Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): CATCH ME: Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly Background We recently demonstrated that in human atria, endomysial fibrosis causes conduction disturbances during atrial fibrillation (AF), while overall connective tissue content (over-all fibrosis) has no effect. Etiological and molecular determinants of endomysial fibrosis are largely unknown. Methods We quantified over-all and endomysial atrial fibrosis using staining with WGA in left (LA, n=95) and right (RA, n=76) atrial appendages sampled from a European cohort (CATCH ME) of patients undergoing cardiac surgery. The contributions of AF, heart failure (HF), sex, age, and 4 principal components accounting for confounding clinical characteristics to over-all and endomysial fibrosis were determined in a multivariate model. RNA sequencing was performed to explore biological pathways associated with the two types of fibrosis. Results Over-all and endomysial fibrosis were moderately correlated (LA: r=0.69, RA: 0.61, both p<0.001) and more pronounced in RA than in LA samples (p<0.001). In LA, persistent AF, female sex, and HF were independently associated with endomysial fibrosis, while over-all fibrosis was only associated with sex and HF. Likewise, in RA, persistent AF was associated with endomysial fibrosis, while over-all fibrosis was not. Expression of 18 genes was univariately associated with endomysial fibrosis in LA but only 1 in RA. There were no genes associated with over-all fibrosis. After correction for relevant clinical traits, BMP10 showed the strongest association with endomysial fibrosis amongst coding genes (p=3.16E-04, LA). In an independent validation cohort (RACE V Tissue Bank Project, n=162 pts undergoing cardiac surgery), out of 11 biomarkers reflecting inflammation, fibrosis, vascular dysfunction, or ischemia, BMP10 plasma levels were most strongly associated with endomysial fibrosis (p<0.001), but not with over-all fibrosis. Conclusions Taken together, female sex, HF, and AF are the main drivers of fibrosis in human atria. However, endomysial fibrosis is independently associated with AF whereas over-all fibrosis is not. BMP10 is a specific marker of endomysial fibrosis. Our findings suggest that distinct mechanisms are involved in the development of over-all versus endomysial fibrosis in human atria and may provide an explanation for the recently reported predictive value of BMP10 biomarkers levels for AF recurrences after AF ablation and for stroke.

Abstract Funding Acknowledgements Type of funding sources: Other. Main funding source(s): The DEVICE registries were financed by “Stiftung Institut für Herzinfarktforschung (IHF)”, with additional support by grants from Biotronik, Medtronic, and St. Jude Medical. Background Experimental data and early clinical trials suggested that amiodarone may alter the defibrillation threshold of ICD systems. However, because of its potent antiarrhythmic effect and lack of alternatives, amiodarone is frequently used for antiarrhythmic therapy in ICD or CRT-D patients, leading to the question of whether ICD testing with ventricular fibrillation induction should be repeated in these patients after starting amiodarone. Objective This study was designed to assess the impact of amiodarone therapy on the success of ventricular fibrillation induction tests in this "real life" cohort of ICD recipients of the German DEVICE registry. Methods 3,680 patients who underwent ICD implantation, revision, or upgrade in 49 centers participating in the German DEVICE Registry were enrolled 03/2007-02/2014. Results Intraoperative defibrillation testing was conducted in 2,705 patients receiving only beta-blockes as antiarrhythmic therapy and in 422 patients under betablocker plus amiodarone therapy. With regard to ineffective defibrillation tests, no difference could be described between the two groups (0.6% vs. 0.5%; p=0.77). In a similar fashion 488 patients receiving beta-blockers only and 65 patients under beta-blocker plus amiodarone therapy who were scheduled for postoperative defibrillation testing showed comparable rates of ineffective testing (14.5% vs. 15.4%; p=0.86). Conclusions Based on 3,127 intraoperative and 553 postoperative defibrillator testings, our study failed to show a significant association of amiodarone therapy and ineffective defibrillator testings in this "real life" cohort of ICD recipients of the German DEVICE registry. Our results thus underline that, apart from special situations such as right-sided implantation, HCM, extravenous ICD systems, etc., it might not be necessary to perform a DFT test after the start of an amiodarone therapy in ICD patients.

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): CATCH ME: Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly Background Atrial cardiomyopathy is emerging as independent prognostic factor in cardiovascular disease. Fibrotic remodeling, cardiomyocyte hypertrophy and a reduction in capillary density are histological hallmarks of atrial cardiomyopathy. The contribution of etiological factors to atrial cardiomyopathy has not been robustly quantified. Purpose To quantify the relation between histological features of atrial cardiomyopathy and the clinical profile of patients. Methods We examined left (LA, n=91) and right (RA, n=75) atrial appendages sampled from a European cohort of patients undergoing cardiac surgery. Quantification of histological cardiomyopathy features was performed a recently developed and validated imaging analysis algorithm following myocardial triple staining with wheat germ agglutinin (WGA), CD31 and vimentin. The contributions of AF, heart failure (HF), sex, age, and 4 principal components accounting for confounding clinical characteristics to over-all and endomysial fibrosis were determined in a multivariate model. K-means clustering of 6 atrial histological features was performed to identify different types of remodeling. Results LA samples showed less fibrosis (p<0.001), a higher capillary density (p<0.05), a smaller capillary size (p<0.05), and larger cardiomyocytes (p<0.01) than RA samples. In both LA and RA, persistent AF was associated with endomysial fibrosis, while over-all fibrosis was not. Men had larger cardiomyocytes (LAA), while women had a higher degree of endomysial fibrosis (LA). Heart failure patients had more endomysial and over-all fibrosis (LA), a higher capillary density (LA) and capillary size (LA/RA). Samples clustered into 2 distinct clusters. One cluster showed fibrotic cardiomyopathy, with more endomysial (p<0.001) and overall fibrosis (p<0.001), more fibroblasts (p<0,001) and a higher capillary density (p<0.001). The other cluster showed hypertrophic cardiomyopathy, with hypertrophic cardiomyocytes (p<0.001). Patients with fibrotic cardiomyopathy were more often female (LA and RA, p<0.003) and had more often persistent AF (LA, p=0.031) or heart failure (LA, p<0.001). Patients with hypertrophic cardiomyopathy were more often male (LA and RA, p<0.003). Conclusions Fibrotic cardiomyopathy is associated with female sex, persistent AF and heart failure while hypertrophic cardiomyopathy more often occurs in men. More research is needed to establish whether treatment of AF and heart failure prevents the development of atrial cardiomyopathy.

Abstract Background Because of its antiarrhythmic potency and due to the lack of alternatives, amiodarone is often used for antiarrhythmic therapy in patients with ICD or CRT-D systems. To date, robust data on the safety and clinical benefit of amiodarone therapy in these patients are missing. Objective This study was designed to assess the periprocedural and post-procedural outcome of combined therapy with beta-blockers plus amiodarone compared to treatment with single beta-blockers in this "real life" cohort of ICD recipients of the German DEVICE registry. Methods 4,499 patients who underwent ICD implantation, revision, or upgrade in 49 centers participating in the German DEVICE Registry were enrolled 03/2007-02/2014. Patients' characteristics, procedural data, periprocedural complications, and post-procedural clinical outcome, were analyzed. Results 12.7 % (572 patients) received amiodarone in addition to beta-blocker therapy. These patients were slightly older and more frequently male than the 3,927 patients with sole betablocker therapy. The two cohorts of patients had no relevant differences in terms of underlying cardiomyopathy. Stroke, and chronic kidney disease were more often present in the patient group receiving amiodarone. Early implantation-associated complications were similar between the groups. One-year overall mortality was, however, significantly higher in the beta-blocker plus amiodarone cohort (adjusted HR 2.09; p<0.001). This was particularly pronounced in the subgroups of patients with sinus rhythm or severely reduced left ventricular function. Interestingly, amongst the surviving patients, amiodarone was not associated with a significantly reduced risk of ICD discharges, syncopal events. Further, the occurrence of VT storm or incessant VTs and the number of patients scheduled for intracardiac ablation did not differ among both groups while the rate of rehospitalization was lower in the cohort with sole beta-blockers. Conclusions Taken together, these retrospective "real-word" data suggest an increased all-cause mortality under amiodarone therapy, particularly in the subgroups of patients with sinus rhythm or severely reduced left ventricular function. In surviving patients, rates of arrhythmic events were comparable.Abstract Figure

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): European Union Horizon 2020 CATCH ME; Cardiovascular Research Netherlands RACE V Background Little is known about changes in the atrial transcriptome associated with paroxysmal and persistent atrial fibrillation (AF). Purpose To identify major molecular mechanisms in AF, we determined consistent differential expression (DE) between atrial tissue samples from well-characterized patients with paroxysmal or persistent AF and patients without a history of AF (no AF) in two independent patient cohorts. Methods Poly-A tailed RNA from left and right atrial appendage tissue samples from independent discovery and replication cohorts CATCH ME (n=192) and RACE V (n=122) was sequenced and analyzed according to patient AF history. Analyses were performed stratified by atrial side, adjusting for age, sex, heart failure and a combination of clinical characteristics determined by principal component analysis. Transcripts were considered DE in CATCH ME if their fold change reached transcriptome-wide significance (false discovery rate (FDR) < 0.05). DE transcripts in each rhythm comparison were replicated in RACE V if we observed a concordant direction of effect and a within-set FDR < 0.05 in the same comparison. Results Persistent AF compared to no AF was associated with 184 left atrial DE transcripts in CATCH ME of which 85 (46%) were replicated in RACE V, and with 208 right atrial DE transcripts in CATCH ME of which 86 (41%) were replicated in RACE V. Overall, 26 transcripts were discovered and replicated in both atria. Discovered but non-replicated transcripts often did exhibit concordant direction of effect (left: 78%, right: 83%). Replicated transcripts consisted of protein coding genes, antisense and non-coding RNAs. Protein coding genes showed involvement in pathways linking persistent AF to cardiomyocyte structure, conduction properties, fibrosis, inflammation, molecule trafficking, and endothelial dysfunction. Interestingly, paroxysmal AF was not consistently associated with DE transcripts in any comparison. Principal component analysis of the expression of the 26 transcripts strongly associated with persistent AF did however reveal a distinct paroxysmal AF expression profile in-between no AF and persistent AF patients in the first principal component scores (Figure 1). Conclusion RNA sequencing of human atrial tissue samples identified many transcripts associated with persistent AF in left and/or right atria, discovered and replicated using two independent cohorts. These consistent findings of AF-induced changes provide a starting point for targeted proteomic analysis and single-nucleus sequencing to further unravel the molecular mechanisms underlying AF progression to persistent AF, and biomarker development to quantify AF progression and enable precision medicine in individual patients.

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): TRAIN-HEART Innovative Training Network, funded by the European Union’s Horizon 2020 research and innovation program (under the Marie Sklodowska-Curie grant agreement no. 813716) Characterizing Atrial fibrillation by Translating its Causes into Health Modifiers in the Elderly (CATCH ME), funded by the European Union’s Horizon 2020 research and innovation program (under the grant agreement no. 633196) Background Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with heart failure (HF) and stroke. Clinical and experimental data from previous studies suggest gender differences in mechanisms and phenotypes of AF: women may have more atrial fibrosis, worse outcomes after catheter ablation, and some women carry a higher risk for thromboembolic complications than men. The molecular mechanisms underlying these differences are still poorly understood. Methods Gender-based transcriptional patterns were assessed using paired-end, directional RNA sequencing data generated from atrial tissue biopsies in 199 patients either in sinus rhythm or with paroxysmal or persistent AF as part of the CATCH-ME project. Transcript counts were compared between genders separately in the left and right atria using the DESeq2 package in R. The models were adjusted for potential sources of confounding (age, atrial fibrillation status, heart failure status and sequencing batch). Interaction models were implemented using DESeq2 to compare gender*morbidity interactions for persistent AF and HF. Significance was assessed using likelihood ratio tests comparing models with and without the interaction terms. Results with an adjusted P-value 0.05 were considered significant and utilized for subsequent downstream assessments. Differentially expressed (DE) genes were tested for enrichment of gene ontology (GO) terms and KEGG pathways using the WebGestalt toolkit. Results Transcriptome-wide profiling across the cohort identified 33 sex-differentiated genes in the left atria and 51 in the right atrial samples, with 21 of these showing bilateral differences. Interestingly, 36 (44%) of the results from these analyses were comprised of non-coding transcripts, including long non-coding RNAs (lncRNAs), antisense RNAs and pseudogenes. GO and pathway enrichment analyses for these genes revealed their involvement in critical pathways such as the complement and coagulation cascades and RNA transport. Interaction analyses between gender and AF identified two genes (MPP2 & GNAS-AS1) that were differentially transcribed in the right atria and one gene (MYL2) that was DE in the left atria by gender in persistent AF samples. A similar analysis comparing gender*HF morbidity also revealed evidence of DE. Four transcripts (HLA-DQB1-AS1, EIF1AY, UTY and ZFY-AS1) showed gender-specific differences in expression by HF status in left atria, while HLA-DQB1-AS1 was differentially regulated by gender and HF status in right atrial samples. Conclusions These RNA-seq analyses provide novel insights into gender-related differences in the transcriptional landscape of right and left adult human atrial appendages. Moreover, interaction analyses identified three genes DE in female atria in persistent AF and four DE genes in female atria in heart failure, providing a molecular anchor for the observed differences in atrial diseases phenotypes between men and women.

Abstract Background Atrial Fibrillation (AF) is common and is caused and predisposed to by a complex pathophysiology. Aging is among the most important risk factors for AF. Yet, some individuals develop AF in early years, whereas elderly individuals may remain free of AF. Aside from measurable concomitant risks, we hypothesized that a pathophysiologically relevant biological age exists, which outweighs a patient's calendar age. Telomere length is a measurable marker of age, which might reflect biological age. AF and telomere length have previously been associated, but results remained controversial. Here, we tested the relation between AF and telomere length in a well-characterized and so far largest cohort. Methods Since 2005, we enrolled 2475 patients with AF from the prospective AFLMU cohort, preferentially if they developed AF before age 65 years, and 3077 control individuals free of AF from the community-based KORA Study between 2006–08. All participants received a detailed clinical characterization, an electrocardiogram, and a blood draw for biomarker analyses. In all participants, we determined telomere length using a qPCR-based method. In a 384 well format, we employed a multiplex TaqMan assay to determine both telomere length and the single copy gene 36B4. Telomere length was expressed by the delta-CT method and was reformatted to have lower CT values indicate shorter telomere length. We compared telomere length between cases and controls using multi-variably corrected logistic regression models. Results Our cohort's mean age was 58 years in AFLMU and 56 years in KORA F4. Men were enrolled more commonly, with 72.3% in AFLMU and 51.7% in KORA F4. For consistency with available information, we confirmed that telomere length is continuously decreasing with age and that men have shorter telomere length compared to women. As a main result we found that AF patients have significantly shorter telomere length compared to controls (controls: telomere length 13,10 [12.60, 13.63] versus AF: 9.81 [5.98, 13.1], p<0,001). This relation remained significant following multi-variable adjustment for sex, body mass index, hypertension, and diabetes. The odds ratio per unit longer telomer length was 0.77 [95% confidence interval 0.74–0.77], p<0.001. We also calculated a propensity-score matched model of cases with and without AF confirming our main results (controls: telomere length 13.21 [11.65, 13.67] versus AF: 9.03 [5.35, 12.54], p<0.001). The multi-variable adjusted model revealed an odds ratio of 0,75 [95% confidence interval 0.73–0.76], p<0.001. Conclusion AF is significantly associated with telomere length in one of the largest cohorts to date. Assessment of telomere length may adjudicate patients with AF due to premature biological aging. The underlying reasons for such premature aging remain to be identified. Funding Acknowledgement Type of funding source: Public grant(s) – EU funding. Main funding source(s): European Commission - Horizon 2020

Pulmonary vein isolation (PVI) as interventional treatment for atrial fibrillation (AF) aims to eliminate arrhythmogenic triggers from the PVs. Improved signal detection facilitating a more robust electrical isolation might be associated with a better outcome. This retrospective cohort study compared PVI procedures using a novel high-density mapping system (HDM) with improved signal detection vs. age- and sex-matched PVIs using a conventional 3D mapping system (COM). Endpoints comprised freedom from AF and procedural parameters. In total, 108 patients (mean age 63.9 ± 11.2 years, 56.5% male, 50.9% paroxysmal AF) were included (n = 54 patients/group). Our analysis revealed that HDM was not superior regarding freedom from AF (mean follow-up of 494.7 ± 26.2 days), with one- and two-year AF recurrence rates of 38.9%/46.5% (HDM) and 38.9%/42.2% (COM), respectively. HDM was associated with reduction in fluoroscopy times (18.8 ± 10.6 vs. 29.8 ± 13.4 min; p < 0.01) and total radiation dose (866.0 ± 1003.3 vs. 1731.2 ± 1978.4 cGy; p < 0.01) compared to the COM group. HDM was equivalent but not superior to COM with respect to clinical outcome after PVI and resulted in reduced fluoroscopy time and radiation exposure. These results suggest that HDM-guided PVI is effective and safe for AF ablation. Potential benefits in comparison to conventional mapping systems, e.g. arrhythmia recurrence rates, have to be addressed in randomized trials.

Atrial fibrillation (AF) can be challenging to diagnose due to asymptomatic and paroxysmal presentation. Identifying prognostic factors of AF would elucidate potential mechanisms causing AF and refine screening for at risk patients. To identify the main predictors of AF and to develop a prognostic model for prevalent AF. Data of 120 potential predictors were harmonised in individual patient data from 4 independent European studies. A three stage Delphi expert consensus process identified predictors based on clinical knowledge. The predictors were further reduced using statistical selection (backward elimination), and a logistic regression model was fitted. We calculated odds ratios (OR) for each of the selected predictors and evaluated model performance using the C-statistic. Overall, 2420 patients (mean [standard deviation] age = 62.7 [14.5] years, 35.6% female, 43.1% with AF) were included in the analysis. Thirty-one potential predictors identified from the Delphi process which had sufficient data across all datasets were modelled. Of these 14 were deemed prognostic in predicting AF (age, sex, BMI, height, hypertension, diabetes, history of coronary artery disease, left atrial volume, left ventricular end systolic diameter, abnormality on echo, tricuspid valve disease of at least moderate intensity, aldosterone-antagonists, beta-blockers and P2Y12 blockers; see Figure 1). There was a clear interaction between age and sex indicating that males are at higher risk than females early in life, while females are at increased risk of AF at older age (Figure 1). The risk prediction model combining these prognostic factors performed well (C-statistic 0.79; 95% CI 0.77–0.81). Figure 1. (a) Forest plot; (b) Interaction Our preliminary analysis identified important prognostic factors and a complex relationship between age and sex, which predicts prevalent AF, highlighting the different potential causes of AF in different patients. There is a clear need to validate these factors in external datasets and for further investigation into the molecular mechanism underlying these factors. European Commission H2020 framework

BACKGROUND We hypothesized that fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) would be superior to medical therapy as initial treatment in patients with stable coronary artery disease. METHODS Among 1220 patients with angiographically significant stenoses, those in whom at least one stenosis was hemodynamically significant (FFR, <= 0.80) were randomly assigned to FFR-guided PCI plus medical therapy or to medical therapy alone. Patients in whom all stenoses had an FFR of more than 0.80 received medical therapy and were entered into a registry. The primary end point was a composite of death, myocardial infarction, or urgent revascularization. RESULTS A total of 888 patients underwent randomization (447 patients in the PCI group and 441 in the medical-therapy group). At 5 years, the rate of the primary end point was lower in the PCI group than in the medical-therapy group (13.9% vs. 27.0%; hazard ratio, 0.46; 95% confidence interval (CIS, 0.34 to 0.63; P<0.001). The difference was driven by urgent revascularizations, which occurred in 6.3% of the patients in the PCI group as compared with 21.1% of those in the medical-therapy group (hazard ratio, 0.27; 95% CI, 0.18 to 0.41). There were no significant differences between the PCI group and the medical-therapy group in the rates of death (5.1% and 5.2%, respectively; hazard ratio, 0.98; 95% CI, 0.55 to 1.75) or myocardial infarction (8.1% and 12.0%; hazard ratio, 0.66; 95% CI, 0.43 to 1.00). There was no significant difference in the rate of the primary end point between the PCI group and the registry cohort (13.9% and 15.7%, respectively; hazard ratio, 0.88; 95% CI, 0.55 to 1.39). Relief from angina was more pronounced after PCI than after medical therapy. CONCLUSIONS In patients with stable coronary artery disease, an initial FFR-guided PCI strategy was associated with a significantly lower rate of the primary composite end point of death, myocardial infarction, or urgent revascularization at 5 years than medical therapy alone. Patients without hemodynamically significant stenoses had a favorable long-term outcome with medical therapy alone.

S ACCEPTED FOR POSTER PRESENTATIONS ECAS 2018 16-1 Abstract 24-16 LEFT VENTRICULAR MASS PREDICTS RESPONSE TO CARDIAC RESYNCHRONIZATION THERAPY IN MEN BUT NOT WOMEN Chad Ward , Hakeem Ayinde , Casey Adams , Oluwaseun Adeola , Josiah Zubairu , Musab Alqasrawi , Christopher Dezorzi , Ghanshyam Palamaner Subash Shantha , James Hopson , Gardar Sigurdsson , Michael Giudici 1 1 University of Iowa, Iowa City, United States 16-2 Abstract 05-14 A RANDOMISED CONTROLLED TRIAL ANALYSING NOVEL ECMS IN AF MONITORING: THE REMAP-AF TRIAL William Eysenck , Nick Freemantle , Oliver Waller , Rick Veasey , Stephen Furniss , Neil Sulke 1 1 Cardiology Research Department, Eastbourne General Hospital, East Sussex, United Kingdom, 2 Clinical Trials Unit, University College, London, United Kingdom 16-3 Abstract 05-11 THE USE OF A NOVEL SOFTWARE-BASED DATA MANAGEMENT SYSTEM TO STREAMLINE REMOTE MONITORING WORKFLOW IN THE EVALUATION OF IMPLANTABLE LOOP RECORDERS (ILR) Kevin Campbell , Jason Hale , Noemi Ray 1 1 PaceMate, Raleigh, United States 16-4 Abstract 06-13 THE UTILITY AND EFFECTIVENESS OF AUTOMATED REMOTE MONITORING OF DEVICES AFTER HOURS (WEEKENDS AND HOLIDAYS) Kevin Campbell 1 1 PaceMate, Raleigh, United States 16-5 Abstract 22-12 FLUOROSCOPY TIMES IN ELECTROPHYSIOLOGY AND DEVICE PROCEDURES: IMPACT OF SINGLE FRAME LOCATION FLUOROSCOPY Vinit Sawhney , Holly Daw , Sarah Whittaker-Axon , Colin Allan , Pier Lambiase , Martin Lowe , Mark Earley , Simon Sporton , Ross Hunter , Richard Schilling , Mehul Dhinoja 1 1 Barts Heart Centre, London, United Kingdom 16-6 Abstract 05-10 ALTERING INTER-ELECTRODE DISTANCE, BUT NOT ORIENTATION, AFFECTS BIPOLAR ELECTROGRAM MORPHOLOGY Vignesh Dhileepan , Konstantinos N Tzortzis , Ian Mann , Norman A Qureshi , Elaine Lim , Prapa Kanagaratnam , André R Simon , Chris D Cantwell , Nicholas S Peters , Rasheda A Chowdhury 1 1 National Heart and Lung Institute, Imperial College London, London, United Kingdom, 2 Imperial College Healthcare NHS Trust, London, United Kingdom, 3 Royal Brompton & Harefield NHS Foundation Trust, London, United Kingdom

Background: Long QT syndrome (LQTS) is associated with potentially fatal arrhythmias. Treatment is very effective, but its diagnosis may be challenging. Importantly, different methods are used to assess the QT interval, which makes its recognition difficult. QT experts advocate manual measurements with the tangent or threshold method. However, differences between these methods and their performance in LQTS diagnosis have not been established. We aimed to assess similarities and differences between these 2 methods for QT interval analysis to aid in accurate QT assessment for LQTS. Methods: Patients with a confirmed pathogenic variant in KCNQ1(LQT1), KCNH2(LQT2), or SCN5A(LQT3) genes and their family members were included. Genotype-positive patients were identified as LQTS cases and genotype-negative family members as controls. ECGs were analyzed with both methods, providing inter- and intrareader validity and diagnostic accuracy. Cutoff values based on control population’s 95th and 99th percentiles, and LQTS-patients’ 1st and 5th percentiles were established based on the method to correct for heart rate, age, and sex. Results: We included 1484 individuals from 265 families, aged 33±21 years and 55% females. In the total cohort, QTTangent was 10.4 ms shorter compared with QTThreshold (95% limits of agreement±20.5 ms, P<0.0001). For all genotypes, QTTangent was shorter than QTThreshold (P<0.0001), but this was less pronounced in LQT2. Both methods yielded a high inter- and intrareader validity (intraclass correlation coefficient >0.96), and a high diagnostic accuracy (area under the curve >0.84). Using the current guideline cutoff (QTc interval 480 ms), both methods had similar specificity but yielded a different sensitivity. QTc interval cutoff values of QTTangent were lower compared with QTThreshold and different depending on the correction for heart rate, age, and sex. Conclusion: The QT interval varies depending on the method used for its assessment, yet both methods have a high validity and can both be used in diagnosing LQTS. However, for diagnostic purposes current guideline cutoff values yield different results for these 2 methods and could result in inappropriate reassurance or treatment. Adjusted cutoff values are therefore specified for method, correction formula, age, and sex. In addition, a freely accessible online probability calculator for LQTS (www.QTcalculator.org) has been made available as an aid in the interpretation of the QT interval.

Patients with frequent premature ventricular contractions (PVCs) are often highly symptomatic with significantly reduced quality-of-life. We evaluated the outcome and success of PVC ablation in patients in the German Ablation Registry.

Background: Long QT syndrome (LQTS) is associated with malignant arrhythmias and sudden death at young age.Diagnosis is primarily based on prolongation of the QT interval on the electrocardiogram (ECG).However, different methods are used to measure the QT interval.The effect of this practice on diagnosing LQTS is unknown and could result in inappropriate reassurance or treatment.Purpose: To assess possible differences between different methods of QT interval measurements in distinguishing LQTS patients from controls.Methods: Confirmed carriers of a pathogenic mutation in the KCNQ1 (LQTS1), KCNH2 (LQTS2) and SCN5A (LQTS3) genes were included as cases and their genotype-negative family members as controls.Three complexes on the baseline ECG were first marked and then analyzed applying both the tangent (QT-tangent) and threshold method (QT-threshold) in two separate sessions.Measurements were done blinded for subject characteristics.The measured complexes were averaged and corrected for HR with the Bazett formula (QTc).ECGs with a ventricular paced rhythm, complete bundle branch block and atrial-/ventricular arrhythmias were excluded.Sensitivity and specificity were determined for arbitrary cut-offs of 450 milliseconds (ms) in males and 460 ms in females, and for optimal cut-off values based on receiver-operating characteristic analyses.Results: We included 1363 individuals (294 LQTS1, 357 LQTS2, 131 LQTS3 and 581 controls); aged 34 years (standard deviation 21 years); 55% female, median HR 70 (interquartiles 61-83) beats per minute.Compared to controls, LQTS patients were younger (29 years versus 40 years, p<0.001), and more likely to be female (58% versus 52%, p=0.04).There was no difference in HR between the two groups (p=0.40).In LQTS1, LQTS3 and controls, measurements by QTtangent were significantly shorter compared to QT-threshold (absolute difference 7-12ms, p<0.0001).The table summarizes the performance of cut-off values using different methods. Conclusion:The length of the QT interval is different depending on the method used for determination.Particularly, the number of false positives is influenced by the method chosen to distinguish LQTS patients from controls, possibly resulting in inappropriate therapy in these patients.

The rising number of implantable devices has led to an increase in device-related workload, e.g., regular interrogation follow-up visits. Telemonitoring systems for implantable cardioverter-defibrillators (ICDs) seem to be a promising tool for reducing workload and costs, and they have the potential of optimizing patient care. However, issues such as practical functionality of ICD telemonitoring in daily routine may affect its broad implementation. The objective of this study was to evaluate potential problems during the implementation of a telemonitoring system, Medtronic CareLink™ (CL™) with respect to the installation and data transmission process. A total of 159 patients with ICDs who were equipped with the CL™ system were evaluated and followed up for 16 months regarding the success rate of the first data transmission via the telemonitoring system. In this cohort, a high rate of nontransmission of 23.9 % was observed after the 16-month follow-up. A detailed interview of these patients (no transmission) revealed that the main reasons for failed transmissions were due to the patients' loss of interest in the concept (approximately 50 %) as well as technical problems (approximately 25 %) with setting up the system. These results indicate that telemonitoring systems bear potential problems and that the evaluation of patient motivation and technical support options seems to play an important role in establishing the functionality of these systems.