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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.

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

PurposeThe conversion of synaptic glutamate to glutamine in astrocytes by glutamine synthetase (GS) is critical to maintaining healthy brain activity and may be disrupted in several brain disorders. As the GS catalysed conversion of glutamate to glutamine requires ammonia, we evaluated whether [13N]ammonia positron emission tomography (PET) could reliability quantify GS activity in humans.MethodsIn this test–retest study, eight healthy volunteers each received two dynamic [13N]ammonia PET scans on the morning and afternoon of the same day. Each [13N]ammonia scan was preceded by a [15O]water PET scan to account for effects of cerebral blood flow (CBF).ResultsConcentrations of radioactive metabolites in arterial blood were available for both sessions in five of the eight subjects. Our results demonstrated that kinetic modelling was unable to reliably distinguish estimates of the kinetic rate constantk3(related to GS activity) fromK1(related to [13N]ammonia brain uptake), and indicated a non-negligible back-flux of [13N] to blood (k2). Model selection favoured a reversible one-tissue compartmental model, and [13N]ammoniaK1correlated reliably (r2 = 0.72–0.92) with [15O]water CBF.ConclusionThe [13N]ammonia PET method was unable to reliably estimate GS activity in the human brain but may provide an alternative index of CBF.

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.

Ablation of atrial arrhythmias in patients with congenital heart disease (CHD) has markedly improved with advanced mapping systems. However, recurrence rates remain high. The linear ablation strategy is not uncommonly practiced necessitating prolonged ablation times. We report the outcomes of adopting a strategy of minimal, cluster delivery of radiofrequency (RF) energy at critical substrates identified by ultrahigh-definition mapping for atrial arrhythmias in patients with CHD.Non-cavotricuspid isthmus (non-CTI) atrial tachycardias were ablated with a targeted ablation cluster technique (TACT) using an ultrahigh-density mapping system combined with multielectrode monitoring and endpoint determination in preference to linear ablation. The arrhythmia substrates, RF times, and acute- and medium-term success rates were studied.Fifty-eight tachycardias were mapped and ablated in 42 procedures: 34 non-CTIs and 24 CTIs. A targeted ablation cluster was performed for non-CTI tachycardias, with a median ablation time of 3.1 min. In 53% of non-CTI tachycardias, arrhythmia termination was achieved with ≤2 RF applications. After a mean follow-up of 23.6 months, 27 (80%) patients were free of recurrent atrial arrhythmias. One of 34 targeted non-CTI tachycardia recurred, with a final success rate of 91%. Linear ablation was performed for CTI flutters with a median ablation time of 6.8 min (vs. non-CTIs, p = .006). Three of 21 tachycardias recurred due to reconnection of the ablation line but the final success rate was 100%.The TACT approach for non-CTI atrial arrhythmias in congenital patients as guided by the ultrahigh-density mapping is an effective method with short ablation times and excellent medium-term outcomes.

Objectives A new electroanatomic mapping system (Rhythmia, Boston Scientific, Marlborough, Massachusetts) using a 64-electrode mapping basket is now available; we systematically assessed its use in complex congenital heart disease (CHD). Background The incidence of atrial arrhythmias post-surgery for CHD is high. Catheter ablation has emerged as an effective treatment, but is hampered by limitations in the mapping system’s ability to accurately define the tachycardia circuit. Methods Mapping and ablation data of 61 patients with CHD (35 males, age 45 ± 14 years) from 8 tertiary centers were reviewed. Results Causes were as follows: Transposition of Great Arteries (atrial switch) (n = 7); univentricular physiology (Fontans) (n = 8); Tetralogy of Fallot (n = 10); atrial septal defect (ASD) repair (n = 15); tricuspid valve (TV) anomalies (n = 10); and other (n = 11). The total number of atrial arrhythmias was 86. Circuits were predominantly around the tricuspid valve (n = 37), atriotomy scar (n = 10), or ASD patch (n = 4). Although the majority of peri-tricuspid circuits were cavo-tricuspid-isthmus dependent (n = 30), they could follow a complex route between the annulus and septal resection, ASD patch, coronary sinus, or atriotomy. Immediate ablation success was achieved in all but 2 cases; with follow-up of 12 ± 8 months, 7 patients had recurrence. Conclusions We demonstrate the feasibility of the basket catheter for mapping complex CHD arrhythmias, including with transbaffle and transhepatic access. Although the circuits often involve predictable anatomic landmarks, the precise critical isthmus is often difficult to predict empirically. Ultra–high-density mapping enables elucidation of circuits in this complex anatomy and allows successful treatment at the isthmus with a minimal lesion set.

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 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.

Despite medical advancements, the prognosis of patients with heart failure remains poor. While echocardiography and cardiac magnetic resonance imaging remain at the forefront of diagnosing and monitoring patients with heart failure, cardiac computed tomography (CT) has largely been considered to have a limited role. With the advancements in scanner design, technology, and computer processing power, cardiac CT is now emerging as a valuable adjunct to clinicians managing patients with heart failure. In the current manuscript, we review the current applications of cardiac CT to patients with heart failure and also the emerging areas of research where its clinical utility is likely to extend into the realm of treatment, procedural planning, and advanced heart failure therapy implementation.

The Emotional Literacy Support Assistant (ELSA) programme is an evidence-informed intervention delivered by teaching assistants and supervised by educational psychologists. In this research, semi-s...

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.

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.

Background Cardiac Resynchronization Therapy (CRT) is an important therapeutic treatment for chronic heart failure. However, even in carefully selected cases up to 40% of patient fail to respond. First-phase ejection fraction (EF1), the ejection fraction up to the time of maximal ventricular contraction, is a novel and more sensitive echocardiographic measure of early systolic function. Purpose We examined the value of EF1, to predict response to CRT and clinical outcomes after CRT. Methods We analysed echocardiograms from 197 patients who underwent CRT between 2009 and 2018 and were followed to determine clinical outcomes. Results Volumetric response rate (reduction in end-systolic volume ≥15%) was 92.3% vs. 12.1%, for those with EF1 in the highest vs. lowest tertiles (p85% sensitivity and specificity for prediction of response to CRT; on multivariate logistic regression analysis incorporating previously defined predictors, EF1 was the strongest predictor of response (OR: 1.563, 95% CI: 1.371–1.782, p Conclusion EF1 is a promising marker to identify patients likely to respond to CRT and most likely provides a measure of myocardial viability that determines response. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): British Heart Foundation, Wellcome/EPSRC Centre for Medical Engineering

Background Cardiac Resynchronization Therapy (CRT) is an important therapeutic treatment for chronic heart failure. However, even in carefully selected cases up to 40% of patient fail to respond. First-phase ejection fraction (EF1), the ejection fraction up to the time of maximal ventricular contraction, is a novel and more sensitive echocardiographic measure of early systolic function. We examined the value of EF1, to predict response to CRT and clinical outcomes after CRT. Methods Echocardiography was performed in 197 patients (table 1) who underwent CRT between 2009 and 2018 and were followed to determine clinical outcomes. LV volumes were measured by 2D Simpson’s method from apical views at end-diastole, time of peak aortic valve flow and end-systole to give end-diastolic volume (EDV), volume at TPAVF (V1) and ESV. 3D echocardiography was performed in a sub-sample of patients (n=73) allowing automated determination of EF1. EF1 was calculated as the percentage change between EDV and V1: EF 1= (EDV – V1) / EDV x 100 %. Results Volumetric response rate (reduction in end-systolic volume ≥ 15%) was 92.3% vs. 12.1%, for those with EF1 in the highest vs. lowest tertiles (p 85% sensitivity and specificity for prediction of response to CRT; on multivariate binary logistic regression analysis incorporating previously defined predictors (table 2) EF1 was the strongest predictor of response (odds ratio: 1.563, 95% confidence interval: 1.371-1.782, per 1% change in EF1, p Improvement in EF1 at 6 months (figure 1) after CRT implantation (6.5±5.8% vs 1.8±4.3% in responders vs. non-responders, p Conclusion EF1, a simple measure of early systolic function, is a promising predictor of response to CRT and may be useful in selecting patients for CRT and as a target for optimising CRT and other measures to improve outcomes in patients with HFrEF. Conflict of Interest None

Purpose The conversion of synaptic glutamate to glutamine in astrocytes by glutamine synthetase (GS) is critical to maintaining healthy brain activity and may be disrupted in several brain disorders. As the GS catalysed conversion of glutamate to glutamine requires ammonia, we evaluated whether [13N]ammonia positron emission tomography (PET) could reliability quantify GS activity in humans.Methods In this test-retest study, eight healthy volunteers each received two dynamic [13N]ammonia PET scans on the morning and afternoon of the same day. Each [13N]ammonia scan was preceded by a [15O]water PET scan to account for effects of cerebral blood flow (CBF).Results Concentrations of radioactive metabolites in arterial blood were available for both sessions in five of the eight subjects. Our results demonstrated that kinetic modelling was unable to reliably distinguish estimates of the kinetic rate constant k3 (related to GS activity) from K1 (related to [13N]ammonia brain uptake), and indicated a non-negligible back-flux of [13N]ammonia to blood (k2). Model selection favoured a reversible one tissue compartmental model, and [13N]ammonia K1 correlated reliably (r2 = 0.72–0.92) with [15O]water CBF.Conclusion The [13N]ammonia PET method was unable to reliably estimate GS activity in the human brain but may provide an alternative index of CBF.

Purpose The conversion of synaptic glutamate to glutamine in astrocytes by glutamine synthetase (GS) is critical to maintaining healthy brain activity and may be disrupted in several brain disorders. As the GS catalysed conversion of glutamate to glutamine requires ammonia, we evaluated whether [13N]ammonia positron emission tomography (PET) could reliability quantify GS activity in humans. Methods In this test–retest study, eight healthy volunteers each received two dynamic [13N]ammonia PET scans on the morning and afternoon of the same day. Each [13N]ammonia scan was preceded by a [15O]water PET scan to account for effects of cerebral blood flow (CBF). Results Concentrations of radioactive metabolites in arterial blood were available for both sessions in five of the eight subjects. Our results demonstrated that kinetic modelling was unable to reliably distinguish estimates of the kinetic rate constant k3 (related to GS activity) from K1 (related to [13N]ammonia brain uptake), and indicated a non-negligible back-flux of [13N] to blood (k2). Model selection favoured a reversible one-tissue compartmental model, and [13N]ammonia K1 correlated reliably (r2 = 0.72–0.92) with [15O]water CBF. Conclusion The [13N]ammonia PET method was unable to reliably estimate GS activity in the human brain but may provide an alternative index of CBF.

BACKGROUND Cardiac resynchronization therapy (CRT) is typically delivered via quadripolar leads that allow stimulation using either true bipolar pacing, where stimulation occurs between two electrodes (BP) on the quadripolar lead, or extended bipole (EBP) left ventricular (LV) pacing, with the quadripolar electrodes and right ventricular coil acting as the cathode and anode, respectively. True bipolar pacing is associated with reductions in mortality and it has been postulated that these differences are the result of enhanced electrical activation. MATERIALS AND METHODS Patients undergoing a CRT underwent an electrocardiographic imaging study where electrical activation data were recorded while different LV pacing vectors were temporarily programmed. RESULTS There were no differences in the total electrical activation times or dispersion of electrical activation between biventricular pacing with bipolar or corresponding EBP LV vector configurations (left ventricular total activation time [LVtat] BP 74.70 ± 18.07 vs EBP 72.4 ± 22.64; P = 0.45). When dichotomized according to etiology, no difference was observed in the activation time with either BP or EBP pacing (LVtat BP ischemic cardiomyopathy 72.2 ± 17.4 vs BP dilated cardiomyopathy 79.9 ± 18.9; P = 0.38). CONCLUSIONS Bipolar pacing alters the mechanical activation sequence of the LV and is associated with reductions in all-cause mortality. It has been postulated these benefits derive from improvements in electromechanical activation of the LV. Our study would suggest that true bipolar pacing does not necessarily result in more favorable activation of the LV or improved electrical resynchronization and other mechanisms should be explored.

Objectives This study hypothesized that guided implants, in which the optimal left ventricular endocardial (LVENDO) pacing location was identified and targeted, would improve acute markers of contractility and chronic markers of cardiac resynchronization (CRT) response. Background Biventricular endocardial (BiVENDO) pacing may offer a potential benefit over standard CRT; however, the optimal LVENDO pacing site is highly variable. Indiscriminately delivered BiVENDO pacing is associated with a reverse remodeling response rate of between 40% and 60%. Methods Registry of centers implanting a wireless, LVENDO pacing system (WiSE-CRT System, EBR Systems, Sunnyvale, California); John Radcliffe Hospital (Oxford, United Kingdom), Guy's and St. Thomas' Hospital (London, United Kingdom), and The James Cook University Hospital (Middlesbrough, United Kingdom). Centers used a combination of preprocedural imaging and electroanatomical mapping the identify the optimal LVENDO site. Results A total of 26 patients across the 3 centers underwent a guided implant. Patients were predominantly male with a mean age of 68.8 ± 8.4 years, the mean LV ejection fraction was 34.2% ± 7.8%. The mean QRS duration was 163.8 ± 26.7 ms, and 30.8% of patients had an ischemic etiology. It proved technically feasible to selectively target and deploy the pacing electrode in a chosen endocardial segment in almost all cases, with a similar complication rate to that observed during indiscriminate BiVENDO. Ninety percent of patients met the definition of echocardiographic responder. Reverse remodeling was observed in 71%. Conclusions Guided endocardial implants were associated with a higher degree of chronic LV remodeling compared with historical nonguided approaches.

Background: Biventricular pacing has been shown to increase both cardiac contractility and coronary flow acutely but the causal relationship is unclear. We hypothesised that changes in coronary flow are secondary to changes in cardiac contractility. We sought to examine this relationship by modulating coronary flow and cardiac contractility. Methods: Contractility and lusitropy were altered by varying the location of pacing in 8 patients. Coronary autoregulation was transiently disabled with intracoronary adenosine. Simultaneous coronary flow velocity, coronary pressure and left ventricular pressure data were measured in the different pacing settings with and without hyperaemia and wave intensity analysis performed. Results: Multisite pacing was effective at altering left ventricular contractility and lusitropy (pos. dp/dtmax −13% to +10% and neg. dp/dtmax −15% to +17% compared to baseline). Intracoronary adenosine decreased microvascular resistance (362.5 mm Hg/s/m to 156.7 mm Hg/s/m, p

BACKGROUND A proportion of patients who undergo an initial lead extraction procedure will require a second, repeat extraction. Data regarding this clinical entity are scarce and neither the predisposing risk factors for, nor outcomes from, these procedures have been described previously. We sought to determine the incidence, risk factors, and outcomes of repeat lead extraction. METHODS A database of extraction procedures from 2001 to 2015 was analyzed. Repeat extraction procedures were identified and the indication for extraction was dichotomized into infection and lead-related problems. Univariate and multivariate analyses were performed to identify predictors of repeat extraction. RESULTS 807 extraction procedures were identified in 755 patients of whom 6% required a repeat extraction. At multivariate analysis, only suffering a major complication at the initial extraction procedure (odds ratio [OR] 21.5, 95% confidence interval [CI] 2.69-171.92; P

Prior to ventricular tachycardia ablation, this patient's cardiac implantable electronic device (CIED) was temporarily programmed to backup pacing mode with tachycardia therapies disabled. During radiofrequency energy delivery, the patient developed ventricular fibrillation requiring emergent cardioversion. Electrogram interrogation showed that the CIED switched to noise reversion mode during ablation. The consequent asynchronous pacing resulted in a paced QRS landing on an intrinsic T wave, inducing ventricular fibrillation. This serves as an important reminder that asynchronous pacing consequent to CIED oversensing could occur in any procedure that could cause electromagnetic interference such as radiofrequency cathteter ablation.

A 56-year-old man was seen in cardiology clinic with exertional chest pain, most marked when walking uphill. He was a heavy smoker but had no other cardiovascular risk factors. His 12-lead ECG was normal, and a CT coronary angiogram (CTCA) was organised with a suspected diagnosis of angina.

ObjectiveResponders to cardiac resynchronisation therapy whose device has a defibrillator component and who do not receive a therapy in the lifetime of the first generator have a very low incidence of appropriate therapy after box change. We investigated the cost implications of using a risk stratification tool at the time of generator change resulting in these patients being reimplanted with a resynchronisation pacemaker.MethodsA decision tree was created using previously published data which had demonstrated an annualised appropriate defibrillator therapy risk of 2.33%. Costs were calculated at National Health Service (NHS) national tariff rates (2016–2017). EQ-5D utility values were applied to device reimplantations, admissions and mortality data, which were then used to estimate quality-adjusted life-years (QALYs) over 5 years.ResultsAt 5 years, the incremental cost of replacing a resynchronisation defibrillator device with a second resynchronisation defibrillator versus resynchronisation pacemaker was £5045 per patient. Incremental QALY gained was 0.0165 (defibrillator vs pacemaker), resulting in an incremental cost-effectiveness ratio (ICER) of £305 712 per QALYs gained. Probabilistic sensitivity analysis resulted in an ICER of £313 612 (defibrillator vs pacemaker). For reimplantation of all patients with a defibrillator rather than a pacemaker to yield an ICER of less than £30 000 per QALY gained (current NHS cut-off for approval of treatment), the annual arrhythmic event rate would need to be 9.3%. The budget impact of selective replacement was a saving of £2 133 985 per year.ConclusionsImplanting low-risk patients with a resynchronisation defibrillator with the same device at the time of generator change is not cost-effective by current NHS criteria. Further research is required to understand the impact of these findings on individual patients at the time of generator change.

Cardiac resynchronization therapy (CRT) reduces the morbidity and mortality of patients with left ventricular (LV) systolic dysfunction and intra-ventricular conduction delay. However, its clinical outcomes are heterogeneous and not all patients show a beneficial response. Multisite pacing (MSP), by stimulating the myocardium from more than one locations, is a potential therapeutic option in patients requiring CRT. This article provides a current update in the methods and outcomes of MSP, as well as in challenges in this field and opportunities for further research and development. MSP can be delivered either with multiple leads or with quadripolar LV leads which can stimulate the LV from two separate sites. Initial results are promising but not always consistent across studies. Larger patient subgroups and longer follow-up duration are required for more conclusive evaluation of MSP. Routine use of MSP in clinical practice cannot be advocated at present. In selected patient subgroups, however, MSP could be considered. Newer devices and expanding knowledge are expected to facilitate the more widespread implementation of MSP and the assessment of its effects in the clinical outcomes of CRT.

Echocardiography-derived measurements of maximum left ventricular (LV) wall thickness are important for both the diagnosis and risk stratification of hypertrophic cardiomyopathy (HC). Cardiac Magnetic Resonance (CMR) imaging is increasingly being used in the assessment of HC however, little is known about the relationship between wall thickness measurements made by the 2 modalities. We sought to compare measurements made with echocardiography and CMR and to assess the impact of any differences on risk stratification using the current European Society of Cardiology (ESC) guidelines. Maximum LV wall thickness measurements were recorded on 50 consecutive patients with HC. 69% of LV wall thickness measurements were recorded with echocardiography, compared to 69% from CMR (p

Introduction Cardiac resynchronisation therapy (CRT) corrects electrical dyssynchrony. However, the temporal changes in the electrical timing according to substrate are unclear. We used electrocardiographic imaging (ECGi) for serial non-invasive assessment of the underlying electrical substrate and its response to resynchronisation. Material and methods ECGi activation maps were constructed 1 day and 6 months post CRT implant. ECGi maps were analysed offline to determine the total ventricular activation time (TVaT) and the time for the bulk of ventricular activation (10th to 90th percentile activation; VaT10–90 Index). Statistical analysis was performed using repeated measures ANOVA with post-hoc pairwise comparisons using paired t-tests. The % relative change within each time point was also calculated and compared between the two time points. Results Eleven CRT patients were studied. Both total and bulk ventricular activation significantly decreased with CRT turned ON at day 1. Intrinsic (CRT OFF) TVaT and VaT10–90 Index at day 1 were 143 ± 23 and 84 ± 20 ms, respectively, and they significantly decreased post CRT to 115 ± 26 ms (P After 6 months, the relative decrease in TVaT with CRT ON remained stable (19% vs. 18% at day 1 and 6 months, respectively) whereas reduction the in VaT10–90 Index was decreased 39% vs. 26% at day 1 and 6 months, respectively. In non-ischaemic patients both total and bulk activation times reduced following CRT. Volumetric responders exhibited an electrical remodelling for bulk activation not apparent in Non-responders, after 6 months of CRT ON. Conclusions Intrinsic bulk myocardium activation becomes more rapid and synchronous with CRT. The bulk activation time is more susceptible to improvement by CRT in ischaemic patients and volumetric responders. These observations are consistent with CRT causing reverse electrophysiological remodelling in the bulk myocardium, but not in late-activating ischaemic or fibrotic regions.

AIMS The decision to abandon or extract superfluous leads remains controversial. We sought to compare procedural outcome of patients with and without abandoned leads undergoing transvenous lead extraction (TLE). METHODS AND RESULTS An analysis of the ESC-EHRA European Lead Extraction ConTRolled ELECTRa registry was conducted. Patients were stratified into two groups based on the presence (Group 1) or absence (Group 2) of abandoned leads at the time for extraction. Out of 3508 TLE procedures, 422 patients (12.0%) had abandoned leads (Group 1). Group 1 patients were older and more likely to have implantable cardioverter-defibrillator devices, infection indication (78.8% vs. 49.8%), and vegetations (24.6% vs. 15.3%). Oldest lead dwelling time was longer in Group 1 (10.9 vs. 6.3 years) as was the number of extracted leads per patient (3.2 vs. 1.7). Manual traction failure (94.5% vs. 78.8%), powered sheath use (50.7% vs. 28.4%), and femoral approach were higher in Group 1 (P

Suboptimal left ventricular (LV) lead placement in myocardial scar (fibrosis) is associated with cardiac resynchronization therapy (CRT) nonresponse [(1)][1]. Image guidance (echocardiography and cardiac magnetic resonance [CMR]) avoiding fibrosis and targeting late mechanical activation may improve

The high risk of ventricular arrhythmias in patients with heart failure remains despite the benefit of cardiac resynchronization therapy (CRT). An electromechanical interaction between regional myocardial strain patterns and the electrophysiological substrate is thought to be important.We investigated the in vivo relation between left ventricular activation recovery interval (ARI), as a surrogate measure of action potential duration (APD), and local myocardial strain patterns in responders and nonresponders to CRT.ARIs were recorded from the left ventricular epicardium in 20 patients with CRT 6 weeks and 6 months post implantation. Two-dimensional speckle tracking echocardiography was performed at the same time to assess myocardial strains. Patients with ≥15% reduction in end-systolic volume at 6 months were classified as responders.ARI decreased in responders (263 ± 46 ms vs 246 ± 47 ms, P.01) and increased in nonresponders (235 ± 23 ms vs 261 ± 20 ms; P.01). Time-to-peak radial, circumferential, and longitudinal strains increased in responders (41 ± 27, 35 ± 25, 56 ± 37 ms; P.01) and decreased in nonresponders (-58 ± 26, -47 ± 26, -64 ± 27 ms; P.01). There was a nonlinear correlation between changes in time-to-peak strain and ARIs (Spearman correlation coefficient r ≥ 0.70; P.01). Baseline QRS duration145 ms and QRS duration shortening with biventricular pacing were associated with ARI shortening following CRT.Changes in ventricular wall mechanics predict local APD lengthening or shortening during CRT. Nonresponders have a worsening of myocardial strain and local APD. Baseline QRS duration145 ms and QRS duration shortening with biventricular pacing identified patients who exhibited improvement in APD.