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We present two novel approaches to variance estimation of semi-parametric efficient point estimators of the treatment-specific mean: (i) a robust approach that directly targets the variance of the influence function (IF) as a counterfactual mean outcome and (ii) a modified non-parametric bootstrap-based approach. The performance of these approaches to variance estimation is compared to variance estimation based on the sample variance of the empirical IF in simulations across different levels of positivity violations and treatment effect sizes. In this article, we focus on estimation of the nuisance parameters using correctly specified parametric models for the treatment mechanism in order to highlight the challenges posed by violation of positivity assumptions (distinct from the challenges posed by non-parametric estimation of the nuisance parameters). Results demonstrate that (1) variance estimation based on the empirical IF may provide highly anti-conservative confidence interval coverage (as reported previously), (2) the proposed robust approach to variance estimation in this setting provides conservative coverage, and (3) the proposed modified bootstrap maintains close to nominal coverage and improves power. In the appendix, we (a) generalize the robust approach of estimating variance to marginal structural working models and (b) provide a proof of the consistency of the targeted minimum loss-based estimation bootstrap.

Background: Patients with atrial fibrillation (AF) often exhibit abnormalities of P wave morphology during sinus rhythm. We examined a novel method for automatic P wave analysis in the 24-hour-Holter-ECG of 60 patients with paroxysmal or persistent AF and 12 healthy subjects.Methods: Recorded ECG signals were transferred to the analysis program where 5-10 P and R waves were manually marked. A wavelet transform performed a time-frequency decomposition to train neural networks. Afterwards, the detected P waves were described using a Gauss function optimized to fit the individual morphology and providing amplitude and duration at half P wave height.Results: >96% of P waves were detected, 47.4 +/- 20.7% successfully analyzed afterwards. In the patient population, the mean amplitude was 0.073 +/- 0.028 mV (mean variance 0.020 +/- 0.008 mV(2)), the mean duration at half height 23.5 +/- 2.7 ms (mean variance 4.2 +/- 1.6 ms(2)). In the control group, the mean amplitude (0.105 +/- 0.020 ms) was significantly higher (P < 0.0005), the mean variance of duration at half height (2.9 +/- 0.6 ms(2)) significantly lower (P < 0.0085).Conclusions: This method shows promise for identification of triggering factors of AF. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Cerebral embolism and stroke are feared complications of left atrial catheter ablation such as pulmonary vein (PV) ablation. In order to assess the thrombogenicity of left atrial catheter ablation, knowledge of both clinically evident as well as silent cerebral embolism is important. The aim of the current study was to examine the use of diffusion-weighted magnetic resonance imaging (DW-MRI) for detection of cerebral embolism, apparent as well as silent, caused by PV catheter ablation. METHODS AND RESULTS: Twenty consecutive patients without structural heart disease undergoing lasso catheter-guided ostial PV ablation using an irrigated-tip ablation catheter were studied. Cerebral MRI including DW single-shot spin echo echoplanar, turbo fluid attenuated inversion recovery, and T2-weighted turbo spin echo sequences were performed the day after the ablation procedure. Ten patients also underwent preprocedure cerebral MRI. All ablation procedures were performed without acute complications. A mean of 3.2 +/- 0.6 PVs were ablated per patient. No patient had neurological symptoms following the procedure. In 2 of 20 patients (10%), DW-MRI revealed new embolic lesions, which were located in the right periventricular white matter in one and in the left temporal lobe in the other patient. There was no statistically significant difference in age, history of hypertension, left atrial volume, and procedure duration between the 2 patients with and the 18 patients without cerebral embolism following AF ablation. CONCLUSION: This is the first study using highly sensitive DW-MRI of the brain to detect asymptomatic cerebral embolism after left atrial catheter ablation. Even small, clinically silent, embolic lesions can be demonstrated with this technique. DW-MRI can be used to monitor and compare the thrombogenicity of different AF ablation approaches. [ABSTRACT FROM AUTHOR]

We describe two male patients with focal epilepsy in whom transitory episodes of atrial fibrillation (AF) lasting for up to 25h were detected in the context of generalized tonic-clonic seizures (GTCSs). In five of seven previously published cases of transitory AF associated with epileptic seizures, AF was also associated with GTCS, suggesting a pathophysiological link via GTCS-related increase in sympathetic tone and release of catecholamines. Importantly, AF increases the risk of thromboembolic cerebral ischemia, prompting the question of whether antithrombotic preventive treatment should be initiated in people with pharmacoresistant epilepsy and prolonged peri-ictal AF. Furthermore, AF can considerably impair cardiac output and may, via this mechanism, contribute to the risk of sudden unexpected death in epilepsy following GTCS. [ABSTRACT FROM AUTHOR]

This paper describes a targeted maximum likelihood estimator (TMLE) for the parameters of longitudinal static and dynamic marginal structural models. We consider a longitudinal data structure consisting of baseline covariates, time-dependent intervention nodes, intermediate time-dependent covariates, and a possibly time-dependent outcome. The intervention nodes at each time point can include a binary treatment as well as a right-censoring indicator. Given a class of dynamic or static interventions, a marginal structural model is used to model the mean of the intervention-specific counterfactual outcome as a function of the intervention, time point, and possibly a subset of baseline covariates. Because the true shape of this function is rarely known, the marginal structural model is used as a working model. The causal quantity of interest is defined as the projection of the true function onto this working model. Iterated conditional expectation double robust estimators for marginal structural model parameters were previously proposed by Robins (2000, 2002) and Bang and Robins (2005). Here we build on this work and present a pooled TMLE for the parameters of marginal structural working models. We compare this pooled estimator to a stratified TMLE (Schnitzer et al. 2014) that is based on estimating the intervention-specific mean separately for each intervention of interest. The performance of the pooled TMLE is compared to the performance of the stratified TMLE and the performance of inverse probability weighted (IPW) estimators using simulations. Concepts are illustrated using an example in which the aim is to estimate the causal effect of delayed switch following immunological failure of first line antiretroviral therapy among HIV-infected patients. Data from the International Epidemiological Databases to Evaluate AIDS, Southern Africa are analyzed to investigate this question using both TML and IPW estimators. Our results demonstrate practical advantages of the pooled TMLE over an IPW estimator for working marginal structural models for survival, as well as cases in which the pooled TMLE is superior to its stratified counterpart.

Gold-Tip Electrodes . Radiofrequency (RF) catheter ablation is widely used to induce focal myocardial necrosis using the effect of resistive heating through high-frequency current delivery. It is current standard to limit the target tissue-electrode interface temperature to a maximum of 60-70°C to avoid char formation. Gold (Au) exhibits a thermal conductivity of nearly four times greater than platinum (Pt-Ir) (3.17 W/cm Kelvin vs 0.716 W/cm Kelvin), it was therefore hypothesized that RF ablation using a gold electrode would create broader and deeper lesions as a result of a better heat conduction from the tissue-electrode interface and additional cooling of the gold electrode by 'heat loss' to the intracardiac blood. Both mechanisms would allow applying more RF power to the tissue before the electrode-tissue interface temperature limit is reached. To test this hypothesis, we performed in vitro isolated liver and pig heart investigations comparing lesion depths of a new Au-alloy-tip electrode to standard Pt-Ir electrode material. Mean lesion depth in liver tissue for Pt-Ir was 4.33 ± 0.45 mm (n = 60) whereas Au electrode was able to achieve significantly deeper lesions (5.86 ± 0.37 mm [n = 60; P < 0.001]). The mean power delivered using Pt-Ir was 6.95 ± 2.41 W whereas Au tip electrode delivered 9.64 ± 3.78 W indicating a statistically significant difference (P < 0.05). In vitro pig heart tissue Au ablation (n = 20) increased significantly the lesion depth (Au: 4.85 ± 1.01 mm, Pt-Ir: 2.96 ± 0.81 mm, n = 20; P < 0.001). Au tip electrode again applied significantly more power (P < 0.001). Gold-tip electrode catheters were able to induce deeper lesions using RF ablation in vitro as compared to Pt-Ir tip electrode material. In liver and in pig heart tissue, the increase in lesion depth was associated with a significant increase in the average power applied with the gold electrode at the same level of electrode-tissue temperature as compared to platinum material. (J Cardiovasc Electrophysiol, Vol. 16, pp. 1-3, June 2005) [ABSTRACT FROM AUTHOR]

OBJECTIVE: Evaluation of the significance of the Wedensky Modulation (WM) examination for ventricular tachyarrhythmias (VT) in patients with coronary artery disease and implantable cardioverter-defibrillator therapy (ICD). DESIGN: Prospective, single-centre study conducted from 2004 to 2006. SETTING: University of Bonn, Department of Medicine - Cardiology, Bonn, Germany. PATIENTS: 37 consecutive patients with coronary artery disease receiving an ICD for primary or secondary prevention. MAIN OUTCOME MEASURES: Correlation of a positive WM-Index (WMI) with established non-invasive Holter parameter, the occurrence of VT after ICD implantation with regard to primary or secondary prevention, and inducibility of VT during electrophysiological (EP) studies. RESULTS: The WMI was positive in 15 patients (67 (SD 8) years, 31% (SD 12%) EF) and showed significant correlation with heart rate variability (standard deviation of normal to normal intervals (SDNN): 143 (SD 80) ms vs 102 (SD 29) ms, p = 0.04, r = 0.45; total power (TP). 11 885 (SD 19 674) ms(2) vs 2229 (SD 1779) ms(2), p = 0.03, r = 0.384; very low frequency component (VLF): 2777 (SD 3039) ms(2) vs 1184 (SD 565) ms(2), p = 0.03; low frequency component (LF): 2955 (SD 5734) ms(2) vs 468 (SD 725) ms(2), p = 0.05, r = 0.375; high frequency component (HF): 4885 (SD 9939) ms(2) vs 382 (SD 609) ms(2), p = 0.05, r = 0.315) and turbulence (turbulence onset (TO): -0.002 (SD 0.008) vs +0.005 (SD 0.01), p = 0.05, r = 0.301; turbulence slope (TS): 3.4 (SD 3.1) vs 1.7 (SD 1.5), p = 0.04, r = 0.419). The positive predictive value of the WMI considering the inducibility of VT during EP testing was 100%. Those patients who received an ICD for primary prevention showed a higher WMI (p = 0.049) than the secondary prevention group. With respect to the occurrence of adequate VT episodes, a negative WM test result demonstrated a negative predictive value of 95%. CONCLUSION: The data presented show that the WM-Index predicts VT inducibility during EP testing and indicates a high negative predictive value regarding the occurrence of VT. [ABSTRACT FROM AUTHOR]

Background: In Germany, contemporary data on the prevalence of patients with an implantable cardioverter-defibrillator (ICD) is lacking. Recently, ICD patients with heart failure (HF) fulfilling pre-defined criteria by the G-BA (Federal Joined Committee) are eligible for remote monitoring (RM) reimbursement. This investigation aims to evaluate the prevalence of HF patients with an ICD meeting these criteria., Methods: Annual national quality assurance data from all German hospitals on newly implanted ICDs, New York Heart Association (NYHA) class and left ventricular ejection fraction (LVEF) between 2010 and 2021 were obtained to build a prevalence model. The number of ICD patients eligible for RM was calculated by applying the main G-BA inclusion criteria., Results: The ICD prevalence increased continuously from 2010 to 2017 (202.637 patients in 2017) and decreased with a lower rate until 2022. The model calculated an ICD prevalence of 190.698 patients in 2022 of which an estimated 120.941 ICD patients with HF were eligible for RM. This reflects approximately 63% of the actual total estimated ICD patient population in Germany., Conclusions: The model identified a large patient population currently eligible for RM. To our knowledge, this is the first study providing information on the size of this ICD patient population with HF in Germany. With only a fraction of eligible patients currently receiving RM, these findings may facilitate future planning, resource calculations and scale-up of RM. The building of a specific infrastructure focussing on efficient use of resources reflects a mandatory prerequisite for successful RM implementation., (© 2024. The Author(s).)

Aims: During the early phase of the COVID-19 pandemic, hospital admissions for several medical and surgical conditions declined. Few data are available with respect to elective cardiac implantable electronic device (CIED) implantation. The aim of the present study was to determine the impact of the COVID-19 pandemic on the monthly CIED implantation rates in Germany (January-September 2020 vs. 2019)., Methods and Results: The monthly rates of CIED implantation for the 2019 pre- and 2020 pandemic periods were retrieved from the Institute für das Entgeltsystem im Krankenhaus using German Operation and Procedure Classification codes to identify pacemakers (PMs), implantable cardioverter/defibrillators (ICDs), and cardiac resynchronization therapy (CRT) systems. Compared with 2019, the COVID-19 pandemic was associated with an overall decline of CIED implantation rates of -2.6%, reaching -22.9% in April 2020. Stratified by device type, the patterns of implantation were similar between PMs and ICDs, with maximal declines of -24.3% and -23.2% in April, respectively. Thereafter, the implantation rates gradually increased before stabilizing to rates similar to those observed in 2019. CRT implantation rates also declined in the early pandemic wave, but the overall 2020 rates increased by +4.3% likely driven by an increase of +16.5% (June-September). All the observed percentage differences of monthly device type related implantation rates demonstrated a statistical significance., Conclusion: The COVID-19 pandemic had a significant impact on the implantation of CIEDs in Germany. A differential pattern of resource utilization was observed with a catch-up effect for PMs and ICDs. The implantation rates of CRT systems also declined, but they increased rapidly and remained higher than those of 2019., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Very little is known about the long-term prevalence of severe venous obstruction and occlusion in patients with transvenous implantable cardioverter-defibrillator leads. The objective of the current investigation was to elucidate the incidence and prevalence and to identify predisposing conditions in an ICD cohort over a long follow-up period., Methods: Based on a prospective database, we analyzed consecutive patients who received an ICD implantation in our hospital between 06/1988 and 2009 as well as all corresponding follow-up data until 02/2018. Cavographies were used for analysis, and all patients with at least one device replacement and one follow-up cavography were included., Results: Over a mean follow-up period of 94 ± 50 months, severe venous obstruction was found in 147 (33%) of 448 patients. Kaplan-Meier analysis shows a severe obstruction or occlusion in 50% of patients after a period of 14.3 years. The total number of leads (p < .001, HR 2.01, CI 2.000-2.022), an advanced age (p = .004, HR 1.023 per year, CI 1.022-1.024) and the presence of dilated cardiomyopathy (p = .035, HR 1.49, CI 1.47-1.51) were predictive of venous obstruction whereas the presence of anticoagulation was not., Conclusion: Severe obstruction of the access veins after ICD implantation occurs frequently and its prevalence shows a nearly linear increase over long-time follow-up. Multiple leads, an advanced age and DCM as underlying disease are associated with an increased risk of venous obstruction while the role of anticoagulation to prevent venous obstruction in ICD patients is unclear., (© 2021 The Authors. Pacing and Clinical Electrophysiology published by Wiley Periodicals LLC.)

The possibility of outpatient implantation of defibrillators, devices for cardiac resynchronization, and event recorders (collectively called cardiac implantable electronic devices, CIEDs) is becoming increasingly important. In Germany, only a few options for outpatient implantation are currently realized. Furthermore, there is a lack of uniform, recognized, and binding quality criteria. This article provides insight into the current contract constellations for outpatient surgery and defines a first, holistic quality concept for outpatient implantations of CIEDs. The present works aims to initiate a discourse in the specialist society in order to define a coordinated, binding quality concept. Then, this should serve as the basis for future outpatient implantation services, enabling comparability and to contribute long-term evidence.

Background: The use of remote monitoring has increased due to recently published randomised studies. However, its benefit during acute rhythm disorders still remains controversial., Objectives: The current review describes the current status and highlights possible application of telemedicine during acute rhythm disorders., Materials and Methods: The prerequisites, structural properties of the sender/patient and the receiver of the data/physician are examined and the results of the current literature are presented., Results: Telemedicine during emergency rhythm disorders are normally reserved for specific scenarios. The lack of 24/7 staff of the receiver/hospital represents the main barrier., Conclusions: Remote medicine in the current form is not yet ready to be implemented for acute rhythm disorders. Expansion of currently existing chest pain units (CPUs) might enable this 24/7 service in the near future.

The position paper of the working group 33/Telemonitoring in the German Society for Cardiology e. V. (DGK) discusses the importance of digital solutions in the German health care system and highlights the application possibilities and potentials of telemonitoring in the treatment of patients with cardiac diseases. In addition to telemonitoring of acute ischaemic diseases, acute coronary syndrome and acute cardiac arrhythmias, telemonitoring of chronic cardiac diseases is discussed. Chronic diseases, such as chronic heart failure, are age-associated and present society with the great challenge of providing high-quality, yet cost-efficient care to an increasing number of patients in the future. Telemonitoring offers an opportunity to meet this challenge. However, the introduction of telemonitoring and the associated changes for patients, doctors and other service providers must be accompanied by measures to ensure the acceptance of telemonitoring and the secure handling of sensitive data as well as the quality of telemonitoring services.

The specification of standard operating procedures (SOPs) is a basic requirement for a successful implementation of telemonitoring with implanted cardiac devices and with external measuring devices in patients with heart failure, cardiac arrhytmia or increased risk of sudden cardiac death. The following article summarizes the possibilities of telemonitoring from a technical and organizational point of view and descibes basic requirements on SOPs. these basic requirements should be further specified and anchored in the organizational structure of the individual telemonitoring concept. Moreover, they should de understood as a basic guideline fpr the actions of telemonitoring center (TMC) employees.

Heart failure is one of the most common diseases. It is associated with high morbidity and mortality. Since heart failure is age-associated, the number of patients with heart failure is constantly increasing. At the same time, the imbalance between the need for treatment and the provision of care is growing. Telemonitoring/telemedicine offers patients in rural or remote areas access to high-quality health care and enables fast access to specialists. The working group 33 Telemonitoring of the German Cardiac Society describes the characteristics and possible applications of telemonitoring/telemedicine in the treatment of patients with heart failure. Furthermore, quality criteria for cardiological telemedicine centres are defined. In addition to the personnel structure of a telemedicine centre and the competencies of employees, requirements for the technical infrastructure and the management of incoming data and alarms are described.

Patients receiving dual-chamber implantable cardioverter-defibrillator (DR-ICD) therapy are at risk of developing atrial arrhythmia because of the increased rate of ventricular pacing and the progression of heart failure. Remote monitoring (RM) may identify the patients at highest risk of adverse events such as atrial arrhythmias. A total of 283 patients with 91,632 remote transmissions during a 15-month follow-up (FU) period enrolled in the LION registry were analysed. The parameters retrieved included the pacing mode, lower rate limit, percentage of atrial (%AP) and ventricular pacing (%VP), and percentage of atrial arrhythmia burden (%AB). In 92.7% of patients, the devices were initially programmed in DDD(R) or DDI(R), with changes of the pacing mode in 19.3% only. The lower rate limit remained stable in 80.4% of patients. At the first transmission, 8.7% of patients suffered from RM-detected atrial arrhythmia, which reached 36% during FU. The %AP was not associated with increased AB ( p = 0.67), but the %VP was different in patients developing RM-detected atrial arrhythmia (26.9% vs. 13.7%, p < 0.00001). The %VP increased in 105 patients (significance level of α = 0.05), and 11 patients crossed the border of 50% VP. The LION substudy supports the concept of using RM in a real-world DR-ICD population. Remote monitoring of DR-ICDs allows for the quantification of the course of the pacing parameters and AB. Based on these observations, device parameters can be adjusted and optimized.

Background: Patient-reported outcomes of implantable cardioverter defibrillator (ICD), such as those with shock anxiety, have emerged as important endpoints that are related to quality of life (QOL), but they have not been well studied in a sample of the Japanese population. Therefore, we prospectively examined changes in shock anxiety in a large sample of Japanese patients with an ICD., Methods: We recruited 214 consecutive patients with an ICD who visited the outpatient clinic. At registration and 12 months later, all patients completed the Florida Shock Anxiety Scale (FSAS) questionnaire to allow us to examine changes in shock anxiety over the course of the first year after registration., Results: During the 12-month follow-up period, 10.5% of the patients received ICD shock therapy. Female sex, secondary prevention, and experience of ICD shock therapy were associated with high FSAS scores at registration. The FSAS scores in both patients with appropriate and inappropriate shock were significantly higher at the 12-month follow-up interval than at registration, and there was no significant difference in the extent of changes in FSAS scores (Δ = 5.2 ± 5.1 and Δ = 6.3 ± 9.9, respectively, P = 0.62)., Conclusions: Female sex, secondary prevention, and experience of ICD shock therapy are important risk factors affecting shock anxiety in Japanese patients. Attention should be paid to the after-effects of ICD shock in these patients, regardless of the shock type, with particular attention to women and patients who require secondary prevention., (© 2018 Wiley Periodicals, Inc.)

There has been a significant increase in the number of patients receiving cardiovascular implantable electronic devices (CIED) over the last two decades. CIED infection represents a serious complication after CIED implantation and is associated with significant morbidity and mortality. Recently, newly advanced technologies have offered attractive and suitable therapeutic alternatives. Notably, the leadless pacemaker and anti-bacterial envelope decrease the potential risk of CIED infection and the resulting mortality, when it does occur. A completely subcutaneous implantable cardioverter defibrillator is also an alternative to the transvenous implantable cardioverter defibrillator (ICD), as it does not require implantation of any transvenous or epicardial leads. Among the patients who require ICD removal and subsequent antibiotics secondary to infection, the wearable cardioverter defibrillator represents an alternative approach to inpatient monitoring for the prevention of sudden cardiac death. In this review paper, we aimed to introduce the advanced technologies and devices for prevention of CIED infection.

The programming of implantable cardioverter-defibrillators (ICDs) influences inappropriate shock rates. The aim of the study is to analyse rates of patients with appropriate and inappropriate shocks according to detection zones in the OPTION trial. All patients received dual chamber (DC) ICDs randomly assigned to be programmed either to single chamber (SC) or to DC settings including PARAD+ algorithm. In a post-hoc analysis, rates of patients with inappropriate and appropriate shocks were calculated for shocks triggered at heart rates ≥ 170 bpm (ventricular tachycardia zone) and at rates ≥ 200 bpm (ventricular fibrillation zone). In the SC group, higher rates of patients with total and inappropriate shocks were delivered at heart rates ≥ 170 bpm than at rates ≥ 200 bpm (total shocks: 21.1% vs. 16.6%; p = 0.002; inappropriate shocks: 7.6% vs. 4.5%, p = 0.016; appropriate shocks: 15.2% vs. 13.5%; p = n.s.). No such differences were observed in the DC group (total shocks: 14.3% vs. 12.6%; p = n.s.; inappropriate shocks: 3.9% vs. 3.6%; p = n.s.; appropriate shocks: 12.2% vs. 10.4%; p = n.s.). The higher frequency of patients with total shocks with SC settings than with DC settings that benefit from PARAD+ was driven by a higher percentage of patients with inappropriate shocks in the VT zone (170-200 bpm) in the SC population.

A growing body of evidence indicates that sudden cardiac death constitutes a major cause of mortality in pulmonary hypertension (PH). As validated method to evaluate cardiac autonomic system dysfunction, alterations in heart rate variability (HRV) are predictive of arrhythmic events, particularly in left ventricular disease. Here, we sought to determine the clinical value of HRV assessment in PH. Sixty-four patients were allocated to different PH-subgroups in this prospectively conducted trial: 25 patients with pulmonary arterial hypertension (PAH), 11 patients with chronic thromboembolic PH (CTEPH), and 28 patients with COPD-induced PH. All patients underwent 24-h Holter electrocardiogram for HRV assessment by time- and frequency-domain analysis. Arrhythmic burden was evaluated by manual analysis and complementary automatic measurement of premature atrial and ventricular contractions. The results were compared to 31 healthy controls. The PAH patients offered a significantly higher mean heart rate (78.6 ± 10.4 bpm vs. 70.1 ± 10.3 bpm, p = 0.04), a higher burden of premature ventricular contractions (p < 0.01), and decreases in HRV (SDNN: p < 0.01; SDANN: p < 0.01; very low frequency: p < 0.01; low frequency/high frequency ratio: p < 0.01; total power: p = 0.02). In CTEPH patients, only the amount of premature ventricular contractions differed from controls (p < 0.01), whereas in COPD both premature atrial contraction count and frequency-domain-based HRV manifested significant differences. In conclusion, PAH appears to be primarily affected by HRV alterations and ventricular arrhythmic burden, indicating a high risk for malignant arrhythmic events.

Purpose: To assess the diagnostic value of contrast-enhanced multi-detector computed tomography (MD-CT) for identifying patients with left atrial appendage (LAA) thrombus or circulatory stasis., Materials and Methods: 124 patients with a history of atrial fibrillation and/or cerebral ischemia (83 men, mean age 58.6 ± 12.4 years) and with a clinical indication for MD-CT of the heart and for transesophageal echocardiography (TEE) were included in the study. LAA thrombus or thrombogenic milieu was visually identified in TEE and MD-CT. In addition, MD-CT was analyzed quantitatively measuring the Hounsfield units (HU) of the left atrium (LA), the LAA and the ascending aorta (AA), and calculating the HU ratios LAA/AA (HU [LAA/AA]) und LAA/LA (HU [LAA/LA]). Sensitivity, specificity, negative predictive value (NPV) and positive predictive value (PPV) were calculated., Results: The prevalence of a thrombus or thrombogenic milieu as assessed by TEE was 21.8 %. The HU ratio was lower in patients with thrombus or thrombogenic milieu (HU [LAA/AA]: 0.590 ± 0.248 vs. 0.909 ± 0.141; p < 0.001 und HU [LAA/LA] 0.689 ± 0.366 vs. 1.082 ± 0.228; p < 0.001). For the diagnosis of thrombus or a thrombogenic milieu, visual analysis yielded a sensitivity of 81.5 %, a specificity of 96.9 %, a PPV of 87.5 % and a NPV of 95.2 %. By combining visual and quantitative analysis with one criterion being positive, the specificity decreased to 91.8 %, the sensitivity to 77.8 %, the PPV to 72.4 %, and the NPV to 94.9 %., Conclusion: Visual analysis of the LAA in the evaluation of thrombus or thrombogenic milieu yields a high NPV of 95.1 % and may especially be useful to rule out LAA thrombi in patients with contraindications for TEE. Additional calculation of HU ratios did not improve the diagnostic performance of MD-CT., Key Points: • MD-CT can reliably exclude atrial appendage thrombi/thrombogenic milieu. • MD-CT is an alternative method in patients with contraindications to TEE. • Calculation of relative HU ratios does not improve the diagnostic value of MD-CT., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: A significant number of patients with an implantable cardioverter/defibrillator (ICD) for primary prevention receive inappropriate shocks. Previous studies have reported a reduction of inappropriate therapies with simple modifications of ICD detection settings, however, inclusion criteria and settings varied markedly between studies. Our aim was to investigate the effect of raising the ICD detection zone in the entire primary prevention ICD population., Methods and Results: 543 patients receiving an ICD for primary prevention were randomized to either conventional or progressive ICD programming. The detection rate was programmed at 171 bpm for ventricular tachycardia (VT) and 214 bpm for ventricular fibrillation (VF) in the Conventional group and 187 bpm for VT and 240 bpm for VF in the Progressive group. 43 % of patients received single-chamber and 57 % dual-chamber detection devices (DDD-ICD 19 %; CRT-D 38 %). The primary endpoint consisted of inappropriate therapies and untreated VT/VF. The primary endpoint was reached in 35 patients (13 %) in the Conventional group and 17 patients (6 %) in the Progressive group (p = 0.004). Progressive ICD programming led to significantly fewer amount of patients with ICD therapies (26 vs. 14 %; p < 0.001) and shocks (11 vs. 5 %; p = 0.023) compared to conventional ICD programming. Sub-analyses showed the greatest reduction of inappropriate therapies and shocks in dual-chamber detection devices with progressive compared to single-chamber detection devices with conventional ICD programming (p < 0.001)., Conclusions: Progressive ICD programming reduces the number of inappropriate therapies and shocks in a broad primary prevention ICD population particularly in combination with dual-chamber detection algorithms., Clinical Trial Registration: http://clinicaltrials.gov ; ClinicalTrials.gov identifier NCT01217528.

Background: The effectiveness of the wearable cardioverter defibrillator (WCD) therapy in early post-myocardial infarction (MI) patients remains uncertain., Methods: We analyzed the characteristics and outcomes of patients who received a WCD in the early post-MI phase., Results: Twenty-four patients were followed-up for 8 months (range, 4-16 months). Two patients (8.3%) received appropriate shocks. Left ventricular ejection fraction improved after the WCD therapy (P<0.01). Fourteen patients (58%) received an implantable cardioverter defibrillator at the end of the follow-up period., Conclusion: Early post-MI patients at high risk of sudden cardiac death may benefit from WCD therapy.

A 65-year-old man with severe coronary artery disease and coronary artery bypass graft presented with an acute posterior ST-elevation myocardial infarction. Immediate percutaneous coronary intervention resulted in successful revascularisation of the culprit lesion (RCx) with several remaining coronary stenoses. Despite the reduced left ventricular ejection fraction, no primary prevention indication for an implantable cardioverter/defibrillator early after myocardial infarction existed. Due to the complex coronary anatomy with several remaining stenotic vessels we regarded the patient to be at a particularly high risk for lethal ventricular arrhythmias and provided him with a wearable cardioverter defibrillator (WCD). Twenty-six days later, he experienced spontaneous ventricular tachycardia and fibrillation which was successfully treated with high voltage therapy by the WCD. Subsequently, we decided to implant him an ICD following secondary prevention indication. Besides established indications for primary prevention ICD therapy, some patients early after myocardial infarction may be at a particularly high risk for sudden cardiac death. Temporary protection with a WCD in carefully selected patients can offer a safe opportunity for later reevaluation of permanent ICD implantation depending on the course of left ventricular ejection fraction and the occurrence of arrhythmia.

Background: The possibilities of telemonitoring (TM) of patients with implantable cardioverter-defibrillators (ICD) have been rapidly improving over the last few years. Numerous studies have examined the effects of this development on the follow-up care of ICD patients., Objectives: Technical implementation and safety of ICD telemonitoring. Effects on the treatment of cardiac arrhythmias, the management of cardiac insufficiency patients and morbidity as well as mortality. Illustration of patient acceptance and cost-benefit assessment., Materials and Methods: The current research situation regarding TM of ICDs is analyzed and the available evidence for the postulated advantages in the follow-up care of ICD patients are discussed. The current treatment guidelines and recommendations for implementation of TM in daily clinical praxis are presented., Results and Conclusions: TM offers the possibility of faster reaction times to arrhythmias, cardiac decompensation and ICD malfunctions. At the same time, the outpatient follow-ups can be reduced without negatively affecting safety, quality of life or patient acceptance. TM has the potential to cost-neutrally improve the safety of ICD therapy and could lead to optimized management of heart insufficiency patients, while reducing morbidity and mortality. Following the evidence of these benefits as shown in numerous studies, TM has already been included in the current therapy guidelines.

While the implantable cardioverter-defibrillator (ICD) has been proven to be the best choice for patients with long-term risk for sudden cardiac arrest/sudden cardiac death (SCA/SCD), the question is how to manage patients with only temporary risk, e.g., during the guidelines-recommended waiting period until the decision for an ICD can be made. These patient groups should be monitored around the clock to guarantee a lifesaving shock within a few minutes, if necessary.These conditions can be accomplished by the wearable cardioverter-defibrillator (WCD) in the outpatient sector. The WCD is worn on the skin and consists of four nonadhesive ECG electrodes as well as three defibrillation electrodes-two at the back and one at the front-embedded in a garment. The defibrillation unit is connected via a cord and can be worn over the shoulder or on a belt. Cardiac events can be recorded and retrospectively analyzed by the treating physician.The WCD is a safe and effective measure to terminate potentially lethal ventricular tachycardia and ventricular fibrillation. It may be used early after myocardial infarction with reduced left ventricular ejection fraction (LVEF), as well as for patients with acute heart failure in nonischemic cardiomyopathy with uncertain cause and prognosis. In addition, it may be used for patients waiting for heart transplantation, for patients who cannot be implanted an ICD due to comorbidities, and for patients after explantation of their ICD, e.g., because of infection until reimplantation.One may expect that risk stratification of patients with the WCD will lead to even better selection for ICD use.

Implantable cardioverter-defibrillators are complex technical devices with a multitude of programming options for the physician. In recent years, numerous randomized trials have been performed to define the optimal programming strategies and have provided valuable insights, especially in primary prevention patients. This article provides an actual overview on the existing evidence on the most important programming features for accurate detection and therapy of ventricular arrhythmias.

Background: Smoking is known as a relevant risk factor for severe cardiac morbidities and mortality. This study was initiated to explore the influence of smoking dosage and presence of chronic obstructive lung disease (COPD) on the incidence of appropriate implantable cardioverter defibrillator (ICD) interventions and on mortality., Methods: Prior studies on patients equipped with an ICD suggested that nicotine consumption increases the risk of experiencing an appropriate ICD therapy. There is no substantial data regarding the influence of cigarette smoking dosage on overall mortality in such endangered patients. A total of 349 patients with structural heart disease, either coronary artery disease or nonischemic cardiomyopathy equipped with an ICD, were included. Every patient answered a questionnaire regarding his smoking status and performed a spirometry and body plethysmography., Results: A total of 104 patients (30%) suffered from COPD. Fifty-eight patients (17%) were "current smokers," 196 patients (56%) were revealed as "former smokers," while 93 (27%) patients were registered as "never smokers." A total of 163 patients (47%) received at least one appropriate ICD intervention during follow-up (median 48 ± 8 months). Twenty-three patients died during this study (6.6%). There was no association of COPD with the incidence of appropriate ICD therapies or mortality. Smoking dosage revealed as a significant risk factor for both appropriate ICD interventions (hazard ratio [HR] 1.5 for 60 pack years [PY] P = 0.04) and mortality (HR 2.3 for 60 PY P = 0.02)., Conclusion: This study demonstrates a dose-related increased risk of smokers for appropriate ICD interventions and mortality. The results of this trail urge a strict nicotine abstinence, especially in patients with a structural heart disease undergoing ICD therapy., (©2014 Wiley Periodicals, Inc.)

Objectives: The OPTION (Optimal Anti-Tachycardia Therapy in Implantable Cardioverter-Defibrillator Patients Without Pacing Indications) trial sought to compare long-term rates of inappropriate shocks, mortality, and morbidity between dual-chamber and single-chamber settings in implantable cardioverter-defibrillators (ICDs) patients., Background: The use of dual-chamber ICDs potentially allows better discrimination of supraventricular arrhythmias and thereby reduces inappropriate shocks. However, it may lead to detrimental ventricular pacing., Methods: This prospective multicenter, single-blinded trial enrolled 462 patients with de novo primary or secondary prevention indications for ICD placement and with left ventricular ejection fractions ≤40% despite optimal tolerated pharmacotherapy. All patients received atrial leads and dual-chamber defibrillators that were randomized to be programmed either with dual-chamber or single-chamber settings. In the dual-chamber setting arm, the PARAD+ algorithm, which differentiates supraventricular from ventricular arrhythmias, and SafeR mode, to minimize ventricular pacing, were activated. In the single-chamber setting arm, the acceleration, stability, and long cycle search discrimination criteria were activated, and pacing was set to VVI 40 beats/min. Ventricular tachycardia detection was required at rates between 170 and 200 beats/min, and ventricular fibrillation detection was activated above 200 beats/min., Results: During a follow-up period of 27 months, the time to the first inappropriate shock was significantly longer in the dual-chamber setting arm (p = 0.012, log-rank test), and 4.3% of patients in the dual-chamber setting group compared with 10.3% in the single-chamber setting group experienced inappropriate shocks (p = 0.015). Rates of all-cause death or cardiovascular hospitalization were 20% for the dual-chamber setting group and 22.4% for the single-chamber setting group and satisfied the pre-defined margin for equivalence (p < 0.001)., Conclusions: Therapy with dual-chamber settings for ICD discrimination combined with algorithms for minimizing ventricular pacing was associated with reduced risk for inappropriate shock compared with single-chamber settings, without increases in mortality and morbidity. (Optimal Anti-Tachycardia Therapy in Implantable Cardioverter-Defibrillator [ICD] Patients Without Pacing Indications [OPTION]; NCT00729703)., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

A woman presented with a solitary cardiac metastasis 5 months after curative surgery for endometrial adenocarcinoma (FIGO IB). The tumor was deemed inoperable and palliative ambulatory chemotherapy was initiated. We aimed at a palliative reduction of tumor mass after chemotherapy and atypical vascularization of the metastasis was demonstrated by coronary angiography. We identified two tumor vessels originating from the ramus circumflexus suitable to palliative percutaneous coronary intervention. Within 5 weeks, the initially mild dyspnea increased to New York Heart Association class III and readmission was planned. Regrettably, our patient died from congestive right heart failure only 2 months after diagnosis of tumor recurrence. This report illustrates the need for resolute action without delay even in cases of only mild right heart failure. < Learning objective: Right ventricular metastasis of gynecologic cancer is a rare phenomenon and prognosis of symptomatic patients is poor. In carefully selected patients with symptomatic disease, a palliative percutaneous intervention is feasible and, if appropriate, should be discussed in an interdisciplinary fashion without delay.>.

Purpose: To evaluate the diagnostic value of cardiac magnetic resonance (MR) imaging at 3 T in patients suspected of having acute myocarditis by using a multiparametric cardiac MR imaging approach including T1 relaxation time as an additional tool for tissue characterization., Materials and Methods: Ethics commission approval was obtained for this prospective study, and written informed consent was obtained from all subjects. Twenty four patients with acute myocarditis (mean age ± standard deviation, 34.7 years ± 15.1; 75% men) and 42 control subjects (mean age, 38.7 years ± 10.2; 64% men) were included. Cardiac MR imaging approaches included relative T2 short tau inversion-recovery signal intensity ratio (T2 ratio), early gadolinium enhancement ratio, late gadolinium enhancement, native T1 relaxation times, and extracellular volume fraction. Receiver operating characteristic analysis was performed to compare diagnostic performance. The reference standard was the clinical evidence for acute myocarditis., Results: Native T1 relaxation times were significantly longer in patients with acute myocarditis than in control subjects (1185.3 msec ± 49.3 vs 1089.1 msec ± 44.9, respectively; P < .001). Areas under the curve of native T1 relaxation times (0.94) were higher compared with those of other cardiac MR parameters (late gadolinium enhancement, 0.90; T2 ratio, 0.79; extracellular volume fraction, 0.71; early gadolinium enhancement ratio, 0.63; P = .390, .018, .002, and < .001, respectively). Sensitivity (92%), specificity (91%), and diagnostic accuracy (91%) for native T1 relaxation times (cutoff, 1140 msec) were equivalent compared with those of the established combined Lake Louise criteria (sensitivity, 92%; specificity, 80%; diagnostic accuracy, 85%)., Conclusion: Diagnostic performance with native T1 mapping was superior to that with T2 ratio and early gadolinium enhancement ratio, and specificity was higher with native T1 mapping than that with Lake Louise criteria. This study underlines the potential of native T1 relaxation times to complement current cardiac MR approaches in patients suspected of having acute myocarditis.

Background: Remote patient monitoring is a safe and effective alternative for the in-clinic follow-up of patients with cardiovascular implantable electronic devices (CIEDs). However, evidence on the patient perspective on remote monitoring is scarce and inconsistent., Objectives: The primary objective of the REMOTE-CIED study is to evaluate the influence of remote patient monitoring versus in-clinic follow-up on patient-reported outcomes. Secondary objectives are to: 1) identify subgroups of patients who may not be satisfied with remote monitoring; and 2) investigate the cost-effectiveness of remote monitoring., Methods: The REMOTE-CIED study is an international randomised controlled study that will include 900 consecutive heart failure patients implanted with an implantable cardioverter defibrillator (ICD) compatible with the Boston Scientific LATITUDE® Remote Patient Management system at participating centres in five European countries. Patients will be randomised to remote monitoring or in-clinic follow-up. The In-Clinic group will visit the outpatient clinic every 3-6 months, according to standard practice. The Remote Monitoring group only visits the outpatient clinic at 12 and 24 months post-implantation, other check-ups are performed remotely. Patients are asked to complete questionnaires at five time points during the 2-year follow-up., Conclusion: The REMOTE-CIED study will provide insight into the patient perspective on remote monitoring in ICD patients, which could help to support patient-centred care in the future.

Aims: Heart rate turbulence (HRT) is a prognostic parameter for risk stratification in patients suffering from coronary artery disease. The aims of this study were to demonstrate the feasibility of quantifying HRT in mice, both in long-term electrocardiograms (ECGs) as well as after extrastimulus pacing, and to analyse its characteristics., Methods and Results: We performed long-term ECG recordings using implanted telemetric chips and electrophysiological (EP) investigations, using transvenously inserted EP catheters, in healthy mice. Heart rate turbulence was calculated using the established turbulence onset (TO) and slope (TS) algorithm. After spontaneous ventricular premature complexes (VPCs), we found a negative TO (-2.2 ± 7.5%) and positive TS (15.5 ± 18.3 ms/RR interval). Electrophysiological investigations revealed positive values for TO (0.6 ± 1.1%) and TS (6.5 ± 2.9 ms/RR interval) after extrastimulus pacing maneuvers. The shortening of the extrastimuli coupling intervals delivered during EP investigations significantly influenced TO (r = 0.57; P = 0.01): shorter coupling intervals provoked more positive TO values., Conclusion: Mice display both spontaneous and induced HRT. In terms of TO, VPCs generated by extrastimulus pacing are significantly dependent on the coupling interval. Determining HRT in mice is feasible and provides insight into basic mechanisms of blood pressure regulation, which is realized by the baroreflex., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Background: Transcatheter aortic valve implantation (TAVI) is known to be associated with silent cerebral injury, which could contribute to cognitive impairment. Considering its increasing use, thorough longitudinal investigation of cognitive trajectory after TAVI is pivotal., Methods and Results: Repeatable battery for the assessment of neuropsychological status was performed before (E1), 3 days (E2), 3 months (E3), 1 (E4) year, and 2 years (E5) after TAVI. Baseline characteristics, procedural data, imaging parameters of brain injury (diffusion-weighted MRI), and the use of conceivable neuroprotective approaches were investigated for their effect on cognitive function. Cognitive performance was investigated in 111 patients (mean log EuroSCORE, 30±13%). Global cognitive function (repeatable battery for the assessment of neuropsychological status total score) increased transiently at E2 (P=0.02) and was comparable with baseline levels at E3, E4, and E5. Six patients (5.4%) demonstrated early cognitive decline. Persistence and late onset were seen infrequently (n=3, 2.7% and n=4, 3.6%, respectively). Hence, early cognitive decline was ruled out in 105 patients (94.6%), and a majority of patients (91%) demonstrated sustained cognitive performance throughout all investigated time points. Interestingly, only patient age (P=0.012), but not prior cerebrovascular events, cognitive status, direct TAVI, cerebral embolism in diffusion-weighted MRI, or the use of a cerebral embolic protection device was found to be independently associated with cognitive decline, linking higher age to cognitive impairment along the first 2 years after TAVI., Conclusions: Long-term cognitive performance was preserved in the great majority (91%) of patients throughout the first 2 years after TAVI, despite the high intrinsic risk for cognitive deterioration., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00883285.

Advanced heart failure (HF) is associated with severe sleep-disordered breathing (SDB). In addition, most patients with HF are treated with an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death. The incidence of ICD therapy in such a patient cohort with SDB has never been investigated. The present study sought to determine the effect of SDB on the incidence of appropriate and inappropriate ICD therapy in patients with a categorical primary prevention ICD indication. A total of 133 consecutive ICD patients with New York Heart Association class II-III HF and depressed left ventricular function (≤35%) with no history of ventricular arrhythmia underwent a sleep study before ICD implantation and were followed for 24 ± 8 months, prospectively. A relevant SDB was defined as an apnea-hypopnea index of ≥10 events/hour. Of these 133 patients, 82 (62%) had SDB. Overweight (body mass index >29.1 vs 24.7 kg/m(2); p <0.001) was identified as the only independent risk factor for SDB. Appropriate ICD therapy intervention was significantly greater among patients with SDB than among patients without SDB (54% vs 34%, p = 0.03). Inappropriate ICD therapy intervention was documented more often in patients with SDB (n = 24 [29%] vs 7 [14%]; p = 0.04). An apnea-hypopnea index >10 events/hour was an independent predictor of appropriate ICD therapy on multivariate analysis (odds ratio 2.5, 95% confidence interval 1.8 to 4.04; p = 0.01). In conclusion, the present study is the first trial exploring the effect of SDB on the incidence of appropriate and inappropriate ICD therapy in patients with HF with a primary prevention indication. These results indicate that a preimplantation sleep study will identify patients with HF prone to receive appropriate and inappropriate ICD therapy., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Aims: To evaluate the impact of serological, imaging and clinical measures of cerebral injury on patient self-sufficiency and survival after transcatheter aortic valve implantation (TAVI)., Methods and Results: Before and three days after TAVI, neuron-specific enolase (NSE), cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) and neurological performance utilising National Institutes of Health Stroke Scale (NIHSS) were assessed. Self-sufficiency was determined with established score systems (instrumental activities of daily living score, Barthel Index). Parameters of cerebral injury were investigated for their impact on self-sufficiency and all-cause mortality after 30 days and one year. Sixty-one patients were enrolled (logistic EuroSCORE: 26.4±18.1, STS score: 7.9±5.7), of whom 39 completed the imaging protocol. The incidences of NSE increase, new embolic events in DW-MRI, and neurological deficit early after TAVI were 52.4%, 71.8% and 6.6%, respectively. The degree of concomitant comorbidities, reflected by higher risk scores, had significant impact on outcome. Plasma levels of NSE and new emboli in DW-MRI were neither related to self-sufficiency nor to survival one year after TAVI., Conclusions: In this observational pilot study, "silent" cerebral injury is neither related to dependent lifestyle nor to mortality during the first year after TAVI. However, long-term follow-up is needed to elucidate fully the impact of silent stroke. Clinical trials number: NCT00883285.

Introduction: Implantable cardioverter-defibrillator (ICD) longevity is crucial for both patients and public health systems because it determines the number of surgical ICD replacements, which can generally be considered an additional risk factor for complications, and the cost-effectiveness of ICD therapy. Our objective was to obtain insight into the "real-world" longevities of implantable cardioverter-defibrillators, which quite often differ from those stated in the manufacturers' declarations., Methods and Results: On the basis of a prospective database, we analyzed all ICD implantations performed in our hospital from June 1988 to June 2009. We studied 980 patients (follow-up 58 ± 51 months) with 1,502 ICDs and all respective data until August 2010. We compared the percentage of still operating ICDs at different points in time in relation to manufacturers, types of device (single chamber 623, dual chamber 588, cardiac resynchronization therapy ICDs [CRT-D] 291), and amount of right ventricular pacing (VP). We found distinct differences between the mean lifespans of ICDs of different manufacturers (Biotronik 4.3 years, Sorin 4.5 years, Guidant/Boston Scientific 4.7 years, St. Jude Medical 5 years, Medtronic 5.8 years). CRT-D devices (hazard ratio [HR] 1.778, P = 0.0005) were associated with an elevated annual relative risk for device replacement while a decrease in the proportion of VP (HR 0.934 for each 10% decrease in VP, P < 0.0001) and Medtronic ICDs were associated with a reduced risk of device replacement (HR 0.544, P < 0.0001)., Conclusion: CRT-Ds and an elevated percentage of VP are associated with a significantly elevated risk for device replacement, while Medtronic ICDs showed the longest lifespans., (© 2012 Wiley Periodicals, Inc.)

Aims: To evaluate the impact of serological, imaging and clinical measures of cerebral injury on patient self-sufficiency and survival after transcatheter aortic valve implantation (TAVI). Methods and results: Before and three days after TAVI, neuron-specific enolase (NSE), cerebral diffusion-weighted magnetic resonance imaging (DW-MRI) and neurological performance utilising National Institutes of Health Stroke Scale (NIHSS) were assessed. Self-sufficiency was determined with established score systems (instrumental activities of daily living score, Barthel Index). Parameters of cerebral injury were investigated for their impact on self-sufficiency and all-cause mortality after 30 days and one year. Sixty-one patients were enrolled (logistic EuroSCORE: 26.4±18.1, STS score: 7.9±5.7), of whom 39 completed the imaging protocol. The incidences of NSE increase, new embolic events in DW-MRI, and neurological deficit early after TAVI were 52.4%, 71.8% and 6.6%, respectively. The degree of concomitant comorbidities, reflected by higher risk scores, had significant impact on outcome. Plasma levels of NSE and new emboli in DW-MRI were neither related to self-sufficiency nor to survival one year after TAVI. Conclusions: In this observational pilot study, "silent" cerebral injury is neither related to dependent lifestyle nor to mortality during the first year after TAVI. However, long-term follow-up is needed to elucidate fully the impact of silent stroke. Clinical trials number: NCT00883285.

Aims: The current study includes all consecutive patients with advanced heart failure and cardiac resynchronization therapy (CRT) with an implantable cardioverter defibrillator (ICD) over a 10-year period in a tertiary referral centre. It aims at identifying independent risk factors for mortality during CRT-defibrillator (CRT-D) treatment., Methods and Results: This study includes 239 consecutive patients who had undergone implantation of a CRT-D system (ejection fraction 25.9 ± 8%; 139 patients with ischaemic, 100 patients with non-ischaemic cardiomyopathy). Enrolment took place between 2001 and 2010, resulting in a median follow-up of 43 ± 30 months. During follow-up, 59 patients (25%) died. An impaired baseline kidney function [hazard ratio (HR) 1.98; 95% confidence interval (CI) 1.7-3; P< 0.0001], appropriate ICD therapy during follow-up (HR 2.1; CI 1.1-3.4; P= 0.001), lack of beta-blocker therapy (HR 2.3; CI 1.6-3.8; P= 0.004), and intake of amiodarone (HR 2; CI 1.8-4.1; P< 0.0001) were identified as predictors of overall mortality., Conclusion: This study demonstrates the benefit of beta-blocker therapy also in patients on long-term CRT-D treatment. It confirms the prognostic significance of impaired renal function and the occurrence of appropriate ICD therapies also in CRT-D patients. It argues for an intensified follow-up regimen and adjustment of heart failure treatment whenever these prognostic markers are identified in a patient treated with CRT-D.