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Introduction This study sought to examine gender differences in patients with structural heart disease (SHD) referred for ablation of ventricular tachycardia (VT). Background Female patients are often underrepresented in large studies. Significant differences in the clinical presentation, treatment, and prognosis of female patients have been described in previous studies. Methods and results We investigated 88 female patients with SHD undergoing VT ablation (mean age 59 years, 56% nonischemic cardiomyopathy, mean left ventricular ejection fraction 35%, 82% in electrical storm). A case-control study with 88 male patients was performed and the results regarding clinical and procedural characteristics, acute and long-term results of the two groups were compared. The female patients had more arrhythmogenic substrate, as they more commonly presented with electrical storm (p = .016) and had a higher number of inducible VT morphologies during the procedure (p = .018). Moreover, the female patients were less likely to have an optimized heart failure medical treatment at baseline (p = .030) and required more time from the first manifestation of the VT to ablation referral (p = .034). Although fewer epicardial ablations were performed in female patients (p = .019), the two groups showed similar results regarding VT noninducibility as ablation endpoint (p = .844), major procedure-related complications (p = .719) and freedom from VT during follow-up (p = .268). Moreover, the overall mortality in the two groups was similar (p = .176). Advanced NYHA class was associated with worse transplant and assist-device-free survival in the female group. Conclusion Female patients presenting for VT ablation had more arrhythmogenic substrate and were less likely to have an optimized heart failure medical treatment. Nevertheless, the procedural acute and long-term outcomes between the two genders were similar.

Aims Several reports indicate lower rates of emergency admissions in the cardiovascular sector and reduced admissions of patients with chronic diseases during the Coronavirus SARS-CoV-2 (COVID-19) pandemic. The aim of this study was therefore to evaluate numbers of admissions in incident and prevalent atrial fibrillation and flutter (AF) and to analyse care pathways in comparison to 2019.Methods A retrospective analysis of claims data of 74 German Helios hospitals was performed to identify consecutive patients hospitalized with a main discharge diagnosis of AF. A study period including the start of the German national protection phase (13 March 2020 to 16 July 2020) was compared to a previous year control cohort (15 March 2019 to 18 July 2019), with further sub-division into early and late phase. Incidence rate ratios (IRRs) were calculated. Numbers of admission per day (A/day) for incident and prevalent AF and care pathways including readmissions, numbers of transesophageal echocardiogram (TEE), electrical cardioversion (CV), and catheter ablation (CA) were analysed.Results During the COVID-19 pandemic, there was a significant decrease in total AF admissions both in the early (44.4 vs. 77.5 A/day, IRR 0.57 [95% confidence interval (CI) 0.54–0.61], P Conclusion During the COVID-19 pandemic, AF admission rates declined significantly, with a more pronounced reduction in incident than in prevalent AF. Overall AF care was maintained during early and late pandemic phases with only minor changes, namely less frequent use of TEE. Confirmation of these findings in other study populations and identification of underlying causes are required to ensure optimal therapy in patients with AF during the COVID-19 pandemic.

ObjectiveAtrial fibrillation or atrial flutter (AF) and heart failure (HF) often go hand in hand and, in combination, lead to an increased risk of death compared with patients with just one of both entities. Sex-specific differences in patients with AF and HF are under-reported. Therefore, the aim of this study was to investigate sex-specific catheter ablation (CA) use and acute in-hospital outcomes in patients with AF and concomitant HF in a retrospective cohort study.MethodsUsing International Statistical Classification of Diseases and Related Health Problems and Operations and Procedures codes, administrative data of 75 hospitals from 2010 to 2018 were analysed to identify cases with AF and HF. Sex differences were compared for baseline characteristics, right and left atrial CA use, procedure-related adverse outcomes and in-hospital mortality.ResultsOf 54 645 analysed cases with AF and HF, 46.2% were women. Women were significantly older (75.4±9.5 vs 68.7±11.1 years, pConclusionsThere are sex differences in patients with AF and HF with respect to demographics, resource utilisation and in-hospital outcomes. This needs to be considered when treating women with AF and HF, especially for a sufficient patient informed decision making in clinical practice.

BackgroundAfter the first Covid-19 infection wave, a constant increase of pulmonary embolism (PE) hospitalizations not linked with active PCR-confirmed Covid-19 has been observed but potential contributors to this observation are unclear. Therefore, we analyzed associations between changes in PE hospitalizations and (1) the incidence of non-Covid-19 pneumonia, (2) the use of computed tomography pulmonary angiography (CTPA), (3) volume depletion and (4) preceding Covid-19 infection numbers in Germany.MethodsClaims data of Helios hospitals in Germany were used and consecutive cases with a hospital admission between May 6 and December 15, 2020 (PE surplus period) were analyzed and compared to corresponding periods covering the same weeks in 2016–2019 (control period). We analyzed the number of PE cases in the target period with multivariable Poisson general linear mixed models (GLMM) including (a) cohorts of 2020 versus 2016– 2019, (b) the number of cases with pneumonia, (c) CTPA, and (d) volume depletion and adjusted for age and sex. In order to associate the daily number of PE cases in 2020 with the number of preceding SARS-CoV-2 infections in Germany, we calculated the average number of daily infections (divided by 10,000) occurring 14 up to 90 days with increasing window sizes before PE cases and modelled the data with Poisson regression.ResultsThere were 2,404 PE hospitalizations between May 6 and December 15, 2020 as opposed to 2,112 – 2,236 (total 8,717) in the corresponding 2016 – 2019 control periods. (crude rate ratio [CRR] 1.10, 95% CI 1.05 – 1.15, PPPPPConclusionsThere is an increase in PE cases since early May 2020 compared to corresponding periods in 2016 – 2019. This surplus was significant even when controlling for changes in potential modulators such as demographics, volume depletion, non-Covid-19 pneumonia, CTPA use and preceding Covid-19 infections. Future studies are needed (1) to investigate a potential causal link for increased risk of delayed PE with preceding SARS-CoV-2 infection, and (2) to define optimal screening for SARS-CoV-2 in patients presenting with pneumonia and PE.

Anticoagulation in patients with atrial fibrillation (AF) should be guided by considerations of the risk of thromboembolism, stroke, and bleeding as well as the patient's preference. Well-recognized scores have been developed to help the clinician in daily risk assessment, but there are several special patient populations for whom scores are not developed or validated. Furthermore, these patients were not adequately represented in the pivotal randomized trials for non-vitamin K antagonist oral anticoagulants (NOACs). In patients with cancer, the intrinsic hypercoagulable state has to be balanced against an increased risk of bleeding, and a dynamic concept should be applied, taking into account the cancer type, current disease state, therapeutic strategy, and patient-related factors, with NOACs playing an increasingly larger role. In women with planned pregnancy or already pregnant, NOACs should be avoided. However, accidental exposure during pregnancy should not lead to recommendations for pregnancy termination in view of current observational data. Whether patients on dialysis with AF benefit from anticoagulation at all is questionable. But if the decision for anticoagulation is made, NOACs may contribute to a more favorable risk-benefit profile than vitamin- K antagonists. Finally, patients on the ward deserve special considerations regarding periprocedural management of anticoagulation. Although for the majority of procedures a short discontinuation of oral anticoagulation seems appropriate, there are some low-bleeding-risk procedures that do not require cessation. The aim of the present review is to discuss the major particularities of these four patient subgroups and thus to facilitate the clinical decision-making.Die Entscheidung zur Antikoagulation in Patienten mit Vorhofflimmern (VHF) sollte von Überlegungen zum Risiko für Thrombembolien, Schlaganfall und Blutungen sowie den Vorlieben des Patienten geprägt sein. Im klinischen Alltag helfen Scores bei der Einschätzung dieser Fragestellung weiter, für einige spezielle Patientenkohorten ist jedoch kein Score entwickelt und validiert worden. Zudem wurden diese Patienten auch nicht adäquat in den großen randomisierten Studien zur Zulassung von nicht-Vitamin-K-abhängigen oralen Antikoagulanzien (NOAC) berücksichtigt. Bei Krebspatienten muss der spezielle hyperkoagulable Status vor dem Hintergrund eines ebenfalls erhöhten Blutungsrisikos bewertet werden. Entscheidend sind neben der Art der Krebserkrankung auch die aktuelle Krankheitsphase, die therapeutische Strategie und patientenbedingte Faktoren, wobei im dadurch notwendigen dynamischen Konzept der Antikoagulation NOAC eine zunehmende Rolle spielen. Bei Frauen mit geplanter oder bereits eingetretener Schwangerschaft sollten keine NOAC angewendet werden. Dennoch zeigen die wenigen vorhandenen Beobachtungsdaten, dass bei akzidenteller Exposition nicht zum Abbruch geraten werden muss. Ob Dialysepatienten überhaupt von einer Antikoagulation profitieren, ist fraglich. Falls aber der Entschluss zu einer oralen Antikoagulation gefällt wird, scheinen NOAC ein besseres Risiko-Nutzen-Profil als die Vitamin-K-Antagonisten mit sich zu bringen. Schließlich verlangt der stationäre Patient besonderes Augenmerk: Obwohl für die meisten Prozeduren eine kurze Unterbrechung der oralen Antikoagulation die beste Lösung darstellt, gibt es Interventionen mit niedrigem Blutungsrisiko, bei welchen die Antikoagulation auch ohne Unterbrechung sicher fortgesetzt werden kann. Das Ziel dieses Übersichtsartikels ist es, auf die Besonderheiten dieser 4 Patientengruppen einzugehen und so die Entscheidung im Alltag zu erleichtern.

BackgroundThere is discussion evolving around the emergence of different phenotypes of Covid-19-associated thromboembolic disease, i.e. acute pulmonary embolism vs pulmonary thrombosis and different phenotypes of in situ thrombosis. With this study, we wish to provide hospitalization, treatment and in-hospital outcome data for pulmonary embolism during the 2020 Covid-19 pandemic and a corresponding 2016 – 2019 control period.MethodsWe performed a retrospective analysis of claims data of Helios hospitals in Germany. Consecutive cases with a hospital admission between January 1 and December 15, 2020 and pulmonary embolism as primary discharge diagnosis were analyzed and compared to a corresponding period covering the same weeks in 2016 – 2019.ResultsAs previously reported for other emergent medical conditions, there was a hospitalization deficit coinciding with the 1st pandemic wave. Beginning with the 12-week interval May 6 – July 28, there was a stable surplus of hospital admissions in 2020. During this surplus period (May 6 – December 15, 2020), there were 2,449 hospitalizations including 45 PCR-confirmed Covid-19 cases (1.8%) as opposed to 8,717 in 2016 – 2019 (IRR 1.12, 95% CI 1.07 – 1.18, PPP=0.28), the presence of thrombosis (46.1 vs 45.4%, P=0.55) and surgery (3.8 vs. 4.3%, P=0.33) were comparable, coagulopathy (3.3 vs 4.5%, P=0.01) and metastatic cancer (3.0 vs 4.0%, P=0.03) as contributing factors were less frequently observed during the 2020 surplus. Interventional treatments (thrombolytic therapy, thrombectomy or inferior vena cava filter placement) were less frequently used (4.7 vs 6.6%, OR 0.72, 95% CI 0.58 − 0.89, P< 0.01). Similarly, intensive care (35.1 vs 38.8%, OR 0.83, 95% CI 0.75 − 0.92, P< 0.01) and mechanical ventilation utilization (7.2 vs 8.1%, OR 0.88, 95% CI 0.74 – 1.04, P=0.14) as well as in-hospital-mortality rates (7.8 vs 9.8%, OR 0.76, 95% CI 0.64 − 0.90, P< 0.01) were lower in 2020 compared with 2016 – 2019. This was associated with a shorter length of hospital stay (6.4 ±5.4 vs. 7.2 ±5.7 days, P< 0.01) during the 2020 surplus period.ConclusionsOnly a minority of cases were associated with PCR-confirmed Covid-19 but this does not rule out preceding or undetected SARS-CoV-2 infection. Although there is a shift towards milder disease course, the increased incidence of hospitalizations for pulmonary embolism requires immediate attention, close surveillance and further studies.

BackgroundWhile there are numerous reports that describe emergency care during the early Covid-19 pandemic, there is scarcity of data for later stages. This study analyzes hospitalization rates for 37 emergency-sensitive conditions in the largest German-wide hospital network during different pandemic phases.MethodsUsing claims data of 80 hospitals, consecutive cases between January 1 and November 17, 2020 were analyzed and compared to a corresponding period in 2019. Incidence-rate ratios (IRR) comparing the both periods were calculated using Poisson regression to model the number of hospitalizations per day.ResultsThere was a hospitalization deficit between March 12 and June 13, 2020 (coinciding with the 1st pandemic wave) with 32,807 hospitalizations as opposed to 39,379 in 2019 (IRR 0.83, 95% CI 0.82 – 0.85, Pnd wave), hospitalizations were reduced from 63,799 in 2019 to 59,910 in 2020, but this reduction was not that pronounced (IRR 0.94, 95% CI 0.93 – 0.95, Pst wave during which hospitalizations had been reduced for those conditions. In contrast, hospitalizations for sepsis, pneumonia, obstructive pulmonary disease, and intracranial injuries were reduced during the entire pandemic.ConclusionsThere was an overall reduction of hospitalizations for emergency-sensitive conditions in Germany during the Covid-19 pandemic with heterogeneous effects on different disease categories. The increase of hospitalizations for acute myocardial infarction, aortic aneurism/dissection and pulmonary embolism is an alarming signal that requires attention and further studies.KEY MESSAGESWhat is already known on this subjectThere has been a reduction in emergency room visits and hospital admissions for several emergent medical and surgical conditions during the early Covid-19 pandemic (1st wave).What this study addsUsing claims data of 80 German-wide Helios hospitals, we found an overall reduction of hospitalizations for emergency-sensitive conditions in Germany during the Covid-19 pandemic until mid November 2020 with heterogeneous effects on different disease categories. While hospitalizations for sepsis, pneumonia, obstructive pulmonary disease, and intracranial injuries were reduced during the entire pandemic. There was an alarming increase of hospitalizations for acute myocardial infarction, aortic aneurism/dissection and pulmonary embolism after the 1st wave.

Background: Ablation is a widely used therapy for atrial fibrillation (AF); however, arrhythmia recurrence and repeat procedures are common. Studies examining surrogate markers of genetic susceptibility to AF, such as family history and individual AF susceptibility alleles, suggest these may be associated with recurrence outcomes. Accordingly, the aim of this study was to test the association between AF genetic susceptibility and recurrence after ablation using a comprehensive polygenic risk score for AF. Methods: Ten centers from the AF Genetics Consortium identified patients who had undergone de novo AF ablation. AF genetic susceptibility was measured using a previously described polygenic risk score (N=929 single-nucleotide polymorphisms) and tested for an association with clinical characteristics and time-to-recurrence with a 3 month blanking period. Recurrence was defined as >30 seconds of AF, atrial flutter, or atrial tachycardia. Multivariable analysis adjusted for age, sex, height, body mass index, persistent AF, hypertension, coronary disease, left atrial size, left ventricular ejection fraction, and year of ablation. Results: Four thousand two hundred seventy-six patients were eligible for analysis of baseline characteristics and 3259 for recurrence outcomes. The overall arrhythmia recurrence rate between 3 and 12 months was 44% (1443/3259). Patients with higher AF genetic susceptibility were younger ( P P =0.001). Persistent AF (hazard ratio [HR], 1.39 [95% CI, 1.22–1.58]; P P P =0.008) were associated with increased risk of recurrence. In univariate analysis, higher AF genetic susceptibility trended towards a higher risk of recurrence (HR, 1.08 [95% CI, 0.99–1.18]; P =0.07), which became less significant in multivariable analysis (HR, 1.06 [95% CI, 0.98–1.15]; P =0.13). Conclusions: Higher AF genetic susceptibility was associated with younger age and fewer clinical risk factors but not recurrence. Arrhythmia recurrence after AF ablation may represent a genetically different phenotype compared to AF susceptibility.

Atrial fibrillation (AF) is associated with significant risk of stroke and other thromboembolic events, which can be effectively prevented using oral anticoagulation (OAC) with either vitamin K antagonists (VKAs) or non-VKA oral anticoagulants (NOACs) dabigatran, rivaroxaban, apixaban, or edoxaban. Until recently, VKAs were the only available means for OAC treatment. NOACs had similar efficacy and were safer than or as safe as warfarin with respect to reduced rates of hemorrhagic stroke or other intracranial bleeding in the respective pivotal randomized clinical trials (RCTs) of stroke prevention in non-valvular AF patients. Increasing “real-world” evidence on NOACs broadly confirms the results of the RCTs. However, individual patient characteristics including renal function, age, or prior bleeding should be taken into account when choosing the OAC with best risk–benefit profile. In patients ineligible for OACs, surgical or interventional stroke prevention strategies should be considered. In patients undergoing cardiac surgery for other reasons, the left atrial appendage excision, ligation, or amputation may be the best option. Importantly, residual stumps or insufficient ligation may result in even higher stroke risk than without intervention. Percutaneous left atrial appendage occlusion, although requiring minimally invasive access, failed to demonstrate reduced ischemic stroke events compared to warfarin. In this review article, we summarize current treatment options and discuss the strengths and major limitations of the therapies for stroke risk reduction in patients with AF.

AimsCatheter ablation (CA) of ventricular arrhythmias is one of the most challenging electrophysiological interventions with an increasing use over the last years. Several benefits must be weighed against the risk of potentially life-threatening complications which necessitates a steady reevaluation of safety endpoints. Therefore, the aims of this study were (i) to investigate overall in-hospital mortality in patients undergoing such procedures and (ii) to identify variables associated with in-hospital mortality in a German-wide hospital network.Methods and resultsBetween January 2010 and September 2018, administrative data provided by 85 Helios hospitals were screened for patients with main or secondary discharge diagnosis of ventricular tachycardia (VT) or premature ventricular contractions (PVCs) in combination with an arrhythmia-related CA using ICD- and OPS codes. In 5052 cases (mean age 60.9 ± 14.3 years, 30.1% female) of 30 different hospitals, in-hospital mortality was 1.27% with a higher mortality in patients ablated for VT (1.99%, n = 2, 955) compared to PVC (0.24%, n = 2, 097, P 24 h after initial admission (n = 861, P 24 h [odds ratio (OR) 2.28, 95% confidence interval (CI) 1.59–3.28, P ConclusionsWe reported in-hospital mortality rates after CA of ventricular arrhythmias in the largest multicentre, administrative dataset in Germany which can be implemented in quality management programs. Aside from comorbidities, a delayed hospital transfer to a CA performing centre is associated with an increased in-hospital mortality. This deserves further studies to determine the optimal management strategy.

Background Rivaroxaban is a non-vitamin K oral anticoagulant and has been approved for prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF). Current labeling recommends 20 mg once a day (q.d.) as a standard dose and a reduced dose of 15 mg q.d. in patients with renal impairment. Hypothesis The aim of this study was to analyze the adherence to current labeling concerning initial rivaroxaban dosing and to determine whether potential lack of such adherence is medically justified. Methods Patients with AF initiated on rivaroxaban between January 1, 2016 and January 31, 2017, were identified in the Heart Center Leipzig database. Health records were screened to identify prescribed rivaroxaban dose, presence or absence of renal impairment, patient characteristics, further dosing-relevant diagnoses and co-medication with antiplatelet drugs and non-vitamin K oral anticoagulants (NOACs). Results We identified a total of 378 consecutive patients. In 282 cases (74.6%), rivaroxaban was prescribed in a standard dose and in 96 (25.4%) in a reduced dose. Out of 96 patients receiving a reduced dose, 50 (52.1%) did not meet labeling criteria for dose reduction. In uni- and multivariate regression analysis, estimated glomerular filtration rate (eGFR) (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.12-0.95, P = .04) was the only independent predictor of rivaroxaban underdosage. Conclusions In clinical practice, rivaroxaban dosing is frequently incoherent with labeling. In this study, rivaroxaban was often administered underdosed. Potentially inappropriate dose reduction was significantly associated with eGFR, the same factor that is used as criterion for dose adjustment.

Remote ischemic preconditioning (RIPC) has been studied in models of different cardiovascular entities. Recently, a beneficial effect of RIPC on incidence of atrial fibrillation (AF) in postsurgical patients has been suggested. However, the potential impact of RIPC on electrophysiological- and thrombogenesis-related parameters in the setting of paroxysmal nonvalvular AF has not been investigated. The aim of the study is to answer the following questions: (1) Does RIPC have impact on inducibility of AF in patients with known paroxysmal AF? If yes, what are the direct electrophysiological mechanisms of this phenomenon, and could RIPC be implemented to reduce AF burden? (2) Does RIPC have the potential to minimize thrombogenic effects of simulated episodes of AF? If so, what are inhibited components of thrombogenesis and can this be used to reduce thromboembolic risk related to paroxysmal AF? The presented study is a 2-arm, randomized, placebo-controlled, double-blinded, single-center trial in a cohort of 146 patients with paroxysmal AF referred for AF ablation in sinus rhythm. The study will collect electrophysiological data such as variability of P-wave morphology, atrial refractory period, conduction times, and inducibility/sustainability of AF. Furthermore, AF-induced prothrombotic processes will be analyzed by quantification of platelet aggregates, analysis of platelet function, and measurement of thrombogenesis-related plasma markers. Moreover, the study will provide a unique bio-database for further analysis of molecular and genetic mechanisms responsible for observed results.

Background Stage of platelet activation is an important modulator of stroke risk associated with atrial fibrillation (AF). However, factors determining such activation status of thrombocytes in patients with AF are still not well studied. Methods and results We enrolled 83 patients (mean age 61 ± 10 years, 61% male, mean CHA2DS2-VASc 2.1 ± 1.4) with paroxysmal (75%) or persistent (25%) AF admitted for catheter ablation. Blood samples were collected directly from the left atrium (LA) and platelet activation status was measured by means of flow cytometric assessment in whole blood and light transmission aggregometry (LTA) in unstimulated and Thrombin-receptor-activated-peptide-6 (TRAP-6)-stimulated platelet rich plasma. In flow cytometry, we measured fractions of platelet microparticles and aggregates as well as P-selectin expression on platelets' surfaces. LTA findings are expressed as maximal aggregation (MA), primary slope (PS) and area under curve (AUC). Cardiac anatomy has been assessed by means of echocardiography and magnetic resonance imaging. Left atrial appendage (LAA) volume, but not LAA morphology nor morphological and functional parameters describing LA, was significantly correlated with increased pre-activation of platelets (R = 0.224, p = 0.043) and consecutive reduced response to TRAP-6 (R = 0.231, p = 0.037) measured by P-selectin expression in flow cytometry. Similarly, a reduced response to TRAP-6 in patients with larger LAA volume (PS: R = −0.240; p = 0.042; AUC: R = −0.244; p = 0.035; MA: R = −0.270; p = 0.019) as well as with heart failure (PS 54.75 vs 71.45, p = 0.026) was observed in LTA. Conclusion In patients with AF, LAA volume correlates with extent of platelet activation status, this effect is aggravated in patients with heart failure.

BACKGROUND: Apixaban is a non–vitamin K oral anticoagulant approved for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation (AF). Current labeling recommends dose reduction based on patient age, weight, and renal function. HYPOTHESIS: The aim of this study was to analyze adherence to current labeling instructions concerning initial apixaban dosing in clinical practice and identify factors associated with inappropriate dose reduction. METHODS: Patients with AF initiated on apixaban in 2016 were identified in the Heart Center Leipzig database. Records were screened to identify patient characteristics, prescribed apixaban dose, renal function, and further dosing‐relevant secondary diagnoses and co‐medication. RESULTS: We identified 569 consecutive patients with AF initiated on apixaban. In 301 (52.9%) patients, apixaban was prescribed in standard dose (5 mg b.i.d.) and in 268 (47.1%) in a reduced dose (2.5 mg b.i.d.). Of 268 patients receiving a reduced dose, 163 (60.8%) did not meet labeling criteria for dose reduction. In univariate and multivariate regression analysis, age (OR: 0.736, 95% CI: 0.664–0.816, P

Aims Ablation of atrial fibrillation (AF) is recommended in the guidelines as a Class Ia/IIa indication. However, associated complications should not be dismissed; specifically, inguinal vascular complications (IVC). Although IVCs are generally considered trivial, they represent an economic burden for the procedure-performing hospital and the patient. Therefore, the ability to monitor and ultimately minimize potential complications is of considerable interest. Methods and results An economic model was developed to calculate the economic impact for certain IVC-types from a large German single-centre perspective in 2015 and 2016. Twenty-nine of 1040 (2.79%) and 48 of 1152 (4.17%) AF-ablation patients had documented IVC in 2015 and 2016 (P = 0.08), respectively. Inguinal vascular complications that required invasive treatment (thrombin, intervention, surgery) occurred in 0.58% of the 2015 and in 0.87% of the 2016 AF-ablation cases. The expected excess costs (incorporating direct costs, benefit lost adjusted for reimbursement) per patient treated with AF-ablation were 139.54€ and 153.31€ in 2015 and 2016, respectively. This was mostly driven by opportunity costs, which could reach 15 544.71€ for certain IVC. Sensitivity analysis revealed the probability of occurrence, length of stay of certain IVC types, and the revenue per day influenced the expected costs per AF-ablation patient. Conclusion Even relatively benign complications such as IVC can result in considerable cost increases. Therefore, measures to reduce them should be established and implemented.

Aims: Catheter ablation is an established therapy in patients with symptomatic atrial fibrillation (AF) with increasing popularity. Pericardial effusion requiring intervention (PE) is one of the most threatening adverse outcomes. The aim of this study was to examine rates of PE after catheter ablation in a large 'real-world' data set in a German-wide hospital network. Methods and results: Using ICD and OPS codes, administrative data of 85 Helios hospitals from 2010 to 2017 was used to identify AF catheter ablation cases [Helios atrial fibrillation ablation registry (SAFER)]. PE occurred in 0.9% of 21 141 catheter ablation procedures. Patients with PE were significantly older, to a higher percentage female, had more frequently hypertension, mild liver disease, diabetes with chronic complications, and renal disease. Low hospital volume (

Aims: Atrial fibrillation (AFib) and atrial flutter (AFlut) are common arrhythmias with increased use of invasive procedures. A steady re-evaluation of relevant safety endpoints is recommended and both quality management and pay-for-performance programs are evolving. Therefore, the aims of this study were (i) to investigate and report overall in-hospital mortality and mortality of invasive arrhythmia-related procedures and (ii) to identify mortality predictors in a German-wide hospital network. Methods and results: Administrative data provided by 78 Helios hospitals between 2010 and 2017 were examined using International Statistical Classification of Diseases and Related Health Problems- and Operations and Procedures-codes to identify patients with AFib or AFlut as main discharge diagnosis or secondary diagnosis combined with invasive arrhythmia-related interventions. In 161 502 patients, in-hospital mortality was 0.6% with a significant decrease from 0.75% to 0.5% (P

Background Hypertrophic cardiomyopathy (HCM) is the most common inherited heart disease. Reported prevalence rates vary substantially between 1:500 (0.2%) and 1:3,000 (0.03%), which may be attributed to different study designs and population characteristics. Prevalence data for Germany is not available. Consequently, this study aimed (1) to quantify age- and gender-specific clinically diagnosed HCM prevalence in Germany based on the analysis of health care claims data of > 5 million insurants in 2015, and (2) to analyze temporal prevalence trends from 2011 to 2015. Methods Data were extracted from the InGef (Insitute for Applied Health Research) database, which is an anonymized healthcare claims database with longitudinal data from patients insured in one of approximately 70 German social health insurances (SHIs). Patients were classified as HCM prevalent, if they had at least one verified ambulatory or one hospital main- or secondary discharge diagnosis of HCM (I42.1 or I42.2). Results In 2015, HCM was prevalent in 4,000 out of 5,490,810 patients (0.07%; 1:1,372). HCM prevalence increased gradually with age from 7.4/100,000 persons (95% CI 5.2–10.1) in 0–9 years old to 298.7/100,000 persons (95% CI 276.4–322.4) in patients > 80 years. In all age categories, men had a numerically higher prevalence than women with significant differences in patients > 30 years. There was a gradual annual prevalence increase from 75.8 (95% CI 75.2–76.4) in 2011 to 84.2 (95% CI 83.5–84.8) in 2015 per 100,000 persons. Conclusions Overall, prevalence of clinically diagnosed HCM in Germany is lower than in systematic population studies based on echocardiographic diagnosis. Prevalence increased with advancing age and showed a constant yearly rise. Those observations may improve our understanding of the burden of this genetic heart disease on the health care system in Germany, increase the diagnostic awareness among clinicians and shape future screening and management strategies.

Background: PR interval prolongation has recently been shown to associate with advanced left atrial remodeling and atrial fibrillation (AF) recurrence after catheter ablation. While different genome-wide association studies (GWAS) have implicated 13 loci to associate with the PR interval as an AF endophenotype their subsequent associations with AF remodeling and response to catheter ablation are unknown. Here, we perform a gene-based analysis of GWAS data to test the hypothesis that PR interval candidate genes also associate with left atrial remodeling and arrhythmia recurrence following AF catheter ablation. Methods and Results: Samples from 660 patients with paroxysmal (n = 370) or persistent AF (n = 290) undergoing AF catheter ablation were genotyped for ~1,000,000 SNPs. Gene-based association was investigated using VEGAS (versatile gene-based association study). Among the 13 candidate genes, SLC8A1, MEIS1, ITGA9, SCN5A, and SOX5 associated with the PR interval. Of those, ITGA9 and SOX5 were significantly associated with left atrial low voltage areas and left atrial diameter and subsequently with AF recurrence after radiofrequency catheter ablation. Conclusion: This study suggests contributions of ITGA9 and SOX5 to AF remodeling expressed as PR interval prolongation, low voltage areas and left atrial dilatation and subsequently to response to catheter ablation. Future and larger studies are necessary to replicate and apply these findings with the aim of designing AF pathophysiology-based multi-locus risk scores.

Aim Rare variants of genes encoding the cardiac sodium channel and associated compounds have been linked with atrial fibrillation (AF). Nevertheless, current expert consensus does not support genetic testing in AF, which is in part based on the fact that “there is no therapeutic impact derived from AF genetic test results”. However, there are no studies available supporting this recommendation. Consequently, this study analyzed the impact of rare variants affecting the cardiac sodium channel on rhythm outcome of AF catheter ablation. Methods and results In 137 consecutive patients with lone AF enrolled in the Leipzig Heart Center AF ablation registry, screening for mutations in SCN5A, SCN1B – 4B, CAV3, GPD1L, SNTA1 and MOG1 was performed. We identified 3 rare non-synonymous variants in SCN5A, 5 in SCN1B, 1 in SCN4B, 1 in CAV3, 6 in GPD1L, 3 in SNTA1 and 3 in MOG1 (16%). Variant carriers were otherwise comparable with non-variant carriers. Analysis of AF recurrence rates after radiofrequency AF catheter ablation by serial 7-day Holter ECG monitoring between 3 and 12 months revealed no difference between groups, i.e. 45% in variant carriers vs. 49% in non-variant carriers. Conclusions Rare variants in genes encoding the cardiac sodium channel and associated compounds are frequently found in lone AF but were not found to impact the outcome of AF catheter ablation. This finding supports current recommendations not to screen for rare variants for the ablation outcome in AF. Nevertheless, it may at least be helpful for understanding AF mechanisms and larger studies are needed to further explore the possible association between genotype and response to AF therapies.

In atrial fibrillation (AF), left atrial diameter (LAD) and low voltage area (LVA) are intermediate phenotypes that are associated with AF type and progression. In this study, we tested the hypothesis, that these phenotypes share common, genetically-determined pathways using pathway enrichment analysis of GWAS data. Samples from 660 patients with paroxysmal (n = 370) or persistent AF (n = 290) were genotyped for ~1,000,000 SNPs. SNPs found significantly associated with LAD, LVA or AF type were used for gene-based association tests in a systematic biological Knowledge-based mining system for Genome-wide Genetic studies (KGG). Associated genes were tested for pathway enrichment using two enrichment tools (WebGestalt and GATHER) and the databases provided by Kyoto Encyclopedia of Genes and Genomes. The calcium signaling pathway (hsa04020) was the only pathway that reached statistical significance for LAD and LVA in both enrichment tools and was also significantly associated with AF type. Within this pathway, there were 39 genes (i.e. CACNA1C, RyR2) that were associated with LAD, LVA and AF type. In conclusion, there is a genomic contribution to electroanatomical remodeling (LAD, LVA) and AF type via the calcium signaling pathway. Future and larger studies are necessary to replicate and apply these findings.

Background Left atrial enlargement and persistent atrial fibrillation (AF) are well-known predictors for arrhythmia recurrence after AF catheter ablation (LRAF). In this study, by using pathway enrichment analysis of GWAS data, we tested the hypothesis that genetic pathways associated with these phenotypes are also associated with LRAF. Methods Samples from 660 patients with paroxysmal (n = 370) or persistent AF (n = 290) undergoing de-novo AF catheter ablation were genotyped for ~1,000,000 SNPs. SNPs found to be significantly associated with left atrial diameter (LAD) or AF type were used for gene-based association tests in a systematic biological Knowledge-based mining system for Genome-wide Genetic studies (KGG). Associated genes were tested for pathway enrichment using WEB-based Gene SeT AnaLysis Toolkit (WebGestalt), the Gene Annotation Tool to Help Explain Relationships (GATHER) and the databases provided by Kyoto Encyclopedia of Genes and Genomes (KEGG). In a second step, the association of consistently enriched pathways and LRAF was tested. Results By using sequential 7-day Holter ECGs, LRAF between 3 and 12 months was observed in 48% and was associated with LAD (B = 1.801, 95% CI 0.760–2.841, p = 1.0E-3) and persistent AF (OR = 2.1; 95% CI 1.567–2.931, p = 2.0E-6). WebGestalt (adj. p = 2.7E-22) and GATHER (adj. p = 5.2E-3) identified the calcium signaling pathway (hsa04020) as the only consistently enriched pathway for LAD, while the extracellular matrix (ECM) -receptor interaction pathway (hsa04512) was the only consistently enriched pathway for AF type (adj. p = 2.1E-15 in WebGestalt; adj. p = 9.3E-4 in GATHER). Both calcium signaling (adj. p = 2.2E-17 in WebGestalt; adj. p = 2.9E-2 in GATHER) and ECM-receptor interaction (adj. p = 1.2E-10 in WebGestalt; adj. p = 2.9E-2 in GATHER) were significantly associated with LRAF. Conclusions Calcium signaling and ECM-receptor interaction pathways are associated with LAD and AF type and, in turn, with LRAF. Future and larger studies are necessary to replicate and apply these findings.

Background— Common single nucleotide polymorphisms (SNPs) at chromosomes 4q25 (rs2200733, rs10033464 near PITX2 ), 1q21 (rs13376333 in KCNN3 ), and 16q22 (rs7193343 in ZFHX3 ) have consistently been associated with the risk of atrial fibrillation (AF). Single-center studies have shown that 4q25 risk alleles predict recurrence of AF after catheter ablation of AF. Here, we performed a meta-analysis to test the hypothesis that these 4 AF susceptibility SNPs modulate response to AF ablation. Methods and Results— Patients underwent de novo AF ablation between 2008 and 2012 at Vanderbilt University, the Heart Center Leipzig, and Massachusetts General Hospital. The primary outcome was 12-month recurrence, defined as an episode of AF, atrial flutter, or atrial tachycardia lasting >30 seconds after a 3-month blanking period. Multivariable analysis of the individual cohorts using a Cox proportional hazards model was performed. Summary statistics from the 3 centers were analyzed using fixed effects meta-analysis. A total of 991 patients were included (Vanderbilt University, 245; Heart Center Leipzig, 659; and Massachusetts General Hospital, 87). The overall single procedure 12-month recurrence rate was 42%. The overall risk allele frequency for these SNPs ranged from 12% to 35%. Using a dominant genetic model, the 4q25 SNP, rs2200733, predicted a 1.4-fold increased risk of recurrence (adjusted hazard ratio,1.3 [95% confidence intervals, 1.1–1.6]; P =0.011). The remaining SNPs, rs10033464 (4q25), rs13376333 (1q21), and rs7193343 (16q22) were not significantly associated with recurrence. Conclusions— Among the 3 genetic loci most strongly associated with AF, the chromosome 4q25 SNP rs2200733 is significantly associated with recurrence of atrial arrhythmias after catheter ablation for AF.

Background Galectin-3 (Gal-3) is an emerging biomarker in heart failure that is involved in fibrosis and inflammation. However, its potential value as a prognostic marker in atrial fibrillation (AF) is unknown. The aim of this study was to assess the impact of AF catheter ablation on Gal-3 and evaluate its prognostic impact for predicting rhythm outcome after catheter ablation. Methods Gal-3 was measured at baseline and after 6 months using specific ELISA. AF recurrences were defined as any atrial arrhythmia lasting longer than 30 sec within 6 months after ablation. Results In 105 AF patients (65% males, age 62±9 years, 52% paroxysmal AF) undergoing catheter ablation, Gal-3 was measured at baseline and after 6 months and compared with an AF-free control cohort (n=14, 50 % males, age 58±11 years). Gal-3 was higher in AF patients compared with AF-free controls (7.8±2.9 vs. 5.8±1.8, ng/mL, p=0.013). However, on multivariable analysis, BMI (p=0.007) but not AF (p=0.068) was associated with Gal-3. In the AF cohort, on univariable analysis higher Gal-3 levels were associated with female gender (p=0.028), higher BMI (p=0.005) and both CHADS2 (p=0.008) and CHA2DS2-VASC (p=0.016) scores, however, on multivariable analysis only BMI remained significantly associated with baseline Gal-3 (p=0.016). Gal-3 was similar 6 months after AF catheter ablation and was not associated with sinus rhythm maintenance. Conclusions Although galectin-3 levels are higher in AF patients, this is driven by cardiometabolic co-morbidities and not heart rhythm. Gal-3 is not useful for predicting rhythm outcome of catheter ablation.

Recent genome-wide association studies identified KCNN3 variants on chromosome 1q21 to confer risk for atrial fibrillation (AF). In this study, we tested the hypothesis that the chromosome 1q21 variant rs13376333 associates with AF recurrence after catheter ablation (CA). 265 patients (70.2&percnt

Mutations in genes encoding the cardiac sodium channel and associated compounds have been linked with atrial fibrillation (AF). Nevertheless, current expert consensus does not support genetic testing in AF which is in part based on the fact that “there is no therapeutic impact derived from AF