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Background Longer-term outcomes of patients post transvenous lead extraction (TLE) are poorly understood in patients with cardiac resynchronization therapy (CRT) devices. Objectives A propensity score (PS)–matched analysis evaluating outcomes post TLE in CRT and non-CRT populations was performed. Methods Data from consecutive patients undergoing TLE between 2000 and 2019 were prospectively collected. Patients surviving to discharge and reimplanted with the same device were included. The cohort was split depending on presence of CRT device. Associations with all-cause mortality and hospitalization were assessed by Kaplan-Meier estimates. An exploratory endpoint was evaluated whether early (7 days) reimplantation was associated with poorer outcomes. Results Of 1005 patients included, 285 (25%) had a CRT device. Median follow-up was 57.00 [27.00–93.00] months, age at explant was 67.7 ± 12.1 years, 83.3% were male, and 54.4% had an infective indication for TLE. PS was calculated using 43 baseline characteristics. After matching, 192 CRT patients were compared with 192 non-CRT patients. In the matched cohort, no significant difference with respect to mortality (hazard ratio [HR] = 1.01, 95% confidence interval [CI] [0.74–1.39], P = .093) or hospitalization risk (HR = 1.2, 95% CI [0.87–1.66], P = .265) was observed. In the matched CRT group, late reimplantation was associated with increased mortality (HR = 1.64, [1.04–2.57], P = .032) and hospitalization risk (HR = 1.57, 95% CI [1.00–2.46], P = .049]. Conclusion Outcomes of CRT patients post TLE are similarly as poor as those of non-CRT patients in matched populations. Reimplantation within 7 days was associated with better outcomes in a CRT population but was not observed in a non-CRT population, suggesting prolonged periods without biventricular pacing should be avoided.

Cardiac resynchronization therapy (CRT) is an effective treatment for dyssynchronous heart failure; however, 30-50% of patients fail to improve after implant. Endocardial left ventricular (LV) pacing is an alternative therapy for patients who do not respond to conventional CRT or in whom placement of a lead via the coronary sinus is not possible. It enables pacing at a wide variety of sites, without restrictions due to coronary sinus anatomy, and there is evidence of superior electrical resynchronization and hemodynamic response compared with conventional epicardial CRT. In this article, we discuss the potential advantages and disadvantages of endocardial LV pacing compared with conventional CRT, review the evidence for the delivery of endocardial LV pacing using both lead-based and leadless systems, and explore possible future directions of this novel technology.Die kardiale Resynchronisationstherapie (CRT) stellt eine effektive Behandlung der dyssynchronen Herzinsuffizienz dar, jedoch kommt es bei 30–50 % der Patienten nach Implantation nicht zu einer signifikanten klinischen Verbesserung. Die endokardiale linksventrikuläre (LV-)Stimulation bietet eine alternative Therapie für Patienten, deren Erkrankung sich unter konventioneller CRT nicht bessert oder bei denen die Implantation einer Elektrode über den Koronarsinus nicht möglich ist. Sie ermöglicht eine Stimulation von einer Vielzahl linksventrikulärer Positionen aus ohne die Limitationen der Koronarsinusanatomie, und es bestehen Belege für eine überlegene elektrische Resynchronisation und Hämodynamik durch endokardiale verglichen mit konventioneller epikardialer CRT. In dieser Übersicht diskutieren die Autoren die möglichen Vor- und Nachteile einer endokardialen LV-Stimulation im Vergleich zur konventionellen CRT, fassen die Evidenz für die endokardiale LV-Stimulation sowohl für elektrodenbasierte wie auch für kabellose Systeme zusammen und untersuchen mögliche zukünftige Entwicklungen dieser neuen Technologie.

Long-term outcomes are poorly understood, and data in patients undergoing transvenous lead extraction (TLE) are lacking.The purpose of this study was to evaluate factors influencing survival in patients undergoing TLE depending on extraction indication.Clinical data from consecutive patients undergoing TLE in the reference center between 2000 and 2019 were prospectively collected. The total cohort was divided into groups depending on whether there was an infective or noninfective indication for TLE. We evaluated the association of demographic, clinical, and device-related and procedure-related factors on mortality.A total of 1151 patients were included. Mean follow-up was 66 months, and mortality was 34.2% (n = 392). Of these patients, 632 (54.9%) and 519 (45.1%) were for infective and noninfective indications, respectively. A higher proportion in the infection group died (38.6% vs 28.5%; P.001). In the total cohort, multivariable analysis demonstrated increased mortality risk with age75 years (hazard ratio [HR] 2.98; 95% confidence interval [CI] 2.35-3.78; P.001), estimated glomerular filtration rate60 mL/min/1.73 mLong-term mortality for patients undergoing TLE remains high. Consensus guidelines recommend evaluating risk for major complications when determining whether to proceed with TLE. This study suggests also assessing longer-term outcomes when considering TLE in those with a high risk of medium- and long-term mortality, particularly for noninfective indications.

INTRODUCTION Multipoint pacing (MPP) has been proposed as an effective way to improve cardiac resynchronisation therapy (CRT) response. We performed a systematic review and meta-analysis evaluating the efficacy of CRT delivered via MPP compared to conventional CRT. METHODS A literature search was performed from inception to January 2021 for studies in Medline, Embase and Cochrane databases, comparing MPP to conventional CRT with a minimum of 6 months follow-up. Randomised and nonrandomised studies were assessed for relevant efficacy data including echocardiographic (left ventricular end systolic volume [LVESV] and ejection fraction) or functional changes (New York Heart Association [NYHA] class/Clinical Composite Score). Subgroup analyses were performed by study design and programming type. RESULTS A total of 7 studies with a total of 1390 patients were included in the final analysis. Overall, MPP demonstrated greater echocardiographic improvement than conventional CRT in nonrandomised studies (odds ratio [OR]: 5.33, 95% confidence interval [CI]: [3.05-9.33], p 15% (OR: 1.96, 95% CI: [0.69-5.55], p = .20) or improvement by ≥1 NYHA class (OR: 2.49, 95% CI: [0.74-8.42], p = .141) when comparing MPP to conventional CRT. In a sub analysis, MPP programmed by widest anatomical separation (MPP-AS) signalled greater efficacy, however, only 120 patients were included in this analysis. CONCLUSION Overall MPP was more efficacious in nonrandomised studies, and not superior when assessed in randomised studies. There was considerable heterogeneity in study design making overall interpretation of results challenging. Widespread MPP programming in all CRT patients is currently not justified. Further large, randomised studies with patient-specific programming may clarify its effectiveness.

Background Patients who improve following cardiac resynchronization therapy (CRT) have left ventricular (LV) remodeling and improved cardiac output (CO). Effects on the systemic circulation are unknown. Objective To explore the effects of CRT on aortic and pulmonary blood flow and systemic afterload. Methods At CRT implant patients underwent a noninvasive assessment of central hemodynamics, including wave intensity analysis (n = 28). This was repeated at 6 months after CRT. A subsample (n = 11) underwent an invasive electrophysiological and hemodynamic assessment immediately following CRT. CRT response was defined as reduction in LV end-systolic volume ≥15% at 6 months. Results In CRT responders (75% of those in the noninvasive arm), there was a significant increase in CO (from 3 ± 2 L/min to 4 ± 2 L/min, P = .002) and LV dP/dtmax (from 846 ± 162 mm Hg/s to 958 ± 194 mm Hg/s, P = .001), immediately after CRT in those in the invasive arm. They demonstrated a significant increase in aortic forward compression wave (FCW) both acutely and at follow-up. The relative change in LV dP/dtmax strongly correlated with changes in the aortic FCW (Rs 0.733, P = .025). CRT responders displayed a significant reduction in afterload, and a decrease in systemic vascular resistance and pulse wave velocity acutely; there was a significant decrease in acute pulmonary afterload measured by the pulmonary FCW and forward expansion wave. Conclusion Improved cardiac function following CRT is attributable to a combination of changes in the cardiac and cardiovascular system. The relative importance of these 2 mechanisms may then be important for optimizing CRT., Graphical abstract

Background Cardiac resynchronization therapy (CRT) produces acute changes in electric resynchronization that can be measured noninvasively with electrocardiographic body surface mapping (ECGi). The relation between baseline acute electrophysiology metrics and their manipulation with CRT and reverse remodeling is unclear. Objective To test (ECGi) derived parameters of electrical activation as predictors of volumetric response to CRT. Methods ECGi was performed in 21 patients directly following CRT implant. Activation parameters (left ventricular total activation time [LVtat], global biventricular total activation time [VVtat], global left/right ventricular electrical synchrony [VVsync], and global left ventricular dispersion of activation times [LVdisp]) were measured at baseline and following echocardiographically optimized CRT. Remodeling response (>15% reduction left ventricular end-systolic volume) was assessed 6 months post CRT. Results Patients were aged 68.9 ± 12.1 years, 81% were male, and 57% were ischemic. Baseline measures of dyssynchrony were more pronounced in left bundle branch block (LBBB) vs non-LBBB. ECGi demonstrated a trend of greater interventricular dyssynchrony between responders and nonresponders that did not reach statistical significance (VVsync: -45.7 ± 22.4 ms vs -25.1 ± 29.3 ms, P = .227). Remaining activation parameters were similar between responders and nonresponders (VVtat 101 ± 22.0 ms vs 98.9 ± 23.4 ms, P = .838; LVtat 86.4 ± 17.1 ms vs 85.1 ± 27.7 ms, P = .904; LVdisp 28.2 ± 6.3 ms vs 27.0 ± 8.7 ms, P = .726). In volumetric responders activation parameters were significantly improved with CRT compared to nonresponders: VV sync (-45.67 ± 22.41 ms vs 2.33±18.87 ms, P = .001), VVtat (101 ± 22.04 ms vs 71 ± 14.01 ms, P = .002), LVtat (86.44 ± 17.15 ms vs 67.67 ± 11.31 ms, P = .006), and LVdisp (28.22 ± 6.3 ms vs 21.56 ± 4.45 ms, P = .008). Conclusion Baseline ECGi activation times did not predict CRT volumetric response. Volumetric responders exhibited significant improvements in ECGi-derived metrics with CRT. ECGi does not select CRT candidates but may be a useful adjunct to guide left ventricle lead implants and to perform postimplant CRT optimization., Graphical abstract

Cardiac resynchronisation therapy is an important intervention to reduce mortality and morbidity, but even in carefully selected patients approximately 30% fail to improve. This has led to alternative pacing approaches to improve patient outcomes. Left ventricular (LV) endocardial pacing allows pacing at site-specific locations that enable the operator to avoid myocardial scar and target areas of latest activation. Left bundle branch area pacing (LBBAP) provides a more physiological activation pattern and may allow effective cardiac resynchronisation. This article discusses LV endocardial pacing in detail, including the indications, techniques and outcomes. It discusses LBBAP, its potential benefits over His bundle pacing and procedural outcomes. Finally, it concludes with the future role of endocardial pacing and LBBAP in heart failure patients.

Background Epicardial pacing increases risk of ventricular tachycardia (VT) in patients with ischemic cardiomyopathy (ICM) when pacing in proximity to scar. Endocardial pacing may be less arrhythmogenic as it preserves the physiological sequences of activation and repolarization. Objective The purpose of this study was to determine the relative arrhythmogenic risk of endocardial compared to epicardial pacing, and the role of the transmural gradient of action potential duration (APD) and pacing location relative to scar on arrhythmogenic risk during endocardial pacing. Methods Computational models of ICM patients (n = 24) were used to simulate left ventricular (LV) epicardial and endocardial pacing 0.2–3.5 cm from a scar. Mechanisms were investigated in idealized models of the ventricular wall and scar. Simulations were run with/without a 20-ms transmural APD gradient in the physiological direction and with the gradient inverted. Dispersion of repolarization was computed as a surrogate of VT risk. Results Patient-specific models with a physiological APD gradient predict that endocardial pacing decreases VT risk (34%; P

BACKGROUND Antitachycardia pacing (ATP), which may avoid unnecessary implantable cardioverter-defibrillator (ICD) shocks, does not always terminate ventricular arrhythmias (VAs). Mean entropy calculated using cardiac magnetic resonance texture analysis (CMR-TA) has been shown to predict appropriate ICD therapy. We examined whether scar heterogeneity, quantified by mean entropy, is associated with ATP failure and explore potential mechanisms using computer modeling. METHODS A subanalysis of 114 patients undergoing CMR-TA where the primary endpoint was delivery of appropriate ICD therapy (ATP or shock therapy) was performed. Patients receiving appropriate ICD therapy (n = 33) were dichotomized into "successful ATP" versus "shock therapy" groups. In silico computer modeling was used to explore underlying mechanisms. RESULTS A total of 16 of 33 (48.5%) patients had successful ATP to terminate VA, and 17 of 33 (51.5%) patients required shock therapy. Mean entropy was significantly higher in the shock versus successful ATP group (6.1 ± 0.5 vs 5.5 ± 0.7, P = .037). Analysis of patients receiving ATP (n = 22) showed significantly higher mean entropy in the six of 22 patients that failed ATP (followed by rescue ICD shock) compared to 16 of 22 that had successful ATP (6.3 ± 0.7 vs 5.5 ± 0.7, P = .048). Computer modeling suggested inability of the paced wavefront in ATP to successfully propagate from the electrode site through patchy fibrosis as a possible mechanism of failed ATP. CONCLUSIONS Our findings suggest lower scar heterogeneity (mean entropy) is associated with successful ATP, whereas higher scar heterogeneity is associated with more aggressive VAs unresponsive to ATP requiring shock therapy that may be due to inability of the paced wavefront to propagate through scar and terminate the VA circuit.

Background Left bundle branch area pacing (LBBAP) is a novel form of conduction system pacing which can reverse left bundle branch block and deliver cardiac resynchronization therapy (CRT). The WiSE-CRT system delivers leadless endocardial pacing with symptomatic and left ventricular (LV) remodelling improvements following intervention. We report the technical feasibility of delivering leadless LBBAP using the WiSE-CRT system. Case summary In Case 1, a 57-year-old male with ischaemic cardiomyopathy and complete heart block underwent implantation of the WiSE-CRT system, using a retrograde transaortic approach, after failed conventional CRT. Temporary left bundle stimulation from the LV septum achieved superior electrical resynchronization and equivalent haemodynamic response compared to endocardial pacing at the lateral LV wall. In Case 2, an 82-year-old gentleman with tachyarrhythmia-induced cardiomyopathy underwent WiSE-CRT implantation via a trans-septal inter-atrial approach, with the endocardial electrode successfully deployed in the LV septum. Discussion Here we report the first case of deployment of the WiSE-CRT endocardial electrode in the LV septum and demonstrate the technical feasibility of leadless LBBAP. Entirely leadless CRT is an attractive option for patients with venous access issues or recurrent lead complications and has previously been successful using the WiSE-CRT system and a leadless pacemaker in the right ventricle. Further studies are required to assess long-term efficacy and safety of leadless LBBAP.

Background Computational models of the heart built from cardiac MRI and electrophysiology (EP) data have shown promise for predicting the risk of and ablation targets for myocardial infarction (MI) related ventricular tachycardia (VT), as well as to predict paced activation sequences in heart failure patients. However, most recent studies have relied on low resolution imaging data and little or no EP personalisation, which may affect the accuracy of model-based predictions. Objective To investigate the impact of model anatomy, MI scar morphology, and EP personalisation strategies on paced activation sequences and VT inducibility to determine the level of detail required to make accurate model-based predictions. Methods Imaging and EP data were acquired from a cohort of six pigs with experimentally induced MI. Computational models of ventricular anatomy, incorporating MI scar, were constructed including bi-ventricular or left ventricular (LV) only anatomy, and MI scar morphology with varying detail. Tissue conductivities and action potential duration (APD) were fitted to 12-lead ECG data using the QRS duration and the QT interval, respectively, in addition to corresponding literature parameters. Paced activation sequences and VT induction were simulated. Simulated paced activation and VT inducibility were compared between models and against experimental data. Results Simulations predict that the level of model anatomical detail has little effect on simulated paced activation, with all model predictions comparing closely with invasive EP measurements. However, detailed scar morphology from high-resolution images, bi-ventricular anatomy, and personalized tissue conductivities are required for predict experimental VT outcome. Conclusion This study provides clear guidance for model generation based on clinical data. While a representing high level of anatomical and scar detail will require high-resolution image acquisition, EP personalisation based on 12-lead ECG can be readily incorporated into modelling pipelines, as such data is widely available.

Aims Cardiac resynchronization therapy (CRT) upgrades may be less likely to improve following intervention. Leadless left ventricular (LV) endocardial pacing has been used for patients with previously failed CRT or high-risk upgrades. We compared procedural and long-term outcomes in patients undergoing coronary sinus (CS) CRT upgrades with high-risk and previously failed CRT upgrades undergoing LV endocardial upgrades. Method and results Prospective consecutive CS upgrades between 2015 and 2019 were compared with those undergoing WiSE-CRT implantation. Cardiac resynchronization therapy response at 6 months was defined as improvement in clinical composite score (CCS) and a reduction in LV end-systolic volume (LVESV) ≥15%. A total of 225 patients were analysed; 121 CS and 104 endocardial upgrades. Patients receiving WiSE-CRT tended to have more comorbidities and were more likely to have previous cardiac surgery (30.9% vs. 16.5%; P = 0.012), hypertension (59.2% vs. 34.7%; P, Graphical Abstract

Background: No periprocedural metric has demonstrated improved cardiac resynchronization therapy (CRT) outcomes in a multicenter setting. Objective: We sought to determine if left ventricular (LV) lead placement targeted to the coronary sinus (CS) branch generating the best acute hemodynamic response (AHR) results in improved outcomes at 6 months. Methods: In this multicenter randomized controlled trial, patients were randomized to guided CRT or conventional CRT. Patients in the guided arm had LV dP/dtmax measured during biventricular (BIV) pacing. Target CS branches were identified and the final LV lead position was the branch with the best AHR and acceptable threshold values. The primary endpoint was the proportion of patients with a reduction in LV end-systolic volume (LVESV) of ≥15% at 6 months. Results: A total of 281 patients were recruited across 12 centers. Mean age was 70.8 ± 10.9 years and 54% had ischemic etiology. Seventy-three percent of patients in the guided arm demonstrated a reduction in LVESV of ≥15% at 6 months vs 60% in the conventional arm (P = .02). Patients with AHR ≥ 10% were more likely to demonstrate a reduction of ESV ≥ 15% (84% of patients with an AHR ≥10% vs 28% with an AHR

AIMS Electrocardiographic imaging (ECGi) and the ECG belt are body surface potential mapping systems which can assess electrical dyssynchrony in patients undergoing cardiac resynchronization therapy (CRT). ECGi-derived dyssynchrony metrics are calculated from reconstructed epicardial potentials based on body surface potentials combined with a thoracic CT scan, while the ECG belt relies on body surface potentials alone. The relationship between dyssynchrony metrics from these two systems is unknown. In this study we aim to compare intra-ventricular and inter-ventricular dyssynchrony metrics between ECGi and the ECG belt. METHODS Seventeen patients underwent ECGi after CRT. A subsample of 40 body surface potentials was used to simulate the ECG belt. ECGi dyssynchrony metrics, calculated from reconstructed epicardial potentials, and ECG belt dyssynchrony metrics, calculated from the sampled body surface potentials were compared. RESULTS There was a strong positive correlation between ECGi left ventricular activation time (LVAT) and ECG belt left thorax activation time (LTAT) (R = 0.88 ; P < 0.001) and between ECGi standard deviation of activation times (SDAT) and ECG belt-SDAT (R = 0.76; P < 0.001) during intrinsic rhythm. The correlation for both pairs was also strong during biventricular pacing. Ventricular electrical uncoupling, a well validated ECGi inter-ventricular dyssynchrony metric, correlated strongly with ECG belt-SDAT during intrinsic rhythm (R = 0.76; P < 0.001) but not biventricular pacing (R = 0.29; P = 0.26). Cranial or caudal displacement of the simulated ECG belt did not affect LTAT or SDAT. CONCLUSION ECGi- and ECG belt-derived intra-ventricular and inter-ventricular dyssynchrony metrics were strongly correlated. The ECG belt may offer comparable dyssynchrony assessment to ECGi, with associated practical and cost advantages.

Background Pre-procedural assessment of patients undergoing cardiac resynchronization therapy (CRT) is heterogenous and patients implanted with unfavorable characteristics may account for non-response. A dedicated CRT pre-assessment clinic (CRT PAC) was developed to standardize the review process and undertake structured pre-procedural evaluation. The aim of this analysis was to determine the effectiveness on patient selection and outcomes. Methods A prospective database of consecutive patients attending the CRT PAC between 2013 and 2018 was analyzed. Pre-operative assessment included cardiac magnetic resonance (CMR) and cardiopulmonary exercise testing (CPET). Patients were considered CRT responders based on improvement in clinical composite score (CCS) and/or reduction in left ventricular end-systolic volume (LVESV) ≥ 15% at 6-months follow-up. Results Of 252 patients reviewed in the CRT PAC during the analysis period, 192 fulfilled consensus guidelines for implantation. Of the patients receiving CRT, 82% showed improvement in their CCS and 57% had a reduction in LVESV ≥ 15%. The presence of subendocardial scar on CMR and a peak VO2 ≤ 12 ml/kg/min on CPET predicted CRT non-response. Two patients were unsuitable for CRT as they had end-stage heart failure and died during follow-up. The majority of patients initially deemed unsuitable for CRT did not suffer from unexpected hospitalization for decompensated heart failure or died from cardiovascular disease; only 8 patients (13%) received CRT devices during follow-up because of symptomatic left ventricular systolic impairment. Conclusion A dedicated CRT PAC is able to appropriately select patients for CRT. Pre-procedural investigation/imaging can identify patients unlikely to respond to, or may not yet be suitable for CRT.

Funding Acknowledgements Type of funding sources: None. Background Relative benefits of transvenous lead extraction (TLE) should be weighed against the risks on an individual basis. Observational studies have identified disparate risk factors for major adverse events (MAEs), however there are few available tools to aid the clinician risk-stratifying patients. Purpose The purpose of this study was to develop a machine learning (ML)-based risk stratification system to predict risk of MAEs following transvenous lead extraction (TLE). Methods Multiple ML models were derived from a training cohort of 3555 patients undergoing TLE to pre-procedurally identify patients at high and low risk of major adverse events (procedure-related major complication, including procedure-related death). The ML models were then tested on an independent, reference centre cohort of 1171 patients undergoing TLE. Clinical features were selected based on whether they were available in both datasets without large gaps. For model selection we compared the ML algorithms logistic regression, ridge regression, support vector machines (SVM), gradient boosting classifier and random forest. The best performing of these was then compared to a self-normalising network (SNN). Results In total 3122 cases with the required features were included from the training cohort with 53 MAEs (1.7%), and 998 cases in the test cohort with 24 MAEs (2.4%). SVM identified lead dwell time, left ventricular ejection fraction (LVEF), estimated glomerular filtration rate (eGFR), chronic respiratory disease, local infection, heart failure, sepsis and male gender as predictors of MAEs in order of decreasing importance (see figure). For the training data, the SVM provided a more sensitive result compared with SNN (0.83 vs 0.71) at the cost of specificity (0.63 vs 0.79). For the test data, the SVM identified MAEs in 12 out of 123 (9.8%) "high risk" patients, 10 out of 552 (1.8%) "medium risk" patients, and 2 out of 323 (0.006%) "low risk" patients. Conclusion Machine learning provided good discriminative capabilities for identifying patients in a "high risk" and "low risk" category for MAEs. Abstract Figure. 8 most important predictors of MAEs

Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): Medtronic Background / Introduction Endocardial pacing and conduction system pacing are emerging as alternative methods to deliver cardiac resynchronization therapy (CRT) and have been shown to achieve superior acute hemodynamic response (AHR) compared to conventional epicardial pacing. However, a direct comparison of all the methods of delivering CRT has not yet been performed. Purpose To directly compare the AHR of conventional CRT (BiV Epi), endocardial pacing (BiV Endo), His bundle pacing (HBP) and left bundle branch pacing (LBBP) during a temporary CRT study. Methods 4 patients underwent a temporary CRT and hemodynamic study. Temporary pacing was achieved using quadripolar catheters in the right atrium and coronary sinus, and roving decapolar catheters in the right ventricle (RV) and left ventricle (LV) via retrograde aortic access. Hemodynamic assessment was performed with a PressureWire X (Abbott, CA, USA) in the LV cavity. AHR was calculated as the percentage improvement in LV dP/dtmax from baseline AAI or RV pacing (if underlying complete heart block). Results The patients had a mean age of 67.5 ±5.8 years and all had non-ischemic cardiomyopathy with severe LV impairment (mean ejection fraction 22.5 ±7.4%). 3 patients had left bundle branch block and 1 patient had complete heart block with an RV paced rhythm (mean QRS duration 157 ±24 ms). All methods of delivering CRT achieved a mean AHR of >10%, which is considered clinically significant and is predictive of LV remodelling at 6 months. Mean AHR during BiV Epi pacing was 12.6 ±5.0%. There was a trend towards higher AHR for BiV Endo pacing (23.6 ±7.6%), HBP (17.4 ± 9.5%) and LBBP (16.1 ±7.8%) as shown in figure 1, however there was no significant difference between groups on one-way analysis of variance (p = 0.348). Conclusions All methods of delivering CRT achieved an AHR >10%. The AHR during BiV Endo pacing, HBP and LBBP was higher than for BiV Epi pacing, but this did not reach statistical significance. Further investigation with larger studies is required to determine which method of delivering CRT achieves the best hemodynamic response. Figure 1. Box plot of acute hemodynamic response (AHR) for conventional cardiac resynchronization therapy (BiV Epi), endocardial pacing (BiV Endo), His bundle pacing (HBP) and left bundle branch pacing (LBBP). Data displayed as median (solid line), mean (+), 1st and 3rd quartiles (box) and minimum and maximum values (whiskers). Abstract Figure 1

Funding Acknowledgements Type of funding sources: None. Background/Introduction: The significant rise in cardiac implantable electronic devices (CIED) has been paralleled by an increase in the number of procedures required for the removal of such devices and their associated leads. High procedural success rates with low rates of major in hospital complications is well recognised. Longer term mortality following transvenous lead extraction (TLE) is less well characterised. Long term outcomes are important as they should inform the decision making and consent process, especially in non-infected cases where there may not be a class I indication for lead removal. Purpose The purpose of this study was to evaluate the factors influencing survival in patients undergoing TLE depending on extraction indication. Methods Clinical data from consecutive patients undergoing TLE in the reference centre between the years 2000 to 2019 were prospectively collected. Only patients surviving to discharge were included. The total cohort was divided into groups depending on whether there was an infective or non-infective indication for TLE. We evaluated the association of demographic, clinical, device related and procedure-related factors on mortality. Results A total of 1151 patients were included in the analysis. 632 (54.9%) and 519 patients (45.1%) were for infective and non-infective indications respectively. Analysis of long-term outcomes on the total cohort (mean 66-month follow-up) revealed a mortality of 34.1% (392 deaths). A higher proportion of patients died in the infection vs the non-infection group (38.6% vs 28.5%, p Conclusion Long-term mortality for patients undergoing TLE remains high. Consensus guidelines recommend evaluating risk for major complications when determining whether to proceed with TLE. This study suggests assessing longer-term outcomes when considering TLE, particularly for non-infective indications. Abstract Figure.

Funding Acknowledgements Type of funding sources: None. Background Among patients undergoing transvenous lead extraction (TLE), differences in complication rate and 1-year mortality has been explored in patients with cardiac resynchronisation therapy (CRT) devices. Longer term outcomes and the influence of timing of reimplantation of device, with respect to rehospitalisation and longer-term mortality is poorly understood. Purpose The purpose of this study was to evaluate whether early reimplantation following TLE in patients with CRT devices influenced survival and rehospitalisation. Methods Clinical data from consecutive patients undergoing TLE in the reference centre between the years 2000 to 2019 were prospectively collected. Patients surviving to discharge who were re-implanted with the same device were included. The cohort was split depending on whether or not they had a CRT device at time of explant. The association between TLE in CRT patients and all-cause mortality and re-hospitalisation was assessed by Kaplan Meier estimates in a 1:1 propensity-score matched cohort, with a calliper of 0.10. Early reimplantation was defined as reimplantation within 7 days of TLE, and late reimplantation as reimplantation after greater than 7 days of TLE. Results Of 1005 patients included in the analysis, 285 (25%) had a CRT device. After matching, 192 CRT patients were compared with 192 non-CRT patients. Propensity scores were calculated using 39 baseline characteristics, including age, gender, co-morbidities, TLE indication, left ventricular ejection fraction, baseline creatinine and technical extraction data. Mean follow up was 53.5 ± 38.3 months, mean age at explant was 67.7 ± 12.1 years, 83.3% were male and 54.4% had an infective indication for TLE. In the matched cohort, there was no significant difference between the CRT and non-CRT group with respect to long-term mortality (hazard ratio [HR] = 1.01, 95% confidence interval [CI] [0.74-1.39], p = 0.093) or rehospitalisation (HR = 1.2 [0.87-1.66], p = 0.265). A similar proportion of patients were reimplanted within 7 days in the CRT and non-CRT groups (59.4% vs 61.5%, p = 0.754). In the matched non-CRT group, late reimplantation was associated with similar mortality to early reimplantation (HR = 1.33 [0.86-2.05], p = 0.208) and rehospitalisation (HR = 0.88 [0.53-1.45], p = 0.603). In the matched CRT group, late reimplantation was associated with higher mortality (HR = 1.64 [1.04-2.57], p = 0.032) and rehospitalisation (HR = 1.57 [1.00-2.46], p = 0.049] (see figure). Conclusion In this closely matched population, TLE in CRT patients resulted in similar long-term outcomes compared with non-CRT patients. Early reimplantation post CRT explant was associated with reduced long-term mortality and rehospitalisation. This suggests a longer duration without biventricular pacing post TLE may induce negative reverse-remodelling and should be avoided in a CRT population. Abstract Figure. Kaplan-Meier survival curves

Introduction: Left bundle branch pacing is a recently described form of conduction system pacing which can correct left-bundle branch block and deliver cardiac resynchronization therapy (CRT). The WiSE-CRT system delivers leadless endocardial pacing and can improve symptoms and left ventricular remodelling in CRT non-responders. Case Report: We describe the case of a 57 year old male who underwent implantation of the WiSE-CRT system after failed conventional CRT. Pacing the left bundle during implant achieved superior electrical resynchronization and equivalent hemodynamic response compared to pacing the lateral wall. Conclusion: This case demonstrates the potential for leadless left bundle branch pacing.

Aims Transvenous lead extraction is associated with a significant risk of complications and identifying patients at highest risk pre-procedurally will enable interventions to be planned accordingly. We developed the ELECTRa Registry Outcome Score (EROS) and applied it to the ELECTRa registry to determine if it could appropriately risk-stratify patients. Methods and results EROS was devised to risk-stratify patients into low risk (EROS 1), intermediate risk (EROS 2), and high risk (EROS 3). This was applied to the ESC EORP European Lead Extraction ConTRolled ELECTRa registry; 57.5% EROS 1, 31.8% EROS 2, and 10.7% EROS 3. Patients with EROS 3 or 2 were significantly more likely to require powered sheaths and a femoral approach to complete procedures. Patients with EROS 3 were more likely to suffer procedure-related major complications including deaths (5.1 vs. 1.3%; P Conclusion EROS successfully identified patients who were at increased risk of significant procedural complications that require urgent surgical intervention.

Background: Endocardial pacing may be beneficial in patients who fail to improve following conventional epicardial cardiac resynchronization therapy (CRT). The potential to pace anywhere inside the left ventricle thus avoiding myocardial scar and targeting the latest activating segments may be particularly important. The WiSE-CRT system (EBR systems, Sunnyvale, CA) reliably produces wireless, endocardial left ventricular (LV) pacing. The purpose of this analysis was to determine whether this system improved symptoms or led to LV remodeling in patients who were nonresponders to conventional CRT. Method: An international, multicenter registry of patients who were nonresponders to conventional CRT and underwent implantation with the WiSE-CRT system was collected. Results: Twenty-two patients were included; 20 patients underwent successful implantation with confirmation of endocardial biventricular pacing and in 2 patients, there was a failure of electrode capture. Eighteen patients proceeded to 6-month follow-up; endocardial pacing resulted in a significant reduction in QRS duration compared with intrinsic QRS duration (26.6 ± 24.4 ms; P =.002) and improvement in left ventricular ejection fraction (LVEF) (4.7 ± 7.9%; P =.021). The mean reduction in left ventricular end-diastolic volume was 8.3 ± 42.3 cm3 (P =.458) and left ventricular end-systolic volume (LVESV) was 13.1 ± 44.3 cm3 (P =.271), which were statistically nonsignificant. Overall, 55.6% of patients had improvement in their clinical composite score and 66.7% had a reduction in LVESV ≥15% and/or absolute improvement in LVEF ≥5%. Conclusion: Nonresponders to conventional CRT have few remaining treatment options. We have shown in this high-risk patient group that the WiSE-CRT system results in improvement in their clinical composite scores and leads to LV remodeling.

Background: More than half of the patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) have multi-vessel coronary artery disease. This is associated with worse outcomes compared with single vessel disease. Whilst evidence now exists to support complete revascularisation for bystander disease the optimal timing is still debated. This study aimed to compare clinical outcomes in patients with STEMI and multi-vessel disease who underwent complete revascularisation as inpatients in comparison to patients who had staged PCI as early outpatients. Methods and results: We conducted an observational cohort study consisting of 1522 patients who underwent primary PCI with multi-vessel disease from 2012 to 2019. Exclusions included patients with cardiogenic shock and previous CABG. Patients were split into 2 groups depending on whether they had complete revascularisation performed as inpatients or as staged PCI at later outpatient dates. The primary outcome of this study was major adverse cardiac events (consisting of myocardial infarction, target vessel revascularisation and all-cause mortality). 834 (54.8%) patients underwent complete inpatient revascularisation and 688 patients (45.2%) had outpatient PCI (median 43 days post discharge). Of the inpatient group, 652 patients (78.2%) underwent complete revascularisation during the index procedure whilst 182 (21.8%) patients underwent inpatient bystander PCI in a second procedure. Overall, there were no significant differences between the groups with regards to their baseline or procedural characteristics. Over the follow-up period there was no significant difference in MACE between the cohorts ( P = .62), which persisted after multivariate adjustment (HR 1.21 [95% CI 0.72-1.96]). Furthermore, in propensity-matched analysis there was no significant difference in outcome between the groups (HR: 0.86 95% CI: 0.75-1.25). Conclusions: Our study demonstrated that the timing of bystander PCI after STEMI did not appear to have an effect on cardiovascular outcomes. We suggest that patients with multi-vessel disease can potentially be discharged promptly and undergo early outpatient bystander PCI. This could significantly reduce length of stay in hospital.

Funding Acknowledgements WT 203148/Z/16/Z; MR/N011007/1; RE/08/003; PG/15/91/31812; PG/16/81/32441 Background Endocardial pacing has been shown to improve response to cardiac resynchronization therapy (CRT) in comparison to conventional epicardial pacing and the physiological activation, endocardium to epicardium, is proposed to make it less arrhythmogenic. However, the relative arrhythmic risk of endocardial and epicardial pacing has not been systematically investigated. Pacing in proximity to scar increases susceptibility to arrhythmogenesis during epicardial pacing. Whether this is also the case during endocardial pacing is currently unknown. Purpose We investigate 1) whether endocardial pacing is less arrhythmogenic than epicardial pacing, 2) whether pacing location relative to scar plays a role in arrhythmogenesis during endocardial pacing, and 3) whether these findings could be explained by the direction of the transmural action potential duration (APD) gradient. Methods We used computational models of ischemic heart failure and patient-specific (n = 24) left ventricular anatomy and scar morphology to simulate repolarization during endocardial and epicardial pacing. Pacing locations were selected 0.2-3.5cm from a scar. We ran simulations with a 20ms transmural APD gradient, as found in heart failure, from the epicardium to endocardium (physiological) and with this gradient inverted. We computed the volume of high (>3ms/mm) repolarization gradients (HRG) within 1cm around a scar, as a surrogate for arrhythmia risk, and analysed these with ANOVA and Tukey-Kramer post-hoc tests. Results Simulations with a physiological APD gradient predict that endocardial pacing creates a smaller (34%) volume of HRG around (1cm) a scar compared to epicardial pacing when pacing 0.2cm from scar (Figure 1-A). The volume of HRG decreases (P from scar for epicardial pacing but not endocardial pacing (Figure 1-A). Inverting the transmural APD gradient, inverts the trend observed with a physiological gradient. In this case, the volume of HRG is unaffected by pacing location during epicardial pacing, whereas it decreases (19%) with the distance from scar for endocardial pacing. This is illustrated in the regions highlighted in yellow in Figure 1 for endocardial pacing at 0.2 and 3.5cm from a scar with a physiological (B) and an inverted (C) gradient. Conclusions Endocardial pacing is less arrhythmogenic (purpose 1) than conventional epicardial pacing when pacing in proximity to scar and is also less susceptible to pacing location relative to scar (purpose 2). The direction of the transmural APD gradient offers a mechanistic explanation for reduced susceptibility to arrhythmogenesis during endocardial pacing compared to epicardial pacing (purpose 3). Endocardial pacing is an attractive alternative to conventional epicardial pacing in patients with scar, as it allows pacing in proximity to scar while avoiding increasing arrhythmogenic risk in patients with ischemic heart failure. Abstract Figure.

His-bundle pacing (HBP) and left bundle pacing (LBP) are emerging as novel delivery methods for cardiac resynchronization therapy (CRT) in heart failure patients with left bundle branch block (LBBB). HBP and LBP have never been compared to biventricular endocardial (BiV-endo) pacing. Furthermore, there are indications of negative effects of LBP on right ventricular (RV) activation times (ATs), but these effects have not been quantified.The purpose of this study was to compare changes in ventricular activation induced by HBP, LBP, left ventricular (LV) septal pacing, BiV-endo, and biventricular epicardial (BiV-epi) pacing using computer simulations.We simulated ventricular activation on 24 four-chamber heart meshes inclusive of the His-Purkinje network in the presence of LBBB. We simulated BiV-epi pacing, BiV-endo pacing with left ventricular (LV) lead at the lateral wall, BiV-endo pacing with LV lead at the LV septum, HBP, and LBP.HBP was superior to BiV-endo and BiV-epi in terms of reduction in LV ATs and interventricular dyssynchrony (P.05). LBP reduced LV ATs but not interventricular dyssynchrony compared to BiV-epi and BiV-endo pacing. RV latest AT was higher with LBP than with HBP (141.3 ± 10.0 ms vs 111.8 ± 10.4 ms). Optimizing AV delay during LBP reduced RV latest AT (104.7 ± 8.7 ms) and led to comparable response to HBP. In case of complete AV block, BiV-endo septal pacing was equivalent to LBP.HBP is superior to BiV-epi and BiV-endo. To achieve comparable response to HBP, AV delay optimization during LBP is required in order to reduce RV ATs.

A 63-year-old patient with ischemic cardiomyopathy, severe left ventricular systolic dysfunction, atrial fibrillation with underlying complete heart block, and a conventional cardiac resynchronization therapy-defibrillator (CRT-D), was diagnosed with a device-related infection. This device was

Aims Transvenous lead extraction (TLE) should ideally be undertaken by experienced operators in a setting that allows urgent surgical intervention. In this analysis of the ELECTRa registry, we sought to determine whether there was a significant difference in procedure complications and mortality depending on centre volume and extraction location. Methods and results Analysis of the ESC EORP European Lead Extraction ConTRolled ELECTRa registry was conducted. Low-volume (LoV) centres were defined as Conclusion Primary operator cardiologists in LoV centres are more likely to have extractions complicated by procedure-related deaths. There was no significant difference in procedure complications between different extraction settings. These findings support the need for TLE to be performed in experienced centres with appropriate personnel present.

Background Cardiac Resynchronization Therapy (CRT) in dyssynchronous heart failure patients is ineffective in 20–30% of cases. Sub-optimal left ventricular (LV) pacing location can lead to non-response, thus there is interest in LV lead location optimization. Invasive acute haemodynamic response (AHR) measurements have been used to optimize the LV pacing location during CRT implantation. In this manuscript, we aim to predict the optimal lead location (AHR>10%) with non-invasive computed tomography (CT) based measures of cardiac anatomical and mechanical properties, and simulated electrical activation times. Methods Non-invasive measurements from CT images and ECG were acquired from 34 patients indicated for CRT upgrade. The LV lead was implanted and AHR was measured at different pacing sites. Computer models of the ventricles were used to simulate the electrical activation of the heart, track the mechanical motion throughout the cardiac cycle and measure the wall thickness of the LV on a patient specific basis. Results We tested the ability of electrical, mechanical and anatomical indices to predict the optimal LV location. Electrical (RV-LV delay) and mechanical (time to peak contraction) indices were correlated with an improved AHR, while wall thickness was not predictive. A logistic regression model combining RV-LV delay and time to peak contraction was able to predict positive response with 70 ± 11% accuracy and AUROC curve of 0.73. Conclusion Non-invasive electrical and mechanical indices can predict optimal epicardial lead location. Prospective analysis of these indices could allow clinicians to test the AHR at fewer pacing sites and reduce time, costs and risks to patients.

Purpose of review Cardiovascular events are the major cause of death in chronic kidney disease (CKD). Individuals with CKD have a substantially greater risk of cardiovascular disease compared with the general population but have largely been excluded from clinical trials. This review highlights the complex pathogenesis of cardiovascular disease, discusses the evidence for cardiovascular risk reduction and assesses the achievement of cardiovascular treatment targets in CKD. Recent findings There is evidence to support both blood pressure and cholesterol reduction in the CKD population. The risk of bleeding with antiplatelet drugs is high in CKD and these should be used with caution. Although there has been recent interest in targeting nonclassical cardiovascular risk factors in CKD, few trials have demonstrated any significant reduction in cardiovascular risk. Smoking cessation remains important but is poorly studied in CKD with many dialysis patients still smoking. Summary The pathogenesis of cardiovascular disease in CKD differs subtly from that of non-CKD patients. As renal function declines, the role and impact of treating classical risk factors may change and diminish. However, hypertension, hypercholesterolaemia and smoking cessation management should be optimized and may require multiple agents and approaches, particularly as CKD advances. Treatment of hypertension would appear to be one management area in which performance is less than ideal. Future work should focus on new management strategies and drug combinations that tackle the classical risk factors as well as better designed longitudinal and randomized control trials of nonclassical risk factors. Patients with CKD should be included in all cardiovascular intervention studies, given their poor outcomes without interventions.

Intussusception is a rare cause of obstruction in adults and has a variable, non-specific presentation. Adult intussusception is usually associated with an underlying organic pathology, such as a benign or malignant tumour which acts as the lead point. Prolapse of the lead-point mass through the anal canal is an extremely rare presentation with very few reported cases in the literature. We describe a case of a 67-year-old man who presented with rectal prolapse of a large soft tissue mass. CT of the abdomen and barium enema revealed partial intussusception of an upper sigmoid lipomatous polyp. Examination under anaesthesia was performed and the prolapse reduced. A laparoscopic sigmoid colectomy was planned. The patient subsequently re-presented clinically unwell with a recurrent necrotic prolapsing mass. Laparotomy and sigmoid colectomy was performed and the patient recovered fully. The resected mass was a 7×4.5×4.0 cm necrotic sigmoid lipoma.

Vascular dementia (VaD) accounts for approximately 15%-20% of all dementias, but the relationship of progressive cognitive impairment to neurochemical changes is poorly understood. We have therefore investigated glutamatergic synaptic markers in VaD.We used homogenates prepared from gray matter from 2 neocortical regions (Brodmann area [BA] 9 and BA 20) and Western blotting to determine the concentrations of key components of the glutamatergic neurotransmitter system, vesicular glutamate transporter 1 (VGLUT1) and excitatory amino acid transporter EAAT2 (GLT-1), and the ubiquitous synaptic protein, synaptophysin, in 73 individuals-48 patients with cerebrovascular disease with and without dementia, 10 patients with AD, and 15 controls-in a case-control design.VGLUT1 concentrations in BA 20 and BA 9 were correlated with CAMCOG total (Rs 0.525, p = 0.018, n = 20; Rs 0.560, p = 0.002, n = 27) and CAMCOG memory scores (Rs 0.616, p = 0.004, n = 20; Rs 0.675, p = 0.000, n = 27). VGLUT1 concentration in BA 9 differed between the different dementia groups and the stroke no dementia group (1-way analysis of variance F = 6.69, p = 0.001 and Bonferroni p0.01 in each case), with subjects with stroke who did not develop dementia exhibiting the highest mean value for VGLUT1.These data suggest that loss of glutamatergic synapses is a feature of VaD and Alzheimer disease but the preservation of synapses, in particular glutamatergic synapses, in the frontal cortex against the temporal cortex plays a role in sustaining cognition and protecting against dementia following a stroke.