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Background: Atrial fibrillation (AF) is common in heart failure with mildly reduced or preserved ejection fraction (HFmrEF/HFpEF) and has a negative impact on outcome. Reliable data on prevalence, incidence, and detection of AF from contemporary, prospective HFmrEF/HFpEF studies are scarce., Methods: This was a prespecified sub-analysis from a prospective, multicenter study. Patients with HFmrEF/HFpEF underwent 12-lead electrocardiography (ECG), 24 h Holter monitoring, and received an implantable loop recorder (ILR) at the study start. During the 2 year follow-up, rhythm monitoring was performed via ILR, yearly ECG, and two yearly 24 h Holter monitors., Results: A total of 113 patients were included (mean age 73 ± 8 years, 75% HFpEF). At baseline, 70 patients (62%) had a diagnosis of AF: 21 paroxysmal, 18 persistent, and 31 permanent AF. At study start, 45 patients were in AF. Of the 43 patients without a history of AF, 19 developed incident AF during a median follow-up of 23 [15-25] months (44%; incidence rate 27.1 (95% confidence interval 16.3-42.4) per 100 person-years). Thus, after the 2-year follow-up, 89 patients (79%) had a diagnosis of AF. In 11/19 incident AF cases (i.e., 58%), AF was solely detected on the ILR. Yearly 12-lead ECG detected six incident AF cases and four of these cases were also detected on two yearly 24 h Holter monitors. Two incident AF cases were detected on an unplanned ECG/Holter., Conclusions: Atrial fibrillation is extremely common in heart failure with HFmrEF/HFpEF and may inform on symptom evaluation and treatment options. AF screening with an ILR had a much higher diagnostic yield than conventional modalities.

Cardiac implantable electronic device (CIED) therapy is an essential element in treating cardiac arrhythmias. Despite their benefits, conventional transvenous CIEDs are associated with a significant risk of mainly pocket- and lead-related complications. To overcome these complications, extravascular devices (EVDs), such as the subcutaneous implantable cardioverter-defibrillator and intracardiac leadless pacemaker, have been developed. In the near future, several other innovative EVDs will become available. However, it is difficult to evaluate EVDs in large studies because of high costs, lack of long-term follow-up, imprecise data or selected patient populations. To improve evaluation of these technologies, real-world, large-scale, long-term data are of utmost importance. A Dutch registry-based study seems to be a unique possibility for this goal due to early involvement of Dutch hospitals in novel CIEDs and an existing quality control infrastructure, the Netherlands Heart Registration (NHR). Therefore, we will soon start the Netherlands-ExtraVascular Device Registry (NL-EVDR), a Dutch nationwide registry with long-term follow-up of EVDs. The NL-EVDR will be incorporated in NHR's device registry. Additional EVD-specific variables will be collected both retrospectively and prospectively. Hence, combining Dutch EVD data will provide highly relevant information on safety and efficacy. As a first step, a pilot project has started in selected centres in October 2022 to optimise data collection., (© 2023. The Author(s).)

Introduction: We aimed to investigate the impact of the 2021 European Society of Cardiology (ESC) guideline changes in left bundle branch block (LBBB) definition on cardiac resynchronization therapy (CRT) patient selection and outcomes., Methods: The MUG (Maastricht, Utrecht, Groningen) registry, consisting of consecutive patients implanted with a CRT device between 2001 and 2015 was studied. For this study, patients with baseline sinus rhythm and QRS duration ≥ 130ms were eligible. Patients were classified according to ESC 2013 and 2021 guideline LBBB definitions and QRS duration. Endpoints were heart transplantation, LVAD implantation or mortality (HTx/LVAD/mortality) and echocardiographic response (LVESV reduction ≥15%)., Results: The analyses included 1.202, typical CRT patients. The ESC 2021 definition resulted in considerably less LBBB diagnoses compared to the 2013 definition (31.6% vs. 80.9%, respectively). Applying the 2013 definition resulted in significant separation of the Kaplan-Meier curves of HTx/LVAD/mortality (p < .0001). A significantly higher echocardiographic response rate was found in the LBBB compared to the non-LBBB group using the 2013 definition. These differences in HTx/LVAD/mortality and echocardiographic response were not found when applying the 2021 definition., Conclusion: The ESC 2021 LBBB definition leads to a considerably lower percentage of patients with baseline LBBB then the ESC 2013 definition. This does not lead to better differentiation of CRT responders, nor does this lead to a stronger association with clinical outcomes after CRT. In fact, stratification according to the 2021 definition is not associated with a difference in clinical or echocardiographic outcome, implying that the guideline changes may negatively influence CRT implantation practice with a weakened recommendation in patients that will benefit from CRT., (© 2023 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background: Primary prophylactic implantable cardioverter-defibrillators (ICDs) in patients with non-ischaemic cardiomyopathy (NICMP) remains controversial. This study sought to assess the benefit of ICD therapy with or without cardiac resynchronisation therapy (CRT) in patients with NICMP. In addition, data were compared with real-world clinical data to perform a risk/benefit analysis., Methods: Relevant randomised clinical trials (RCTs) published in meta-analyses since DANISH, and in PubMed, EMBASE and Cochrane databases from 2016 to 2020 were identified. The benefit of ICD therapy stratified by CRT use was assessed using random effects meta-analysis techniques., Results: Six RCTs were included in the meta-analysis. Among patients without CRT, ICD use was associated with a 24% reduction in mortality (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.62-0.93; P = 0.008). In contrast, among patients with CRT, a CRT-defibrillator was not associated with reduced mortality (HR: 0.74, 95% CI 0.47-1.16; P = 0.19). For ICD therapy without CRT, absolute risk reduction at 3‑years follow-up was 3.7% yielding a number needed to treat of 27., Conclusion: ICD use significantly improved survival among patients with NICMP who are not eligible for CRT. Considering CRT, the addition of defibrillator therapy was not significantly associated with mortality benefit compared with CRT pacemaker., (© 2022. The Author(s).)

Aims: This study aims to identify and visualize electrocardiogram (ECG) features using an explainable deep learning-based algorithm to predict cardiac resynchronization therapy (CRT) outcome. Its performance is compared with current guideline ECG criteria and QRSAREA., Methods and Results: A deep learning algorithm, trained on 1.1 million ECGs from 251 473 patients, was used to compress the median beat ECG, thereby summarizing most ECG features into only 21 explainable factors (FactorECG). Pre-implantation ECGs of 1306 CRT patients from three academic centres were converted into their respective FactorECG. FactorECG predicted the combined clinical endpoint of death, left ventricular assist device, or heart transplantation [c-statistic 0.69, 95% confidence interval (CI) 0.66-0.72], significantly outperforming QRSAREA and guideline ECG criteria [c-statistic 0.61 (95% CI 0.58-0.64) and 0.57 (95% CI 0.54-0.60), P < 0.001 for both]. The addition of 13 clinical variables was of limited added value for the FactorECG model when compared with QRSAREA (Δ c-statistic 0.03 vs. 0.10). FactorECG identified inferolateral T-wave inversion, smaller right precordial S- and T-wave amplitude, ventricular rate, and increased PR interval and P-wave duration to be important predictors for poor outcome. An online visualization tool was created to provide interactive visualizations (https://crt.ecgx.ai)., Conclusion: Requiring only a standard 12-lead ECG, FactorECG held superior discriminative ability for the prediction of clinical outcome when compared with guideline criteria and QRSAREA, without requiring additional clinical variables. End-to-end automated visualization of ECG features allows for an explainable algorithm, which may facilitate rapid uptake of this personalized decision-making tool in CRT., Competing Interests: Conflict of interest: Dr. Vernooy received research grants from Abbott, Biosense Webster and Medtronic; and is a consultant for Medtronic, Philips, Biosense Webster, Boston Scientific and Abbott. Dr. Stipdonk received speaker honoraria from Abbott. The other authors report no conflicts., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Judicious patient selection for cardiac resynchronization therapy (CRT) may further enhance treatment response. Progress has been made by using improved markers of electrical dyssynchrony and mechanical discoordination, using QRSAREA, and systolic rebound stretch of the septum (SRSsept) or systolic stretch index (SSI), respectively. To date, the relation between these measurements has not yet been investigated., Methods and Results: A total of 240 CRT patients were prospectively enrolled from six centres. Patients underwent standard 12-lead electrocardiography, and echocardiography, at baseline, 6-month, and 12-month follow-up. QRSAREA was derived using vectorcardiography, and SRSsept and SSI were measured using strain-analysis. Reverse remodelling was measured as the relative decrease in left ventricular end-systolic volume, indexed to body surface area (ΔLVESVi). Sustained response was defined as ≥15% decrease in LVESVi, at both 6- and 12-month follow-up. QRSAREA and SRSsept were both strong, multivariable adjusted, variables associated with reverse remodelling. SRSsept was associated with response, but only in patients with QRSAREA ≥ 120 μVs (AUC = 0.727 vs. 0.443). Combined presence of SRSsept ≥ 2.5% and QRSAREA ≥ 120 μVs significantly increased reverse remodelling compared with high QRSAREA alone (ΔLVESVi 38 ± 21% vs. 22 ± 21%). As a result, 92% of left bundle branch block (LBBB)-patients with combined electrical and mechanical dysfunction were 'sustained' volumetric responders, as opposed to 51% with high QRSAREA alone., Conclusion: Parameters of mechanical dyssynchrony are better associated with response in the presence of a clear underlying electrical substrate. Combined presence of high SRSsept and QRSAREA, but not high QRSAREA alone, ensures a sustained response after CRT in LBBB patients., Competing Interests: Conflict of interest: K.V. has received research grants from Medtronic and Abbott, consultancy agreement with Medtronic, Philips, and Abbott. F.W.P. has received research grants from Medtronic, Abbott, MicroPort CRM, and Biotronik. M.A.V. received grants from Medtronic, AMGEN, and The Dutch Heart Foundation. All other authors have reported that they have no relationships relevant to the contents of this article to disclose., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Objective: Atrial fibrillation (AF) often progresses from paroxysmal AF (PAF) to more permanent forms. To improve personalised medicine, we aim to develop a new AF progression risk prediction model in patients with PAF., Methods: In this interim-analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF study, patients with PAF undergoing extensive phenotyping at baseline and continuous rhythm monitoring during follow-up of ≥1 year were analysed. AF progression was defined as (1) progression to persistent or permanent AF or (2) progression of PAF with >3% burden increase. Multivariable analysis was done to identify predictors of AF progression., Results: Mean age was 65 (58-71) years, 179 (43%) were female. Follow-up was 2.2 (1.6-2.8) years, 51 of 417 patients (5.5%/year) showed AF progression. Multivariable analysis identified, PR interval, impaired left atrial function, mitral valve regurgitation and waist circumference to be associated with AF progression. Adding blood biomarkers improved the model (C-statistic from 0.709 to 0.830) and showed male sex, lower levels of factor XIIa:C1-esterase inhibitor and tissue factor pathway inhibitor, and higher levels of N-terminal pro-brain natriuretic peptide, proprotein convertase subtilisin/kexin type 9 and peptidoglycan recognition protein 1 were associated with AF progression., Conclusion: In patients with PAF, AF progression occurred in 5.5%/year. Predictors for progression included markers for atrial remodelling, sex, mitral valve regurgitation, waist circumference and biomarkers associated with coagulation, inflammation, cardiomyocyte stretch and atherosclerosis. These prediction models may help to determine risk of AF progression and treatment targets, but validation is needed., Trial Registration Number: NCT02726698., Competing Interests: Competing interests: US reports grants from Roche Diagnostics, EP Solutions, Dutch Heart Foundation, European Union, personal fees from Roche Diagnostics, EP Solutions, other from YourRhythmics BV, outside the submitted work. In addition, US has a patent Noninvasive classification of AF licensed to YourRhythmics. JDeG reports grants and personal fees from Atricure, Bayer, Daiichi Sankyo, Johnson&Johnson, grants from Boston Scientific, personal fees from Novartis and Servier, outside the submitted work. JL reports consultancy agreement Medtronic. HTC reports grants from Bayer and Pfizer and consultancy agreements for Pfizer, Alveron, STAGO, Leo Pharma, Daiichi Sankyo, Gilead/Galapagos, Portola/Aexia and Coagulation Profile. All other authors have nothing to disclose., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY. Published by BMJ.)

Introduction: Cardiac resynchronization therapy (CRT) is an established therapy for patients with heart failure with reduced ejection fraction (HFrEF). Women appear to respond differently to CRT, yet it remains unclear whether this is inherent to the female sex itself, or due to other patient characteristics. In this study, we aimed to investigate sex differences in response to CRT., Methods: This is a post-hoc analysis of a prospective, multicenter study (MARC) in the Netherlands, studying HFrEF patients with an indication for CRT according to the guidelines ( n = 240). Primary outcome measures are left ventricular ejection fraction (LVEF) and left ventricular end systolic volume (LVESV) at 6 months follow-up. Results were validated in an independent retrospective Belgian cohort ( n = 818)., Results: In the MARC cohort 39% were women, and in the Belgian cohort 32% were women. In the MARC cohort, 70% of the women were responders (defined as >15% decrease in LVESV) at 6 months, compared to 55% of men ( p = 0.040) (79% vs. 67% in the Belgian cohort, p = 0.002). Women showed a greater decrease in LVESV %, LVESV indexed to body surface area (BSA) %, and increase in LVEF (all p < 0.05). In regression analysis, after adjustment for BSA and etiology, female sex was no longer associated with change in LVESV % and LVESV indexed to BSA % and LVEF % ( p > 0.05 for all). Results were comparable in the Belgian cohort., Conclusions: Women showed a greater echocardiographic response to CRT at 6 months follow-up. However, after adjustment for BSA and ischemic etiology, no differences were found in LV-function measures or survival, suggesting that non-ischemic etiology is responsible for greater response rates in women treated with CRT.

Purpose: Effectiveness of cardiac resynchronization therapy (CRT) in patients without left bundle branch block (non-LBBB) QRS morphology is limited. Additional selection criteria are needed to identify these patients., Methods: Seven hundred ninety consecutive patients with non-LBBB morphology, who received a CRT-device in 3 university centers in the Netherlands, were selected. Pre-implantation 12-lead ECGs were evaluated on morphology, duration, and area of the QRS complex, as well as on PR interval, left ventricular activation time (LVAT), and the presence of fragmented QRS (fQRS). Association of these ECG features with the primary endpoint: a combination of left ventricular assist device (LVAD) implantation, cardiac transplantation and all-cause mortality, and secondary endpoint-echocardiographic reduction of left ventricular end-systolic volume (LVESV)-were evaluated., Results: The primary endpoint occurred more often in non-LBBB patients with with PR interval ≥ 230ms, QRS area < 109μVs, and with fQRS. Multivariable regression analysis showed independent associations of QRS area (HR 2.33 [1.44, 3.77], p = 0.001) and PR interval (HR 2.03 [1.51, 2.74], p < 0.001) only. Mean LVESV reduction was significantly lower in patients with baseline RBBB, QRS duration < 150 ms, PR interval ≥ 230 ms, and in QRS area < 109 μVs. Multivariable regression analyses only showed significant associations between QRS area ≥ 109 μVs (OR 2.00 [1.09, 3.66] p = 0.025) and probability of echocardiographic response to CRT., Conclusions: In the heterogeneous non-LBBB patient population, QRS area and PR prolongation rather than traditional QRS duration and morphology are associated to both clinical and echocardiographic outcomes of CRT., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Implantable cardioverter-defibrillator (ICD) therapy is associated with several deleterious effects, which can be reduced by antiarrhythmic drugs or catheter ablation. However, it is largely unknown which patients might benefit from these therapies. Therefore, this study aimed to investigate whether myocardial scar characterization improves risk stratification for ventricular arrhythmia (VA) occurrence in patients with ischemic cardiomyopathy and an ICD. Methods: In this study, 82 patients with ischemic cardiomyopathy who received an ICD were enrolled retrospectively. Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) images were analyzed using an investigational software tool to obtain quantitative data regarding the total scar, core, and border zone (BZ). Data regarding the QRS complex was obtained from electrocardiography (ECG). The primary endpoint was appropriate ICD therapy. Results: During a median follow-up duration of 3.98 years [interquartile range (IQR) 2.89-5.14 years], appropriate therapy occurred in 24 (29.3%) patients. Patients with appropriate ICD therapy had a significantly larger total scar mass [60.0 (IQR 41.2-73.4) vs. 43.3 (IQR 31.2-61.2) g; P = 0.009] and BZ mass [32.9 (IQR 26.9-42.4) vs. 24.5 (IQR 18.8-32.5) g; P = 0.001] than those without appropriate therapy. In multivariable Cox regression analyses, total scar mass [hazard ratio (HR) 1.02 [95% confidence interval (CI) 1.00-1.04]; P = 0.014] and BZ mass (HR 1.04 [95% CI 1.01-1.07]; P = 0.009) independently predicted appropriate ICD therapy. Core mass and the QRS complex, however, were not significantly associated with the primary endpoint. Conclusion: LGE-CMR-based, but not ECG-based myocardial scar characterization improves risk stratification for VA occurrence in patients with ischemic cardiomyopathy who received an ICD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Noordman, Maass, Groenveld, Mulder, Rienstra and Blaauw.)

Erythropoietin (EPO) is a haematopoietic hormone that regulates erythropoiesis, but the EPO-receptor (EpoR) is also expressed in non-haematopoietic tissues. Stimulation of the EpoR in cardiac and skeletal muscle provides protection from various forms of pathological stress, but its relevance for normal muscle physiology remains unclear. We aimed to determine the contribution of the tissue-specific EpoR to exercise-induced remodelling of cardiac and skeletal muscle. Baseline phenotyping was performed on left ventricle and m. gastrocnemius of mice that only express the EpoR in haematopoietic tissues (EpoR-tKO). Subsequently, mice were caged in the presence or absence of a running wheel for 4 weeks and exercise performance, cardiac function and histological and molecular markers for physiological adaptation were assessed. While gross morphology of both muscles was normal in EpoR-tKO mice, mitochondrial content in skeletal muscle was decreased by 50%, associated with similar reductions in mitochondrial biogenesis, while mitophagy was unaltered. When subjected to exercise, EpoR-tKO mice ran slower and covered less distance than wild-type (WT) mice (5.5 ± 0.6 vs. 8.0 ± 0.4 km/day, p < 0.01). The impaired exercise performance was paralleled by reductions in myocyte growth and angiogenesis in both muscle types. Our findings indicate that the endogenous EPO-EpoR system controls mitochondrial biogenesis in skeletal muscle. The reductions in mitochondrial content were associated with reduced exercise capacity in response to voluntary exercise, supporting a critical role for the extra-haematopoietic EpoR in exercise performance., (© 2021. The Author(s).)

Aims: This study was performed to develop and externally validate prediction models for appropriate implantable cardioverter-defibrillator (ICD) shock and mortality to identify subgroups with insufficient benefit from ICD implantation., Methods and Results: We recruited patients scheduled for primary prevention ICD implantation and reduced left ventricular function. Bootstrapping-based Cox proportional hazards and Fine and Gray competing risk models with likely candidate predictors were developed for all-cause mortality and appropriate ICD shock, respectively. Between 2014 and 2018, we included 1441 consecutive patients in the development and 1450 patients in the validation cohort. During a median follow-up of 2.4 (IQR 2.1-2.8) years, 109 (7.6%) patients received appropriate ICD shock and 193 (13.4%) died in the development cohort. During a median follow-up of 2.7 (IQR 2.0-3.4) years, 105 (7.2%) received appropriate ICD shock and 223 (15.4%) died in the validation cohort. Selected predictors of appropriate ICD shock were gender, NSVT, ACE/ARB use, atrial fibrillation history, Aldosterone-antagonist use, Digoxin use, eGFR, (N)OAC use, and peripheral vascular disease. Selected predictors of all-cause mortality were age, diuretic use, sodium, NT-pro-BNP, and ACE/ARB use. C-statistic was 0.61 and 0.60 at respectively internal and external validation for appropriate ICD shock and 0.74 at both internal and external validation for mortality., Conclusion: Although this cohort study was specifically designed to develop prediction models, risk stratification still remains challenging and no large group with insufficient benefit of ICD implantation was found. However, the prediction models have some clinical utility as we present several scenarios where ICD implantation might be postponed., (© The Author(s) 2021. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Implantable cardioverter defibrillators are implanted on a large scale in patients with heart failure (HF) for the prevention of sudden cardiac death. There are different scenarios in which defibrillator therapy is no longer desired or indicated, and this is occurring increasingly in elderly patients. Usually device therapy is continued until the device has reached battery depletion. At that time, the decision needs to be made to either replace it or to downgrade to a pacing-only device. This decision is dependent on many factors, including the vitality of the patient and his/her preferences, but may also be influenced by changes in recommendations in guidelines. In the last few years, there has been an increased awareness that discussions around these decisions are important and useful. Advanced care planning and shared decision-making have become important and are increasingly recognised as such. In this short review we describe six elderly patients with HF, in whose cases we discussed these issues, and we aim to provide some scientific and ethical rationale for clinical decision-making in this context. Current guidelines advocate the discussion of end-of-life options at the time of device implantation, and physicians should realise that their choices influence patients' options in this critical phase of their illness.

Introduction: Recent studies have shown that the baseline QRS area is associated with the clinical response after cardiac resynchronization therapy (CRT). In this study, we investigated the association of QRS area reduction (∆QRS area) after CRT with the outcome. We hypothesize that a larger ∆QRS area is associated with a better survival and echocardiographic response., Methods and Results: Electrocardiograms (ECG) obtained before and 2-12 months after CRT from 1299 patients in a multi-center CRT-registry were analyzed. The QRS area was calculated from vectorcardiograms that were synthesized from 12-lead ECGs. The primary endpoint was a combination of all-cause mortality, heart transplantation, and left ventricular (LV) assist device implantation. The secondary endpoint was the echocardiographic response, defined as LV end-systolic volume reduction ≥ of 15%. Patients with ∆QRS area above the optimal cut-off value (62 µVs) had a lower risk of reaching the primary endpoint (hazard ratio: 0.43; confidence interval [CI] 0.33-0.56, p < .001), and a higher chance of echocardiographic response (odds ratio [OR] 3.3;CI 2.4-4.6, p < .0001). In multivariable analysis, ∆QRS area was independently associated with both endpoints. In patients with baseline QRS area ≥109 µVs, survival, and echocardiographic response were better when the ∆QRS area was ≥62 µVs (p < .0001). Logistic regression showed that in patients with baseline QRS area ≥109 µVs, ∆QRS area was the only significant predictor of survival (OR: 0.981; CI: 0.967-0.994, p = .006)., Conclusion: ∆QRS area is an independent determinant of CRT response, especially in patients with a large baseline QRS area. Failure to achieve a large QRS area reduction with CRT is associated with a poor clinical outcome., (© 2021 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background: Segment length in cine (SLICE) strain analysis on standard cardiovascular magnetic resonance (CMR) cine images was recently validated against gold standard myocardial tagging. The present study aims to explore predictive value of SLICE for cardiac resynchronization therapy (CRT) response., Methods and Results: Fifty-seven patients with heart failure and left bundle branch block (LBBB) were prospectively enrolled in this multi-center study and underwent CMR examination before CRT implantation. Circumferential strains of the septal and lateral wall were measured by SLICE on short-axis cine images. In addition, timing and strain pattern parameters were assessed. After twelve months, CRT response was quantified by the echocardiographic change in left ventricular (LV) end-systolic volume (LVESV). In contrast to timing parameters, strain pattern parameters being systolic rebound stretch of the septum (SRS sep ), systolic stretch index (SSI sep-lat ), and internal stretch factor (ISF sep-lat ) all correlated significantly with LVESV change (R - 0.56; R - 0.53; and R - 0.58, respectively). Of all strain parameters, end-systolic septal strain (ESS sep ) showed strongest correlation with LVESV change (R - 0.63). Multivariable analysis showed ESS sep to be independently related to LVESV change together with age and QRS AREA ., Conclusion: The practicable SLICE strain technique may help the clinician to estimate potential benefit from CRT by analyzing standard CMR cine images without the need for commercial software. Of all strain parameters, end-systolic septal strain (ESS sep ) demonstrates the strongest correlation with reverse remodeling after CRT. This parameter may be of special interest in patients with non-strict LBBB morphology for whom CRT benefit is doubted.

Background: Women are less likely to receive cardiac resynchronization therapy, yet, they are more responsive to the therapy and respond at shorter QRS duration. The present study hypothesized that a relatively larger left ventricular (LV) electrical dyssynchrony in smaller hearts contributes to the better cardiac resynchronization therapy response in women. For this, the vectorcardiography-derived QRS area is used, since it allows for a more detailed quantification of electrical dyssynchrony compared with conventional electrocardiographic markers., Methods: Data from a multicenter registry of 725 cardiac resynchronization therapy patients (median follow-up, 4.2 years [interquartile range, 2.7-6.1]) were analyzed. Baseline electrical dyssynchrony was evaluated using the QRS area and the corrected QRS area for heart size using the LV end-diastolic volume (QRSarea/LVEDV). Impact of the QRSarea/LVEDV ratio on the association between sex and LV reverse remodeling (LV end-systolic volume change) and sex and the composite outcome of all-cause mortality, LV assist device implantation, or heart transplantation was assessed., Results: At baseline, women (n=228) displayed larger electrical dyssynchrony than men (QRS area, 132±55 versus 123±58 μVs; P =0.043), which was even more pronounced for the QRSarea/LVEDV ratio (0.76±0.46 versus 0.57±0.34 μVs/mL; P <0.001). After multivariable analyses, female sex was associated with LV end-systolic volume change (β=0.12; P =0.003) and a lower occurrence of the composite outcome (hazard ratio, 0.59 [0.42-0.85]; P =0.004). A part of the female advantage regarding reverse remodeling was attributed to the larger QRSarea/LVEDV ratio in women (25-fold change in β from 0.12 to 0.09). The larger QRSarea/LVEDV ratio did not contribute to the better survival observed in women. In both volumetric responders and nonresponders, female sex remained strongly associated with a lower risk of the composite outcome (adjusted hazard ratio, 0.59 [0.36-0.97]; P =0.036; and 0.55 [0.33-0.90]; P =0.018, respectively)., Conclusions: Greater electrical dyssynchrony in smaller hearts contributes, in part, to more reverse remodeling observed in women after cardiac resynchronization therapy, but this does not explain their better long-term outcomes.

Aims: Patient selection for cardiac resynchronization therapy (CRT) may be enhanced by evaluation of systolic myocardial stretching. We evaluate whether systolic septal rebound stretch (SRSsept) derived from speckle tracking echocardiography is a predictor of reverse remodelling after CRT and whether it holds additive predictive value over the simpler visual dyssynchrony assessment by apical rocking (ApRock)., Methods and Results: The association between SRSsept and change in left ventricular end-systolic volume (ΔLVESV) at 6 months of follow-up was assessed in 200 patients. Subsequently, the additive predictive value of SRSsept over the assessment of ApRock was evaluated in patients with and without left bundle branch block (LBBB) according to strict criteria. SRSsept was independently associated with ΔLVESV (β 0.221, P = 0.002) after correction for sex, age, ischaemic cardiomyopathy, QRS morphology and duration, and ApRock. A high SRSsept (≥optimal cut-off value 2.4) also coincided with more volumetric responders (ΔLVESV ≥ -15%) than low SRSsept in the entire cohort (70.0% and 56.4%), in patients with strict LBBB (83.3% vs. 56.7%, P = 0.024), and non-LBBB (70.7% vs. 46.3%, P = 0.004). Moreover, in non-LBBB patients, SRSsept held additional predictive information over the assessment of ApRock alone since patients that showed ApRock and high SRSsept were more often volumetric responder than those with ApRock but low SRSsept (82.8% vs. 47.4%, P = 0.001)., Conclusion: SRSsept is strongly associated with CRT-induced reduction in left ventricular end-systolic volume and holds additive prognostic information over QRS morphology and ApRock. Our data suggest that CRT patient selection may be improved by assessment of SRSsept, especially in the important subgroup without strict LBBB., Clinical Trial Registration: The MARC study was registered at clinicaltrials.gov: NCT01519908., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

The adverse effects of ventricular dyssynchrony induced by right ventricular (RV) pacing has led to alternative pacing strategies, such as biventricular, His bundle (HBP), LV septal (LVSP) and left bundle branch pacing (LBBP). Given the overlap, LVSP and LBBP are also collectively referred to as left bundle branch area pacing (LBBAP). Although among these alternative pacing sites HBP is theoretically the ideal strategy as it maintains a physiological ventricular activation, its application requires more skills and is associated with the most complications. LBBAP, where the ventricular pacing lead is advanced through the interventricular septum to its left side, creates ventricular activation that is only slightly more dyssynchronous. Preliminary studies have shown that LBBAP is feasible, safe and encounters less limitations than HBP. Further studies are needed to differentiate between LVSP and LBBP with regard to acute functional and long-term clinical outcome., Competing Interests: Competing interests: PV: fellowship support and research grant from Medtronic; honorarium from Abbott, Biotronik, Boston Scientific and Medtronic. Patent pending for His delivery tool. FWP: research grants from Medtronic, Abbott, MicroPort CRM, Biotronik. KV: research grants from Medtronic, Abbott and Biotronik, consultancy agreement with Medtronic. AHM: lecture fees from Abbott. TvS: lecture fees from Abbott. JL: consultancy agreement Medtronic., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Cardiac resynchronization therapy (CRT) is an established treatment in patients with heart failure and conduction abnormalities. However, a significant number of patients do not respond to CRT. Currently employed criteria for selection of patients for this therapy (QRS duration and morphology) have several shortcomings. QRS area was recently shown to provide superior association with CRT response. However, its assessment was not fully automated and required the presence of an expert., Objective: Our objective was to develop a fully automated method for the assessment of vector-cardiographic (VCG) QRS area from electrocardiographic (ECG) signals., Methods: Pre-implantation ECG recordings (N = 864, 695 left-bundle-branch block, 589 men) in PDF files were converted to allow signal processing. QRS complexes were found and clustered into morphological groups. Signals were converted from 12‑lead ECG to 3‑lead VCG and an average QRS complex was built. QRS area was computed from individual areas in the X, Y and Z leads. Practical usability was evaluated using Kaplan-Meier plots and 5-year follow-up data., Results: The automatically calculated QRS area values were 123 ± 48 μV.s (mean values and SD), while the manually determined QRS area values were 116 ± 51 ms; the correlation coefficient between the two was r = 0.97. The automated and manual methods showed the same ability to stratify the population (hazard ratios 2.09 vs 2.03, respectively)., Conclusion: The presented approach allows the fully automatic and objective assessment of QRS area values., Significance: Until this study, assessing QRS area values required an expert, which means both additional costs and a risk of subjectivity. The presented approach eliminates these disadvantages and is publicly available as part of free signal-processing software., Competing Interests: Declaration of Competing Interest A.H.M reports lecture fees from Medtronic and Microport CRM. K.V. reports consultancy for Medtronic; research grants from Medtronic; speaker fees from Abbott. F.W.P. reports research grants from Medtronic, Abbott, Biotronik, Microport CRM, Biosense Webster and EBR Systems., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: The primary aim of the VIP-HF study was to examine the incidence of sustained ventricular tachyarrhythmias (VTs) in heart failure (HF) with mid-range (HFmrEF) or preserved ejection fraction (HFpEF). Secondary aims were to examine the incidence of non-sustained VTs, bradyarrhythmias, HF hospitalizations and mortality., Methods and Results: This was an investigator-initiated, prospective, multicentre, observational study of patients with HF and left ventricular ejection fraction (LVEF) >40%. Patients underwent extensive phenotyping, after which an implantable loop recorder was implanted. We enrolled 113 of the planned 250 patients [mean age 73 ± 8 years, 51% women, New York Heart Association class II/III 54%/46%, median N-terminal pro B-type natriuretic peptide 1367 (710-2452) pg/mL and mean LVEF 54 ± 6%; 75% had LVEF >50%]. Eighteen percent had non-sustained VTs and 37% had atrial fibrillation on Holter monitoring. During a median follow-up of 657 (219-748) days, the primary endpoint of sustained VT was observed in one patient. The incidence of the primary endpoint was 0.6 (95% confidence interval 0.2-3.5) per 100 person-years. The incidence of the secondary endpoint of non-sustained VT was 11.5 (7.1-18.7) per 100 person-years. Five patients developed bradyarrhythmias [3.2 (1.4-7.5) per 100 person-years], three were implanted with a pacemaker. In total, 23 patients (20%) were hospitalized for HF [16.3 (10.9-24.4) per 100 person-years]. Fourteen patients (12%) died [8.7 (5.2-14.7) per 100 person-years]; 10 due to cardiovascular causes, and four sudden deaths, one with implantable loop recorder-confirmed bradyarrhythmias as terminal event, three others undetermined., Conclusion: Despite the lower than expected number of included patients, the incidence of sustained VTs in HFmrEF/HFpEF was low. Clinically relevant bradyarrhythmias were more often observed than expected., (© 2020 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aims: Atrial fibrillation (AF) often starts as a paroxysmal self-terminating arrhythmia. Limited information is available on AF patterns and episode duration of paroxysmal AF. In paroxysmal AF patients, we longitudinally studied the temporal AF patterns, the association with clinical characteristics, and prevalence of AF progression., Methods and Results: In this interim analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) registry, 202 patients with paroxysmal AF were followed with continuous rhythm monitoring (implantable loop recorder or pacemaker) for 6 months. Mean age was 64 ± 9 years, 42% were women. Atrial fibrillation history was 2.1 (0.5-4.4) years, CHA2DS2-VASc 1.9 ± 1.3, 101 (50%) had hypertension, 69 (34%) heart failure. One-third had no AF during follow-up. Patients with long episodes (>12 hours) were often men with more comorbidities (heart failure, coronary artery disease, higher left ventricular mass). Patients with higher AF burden (>2.5%) were older with more comorbidities (worse renal function, higher calcium score, thicker intima media thickness). In 179 (89%) patients, 1-year rhythm follow-up was available. On a quarterly basis, average daily AF burden increased from 3.2% to 3.8%, 5.2%, and 6.1%. Compared to the first 6 months, 111 (62%) patients remained stable during the second 6 months, 39 (22%) showed progression to longer AF episodes, 8 (3%) developed persistent AF, and 29 (16%) patients showed AF regression., Conclusions: In paroxysmal AF, temporal patterns differ suggesting that paroxysmal AF is not one entity. Atrial fibrillation burden is low and determined by number of comorbidities. Atrial fibrillation progression occurred in a substantial number., Trial Registration Number: Clinicaltrials.gov identifier NCT02726698., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: The timing of onset and associated predictors of late new conduction disturbances (CDs) leading to permanent pacemaker implantation (PPI) following transcatheter aortic valve implantation (TAVI) are still unknown, however, essential for an early and safe discharge. This study aimed to investigate the timing of onset and associated predictors of late onset CDs in patients requiring PPI (LCP) following TAVI., Methods and Results: We performed retrospective analysis of prospectively collected data from five large volume centres in Europe. Post-TAVI electrocardiograms and telemetry data were evaluated in patients with a PPI post-TAVI to identify the onset of new advanced CDs. Early onset CDs were defined as within 48 hours after procedure, and late onset CDs as after 48 hours. A total of 2804 patients were included for analysis. The PPI rate was 12%, of which 18% was due to late onset CDs (>48 hours). Independent predictors for LCP were pre-existing non-specific intraventricular conduction delay, pre-existing right bundle branch block, self-expandable valves and predilation. At least one of these risk factors was present in 98% of patients with LCP. Patients with a balloon-expandable valve without predilation did not develop CDs requiring PPI after 48 hours., Conclusions: Safe early discharge might be feasible in patients without CDs in the first 48 hours after TAVI if no risk factors for LCP are present., Competing Interests: Competing interests: PRS was a member of the Keystone Heart advisory board., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: Echocardiographic response after cardiac resynchronization therapy (CRT) is often lesser in ischaemic cardiomyopathy (ICM) than non-ischaemic dilated cardiomyopathy (NIDCM) patients. We assessed the association of heart failure aetiology on the amount of reverse remodelling and outcome of CRT., Methods and Results: Nine hundred twenty-eight CRT patients were retrospectively included. Reverse remodelling and endpoint occurrence (all-cause mortality, heart transplantation, or left ventricular assist device implantation) was assessed. Two response definitions [≥15% reduction left ventricular end systolic volume (LVESV) and ≥5% improvement left ventricular ejection fraction] and the most accurate cut-off for the amount of reverse remodelling that predicted endpoint freedom were assessed. Mean follow-up was 3.8 ± 2.4 years. ICM was present in 47%. ICM patients who were older (69 ± 7 vs. 63 ± 11), more often men (83% vs. 58%), exhibited less LVESV reduction (13 ± 31% vs. 23 ± 32%) and less left ventricular ejection fraction improvement (5 ± 11% vs. 10 ± 12%) than NIDCM patients (all P < 0.001). Nevertheless, every 1% LVESV reduction was associated with a relative reduction in endpoint occurrence: NIDCM 1.3%, ICM 0.9%, and absolute risk reduction was similar (0.4%). The most accurate cut-off of LVESV reduction that predicted endpoint freedom was 17.1% in NIDCM and 13.2% in ICM., Conclusions: ICM patients achieve less reverse remodelling than NIDCM, but the prognostic gain in terms of survival time is the same for every single percentage of reverse remodelling that does occur. The assessment and expected magnitude of reverse remodelling should take this effect of heart failure aetiology into account., (© 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Objectives: This study aimed to evaluate the association of 4 left bundle branch block (LBBB) definitions and their individual ECG characteristics with clinical outcome. Furthermore, it aimed to combine relevant outcome-associated electrocardiographic (ECG) characteristics into a novel outcome-based definition., Background: LBBB morphology is associated with positive response to cardiac resynchronization therapy. However, there are multiple LBBB definitions. Associations with outcomes may differ between definitions and depend on varying contributions of the individual ECG characteristics that these LBBB definitions are composed of., Methods: A retrospective multicenter study was conducted in 1,492 cardiac resynchronization therapy patients. Patients were classified as LBBB or non-LBBB according to definitions provided by the European Society of Cardiology, American Heart Association, MADIT-CRT (Multicenter Automatic Defibrillator Implantation with Cardiac Resynchronization Therapy) trial, and according to Strauss et al., the primary endpoint was left ventricular assist device implantation, cardiac transplantation, and all-cause mortality., Results: LBBB classification differed significantly between the 4 definitions (kappa coefficients ranging from 0.09 to 0.92). The American Heart Association definition correlated the least (0.09 to 0.12) with the other definitions. Only 13.8% of patients were classified as LBBB by all definitions. During a follow-up period of 3.4 ± 2.4 years, 472 (32%) patients experienced the primary endpoint. For each LBBB definition survival analysis showed a significant association of LBBB with outcome, with relative risk reduction ranging from 39% to 43%. Each LBBB definition included characteristics that were not associated with outcome. Combining outcome-associated ECG characteristics into a novel prediction model did not significantly improve diagnostic performance (relative risk reduction 43%)., Conclusions: The classification of LBBB is highly dependent on the LBBB definition used. However, each LBBB definition provides a comparable difference in risk of adverse clinical events between LBBB and non-LBBB patients. Combining individual outcome-associated ECG-characteristics into a novel prediction model does not improve association with outcome., (Copyright © 2020 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction: Limited data are available concerning the effect of severe chronic kidney disease (CKD) on the response to cardiac resynchronization therapy (CRT) because these patients are commonly excluded from trials. Therefore, we aimed to assess the effect of CRT on renal function, reverse remodeling and outcome across all stages of CKD in a large patient population of recipients of CRT., Methods: We retrospectively evaluated 798 consecutive patients with heart failure who were undergoing CRT implantation between October 2008 and September 2016. Renal function data were available at baseline and at 6 months following CRT. Remodeling based on left ventricular end diastolic volume/left ventricular ejection fraction (LVESV/LVEF) and clinical outcome was assessed using a combined endpoint of all-cause mortality and hospitalization because of heart failure., Results: Median baseline estimated glomerular filtration rate was 62.8 (43.6-77.8) mL/min/1.73 m 2 . Of the patients, 33.6% were in CKD stage 3, 11.0% in stage 4 and 1.1% in stage 5. LVEF and LVESV improved across all CKD stages; however, patients with CKD stages 1 and 2 exhibited a greater degree of improvement in LVEF (median 15% vs 10%, P < 0.001) and LVESV (median -37.2% vs -29.9%, P < 0.001) compared to patients with CKD stages 3-5. Despite a greater degree of reverse remodeling in CKD stages 1 and 2, the most accurate cut-off of remodeling predicting good clinical outcome was lower for patients with CKD stage 3-5, respectively: 5.5% vs 9.5% (LVEF) and -6.67% vs -12.41% (LVESV)., Conclusions: CRT results in reverse remodeling across all stages of CKD, although to a lesser extent in patients with renal dysfunction (CKD stage 3-5). However, patients with CKD derive benefit on outcome at a lesser degree of remodeling., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Left bundle branch block (LBBB) morphology is associated with improved outcome of cardiac resynchronisation therapy (CRT) and is an important criterion for patient selection. There are, however, multiple definitions for LBBB. Moreover, applying these definitions seems subjective. We investigated the inter- and intraobserver agreement in the determination of LBBB using available definitions, and clinicians' judgement of LBBB., Methods: Observers were provided with 12‑lead ECGs of 100 randomly selected CRT patients. Four observers judged the ECGs based on different LBBB-definitions (ESC, AHA/ACC/HRS, MADIT, and Strauss). Additionally, four implanting cardiologists scored the same 100 ECGs based on their clinical judgement. Observer agreement was summarized through the proportion of agreement (P) and kappa coefficient (k)., Results: Relative intra-observer agreement using different LBBB definitions, and within clinical judgement was moderate (range k 0.47-0.74 and k = 0.76 (0.14), respectively). The inter-observer agreement between observers using LBBB definitions as well as between clinical observers was minimal to weak (range k 0.19-0.44 and k = 0.35 (0.20), respectively). The probability of classifying an ECG as LBBB by available definitions varied considerably (range 0.20-0.76). The agreement between different definitions of LBBB ranged from good (P = 0.95 (0.07)) to weak (P = 0.40 (0.22)). Furthermore, correlation between the different LBBB definitions and clinical judgement was poor (range phi 0.30-0.55)., Conclusion: Significant variation in the probability of classifying LBBB is present in using different definitions and clinical judgement. Considerable intra- and inter-observer variability adds to this variation. Interdefinition agreement varies significantly and correlation of clinical judgement with LBBB classification by definitions is modest at best., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Heart failure with preserved ejection fraction (HFpEF) and atrial fibrillation (AF) are very common conditions, particularly in the elderly. However, the mechanisms underlying the two disorders, including their intricate interaction have not been fully resolved. Here, our aim is to review the evidence on the role of the two types of senile amyloidosis in this connection. Two types of senile amyloidosis can be identified: wild-type transthyretin (TTR)-derived amyloidosis (ATTRwt) and isolated atrial amyloidosis (IAA). ATTRwt is an underlying condition that is being increasingly recognized in patients with HFpEF and often accompanied by AF. IAA is an established cause of AF, adding to the mechanism problem. New diagnostic and therapeutic possibilities have emerged that may facilitate clinical management of (senile) amyloidosis, which in turn may have implications for the management of HFpEF and AF., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

In recent years the prevalence of implantation of a cardiac implantable electronic device (CIED) has increased due to expanding implantation indications and prolonged life expectancy. Diagnostic strategies increasingly employ magnetic resonance imaging (MRI) to aid therapeutic strategies. In earlier guidelines, MRI was contra-indicated in patients with CIEDs, mainly due to previous reports of severe complications. With the development of MRI-conditional CIEDs and recent evidence concerning non-MRI-conditional CIEDs, MRIs in CIED patients can be safely performed in many hospitals.However, there are several questions that need to be addressed. Which patients can we scan? How can the scans be performed safely? And last but not least, can cardiac MRI provide diagnostic yield in patients with CIEDs?Current European guidelines are rather outdated and vague about patient selection and practical issues. There are national guidelines on this topic but several issues need extra attention and those are addressed in this point of view. It is important to create an environment with proper patient selection without unnecessary MRI scans in CIED patients, but also without unnecessary fear of complications, preventing access to MRI in patients who can benefit from this powerful diagnostic tool.

Background: The combination of left bundle branch block (LBBB) morphology and QRS duration is currently used to select patients for cardiac resynchronization therapy (CRT). These parameters, however, have limitations. This study evaluates the value of QRS area compared with that of QRS duration and morphology in the association with clinical and echocardiographic outcomes in a large cohort of CRT patients., Methods: A retrospective multicentre study was conducted in 1492 CRT patients. LBBB morphology, QRS duration, and QRS area in the baseline 12-lead ECG were evaluated for their association with the occurrence of the combined primary end point of all-cause mortality, cardiac transplantation, and left ventricular assist device implantation. Secondary end points were heart failure hospitalization within the first year after implantation and echocardiographic reduction in left ventricular end-systolic volume., Results: During a mean follow-up period of 3.4 years, 32% of patients reached the primary end point. The association of QRS area with all outcomes was stronger than that of LBBB morphology and QRS duration separately and at least as strong as their combination. QRS area identified patients who did not experience the primary end point better than QRS morphology and QRS duration (area under the curve, 0.61 versus 0.55 and 0.51, respectively; P<0.001). Furthermore, QRS area identifies patients with echocardiographic remodeling in response to CRT better than QRS morphology and duration (area under the curve, 0.69 versus 0.58 and 0.58, respectively; P<0.001). QRS area was the only independent electrocardiographic determinant associated with the primary end point; hazard ratio, 0.50 (0.35-0.71). Furthermore, QRS area showed significant association with outcomes in both patients with and without LBBB and QRS ≥150 ms., Conclusions: QRS area has a strong association to clinical and echocardiographic response to CRT, at least as strong as current patient selection parameters. QRS area may be particularly useful to predict CRT response in patients without a wide LBBB.

Aims: Various strain parameters and multiple imaging techniques are presently available including cardiovascular magnetic resonance (CMR) tagging (CMR-TAG), CMR feature tracking (CMR-FT), and speckle tracking echocardiography (STE). This study aims to compare predictive performance of different strain parameters and evaluate results per imaging technique to predict cardiac resynchronization therapy (CRT) response., Methods and Results: Twenty-seven patients were prospectively enrolled and underwent CMR and echocardiographic examination before CRT implantation. Strain analysis was performed in circumferential (CMR-TAG, CMR-FT, and STE-circ) and longitudinal (STE-long) orientations. Regional strain values, parameters of dyssynchrony, and discoordination were calculated. After 12 months, CRT response was measured by the echocardiographic change in left ventricular (LV) end-systolic volume (LVESV). Twenty-six patients completed follow-up; mean LVESV change was -29 ± 27% with 17 (65%) patients showing ≥15% LVESV reduction. Measures of dyssynchrony (SD-TTP LV ) and discoordination (ISF LV ) were strongly related to CRT response when using CMR-TAG (R 2 0.61 and R 2 0.57, respectively), but showed poor correlations for CMR-FT and STE (all R 2  ≤ 0.32). In contrast, the end-systolic septal strain (ESS sep ) parameter showed a consistent high correlation with LVESV change for all techniques (CMR-TAG R 2 0.60; CMR-FT R 2 0.50; STE-circ R 2 0.43; and STE-long R 2 0.43). After adjustment for QRS duration and QRS morphology, ESS sep remained an independent predictor of response per technique., Conclusions: End-systolic septal strain was the only parameter with a consistent good relation to reverse remodelling after CRT, irrespective of assessment technique. In clinical practice, this measure can be obtained by any available strain imaging technique and provides predictive value on top of current guideline criteria., (© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Background: To date, there are no data from randomized controlled studies on the benefit of cardiac resynchronization therapy (CRT) when implanted as an upgrade in patients with a previous device as compared to de novo CRT. In the CRT Survey II we compared the baseline data of patients upgraded to CRT (CRT-P/CRT-D) from a previous pacemaker (PM) or implantable cardioverter-defibrillator (ICD) to de novo CRT implantation., Methods and Results: In the European CRT Survey II, clinical practice data of patients undergoing CRT and/or ICD implantation across 42 European Society of Cardiology (ESC) countries were collected between October 2015 and December 2016. Out of a total of 11 088 patients, 2396 (23.2%) were upgraded from a previous PM or ICD and 7933 (76.8%) underwent de novo implantation. Compared to de novo implantations, upgraded patients were older, more often male, more frequently had ischaemic heart failure aetiology, atrial fibrillation, reduced renal function, worse heart failure symptoms, and higher N-terminal pro-B-type natriuretic peptide levels. Upgraded patients were more often PM-dependent and less frequently received CRT-D. Total peri-procedural, in-hospital complications and length of hospital stay were similar. Upgraded patients were less frequently treated with heart failure medication at discharge., Conclusion: Despite a lack of evidenced-based data, close to one quarter of all CRT implantations across 42 ESC countries were upgrades from a previous PM or ICD. Despite older age and worse symptoms, the CRT implantation procedures in upgraded patients were equally frequently successful and complications similar to de novo implantations. These results call for more studies., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Introduction: Experience with the subcutaneous implantable cardioverter-defibrillator (S-ICD) is expanding rapidly. However, data on long-term performance or complications related to elective generator replacement are lacking., Methods: Follow-up (FU) data of all patients implanted between December 2008 and April 2011 were collected. Complications were defined as those requiring surgical intervention. Kaplan-Meier estimates for complication and shock rates, with corresponding 95% confidence intervals (CI), were calculated., Results: One hundred and eighteen patients were included. Median FU was 6.1 years (IQR 5.6-6.5 years). Short-term complication rate (0-30 days) was 3% (CI 0-6%). Long-term complication rate at 6 years was 19% (CI 12-26%), corresponding with an annual complication rate of 3%. One patient in this cohort developed a need for a transvenous ICD (TV-ICD) in order to provide pacing for bradycardia (1%). Six patients were implanted with a TV-ICD after experiencing an S-ICD complication for which extraction was necessary. In total, 10 S-ICDs were extracted; none resulted in a complication. Eight patients had a nonsystemic ICD-related infection and no lead failures were observed. The majority, 68 (58%) patients, received an elective generator replacement. Two patients had a complication related to generator replacement (3%). Battery longevity was 5.6 years (IQR 5.2-6.1). Appropriate and inappropriate shock rates of 6-year estimates were 17% (CI 9-25%) and 21% (CI 15-27%), respectively., Conclusions: This cohort represents the longest follow-up to date and shows a low annual complication rate without lead failures or systemic infections. Battery longevity of the first S-ICD generation results in relative early generator replacement procedures., (© 2018 Wiley Periodicals, Inc.)

Aims: Left ventricular (LV) fusion pacing appears to be at least as beneficial as biventricular pacing in cardiac resynchronization therapy (CRT). Optimal LV fusion pacing critically requires adjusting the atrioventricular (AV)-delay to the delay between atrial pacing and intrinsic right ventricular (RV) activation (Ap-RV). We explored the use of electrogram (EGM)-based vectorloop (EGMV) derived from EGMs of implanted pacing leads to achieve optimal LV fusion pacing and to compare it with conventional approaches., Methods and Results: During CRT-device implantation, 28 patients were prospectively studied. During atrial-LV pacing (Ap-LVp) at various AV-delays, LV dP/dtmax, 12-lead electrocardiogram (ECG), and unipolar EGMs were recorded. Electrocardiogram and electrogram were used to reconstruct a vectorcardiogram (VCG) and EGMV, respectively, from which the maximum QRS amplitude (QRSampl), was extracted. Ap-RV was determined: (i) conventionally as the longest AV-delay at which QRS morphology was visually unaltered during RV pacing at increasing AV-delays(Ap-RVvis; reference-method); (ii) 70% of delay between atrial pacing and RV sensing (Ap-RVaCRT); and (iii) the delay between atrial pacing and onset of QRS (Ap-QRSonset). In both the EGMV and VCG, the longest AV-delay showing an unaltered QRSampl as compared with Ap-LVp with a short AV-delay, corresponded to Ap-RVvis. In contrast, Ap-QRSonset and Ap-RVaCRT were larger. The Ap-LVp induced increase in LV dP/dtmax was larger at Ap-RVvis, Ap-RVEGMV, and Ap-RVVCG than at Ap-QRSonset (all P < 0.05) and Ap-RVaCRT (P = 0.02, P = 0.13, and P = 0.03, respectively)., Conclusion: In this acute study, it is shown that the EGMV QRSampl can be used to determine optimal and individual CRT-device settings for LV fusion pacing, possibly improving long-term CRT response.

Parameters using myocardial strain analysis may predict response to cardiac resynchronization therapy (CRT). As the agreement between currently available strain imaging modalities is unknown, three different modalities were compared. Twenty-seven CRT-candidates, prospectively included in the MARC study, underwent cardiac magnetic resonance (CMR) imaging and echocardiographic examination. Left ventricular (LV) circumferential strain was analysed with CMR tagging (CMR-TAG), CMR feature tracking (CMR-FT), and speckle tracking echocardiography (STE). Basic strain values and parameters of dyssynchrony and discoordination obtained with CMR-FT and STE were compared to CMR-TAG. Agreement of CMR-FT and CMR-TAG was overall fair, while agreement between STE and CMR-TAG was often poor. For both comparisons, agreement on discoordination parameters was highest, followed by dyssynchrony and basic strain parameters. For discoordination parameters, agreement on systolic stretch index was highest, with fair intra-class correlation coefficients (ICC) (CMR-FT: 0.58, STE: 0.55). ICC of septal systolic rebound stretch (SRS sept ) was poor (CMR-FT: 0.41, STE: 0.30). Internal stretch factor of septal and lateral wall (ISF sep-lat ) showed fair ICC values (CMR-FT: 0.53, STE: 0.46), while the ICC of the total LV (ISF LV ) was fair for CMR-FT (0.55) and poor for STE (ICC: 0.32). The CURE index had a fair ICC for both comparisons (CMR-FT: 0.49, STE 0.41). Although comparison of STE to CMR-TAG was limited by methodological differences, agreement between CMR-FT and CMR-TAG was overall higher compared to STE and CMR-TAG. CMR-FT is a potential clinical alternative for CMR-TAG and STE, especially in the detection of discoordination in CRT-candidates.

Background: Although mechanical dyssynchrony parameters derived by speckle tracking echocardiography (STE) may predict response to cardiac resynchronization therapy (CRT), comparability of parameters derived with different STE vendors is unknown., Methods: In the MARC study, echocardiographic images of heart failure patients obtained before CRT implantation were prospectively analysed with vendor specific STE software (GE EchoPac and Philips QLAB) and vendor-independent software (TomTec 2DCPA). Response was defined as change in left ventricular (LV) end-systolic volume between examination before and six-months after CRT implantation. Basic longitudinal strain and mechanical dyssynchrony parameters (septal to lateral wall delay (SL-delay), septal systolic rebound stretch (SRSsept), and systolic stretch index (SSI)) were obtained from either separate septal and lateral walls, or total LV apical four chamber. Septal strain patterns were categorized in three types. The coefficient of variation and intra-class correlation coefficient (ICC) were analysed. Dyssynchrony parameters were associated with CRT response using univariate regression analysis and C-statistics., Results: Two-hundred eleven patients were analysed. GE-cohort (n = 123): age 68 years (interquartile range (IQR): 61-73), 67% male, QRS-duration 177 ms (IQR: 160-192), LV ejection fraction: 26 ± 7%. Philips-cohort (n = 88): age 67 years (IQR: 59-74), 60% male, QRS-duration: 179 ms (IQR: 166-193), LV ejection fraction: 27 ± 8. LV derived peak strain was comparable in the GE- (GE: -7.3 ± 3.1%, TomTec: -6.4 ± 2.8%, ICC: 0.723) and Philips-cohort (Philips: -7.7 ± 2.7%, TomTec: -7.7 ± 3.3%, ICC: 0.749). SL-delay showed low ICC values (GE vs. TomTec: 0.078 and Philips vs. TomTec: 0.025). ICC's of SRSsept and SSI were higher but only weak (GE vs. TomTec: SRSsept: 0.470, SSI: 0.467) (Philips vs. QLAB: SRSsept: 0.419, SSI: 0.421). Comparability of septal strain patterns was low (Cohen's kappa, GE vs. TomTec: 0.221 and Philips vs. TomTec: 0.279). Septal strain patterns, SRSsept and SSI were associated with changes in LV end-systolic volume for all vendors. SRSsept and SSI had relative varying C-statistic values (range: 0.530-0.705) and different cut-off values between vendors., Conclusions: Although global longitudinal strain analysis showed fair comparability, assessment of dyssynchrony parameters was vendor specific and not applicable outside the context of the implemented platform. While the standardization taskforce took an important step for global peak strain, further standardization of STE is still warranted.

Aim: To perform a meta-analysis and systematic review of published data to assess the relationship between contractile reserve and response to cardiac resynchronization therapy (CRT) in patients with heart failure., Methods and Results: We searched MEDLINE/PubMed and Cochrane for all papers published up to 26 April 2016, supplemented by manual searches of reference lists from retrieved articles. The search strategy yielded nine observational studies that met our eligibility criteria with a total of 767 patients of which 757 provided data for this analysis. Contractile reserve after dobutamine infusion was present in 496 patients (66%). During follow-up 474 patients (63%) qualified as CRT responders. The presence of contractile reserve was associated with a higher chance of CRT response (odds ratio 4.42, 95% confidence interval 2.15-9.07, P < 0.001) using a random-effects model. There was evidence of publication bias. Imputation of missing studies attenuated the association to some extent, but the positive association between contractile reserve and CRT response remained with an odds ratio of 2.42 (95% confidence interval 1.17-5.05, P = 0.018)., Conclusion: The presence of global contractile reserve at baseline, as assessed by dobutamine stress echocardiography, is associated with a higher chance of CRT response in patients with heart failure., (© 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.)