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Recent studies suggest cardiac involvement with an increased incidence of arrhythmias in the setting of coronavirus disease 2019 (COVID-19). The aim of this study was to evaluate the risk of potentially lethal arrhythmias and atrial fibrillation in patients with COVID-19-induced acute respiratory distress syndrome (ARDS) and to elicit possible predictors of arrhythmia occurrence.A total of 107 patients (82 male, mean age 60 ± 12 years, median body mass index 28 kg/mIn this relatively young population with COVID-19-induced ARDS, the incidence of potentially lethal arrhythmias was low. While overall mortality was high in these severely affected patients, cardiac involvement and arrhythmia occurrence was not a significant driver of mortality.

Introduction Patients with high blood pressure levels are at high risk for acute complications as well as serious long-term consequences. Women with preeclampsia often experience very high blood pressure levels during pregnancy and postpartum and are also known to have a higher cardiovascular risk in later life. Material and Methods In our single-centre retrospective cohort study, we analysed 158 pregnancies complicated by preeclampsia in regard to maternal outcome. We divided the patient cohort into three subgroups according to the blood pressure levels during hospital stay. Results Pre-existing arterial hypertension was significantly more common in patients with a hypertensive crisis (systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 120 mmHg) during pregnancy than in patients with moderate or severe hypertension (p = 0.001). Women with a hypertensive crisis had an unfavourable outcome compared to women with lower blood pressure levels. These women developed a HELLP-syndrome significantly more often (p = 0.013). Moreover, most of the women with a hypertensive crisis during pregnancy were still hypertensive at hospital discharge (p = 0.004), even though they were administrated antihypertensive agents more often (p Conclusion Preeclamptic women with hypertensive crises should be identified quickly and monitored closely to avoid further complications. Standardized follow-up programs are lacking, but especially these patients seem to be at high risk for persistent hypertension and increased cardiovascular morbidity and therefore should receive specialist follow-up, including hypertensiologists, cardiologists and gynaecologists. Large prospective trials are required for a better understanding of these interrelations and to develop a specific follow-up program.

Machine learning has immense novel but also disruptive potential for medicine. Numerous applications have already been suggested and evaluated concerning cardiovascular diseases. One important aspect is the detection and management of potentially thrombogenic arrhythmias such as atrial fibrillation. While atrial fibrillation is the most common arrhythmia with a lifetime risk of one in three persons and an increased risk of thromboembolic complications such as stroke, many atrial fibrillation episodes are asymptomatic and a first diagnosis is oftentimes only reached after an embolic event. Therefore, screening for atrial fibrillation represents an important part of clinical practice. Novel technologies such as machine learning have the potential to substantially improve patient care and clinical outcomes. Additionally, machine learning applications may aid cardiologists in the management of patients with already diagnosed atrial fibrillation, for example, by identifying patients at a high risk of recurrence after catheter ablation. We summarize the current state of evidence concerning machine learning and, in particular, artificial neural networks in the detection and management of atrial fibrillation and describe possible future areas of development as well as pitfalls. Graphical abstract Typical data flow in machine learning applications for atrial fibrillation detection.

Introduction: Hormone-mediated therapies are on the rise and are key therapies in the treatment of some of the most common cancer entities. Proarrhythmic effects have been described in patients treated with SERMs while little to none is known about the electrophysiological effects of the potentially less arrhythmogenic selective estrogen receptor degraders. Methods: Twenty hearts of female New Zealand White rabbits were excised and retrogradely perfused employing a Langendorff setup. An electrophysiology study was performed to obtain CL-dependent action potential duration at 90% of repolarization (APD90), QT interval, effective refractory period (ERP), and post-repolarization refractoriness (PRR = ERP-APD90). After generating baseline data, the hearts were assigned to two groups and perfused with (n = 10) increasing doses of fulvestrant (1 µM and 5 µM; n = 10) or tamoxifen (2.5 µM and 7.5 µM; n = 10), and the protocol was repeated again. Results: Fulvestrant led to a decrease in APD90 and QT interval and an increased PRR. The inducibility of ventricular tachycardia (VT) episodes was unaltered. Tamoxifen showed similar effects, resulting in a shortened APD90 and QT interval and no increased VT incidence in the setting of a prolonged PRR. Conclusion: The present study shows no acute proarrhythmic effect of tamoxifen and fulvestrant in an established whole heart model when employing clinically relevant concentrations.

BACKGROUND Previous studies have raised serious concerns on cardiovascular safety of widely prescribed nonsteroidal anti-inflammatory drugs (NSAIDs). Therefore, the aim of this study was to characterize the electrophysiological effects of certain NSAIDs in an established whole heart model of proarrhythmia. METHODS AND RESULTS Thirty-eight hearts of New Zealand White rabbits were harvested and retrogradely perfused employing a Langendorff setup, and electrophysiology studies were performed to investigate action potential duration at 90% of repolarization (APD90 ), QT intervals, and effective refractory period (ERP). After generating baseline data, hearts were perfused with ibuprofen (Group 1, n = 12; 10 and 30 μM), indomethacin (Group 2, n = 13; 10 and 20 μM) and diclofenac (Group 3, n = 13; 10 and 20 μM), respectively, and the pacing protocols were repeated for each concentration. In all groups, perfusion with the NSAIDs resulted in a significant and reproducible shortening of APD90 and QT interval. In all groups, the arrhythmia susceptibility was significantly raised as occurrence of monomorphic ventricular tachycardia under programmed ventricular stimulation was significantly increased under perfusion with ibuprofen, indomethacin and diclofenac in all concentrations. CONCLUSION The perfusion with ibuprofen, indomethacin and diclofenac in commonly used doses raised the arrhythmia susceptibility in an established rabbit whole-heart model while APD shortening and shortened ERP seem to be crucial for arrhythmogenesis.

Aims The present study aims at analyzing the role of a preimplantation 12-lead electrocardiogram (ECG) on the prediction of inappropriate S-ICD® episodes. Methods N=116 screened patients (pts) with an S-ICD® and a follow-up of at least 6 months were included. A preimplantation 12-lead ECG (50 mm/s, 10 mm/mV) was analyzed with regard to QRS and T-wave amplitude, T wave concordance or discordance and QRS/T wave ratio in all 12 leads. To ensure an exact determination of parameters Datinf® Measure software was used. Results were correlated to the occurrence of oversensing of cardiac signals during follow-up. Results N = 116 pts. (63,8% male, mean age 40,9 ± 15,5 years) were included (primary prevention in 47.4% of pts). The most frequent cardiac diseases were hypertrophic cardiomyopathy (HCM) in n = 25 (21,6%), electrical heart disease in n = 20 (17,2%), and dilated cardiomyopathy in n = 17 (14,7%). Mean follow-up was 740 ± 549 days. During follow- up n = 17 (14.7%) pts. experienced n = 27 inappropriate episodes due to T-wave oversensing. Besides HCM (OR 6.16, CI 1.79–21.15, p = 0.004) a discordance of QRS to T-wave in lead I (OR 6.5, CI 1.86–22.67, p = 0.003) was found to be a strong predictor for inappropriate shocks. In multivariate analysis the pts. with a combination of both had an 8.4-fold higher risk of misclassification of intracardiac signals (p = 0.003) with consecutive inappropriate therapy. Conclusion A discordance of QRS to T-wave in lead I turned out to be a strong predictor for future inappropriate shocks in a typical S-ICD® cohort with special impact on HCM pts.

The implantation of cardiac devices significantly reduces morbidity and mortality in patients with cardiac arrhythmias. Arrhythmias as well as therapy delivered by the device may impact quality of life of patients concerned considerably. Therefore we aimed at conducting a systematic search and meta-analysis of trials examining the impact of the implantation of cardiac devices, namely implantable cardioverter-defibrillators (ICD), pacemakers and left-ventricular assist devices (LVAD) on quality of life. After pre-registering the trial with the PROSPERO database, we searched Medline, PsycINFO, Web of Science and the Cochrane databases for relevant publications. Study quality was assessed by two independent reviewers using standardized protocols. A total of 37 trials met our inclusion criteria. Of these, 31 trials were cohort trials while 6 trials used a randomized controlled design. We found large pre-post effect sizes for positive associations between quality of life and all types of devices. The effect sizes for LVAD, pacemaker and ICD patients were g = 1.64, g = 1.32 and g = 0.64, respectively. There was a lack of trials examining the effect of implantation on quality of life relative to control conditions. Trials assessing quality of life in patients with cardiac devices are still scarce. Yet, the existing data suggest beneficial effects of cardiac devices on quality of life. We recommend that clinical trials on cardiac devices routinely assess quality of life or other parameters of psychological well-being as a decisive study endpoint. Furthermore, improvements in psychological well-being should influence decisions about implantations of cardiac devices and be part of patient education and may impact shared decision-making.

1. Introduction: Pulmonary vein isolation (PVI) is an established procedure used to achieve rhythm control in atrial fibrillation (AF). In obese patients (pts), in whom AF occurs more frequently, a reduced effectiveness of PVI has been observed. Therefore, this study’s aim was to compare the long-term efficacy of PVI between obese and non-obese patients. 2. Methods: We enrolled 111 consecutive pts with a body mass index (BMI) of >30 kg/m2 undergoing PVI from our large registry. Procedural data and outcomes were compared with a matched group of 115 non-obese PVI pts and the long-term outcomes were analyzed. 3. Results: Overall follow-up duration was 314 patient-years in the obese and 378 patient-years in the non-obese group. The follow-up rate was 71% in the obese and 76% in the non-obese group. In both groups, their AF-characteristics did not differ significantly, while known risk factors were significantly more prevalent in the obese group. Procedural characteristics were similar in both groups. During follow-up, the obese pts demonstrated significant weight loss compared to the non-obese pts, while at the same time, the overall recurrence rate during follow-up did not differ significantly between both groups (obese: 39.2% and non-obese: 43.7%). PVI related and long-term complications were comparable between both groups. In the univariate analysis, obesity was not found to be associated with an increased AF recurrence risk. 4. Conclusion: These real-life data demonstrate that obese pts may not show higher AF recurrence rates after PVI compared to pts with normal body weight. Furthermore, PVI was found to be safe and effective in obese patients; thus, a BMI alone may not be a criterion for refusal of PVI.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology characterized by noncaseating granulomas. Cardiac involvement is often limiting patients' prognosis. Cardiac sarcoidosis can manifest with variant cardiac arrhythmias, of which atrioventricular (AV)-block-related bradycardia and ventricular tachycardias are the most common. Although cardiac sarcoidosis remains a histopathological diagnosis, the significance of imaging modalities, especially cardiac magnetic resonance imaging is increasing rapidly but mainly remains reserved for patients with a high suspicion due to a previous arrhythmia or unknown cardiomyopathy. Thus, there is a need for screening in daily clinical practice so that possible characteristic electrocardiographic (ECG) findings may guide the way to detect the disease. We therefore evaluated the ECG as a potential tool for screening of cardiac sarcoidosis and present different electrophysiological manifestations of cardiac sarcoidosis based on a literature review. The ECG is a valuable tool for screening of cardiac involvement in patients with sarcoidosis. Several parameters have been shown to be associated with cardiac involvement in sarcoidosis such as higher-degree AV-block, QRS complex fragmentation and widening, as well as certain T wave abnormalities that may indicate cardiac involvement, of which the latter two are most promising and specific. However, prospective studies examining a large number of trials are desirable.

Syncopes are a very common phenomenon and have a high recurrence rate. The differentiation between the psychogenic and physical, especially of arrhythmic origin, remains difficult. In many cases, an implantable loop recorder is used for the detection of possible arrhythmias, leading to syncopes. Yet, the existing literature suggests that psychological factors may play a significant role in recurrent syncopes. We aimed at analyzing the potential role of several psychological factors on the recurrence of arrhythmic or non-arrhythmic syncopes. Methods and results: A total of 119 patients, who had received an implantable loop recorder for recurrent syncopes at our center between 01/2018 and 12/2021, participated in this retrospective cohort study. Anxiety, depression and quality of life were assessed using extensively validated questionnaires (GAD-7, PHQ-9 and SF-12). The mean follow-up after loop recorder implantation was 710 ± 430 days and 50% of patients were female. The mean patient age was 54.8 ± 18.6 years. Most patients had no evidence of structural heart disease (84%), and normal LV function (92%). A statistical analysis revealed that the presence of structural heart disease was the strongest predictor for arrhythmic syncope during follow-up. In patients with non-arrhythmic syncopes, we found significantly higher levels of anxiety (GAD-7 score: 2.5 ± 2.6 vs. 4.8 ± 4.3) and depression (PHQ-9 score: 3.9 ± 3.6 vs. 6.8 ± 5.1), and a lower quality of life (SF-12 score: 33.7 ± 6.4 vs. 29.6 ± 7.8). Discussion: We identified factors as contributors to a better identification of patients at risk for arrhythmic as well as non-arrhythmic syncopes. Especially anxious or depressive symptoms may hinted at non-arrhythmic causes of syncope. However, the study was limited by its retrospective design and low patient number. Further trials should likewise combine the diagnostic yield of loop recorders with psychometric evaluations before implantation and combine it with additional diagnostic measures, such as video monitoring, to further examine the role of psychological factors in the pathomechanism and treatment of syncope.

The long-QT syndrome (LQTS) is the most common ion channelopathy, typically presenting with a prolonged QT interval and clinical symptoms such as syncope or sudden cardiac death. Patients may present with a concealed phenotype making the diagnosis challenging. Correctly diagnosing at-risk patients is pivotal to starting early preventive treatment.Identification of congenital and often concealed LQTS by utilizing novel deep learning network architectures, which are specifically designed for multichannel time series and therefore particularly suitable for ECG data.A retrospective artificial intelligence (AI)-based analysis was performed using a 12-lead ECG of genetically confirmed LQTS (In this study, the XceptionTime model outperformed the FCN model for LQTS patients with even better results than in prior studies. Even when a patient cohort with cardiovascular comorbidities is used. AI-based ECG analysis is a promising step for correct LQTS patient identification, especially if common diagnostic measures might be misleading.

Decision-making in primary prevention is not always trivial and many clinical scenarios are not reflected in current guidelines. To help evaluate a patient's individual risk, a new score to predict the benefit of an implantable defibrillator (ICD) for primary prevention, the MADIT-ICD benefit score, has recently been proposed. The score tries to predict occurrence of ventricular arrhythmias and non-arrhythmic death based on data from four previous MADIT trials. We aimed at examining its usefulness in a large single-center register of S-ICD patients with various underlying cardiomyopathies.All S-ICD patients with a primary preventive indication for ICD implantation from our large single-center database were included in the analysis (The MADIT-ICD benefit score adds a new option to evaluate expected benefit of ICD implantation for primary prevention. In a large S-ICD cohort of primary prevention, the value of the score was limited to patients with ischemic cardiomyopathy. Future research should evaluate the performance of the score in different subgroups and compare it to other risk scores to assess its value for daily clinical practice.

Background The benefits of de novo cardiac resynchronization therapy (CRT) in patients with QRS-prolongation and impaired left-ventricular function (LVEF) are well established. Current guidelines also recommend CRT-upgrade in patients requiring permanent or frequent right ventricular pacing (RVP) with symptomatic heart failure and reduced LVEF. Whereas several predictors of response to de novo CRT-implantation such as female gender, QRS-duration, non-ischemic cardiomyopathy (NICM) are known due to large prospective trials, similar factors regarding CRT-upgrade are currently lacking. Methods and results We examine 114 patients 3–6 months after CRT-upgrade due to frequent RVP (> 50%) and symptomatic heart failure. Response to CRT was evaluated by improvement in NYHA class referring to the Minnesota Living With Heart Failure Questionnaire. Only cardiomyopathy type and use of Angiotensin-converting-enzyme (ACE) inhibitor had an impact on response to CRT-upgrade in a linear regression model. Patients with NICM presented a greater responder rate than patients with ischemic cardiomyopathy (ICM) (80.4 vs. 60.3%, p Conclusion Only underlying heart disease (NICM vs. ICM) and the use of ACE inhibitor were significant predictors of response to CRT-upgrade. In contrast to de novo CRT-recipients, where pre-implant QRS-duration is a key predictor, QRS-duration during RV-pacing has no significant impact on CRT-response in this cohort. Graphic abstract

Several case reports suggest QT prolongation leading to ventricular arrhythmias with fatal outcome after intoxication with the μ-opioid receptor agonist and anti-diarrheal agent loperamide. The number of cases of loperamide misuse are growing due to its potential stimulating effects. Loperamide intoxications can be treated by naloxone. However, previous reports described a further QT prolongation associated with naloxone administration. Therefore, the aim of this study was to investigate the effects of loperamide and naloxone on the cardiac electrophysiology in a sensitive whole-heart model. Twenty-six hearts of New Zealand White rabbits were retrogradely perfused in a modified Langendorff apparatus. Monophasic action potentials were recorded by endo- and epicardially positioned catheters. Hearts were stimulated at different cycle lengths, thereby obtaining action potential duration at 90% of repolarization (APD90) and QT intervals. Programmed ventricular stimulation was used to assess ventricular vulnerability. Fourteen hearts were perfused with ascending concentrations of loperamide (0.2 μM, 0.35 μM, and 0.5 μM) after obtaining baseline data. Another 12 hearts were treated with naloxone (0.1 μM, 0.5 μM, 2 μM). Loperamide led to a significant increase in QT interval, APD90, and ventricular tachycardia (VT) episodes. In contrast, naloxone led to a decrease in QT interval and APD90. Accordingly, the number of VT episodes was unaltered. To the best of our knowledge, this is the first experimental study that investigated the effects of loperamide and naloxone in a whole-heart model. Loperamide led to a significant increase in action potential duration and QT interval. Simultaneously, the number of ventricular tachycardias was significantly increased. In contrast, naloxone led to a shortening of the action potential duration without altering arrhythmia susceptibility.

Zusammenfassung Hintergrund Die rhythmologische Ausbildung junger Kardiologinnen und Kardiologen bildet das Fundament für eine optimale Versorgung von Patienten mit Herzrhythmusstörungen. Die Rhythmologie zeichnet sich durch einen hohen Innovationsgrad aus und hat sich innerhalb der letzten Jahre rasant weiterentwickelt. Dies könnte zu einer Kluft zwischen der klinischen Ausbildung und neuer Technologien geführt haben und die Ausbildungsanforderungen maßgeblich verändern. Fragestellung Das Ziel der Umfrage war es, ein Meinungsbild junger Kardiologinnen und Kardiologen über den Stellenwert und die Zufriedenheit der rhythmologischen Ausbildung zu erheben und Verbesserungsansätze zu formulieren. Methoden Die Umfrage wurde im Mai 2020 durchgeführt. Mitglieder der Sektion Young-DGK der deutschen Gesellschaft für Kardiologie wurden via E‑Mail kontaktiert und gebeten einen onlinebasierten Fragebogen zu beantworten. Der Fragebogen beinhaltete Informationen über den aktuellen Stellenwert, die Zufriedenheit und die Strukturen der rhythmologischen Ausbildung in Deutschland. Ergebnisse Insgesamt 131 Young DGK-Mitglieder (68 % männlich) nahmen an der Umfrage teil. Das Durchschnittsalter betrug 33 ± 3,3 Jahre und der Ausbildungsstand gliederte sich wie folgt: 64 % Assistenzärzte, 20 % Fachärzte und 16 % Oberärzte. 72 Teilnehmer (53 %) berichteten, mit ihrer kardiologischen Weiterbildung sehr zufrieden zu sein. Die Hälfte der Teilnehmer wünschte sich einen höheren Umfang an rhythmologischen Inhalten in ihrer Weiterbildung. Rhythmologische Fortbildungsveranstaltungen und Fellowships wurden überwiegend positiv bewertet (70 % bzw. 93 %), jedoch waren diese jeweils für knapp die Hälfte der Teilnehmer unbekannt. Verbesserungsansätze sahen die Teilnehmer in der Einführung einer generellen rhythmologischen Rotation, einem gesteigerten Zugang zu Prozeduren um invasive Fähigkeiten zu erlernen (falls nötig auch klinikübergreifend), einer intensivierten Werbung für Fortbildungsveranstaltungen und Fellowships sowie einer Zunahme onlinebasierter Fortbildungsveranstaltungen. Schlussfolgerung Die Umfrage unterstreicht das Interesse junger Kardiologinnen und Kardiologen an einer strukturierten und intensivierten rhythmologischen Ausbildung innerhalb ihrer kardiologischen Weiterbildung.

Background The subcutaneous implantable-cardioverter defibrillator (S-ICD™, Boston Scientific, Natick, MA, USA) is an important advance in device therapy for the prevention of sudden cardiac death (SCD). Although current guidelines recommend S-ICD™ use, long-term data are still limited, especially in subgroups. Dilated cardiomyopathy (DCM) is a common reason for the implantation of an ICD. However, there are no sufficient data on the performance of the S-ICD™ in this patient cohort. Materials and methods All S-ICD™ patients with DCM as the main indication for ICD implantation (n = 47 patients) in our large-scaled single-center S-ICD™ registry (n = 294 patients) were included in this study. Baseline characteristics, appropriate and inappropriate shocks, and complications were documented in a mean follow-up of 22.9 ± 18.5 months. Results A total of 47 patients with DCM as the underlying structural heart disease received an S-ICD™ in our institution. Mean left ventricular ejection fraction was 37 ± 12% and a 28% had a history of ventricular tachyarrhythmia. During follow-up eight ventricular tachyarrhythmias were adequately terminated in three patients. In four patients, oversensing resulting in an inappropriate shock was observed, which could be managed by changing the sensing vector. There was no need for a change to a cardiac resynchronization (CRT) system while one system was changed to a VVI-ICD due to S-ICD™ wound infection. Conclusion The S-ICD™ seems to be a valuable option for the prevention of SCD in patients with DCM and no indication for CRT. As clinically relevant ventricular arrhythmias consisted of ventricular fibrillation or fast ventricular tachycardia in all patients in our cohort, no change to transvenous ICDs for anti-tachycardia pacing delivery was necessary.

Introduction: Transesophageal echocardiography (TEE) is routinely performed before catheter ablation of atrial tachyarrhythmias to rule out the presence of left atrial thrombi. However, data to support this practice are inconsistent. Methods: We analyzed consecutive pre-procedural TEE in a high-volume electrophysiology center for the presence of left atrial thrombi and a relevant flow reduction in the left atrial appendage (LAA) defined as LAA sludge or LAA emptying velocity (LAAEV) < 20 cm/s. The possible predictors of reduced flow were recorded and compared in a multivariate logistic regression analysis. Results: 1676 TEE were included (1122 before pulmonary vein isolation, 436 before atrial flutter ablation, 166 before other ablations). 543 patients (32%) were female and 991 (59%) were on DOAC. Nine patients (0.5%) had an LAA thrombus on pre-procedural TEE. Ninety-five further patients (5.7%) had a relevant reduction in LAA flow. The underlying rhythm showed a significant association with the presence of LAA thrombus or reduced LAA flow (p = 0.003). Patients in sinus rhythm and cavotricuspid isthmus-dependent atrial flutter exhibited the lowest risk. Additionally, reduced kidney function was associated with a reduction in LAA flow velocities (p = 0.04). Of note, two LAA thrombi occurred in patients in sinus rhythm and six out of nine patients with an LAA thrombus were on vitamin-K antagonists. Conclusions: LAA thrombus is a rare occurrence before an elective catheter ablation. The underlying rhythm and kidney function may serve as markers of a higher likelihood of significantly reduced LAAEV and LAA thrombus.

Several case reports have suggested an increased risk of sudden cardiac death due to energy drinks. Therefore, the purpose of this study was to assess acute electrophysiologic effects of caffeine and taurine, two of the main ingredients of energy drinks, in an experimental whole-heart model.Twenty-five rabbit hearts were excised, retrogradely perfused, and assigned to two groups. Hearts were perfused with caffeine (2, 10, and 50 µM) or taurine (2, 10, and 50 µM) after generating baseline data. Eight monophasic action potentials and electrocardiography recordings showed a significant abbreviation of action potential duration (APDIn this experimental whole-heart study, treatment with caffeine and taurine provoked ventricular arrhythmias. The underlying mechanism was an abbreviation of cardiac repolarizations and effective refractory periods that may facilitate re-entry and thereby provokes arrhythmias. These findings help to understand the potentially hazardous and fatal outcomes after intoxication with energy drinks.

Registry data add important information to randomized controlled trials (RCT) on real-life aspects of implantable cardioverter-defibrillator (ICD) patients with and without cardiac resynchronization therapy (CRT-D). This analysis of the prospectively conducted German Device Registry aims at comparing mortality rates, comorbidities, complication rates to results from RCT.The German Device registry (DEVICE) prospectively collected data on ICD and CRT-D first implantations from 50 German centres. Demographic data, details on cardiac disease, electrocardiogram (ECG), medication, and data about procedure, complications, and hospital stay were stored in electronic case report forms. One year after device implantation patients were contacted for follow-up.DEVICE included n = 4384 first ICD/CRT-D implantations (29.3% CRT-D devices). We found a strong adherence to guidelines with over 90% of patients being on ß-blocker and ACE-inhibitor medication and adequate QRS width in the majority of CRT-D patients. Patients receiving a CRT-D were older (67.6 ± 11.0 years vs. 63.9 ± 13.4 years, p .001) and had lower ejection fractions (mean 25% vs. 30%, p .001) compared to ICD patients. Dilated cardiomyopathy was the predominant underlying heart disease in CRT-D (53.3%), coronary artery disease in ICD patients (64.7%). Compared to RCT our DEVICE patients had more comorbidities (17.9% chronic kidney disease [CKD]) and higher 1-year mortality rates (10.7% ICD group, 12.3% CRT group). In multivariate analysis, CKD patients had an almost 2-fold higher risk of 1-year mortality.Despite relevant limitations of registry data, DEVICE highlights important differences between RCT and real-world registry data and the impact of comorbidities on mortality of ICD and CRT-D recipients.

Introduction: Automated echocardiography image interpretation has the potential to transform clinical practice. However, neural networks developed in general cohorts may underperform in the setting of altered cardiac anatomy. Methods: Consecutive echocardiographic studies of patients with congenital or structural heart disease (C/SHD) were used to validate an existing convolutional neural network trained on 14,035 echocardiograms for automated view classification. In addition, a new convolutional neural network for view classification was trained and tested specifically in patients with C/SHD. Results: Overall, 9793 imaging files from 262 patients with C/SHD (mean age 49 years, 60% male) and 62 normal controls (mean age 45 years, 50.0% male) were included. Congenital diagnoses included among others, tetralogy of Fallot (30), Ebstein anomaly (18) and transposition of the great arteries (TGA, 48). Assessing correct view classification based on 284,250 individual frames revealed that the non-congenital model had an overall accuracy of 48.3% for correct view classification in patients with C/SHD compared to 66.7% in patients without cardiac disease. Our newly trained convolutional network for echocardiographic view detection based on over 139,910 frames and tested on 35,614 frames from C/SHD patients achieved an accuracy of 76.1% in detecting the correct echocardiographic view. Conclusions: The current study is the first to validate view classification by neural networks in C/SHD patients. While generic models have acceptable accuracy in general cardiology patients, the quality of image classification is only modest in patients with C/SHD. In contrast, our model trained in C/SHD achieved a considerably increased accuracy in this particular cohort.

Atrial fibrillation and other atrial tachyarrhythmias are increasing with age and concomitant morbidity. First options in symptomatic patients are drug treatment and catheter ablation. Nevertheless, a considerable number of patients suffer from refractory atrial tachyarrhythmias despite treatment. Atrioventricular node ablation (AVNA) may be helpful in many of these patients. Therefore, we investigated AVNA patients with a long-term follow-up. We enrolled 82 patients with a follow-up longer than 1 year receiving AVNA for drug- and ablation-resistant atrial tachyarrhythmias (AA) in a retrospective manner. Mean follow-up duration was 48 ± 24 months. 50% of the patients initially received AVNA to optimize biventricular pacing in cardiac resynchronization therapy, the other 50% because of refractory symptomatic tachyarrhythmias. Persistent AV block was achieved in every patient. Symptom relief and patient satisfaction were high during follow-up. Due to system upgrades there were 63% of patients with a biventricular system during follow-up. In these patients, left-ventricular ejection fraction (LV-EF) increased by 7% (42-49%) after ablation. AVNA is effective in increasing biventricular pacing as well as for symptom relief in patients with refractory atrial tachyarrhythmias. AVNA should be considered as a valuable option in patients with refractory atrial tachyarrhythmias lacking other treatment options.

The subcutaneous ICD (S-ICD™) is an important advance in device therapy for the prevention of sudden cardiac death (SCD). Although current guidelines recommend S-ICD™ use, long-term data are still limited, especially in subgroups. Among several cardiac diseases that prone to SCD, coronary artery disease (CAD) carries several peculiarities that may hamper S-ICD™ therapy in this cohort. CAD can lead to an ischemic cardiomyopathy (ICM) with a reduced left-ventricular ejection fraction (LVEF) and bundle branch blocks, which can be difficult for ICD sensing and discrimination of arrhythmia. CAD is mainly driven by risk factors such as diabetes mellitus, which put these patients at an elevated risk for infectious complications of cardiac devices. Furthermore, in ICM myocardial scars are frequent and are a potential substrate for ventricular tachycardia, which may be accessible for antitachycardia pacing. At the moment, it remains unclear if there is a value of S-ICD™ therapy in this subgroup. Therefore, this study analysed patients with CAD. All S-ICD™ patients with CAD as the main indication for ICD implantation (n = 45 patients) in our large-scaled single-center S-ICD™ registry (n = 249 patients) were included in this study. Baseline characteristics, appropriate and inappropriate shocks, and complications were documented in a mean follow-up of 22.5 ± 8.3 months. Primary prevention of SCD was the indication for implantation of an S-ICD™ in 28 patients (62%). Of all 45 patients with an overall mean age of 58.1 ± 11.4 years, 40 were male (88%). The mean LVEF was 37.7 ± 12.6%. Three episodes of ventricular arrhythmia (one monomorphic, one polymorphic, one ventricular fibrillation) were adequately terminated in three patients (7%). In only one patient, oversensing resulting in an inappropriate shock was observed, which could be managed by changing the sensing vector. 15 of the examined 45 patients previously had a transvenous ICD, which was explanted due to system-related infections. In only two patients, S-ICD™ was changed to transvenous ICD because of the need of antibradycardia stimulation. There were no S-ICD™ system-related infections. The S-ICD™ seems to be a valuable option for the prevention of SCD in CAD patients. Patients with systemic infections of a transvenous ICD and, therefore, a need for an alternative might benefit from the absence of intracardiac leads as the S-ICD™ is safe and works flawlessly in these patients. Inadequate shock delivery was very rare, while every episode of ventricular arrhythmia was terminated by the first shock.

Background: The subcutaneous ICD (S-ICD) is used in an increasing number of patients for primary and secondary prevention of sudden cardiac death. Decision-making in primary prevention is not always trivial and many clinical scenarios are not reflected in current ICD guidelines. To help evaluating the patient’s individual risk, a new score trying to predict the benefit of an ICD implantation for primary prevention, the MADIT-ICD benefit score, which tries to predict occurrence of ventricular arrhythmias and non-arrhythmic death, has been proposed. We therefore aimed at examining its usefulness in a large single centre register of S-ICD patients Methods and results: All S-ICD patients with a primary preventive indication for ICD implantation from our large single centre database were included in the analysis (n=173). During a follow-up of 1227±978 days 27 patients developed sustained ventricular arrhythmias, while 6 patients died for non-arrhythmic reasons. Occurrence of ventricular arrhythmias could not sufficiently be predicted by the MADIT-ICD VT/VF score (p=0.3) in patients with (n=142, p=0.19) as well as patients without structural heart disease (n=31, p=0.88). However, there was a significant correlation for patients with ischemic cardiomyopathy (ICM) (n=29, p=0.04). Only one parameter (non-sustained ventricular tachycardia) was significantly associated with sustained ventricular arrhythmias (p=0.02). Of note, non-arrhythmic death could effectively be predicted by the proposed non-arrhythmic mortality score as part of the benefit score (p=0.001, r=0.3) also mainly driven by ICM patients. Age, diabetes mellitus, and a BMI 2 were key predictors of non-arrhythmic death implemented in the score.Conclusion: The MADIT-ICD benefit score adds a new option to evaluate expected benefit of ICD implantation for primary prevention. However, in our S-ICD cohort, the only group in which the score worked properly for prediction of sudden and non-sudden death were ICM patients, so that a larger validation in more heterogeneous cohorts in mandatory to claim general validity for this score in risk stratification for primary preventive ICD implantation.

Fortunately, the population of adults with congenital heart disease (ACHD) is growing due to improved operation techniques. Life expectancy is continuously rising, nevertheless, sudden cardiac death is one of the leading causes of mortality in ACHD late after initial diagnosis. Risk stratification in ACHD remains challenging as large study results are missing, congenital defects and operation methods differ considerably between individual patients and results from acquired heart diseases are often not conferrable. The purpose of this narrative review is to objectively summarize the current knowledge on arrhythmogenic risk of ACHD and to give an overview on implantable cardioverter-defibrillator (ICD) therapy in this collective. Remarkable progress has been made in electrophysiological understanding of critical areas of slow conduction especially in patients with Tetralogy of Fallot (ToF). In patients with transposition of the great arteries after atrial baffling (Mustard/Senning procedure) atrial arrhythmias play a crucial role in sudden cardiac death. ICD therapy in ACHD may pose special technical challenges due to limited access for intracardiac leads. The introduction of the totally subcutaneous ICD improved therapeutic options for ACHD especially when contraindications for transvenous leads are present. Risk stratification in ACHD has to be seen as a team approach, requires thorough understanding of congenital heart defects and the operation techniques and needs unconventional technical approaches in some cases.

Background The role and technique of catheter ablation of atrial fibrillation (AF) in the elderly is unclear. While in young patients pulmonary vein isolation (PVI) has evolved as first option, in older patients decision is often made in favor of drugs as higher complication rates and less benefit are suspected. Therefore, data on PVI of paroxysmal and persistent AF in these patients is still sparse but of eminent importance. Hypothesis PVI is comparably safe in the very elderly with similar recurrence and complication rates. Methods We enrolled all patients (n = 146) aged >75 years who underwent a first PVI over a period of 10 years (2009‐2019) from our prospective single‐center ablation registry. Mean follow‐up time was 231 ± 399 days. Results Acute ablation success defined as complete PVI and sinus rhythm at the end of the ablation procedure was high (99%). Severe periprocedural complications occurred in 3.3% (stroke/TIA n = 2; 1.3%; pericardial effusion n = 3; 2%). In 4.6% of patients symptomatic sick‐sinus‐syndrome was unmasked after PVI resulting in pacemaker implantation. There were no deaths related to PVI. Recurrence rate of symptomatic AF was 37.3% resulting in a Re‐PVI and/or substrate ablation in 32 pts (20.9%). During follow‐up pacemaker implantation plus atrioventricular node ablation was performed in 10 pts (6.8%). There was a trend toward lower recurrence rates with single‐shot devices (cryoballoon, multielectrode phased‐radiofrequency ablation catheter) than with point‐by‐point radiofrequency while complication rates did not differ. Conclusion PVI for AF is a feasible treatment option also in patients >75 years with a reasonable success and safety profile. Higher success rates occurred in patients treated with a single‐shot device as compared to point‐by‐point ablation.

Background Ablation emerged as first line therapy in the treatment of various arrhythmias. Nevertheless, in older patients (pts), decision is often made pro drug treatment as more complications and less benefit are suspected. Hypothesis We hypothesized that different kind of ablations can be performed safely regardless of the pts age. Methods We enrolled all pts aged >80 years (yrs) who underwent ablation for three different arrhythmias (atrial flutter [AFL], atrioventricular nodal re‐entry tachycardia [AVNRT], ventricular tachycardia [VT]) between August 2002 and December 2018. Procedural data and outcome were compared with matched groups aged 60 to 80 years and 40 to 60 years, respectively. Periprocedural and in‐hospital complications were analyzed. Results The analysis included 1191 patients (397 pts per group: 63% AFL, 23% AVNRT, 14% VT) who underwent ablation. Acute success was high in all types of arrhythmias irrespective of age (>80, 60‐80, 40‐60 years: AFL 97%/98%/98%, AVNRT 97%/95%/97%, VT 82%/86%/93%). Rate of periprocedural complications were similar in all groups treated for AFL and AVNRT. For VT ablations significant differences were noted between pts > 80 or 60 to 80 years and those aged 40‐60 years (16.1%/14.3%/3.6%). Most complications were infections and groin haematoma. No strokes, iatrogenic atrioventricular blocks and deaths related to the ablation occurred. Conclusion Ablation appears safe in pts > 80 years. Success rates were comparable to matched younger cohorts. A significant difference was observed for VT patients.

Previous studies report conflicting data regarding anti- or proarrhythmic effects of sacubitril. Aim of this study was to assess the impact of acute sacubitril treatment in different arrhythmia models.Sacubitril was administered (3, 5, 10 μM) in 12 isolated rabbit hearts. Further 12 hearts were treated with erythromycin to simulate long-QT-syndrome-2 (LQT2). Other 12 hearts were perfused with veratridine to mimic long-QT-syndrome-3 (LQT3). Both LQT-groups were treated with sacubitril (5 μM) additionally. Ventricular vulnerability was assessed by a pacing protocol. AV-blocked bradycardic hearts were perfused with a hypokalemic solution to trigger torsade de pointes (TdP). In further 13 hearts, AF was induced by a combination of acetylcholine and isoproterenol and sacubitril (5 μM) was added afterwards.With sacubitril, action potential duration (APD) was abbreviated whereas spatial dispersion of repolarisation (SDR) remained stable. In both LQT groups, APD and SDR were increased. Infusion of sacubitril reduced APD (- 21 ms, p 0.01) and SDR (- 8 ms) in the LQT2-group and did not alter APD (+2 ms) but reduced SDR (-19 ms, p 0.01) in the LQT3-group. Ventricular vulnerability was not altered by sacubitril. No TdP were observed with sacubitril or under baseline conditions in any group. Sacubitril significantly suppressed TdP in the LQT2-group (3 vs. 43 episodes, p 0.05) but not in the LQT3-group (10 vs. 16 episodes, p = ns). Sacubitril reduced inducibility of AF (9 vs. 31 episodes).Sacubitril abbreviated APD. In addition, sacubitril exhibits potential antiarrhythmic effects in LQT2 and may be beneficial in LQT3 and AF.

ZusammenfassungDas Verhältnis von Vorhofflimmern und Herzinsuffizienz geht über eine Koinzidenz hinaus. Vielmehr bedingen sich beide Erkrankungen pathogenetisch wechselseitig. In der jüngeren Vergangenheit hat es einige Studien gegeben, die den direkten Effekt einer Behandlung von Vorhofflimmern auf eine begleitend vorliegende Herzinsuffizienz untersucht haben. Die CASTLE-AF-Studie konnte kürzlich zeigen, dass eine katheterinterventionelle Behandlung des Vorhofflimmerns die Prognose und Symptomatik herzinsuffizienter Patienten verbessert. Deshalb könnte diese Therapie zukünftig ein effektiver Pfeiler der Herzinsuffizienztherapie sein und wird vermutlich in zukünftigen Leitlinien einen größeren Raum einnehmen. Zudem hat mit Sacubitril/Valsartan ein neuer und jetzt schon bedeutsamer Baustein der Herzinsuffizienzmedikation möglicherweise ein antiarrhythmisches Potenzial, dessen Einfluss auf Vorhofflimmern interessant zu beobachten sein wird. Insgesamt ist damit die Interaktion von Vorhofflimmern und Herzinsuffizienz nicht nur pathogenetisch relevant, sondern wahrscheinlich auch therapeutisch von großer Bedeutung.

Background: Vascular calcification is a common phenomenon in patients with chronic kidney disease and strongly associated with increased cardiovascular mortality. Vascular calcification is an active process mediated in part by inflammatory processes in vascular smooth muscle cells (VSMC). These could be modified by the insufficient removal of proinflammatory cytokines through conventional high-flux (HF) membranes. Recent trials demonstrated a reduction of inflammation in VSMC by use of dialysis membranes with a higher and steeper cut-off. These membranes caused significant albumin loss. Therefore, the effect of high retention Onset (HRO) dialysis membranes on vascular calcification and its implications in vitro was evaluated. Methods: In the PERCI II trial, 48 chronic dialysis patients were dialyzed using HF and HRO dialyzers and serum samples were collected. Calcifying VSMC were incubated with the serum samples. Calcification was determined using alizarin red staining (AZR) and determination of alkaline phosphatase (ALP) activity. Furthermore, apoptosis was evaluated, and release of matrix Gla protein (MGP), osteopontin (OPN) and growth differentiation factor 15 (GDF-15) were measured in cell supernatants. Results: Vascular calcification in vitro was significantly reduced by 24% (ALP) and 36% (AZR) after 4 weeks of HRO dialysis and by 33% (ALP) and 48% (AZR) after 12 weeks of dialysis using HRO membranes compared to HF dialysis. Apoptosis was significantly lower in the HRO group. The concentrations of MGP and OPN were significantly elevated after incubation with HF serum compared to HRO serum and healthy controls. Similarly, GDF-15 release in the supernatant was elevated after incubation with HF serum, an effect significantly ameliorated after treatment with HRO medium. Conclusions: Expanded haemodialysis therapy reduces the pro-calcific potential of serum from dialysis patients in vitro. With a markedly reduced albumin filtration compared to high cut-off dialysis, use of the HRO dialyzers may possibly provide a treatment option for chronic dialysis patients to reduce the progression of vascular calcification.

Recently developed high-flux (HF) dialysis membranes with extended permeability provide better clearance of middle-sized molecules such as interleukins (ILs). Whether this modulation of inflammation influences the procalcific effects of septic plasma on vascular smooth muscle cells (VSMCs) is not known. To assess the effects of high cut-off (HCO) and medium cut-off (MCO) membranes on microinflammation and in vitro vascular calcification we developed a miniature dialysis model. Plasma samples from lipopolysaccharide-spiked blood were dialyzed with HF, HCO, and MCO membranes in an in vitro miniature dialysis model. Afterwards, IL-6 concentrations were determined in dialysate and plasma. Calcifying VSMCs were incubated with dialyzed plasma samples and vascular calcification was assessed. Osteopontin (OPN) and matrix Gla protein (MGP) were measured in VSMC supernatants. IL-6 plasma concentrations were markedly lower with HCO and MCO dialysis. VSMC calcification was significantly lower after incubation with MCO- and HCO-serum compared to HF plasma. MGP and OPN levels in supernatants were significantly lower in the MCO but not in the HCO group compared to HF. In vitro dialysis of cytokine-enriched plasma samples with MCO and HCO membranes reduces IL-6 levels. The induction of vascular calcification by cytokine-enriched plasma is reduced after HCO and MCO dialysis.

The performance of the subcutaneous ICD (S-ICD™) has been described in different kinds of heart disease and has been proven to be an important advance in prevention of sudden cardiac death (SCD). While positive experiences with the S-ICD™ initially came from collectives of patients without structural heart diseases, positive results have also been collected from cohorts with structural heart disease. All S-ICD™ patients with either ischemic cardiomyopathy (ICM), dilated cardiomyopathy (DCM) or hypertrophic cardiomyopathy (HCM) as the main indication for ICD implantation (n = 144 patients) or electrical heart disease/idiopathic ventricular fibrillation (n = 83 patients) in our large-scaled single-center S-ICD™ registry were included in this study. Baseline characteristics, appropriate and inappropriate shocks, and complications were documented in a mean follow-up of 18 ± 15 months. Baseline characteristics were significantly different between the two groups in most categories. In contrast, there was no difference concerning neither appropriate nor inappropriate shock delivery between the two groups. Also other outcome parameters such as need for surgical revisions and all-cause mortality did not differ. There was a significant difference between the first- and second-generation S-ICDs™ in inadequate shocks mainly driven by patients with HCM. In our study, S-ICD™ performance was similar in patients with and without structural heart disease. Decision pro- or contra-S-ICD™ should be made rather on the basis of expected shock rate and probability of the need for future anti-tachycardia or anti-bradycardia pacing than in dependence of the underlying heart disease.

Background Sarcoidosis is a multisystem granulomatous disease of not sufficiently understood origin. Some patients develop cardiac involvement in course of the disease which is mostly responsible for adverse outcome. In addition to complications like high degree atrioventricular (AV) block or ventricular tachyarrhythmias, there is a certain percentage of patients developing atrial tachyarrhythmias. Data is limited and the role of catheter ablation uncertain. Therefore, we studied sarcoid patients who presented with supraventricular tachyarrhythmias. Hypothesis Treatment and ablation of supraventricular tachycardia could be hampered by inflammation in patients with cardiac sarcoidosis. Methods We enrolled 37 consecutive patients with cardiac sarcoidosis who presented with atrial tachyarrhythmias and underwent an electrophysiologic study over a period of 6 years (03/2013‐04/2019). In total, 16 catheter ablations for atrial tachyarrhythmias were performed. Mean follow‐up duration was 2.5 years. Results Most common ablation performed was cavo‐tricuspid isthmus ablation for typical atrial flutter in seven patients (54%). Pulmonary vein isolation for treatment of atrial fibrillation (AF) was performed in five patients (38%). Two patients received slow‐pathway modulation for treatment of recurrent atrioventricular nodal reentry tachycardia (AVNRT). All but two patients with AF had no clinical recurrence during follow‐up. Two patients had recurrence of AF but still reported markedly improved european heart rhythm association (EHRA) class. Periprocedural safety was very high. There were no adverse events related to the ablation procedure. One patient died during follow‐up in the presence of electrical storm. Conclusion Catheter ablations of supraventricular tachycardias seem to be safe and effective in patients with cardiac sarcoidosis. Outcome is comparable to patients without inflammatory heart disease, although data from larger patient collectives are mandatory to make recommendations in this special entity.

Recent experimental studies showed a protective effect of the renin inhibitor aliskiren regarding atrial structural remodeling. Purpose of this study was to assess acute electrophysiologic effects of aliskiren in a whole-heart model of atrial fibrillation (AF) and to investigate its impact on the ventricle. Twelve rabbit hearts were excised, retrogradely perfused, and paced at different cycle lengths. To enhance atrial vulnerability, a combination of acetylcholine (ACh) and isoproterenol (Iso) was infused and significantly reduced atrial action potential duration (aAPD90) and atrial effective refractory period (aERP). Additional infusion of aliskiren prolonged aAPD90 but did not alter aERP. A triangulation of action potential with ACh/Iso and a further triangulation after treatment with aliskiren were noted. Vulnerability to AF was tested by employing trains of burst pacing. Administration of ACh/Iso provoked more episodes of AF (baseline: 26 episodes, Iso/Ach: 48 episodes). Additional treatment with aliskiren induced AF significantly more often (108 episodes). Another nine hearts were perfused with aliskiren to examine its ventricular effects. Infusion with aliskiren abbreviated ventricular APD90 and ERP. Utilizing programmed ventricular stimulation, a trend towards more ventricular arrhythmias in aliskiren-treated hearts was observed. Though aliskiren did not reduce aAPD90 or aERP, acute treatment with aliskiren promoted AF. Triangulation of atrial action potentials, which is an established risk factor for ventricular proarrhythmia, may contribute to the increased atrial vulnerability. This effect may interfere with its recently demonstrated beneficial properties in atrial remodeling. Of note, aliskiren might have a proarrhythmic effect on the ventricular level.

The subcutaneous ICD (S-ICD™) is an important advance in device therapy for prevention of sudden cardiac death (SCD). In some patients, decision pro- or contra-ICD implantation is particularly challenging due to inconsistent data on risk of ventricular tachyarrhythmias or sudden cardiac death, rare entities, special medical or family history, or patients’ wishes. Whether decision-making in these borderline cases has been facilitated with the new option of a S-ICD™ is unknown. All patients with an implanted S-ICD™ without a class I or IIa recommendation for primary prophylaxis of sudden cardiac death in the current guidelines (n = 30 patients) in our large-scaled single-centre S-ICD™ registry (n = 249 patients) were included in this study. Baseline characteristics, appropriate and inappropriate shocks, and complications were documented in a mean follow-up of 40 months. In all patients S-ICD™ implantation was performed for primary prevention of SCD. Of all 30 patients with an overall mean age of 40.5 ± 15.6 years, 17 were male (57%). The mean left ventricular ejection fraction (LVEF) was 54.5 ± 9.9%. Indication were highly variable and ranged from structural heart disease, nsVT and LV-EF > 35% to patients with polymorphic non-sustained ventricular tachycardia (nsVT) and suspect syncope. During follow-up, six episodes of sustained ventricular tachyarrhythmias and four episodes of ventricular fibrillation (VF) were adequately terminated in three patients (10%). Two of these patients were implanted for polymorphic nsVT and previous syncope without structural heart disease. In three patients, T-wave-oversensing and in one patient also P-wave-oversensing resulted in an inappropriate shock (five in total), two additional episodes of oversensing ended before shock delivery. There were no S-ICD™ system-related infections. In five patients S-ICD™ replacement was performed due to battery depletion (four regular, one premature). In five patients, ablation procedures were performed after implantation (four because of frequent symptomatic ventricular extra beats, one because of atrial flutter). Change to a transvenous system was necessary in two patients due to need for antibradycardia pacing. The use of the S-ICD™ was safe in patients with borderline or unclear indication for ICD implantation in our study. Of note, during a relatively short mean follow-up there were several appropriate therapies, especially for VF in these patients. On the other hand, oversensing also occurred in about 10% of patients, while lead problems were not problematic in this collective. S-ICD™ implantation may be considered as a possible alternative in cases of borderline indications and clinical uncertainty when decision pro-ICD implantation is made. Incidence of arrhythmias was quite high and mostly consisted of VF. Nevertheless, patient education seems even more important as there is a considerable risk for inappropriate therapies as well.

Aims The subcutaneous implantable cardioverter-defibrillator (S-ICDTM) is an important advance in device therapy for the prevention of sudden cardiac death (SCD). Although current guidelines recommend S-ICDTM use, long-term data are still limited, especially in subgroups such as adult patients with congenital heart diseases. This cohort is of high interest because of the difficult anatomic conditions in these patients. Methods and results All S-ICDTM patients with an underlying congenital heart disease (CHD) resulting in an indication for ICD implantation (n = 20 patients) in our large-scaled single-centre S-ICDTM registry (n = 249 patients) were included in this study. Baseline characteristics, appropriate and inappropriate shocks, and complications were documented in a mean follow-up of 36 months. Primary prevention of SCD was the indication for implantation of an S-ICDTM in six patients (30%). Of all 20 patients with an overall mean age of 40.5 ± 11.5 years, 12 were male (60%). The mean left ventricular ejection fraction was 46.5 ± 11.3%. Nine episodes of ventricular tachycardia (two monomorphic and seven polymorphic) were adequately terminated in three patients (15%). In two patients, T-Wave-Oversensing resulting in an inappropriate shock was observed, which could be managed by changing the sensing vector or activation of the SMART PASSTM filter. There were no S-ICDTM system-related infections. In one patient, surgical revision was necessary due to a persistent haematoma. Conclusion The S-ICDTM seems to be a valuable option for the prevention of SCD in patients with various CHDs and complex anatomical anomalies. The S-ICDTM is safe and works effectively, also in these complex patients. Inadequate shock delivery was rare and could be managed by reprogramming.

Introduction Patients with chronic kidney disease maintained on intermittent hemodialysis suffer from systemic chronic inflammation which is causally associated with high mortality. Inflammation mediators of 15–45 kDa range cannot be effectively removed by conventional dialysis membranes. In this study, we tested the influence of serum and dialysates obtained from patients maintained on High cut-off or High flux membranes on the inflammation profile of THP-1 monocytes. Methods THP-1 monocytes were treated with serum or dialysates obtained from patients maintained on High cut-off and High flux membranes within a randomized crossover pilot trial. Serum-treated cells were subjected to qPCR analyses with TaqMan probes specific for IL6, TNFa, osteopontin and osteocalcin, and transcriptional screening with Inflammatory Array. Apoptosis assay was performed flow cytometrically with 7-AAD and Annexin V staining. Findings Treatment of the cells with High cut-off serum led to significant reduction of TNFa and IL-6 expression as well as inflammation-related osteopontin and osteocalcin as compared to High flux membrane treatment. As a complementary finding, treatment with High cut-off dialysates induced a pro-apoptotic phenotype in the cells as demonstrated by a significantly increased percentage of 7-AAD and Annexin V positivity. Global screening of serum-treated cells revealed noticeably decreased inflammation profile under High cut-off serum as compared to High flux treatment. Discussion Taken together, these data demonstrate that High cut-off -membranes eliminate a spectrum of mediators from serum into the dialysate that possess proinflammatory properties and may impair cellular viability.

Background Vascular calcification is enhanced in chronic dialysis patients, possibly due to the insufficient removal of various intermediate molecular weight uraemic toxins such as interleukins with conventional membranes. In this study, we assessed the modulation of in vitro vascular calcification with the use of high cut-off (HCO) membranes in chronic dialysis patients. Methods In a PERCI trial, 43 chronic dialysis patients were treated with conventional high-flux and HCO filters for 3 weeks in a randomized order following a 2-period crossover design. After each phase, serum predialysis samples were drawn. Calcifying human coronary vascular smooth muscle cells (VSMCs) were incubated with the patient's serum samples. Calcification was assessed with alkaline phosphatase (ALP) and alizarin red staining. In the clinical trial, HCO dialysis reduced the serum levels of the soluble tumour necrosis factor receptor (sTNFR) 1 and 2, vascular cell adhesion molecule 1 (VCAM-1) and soluble interleukin-2 receptor (sIL2R). We therefore investigated the in vitro effects of these mediators on vascular calcification. Results VSMCs incubated with HCO dialysis serum showed a 26% reduction of ALP with HCO serum compared with high-flux serum. Alizarin was 43% lower after incubation with the HCO serum compared with the high-flux serum. While sIL2R and sTNFR 1 and 2 showed no effects on VSMC calcification, VCAM-1 caused a dose-dependent enhancement of calcification. Conclusions The use of HCO dialysis membranes in chronic dialysis patients reduces the procalcific effects of serum on VSMC in vitro. The mechanisms of the strong effect of HCO on in vitro calcification are not completely understood. One factor may be lower levels of VCAM-1 in HCO serum samples, since VCAM-1 was able to induce vascular calcification in our experiments. Neither sTNFR 1, sTNFR 2 nor sIL2R enhance vascular calcification in vitro. Regardless of the mechanisms, our results encourage further studies of highly permeable filters in chronic dialysis patients.

Subcutaneous ICD (S-ICD™) therapy has been established in initial clinical trials and current international guideline recommendations for patients without demand for pacing, cardiac resynchronization, or antitachycardia pacing. The promising experience in ‘ideal’ S-ICD™ candidates increasingly encourages physicians to provide the benefits of S-ICD™ therapy to patients in clinical constellations beyond ‘classical’ indications of S-ICD™ therapy, which has led to a broadening of S-ICD™ indications in many centres. However, the decision for S-ICD™ implantation is still not covered by controlled randomized trials but rather relies on patient series or observational studies. Thus, this review intends to give a contemporary update on available empirical evidence data and technical advancements of S-ICD™ technology and sheds a spotlight on S-ICD™ therapy in recently discovered fields of indication beyond ideal preconditions. We discuss the eligibility for S-ICD™ therapy in Brugada syndrome as an example for an adverse and dynamic electrocardiographic pattern that challenges the S-ICD™ sensing and detection algorithms. Besides, the S-ICD™ performance and defibrillation efficacy in conditions of adverse structural remodelling as exemplified for hypertrophic cardiomyopathy is discussed. In addition, we review recent data on potential device interactions between S-ICD™ systems and other implantable cardio-active systems (e.g. pacemakers) including specific recommendations, how these could be prevented. Finally, we evaluate limitations of S-ICD™ therapy in adverse patient constitutions, like distinct obesity, and present contemporary strategies to assure proper S-ICD™ performance in these patients. Overall, the S-ICD™ performance is promising even for many patients, who may not be ‘classical’ candidates for this technology.

Background High mortality of haemodialysis patients is associated with systemic chronic inflammation and overactivation of the renin-angiotensin system (RAS). Insufficient elimination of pro-inflammatory immune mediators, especially in the molecular weight range of 15-45 kDa, may be one of the reasons for this. Employment of haemodialysis membranes with increased permeability was shown to ameliorate the inflammatory response and might modulate the effects of local RAS. In this study, we tested the impact of high cut-off (HCO), medium cut-off (MCO) and high-flux (HF) dialysis on leucocytic transcripts of angiotensin-converting enzymes (ACE and ACE2). Additionally, the impact of HCO, MCO and HF sera and dialysates on local ACEs and inflammation markers was tested in THP-1 monocytes. Methods Patients' leucocytes were obtained from our recent clinical studies comparing HCO and MCO dialysers with HF. The cells were subjected to quantitaive polymerase chain reaction (qPCR) analyses with TaqMan probes specific for ACE, ACE2 and angiotensin II (AngII) and Ang1-7 receptors. Sera and dialysates from the clinical trials as well as samples from in vitro dialysis were tested on THP-1 monocytic cells. The cells were subjected to qPCR analyses with TaqMan probes specific for ACE, ACE2, interleukin-6 and tumour necrosis factor α and immunocytochemistry with ACE and ACE2 antibodies. Results Leucocytes obtained from patients treated with HCO or MCO demonstrated decreased transcript expression of ACE, while ACE2 was significantly upregulated as compared with HF. Receptors for AngII and Ang1-7 remained unchanged. THP-1 monocytes preconditioned with HCO and MCO patients' or in vitro dialysis sera reflected the same expressional regulation of ACE and ACE2 as those observed in HCO and MCO leucocytes. As a complementary finding, treatment with HCO and MCO in vitro dialysates induced a pro-inflammatory response of the cells as demonstrated by elevated messenger RNA expression of tumour necrosis factor α and interleukin-6, as well as upregulation of ACE and decreased levels of ACE2. Conclusions Taken together, these data demonstrate that employment of membranes with high permeability eliminates a spectrum of mediators from circulation that affect the RAS components in leucocytes, especially ACE/ACE2.

Background Vascular calcification is enhanced in uraemic chronic haemodialysis patients, likely due to the accumulation of midsize uraemic toxins, such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Here we have assessed the impact of uraemia on vascular smooth muscle cell (VSMC) calcification and examined the role of IL-6 and TNF-α as possible mediators and, most importantly, its underlying signalling pathway in VSMCs. Methods VSMCs were incubated with samples of uraemic serum obtained from patients treated with haemodialysis for renal failure in the Permeability Enhancement to Reduce Chronic Inflammation-I clinical trial. The VSMCs were assessed for IL-6 gene regulation and promoter activation in response to uraemic serum and TNF-α with reporter assays and electrophoretic mobility shift assay and for osteoblastic transition, cellular calcification and cell viability upon osteogenic differentiation. Results Uraemic serum contained higher levels of TNF-α and IL-6 compared with serum from healthy individuals. Exposure of VSMCs to uraemic serum or recombinant TNF-α lead to a strong upregulation of IL-6 mRNA expression and protein secretion, which was mediated by activator protein 1 (AP-1)/c-FOS-pathway signalling. Uraemic serum induced osteoblastic transition and calcification of VSMCs could be strongly attenuated by blocking TNF-α, IL-6 or AP-1/c-FOS signalling, which was accompanied by improved cell viability. Conclusion These results demonstrate that uraemic serum contains higher levels of uraemic toxins TNF-α and IL-6 and that uraemia promotes vascular calcification through a signalling pathway involving TNF-α, IL-6 and the AP-1/c-FOS cytokine-signalling axis. Thus treatment modalities aiming to reduce systemic TNF-α and IL-6 levels in chronic haemodialysis patients should be evaluated in future clinical trials.

Background To increase the removal of middle-sized uremic toxins a new membrane with enhanced permeability and selectivity, called Medium Cut-Off membrane (MCO-Ci) has been developed that at the same time ensures the retention of albumin. Because many middle-sized substances may contribute to micro-inflammation we hypothesized that the use of MCO-Ci influences the inflammatory state in hemodialysis patients. Methods The randomized crossover trial in 48 patients compared MCO-Ci dialysis to High-flux dialysis of 4 weeks duration each plus 8 weeks extension phase. Primary endpoint was the gene expression of TNF-α and IL-6 in peripheral blood mononuclear cells (PBMCs), secondary endpoints were plasma levels of specified inflammatory mediators and cytokines. Results After four weeks of MCO-Ci the expression of TNF-α mRNA (Relative quantification (RQ) from 0.92 ± 0.34 to 0.75 ± 0.31, -18.5%, p

Recently developed high-flux (HF) dialysis membranes with extended permeability provide better clearance of middle-sized molecules such as interleukins (ILs). Whether this modulation of inflammation influences the procalcific effects of septic plasma on vascular smooth muscle cells (VSMCs) is not known. To assess the effects of high cut-off (HCO) and medium cut-off (MCO) membranes on microinflammation and in vitro vascular calcification we developed a miniature dialysis model. Plasma samples from lipopolysaccharide-spiked blood were dialyzed with HF, HCO, and MCO membranes in an in vitro miniature dialysis model. Afterwards, IL-6 concentrations were determined in dialysate and plasma. Calcifying VSMCs were incubated with dialyzed plasma samples and vascular calcification was assessed. Osteopontin (OPN) and matrix Gla protein (MGP) were measured in VSMC supernatants. IL-6 plasma concentrations were markedly lower with HCO and MCO dialysis. VSMC calcification was significantly lower after incubation with MCO- and HCO-serum compared to HF plasma. MGP and OPN levels in supernatants were significantly lower in the MCO but not in the HCO group compared to HF. In vitro dialysis of cytokine-enriched plasma samples with MCO and HCO membranes reduces IL-6 levels. The induction of vascular calcification by cytokine-enriched plasma is reduced after HCO and MCO dialysis.

Patients with chronic kidney disease maintained on intermittent hemodialysis suffer from systemic chronic inflammation which is causally associated with high mortality. Inflammation mediators of 15-45 kDa range cannot be effectively removed by conventional dialysis membranes. In this study, we tested the influence of serum and dialysates obtained from patients maintained on High cut-off or High flux membranes on the inflammation profile of THP-1 monocytes.THP-1 monocytes were treated with serum or dialysates obtained from patients maintained on High cut-off and High flux membranes within a randomized crossover pilot trial. Serum-treated cells were subjected to qPCR analyses with TaqMan probes specific for IL6, TNFa, osteopontin and osteocalcin, and transcriptional screening with Inflammatory Array. Apoptosis assay was performed flow cytometrically with 7-AAD and Annexin V staining.Treatment of the cells with High cut-off serum led to significant reduction of TNFa and IL-6 expression as well as inflammation-related osteopontin and osteocalcin as compared to High flux membrane treatment. As a complementary finding, treatment with High cut-off dialysates induced a pro-apoptotic phenotype in the cells as demonstrated by a significantly increased percentage of 7-AAD and Annexin V positivity. Global screening of serum-treated cells revealed noticeably decreased inflammation profile under High cut-off serum as compared to High flux treatment.Taken together, these data demonstrate that High cut-off -membranes eliminate a spectrum of mediators from serum into the dialysate that possess proinflammatory properties and may impair cellular viability.