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Aims There is little evidence of the impact of syncope in implantable cardioverter-defibrillator (ICD) patients in routine community hospital care. This single-centre retrospective study sought to evaluate the incidence and prognostic significance of syncope in consecutive ICD patients. Methods and results Data were collected on consecutive patients undergoing first ICD implantation between January 2009 and December 2019. The primary endpoints were the first occurrence of all-cause syncope, all-cause mortality, and all-cause hospitalization. Multivariate Cox proportional hazard models were used to identify risk factors associated with syncope and to analyse the subsequent risk of mortality and hospitalization. 1003 patients (58% primary prevention) were included in the final analysis. During a mean follow-up of 1519 ± 1055 days, 106 (10.6%) experienced syncope, 304 died (30.3%), and 477 (47.5%) were hospitalized for any cause. In an analysis adjusted for baseline variables, the first occurrence of syncope was associated with a significantly increased risk of mortality (HR 2.82, P < 0.001) and the first occurrence of hospitalization (HR 2.46, P = 0.002). Conclusion Syncope in ICD recipients is common and associated with a poor prognosis irrespective of baseline variables and ICD programming. The occurrence of syncope is associated with a significant increase in the risk of mortality and hospitalization.

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.

The aim of this study was to examine the value of first-phase ejection fraction (EF1), to predict response to cardiac resynchronization therapy (CRT) and clinical outcomes after CRT.CRT is an important treatment for patients with chronic heart failure. However, even in carefully selected cases, up to 40% of patients fail to respond. EF1, the ejection fraction up to the time of maximal ventricular contraction, is a novel sensitive echocardiographic measure of early systolic function and might relate to response to CRT.An initial retrospective study was performed in 197 patients who underwent CRT between 2009 and 2018 and were followed to determine clinical outcomes at King's Health Partners in London. A validation study (n = 100) was performed in patients undergoing CRT at Barts Heart Centre in London.Volumetric response rate (reduction in end-systolic volume ≥15%) was 92.3% and 12.1% for those with EF1 in the highest and lowest tertiles (P 0.001). A cutoff value of 11.9% for EF1 had85% sensitivity and specificity for prediction of response to CRT; on multivariate binary logistic regression analysis incorporating previously defined predictors, EF1 was the strongest predictor of response (odds ratio [OR]: 1.56 per 1% change in EF1; 95% CI: 1.37-1.78; P 0.001). EF1 was also the strongest predictor of improvement in clinical composite score (OR: 1.11; 95% CI: 1.04-1.19; P = 0.001). Improvement in EF1 at 6 months after CRT implantation (6.5% ± 5.8% vs 1.8% ± 4.3% in responders vs nonresponders; P 0.001) was the best predictor of heart failure rehospitalization and death after median follow-up period of 20.3 months (HR: 0.81; 95% CI: 0.73-0.90; P 0.001). In the validation cohort, EF1 was a similarly 1strong predictor of response (OR: 1.45; 95% CI: 1.23-1.70; P 0.001) as in the original cohort.EF1 is a promising marker to identify patients likely to respond to CRT.

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.

OBJECTIVES Atrial fibrillation (AF) is common and can cause significant morbidity and detriment to quality of life. Success rates for conventional catheter ablation are suboptimal in persistent AF (PsAF), especially when longstanding. Convergent hybrid ablation combines endoscopic surgical epicardial and endocardial catheter ablation. It offers promise in treating PsAF. We aimed to evaluate outcomes at our centre following convergent ablation. METHODS We conducted an observational study of patients undergoing ablation from 2012 to 2019 at a London cardiac centre. Sixty-seven patients underwent convergent ablation entailing epicardial ablation, mostly via sub-xiphoid access, followed by endocardial left atrial catheter ablation. Baseline and follow-up data were obtained retrospectively from clinical records. Primary outcome was freedom from AF on/off anti-arrhythmic drugs after 12-month follow-up. Secondary outcomes included freedom from AF over the entire follow-up, freedom from anti-arrhythmic drugs, freedom from atrial arrhythmias, symptom status, repeat ablation and complications. RESULTS At baseline, 80.6% had PsAF >1 year (80.6%), 49.3% had body mass index >30 kg/m2 at baseline and 19.4% had left ventricular ejection fraction of 40% or less. The median follow-up was 2.3 (1.4–3.7) years. Freedom from AF recurrence was 81.3% at 1 year and 61.5% over overall follow-up. Eleven patients (16.4%) required redo AF ablation. Prolonged AF duration was associated with increased recurrence at 12 months and duration >5 years with a shorter time to recurrence on Kaplan–Meier analysis, but this and other factors did not significantly impact the AF recurrence during the overall follow-up period. CONCLUSIONS Convergent ablation had good 1-year and overall success rates for treating PsAF. Our results in a diverse, real-world population support the potential of convergent ablation in patients with challenging to treat PsAF.

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.

The effect of chronic ischemic scar on repolarization is unclear, with conflicting results from human and animal studies. An improved understanding of electrical remodeling within scar and border zone tissue may enhance substrate-guided ablation techniques for treatment of ventricular tachycardia. Computational modeling studies have suggested increased dispersion of repolarization during epicardial, but not endocardial, left ventricular pacing, in close proximity to scar. However, the effect of endocardial pacing near scarThe purpose of this study was to investigate the effect of scar and pacing location on local repolarization in a porcine myocardial infarction model.Six model pigs underwent late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging followed by electroanatomic mapping of the left ventricular endocardium. LGE-CMR images were registered to the anatomic shell and scar defined by LGE. Activation recovery intervals (ARIs), a surrogate for action potential duration, and local ARI gradients were calculated from unipolar electrograms within areas of late gadolinium enhancement (aLGE) and healthy myocardium.There was no significant difference between aLGE and healthy myocardium in mean ARI (304.20 ± 19.44 ms vs 300.59 ± 19.22 ms;Our findings suggest that changes in ARI are not an intrinsic property of surviving myocytes within scar, and endocardial pacing close to scar does not affect local repolarization.

Leadless left ventricular (LV) endocardial pacing to achieve cardiac resynchronization therapy (CRT) is a novel procedure for treatment of patients with dyssynchronous heart failure. Current evidence is limited to observational studies with small patient numbers.The purpose of this systematic review and meta-analysis was to assess the safety and efficacy of leadless LV endocardial pacing.A literature search was conducted through PubMed, EMBASE, and Cochrane databases. Mean differences (MDs) in New York Heart Association (NYHA) functional class and LV ejection fraction (LVEF) from baseline to 6 months postprocedure were combined using a random effects model. Heterogeneity was evaluated using the Cochrane Q test, IFive studies with 181 patients were included in the final analysis. Procedural success rate was 90.6%. Clinical response rate was 63%, with mean improvement in NYHA functional class of 0.43 (MD -0.43; 95% confidence interval [CI] -0.76 to -0.1; P = .01), with high heterogeneity (P.001; IThe efficacy of leadless LV endocardial pacing for CRT supports its use as a second-line therapy in patients in whom standard CRT is not possible or has been ineffective. Improvements in safety profile will facilitate widespread uptake in the treatment of these patients.

BACKGROUND Transvenous lead extraction (TLE) remains a high-risk procedure. OBJECTIVE The purpose of this study was to develop a machine learning (ML)-based risk stratification system to predict the risk of major adverse events (MAEs) after TLE. A MAE was defined as procedure-related major complication and procedure-related death. METHODS We designed and evaluated an ML-based risk stratification system trained using the European Lead Extraction ConTRolled (ELECTRa) registry to predict the risk of MAEs in 3555 patients undergoing TLE and tested this on an independent registry of 1171 patients. ML models were developed, including a self-normalizing neural network (SNN), stepwise logistic regression model ("stepwise model"), support vector machines, and random forest model. These were compared with the ELECTRa Registry Outcome Score (EROS) for MAEs. RESULTS There were 53 MAEs (1.7%) in the training cohort and 24 (2.4%) in the test cohort. Thirty-two clinically important features were used to train the models. ML techniques were similar to EROS by balanced accuracy (stepwise model: 0.74 vs EROS: 0.70) and superior by area under the curve (support vector machines: 0.764 vs EROS: 0.677). The SNN provided a finite risk for MAE and accurately identified MAE in 14 of 169 "high (

Aims Multi-lead pacing is a potential therapy to improve response to cardiac resynchronization therapy (CRT) by providing rapid activation of the myocardium from multiple sites. Here, we perform a meta-analysis of randomized controlled trials to assess the efficacy of multi-lead pacing. Methods and results A literature search was performed which identified 251 unique records. After screening, 6 studies were found to meet inclusion criteria, with 415 patients included in the meta-analysis. Four studies performed multi-lead pacing with two left ventricular (LV) leads and one right ventricular (RV) lead. One study used two RV leads and one LV lead, and one study used both configurations. There was no difference between multi-lead pacing and conventional CRT in LV end-systolic volume [mean difference (MD) −0.54 mL, P = 0.93] or LV ejection fraction (MD 1.42%, P = 0.40). There was a borderline significant improvement in Minnesota Living With Heart Failure Questionnaire score for multi-lead pacing vs. conventional CRT (MD −4.46, P = 0.05), but the difference was not significant when only patients receiving LV-only multi-lead pacing were included (MD −3.59, P = 0.25). There was also no difference between groups for 6-min walk test (MD 15.06 m, P = 0.38) or New York Heart Association class at follow-up [odds ratio (OR) 1.49, P = 0.24]. There was no difference in mortality between groups (OR 1.11, P = 0.77). Conclusion This meta-analysis does not support the use of multi-lead pacing for CRT delivery. However, significant variation between studies was noted, and therefore a benefit for multi-lead pacing in select patients cannot be excluded, and further investigation may be warranted.

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.

ObjectivesTransvenous lead extraction (TLE) poses a significant economic and resource burden on healthcare systems; however, limited data exist on its true cost. We therefore estimate real-world healthcare reimbursement costs of TLE to the UK healthcare system at a single extraction centre.MethodsConsecutive admissions entailing TLE at a high-volume UK centre between April 2013 and March 2018 were prospectively recorded in a computer registry. In the hospital’s National Health Service (NHS) clinical coding/reimbursement database, 447 cases were identified. Mean reimbursement cost (n=445) and length of stay (n=447) were calculated. Ordinary least squares regressions estimated the relationship between cost (bed days) and clinical factors.ResultsMean reimbursement cost per admission was £17 399.09±£13 966.49. Total reimbursement for all TLE admissions was £7 777 393.51. Mean length of stay was 16.3±15.16 days with a total of 7199 bed days. Implantable cardioverter-defibrillator and cardiac resynchronisation therapy defibrillator devices incurred higher reimbursement costs (70.5% and 68.7% higher, respectively, both pConclusionsFinancial costs to the NHS from TLE are substantial. Consideration should therefore be given to cost/resource-sparing potential of leadless/extravascular cardiac devices that negate the need for TLE particularly in patients with prior valve surgery and/or heart failure. Additionally, use of antibiotic envelopes and other interventions that reduce infection risk in patients receiving transvenous leads should be considered.

Cardiac resynchronization therapy (CRT) is an important treatment for heart failure. Low female enrollment in clinical trials means that current CRT guidelines may be biased toward males. However, females have higher response rates at lower QRS duration (QRSd) thresholds. Sex differences in the left ventricle (LV) size could provide an explanation for the improved female response at lower QRSd. We aimed to test if sex differences in CRT response at lower QRSd thresholds are explained by differences in LV size and hence predict sex-specific guidelines for CRT. We investigated the effect that LV size sex difference has on QRSd between male and females in 1093 healthy individuals and 50 CRT patients using electrophysiological computer models of the heart. Simulations on the healthy mean shape models show that LV size sex difference can account for 50–100% of the sex difference in baseline QRSd in healthy individuals. In the CRT patient cohort, model simulations predicted female-specific guidelines for CRT, which were 9–13 ms lower than current guidelines. Sex differences in the LV size are able to account for a significant proportion of the sex difference in QRSd and provide a mechanistic explanation for the sex difference in CRT response. Simulations accounting for the smaller LV size in female CRT patients predict 9–13 ms lower QRSd thresholds for female CRT guidelines.

Background: Transvenous lead extraction (TLE) may be performed by superior approach using the original implant vein or via a femoral approach; however, limited comparative data exists. We compare outcomes between femoral versus nonfemoral TLE approaches and determine predictors of bailout transfemoral lead extraction in patients undergoing initial TLE via the original implant vein by a superior approach. Methods: All consecutive TLEs between October 2000 and March 2018 were prospectively collected (n = 1052). Patients were dichotomized into femoral (n = 118) and nonfemoral (n = 934) groups. Results: Demographics were balanced between femoral vs nonfemoral groups. Patients in the femoral group had significantly higher mean lead dwell times (11.6 ± 9.7 vs 6.6 ± 6.6 years, P

Background Risk stratification of ventricular arrhythmia remains complex in patients with ischemic and nonischemic cardiomyopathy. Objective The purpose of this study was to determine whether scar heterogeneity, quantified by mean entropy, predicts appropriate implantable cardioverter-defibrillator (ICD) therapy. We hypothesized that higher mean entropy calculated from cardiac magnetic resonance texture analysis (CMR-TA) will predict appropriate ICD therapy. Methods Consecutive patients underwent CMR imaging before ICD implantation. Short-axis left ventricular scar was manually segmented. CMR-TA was performed using a Laplacian filter to extract and augment image features to create a scar texture from which histogram analysis of pixel intensity was used to calculate mean entropy. The primary end point was appropriate ICD therapy. Results A total of 114 patients underwent CMR-TA (ischemic cardiomyopathy [ICM]: n = 70; nonischemic cardiomyopathy [NICM]: n = 44) with a median follow-up of 955 days (interquartile range 691–1185 days). Mean entropy was significantly higher in the ICM group (5.7 ± 0.7 vs 5.5 ± 0.7; P= .045). Overall, 33 patients received appropriate ICD therapy. Using optimized cutoff values from receiver operating characteristic curves, Kaplan-Meier survival analysis demonstrated time until first appropriate therapy was significantly shorter in the high mean entropy group (P = .003). Multivariable analysis showed that mean entropy was the sole predictor of appropriate ICD therapy (hazard ratio 1.882; 95% confidence interval 1.083–3.271; P = .025). In the ICM group, mean entropy remained an independent predictor of appropriate ICD therapy, whereas in the NICM group, precontrast T1 values were the sole predictor. Conclusion Scar heterogeneity, quantified by mean entropy using CMR-TA, was an independent predictor of appropriate ICD therapy in the mixed cardiomyopathy cohort and ICM-only group, suggesting a potential role for CMR-TA in predicting ventricular arrhythmia and risk-stratifying patients for ICD implantation.

We shall discuss a patient who underwent a tricuspid valve‐in‐valve implantation for a failing bioprosthetic valve replacement. The procedure was complicated by detachment of the valve deployment apparatus which was removed in its entirety, using percutaneous extraction techniques. We believe this was the first ever case to report such a complication.

Aim Quadripolar lead technology and multi‐point pacing (MPP) are important clinical adjuncts in cardiac resynchronization therapy (CRT) pacing aimed at reducing the rate of non‐response to therapy. Mixed results have been achieved using MPP and it is critical to identify which patients require this approach and how to configure their MPP stimulation, in order to achieve optimal electrical resynchronization. Methods & Results We sought to investigate whether electrocardiographic imaging (ECGi), using the CARDIOINSIGHT ™ inverse ECG mapping system, could identify alterations in electrical resynchronization during different methods of device optimization. In no patient did a single form of programming optimization provide the best electrical response. The effects of utilizing MPP were idiosyncratic and highly patient specific. ECGi activation maps were clearly able to discern changes in bulk LV activation during differing MPP programming. In two of the five subjects, MPP resulted in more rapid activation of the left ventricle compared to standard CRT; however, in the remaining three patients, the use of MPP did not appear to acutely improve electrical resynchronization. Crucially, this cohort showed evidence of extensive LV scarring which was well visualized using both CMR and ECGi voltage mapping. Conclusions Our work suggests a potential role for ECGi in the optimization of non‐responders to CRT, as it allows the fusion of activation maps and scar analysis above and beyond interrogation of the 12 lead ECG.

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

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.

Advances in deep learning (DL) have resulted in impressive accuracy in some medical image classification tasks, but often deep models lack interpretability. The ability of these models to explain their decisions is important for fostering clinical trust and facilitating clinical translation. Furthermore, for many problems in medicine there is a wealth of existing clinical knowledge to draw upon, which may be useful in generating explanations, but it is not obvious how this knowledge can be encoded into DL models - most models are learnt either from scratch or using transfer learning from a different domain. In this paper we address both of these issues. We propose a novel DL framework for image-based classification based on a variational autoencoder (VAE). The framework allows prediction of the output of interest from the latent space of the autoencoder, as well as visualisation (in the image domain) of the effects of crossing the decision boundary, thus enhancing the interpretability of the classifier. Our key contribution is that the VAE disentangles the latent space based on `explanations' drawn from existing clinical knowledge. The framework can predict outputs as well as explanations for these outputs, and also raises the possibility of discovering new biomarkers that are separate (or disentangled) from the existing knowledge. We demonstrate our framework on the problem of predicting response of patients with cardiomyopathy to cardiac resynchronization therapy (CRT) from cine cardiac magnetic resonance images. The sensitivity and specificity of the proposed model on the task of CRT response prediction are 88.43% and 84.39% respectively, and we showcase the potential of our model in enhancing understanding of the factors contributing to CRT response., Comment: MICCAI 2020 conference

Aims To determine whether triventricular (TriV) pacing is feasible and improves CRT response compared to conventional biventricular (BiV) pacing in patients with left bundle branch block (LBBB) and intermediate QRS prolongation (120–150 ms). Methods and results Between October 2015 and November 2019, 99 patients were recruited from 11 UK centres. Ninety-five patients were randomized 1:1 to receive TriV or BiV pacing systems. The primary endpoint was feasibility of TriV pacing. Secondary endpoints assessed symptomatic and remodelling response to CRT. Baseline characteristics were balanced between groups. In the TriV group, 43/46 (93.5%) patients underwent successful implantation vs. 47/49 (95.9%) in the BiV group. Feasibility of maintaining CRT at 6 months was similar in the TriV vs. BiV group (90.0% vs. 97.7%, P = 0.191). All-cause mortality was similar between TriV vs. BiV groups (4.3% vs. 8.2%, P = 0.678). There were no significant differences in echocardiographic LV volumes or clinical composite scores from baseline to 6-month follow-up between groups. Conclusion Implantation of two LV leads to deliver and maintain TriV pacing at 6 months is feasible without significant complications in the majority of patients. There was no evidence that TriV pacing improves CRT response or provides additional clinical benefit to patients with LBBB and intermediate QRS prolongation and cannot be recommended in this patient group. Clinical trial registration number Clinicaltrials.gov: NCT02529410.

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

Objectives: The aim of this study is to develop a scar detection method for routine computed tomography angiography (CTA) imaging using deep convolutional neural networks (CNN), which relies solely on anatomical information as input and is compatible with existing clinical workflows.Background: Identifying cardiac patients with scar tissue is important for assisting diagnosis and guiding interventions. Late gadolinium enhancement (LGE) magnetic resonance imaging (MRI) is the gold standard for scar imaging; however, there are common instances where it is contraindicated. CTA is an alternative imaging modality that has fewer contraindications and is faster than Cardiovascular magnetic resonance imaging but is unable to reliably image scar.Methods: A dataset of LGE MRI (200 patients, 83 with scar) was used to train and validate a CNN to detect ischemic scar slices using segmentation masks as input to the network. MRIs were segmented to produce 3D left ventricle meshes, which were sampled at points along the short axis to extract anatomical masks, with scar labels from LGE as ground truth. The trained CNN was tested with an independent CTA dataset (25 patients, with ground truth established with paired LGE MRI). Automated segmentation was performed to provide the same input format of anatomical masks for the network. The CNN was compared against manual reading of the CTA dataset by 3 experts.Results: Note that 84.7% cross-validated accuracy (AUC: 0.896) for detecting scar slices in the left ventricle on the MRI data was achieved. The trained network was tested against the CTA-derived data, with no further training, where it achieved an 88.3% accuracy (AUC: 0.901). The automated pipeline outperformed the manual reading by clinicians.Conclusion: Automatic ischemic scar detection can be performed from a routine cardiac CTA, without any scar-specific imaging or contrast agents. This requires only a single acquisition in the cardiac cycle. In a clinical setting, with near zero additional cost, scar presence could be detected to triage images, reduce reading times, and guide clinical decision-making.

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.

We present a novel multimodal deep learning framework for cardiac resynchronisation therapy (CRT) response prediction from 2D echocardiography and cardiac magnetic resonance (CMR) data. The proposed method first uses the `nnU-Net' segmentation model to extract segmentations of the heart over the full cardiac cycle from the two modalities. Next, a multimodal deep learning classifier is used for CRT response prediction, which combines the latent spaces of the segmentation models of the two modalities. At inference time, this framework can be used with 2D echocardiography data only, whilst taking advantage of the implicit relationship between CMR and echocardiography features learnt from the model. We evaluate our pipeline on a cohort of 50 CRT patients for whom paired echocardiography/CMR data were available, and results show that the proposed multimodal classifier results in a statistically significant improvement in accuracy compared to the baseline approach that uses only 2D echocardiography data. The combination of multimodal data enables CRT response to be predicted with 77.38% accuracy (83.33% sensitivity and 71.43% specificity), which is comparable with the current state-of-the-art in machine learning-based CRT response prediction. Our work represents the first multimodal deep learning approach for CRT response prediction.