Background: Pulsed field ablation [PFA] is a novel ablation technique for pulmonary vein isolation [PVI] in patients with paroxysmal and persistent atrial fibrillation. However, data for the efficacy and safety of PFA for left atrial substrate modification using a single shot PFA system, in patients with long-standing persistent atrial fibrillation [AF] and left atrial macro- as well as micro-reentrant atrial tachycardia [LAMRT], are scarce. Here, we provide a small, single-center case series regarding the efficacy and safety of left atrial substrate modification using a single-shot PFA system. Methods: Nine patients with long-standing persistent AF and LAMRT underwent redo-PVI and left atrial substrate modification using a single-shot PFA system. Patients were subsequently followed up for 1 year. Results: The median age was 64 years [IQR 55.5–75], with 44% of the participants being female. The median time since the first diagnosis of AF was 7 years [IQR 4–15.5]. After re-PVI, posterior wall isolation was performed in five patients, roof isolation in six patients, and anterior wall ablation between the superior mitral annulus and the right superior pulmonary vein [RSPV] in five patients. In two patients, cavotricuspid isthmus ablation was additionally performed to treat typical atrial flutter. The acute procedural success rate was 100%, with all LAMRTs and typical flutters successfully terminating by ablation. At 1-year follow-up, four patients [44%] experienced a recurrence of any atrial arrhythmia. Median time to recurrence was 164 days [138–212.8]. Importantly, no acute or chronic complications were observed. Conclusions: In this small, single-center case series, left atrial substrate modification for long-standing persistent AF and AT using a single-shot PFA system was safe and showed an excellent acute success rate.

Abstract Background Pulsed field ablation (PFA) is a novel ablation technique for pulmonary vein isolation (PVI) in patients with paroxysmal and persistent atrial fibrillation. However, data for efficacy and safety of PFA for left atrial substrate modification in patients with long-standing persistent atrial fibrillation (AF) and macro- as well as microreentrant atrial tachycardia (AT) is scarce. Aim Here we provide a retrospective, single-centre case series regarding efficacy and safety of left atrial substrate modification, using a single-shot PFA system. Methods and Results Over a period of 6 months, 8 patients with long-standing persistent AF and AT underwent Re-PVI with left atrial substrate modification using a single-shot PFA system. Median age was 63 years (IQR 58 - 75), and 4/8 of patients were female. Time from first diagnosis of AF was 7 years (IQR 4 –10). All but 1 patient underwent previous PVI (IQR 1-3) with (5/7) or without (2/7) prior substrate modification using radiofrequency ablation. On transthoracic echocardiography, all patients showed severe left- and right-atrial enlargement, with LA volume of 58 ml/m2 (IQR 49.7–72) and RA diameter of 62 mm (IQR 55-75). In 8 patients, 9 ATs and 2 typical flutters were treated with PFA. Following PVI, additional posterior wall isolation was performed in 6/8 patients, roof in 6/8, and anterior wall (between superior mitral anulus and RSPV) in 4/8 patients. In addition, 2/8 patients had cavotricuspid isthmus ablation for typical atrial flutter. All patients received atropine prior to PVI, as well as bolus of nitro-glycerine prior to PFA of anterior wall and/or cavotricuspid isthmus. Acute success rate was 100% and all ATs as well as typical flutter terminated with PFA. After median follow-up time of 88 days (IQR 61-112), 3 patients had a documented recurrence of AF/AT, in 2 of which electrical cardioversion was necessary. We observed no acute and/or chronic complications following PFA, i.e. no pericardial effusion/tamponade, TIA/stroke, myocardial infarction, coronary artery spasm, AV-block, bleeding, or atrioesophageal fistula. Conclusion In this small, single-centre case series, left atrial substrate modification for long-standing persistent AF and AT using a single-shot PFA system was safe and showed an excellent acute success rate.

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Patient-device mismatch in patients undergoing left atrial appendage closure (LAAC) may lead to failure to implant, dislocation, and cardiac tamponade. There is limited data about patient cohorts that are especially susceptible to these complications. Objective To analyse the association between body height, weight and acute complications due to probable device mismatch. Methods A retrospective analysis from a multicentre registry including consecutive patients undergoing LAAC was performed. Device related complications were defined as dislocation, failure to implant or cardiac tamponade requiring intervention. Results A total of 431 patients from 9 centres were included. Median age was 75 (interquartile range, IQR 70-79) years and 35.7% were female. Mean±SD body height was 171.3±8.8 cm and median weight was 80 (IQR 70-90) kg. Median CHADS-VASc score was 5 (IQR 3-5) and HAS-BLED score was 3 (IQR 3-4). Indications were bleeding (66.6%), stroke (9.7%) and other (23.6%). Acute device-related complications after LAAC occurred in 5.6% of cases (24/431): Failure to implant (3.0%), cardiac tamponade (2.1%), and dislocation (0.7%). Complications occurred significantly more often in the tercile with lowest body weight and highest body height (23.5% vs. 4.3%, p=0.01, Figure). Conclusion Acute device-related complications as sign of patient-device mismatch are most pronounced in patients with lowest body weight and highest body height.

Background Diagnosis of cardiac amyloidosis (CA) requires advanced imaging techniques. Typical surface ECG patterns have been described, but their diagnostic abilities are limited. Objective The aim was to perform a thorough electrophysiological characterisation of patients with CA and derive an easy-to-use tool for diagnosis. Methods We applied electrocardiographic imaging (ECGI) to acquire electroanatomical maps in patients with CA and controls. A machine learning approach was then used to decipher the complex data sets obtained and generate a surface ECG-based diagnostic tool. Findings Areas of low voltage were localised in the basal inferior regions of both ventricles and the remaining right ventricular segments in CA. The earliest epicardial breakthrough of myocardial activation was visualised on the right ventricle. Potential maps revealed an accelerated and diffuse propagation pattern. We correlated the results from ECGI with 12-lead ECG recordings. Ventricular activation correlated best with R-peak timing in leads V1–V3. Epicardial voltage showed a strong positive correlation with R-peak amplitude in the inferior leads II, III and aVF. Respective surface ECG leads showed two characteristic patterns. Ten blinded cardiologists were asked to identify patients with CA by analysing 12-lead ECGs before and after training on the defined ECG patterns. Training led to significant improvements in the detection rate of CA, with an area under the curve of 0.69 before and 0.97 after training. Interpretation Using a machine learning approach, an ECG-based tool was developed from detailed electroanatomical mapping of patients with CA. The ECG algorithm is simple and has proven helpful to suspect CA without the aid of advanced imaging modalities.

Abstract Introduction Left atrial appendage closure is associated with a relevant procedural complication rate. Baseline risk factors, such as pre-procedural lab results, may identify patients that develop acute complications. Methods We performed a retrospective analysis of the impact of baseline characteristics and preprocedural lab results on the acute procedural outcome in patients undergoing left atrial appendage closure from the Austrian Left Atrial Appendage Closure Registry between 2010 and 2019. The endpoint for procedural complications was defined as death, stroke, major bleeding, necessity for intensive care, other complications requiring invasive interventions or failure to implant the device. We also evaluated a modified endpoint with the exclusion of bleeding events. Logistic regression was performed using stepwise approach (backward method with p_out = 0.1) and forced inclusion of age, left-ventricular function and kidney function. Results A total of 320 consecutive patients from 9 centres with a median age of 75 years (36.6% female) were included. Seventy-eight percent had a history of bleeding and 35% had a history of stroke. Median CHA2DS2-VASc score was 5 (interquartile range, 3–5) and median HAS-BLED score was 3 (2–4). Procedural complications occurred in 15.3% of cases. Low haemoglobin and low activated partial thromboplastin time were associated with an increased complication rate. Other significant baseline factors were liver disease, absence of intracranial haemorrhage and severe aortic stenosis. In multivariate analysis, low haemoglobin remained a significant predictor, even after adjustment for age, left-ventricular function and kidney function (Table). In the modified procedural complication endpoint excluding major bleeding events (14.1%), low haemoglobin remained a significant predictor (haemoglobin 11.9±2.0 vs. 12.8±2.0 g/dL in patients with vs. without modified endpoint, p=0.013). A baseline haemoglobin lower than 12 g/dL was present in 39.4% and it increased relative risk of procedural complications by 89% (21.4 vs. 11.3% in patients with reduced vs. normal haemoglobin), and risk of complications without bleeding by 92% (19.8 vs. 10.3%). Conclusion Low baseline haemoglobin is independently associated with a higher complication rate after left appendage closure compared to patients with normal haemoglobin levels, even in a modified endpoint excluding bleeding and requirement for transfusion. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Boston Scientific - unrestricted grant Table 1

Background Transcatheter tricuspid valve intervention became an option for pacemaker lead-associated tricuspid regurgitation. This study investigated the progression of tricuspid regurgitation (TR) in patients with or without pre-existing right ventricular dilatation (RVD) undergoing pacemaker implantation. Methods Patients were included if they had implantation of transtricuspid pacemaker lead and completed echocardiography before and after implantation. The cohort was divided in patients with and without RVD (cut-off basal RV diameter ≥ 42 mm). TR was graded in none/mild, moderate, and severe. Worsening of one grade was defined as progression. Survival analyses were plotted for 10 years. Results In total, 990 patients were analyzed (24.5% with RVD). Progression of TR occurred in 46.1% of patients with RVD and in 25.6% of patients without RVD ( P < 0.001). Predictors for TR progression were RV dilatation (OR 2.04; 95% CI 1.27–3.29; P = 0.003), pre-existing TR (OR 4.30; 95% CI 2.51–7.38; P < 0.001), female sex (OR 1.68; 95% CI 1.16–2.43; P = 0.006), single RV lead (OR 1.67; 95% CI 1.09–2.56; P = 0.018), mitral regurgitation (OR 2.08; 95% CI 1.42–3.05; P < 0.001), and enlarged left atrium (OR 1.98; 95% CI 1.07–3.67; P = 0.03). Survival-predictors were pacemaker lead-associated TR (HR 1.38; 95% CI 1.04–1.84; P = 0.028), mitral regurgitation (HR 1.34; 95% CI 1.02–1.77; P = 0.034), heart failure (HR 1.75; 95% CI 1.31–2.33; P < 0.001), kidney disease (HR 1.62; 95% CI 1.25–2.11; P < 0.001), and age ≥ 80 years (HR 2.84; 95% CI 2.17–3.71; P < 0.001). Conclusions Patients with RVD receiving pacemaker suffered from increased TR progression, leading to decreased survival. Graphic abstract

Abstract Background Cardiotoxicity caused by anticancer treatment affects cardiac conduction. Clinical outcomes of pacemaker patients with newly diagnosed cancer are insufficiently understood. Purpose The aim was to investigate the effect of anticancer therapy on pacemaker properties. Methods All patients with pacemaker and confirmed cancer diagnosis treated with chemotherapy at our tertiary university hospital were included in this study. The pacemaker database (containing pacemaker related information) was matched with hospital-wide electronic health records (containing cancer types, comorbidities and echo data). Survival data were retrieved from the Statistics Austria Federal Institute. Clinical and pacemaker data of patients with previously diagnosed cancer requiring pacemaker implantation (Group A) were compared to patients with pre-existing pacemaker followed by cancer diagnosis (Group B). Results Out of 972 included patients, 295 patients (30.3%) had the pacemaker implantation after their first cancer diagnosis (Group A), and 677 patients (69.7%) had already a pacemaker before their first cancer diagnosis (Group B). Cancer types are displayed in Figure 1. The following cancer types were associated with increased likelihood for pacemaker implantation after cancer diagnosis (Group A): kidney cancer (OR 2.07, 95% CI 1.12 to 3.83, P=0.02), lymphomas (OR 2.27, 95% CI 1.21 to 4.26, P=0.01), and eye cancer (OR 9.29, 95% CI 1.03 to 83.50, P=0.047). Patients in Group A were older at pacemaker implantation (76.0 years [IQR 68.0–82.2] vs. 72.1 years [IQR 64.3–78.0], P<0.001), and single-chamber pacemakers were less frequent (21.8% vs. 32.1%, P=0.001). Pacemaker implantation due to bradycardic atrial fibrillation was less frequent in Group A (15.6% vs. 21.8%, P=0.03), but implantation due to an “unspecified” indication was increased (20.6% vs. 12.7%, P=0.002). Patients in Group A had lower pacing threshold at baseline but had a stronger increase in pacing threshold during the follow-up as indicated in Table 1. No differences regarding left or right ventricular function, left or right end-diastolic diameter, or mitral or tricuspid regurgitation were detected between the groups. Patients in Group A had smaller left atria (59.7±10.7mm vs. 63.9±24.0mm, P=0.02) and smaller right atria (57.9±10.4mm vs. 61.2±11.8mm, P=0.001). Patients with cancer diagnosis requiring pacemaker had worse 10-year survival (31.2% vs. 51.1%, log-rank P<0.001) as shown in Figure 1. Conclusion Kidney cancer, lymphoma, and cancer of the eye were associated with increased probability of pacemaker implantation after cancer diagnosis. The significant increase in pacing threshold in patients undergoing chemotherapy could be associated with chemotherapy-induced cardiotoxicity. Funding Acknowledgement Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union's Horizon 2020 Future and Emerging Technologies Programme Figure 1. Cancer types and survivalTable 1. Baseline characteristics

Abstract Background Currently no data are available whether the implantation of right ventricular (RV) pacemaker (PM) lead worsens preexisting primary or secondary (functional due to RV dilatation, RVD) tricuspid regurgitation (TR). Purpose The aim of the present retrospective analysis was to assess TR after PM implantation with a RV lead. Methods Patients with PM implantation (n=990) were enrolled if they had routine echocardiography including assessment of TR before first implantation and immediately after. RVD and severity of TR were characterized visually. Based on RVD in baseline echocardiography, patients were divided into 2 groups: with primary TR (without preexisting RVD, n=743) or secondary TR (with preexisting RVD, n=243). Results Lead-induced worsening of TR was present in both groups (Table 1). Progression from mild/moderate to severe TR was observed in 6.7% of patients with primary TR, compared to 25.6% of patients with secondary TR (P=0.001). Using an ordinal regression model, the probability to progress to severe TR with primary TR was 14.8% (95% CI 11.0%-19.7%), compared to 41.6% (95% CI 40.3%-42.8%) with secondary TR (P<0.001). Conclusion Preexisting secondary TR was associated with higher rates of lead-induced progression to severe TR compared to primary TR. Leadless pacing or tricuspid valve clipping post-PM implantation could be an option for patients with preexisting secondary TR and indication for a PM. Table 1. Patient characteristics. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): This study was supported by the European Union's Horizon 2020 Future and Emerging Technologies Programme [Grant number 732170].

Abstract Background The wearable cardioverter-defibrillator (WCD) is a temporary treatment option for patients at high risk for sudden cardiac death (SCD) and/or for patients in whom implantation of a cardioverter defibrillator (ICD) is temporarily not possible. Purpose To investigate incidence and predictors of appropriate WCD shocks. Methods We performed a retrospective analysis of all patients with appropriate shocks delivered by a WCD in the cohort of the Austrian WCD registry between 2010 and 2018. Within this dataset, we identified predictors within the baseline characteristics, the indication for the WCD and preceding alarms automatically recorded by the WCD. Results: Baseline Within 879 registered in the Austrian WCD registry, 31 patients (3,5%) received appropriate WCD shocks due to ventricular tachycardia (VT) or ventricular fibrillation (VF). Compared to the total cohort, shocked patients were elder (mean age 67 ± 14 vs. 60 ± 14 years, p = 0,001) and the percentage of female patients was lower (11% vs. 21%, p = 0,262). The mean baseline LVEF at prescription was 33 ± 15% in the population with appropriate shocks compared to 32 ± 14% in the all-over cohort (p = ns). In the Austrian WCD population, 378/879 patients had a WCD due to secondary prevention. Within this cohort 5,6% (21/378) had shocks for VT/VF again, compared to 10/501 (2%) shocked patients in the primary prevention cohort. 31/879 (3.5%) patients received 57 appropriate shocks, the per patient shock rate was 2 [1;5]. These shocks were induced by 25 ventricular tachycardia and 26 times ventricular fibrillation. The octagenarians with 11% (7/34) shocked patients, showed a significant higher likelihood to receive shocks (p = 0,008) as well as the cohort of secondary preventive prescribed WCD-patients (p = 0,007). There were more shocks in patients, when prescribed with a WCD due to ICD associated infections (p = 0,001), when used as a bridge to ICD (p = 0,042) and in patients with ongoing risk stratification (p = 0,009). Looking through the automatically recorded alarms preceding a WCD shock, shocked patients experienced significantly more often non sustained VTs (p < 0,0005) and sustained VTs that were haemodynamically tolerated and did not require a treatment (p < 0,0005). Conclusion The WCD is effective in preventing SCD and an important risk stratification tool. We identified advanced age, patients with either already confirmed indication for ICD implantation (either temporary contraindication for implantation or temporary explantation) or risk stratification of an unclear cardiomyopathy, the cohort of secondary prevention and preceding nsVTs and stable VTs as predictors for appropriate WCD therapies.

Abstract Background The wearable cardioverter-defibrillator (WCD) is a treatment option for patients at high risk for ventricular arrhythmia, either if the risk is potentially reversible or if an implantable cardioverter defibrillator (ICD) implantation is currently not possible. Methods We performed a retrospective analysis of all alarms in the cohort of the Austrian WCD registry between 2010 and 2018. Type of arrhythmias was assessed by independent review of two cardiologists. Results 25.540 automatically recorded ECGs in 605 patients (68%) were analyzed. 1125 ECGs showed sustained ventricular arrhythmias in 117 patients, 65 ECGs showed non sustained VTs. 24.415 ECGs in 488 patients showed inadequate alarms Reasons for inadequate alarms were artefacts (97%), pacemaker or t-wave oversensing (0,3%) and in 2,3% atrial fibrillation or SVTs. 5860 manually recorded ECGs in 608 patients (68%) were analyzed. 298 (5%) of these ECGs showed following arrhythmias: atrial fibrillation (34,7%), SVTs (28%), sinustachycardia (10,7%), non sustained VTs (12%) and sustained VTs or sustained slow VTs (6,7%), premature ventricular beats or bradycardia was identified in 8%. The remaining 5562 ECGs (95%) showed normal sinus rhythm. Of the 895 patients (60±14 years, 20% female), 34 (3,8%) received a total of 65 automatically triggered shocks (median 2; range 1–5). 31/895 (3.5%) patients received 57 appropriate shocks (median 1, range 1–5) for 49 arrhythmic events, whereas 7/895 (0.8%) patients received 8 inappropriate shocks (median 1, range 1–2). 44 events were successfully terminated with the first shock (85,7%) and 4 events were terminated with the second shock. In one patient, a shock treatment for VF was not successful. The time from event onset to shock was median 60 [40; 1187] sec. The median time from WCD prescription to a shock event was 8 days [1–151]. 23/ 34 patients (68%) received their first WCD shock within 30 days. Seven patients (0.8%) received a total of nine inappropriate shocks due to different reasons: artefacts (2 inappropriate shocks), non-shockable rhythms (asystole, weak action, 3 shocks) and atrial fibrillation with a bundle branch block in two cases. In one patient VF terminated spontaneously before the WCD treatment was delivered. Conclusion The WCD is an effective treatment option in patients with a high SCD risk but it also triggers a significant amount of alarms. Although many inadequate alarms occurred, adequate alarms led to arrhythmia detection such as in VT/VF events which were successfully terminated by the WCD in 3,4% of patients.

Background: Under normoxic conditions, the predominant energy metabolism of healthy cardiac cells is based on beta-oxidation of free fatty acids.Under severe myocardial hypoxia, ischemic heart cells switch their energy gain from beta-oxidation to glucose metabolism to increase ATP production per oxygen molecule.This metabolic pathway appears as perfusion-metabolism mismatch in 18F-fluorodeoxyglucose (18F-FDG) PET images, as increased 18F-FDG uptake in underperfused hypoxic myocardial areas.The aim of our study was to evaluate simultaneous perfusion, metabolism and function of the ischemic heart by hybrid 18F-FDG-PET-cMRI with late enhancement images in a translation animal model of heart failure to 1) elaborate the underlying molecular mechanisms of perfusion-metabolism mismatch, and 2) evaluate the predictive value of 18F-FDG-PET-cMRI in development of ischemiatriggered left ventricular dysfunction.Methods: Closed-chest reperfused acute myocardial infarction (AMI) was induced in 36 domestic pigs by 90 min occlusion of the mid left anterior descending artery with a percutaneous intracoronary balloon, followed by reperfusion.Three days and 1 month after AMI, after 12 h fasting, 18F-FDG-PET-cMRI were performed by using standardized acquisition protocols (n = 30).Cardiac functional parameter, such as ejection fraction (EF), end-diastolic volume (EDV), infarct size, and mean tracer uptake of the infarcted area were quantitatively assessed.Six animals were euthanized after the 3-day 18F-FDG-PET-cMRI images to elaborate the differences in gene expression patterns in animals with perfusion-metabolic mismatch by using next generation sequencing (NGS) and pathway network analyses.Results: Eight (group Mismatch) of the 30 animals (group Match) with 1-month follow-up showed high 18F-FDG uptake in the infarcted area (perfusion-metabolism mismatch) at the 3-day 18F-FDG-PET-cMRI-LE images (Fig. 1).The animals in the Mismatch group had significantly lower EF at 3 days (34 ± 8.8 vs. 42 ± 3%) and at the 1-month follow-up (35.8 ± 6 vs. 43 ± 6.6%) and larger infarct size at day 3 (26.6 ± 6.6 vs. 22.1 ± 4.4%) and 1 month (28 ± 5.4 vs. 20.3 ± 4.3%) with higher EDV at 1 month.Mean tracer uptake of the infarcted area was significantly reduced in the Mismatch group at 1 month (56 ± 23.1 vs. 64.7 ± 13.2%), indicating enhanced severity and transmurality of the infarction.NGS revealed downregulation of the cholesterol metabolism pathway, and upregulation of carbohydrate derivative catabolism pathway with highly activated innate immune system and genes responsible for cytokine activation in the infarcted area 3 days post-AMI in the Mismatch group, which explains the paradox high 18F-FDG tracer uptake in the infarction zone.Accordingly, high energy demand of the severe hypoxic area led to "glucose steel phenomenon" at molecular level, subtracting the glucose (18F-FDG) from the normally perfused non-ischemic myocardial regions.Conclusions: Molecular glucose steel phenomenon leading to 18F-FDG perfusion-metabolism mismatch in the severe ischemic area early after AMI predict development of adverse remodeling of the heart.