The naturally occurring peptide, liver-expressed antimicrobial peptide 2 (LEAP2), has gained interest as a ghrelin receptor antagonist. We previously reported reduced food intake and plasma glucose-lowering effects of LEAP2 infusion in lean healthy men; however, the effects of this competitive antagonist and inverse agonist of the ghrelin receptor in men with obesity have not been investigated. In the current study, 20 men with obesity were enrolled in a randomized, double-blind, placebo-controlled, crossover study comprising two experimental visits, each involving a ∼5-h intravenous infusion of LEAP2 (infusion rate 40 pmol/kg/min) or placebo during which a liquid mixed meal test and a subsequent ad libitum meal test were performed. The LEAP2 infusion resulted in a fivefold increase in plasma concentrations of LEAP2 compared with placebo. The infusion lowered postprandial plasma glucose levels and reduced ad libitum food intake by ∼12%. We conclude that a continuous intravenous LEAP2 infusion reduces glycemia and food intake in men with obesity, supporting further exploration of LEAP2's therapeutic potential in obesity and related metabolic conditions. ARTICLE HIGHLIGHTS:Liver-expressed antimicrobial peptide 2 (LEAP2), a ghrelin receptor antagonist and inverse agonist, reduces food intake and improves markers of dysmetabolism in preclinical studies and in lean men; however, the effects of LEAP2 in obesity are unknown. We investigated the effects of exogenous LEAP2 on ad libitum food intake and metabolic parameters in men with obesity. We found that LEAP2 reduces ad libitum food intake and reduces postprandial plasma glucose concentration, revitalizing the ghrelin receptor as a potential target in the treatment of obesity and its related conditions.

BACKGROUND:The long-term glycaemic effects of glucose-dependent insulinotropic polypeptide (GIP) remain unclear. We aimed to assess whether a 6-week subcutaneous infusion of GIP alone and in combination with the GLP-1 receptor agonist semaglutide would enhance glycaemic control in individuals with type 2 diabetes. METHODS:This single-centre, double-blind, parallel-group, randomised, placebo-controlled trial was conducted at the Center for Clinical Metabolic Research (Hellerup, Denmark). Inclusion criteria were age 18-74 years; a diagnosis of type 2 diabetes for at least 6 months; stable treatment; HbA1c of 6·5-10·5% (48-91 mmol/mol); and a BMI of 25-50 kg/m2. Participants were randomly assigned (1:1:1:1), using a block randomisation list, to receive either placebo plus placebo, placebo plus GIP, semaglutide plus placebo, or semaglutide plus GIP (all self-administered subcutaneously). The regimen was 8-week semaglutide or placebo run-in period (4 weeks at 0·25 mg then 4 weeks at 0·50 mg once per week), after which participants continued 0·50 mg semaglutide or placebo for an additional 6 weeks while receiving continuous subcutaneous infusions of GIP or placebo (16 pmol/kg per min). Participants and investigators were masked to treatment assignment. The primary outcome was change in 14-day mean glucose concentration assessed by continuous glucose monitoring from baseline to the end of treatment at 14 weeks, assessed in the efficacy population. This study is registered at ClinicalTrials.gov, NCT05078255 (completed). FINDINGS:Between Jan 31, 2022, and Sept 4, 2024, we assessed 134 individuals with type 2 diabetes for eligibility, of whom 73 were ineligible. We enrolled and randomly assigned 61 participants (15 to placebo plus placebo, 16 to placebo plus GIP, 15 to semaglutide plus placebo, and 15 to semaglutide plus GIP). Ten (16%) participants discontinued the study. Participants had a median age of 64·0 years (IQR 60·0-68·0), HbA1c of 54·0 mmol/mol (49·0-60·0), diabetes duration of 6·3 years (4·2-9·8), and a mean BMI of 31·6 kg/m2 (SD 4·8). 22 (36%) participants were female and 39 (64%) were male and all self-reported as White. Fasting concentrations of intact (bioactive) GIP at the end of treatment on week 14 were mean 7 pmol/L (SD 4) in the placebo plus placebo group, 45 pmol/L (43) in the placebo plus GIP group, 10 pmol/L (6) in the semaglutide plus placebo group, and 85 pmol/L (92) in the semaglutide plus GIP group; whereas fasting concentrations of total GIP were 14 pmol/L (7), 375 pmol/L (377), 18 pmol/L (19), and 527 pmol/L (338), respectively. The estimated effect of GIP on change in 14-day mean sensor-detected glucose from baseline to end of treatment was 0·80 mmol/L (97·5% CI -0·18 to 1·80; p=0·13 in the placebo plus GIP vs placebo plus placebo groups) and 0·05 mmol/L (-0·85 to 0·95; p=1·00 in the semaglutide plus GIP vs semaglutide plus placebo groups). Injection site reactions were the most common adverse event (22 [36%]). Gastrointestinal adverse events were more frequent with semaglutide (nine [60%] with placebo plus placebo, 11 [69%] with placebo plus GIP, 11 [73%] with semaglutide plus placebo, and 12 [80%] with semaglutide plus GIP). INTERPRETATION:6 weeks of subcutaneous GIP infusion as add-on to placebo or semaglutide did not improve glycaemic control in individuals with type 2 diabetes at the prespecified target of 1·50 mmol/L. Due to dropouts, we cannot draw firm conclusions on the effects of GIP as add-on to placebo. FUNDING:Novo Nordisk.

Introduction and Objective: This study investigated the separate and combined effects of a six-week subcutaneous (s.c.) infusion of glucose-dependent insulinotropic polypeptide 1-42 (GIP) and once-weekly s.c. semaglutide on glycemic control in type 2 diabetes (T2D). We hypothesized that the combination would enhance glycemic control. Methods: This randomized, placebo-controlled, double-blind trial engaged 61 participants with T2D (18-75 years, BMI≥25 kg/m², HbA1c≥6.5%, no GLP-1-based medications or insulin). They received either 0.5 mg weekly s.c. semaglutide or placebo injections, and a six-week continuous s.c. infusion of 16 pmol/kg/min GIP or placebo via an infusion pump. The primary endpoint was change in mean glucose levels from baseline to the end of treatment; comparison 1: placebo + placebo vs. placebo + GIP; comparison 2: semaglutide + placebo vs. semaglutide + GIP. Differences were estimated using a constrained linear mixed model with 97.5% confidence intervals (CI). Results: Differences in mean sensor-detected glucose change were 0.80 mmol/l (CI -0.18 to 1.80) (comparison 1) and 0.05 mmol/l (CI -0.85 to 0.95) (comparison 2). The most frequent adverse event (AE) was injection site reaction to GIP infusion. Gastrointestinal AEs were more common and frequent in the semaglutide groups. Conclusion: In individuals with T2D, six weeks of s.c. infusion of GIP, alone or in combination with semaglutide, did not affect mean glucose levels significantly. M.M. Helsted: None. C.C. Fonnesbech-Wulff: Stock/Shareholder; Novo Nordisk. N.L. Schaltz: None. I.W. Lund: None. J. Forman: None. C.K. Nielsen: Stock/Shareholder; Novo Nordisk A/S. A. Englund: None. B. Hartmann: Employee; Bainan Biotech. T. Vilsbøll: Advisory Panel; Boehringer-Ingelheim, AstraZeneca, Bristol-Myers Squibb Company, Carmot Therapeutics, Inc. Research Support; Dexcom, Inc. Advisory Panel; Eli Lilly and Company, GlaxoSmithKline plc. Speaker's Bureau; Medscape. Advisory Panel; Novo Nordisk, Sun Pharmaceutical Industries Ltd, Roche Diabetes Care, Amgen Inc, Sanofi, Zealand Pharma A/S. J.J. Holst: Advisory Panel; Novo Nordisk A/S. Consultant; Novo Nordisk A/S. Other Relationship; Novo Nordisk A/S. Consultant; AstraZeneca, Fractyl Health, Inc., MSD Life Science Foundation, Structure Therapeutics, Inc. A.B. Lund: Consultant; Zealand Pharma A/S. Advisory Panel; Eli Lilly and Company. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk, Boehringer-Ingelheim. M.B. Christensen: None. F.K. Knop: Consultant; 89bio, Inc, AstraZeneca. Speaker's Bureau; AstraZeneca. Advisory Panel; Boehringer-Ingelheim. Consultant; Cytoki Pharma. Advisory Panel; Eli Lilly and Company. Consultant; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Gubra. Advisory Panel; Novo Nordisk A/S. Consultant; Novo Nordisk A/S. Employee; Novo Nordisk A/S. Research Support; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S, Eli Lilly and Company. Advisory Panel; Sanofi. Consultant; Structure Therapeutics, Inc. Advisory Panel; Zealand Pharma A/S. Consultant; Zealand Pharma A/S. Research Support; Zealand Pharma A/S. Speaker's Bureau; Zealand Pharma A/S. Stock/Shareholder; Zealand Pharma A/S, Gubra. Advisory Panel; Zucara Therapeutics. Consultant; Zucara Therapeutics. Stock/Shareholder; Antag Therapeutics. L.S. Gasbjerg: Stock/Shareholder; Antag Therapeutics, Bainan Biotech. This work was supported by the investigator-sponsored studies programme of Novo Nordisk under universal trial number (U1111-1259-1491). The grant was received as pure support without any obligation with Novo Nordisk and covers the expenses of the study.

AIMS:The incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1) influence metabolism through strong effects on pancreatic hormone secretion but also in a pancreas-independent manner. Here, we investigated the isolated extrapancreatic effects of endogenous GIP and GLP-1 by applying hormone receptor antagonists in totally pancreatectomized individuals. METHODS:Twelve totally pancreatectomized individuals each underwent four 270-min liquid mixed meal tests (480 kcal) in a randomized study design with infusions of the GIP receptor antagonist GIP(3-30)NH2 (800 pmol/kg/min), the GLP-1 receptor antagonist exendin(9-39)NH2 (450 pmol/kg/min), GIP(3-30)NH2 + exendin(9-39)NH2, and saline (placebo), respectively. Blood samples, appetite-related measures, heart rate, blood pressure, and ad libitum food intake data were collected. Participants continued their basal insulin but omitted bolus insulin in the morning of the experiment. RESULTS:Infusions of GIP(3-30)NH2 and GIP(3-30)NH2 + exendin(9-39)NH2 attenuated meal-induced inhibition of bone resorption (carboxy-terminal collagen crosslinks) (nadir [mean ± SD] to 84 ± 9% and to 85 ± 8% of baseline, compared to placebo (64 ± 15%) (ps <0.05)). During exendin(9-39)NH2 and exendin(9-39)NH2 + GIP(3-30)NH2 co-infusion, GLP-1 plasma responses increased (ps <0.05). Infusion of GIP(3-30)NH2 or exendin(9-39)NH2 did not affect other measurements. CONCLUSION:Endogenous GIP contributes to the regulation of postprandial bone resorption independently of pancreatic factors. In contrast, GIP receptor and/or GLP-1 receptor antagonism had no measurable effects on glucose metabolism, gastric emptying, appetite, food intake, triglycerides, or haemodynamics, supporting a pancreatic contribution to some of these effects of the endogenous hormones, although the surgical reconstruction may have influenced the sensitivity of the targets.

Introduction and Objective: Liver-expressed antimicrobial peptide 2 (LEAP2) secreted from the liver and the small intestine has gained interest as a ghrelin receptor antagonist. Recently, we reported glucose-lowering effects of intravenous (iv) infusion of LEAP2 during a liquid mixed meal test in lean men and men with obesity. Here, we investigated the effects of LEAP2 infusion on the hepatic metabolic rate of glucose assessed by total-body PET/CT in men with obesity. Methods: Nine men with obesity (mean (SD) age 36 (9.4) years; BMI 36.8 (3.28) kg/m2; waist-hip ratio 1.1 (0.1); HbA1c 34 (2.8) mmol/mol)) were enrolled in a randomized, single-blind, placebo-controlled, crossover study comprising two experimental days each involving a 145-minute iv infusion of LEAP2 (40 pmol/kg/min) or placebo (saline 9 mg/ml). Sixty minutes after infusion start, a low-dose glucose infusion (2 mg/kg/min) was initiated. A glucose analog (2-[18F]fluoro-2-deoxy-D-glucose) was injected 75 minutes after infusion start and participants were scanned in a Biograph Vision Quadra total-body PET/CT scanner (Siemens Healthineers, Germany) for 70 minutes. Glucose net influx rates (mL/(mL × min)) and metabolic rates of glucose (μmol/(g × min)) were assessed using the Patlak method. Results: Compared to placebo (PLA), LEAP2 infusion did not affect the area under the curve for plasma glucose during the low-dose glucose infusion (502 (29.6) (LEAP2) vs. 513 (45.8) (PLA) mmol/L × min, P=0.3). LEAP2 infusion did not affect the hepatic metabolic rate of glucose (0.019 (0.011) (LEAP2) vs. 0.017 (0.011) (PLA) μmol/(g × min, P=0.7) or glucose net influx rates in skeletal muscle or brain compared to placebo. Conclusion: In this exploratory study, we observed no effect of continuous iv LEAP2 infusion on hepatic metabolic rate of glucose or glucose influx rates compared to placebo under the given conditions. The reduced postprandial glucose excursions previously observed in lean men and men with obesity during an oral meal challenge, could possibly be due to postprandial factors not present during the iv glucose infusion. A. Englund: None. A.H. Lange: None. C.A. Hagemann: Employee; Novo Nordisk A/S. A.B. Lund: Consultant; Zealand Pharma A/S. Advisory Panel; Eli Lilly and Company. Research Support; Novo Nordisk. Speaker's Bureau; Novo Nordisk, Boehringer-Ingelheim. T.L. Andersen: None. P.K. Cramon: None. F.K. Knop: Consultant; 89bio, Inc, AstraZeneca. Speaker's Bureau; AstraZeneca. Advisory Panel; Boehringer-Ingelheim. Consultant; Cytoki Pharma. Advisory Panel; Eli Lilly and Company. Consultant; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Gubra. Advisory Panel; Novo Nordisk A/S. Consultant; Novo Nordisk A/S. Employee; Novo Nordisk A/S. Research Support; Novo Nordisk A/S. Speaker's Bureau; Novo Nordisk A/S. Stock/Shareholder; Novo Nordisk A/S, Eli Lilly and Company. Advisory Panel; Sanofi. Consultant; Structure Therapeutics, Inc. Advisory Panel; Zealand Pharma A/S. Consultant; Zealand Pharma A/S. Research Support; Zealand Pharma A/S. Speaker's Bureau; Zealand Pharma A/S. Stock/Shareholder; Zealand Pharma A/S, Gubra. Advisory Panel; Zucara Therapeutics. Consultant; Zucara Therapeutics. Stock/Shareholder; Antag Therapeutics. L.S. Gasbjerg: Stock/Shareholder; Antag Therapeutics, Bainan Biotech. Novo Nordisk Foundation (NNF23OC0084114)

Pulsed field ablation (PFA) offers a safe, non-thermal alternative for pulmonary vein isolation (PVI) in patients with atrial fibrillation (AF). Currently, the pentaspline PFA-system relies heavily on fluoroscopy for catheter manipulation, which poses challenges due to the complexity of left atrium anatomy. Incorporating three-dimensional electroanatomical mapping (3D-EAM) could improve procedural efficiency reducing dependency on fluoroscopy guidance. This study aims to evaluate the effects of integration of 3D-EAM with PFA during PVI. Between September 2022 and December 2023, we retrospectively enrolled 248 patients with paroxysmal or persistent AF undergoing PVI at our center using the pentaspline PFA catheter. The control group (n = 104) received conventional PFA with fluoroscopic guidance alone, while the intervention group (n = 144) underwent PVI with PFA with 3D-EAM integration. Primary outcomes were procedural time, fluoroscopy time (FT), and dose area product (DAP). Secondary endpoints included acute procedural success and incidence of periprocedural complications. In the 3D-EAM-PFA group, procedural time was 63.3 ± 14.3 min, compared to 65.6 ± 14.9 min in the control group (p = 0.22). The 3D-EAM group experienced significantly reduced FT (9.7 ± 4.4 min vs. 16.7 ± 5.2 min) and DAP (119.2 ± 121.7 cGycm2 vs. 338.7 ± 229.9 cGycm2) compared to the control group, respectively (p < 0.001). Acute procedural success was achieved in all cases. No major complications were observed in either group. Integration of 3D-EAM with the pentaspline PFA catheter for PVI in AF treatment offers a promising approach, with significantly reduced fluoroscopy exposure without compromising procedural time and efficacy.

Liver-expressed antimicrobial peptide 2 (LEAP2) and ghrelin have reciprocal effects on their common receptor, the growth hormone secretagogue receptor (GHSR). Ghrelin is considered a gastric hormone and LEAP2 a liver-derived hormone and both have been proposed to be involved in the pathophysiology of obesity and type 2 diabetes (T2D). We investigated the mRNA expression of LEAP2, ghrelin and GHSR along the intestinal tract of individuals with and without TD2, and in the liver of men with and without obesity. Mucosal biopsies retrieved with 30-cm intervals throughout the small intestine and from 7 well-defined locations along the large intestine from 12 individuals with T2D and 12 healthy controls together with liver biopsies from 15 men with obesity and 15 lean men were subjected to bulk transcriptomics analysis. Both in individuals with and without T2D, mRNA expression of LEAP2 increased through the small intestine until dropping at the ileocecal valve, with little LEAP2 mRNA expression in the large intestine. Pronounced LEAP2 expression was observed in the liver of men with and without obesity. Robust ghrelin mRNA expression was observed in the duodenum of individuals with and without T2D, gradually decreasing along the small intestine with little expression in the large intestine. Ghrelin mRNA expression was not detected in the liver biopsies, and GHSR mRNA expression was not. In conclusion, we provide unique mRNA expression profiles of LEAP2, ghrelin and GHSR along the human intestinal tract showing no T2D-associated changes, and in the liver showing no differences between men with and without obesity.

OBJECTIVE:Catheter ablation of atrial fibrillation effectively reduces symptomatic burden. However, its long-term effect on mortality and stroke is unclear. We investigated if patients with atrial fibrillation who undergo catheter ablation have lower risk for all-cause mortality or stroke than patients who are managed medically. METHODS:We retrospectively included 5628 consecutive patients who underwent first-time catheter ablation for atrial fibrillation between 2008 and 2018 at three major Swedish electrophysiology units. Control individuals with an atrial fibrillation diagnosis but without previous stroke were selected from the Swedish National Patient Register, resulting in a control group of 48 676 patients. Propensity score matching was performed to produce two cohorts of equal size (n=3955) with similar baseline characteristics. The primary endpoint was a composite of all-cause mortality or stroke. RESULTS:Patients who underwent catheter ablation were healthier (mean CHA2DS2-VASc score 1.4±1.4 vs 1.6±1.5, p<0.001), had a higher median income (288 vs 212 1000 Swedish krona [KSEK]/year, p<0.001) and had more frequently received university education (45.1% vs 28.9%, p<0.001). Mean follow-up was 4.5±2.8 years. After propensity score matching, catheter ablation was associated with lower risk for the combined primary endpoint (HR 0.58, 95% CI 0.48 to 0.69). The result was mainly driven by a decrease in all-cause mortality (HR 0.51, 95% CI 0.41 to 0.63), with stroke reduction showing a trend in favour of catheter ablation (HR 0.75, 95% CI 0.53 to 1.07). CONCLUSIONS:Catheter ablation of atrial fibrillation was associated with a reduction in the primary endpoint of all-cause mortality or stroke. This result was driven by a marked reduction in all-cause mortality.

Pulmonary vein isolation (PVI) of symptomatic atrial fibrillation is an effective method of maintaining sinus rhythm. Radiofrequency ablation and cryotechnology have been used for this purpose for many years. One disadvantage of these methods is the risk of serious complications such as pulmonary vein stenosis, phrenic nerve palsy and atrio-oesophageal fistula. Pulsed Field Ablation (PFA) is a promising ablation modality for treatment of atrial fibrillation. This technique employs a train of high amplitude electrical pulses with short duration that ablate myocardium with minimal effect on surrounding tissues. 100 patients underwent PFA at the Capio Arrhythmia Center Stockholm. All pulmonary veins could be identified successfully and isolation could be achieved without difficulty. No serious complication during ablation and observation time after the procedure occurred. Our experience with PFA shows that PVI with this technique in symptomatic atrial fibrillation is a safe and effective method.

The naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP2) has gained interest as a ghrelin receptor antagonist. Recently, we reported food intake and plasma glucose-lowering effects of exogenous LEAP2 in lean healthy males. Here, we investigated the effects of LEAP2 infusion on ad libitum food intake and postprandial glucose tolerance in obese men. Twenty obese men (mean (SEM) age 44.2 (2.2) years; BMI 36.3 (0.8) kg/m2; body fat percentage 37.4 (0.9)%) were enrolled in this randomized, double-blind, placebo-controlled, crossover study comprising two experimental days. Experimental days involved a ~5-hour intravenous (iv) infusion of LEAP2 or placebo during which a liquid mixed meal test (MMT) and a subsequent ad libitum meal test were performed. Plasma glucose measures included fasted (preprandial), Cmax and Tmax values as well as area under the curve (AUC) during MMT. Ad libitum food intake was measured in kilojoule (kJ) and kJ/kg body weight. Compared to placebo, LEAP2 infusion lowered preprandial plasma glucose (mean (SEM): 5.03 (0.08) vs. 5.19 (0.06) mmol/L, P=0.0095) as well as Cmax (6.58 (0.18) vs. 6.98 mmol/L (0.18), P=0.0001) and AUC for plasma glucose during MMT (1,506 (33.4) vs. 1564 (30.4) min×mmol/L, P=0.0005), but not Tmax. Ad libitum food intake was reduced by ~13% during LEAP2 infusion compared to placebo (2,939 (266) vs. 3,378 (258) kJ, P=0.0118; 25.0 (2.4) vs. 28.4 (2.0) kJ/kg body weight, P=0.0140). We conclude that a continuous iv LEAP2 infusion reduces pre- and postprandial plasma glucose concentrations as well as ad libitum food intake in obese men. Disclosure A. Englund: None. C. A. Hagemann: Employee; Gubra ApS. L. S. Gasbjerg: Speaker's Bureau; Eli Lilly and Company, Stock/Shareholder; Antag Therapeutics. F. K. Knop: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Novo Nordisk, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Lundbeck.

The naturally occurring peptide liver-enriched antimicrobial peptide 2 (LEAP2) has gained interest as a ghrelin receptor antagonist. Recently, we reported food intake and plasma glucose-lowering effects of exogenous LEAP2 in lean healthy males. Here, we investigated the effects of LEAP2 infusion on ad libitum food intake and postprandial glucose tolerance in obese men. Twenty obese men (mean (SEM) age 44.2 (2.2) years; BMI 36.3 (0.8) kg/m2; body fat percentage 37.4 (0.9)%) were enrolled in this randomized, double-blind, placebo-controlled, crossover study comprising two experimental days. Experimental days involved a ~5-hour intravenous (iv) infusion of LEAP2 or placebo during which a liquid mixed meal test (MMT) and a subsequent ad libitum meal test were performed. Plasma glucose measures included fasted (preprandial), Cmax and Tmax values as well as area under the curve (AUC) during MMT. Ad libitum food intake was measured in kilojoule (kJ) and kJ/kg body weight. Compared to placebo, LEAP2 infusion lowered preprandial plasma glucose (mean (SEM): 5.03 (0.08) vs. 5.19 (0.06) mmol/L, P=0.0095) as well as Cmax (6.58 (0.18) vs. 6.98 mmol/L (0.18), P=0.0001) and AUC for plasma glucose during MMT (1,506 (33.4) vs. 1564 (30.4) min×mmol/L, P=0.0005), but not Tmax. Ad libitum food intake was reduced by ~13% during LEAP2 infusion compared to placebo (2,939 (266) vs. 3,378 (258) kJ, P=0.0118; 25.0 (2.4) vs. 28.4 (2.0) kJ/kg body weight, P=0.0140). We conclude that a continuous iv LEAP2 infusion reduces pre- and postprandial plasma glucose concentrations as well as ad libitum food intake in obese men. Disclosure A. Englund: None. C. A. Hagemann: Employee; Gubra ApS. L. S. Gasbjerg: Speaker's Bureau; Eli Lilly and Company, Stock/Shareholder; Antag Therapeutics. F. K. Knop: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Consultant; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Research Support; Novo Nordisk, Zealand Pharma A/S, Speaker's Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk, Sanofi, Lundbeck.

Aims Catheter ablation is considered the treatment of choice for many tachyarrhythmias, but convincing real-world' data on efficacy and safety are lacking. Using Swedish national registry data, the ablation spectrum, procedural characteristics, as well as ablation efficacy and reported adverse events are reported. Methods and Results Consecutive patients (18years of age) undergoing catheter ablation in Sweden between 01 January 2006 and 31 December 2015 were included in the study. Follow-up (repeat ablation and vital status) was collected through 31 December 2016. A total of 26642 patients (5715years, 62% men), undergoing a total of 34428 ablation procedures were included in the study. In total, 4034 accessory pathway/Wolff-Parkinson-White syndrome (12%), 7358 AV-nodal re-entrant tachycardia (21%), 1813 atrial tachycardia (5.2%), 5481 typical atrial flutter (16%), 11916 atrial fibrillation (AF, 35%), 2415 AV-nodal (7.0%), 581 premature ventricular contraction (PVC, 1.7%), and 964 ventricular tachycardia (VT) ablations (2.8%) were performed. Median follow-up time was 4.7years (interquartile range 2.7-7.0). The spectrum of treated arrhythmias changed over time, with a gradual increase in AF, VT, and PVC ablation (P<0.001). Decreasing procedural times and utilization of fluoroscopy with time, were seen for all arrhythmia types. The rates of repeat ablation differed between ablation types, with the highest repeat ablation seen in AF (41% within 3years). The rate of reported adverse events was low (n=595, 1.7%). Death in the immediate period following ablation was rare (n=116, 0.34%). Conclusion Catheter ablations have shifted towards more complex procedures over the past decade. Fluoroscopy time has markedly decreased and the efficacy of catheter ablation seems to improve for AF.

Background: Catheter ablation has become the treatment of choice for many tachyarrhythmias. The ablation techniques are continuously refined and the indications expanded, enabling treatment of more ...

IntroductionSupraventricular ectopic complexes (SVEC) are known risk factors of recurrent atrial fibrillation (AF). However, the impact of SVEC in different age groups is unknown. We aimed to investigate the risk of AF recurrence with higher SVEC burden in patients ±57years, respectively, after treatment with antiarrhythmic medication (AAD) or catheter ablation (CA).MethodsIn total, 260 patients with LVEF >40% and age ≤70 years were randomized to AAD (N=132) or CA (N=128) as first-line treatment for paroxysmal AF. All patients underwent 7-day Holter monitoring at baseline, and after 3, 6, 12, 18 and 24months and were categorized according to median age ±57years. We used multivariate Cox regression analyses and we defined high SVEC burden at 3months of follow-up as the upper 75th percentile >195SVEC/day. AF recurrence was defined as AF ≥1min, AF-related cardioversion or hospitalization.ResultsAge >57years were significantly associated with higher AF recurrence rate after CA (58% vs 36%, p=0.02). After CA, we observed a higher SVEC burden during follow-up in patients >57years which was not observed in the younger age group treated with CA (p=0.006). High SVEC burden at 3months after CA was associated with AF recurrence in older patients but not in younger patients (>57years: HR 3.4 [1.4–7.9], p=0.005). We did not find any age-related differences after AAD.ConclusionWe found that younger and older patients respond differently to CA and that SVEC burden was only associated with AF recurrence in older patients.

Aims Early identification of patients who could benefit from early re-intervention after catheter ablation is highly warranted. Our aim was to investigate the association between post-procedural burden of supraventricular ectopic complexes (SVEC) and the risk of long-term atrial fibrillation (AF) recurrence. Methods and results A total of 125 patients undergoing catheter ablation for AF were included. Patients underwent 7-day Holter recordings immediately post-procedural. The number of SVEC in post-procedural Holter recordings was categorized into quartiles: 0-72, 73-212, 213-782 and ≥ 783 SVEC/day. Long-term AF recurrence was defined as a combined endpoint of AF ≥ 1 min during follow-up Holter recordings, cardioversion or hospitalization for AF after a 3-month blanking period and within 24 months of follow-up. High post-procedural supraventricular ectopy burden was associated with an increased risk of long-term AF recurrence in a dose-dependent manner (≥ 783 SVEC: HR 4.6 [1.9-11.5], P < 0.001) irrespective of AF recurrence during the blanking period or other risk factors. In patients with early AF recurrence < 90 days after catheter ablation ectopy burden was also highly predictive of long-term AF recurrence (SVEC ≥ 213: HR 3.0 [1.3-6.7], P = 0.007). Correspondingly, patients with early AF recurrence but low ectopy burden remained at low risk of long-term AF recurrence after the blanking period. Conclusion Our results indicate that post-procedural ectopy burden is highly associated with long-term AF recurrence and could be a potent risk marker for selection of patients for early re-ablation. Development of future ablation risk stratification and strategies should include focus on post-procedural ectopy burden.