Time-Resolved X-ray Emission Spectroscopy and Synthetic High-Spin Model Complexes Resolve Ambiguities in Excited-State Assignments of Transition-Metal Chromophores: A Case Study of Fe-Amido Complexes.

To fully harness the potential of abundant metal coordination complex photosensitizers, a detailed understanding of the molecular properties that dictate and control the electronic excited-state population dynamics initiated by light absorption is critical. In the absence of detectable luminescence, optical transient absorption (TA) spectroscopy is the most widely employed method for interpreting electron redistribution in such excited states, particularly for those with a charge-transfer character. The assignment of excited-state TA spectral features often relies on spectroelectrochemical measurements, where the transient absorption spectrum generated by a metal-to-ligand charge-transfer (MLCT) electronic excited state, for instance, can be approximated using steady-state spectra generated by electrochemical ligand reduction and metal oxidation and accounting for the loss of absorptions by the electronic ground state. However, the reliability of this approach can be clouded when multiple electronic configurations have similar optical signatures. Using a case study of Fe(II) complexes supported by benzannulated diarylamido ligands, we highlight an example of such an ambiguity and show how time-resolved X-ray emission spectroscopy (XES) measurements can reliably assign excited states from the perspective of the metal, particularly in conjunction with accurate synthetic models of ligand-field electronic excited states, leading to a reinterpretation of the long-lived excited state as a ligand-field metal-centered quintet state. A detailed analysis of the XES data on the long-lived excited state is presented, along with a discussion of the ultrafast dynamics following the photoexcitation of low-spin Fe(II)-Namido complexes using a high-spin ground-state analogue as a spectral model for the 5T2 excited state.

Syncope in ICD recipients: a single centre experience.

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.

Standard care vs. TRIVEntricular pacing in Heart Failure (STRIVE HF): a prospective multicentre randomized controlled trial of triventricular pacing vs. conventional biventricular pacing in patients with heart failure and intermediate QRS left bundle branch block.

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.

Multipoint pacing for cardiac resynchronisation therapy in patients with heart failure: A systematic review and meta-analysis.

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 < .001), however, was not significant in randomised studies (OR: 1.86, 95% CI: [0.91-3.79], p = .086). There was no significant difference in LVESV reduction >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.

Feasibility of intraprocedural integration of cardiac CT to guide left ventricular lead implantation for CRT upgrades.

BACKGROUND: Optimal positioning of the left ventricular (LV) lead is an important determinant of cardiac resynchronization therapy (CRT) response. OBJECTIVE: Evaluate the feasibility of intraprocedural integration of cardiac computed tomography (CT) to guide LV lead implantation for CRT upgrades. METHODS: Patients undergoing LV lead upgrade underwent ECG-gated cardiac CT dyssynchrony and LV scar assessment. Target American Heart Association segment selection was determined using latest non-scarred mechanically activating segments overlaid onto real-time fluoroscopy with image co-registration to guide optimal LV lead implantation. Hemodynamic validation was performed using a pressure wire in the LV cavity (dP/dtmax) ). RESULTS: 18 patients (male 94%, 55.6% ischemic cardiomyopathy) with RV pacing burden 60.0 ± 43.7% and mean QRS duration 154 ± 30 ms underwent cardiac CT. 10/10 ischemic patients had CT evidence of scar and these segments were excluded as targets. Seventeen out of 18 (94%) patients underwent successful LV lead implantation with delivery to the CT target segment in 15 out of 18 (83%) of patients. Acute hemodynamic response (dP/dtmax ≥ 10%) was superior with LV stimulation in CT target versus nontarget segments (83.3% vs. 25.0%; p = .012). Reverse remodeling at 6 months (LV end-systolic volume improvement ≥15%) occurred in 60% of subjects (4/8 [50.0%] ischemic cardiomyopathy vs. 5/7 [71.4%] nonischemic cardiomyopathy, p = .608). CONCLUSION: Intraprocedural integration of cardiac CT to guide optimal LV lead placement is feasible with superior hemodynamics when pacing in CT target segments and favorable volumetric response rates, despite a high proportion of patients with ischemic cardiomyopathy. Multicentre, randomized controlled studies are needed to evaluate whether intraprocedural integration of cardiac CT is superior to standard care.

Risk stratification of patients undergoing transvenous lead extraction with the ELECTRa Registry Outcome Score (EROS): an ESC EHRA EORP European lead extraction ConTRolled ELECTRa registry analysis.

AIMS: Transvenous lead extraction is associated with a significant risk of complications and identifying patients at highest risk pre-procedurally will enable interventions to be planned accordingly. We developed the ELECTRa Registry Outcome Score (EROS) and applied it to the ELECTRa registry to determine if it could appropriately risk-stratify patients. METHODS AND RESULTS: EROS was devised to risk-stratify patients into low risk (EROS 1), intermediate risk (EROS 2), and high risk (EROS 3). This was applied to the ESC EORP European Lead Extraction ConTRolled ELECTRa registry; 57.5% EROS 1, 31.8% EROS 2, and 10.7% EROS 3. Patients with EROS 3 or 2 were significantly more likely to require powered sheaths and a femoral approach to complete procedures. Patients with EROS 3 were more likely to suffer procedure-related major complications including deaths (5.1 vs. 1.3%; P < 0.0001), both intra-procedural (3.5 vs. 0.8%; P = 0.0001) and post-procedural (1.6 vs. 0.5%; P = 0.0192). They were more likely to suffer post-procedural deaths (0.8 vs. 0.2%; P 0.0449), cardiac avulsion or tear (3.8 vs. 0.5%; P < 0.0001), and cardiovascular lesions requiring pericardiocentesis, chest tube, or surgical repair (4.6 vs. 1.0%; P < 0.0001). EROS 3 was associated with procedure-related major complications including deaths [odds ratio (OR) 3.333, 95% confidence interval (CI) 1.879-5.914; P < 0.0001] and all-cause in-hospital major complications including deaths (OR 2.339, 95% CI 1.439-3.803; P = 0.0006). CONCLUSION: EROS successfully identified patients who were at increased risk of significant procedural complications that require urgent surgical intervention.

Leadless left ventricular endocardial pacing for CRT upgrades in previously failed and high-risk patients in comparison with coronary sinus CRT upgrades.

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 < 0.001), chronic obstructive airways disease (19.4% vs. 9.9%; P = 0.046), and chronic kidney disease (46.4% vs. 21.5%; P < 0.01) but similar LV ejection fraction (30.0 ± 8.3% vs. 29.5 ± 8.6%; P = 0.678). WiSE-CRT upgrades were successful in 97.1% with procedure-related mortality in 1.9%. Coronary sinus upgrades were successful in 97.5% of cases with a 2.5% rate of CS dissection and 5.6% lead malfunction/displacement. At 6 months, 91 WiSE-CRT upgrades and 107 CS upgrades had similar improvements in CCS (76.3% vs. 68.5%; P = 0.210) and reduction in LVESV ≥15% (54.2% vs. 56.3%; P = 0.835). CONCLUSION: Despite prior failed upgrades and high-risk patients with more comorbidities, WiSE-CRT upgrades had high rates of procedural success and similar improvements in CCS and LV remodelling with CS upgrades.

Endocardial left ventricular pacing.

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.

Comparison of electrical dyssynchrony parameters between electrocardiographic imaging and a simulated ECG belt.

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.

Tracking the motion of intracardiac structures aids the development of future leadless pacing systems.

BACKGROUND: Leadless pacemakers preclude the need for permanent leads to pace endocardium. However, it is yet to be determined whether a leadless pacemaker of a similar design to those manufactured for the right ventricle (RV) fits within the left ventricle (LV), without interfering with intracardiac structures. METHODS: Cardiac computed tomography scans were obtained from 30 patients indicated for cardiac resynchronisation therapy upgrade. The mitral valve annulus, chordae tendineae, papillary muscles and LV endocardial wall were marked in the end-diastolic frame. Intracardiac structures motions were tracked through the cardiac cycle. Two pacemaker designs similar to commercially manufactured leadless systems (Abbott's Nanostim LCP and Medtronic's Micra TPS) as well as theoretical designs with calculated optimal dimensions were evaluated. Pacemakers were virtually placed across the LV endocardial surface and collisions between them and intracardiac structures were detected throughout the cycle. RESULTS: Probability maps of LV intracardiac structures collisions on a 16-segment AHA model indicated possible placement for the Nanostim LCP, Micra TPS, and theoretical designs. Thresholding these maps at a 20% chance of collision revealed only about 36% of the endocardial surface remained collision-free with the deployment of Micra TPS design. The same threshold left no collision-free surface in the case of the Nanostim LCP. To reach at least half of the LV endocardium, the volume of Micra TPS, which is the smaller design, needed to be decreased by 41%. CONCLUSION: Due to the presence of intracardiac structures, placement of leadless pacemakers with dimensions similar to commercially manufactured RV systems would be limited to apical regions.

The effect of centre volume and procedure location on major complications and mortality from transvenous lead extraction: an ESC EHRA EORP European Lead Extraction ConTRolled ELECTRa registry subanalysis.

AIMS: Transvenous lead extraction (TLE) should ideally be undertaken by experienced operators in a setting that allows urgent surgical intervention. In this analysis of the ELECTRa registry, we sought to determine whether there was a significant difference in procedure complications and mortality depending on centre volume and extraction location. METHODS AND RESULTS: Analysis of the ESC EORP European Lead Extraction ConTRolled ELECTRa registry was conducted. Low-volume (LoV) centres were defined as <30 procedures/year, and high-volume (HiV) centres as ≥30 procedures/year. Three thousand, two hundred, and forty-nine patients underwent TLE by a primary operator cardiologist; 17.1% in LoV centres and 82.9% in HiV centres. Procedures performed by primary operator cardiologists in LoV centres were less likely to be successful (93.5% vs. 97.1%; P < 0.0001) and more likely to be complicated by procedure-related deaths (1.1% vs. 0.4%; P = 0.0417). Transvenous lead extraction undertaken by primary operator cardiologists in LoV centres were associated with increased procedure-related major complications including death (odds ratio 1.858, 95% confidence interval 1.007-3.427; P = 0.0475). Transvenous lead extraction locations varied; 52.0% operating room, 9.5% hybrid theatre and 38.5% catheterization laboratory. Rates of procedure-related major complications, including death occurring in a high-risk environment (combining operating room and hybrid theatre), were similar to those undertaken in the catheterization laboratory (1.7% vs. 1.6%; P = 0.9297). CONCLUSION: Primary operator cardiologists in LoV centres are more likely to have extractions complicated by procedure-related deaths. There was no significant difference in procedure complications between different extraction settings. These findings support the need for TLE to be performed in experienced centres with appropriate personnel present.

Leadless left ventricular endocardial pacing in nonresponders to conventional cardiac resynchronization therapy.

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

High mean entropy calculated from cardiac MRI texture analysis is associated with antitachycardia pacing failure.

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.

Evidence of reverse electrical remodelling by non-invasive electrocardiographic imaging to assess acute and chronic changes in bulk ventricular activation following cardiac resynchronisation therapy.

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 < 0.001) and 49 ± 17 ms (P < 0.05), respectively. The relative change at day 1 was also statistically significant for TVaT (19 ± 12%, P < 0.001) and VaT10-90 Index (39 ± 25%, P < 0.001). 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.

Sex-Dependent QRS Guidelines for Cardiac Resynchronization Therapy Using Computer Model Predictions.

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.

Understanding non-response to cardiac resynchronisation therapy: common problems and potential solutions.

Heart failure is a complex clinical syndrome associated with a significant morbidity and mortality burden. Reductions in left ventricular (LV) function trigger adaptive mechanisms, leading to structural changes within the LV and the potential development of dyssynchronous ventricular activation. This is the substrate targeted during cardiac resynchronisation therapy (CRT); however, around 30-50% of patients do not experience benefit from this treatment. Non-response occurs as a result of pre-implant, peri-implant and post implant factors but the technical constraints of traditional, transvenous epicardial CRT mean they can be challenging to overcome. In an effort to improve response, novel alternative methods of CRT delivery have been developed and of these endocardial pacing, where the LV is stimulated from inside the LV cavity, appears the most promising.

Transvenous lead extraction in patients with cardiac resynchronization therapy devices is not associated with increased 30-day mortality.

AIMS: Transvenous lead extraction (TLE) may be necessary due to system infection/erosion or lead malfunction. Cardiac resynchronization therapy (CRT) patients undergoing TLE may be at greater risk due to increased comorbidities. We examined whether patients with CRT systems undergoing TLE had more comorbidities and higher 30-day mortality than those with non-CRT devices. METHODS AND RESULTS: All TLEs between October 2000 and December 2016 were prospectively collected. During this period 925 TLEs occurred (CRT group 231, non-CRT group 694). Cardiac resynchronization therapy patients were older (68.1 ± 10.8 years vs. 64.3 ± 16.1 years, P = 0.024); more likely male (85.7% vs. 69%, P < 0.001); had lower mean left ventricular ejection fraction (34.1 ± 12.7% vs. 48.3 ± 12.9%, P < 0.001); had higher prevalence of renal impairment (33.8% vs. 13.7%, P < 0.001) and were more likely to have ≥2 comorbidities (84% vs. 40.1%, P < 0.001). Mean lead dwell time was lower in the CRT group (5.6 ± 5.5 years vs. 7.6 ± 7.1 years, P = 0.002). There was no significant difference in all-cause 30-day mortality rates between CRT (3.0%, n = 7) and non-CRT patients (2.0%, n = 14) (P = 0.443). The majority of deaths in both groups were due to sepsis. Univariate and multivariate analysis showed age, renal impairment and sepsis were associated with increased risk of 30-day mortality. Transvenous lead extraction of a CRT system did not predict 30-day mortality. CONCLUSION: Transvenous lead extraction in CRT patients was not associated with increased 30-day mortality when compared with non-CRT patients. Age, renal impairment and sepsis were independent predictors of 30-day mortality. Sepsis was the main cause of 30-day mortality.

Prolonged lead dwell time and lead burden predict bailout transfemoral lead extraction.

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 < .001), mean number of leads extracted (2.7 ± 1.3 vs 2.0 ± 1.0, P < .001), 30-day procedure related major complications (including deaths) (8.5% vs 1.1%, P < .001) and emergency thoracotomy rates (4.2% vs 0.7%, P = .007). All-cause 30-day mortality rates were similar between groups (3.4% vs 2.0%, P = .315). Prolonged lead dwell time and increased number of leads extracted were predictive of a bailout transfemoral approach at multivariable analysis. CONCLUSION: Femoral approach TLE is associated with increased risk of 30-day procedure related major complications but not 30-day all-cause mortality. Prolonged lead dwell time and increased number of leads extracted are independent predictors for bailout transfemoral lead extraction. Such patients should be considered high risk of major complications and performed by high-volume lead extraction centers with experience in multiple approaches and techniques including experience with transfemoral lead extraction.

Predictors of mortality and outcomes in transvenous lead extraction for systemic and local infection cohorts.

BACKGROUND: Transvenous lead extraction (TLE) may be necessary due to infective and noninfective indications. We aim to identify predictors of 30-day mortality and risk factors between infective versus noninfective groups and systemic versus local infection subgroups. METHODS: A total of 925 TLEs between October 2000 and December 2016 were prospectively collected and dichotomized (infective group n = 505 vs noninfective group n = 420 and systemic infection n = 164 vs local infection n = 341). RESULTS: All-cause major complication including deaths was significantly higher (5.1%, n = 26 vs 1.2%, n = 5, P = 0.001) as well as 30-day mortality (4.0%, n = 20 vs 0.2%, n = 1, P < 0.001) in the infective group compared to the noninfective group. Both subgroups (systemic vs local infection) were balanced for demographics. All-cause major complication including deaths was significantly higher (9.1%, n = 15 vs 3.2%, n = 11, P = 0.008) as well as all-cause 30-day mortality (7.9%, n  = 13 vs 2.1%, n = 7, P = 0.003) in the systemic infection subgroup compared to the local infection subgroup. CONCLUSION: Patients undergoing TLE for infective indications are at greater risk of 30-day all-cause mortality compared to noninfective patients. Patients undergoing TLE for systemic infective indications are at greater risk of 30-day all-cause mortality compared to patients with local infection. Renal impairment, systemic infection, and elevated preprocedure C-reactive protein are independent predictors of 30-day all-cause mortality in patients undergoing TLE for an infective indication.

Variation in activation time during bipolar vs extended bipolar left ventricular pacing.

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.