ventricular ejection fraction (<40, ≥40 %). After randomization, all the participants will be given the add-on study drug for 24 weeks in addition to their background therapy. The primary endpoint is the percentage change from baseline in NT-proBNP after 24 weeks of treatment. The key secondary endpoints after 24 weeks of treatment are the change from baseline in glycemic control, blood pressure, body weight, lipid profile, quality of life score related to heart failure, and cardiac and renal function., Discussion: The CANDLE trial is the first to assess the safety and non-inferiority of canagliflozin in comparison with glimepiride in patients with type 2 diabetes with chronic heart failure. This trial has the potential to evaluate the clinical safety and efficacy of canagliflozin on heart failure. Trial registration Unique trial Number, UMIN000017669.

A 66-year-old man was admitted to our institute because of chest pain. He had undergone replacement of the ascending aorta due to aortic dissection 9 years previously. We made a diagnosis of acute coronary syndrome, and coronary artery angiography was performed. Although the right coronary artery was successfully cannulated, a severe bend of the artificial aorta made it very difficult to advance the catheter into the left coronary artery. Ultimately, a DIO thrombus aspiration catheter was used to enter the left coronary artery, and a stent was implanted successfully. The DIO catheter is very useful when the selection of a guiding catheter is complicated, such as in the case of severe vessel tortuosity or a bend of the ascending aorta.

Background: Percutaneous coronary intervention (PCI) is an effective treatment for patients with ischemic heart disease. In particular, restenosis is suppressed after drug-eluting stent (DES) implantation. However, several problems remain. Previously, we reported neointimal proliferation after DES implantation, which was associated with insulin resistance (IR). The aim of the present study was to clarify whether IR is associated with mortality and major adverse cardiac and cerebrovascular events (MACCE) after 1st-generation DES implantation., Methods and results: We researched the clinical records of 109 patients who had undergone elective PCI and DES implantation between May 2007 and December 2010. We segregated these patients according to the value of the homeostasis model assessment of IR (HOMA-IR) into Group P (n=63; HOMA-IR ≥2.5, positive) and Group N (n=46; HOMA-IR <2.5, negative), and examined the relationship between HOMA-IR and MACCE. The observation period was 7.4±1.6 years. There were no differences between the 2 groups in the occurrence of all-cause death, cardiac death, restenosis, myocardial infarction, stroke, heart failure, or stent thrombosis. However, the late catch-up phenomenon was significantly more common in Group P than in Group N (12.7% vs. 2.2% P=0.048)., Conclusions: IR is a useful predictor of the late catch-up phenomenon after DES implantation, and improvement of IR may help to prevent the phenomenon. (Circ J 2016; 80: 657-662).

Hyperuricemia is a known cardiovascular risk factor. The angiotensin II receptor blocker (ARB) losartan is known to decrease serum uric acid (UA) level. A recent in vitro study demonstrated a strong interaction between irbesartan and UA transporters that exceeded that of losartan. The purpose of the present study was to evaluate the hypouricemic effect of irbesartan in a clinical setting. A total of 40 high-risk hypertensive outpatients with coronary artery disease, cerebrovascular disease and/or diabetes complications who were taking ARBs other than irbesartan and losartan were enrolled in this study. After a 4-week control period, the patients' prescribed ARBs were exchanged for an equivalent dose of irbesartan. We assessed blood pressure, heart rate, serum UA level, parameters of lipid and glucose metabolism, cardiac and renal function and inflammatory and oxidative stress markers in blood samples taken immediately before the initiation of irbesartan treatment and again after 12 weeks of treatment. All 40 recruited patients were followed (31 men and 9 women, mean age: 68 years) without any dropouts. During the 12 weeks of irbesartan treatment, no significant changes in blood pressure, heart rate, parameters of lipid or glucose metabolism or other biomarkers of cardiac function, renal function, or inflammation were observed. However, UA level (5.9±1.6 to 5.5±1.6 mg ml(-1), P=0.028) and the oxidative stress marker derivative reactive oxygen metabolites (dROMs) (354±83 to 310±65 U.CARR, P<0.001) were significantly lower at 12 weeks of treatment compared with before treatment. These results suggest that irbesartan has beneficial effects on hyperuricemia and oxidative stress.

A coved-type electrocardiogram (ECG) change in Brugada syndrome is suggested to be the result of abnormally delayed depolarization over the right ventricular outflow tract; however, ischemia of the conus branch of the right coronary artery presents the same ECG change. A 63-year-old man with a history of myocardial infarction demonstrated a transient coved-type ECG change during catheter ablation of ventricular tachycardia. The ECG change appeared during left ventricular mapping without any chest symptoms, and recovered spontaneously. A pilsicainide test was negative and a coved-type ECG did not appear during the perioperative or follow-up period.

Percutaneous coronary intervention is established as an effective treatment for patients with ischemic heart disease; in particular, drug-eluting stent implantation is known to suppress in-stent restenosis. Diabetes mellitus is an independent risk factor for restenosis, so reducing insulin resistance is being studied as a new treatment approach. In this prospective study, we sought to clarify the factors associated with in-stent restenosis after percutaneous coronary intervention, and we evaluated the homeostasis model assessment of insulin resistance (HOMA-IR) index as a predictor of restenosis. We enrolled 136 consecutive patients who underwent elective percutaneous coronary intervention at our hospital from February 2010 through April 2013. All were implanted with a 2nd-generation drug-eluting stent. We distributed the patients in accordance with their HOMA-IR index values into insulin-resistant Group P (HOMA-IR, ≥2.5; n=77) and noninsulin-resistant Group N (HOMA-IR, <2.5; n=59). Before and immediately after stenting, we measured reference diameter, minimal lumen diameter, and percentage of stenosis, and after 8 months we measured the last 2 factors and late lumen loss, all by means of quantitative coronary angiography. After 8 months, the mean minimal lumen diameter was smaller in Group P than that in Group N (1.85 ± 1.02 vs 2.37 ± 0.66 mm; P=0.037), and the mean late lumen loss was larger (0.4 ± 0.48 vs 0.16 ± 0.21 mm; P=0.025). These results suggest that insulin resistance affects neointimal tissue proliferation after 2nd-generation drug-eluting stent implantation.

An inferior vena cava filter migrated to the left pulmonary artery during removal. The legs of the filter were not open adequately due to thrombus accumulating around the legs and resulted in the filter floating up and migrating to the pulmonary artery through the right atrium and ventricle. The hook for retrieval placed at the top of the filter faced proximal in the pulmonary artery and the legs of filter remained closed, consequently the filter could be removed safely from the pulmonary artery. An 8-Fr multipurpose catheter with its flexibility was useful to retrieve the filter from the pulmonary artery., (Copyright © 2015. Published by Elsevier B.V.)

The purpose of this study was to evaluate the safety and feasibility of laparoscopic partial nephrectomy with a small renal tumor. Between September 2004 and October 2014, 69 patients who underwent laparoscopic partial nephrectomy in Kansai Rosai Hospial were examined. The mean patient age was 60.3 years, and the mean tumor size was 24.5 mm. The mean estimated blood loss was 111 cc. The mean cold ischemic time was 59.7 minutes, and the mean warm ischemic time was 31.3 minutes. There were 5 complications : intraoperative ureteral injury, blood transfusion, postoperative perinephric hematoma, portsite bleeding, urinary fistula, respectively. All of the cases were cured with non-surgical treatment except ureteral injury which was repaired intraoperatively. The postoperative eGFR loss was 11%. At present, no patients have developed local recurrence or distant metastasis. The initial outcome of laparoscopic partial nephrectomy in our hospital was satisfactory in terms of safety, renal function and cancer control.

Introduction: Left atrial (LA) low voltage areas (LVAs) are suggested as an important factor for maintaining atrial fibrillation (AF). The relationship between focal LVAs and anatomical contact is still unclear., Methods: Thirty paroxysmal AF (PAF) and 30 persistent AF (PsAF) patients underwent high density voltage mapping during sinus rhythm before any radiofrequency applications were performed. The relationship between the LVA (<0.5mV) and contact area (CoA) demonstrated by enhanced CT and the distance to near external structures were investigated., Results: The anterior region, posterior wall and left pulmonary vein (LPV) antrum were the three most frequent LVA sites that corresponded to CoA sites, and LVAs mostly overlapped with CoAs (PAF 47/61: 77%, PsAF 63/74: 85%). In the PAF group, patients with posterior-LVAs had a shorter distance to the vertebrae than those without (2.8 ± 1.1 vs. 4.4 ± 1.9 mm; P=0.0086). The distance to the vertebrae was the only predictive factor of the existence of a posterior-LVA and the cut-off value was ≤2.9 mm (P<0.0001). Similarly, an LPV-LVA also had the same results (2.0 ± 0.5 vs. 2.7 ± 0.8mm, P=0.0127) and the cut-off value was ≤2.6mm (P=0.0391). In contrast, the PsAF patients had no difference in the distance when compared to the existence of an LVA., Conclusions: Anatomical CoAs demonstrated a spatial relationship to the LVAs in AF patients. In PAF patients, the distance to near external structures in the posterior region was a predictive factor for the existence of an LVA and may have had some influence on maintaining AF, while in PsAF patients no relationship was suggested., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Increased epicardial adipose tissue (EAT) volume is associated with atrial fibrillation (AF). However, the efficacy of EAT-based left atrial (LA) ablation for persistent AF (PsAF) is unclear., Objective: The purpose of this study was to assess whether EAT-based LA ablation is effective for PsAF., Methods: In 60 PsAF patients (group I), 3-dimensional reconstructed computed tomography images depicting EAT were merged with NavX-based dominant-frequency (DF) and complex fractionated electrogram (CFE) maps obtained during AF. Pulmonary vein antrum isolation (PVAI) was followed by map-guided EAT-based ablation. Results were compared to those in a historical control group (group II, case-matched patients who underwent generalized stepwise ablation including linear plus CFE-targeted ablation)., Results: In 70% (n = 42) of group I patients, the LA-EAT was located at the pulmonary vein antra; anterior and inferior surfaces, roof, septum, and mitral annulus; and left atrial appendage. EAT was at or near (<3 mm) 71% (390/550) of high-DF (> -8 Hz) sites. In 41 patients with persistent AF despite EAT-targeted ablation, CFE burden decreased significantly (from 96% to 13%, P < .0001), and DF decreased within the coronary sinus (6.9 ± 0.7 Hz vs 5.9 ± 0.7 Hz, P < .0001). Radiofrequency energy duration was significantly less in group I than in group II (25 ± 6 minutes vs 31 ± 12 minutes, P < .05). During 16-month follow-up, freedom from AF on antiarrhythmic drugs was 78% vs 60% (P < .05)., Conclusion: PVAI plus EAT-based ablation efficiently eliminates high-frequency sources and yields relatively high success. EAT-based LA ablation is a simple, clinically feasible PsAF ablation strategy., (Copyright © 2014 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Smoking cessation decreases oxidative stress and restores vascular endothelial function. However, a recent meta-analysis suggests that the use of varenicline, a α4β2 nicotinic acetylcholine receptor partial agonist, increases the risk of cardiovascular events. This study was designed to determine the effect of varenicline-assisted smoking cessation on vascular endothelial function. Study subjects were 11 healthy Japanese males (mean age, 54.4 years) without evidence of cardiovascular disease who were eager to quit smoking. Each subject was treated with varenicline titrated up to 1.0 mg twice daily. We evaluated serum derivatives of reactive oxygen metabolites (d-ROMs) as a marker of oxidative stress, and flow-mediated dilation (FMD) of the brachial artery as a marker of vascular endothelial function. Both measurements were performed before and 3 months after completing smoking cessation. All subjects gained weight (average, 1.7 kg) after smoking cessation. However, there were no significant differences in the following parameters before and after smoking cessation: systolic blood pressure, diastolic blood pressure, heart rate, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, glucose and hemoglobin A1c. Serum d-ROM levels significantly decreased from 340.7±70.4 to 300.0±43.2 U.CARR (P=0.012), and FMD significantly increased from 3.36±1.26 to 5.25±1.33% (P=0.00067) after smoking cessation. There was an inverse correlation between FMD and serum d-ROM levels (R=-0.377; P=0.043). Our observations suggest that varenicline-assisted smoking cessation restores vascular endothelial function, and this is associated with decreased oxidative stress, despite an increase in body weight. As varenicline-assisted smoking cessation possibly has beneficial effects on vascular endothelial function, it might also reduce cardiovascular risk.