Search

Background The association of epicardial adipose tissue (EAT) and its metabolic activity with atrial fibrillation (AF) is an area of active investigation. Left atrial (LA) enhancing EAT (e-EAT) at cardiac CT may be a noninvasive surrogate marker for the metabolic activity of EAT. Purpose To determine the relationship between LA e-EAT and recurrence after AF ablation. Materials and Methods In a secondary analysis of a prospective registry of consecutive patients (from July 2018 to December 2019) undergoing first AF ablation, total and LA EAT were segmented on preprocedural noncontrast- and contrast-enhanced cardiac CT scans. LA e-EAT volume fraction was defined as the LA EAT volume difference between the noncontrast- and contrast-enhanced scan divided by the total LA EAT volume on the noncontrast-enhanced scan (threshold values, -15 HU to -195 HU). Continuous variables were compared between groups by using the Mann-Whitney

Preliminary studies show promise for extrahepatic islet transplantation (ITx). However, clinical comparisons with intraportal ITx outcomes remain limited.This single-center cohort study evaluates patients receiving extrahepatic or intraportal ITx between 1999 and 2018. Primary outcome was stimulated C-peptide level. Secondary outcomes were fasting plasma glucose, BETA-2 scores, and fasting C-peptide level. Multivariable logistic modeling evaluated factors independently associated with a composite variable of early graft failure and primary nonfunction within 60 d of ITx.Of 264 patients, 9 (3.5%) received extrahepatic ITx (gastric submucosal = 2, subcutaneous = 3, omental = 4). Group demographics were similar at baseline (age, body mass index, diabetes duration, and glycemic control). At 1-3 mo post-first infusion, patients receiving extrahepatic ITx had significantly lower stimulated C-peptide (0.05 nmol/L versus 1.2 nmol/L, P0.001), higher fasting plasma glucose (9.3 mmol/L versus 7.3 mmol/L, P0.001), and lower BETA-2 scores (0 versus 11.6, P0.001) and SUITO indices (1.5 versus 39.6, P0.001) compared with those receiving intraportal ITx. Subjects receiving extrahepatic grafts failed to produce median C-peptide ≥0.2 nmol/L within the first 60 d after transplant. Subsequent intraportal infusion following extrahepatic transplants achieved equivalent outcomes compared with patients receiving intraportal transplant alone. Extrahepatic ITx was independently associated with early graft failure/primary non-function (odds ratio 1.709, confidence interval 73.8-39 616.0, P0.001), whereas no other factors were independently predictive.Using current techniques, intraportal islet infusion remains the gold standard for clinical ITx, with superior engraftment, graft function, and glycemic outcomes compared with extrahepatic transplantation of human islets.

Little is known about how early islet graft function evolves in the clinical setting. The BETA-2 score is a validated index of islet function that can be calculated from a single blood sample and lends itself to frequent monitoring of graft function. In this study, we characterized early graft function by calculating weekly BETA-2 score in recipients who achieved insulin independence after single transplant (group 1, n = 8) compared to recipients who required a second transplant before achieving insulin independence (group 2, n = 7). We also determined whether graft function 1-week post-transplant was associated with insulin independence in individuals who received initial transplant between 2000–2017 (n = 125). Our results show that graft function increased rapidly reaching a plateau 4–6 weeks post-transplant. The BETA-2 score was higher in group 1 compared to group 2 as early as 1-week post-transplant (15 + 3 vs. 9 + 2, p = 0.001). In an unselected cohort, BETA-2 at 1-week post-transplant was associated with graft survival as defined by insulin independence during median follow up of 12 months (range 2–119 months) with greater survival among those with BETA-2 score >10 (p < 0.001, log-rank test). These findings suggest that primary graft function is established within 4–6 weeks post-transplant and graft function at 1-week post-transplant predicts long-term transplant outcomes.

Introduction User designed Automated Insulin Delivery systems (AID), termed Do-It-Yourself (DIY) AID include; AndroidAPS, OpenAPS and Loop. These unregulated systems provide challenges for healthcare providers worldwide, with potential legal and ethical barriers to supporting their use. We performed a scoping review of the currently available literature surrounding DIY AID systems, specifically to highlight the evidence available to facilitate healthcare providers to support persons with diabetes who may benefit from DIY AID. Methods Studies relating to DIY AID systems were searched in Embase, Medline, Web of Science, Scopus, Proquest and Cochrane library until 31st December 2021. Publications were screened through title and abstract to identify study type and AID system type described. A thematic synthesis methodology was used for analysis of studies of DIY AID use due to the heterogeneity in study designs (case reports, qualitative, cross-sectional and cohort studies), with similarity in outcome themes. Results Following implementation of the search strategy, 38 relevant full texts were identified; comprising 12 case reports, 9 qualitative studies and 17 cohort studies, and data was also available from 24 relevant conference abstracts. No randomized studies were identified. Common themes were identified in the outcomes across the studies; glycemic variability, safety, quality of life, healthcare provider attitudes and social media. Conclusion There is extensive real-world data, but a lack of randomized control trial evidence supporting DIY AID system use, due to the user-driven, unregulated nature of these systems. Healthcare providers report a lack of understanding surrounding, and confidence in supporting, DIY AID despite impressive observational and user self-reported improvements in glycemic variability, without any reported safety compromises.

Islet transplantation offers an effective treatment for selected people with type 1 diabetes and intractable hypoglycaemia. Long-term experience, however, remains limited. We report outcomes from a single-centre cohort up to 20 years after islet transplantation.This cohort study included patients older than 18 years with type 1 diabetes undergoing allogeneic islet transplantation between March 11, 1999, and Oct 1, 2019, at the University of Alberta Hospital (Edmonton, AB, Canada). Patients who underwent islet-after-kidney transplantation and islet transplantation alone or islet transplantation before whole-pancreas transplantation (follow-up was censored at the time of whole-pancreas transplantation) were included. Patient survival, graft survival (fasting plasma C-peptide0·1 nmol/L), insulin independence, glycaemic control, and adverse events are reported. To identify factors associated with prolonged graft survival, recipients with sustained graft survival (≥90% of patient follow-up duration) were compared with those who had non-sustained graft survival (90% of follow-up duration). Multivariate binary logistic regression analyses were done to determine predictors of sustained graft survival.Between March 11, 1999, and Oct 1, 2019, 255 patients underwent islet transplantation and were included in the analyses (149 [58%] were female and 218 [85%] were White). Over a median follow-up of 7·4 years (IQR 4·4-12·2), 230 (90%) patients survived. Median graft survival was 5·9 years (IQR 3·0-9·5), and graft failure occurred in 91 (36%) patients. 178 (70%) recipients had sustained graft survival, and 77 (30%) had non-sustained graft survival. At baseline, compared with patients with non-sustained graft survival, those with sustained graft survival had longer median type 1 diabetes duration (33·5 years [IQR 24·3-41·7] vs 26·2 years [17·0-35·5]; p=0·0003), median older age (49·4 years [43·5-56·1] vs 44·2 years [35·4-54·2]; p=0·0011), and lower median insulin requirements (0·53 units/kg per day [0·45-0·67] vs 0·59 units/kg per day [0·48-0·70]; p=0·032), but median HbAWe present the largest single-centre cohort study of long-term outcomes following islet transplantation. Although some limitations with our study remain, such as the retrospective component, a relatively small sample size, and the absence of non-transplant controls, we found that the combined use of anakinra plus etanercept and the BETA-2 score were associated with improved outcomes, and therefore these factors could inform clinical practice.None.

BACKGROUND Direct-acting oral anticoagulant use for stroke prevention in atrial fibrillation is limited by bleeding concerns. Asundexian, a novel, oral small molecule activated coagulation factor XIa (FXIa) inhibitor, might reduce thrombosis with minimal effect on haemostasis. We aimed to determine the optimal dose of asundexian and to compare the incidence of bleeding with that of apixaban in patients with atrial fibrillation. METHODS In this randomised, double-blind, phase 2 dose-finding study, we compared asundexian 20 mg or 50 mg once daily with apixaban 5 mg twice daily in patients aged 45 years or older with atrial fibrillation, a CHA2DS2-VASc score of at least 2 if male or at least 3 if female, and increased bleeding risk. The study was conducted at 93 sites in 14 countries, including 12 European countries, Canada, and Japan. Participants were randomly assigned (1:1:1) to a treatment group using an interactive web response system, with randomisation stratified by whether patients were receiving a direct-acting oral anticoagulant before the study start. Masking was achieved using a double-dummy design, with participants receiving both the assigned treatment and a placebo that resembled the non-assigned treatment. The primary endpoint was the composite of major or clinically relevant non-major bleeding according to International Society on Thrombosis and Haemostasis criteria, assessed in all patients who took at least one dose of study medication. This trial is registered with ClinicalTrials.gov, NCT04218266, and EudraCT, 2019-002365-35. FINDINGS Between Jan 30, 2020, and June 21, 2021, 862 patients were enrolled. 755 patients were randomly assigned to treatment. Two patients (assigned to asundexian 20 mg) never took any study medication, resulting in 753 patients being included in the analysis (249 received asundexian 20 mg, 254 received asundexian 50 g, and 250 received apixaban). The mean age of participants was 73·7 years (SD 8·3), 309 (41%) were women, 216 (29%) had chronic kidney disease, and mean CHA2DS2-VASc score was 3·9 (1·3). Asundexian 20 mg resulted in 81% inhibition of FXIa activity at trough concentrations and 90% inhibition at peak concentrations; asundexian 50 mg resulted in 92% inhibition at trough concentrations and 94% inhibition at peak concentrations. Ratios of incidence proportions for the primary endpoint were 0·50 (90% CI 0·14-1·68) for asundexian 20 mg (three events), 0·16 (0·01-0·99) for asundexian 50 mg (one event), and 0·33 (0·09-0·97) for pooled asundexian (four events) versus apixaban (six events). The rate of any adverse event occurring was similar in the three treatment groups: 118 (47%) with asundexian 20 mg, 120 (47%) with asundexian 50 mg, and 122 (49%) with apixaban. INTERPRETATION The FXIa inhibitor asundexian at doses of 20 mg and 50 mg once daily resulted in lower rates of bleeding compared with standard dosing of apixaban, with near-complete in-vivo FXIa inhibition, in patients with atrial fibrillation. FUNDING Bayer.

Aims We hypothesized that an epicardial approach using ethanol infusion in the vein of Marshall (EIVOM) may improve the result of ablation for perimitral flutter (PMF). Methods and results We studied 103 consecutive patients with PMF undergoing high-resolution mapping. The first 71 were treated with radiofrequency (RF) ablation alone (RF-group), and the next 32 underwent EIVOM followed by RF on the endocardial and epicardial mitral isthmus (EIVOM/RF-group). Contact force was not measured during ablation. Acute and 1-year outcomes were compared. Flutter termination rates were similar between the RF-group (63/71, 88.7%) and EIVOM/RF-group (31/32, 96.8%, P = 0.27). Atrial tachycardia (AT) terminated with EIVOM alone in 22/32 (68.6%) in the EIVOM/RF-group. Bidirectional block of mitral isthmus was always achieved in the EIVOM/RF-group, but significantly less frequently achieved in the RF-group (62/71, 87.3%; P = 0.05). Median RF duration for AT termination/conversion was shorter [0 (0–6) s in the EIVOM/RF-group than 312 (55–610) s in the RF-group, P Conclusion Ethanol infusion in the vein of Marshall may reduce RF duration required for PMF termination as well as for mitral isthmus block without severe complications, and the mid-term outcome may be improved by this approach.

Background No study to date has used high-density mapping to investigate the relationship between prior radiofrequency (RF) lesions for persistent atrial fibrillation (PsAF) ablation and subsequent atrial tachycardias (ATs). Methods From 41 consecutive patients who underwent AT ablation at a second procedure using an ultrahigh-density mapping system, 22 patients (38 ATs) were included as they also had complete maps with a multipolar catheter and three-dimensional (3D) mapping system at the time of the first PsAF ablation procedure. We, therefore, compared voltage maps from the first AF ablation procedure to those from the subsequent AT ablation procedure, as well as the lesion sets used for AF ablation vs the activation patterns in AT during the second procedure. Results In the 38 ATs, 211 of 285 analyzed atrial areas displayed low voltage area (LVA) (74%). Eighteen percent (38/211) existed before the index ablation for AF while 82% (173/211) were newly identified as LVA during the second procedure. Ninety-nine percent (172/173) of the newly developed LVA colocalized with RF lesions delivered for PsAF. Of the 38 ATs, 89.5% (34/38) AT circuits were associated with newly developed LVA due to RF lesions whilst 10.5% (4/38) AT circuits were associated with pre-existing LVA observed at the index procedure. No AT circuit was completely independent from index RF lesions in this series. Conclusions Analysis of detailed 3D electroanatomical mapping demonstrates that most ATs after PsAF ablation are involving LVAs due to index RF lesions.

Aims Leadless cardiac pacemaker (PM) implantation differs from conventional PM implantation. While the procedure has been considered safe, recent real-world data raised concerns about the learning curve of new operators and their implantation quality. The goal of this study was to investigate the influence of the first operator’s experience on leadless PM implantation quality and procedural efficiency. Methods and results We performed a bicentric analysis of all Micra TPS™ implantations in two large tertiary referral hospitals. We assessed both leadless PM implantation quality based on the absence of complications (requiring intervention or prolonged hospitalization), good electrical performance (pacing threshold ≤ 1.5 V/0.24 ms, R-wave amplitude > 5 mV), and acceptable fluoroscopy duration ( Conclusion The operator’s learning curve is a critical factor for leadless PM implantation quality and procedural efficiency.

BACKGROUND Use of lesion metric indices is a proposed strategy to support pulmonary vein isolation procedures and these indices show good correlations with lesion sizes. The aim of this in silico study is to provide a detailed analysis of radiofrequency (RF) settings, including high-power short-duration (HPSD) settings, and resulting lesion metric indices. METHODS AND RESULTS A software program was designed which simulated virtual RF ablations. Lesion metric indices (Ablation index: AI, Lesion size index: LSI) were calculated based on underlying RF settings (contact force [CF], power, duration). In series of calculations, the applied settings were varied within defined ranges (CF: 1-80 g, power: 1-60 W, duration: 1-60 seconds). Overall, n = 388 000 virtual ablations were calculated. The resulting lesion metric indices were compared with each other and analyzed in relation to respective RF settings. Increasing contact force from 1 to 10 g resulted in a 4.4-fold LSI value, whilst increasing contact force from 10 to 20g resulted in a 1.5-fold value (P

INTRODUCTION Diaphragmatic myopotential oversensing (dMPO) by implantable cardioverter defibrillators (ICDs) is thought to be a rare condition that can be misdiagnosed as lead failure and lead to unnecessary lead replacement. We observed several cases of dMPO in patients with Sorin/LivaNova ICDs (MicroPort Sci.). We sought to systematically assess the incidence of dMPO in patients with Sorin/LivaNova ICDs. METHODS AND RESULTS A predefined number of 100 consecutive patients with Sorin/LivaNova ICDs were prospectively included in the device clinic of our center. Stored arrhythmia episodes were checked for spontaneous dMPO. In addition, we performed provocation maneuvers by Valsalva. At least one episode of spontaneous or provoked dMPO was seen in 12 (12%) of the 100 patients included in the study (86% males, median age: 66 years). Nine of 89 patients (10%) with true bipolar and 3 of 11 patients (27%) with integrated bipolar sensing configuration were affected. Spontaneous dMPO was observed in 7 of 58 patients (12%) with sensitivity programmed to 0.4 mV and in 2 of 42 patients (5%) with sensitivity programmed to 0.6 mV (not significant). In three patients, dMPO could be provoked with no spontaneous episodes recorded. In two nonpacemaker-dependent patients with a CRT-D, ventricular pacing was temporarily inhibited. No antitachycardia therapy was triggered by dMPO in any patient. CONCLUSIONS DMPO is frequent in patients with Sorin/LivaNova ICDs, especially with sensitivity programmed to 0.4 mV. It also frequently occurs with true bipolar sensing configuration. DMPO should not be misinterpreted as lead failure to avoid unnecessary lead replacement.

OBJECTIVES Our goal was to analyse the implantation and outcome of thoracoscopic epicardial leads after a failed endovascular approach or follow-up (FU) complications after endovascular implantation. METHODS We reviewed the records of patients with failed endovascular left ventricular (LV) lead placement or complications during FU, who were subsequently referred to cardiac surgeons for treatment with thoracoscopic LV lead implantation. We analysed the reasons for endovascular failure; the indications for the surgical procedures; and the clinical, echocardiographic and device FU results. RESULTS Between 2010 and 2013, a total of 23 patients were included. Among them, 17 of the patients had no previous cardiothoracic surgery, 13 (76%) had successful video-assisted thoracoscopy (VAT) LV lead implantation, 3 (18%) had a conversion to thoracotomy and 1 (6%) failed. Of the 6 patients with prior cardiothoracic surgery, 2 (33%) had VAT only, 3 (50%) had primary thoracotomies and 1 (17%) had a conversion. Two major complications occurred. The reasons for LV endovascular lead failure were subclavian vein occlusion (n = 2), implant failure (n = 13) and complications during the FU period (n = 8). FU information was available for 20 patients: 17 (85%) had improved symptoms. The median FU period was 33 months. A total of 78% of patients were in New York Heart Association (NYHA) functional class III–IV before the operation; 30% were in NYHA functional class III–IV at the last FU examination. The left ventricular ejection fraction increased from 25% before surgery to 31% at the last FU examination. Overall, sensing and pacing threshold values remained stable over time. In 1 patient, lead revision was necessary due to an increase in the pacing threshold. CONCLUSIONS VAT implantation of LV leads had an excellent response rate with an improvement in NYHA functional class and left ventricular ejection fraction. The lead measurements were mainly stable over time.

Objectives A new electroanatomic mapping system (Rhythmia, Boston Scientific, Marlborough, Massachusetts) using a 64-electrode mapping basket is now available; we systematically assessed its use in complex congenital heart disease (CHD). Background The incidence of atrial arrhythmias post-surgery for CHD is high. Catheter ablation has emerged as an effective treatment, but is hampered by limitations in the mapping system’s ability to accurately define the tachycardia circuit. Methods Mapping and ablation data of 61 patients with CHD (35 males, age 45 ± 14 years) from 8 tertiary centers were reviewed. Results Causes were as follows: Transposition of Great Arteries (atrial switch) (n = 7); univentricular physiology (Fontans) (n = 8); Tetralogy of Fallot (n = 10); atrial septal defect (ASD) repair (n = 15); tricuspid valve (TV) anomalies (n = 10); and other (n = 11). The total number of atrial arrhythmias was 86. Circuits were predominantly around the tricuspid valve (n = 37), atriotomy scar (n = 10), or ASD patch (n = 4). Although the majority of peri-tricuspid circuits were cavo-tricuspid-isthmus dependent (n = 30), they could follow a complex route between the annulus and septal resection, ASD patch, coronary sinus, or atriotomy. Immediate ablation success was achieved in all but 2 cases; with follow-up of 12 ± 8 months, 7 patients had recurrence. Conclusions We demonstrate the feasibility of the basket catheter for mapping complex CHD arrhythmias, including with transbaffle and transhepatic access. Although the circuits often involve predictable anatomic landmarks, the precise critical isthmus is often difficult to predict empirically. Ultra–high-density mapping enables elucidation of circuits in this complex anatomy and allows successful treatment at the isthmus with a minimal lesion set.

A novel "LUMIPOINT" software in the Rhythmia system (Boston Scientific) displays a histogram of activated area over the entire atrial tachycardia (AT) cycle length (CL) with a normalized score.The purpose of this study was to examine whether the pattern of this global activation histogram (GAH) identified reentrant vs focal AT and whether a decrease in atrial activation area, shown as valleys in the GAH, identifies isthmuses.One hundred eight activation maps of ATs (17 focal, 57 macroreentrant, 21 localized, 13 multiple loop) in 67 patients were reviewed retrospectively with the LUMIPOINT software. The ACTIVATION SEARCH feature highlighted the activated area in a given time period irrespective of the activation map. A 30-ms unit time interval was set, and the GAH patterns and electrophysiological properties of highlighted areas were examined.Focal ATs systematically displayed a plateau with GAH-Score0.1 for at least 30% of the CL. Most reentrant ATs (90/91 [98.9%]) lacked this plateau and displayed activity covering the entire CL, with 2 [1-2] GAH-Valleys per tachycardia. Each GAH-Valley highlighted 1 [1-2] areas in the map. Among 264 highlighted areas, 198 (75.0%) represented slow conduction, 19 (7.2%) lines of block, 27 (10.2%) wavefront collision, 3 (1.1%) unknown, and 17 (6.4%) absence of activation in focal ATs. Practical ablation sites all matched one of the highlighted areas based on GAH-Valleys, and they corresponded better with areas highlighted by GAH-Score ≤0.2 (P.0001).GAH shows focal vs reentrant mechanisms at first glance. Decrease in activated areas (displayed by GAH-Valleys) is mostly due to slow conduction and highlights areas of special interest, with 100% sensitivity for isthmus identification.

BACKGROUND Radiofrequency (RF) ablation is an established treatment for ventricular tachycardia (VT). However, the inability of current RF catheters to address deep or large substrate may explain most of the clinical failures. OBJECTIVES The aim of this study is to assess the efficacy and safety of ablation in the left ventricle (LV) in sheep using a novel 8-Fr deflectable ablation catheter (Sphere-9; Affera, Inc) with a 9-mm expandable spherical monopolar irrigated RF tip vs a standard RF irrigated catheter (Biosense Webster, Diamond Bar, CA). The impact on tissue was assessed on local bipolar electrograms (from nine uniformly distributed mini surface electrodes and an internal central reference electrode), as well as on direct lesion measurement post mortem. METHODS AND RESULTS Eleven sheep underwent LV endocardial ablation in healthy tissue using the Sphere-9 catheter (n = 6), or a conventional irrigated RF catheter (n = 5). Twenty lesions were created with the Sphere-9 (current limit: 2.7 A; temp. limit: 60°C; irrigation: 30 mL/min; and duration: 60-120 seconds). Local bipolar electrograms at the surface of the catheter disappeared during RF delivery in 17 of 20 (85%) lesions. The mean lesion volume was 1707 ± 771 mm 3 (length: 15.8 ± 3.3 mm; width: 11.6 ± 4.2 mm; and depth: 10.3 ± 2.9 mm). Twenty-five lesions were created with a standard RF irrigated catheter (power control 35 W; irrigation: 30 mL/min; duration: 60 seconds; volume 537 ± 398 mm 3 ; length: 8.2 ± 2.3 mm; width: 5.2 ± 1.8 mm; and depth: 5.5 ± 2.4 mm). The novel spherical RF catheter created significantly larger lesions ( P

Successful mapping and ablation of ventricular tachycardias remains a challenging clinical task. Whereas conventional entrainment and activation mapping was for many years the gold standard to identify reentrant circuits in ischaemic ventricular tachycardia ablation procedures, substrate mapping has become the cornerstone of ventricular tachycardia ablation. In the last decade, technology has dramatically improved. In parallel to high-density automated mapping, cardiac imaging and image integration tools are increasingly used to assess the structural ventricular tachycardia substrate. The aim of this review is to describe the technologies underlying these new mapping systems and to discuss their possible role in providing new insights into identification and visualization of reentrant tachycardia mechanisms.

INTRODUCTION Chemical ablation by retrograde infusion of ethanol into the vein of Marshall (VOM-EI) can facilitate the achievement of mitral isthmus block. This study sought to describe the efficacy and safety of this technique. METHODS AND RESULTS Twenty-two consecutive patients (14 males, median age 71 years) with attempted VOM-EI for mitral isthmus ablation were included in the study. VOM-EI was successfully performed with a median of 4���ml of 96% ethanol in 19 patients (86%) and the mitral isthmus was successfully blocked in all (100%). Touch up endocardial and/or epicardial ablation after VOM-EI was necessary for 12 patients (63%). Perimitral flutter was present in 12 patients (63%) during VOM-EI and terminated or slowed by VOM-EI in 4 and 3 patients, respectively. The low-voltage area of the mitral isthmus region increased from 3.1���cm2 (interquartile range [IQR] 0-7.9) before to 13.2���cm2 (IQR: 8.2-15.0) after VOM-EI and correlated significantly with the volume of ethanol injected (p���=���.03). Median high-sensitive cardiac troponin-T increased significantly from 330���ng/L (IQR: 221-516) the evening of the procedure to 598���ng/L (IQR: 382-769; p���=���.02) the following morning. A small pericardial effusion occurred in three patients (16%), mild pericarditis in one (5%), and uneventful VOM dissection in two (11%). After a median follow-up of 3.5 months (IQR: 3.0-11.0), 10 of 18 patients (56%) with VOM-EI and available follow-up had arrhythmia recurrence. Repeat ablation was performed in five patients (50%) and peri-mitral flutter diagnosed in three (60%). CONCLUSION VOM-EI is feasible, safe, and effective to achieve acute mitral isthmus block.

AIMS OF THE STUDY Anticoagulation of patients with screen-detected atrial fibrillation may prevent ischaemic strokes. The STAR-FIB study programme aims to determine the age- and sex-specific prevalence of silent atrial fibrillation and to develop a clinical prediction model to identify patients at risk of undiagnosed atrial fibrillation in a hospitalised patient population. METHODS The STAR-FIB study programme includes a prospective cohort study and a case-control study of hospitalised patients aged 65–84 years, evenly distributed for both age and sex. We recruited 795 patients without atrial fibrillation for the cohort study (49.2% females; median age 74.8 years). All patients had three serial 7-day Holter ECGs to screen for silent atrial fibrillation. The primary endpoint will be any episode of atrial fibrillation or atrial flutter of ≥30 seconds duration. The age- and sex-specific prevalence of newly diagnosed atrial fibrillation will be estimated. For the case-control study, 120 patients with paroxysmal atrial fibrillation were recruited as cases (41.7% females; median age 74.6 years); controls will be randomly selected from the cohort study in a 2:1 ratio. All participants in the cohort study and all cases were prospectively evaluated including clinical, laboratory, echocardiographic and electrical parameters. A clinical prediction model for undiagnosed atrial fibrillation will be derived in the case-control study and externally validated in the cohort study. CONCLUSIONS The STAR-FIB study programme will estimate the age- and sex-specific prevalence of silent atrial fibrillation in a hospitalised patient population, and develop and validate a clinical prediction model to identify patients at risk of silent atrial fibrillation.

BACKGROUND: We investigated residual β cell function in Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study participants with an average 35-year duration of type 1 diabetes mellitus (T1DM). METHODS: Serum C-peptide was measured during a 4-hour mixed-meal tolerance test. Associations with metabolic outcomes and complications were explored among nonresponders (all C-peptide values after meal 0.2), intermediate (>0.03 to ≤0.2), and low (≥ 0.003 to ≤0.03). RESULTS: Of the 944 participants, 117 (12.4%) were classified as responders. Residual C-peptide concentrations were associated with higher DCCT baseline concentrations of stimulated C-peptide (P value for trend = 0.0001). Residual C-peptide secretion was not associated with current or mean HbA1c, HLA high-risk haplotypes for T1DM, or the current presence of T1DM autoantibodies. The proportion of subjects with a history of severe hypoglycemia was lower with high (27%) and intermediate (48%) residual C-peptide concentrations than with low (74%) and no (70%) residual C-peptide concentrations (P value for trend = 0.0001). Responders and nonresponders demonstrated similar rates of advanced microvascular complications. CONCLUSION: β Cell function can persist in long-duration T1DM. With a peak C-peptide concentration of >0.03 nmol/L, we observed clinically meaningful reductions in the prevalence of severe hypoglycemia. TRIAL REGISTRATION: ClinicalTrials.gov NCT00360815 and NCT00360893. FUNDING: Division of Diabetes Endocrinology and Metabolic Diseases of the National Institute of Diabetes and Digestive and Kidney Diseases (DP3-DK104438, U01 DK094176, and U01 DK094157).

Aims Catheter ablation is an effective treatment for post-infarction ventricular tachycardia (VT). However, some patients may experience a worsened arrhythmia phenotype after ablation. We aimed to determine the prevalence and prognostic impact of arrhythmia exacerbation (AE) after post-infarction VT ablation. Methods and results A total of 1187 consecutive patients (93% men, median age 68 years, median ejection fraction 30%) who underwent post-infarction VT ablation at six centres were included. Arrhythmia exacerbation was defined as post-ablation VT storm or incessant VT in patients without prior similar events. During follow-up (median 717 days), 426 (36%) patients experienced VT recurrence. Events qualifying as AE occurred in 67 patients (6%). Median times to VT recurrence with and without AE were 238 [interquartile range (IQR) 35–640] days and 135 (IQR 22–521) days, respectively (P = 0.25). Almost half of the patients (46%) who experienced AE experienced it within 6 months of the index procedure. Patients with AE had had longer ablation times during the ablation procedures compared to the rest of the patients (median 42 vs. 34 min, P = 0.02). Among patients with VT recurrence, the risk of death or heart transplantation was significantly higher in patients with than without AE (hazard ratio 1.99, 95% CI 1.28–3.10; P = 0.002) after adjusting for age, gender, ejection fraction, cardiac resynchronization therapy, post-ablation non-inducibility, and post-ablation amiodarone use. Conclusion Arrhythmia exacerbation after ablation of infarct-related VT is infrequent but is independently associated with an adverse long-term outcome among patients who experience a VT recurrence. The mechanisms and mitigation strategies of AE after catheter ablation require further investigation.

Current approaches to insulin replacement in type 1 diabetes are unable to achieve optimal levels of glycemic control without substantial risk of hypoglycemia and substantial burden of self-management. Advances in biology and technology present beta cell replacement and automated insulin delivery as two alternative approaches. Here we discuss current and future prospects for the relative risks and benefits for biological and psychosocial outcomes from the perspective of researchers, clinicians, and persons living with diabetes. Beta cell replacement using pancreas or islet transplant can achieve insulin independence but requires immunosuppression. Although insulin independence may not be sustained, time in range of 80–90%, minimal glycemic variability and abolition of hypoglycemia is routine after islet transplantation. Clinical trials of potentially unlimited supply of stem cell-derived beta cells are showing promise. Automated insulin delivery (AID) systems can achieve 70–75% time in range, with reduced glycemic variability. Impatient with the pace of commercially available AID, users have developed their own algorithms which appear to be at least equivalent to systems developed within conventional regulatory frameworks. The importance of psychosocial factors and the preferences and values of persons living with diabetes are emerging as key elements on which therapies should be evaluated beyond their impact of biological outcomes. Biology or technology to deliver glucose dependent insulin secretion is associated with substantial improvements in glycemia and prevention of hypoglycemia while relieving much of the substantial burden of diabetes. Automated insulin delivery, currently, represents a more accessible bridge to a biologic cure that we expect future cellular therapies to deliver.

BACKGROUND Radiofrequency (RF) power is routinely considered during RF application. In contrast, impedance has been relatively poorly studied, despite also influencing RF lesion creation. The aim of this study was to examine the influence of electric impedance on RF lesion characteristics and on clinical RF ablation parameters. METHODS AND RESULTS In the first part of the study, power and impedance were systematically varied and the resulting current was calculated using custom-made software. In the second part of the study, ablation lesions (n = 40) were analyzed in a porcine ex vivo model. RF applications were delivered in cardiac muscle preparations with systematically varied values of electric impedance using a contact force ablation catheter. In the third part of the study, n = 3378 clinical RF applications were analyzed, power, impedance, and current data were exported and correlated with clinical patient data. 20 ± 3 W/80 Ω, 30 ± 3 W/120 Ω, 40 ± 3 W/160 Ω, and 50 ± 3 W/200 Ω RF applications resulted in 498 ± 40, 499 ± 26, 500 ± 20, and 500 ± 16 mA RF current, which were not significantly different (p = .32). Ablation lesions were significantly different in depth and diameter when applied with the same power but different impedances (p

Background: Atrial fibrillation ablation–related atrial tachycardia (AT) is complex and may demonstrate several forms: anatomic macroreentrant AT (AMAT), non-AMAT, and focal AT. We aimed to elucidate the recurrence rate and mechanisms of atrial fibrillation ablation–related AT recurrence. Methods: Among 147 patients with ATs treated with the Rhythmia system, 68 (46.3%) had recurrence at mean 4.2 (2.9–11.6) months, and 44 patients received a redo procedure. AT circuits in the first procedure were compared with those in the redo procedure. Results: Although mappable ATs were not observed in 7 patients, 68 ATs were observed in 37 patients during the first procedure: perimitral flutter (PMF) in 26 patients, roof-dependent macroreentrant AT (RMAT) in 18, peritricuspid flutter in 10, non-AMAT in 14, and focal AT in 3. During the redo AT ablation procedure, 54 ATs were observed in 41/44 patients: PMF in 24, RMAT in 14, peritricuspid flutter in 1, non-AMAT in 14, and focal AT in 1. Recurrence of PMF and RMAT was observed in 15 of 26 (57.7%) and 8 of 18 (44.4%) patients, respectively, while peritricuspid flutter did not recur. Neither the same focal AT nor the same non-AMAT were observed except in 1 case with septal scar–related biatrial AT. Epicardial structure–related ATs were involved in 18 of 24 (75.0%) patients in PMF, 4 of 14 (28.6%) in RMAT, and 4 of 14 (28.6%) in non-AMAT. Of 21 patients with a circuit including epicardial structures, 6 patients treated with ethanol infusion in the vein of Marshall did not show any AT recurrence, although 8 of 15 (53.3%) treated with radiofrequency showed AT recurrence ( P =0.04). Conclusions: Although high-resolution mapping may lead to correct diagnosis and appropriate ablation in the first procedure, the recurrence rate is still high. The main mechanism of atrial fibrillation ablation–related AT is the recurrence of PMF and RMAT or non-AMAT different from the first procedure. Epicardial structures (eg, coronary sinus/vein of Marshall system) are often involved, and ethanol infusion in the vein of Marshall may be an additional treatment.

Background: Various strategies for ablation of ventricular tachycardia (VT) have been described, but their impact on ventricular fibrillation (VF) is largely unknown. The aim of our study was to assess the effect of substrate-based VT ablation targeting local abnormal ventricular activity (LAVA) on recurrent VF events in patients with structural heart disease. Methods: A retrospective 2-center study was performed on patients with structural heart disease and both VT and VF, with incident VT ablation procedures targeting LAVAs. Generalized estimating equations with a Poisson loglinear model were used to assess the impact of catheter ablation on VF episodes. The change in VF events before and after catheter ablation was compared with matched controls without ablation. Results: From a total of 686 patients with an incident VT ablation procedure targeting LAVAs, 21 patients (age, 57±14 years; left ventricular ejection fraction, 30±10%) had both VT and VF and met inclusion criteria. A total of 80 VF events were recorded in the implantable cardioverter-defibrillator logs the 6 months preceding ablation. Complete and partial LAVA elimination was achieved in 11 (52%) and 10 (48%) patients, respectively. Catheter ablation was associated with a highly significant reduction in VF recurrences ( P P =0.0003). Conclusions: Substrate-guided VT ablation targeting LAVAs may be associated with a significant reduction in recurrent VF, suggesting that VT and VF share overlapping arrhythmogenic substrates in patients with structural heart disease.

OBJECTIVE Unexplained cardiac arrest (UCA) is often the first manifestation of an inherited arrhythmogenic disease. Genetic testing in UCA is challenging due to the complexities of variant interpretation in the absence of supporting cardiac phenotype. We aimed to investigate if a KCNQ1 variant [p.(Pro64_Pro70del)], previously reported as pathogenic, contributes to the long-QT syndrome phenotype, co-segregates with disease or affects KCNQ1 function in vitro. METHODS DNA was extracted from peripheral blood of a 22-year-old male after resuscitation from UCA. Targeted exome sequencing was performed using the TruSight-One Sequencing Panel (Illumina). Variants in 190 clinically relevant cardiac genes with minor allele frequency A in PKP2 (p.Arg811Ser), classified as likely benign. Two asymptomatic family members with no evident phenotype hosted the KCNQ1 variant. Functional studies showed that the wild-type and mutant channels have no significant differences in current levels, conductance-voltage relationships, as well as activation and deactivation kinetics, in the absence and presence of the auxiliary subunit KCNE1. CONCLUSIONS Based on our data and previous reports, available evidence is insufficient to consider the variant KCNQ1:c.190_210del as pathogenic. Our findings call for cautious interpretation of genetic tests in UCA in the absence of a clinical phenotype.

Background: Catheter ablation of ventricular tachycardia (VT) in structural heart disease is challenging because of noninducibility or hemodynamic compromise. Ablation often depends on elimination of local abnormal ventricular activities (LAVAs) but which may be hidden in far-field signal. We investigated whether altering activation wavefront affects activation timing and LAVA characterization and allows a better understanding of isthmus anatomy. Methods: Patients with ischemic cardiomyopathy underwent mapping using the ultra-high density Rhythmia system (Boston Scientific). Maps were generated for all stable VTs and with pacing from the atrium, right ventricular apex, and an left ventricular branch of the coronary sinus. Results: Fifty-six paced maps and 23 VT circuits were mapped in 22 patients. In 79% of activation maps, there was ≥1 line of block in the paced conduction wavefront, with 93% having fixed block and 32% showing functional partial block. Bipolar scar was larger with atrial than right ventricular (31.7±18.5 versus 27.6±16.3 cm 2 , P =0.003) or left ventricular pacing (31.7±18.5 versus 27.0±19.2 cm 2 , P =0.009); LAVA areas were smaller with atrial than right ventricular (12.3±10.5 versus 18.4±11.0 cm 2 , P 2 , P 2 , P =0.01). All patients had successful VT isthmus ablation. In 11±8 months follow-up, 2 patients had a recurrence. Conclusions: Wavefronts of conduction slowing/block may aid identification of critical isthmuses in unmappable VTs. Altering the activation wavefront leads to significant differences in conduction properties of myocardial tissue, along with scar and LAVA characterization. In patients where few LAVAs are identified during substrate mapping, using an alternate activation wavefront running perpendicular to the VT isthmus may increase sensitivity to detect arrhythmogenic substrate and critical sites for reentry.

Objectives This study reports the use of a novel “Lumipoint” algorithm in ventricular tachycardia (VT) ablation. Background Automatic mapping systems aid rapid acquisition of activation maps. However, they may annotate farfield rather than nearfield signal in low voltage areas, making maps difficult to interpret. The Lumipoint algorithm analyzes the complete electrogram tracing and therefore includes nearfield signals in its analysis. Methods Twenty-two patients with ischemic cardiomyopathy and 5 with dilated cardiomyopathy underwent mapping using the ultra-high density Rhythmia system. Lumipoint algorithms were applied retrospectively. Results In all left ventricular substrate maps, changing the window of interest to the post-QRS phase automatically identified late potentials. In 25 of 27 left ventricular VT activation maps, a minimum spatial window of interest correctly identified the VT isthmus as seen by the manually annotated map, entrainment, and response to ablation. In 6 maps, the algorithm identified the isthmus where the standard automatically annotated map did not. Conclusions The Lumipoint algorithm automatically highlights areas with electrograms having specific characteristics or timings. This can identify late and fractionated potentials and regions that exhibit discontinuous activation, as well as the isthmus of a VT circuit. These features may enhance human interpretation of the electrogram signals during a case, particularly where the circuit lies in partial scar with low amplitude nearfield signals and potentially allow a more targeted ablation strategy.

Background Ethanol infusion of the vein of Marshall (VOM) may be effective to treat Marshall bundle-related atrial tachycardia (MB-AT). However, methods and clinical results of ethanol infusion for MB-AT have been not established. Objective To assess the accessibility of the VOM and the success rate of ethanol infusion using a femoral approach for MB-AT. Methods A single-center observational study included consecutive patients who had MB-AT and in whom we attempted to treat MB-AT during AT by ethanol infusion. When the VOM was able to be cannulated following VOM venogram using a femoral approach, we systematically performed ethanol infusion with selective balloon occlusion of the VOM. We analyzed in detail the efficacy of ethanol infusion of VOM in patients who were in MB-AT during ethanol infusion. Results We enrolled 54 consecutive patients in whom we attempted to treat MB-AT by ethanol infusion. Of those, the VOM was accessible in 92.5% of patients (50 of 54). Of the 50 patients treated by ethanol infusion during MB-AT, AT was successfully terminated in 56% percent of the patients (28 of 50) by solo treatment of ethanol infusion without RF ablation. The remainder required additional RF application to terminate the MB-AT. A mean of 6.2 ± 2.8 mL of ethanol was infused resulting in the low-voltage area significantly larger than that before ethanol infusion (12.7 ± 8.3 vs 6.6 ± 5.3 cm2 , P Conclusion The present study demonstrated that the VOM was highly accessible and MB-AT was amenable to treatment by ethanol infusion by using a femoral approach.

International audience; ObjectiveThis study sought to determine whether 3-dimensionally-reconstructed computed tomography (CT) channels correlate with electrophysiological isthmuses during ventricular tachycardia (VT).MethodsWe retrospectively studied 9 postinfarction patients (aged 57 ± 15 years, 1 female) with 10 complete VT activation maps (cycle length 429 ± 77ms) created using high-resolution mapping. Three-dimensionally-reconstructed WT maps from CT were merged with the activation map during sinus rhythm (SR) and VT. The relationship between WT and electrophysiological characteristics was analyzed.ResultsA total of 41 CT channels were identified (median 4 per patient), of median (range) length 21.2 mm (17.3–36.8 mm), width 9.0 mm (6.7–16.5 mm), and area 1.49 cm2(1.00–1.75 cm2). WT in the channel was significantly thicker in the center than in the edge (median 2.4 mm vs 1.5 mm, P < .0001). Of 3163 (2493–5960) mapping points in SR, 382 (191–1115) local abnormal ventricular activities (LAVAs) were identified. One patient had a maximal proportion of LAVAs in 3–4 mm, 3 patients in 2–3 mm, 2 in 1–2 mm, and 2 in 0–1 mm. The VT isthmuses of all 10 VTs corresponded with 1–4 CT channels. Twenty-one of the 41 CT channels (51.2%) corresponded to a VT isthmus (entrance, mid, or exit). Electrophysiological VT isthmuses were more likely to be associated with CT channels that were longer (P = .04, odds ratio [OR] 1.05/mm), thinner (but not less than 1 mm) (P = .03, OR 0.36/mm), or parallel to the mitral annulus (P = .07, OR 3.93).ConclusionVT isthmuses were always found in CT channels (100% sensitivity), and half of CT channels hosted VT isthmuses (PPV 51%). Longer and thinner (but >1 mm) CT channels were significantly associated with VT isthmuses.

PURPOSE To compare lead failure manifestation and lead performance of the Biotronik Linox/Sorin Vigila defibrillator lead (Linox group) with the St. Jude Medical Riata/Riata ST (Riata group) and Medtronic Sprint Fidelis defibrillator leads (Fidelis group). METHODS We assessed the performance of all aforementioned leads implanted at our center and investigated the manifestation of lead failures. RESULTS Of 93 Linox, 86 Riata, and 81 Fidelis leads implanted at our center, 11 (12%), 22 (26%), and 25 (31%) leads failed during a median follow-up of 46, 61, and 84 months, respectively. Inappropriate shocks were delivered in 64% (Linox), 5% (Riata), and 32% (Fidelis) of lead failures; a device alert was noted in none (Linox), 5% (Riata), and 52% (Fidelis); and lead failure was a coincidental finding in 36% (Linox), 91% (Riata), and 16% (Fidelis) of cases (p

Genetic testing in survivors of sudden cardiac arrest (SCA) with a suspicious cardiac phenotype is considered clinically useful, whereas its value in the absence of phenotype is disputed. We aimed to evaluate the clinical utility of genetic testing in survivors of SCA with or without cardiac phenotype. Sixty unrelated SCA survivors (median age: 34 [interquartile range 20 to 43] years, 82% male) without coronary artery disease were included: 24 (40%) with detectable cardiac phenotype (Ph(+)SCA) after the SCA event and 36 (60%) with no clear cardiac phenotype (Ph(-)SCA). The targeted exome sequencing was performed using the TruSight-One Sequencing Panel (Illumina). Variants in 185 clinically relevant cardiac genes with minor allele frequency

Reentrant circuits are considered to be critically dependent on a single protected slow conducting isthmus.The purpose of this study was to investigate conduction properties and electrogram (EGM) characteristics of the entire circuit in localized atrial reentrant circuits using high-resolution mapping.Fifteen localized reentrant atrial tachycardias were studied with high-resolution mapping (Rhythmia). EGMs along the entire circuit were analyzed offline for fractionation, duration, and amplitude. Maps were exported to MATLAB (MathWorks) to measure bipolar voltage and conduction velocities (CVs) within the circuit. Slow conduction was defined as30 cm/s.Fifteen localized re-entrant circuits (12 left atrial, 3 right atrial) with mean cycle length 273 ± 40 ms were analyzed using high-resolution maps (22,389 ± 13,375 EGMs). A mean of 4.5 ± 1.6 slow conduction corridors were identified per circuit. Although the entire circuit was of low voltage, the bipolar voltage in slow conducting corridors was significantly lower than the rest of the circuit (0.22 ± 0.20 mV vs 0.50 ± 0.48 mV; P.001). The mean conduction velocity of the circuit, excluding slow conduction areas, was 90.3 ± 34.3 cm/s vs 13.9 ± 3.5 cm/s (P.001) in the slow conduction corridors. EGM analysis at the slowest conduction corridors demonstrated fractionation (100%) with longer EGM duration compared to the other slow conduction corridors along the circuit (99 ± 9 ms vs 74 ± 11 ms; P = .003).In contrast to current understanding, localized atrial reentrant circuits have multiple sequential "corridors" of very slow conduction (2-7) that contribute to maintenance of arrhythmia. The localized reentry occurs in low-voltage areas, with voltage further reduced in these multiple slow conducting corridors.

BACKGROUND We present a new, easily applicable approach for the guidance of cryoballoon (CB) pulmonary vein isolation (PVI) procedures that use the combination of a 3D-mapping system image integration module and computed tomographic (CT)-derived anatomy. The aim of this retrospective, nonrandomized study was to investigate: (a) an alternative use for an established radiofrequency image integration module for cryo procedures; (b) a guidance technology for cryo PVI based on integrated CT anatomy; and (c) its clinical impact. METHODS AND RESULTS CT left atrium-angiography was performed in 50 consecutive patients before a CB PVI procedure, and a 3D reconstruction of the cardiac anatomy was segmented. A total of 25 patients were treated using conventional fluoroscopy; 25 patients were treated using the 3D image integration technique. In the image integration group, the CARTO3 UNIVU (Biosense Webster) module was used for image integration of 3D anatomy and fluoroscopic imaging. Transseptal puncture and cryo PVI were guided by 3D-overlay imaging. Procedures were feasible without complications in all patients and cryo PVI procedures were successfully guided using the image integration technique. The intraprocedural time needed to perform image integration was 37 ± 10 seconds. Fluoroscopy time was 31.7 ± 11.7 minutes in the conventional group and 20.1 ± 7.9 minutes in the image integration group (P

ContextClinical islet transplantation (CIT) is an innovative strategy to treat highly selected individuals with type 1 diabetes mellitus (T1DM). Lymphodepletion with alemtuzumab or thymoglobulin is often used for induction therapy in CIT. Alemtuzumab was recently licensed as a treatment of relapsing remitting multiple sclerosis (RRMS). In RRMS, autoimmune thyroid disease (AITD) has developed in up to 40% of individuals treated with alemtuzumab. The appearance of AITD after CIT is not well described. We herein explore factors associated with AITD developing after CIT and any relationship with exposure to lymphodepleting antibodies (alemtuzumab or thymoglobulin).Case DescriptionFive cases of AITD developing after CIT for T1DM are described. All were female. Four cases had received alemtuzumab (20 to 40 mg) prior to at least one islet infusion, and one received thymoglobulin induction. The presentation with AITD was 18 to 135 months after first transplant and 11 to 18 months after withdrawal of all maintenance immunosuppression (IS). Four cases presented with clinical and biochemical evidence of hyperthyroidism from Graves disease. One case presented with biochemical evidence of hypothyroidism and positive TSH receptor antibodies. All were treated with conventional therapies for AITD.ConclusionsDespite routine use of alemtuzumab, clinical presentations of AITD seem to be uncommon in patients with CIT receiving IS. However, AITD can develop after withdrawal of IS, highlighting the need for careful thyroid surveillance in this population.

BACKGROUND The relationship between the local electrograms (EGMs) and wall thickness (WT) heterogeneity within infarct scars has not been thoroughly described. The relationship between WT and voltages and substrates for ventricular tachycardia (VT) was examined. METHODS In 12 consecutive patients with myocardial infarction and VT, WT, defined by a multidetector computed tomography, and voltage were compared. In multicomponent EGMs, amplitudes of both far- and near-field components were manually measured, and the performance of the three-dimensional-mapping system automatic voltage measurement was assessed. RESULTS Of 15 748 points acquired, 2677 points within 5 mm of the endocardial surface were analyzed. In total, 909 (34.0%) multicomponent EGMs were identified; 785 (86.4%) and 883 (97.1%) were distributed in the WT less than 4 and 5 mm, respectively. Far-field EGM voltages increased linearly from 0.14 mV (0.08-0.28 mV) in the WT: 0 to 1 mm to 0.70 mV (0.43-2.62 mV) in the WT: 4 to 5 mm (ρ = 0.430; P

Following islet transplantation, mixed meal tolerance tests (MMTs) are routinely utilized to assess graft function, but how the 90-minute MMTT glucose value relates to a 120-minute glucose concentration of ≥11.1 mmol/L used to diagnose diabetes following a standardized 75 g-OGTT, is not known. We examined this relationship further. Thirteen subjects with Type 1 diabetes and stable transplant grafts, not on exogenous insulin with HbA1c .05. A 90-minute MMTT glucose concentration ≥8.0 mmol/L demonstrated a sensitivity and specificity of ≥80% for the diagnosis of OGTT120 ≥11.1 mmol/L; area under ROC curve (mean ± SEM) 73 ± 13%. A 90-minute MMTT glucose ≥8.0 mmol/L, identifies islet transplant recipients who may require closer monitoring for graft dysfunction.

An 18-year-old woman with a history of anorexia nervosa and multiple episodes of dizziness and syncope of unknown cause was transferred to the emergency department by ambulance 1 hour after starting to feel palpitations, dizziness, tightness in the chest, and presyncope at school. At the time of presentation, she was hemodynamically stable, but the symptoms persisted. The ECG recorded at admission is shown in Figure 1A. A supraventricular tachycardia with aberrancy was suspected. Conversion attempts first with vagal maneuvers (carotid sinus massage and Valsalva maneuver) followed by adenosine (6 mg IV) were unsuccessful, but the ventricular rate and the QRS duration normalized gradually within 12 hours. The full cardiovascular and laboratory workup showed unremarkable findings, and the patient was discharged with prescription of metoprolol 25 mg/d. Figure 1. ECG obtained at the time of initial admission and readmission to the emergency department. A , The ECG recorded at initial admission shows regular wide-QRS complex tachycardia with right bundle-branch block morphology and a ventricular rate of 120 bpm, no identifiable P waves, and no atrioventricular dissociation. B , The ECG recorded at readmission shows agonal heart rhythm with …

Introduction Successful catheter ablation is limited by both poor spatial resolution of abnormal local signals and inability to deliver an effective lesion due to poor tissue contact. We report first worldwide use of the Intellanav MiFi OI catheter (Boston Scientific), providing ultra-high density mapping and incorporating a "DirectSense" algorithm to measure local tissue impedance (LI). Methods and results 31 patients (65±6 years, 20 male) underwent ablation. LI from the catheter, generator impedance (GI) and maximum electrogram amplitude were recorded in the blood pool, and in regions from healthy to dense scar before, during and after ablation. The catheter demonstrated clear nearfield signal where standard bipolar recordings included farfield signal. LI was lower in dense scar than either healthy tissue or blood pool, and demonstrated an exponential relationship with maximum electrogram amplitude. Maximum LI drop on ablation linearly correlated with initial LI. The median LI drop for successful lesions, resulting in lack of local tissue capture, was 16.0Ω (12.1-19.8 Ω) for LV and 14.6 Ω (10.0-18.3 Ω) for LA, which was larger than for unsuccessful lesions (LV: 9.4 Ω [5.4-15.6 Ω] P = 0.001; LA: 6.8 Ω [4.7-13.0 Ω], P = 0.049). LI percentage drop was also significantly larger for successful than unsuccessful lesions (LV: 17.1 Ω [14.0-19.6 Ω] vs. 10.6 Ω (7.1-16.5 Ω) P = 0.002; LA: 14.2 Ω [10.8-19.5 Ω] vs. 7.5Ω [5.1-11.0 Ω], P = 0.005). Conclusion This novel catheter gives reproducible recordings of local impedance, which are dependent on scar level. Absolute LI drop, and also percentage drop, on ablation may give an indication of tissue contact and subsequent effective lesion formation.

Background: Long-term results of substrate modification for ablation of ventricular tachycardia (VT) have not been reported. We report long-term outcomes of substrate elimination targeting local abnormal ventricular activities (LAVA) for post–myocardial infarction VT. Methods and Results: One hundred fifty-nine consecutive patients undergoing first ablation were included (65±11 years, 92% implantable cardioverter defibrillators, 54% storms, and 73% appropriate shocks). LAVA were identified in 92% and VT was inducible in 73%. Complete LAVA elimination and noninducibility after ablation were achieved in 64% and 85%. During a median follow-up of 47 months (interquartile range, 34–82), single-procedure ventricular arrhythmia (VA)–free survival was 55% (10% storms and 19% shocks). The VA-free survival was 73%, 68%, 61%, 55%, and 49% after 1, 2, 3, 4, and 5 years, respectively. Complete LAVA elimination was associated with improved outcomes: VA-free survival of 82% at 1 year and 61% at 5 years. In the subgroup treated with multielectrode mapping and real-time image integration, VA-free survival was 86% and 65% at 1 year and 4 years, respectively. Including repeat procedures in 18% of pts (1.3±0.6 ablations/pt) outcomes improved to 69% VA-free survival (2% storms and 9% shocks) during median 46-month follow-up. Overall survival was 91% at 1 year and 77% at 5 years of follow-up. Conclusions: In this monocentric study, substrate modification targeting LAVA for post–myocardial infarction VT resulted in a substantial reduction of VT storm and implantable cardioverter defibrillator shocks and up to 49% of patients free from arrhythmia at 5 years after a single procedure. Complete LAVA elimination, multielectrode mapping, and real-time integration were associated with improved VA-free survival.

Acute abdominal pain accounts for 5-10% of all emergency department visits. Rapid and accurate diagnosis is critical to ensure optimal outcomes. In the last decade, increased use of CT scans and the introduction of surgical short stay units has changed the way this group of patients is managed. The aim of this study was to evaluate the effects of these changes on patient management.A retrospective clinical study was undertaken including all patients admitted with abdominal pain under general surgery in the years 2004, 2009 and 2014. Two hundred from each of the three years were randomly selected and their care was reviewed.During the study period, more patients were admitted under general surgery, from 1,462 in 2004 to 2,737 in 2014 (P=0.001). There was an increase in the proportion of patients admitted with non-surgical abdominal pain (25% in 2004 vs 34% in 2014, P=0.035). More computed tomography (CT) scans were performed (26.0% in 2004 vs 45.0% in 2014, P=0.001).More patients were admitted under general surgery with abdominal pain and a greater proportion of these patients were admitted with non-surgical problems. Use of CT scans increased during the study period.

Atrial fibrillation may be clearly symptomatic and is easily amenable to state-of-the-art treatment, most importantly oral anticoagulation therapy for the prevention of thromboembolism. However, atrial fibrillation may also go unnoticed for long periods in many patients. This silent or subclinical atrial fibrillation is nevertheless associated with thromboembolic risk just like clinically evident atrial fibrillation. Early detection of atrial fibrillation in patients at increased thromboembolic risk and consequent oral anticoagulation therapy may have a significant impact on public health. This review focuses on screening recommendations for atrial fibrillation and on the impact of silent atrial fibrillation in various clinical scenarios.

Angina pectoris can result in an imbalance between oxygen supply and demand of the heart muscle, resulting in a compromised energy supply to the heart muscle. Currently, the primary approach to treating angina is aimed either at decreasing muscle oxygen demand, or increasing oxygen supply to the muscle. An alternative approach is to increase cardiac efficiency by increasing the amount of cardiac work at a given level of oxygen consumed. This can be achieved by inhibiting myocardial fatty acid oxidation, which leads to an increase in glucose oxidation. Consequently, lactate and proton production decrease, and as a result cardiac efficiency is improved. The approach of partial fatty acid oxidation (pFOX) inhibition is beneficial in the treatment of angina pectoris, both as a monotherapy and when used in combination with conventional therapy. pFOX inhibitors not only lessen the severity and symptoms of an angina attack, they also decrease the incidence of angina attacks in patients with coronary artery disease. The approach of optimizing energy substrate preference in the heart is a new and effective approach to treating angina pectoris.

Tumor immune microenvironment has been gradually recognized as a key contributor to tumor development, progression, and control. Immune cell infiltrates in brain tumors have been increasingly studied, but few have published on immune cell infiltrates in pituitary adenomas. We quantitatively assessed the infiltration of macrophages and lymphocytes in 35 pituitary adenomas, including 9 densely granulated growth hormone (DG-GH), 9 sparsely granulated growth hormone (SG-GH), 9 null cell (NC), and 8 adrenocorticotropic hormone (ACTH) adenomas. All the adenomas showed varying degrees of CD68+ macrophage infiltration. While SG-GH adenomas were significantly larger in size than DG-GH and ACTH adenomas, the infiltration of CD68+ macrophages was significantly greater in SG-GH than in DG-GH and ACTH adenomas. Similarly, NC adenomas that were significantly larger than DG-GH and ACTH adenomas had significantly greater infiltration of CD68+ macrophages than DG-GH and ACTH adenomas. The numbers of CD68+ macrophages were positively correlated with the tumor sizes and Knosp classification grades for tumor invasiveness. The infiltration of CD4+ and CD8+ T cells was relatively scant in these adenomas, but GH adenomas exhibited significantly more CD4+ and CD8+ T cells than non-GH adenomas. Both DG-GH and SG-GH adenomas had significantly more CD4+ cells than ACTH adenomas and significantly more CD8+ cells than NC adenomas. These results suggest an association of CD68+ macrophage infiltration with an increase in the pituitary adenoma size and invasiveness. Our observation contributes to understanding the growth environment of pituitary adenomas, for which adjuvant immunotherapy may help to constrain the tumor enlargement and invasiveness.

BACKGROUND AND AIMS Changes in clinical practice based on research findings are dependent on the dissemination of information, which is a goal at national meetings. Given that evidence for many interventions in nephrology is lacking, it is important to determine predictors of publication of randomized controlled trials (RCTs) presented as abstracts at national conferences. MATERIALS AND METHODS All abstracts submitted to the American Society of Nephrology (ASN) meeting 2005 were reviewed to identify completed RCTs. Univariate logistic regression was used to compare characteristics between published RCTs until June 2010 and those not published. Time to publication was calculated. RESULTS 73 completed RCTs were presented out of 4,280 abstracts. 53% of these were published; median time to publication was 24 months (13.36 IQR). Oral presentations were published more frequently (OR 3.66, p = 0.01) as well as those with stated industry funding (OR 2.92, p = 0.03) and larger sample sizes (OR 2.1, p = 0.01). Blinded RCTs had ~ 4 times the odds of being published. Only ten RCTs used clinical endpoints such as death, hospitalizations etc.; however, all reached publication. CONCLUSIONS Almost 50% of RCTs presented at the ASN 2005 meeting were not published within the studied time-frame. Well-conducted RCTs enhance the body of evidence needed to care for patients, if published. It is important to identify characteristics associated with non-publication, as above, to help us perform and report our studies better.

Fracture Risk Assessment (FRAX) tools are calibrated from country-specific fracture epidemiology. Although hip fracture data are usually available, data on non-hip fractures for most countries are often lacking. In such cases, rates are often estimated by assuming similar non-hip to hip fracture ratios from historical (1987 to 1996) Swedish data. Evidence that countries share similar fracture ratios is limited. Using data from Manitoba, Canada (2000 to 2007, population 1.2 million), we identified 21,850 incident major osteoporotic fractures (MOF) in men and women aged50 years. Population-based age- and sex-specific ratios of clinical vertebral, forearm, and humerus fractures to hip fractures were calculated, along with odds ratios (ORs) and 95% confidence intervals (CIs). All ratios showed decreasing trends with increasing age for both men and women. Men and women showed similar vertebral/hip fracture ratios (all p 0.1, with ORs 0.86 to 1.25). Forearm/hip and humerus/hip fracture ratios were significantly lower among men than women (forearm/hip ratio: p 0.01 for all age groups, with ORs 0.29 to 0.53; humerus/hip ratio: p 0.05 for all age groups [except 80 to 84 years] with ORs 0.46 to 0.86). Ratios for any MOF/hip fracture were also significantly lower among men than women in all but two subgroups (p 0.05 for all age groups [except 80 to 84 and 90+ years] with ORs 0.48 to 0.87). Swedish vertebral/hip fracture ratios were similar to the Canadian fracture ratios (within 7%) but significantly lower for other sites (men and women: 46% and 35% lower for forearm/hip ratios, 19% and 15% lower for humerus/hip ratios, and 19% and 23% lower for any MOF/hip ratios). These differences have implications for updating and calibrating FRAX tools, fracture risk estimation, and intervention rates. Moreover, wherever possible, it is important that countries try to collect accurate non-hip fracture data.

Background Fat deposition (FD) is part of the healing process after myocardial infarction. The characteristics of FD and its impact on the outcome in patients undergoing ventricular tachycardia (VT) ablation have not been thoroughly studied. Methods and Results We studied consecutive patients undergoing post–myocardial infarction VT ablation with pre‐procedural cardiac computed tomography. FD was defined as intra‐myocardial attenuation ≤ −30 HU on computed tomography. Clinical, anatomical, and post‐procedural outcome was assessed in the overall population. Electrophysiological characteristics were assessed is a subgroup of patients with high‐density electro‐anatomical maps. Sixty‐nine patients were included (66±12 years). FD was detected in 44 (64%) patients. The presence of FD related to scar age (odds ratio [OR]: 1.14 per year; P=0.001) and scar extent (OR: 1.27 per segment; P=0.02). On electro‐anatomical maps, FD was characterized by lower bipolar amplitude (P