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Background: There are conflicting data on whether new-onset atrial fibrillation (AF) is independently associated with poor outcomes in COVID-19 patients. This study represents the largest dataset curated by manual chart review comparing clinical outcomes between patients with sinus rhythm, pre-existing AF, and new-onset AF., Objective: The primary aim of this study was to assess patient outcomes in COVID-19 patients with sinus rhythm, pre-existing AF, and new-onset AF. The secondary aim was to evaluate predictors of new-onset AF in patients with COVID-19 infection., Methods: This was a single-center retrospective study of patients with a confirmed diagnosis of COVID-19 admitted between March and September 2020. Patient demographic data, medical history, and clinical outcome data were manually collected. Adjusted comparisons were performed following propensity score matching between those with pre-existing or new-onset AF and those without AF., Results: The study population comprised of 1241 patients. A total of 94 (7.6%) patients had pre-existing AF and 42 (3.4%) patients developed new-onset AF. New-onset AF was associated with increased in-hospital mortality before (odds ratio [OR] 3.58, 95% confidence interval [CI] 1.78-7.06, P < .005) and after (OR 2.80, 95% CI 1.01-7.77, P < .005) propensity score matching compared with the no-AF group. However, pre-existing AF was not independently associated with in-hospital mortality compared with patients with no AF (postmatching OR: 1.13, 95% CI 0.57-2.21, P = .732)., Conclusion: New-onset AF, but not pre-existing AF, was independently associated with elevated mortality in patients hospitalised with COVID-19. This observation highlights the need for careful monitoring of COVID-19 patients with new-onset AF. Further research is needed to explain the mechanistic relationship between new-onset AF and clinical outcomes in COVID-19 patients., (© 2023 Heart Rhythm Society. Published by Elsevier Inc.)

Background: Atrial fibrillation (AF) has several detrimental effects on heart failure patients treated with cardiac resynchronization therapy (CRT). These include suboptimal biventricular pacing and the loss of atrioventricular (AV) synchrony. AV node ablation improves biventricular pacing and clinical outcomes in large observational studies. However, restoration of sinus rhythm with AF ablation may have additional benefits., Objectives: To compare the effects of AV node ablation and AF ablation on echocardiographic and symptomatic outcomes in patients with CRT and suboptimal biventricular pacing., Methods: RHYTHMIC is a multicenter prospective randomized controlled trial. Seventy patients will be recruited and randomized to each ablation strategy in a 1:1 ratio. Key inclusion criteria include a previous CRT implant (with atrial lead) for dyssynchronous heart failure, and biventricular pacing <95% secondary to AF. Patients with permanent AF will be excluded., Results: Patients will undergo baseline assessment including transthoracic echocardiography (TTE), device check, blood tests, electrocardiogram (ECG), 6-minute walk test, and symptom questionnaire. They will then undergo either AV node ablation or AF ablation according to their allocated group. Follow-up will occur at 1 week (TTE and ECG) and at 6 months (repeat of baseline investigations). The primary endpoint will be change in left ventricular ejection fraction on TTE., Conclusion: This is the first randomized controlled trial comparing AV node ablation and AF ablation in patients with CRT. We anticipate it will provide valuable insight into the management of this frequently encountered clinical scenario in a challenging patient cohort., (© 2022 Heart Rhythm Society. Published by Elsevier Inc.)

Background: Positioning the left ventricular lead at the optimal myocardial segment has been proposed to improve cardiac resynchronization therapy (CRT) response., Objectives: We performed a systematic review and network meta-analysis evaluating echocardiographic and clinical response delivered with different guidance modalities compared to conventional fluoroscopic positioning., Methods: Randomized trials with ≥6 months follow-up comparing any combination of imaging, electrical, hemodynamic, or fluoroscopic guidance were included. Imaging modalities were split whether one modality was used: cardiac magnetic resonance (CMR), speckle-tracking echocardiography (STE), single-photon emission computed tomography, cardiac computed tomography (CT), or a combination of these, defined as "multimodality imaging.", Results: Twelve studies were included (n = 1864). Pair-wise meta-analysis resulted in significant odds of reduction in left ventricular end-systolic volume (LVESV) >15% (odds ratio [OR] 1.50, 95% confidence interval [CI] 1.05-2.13, P = .025) and absolute reduction in LVESV (standardized mean difference [SMD] -0.25, 95% CI -0.43 to -0.08, P = .005) with guidance. CMR (OR 55.3, 95% CI 4.7-656.9, P = .002), electrical (OR 17.0, 95% CI 2.9-100, P = .002), multimodality imaging (OR 4.47, 95% CI 1.36-14.7, P = .014), and hemodynamic guidance (OR 1.29-28.0, P = .02) were significant in reducing LVESV >15%. Only STE demonstrated a significant reduction in absolute LVESV (SMD -0.38, 95% CI -0.68 to -0.09, P = .011]. CMR had the highest probability of improving clinical response (OR 17.9, 95% CI 5.14-62.5, P < .001)., Conclusion: Overall, guidance improves CRT outcomes. STE and multimodality imaging provided the most reliable evidence of efficacy. Wide CIs observed for results of CMR guidance suggest more powered studies are required before a clear ranking is possible., (© 2022 Heart Rhythm Society. Published by Elsevier Inc.)

Background: 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 scar in vivo is unknown., Objective: The purpose of this study was to investigate the effect of scar and pacing location on local repolarization in a porcine myocardial infarction model., Methods: 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., Results: There was no significant difference between aLGE and healthy myocardium in mean ARI (304.20 ± 19.44 ms vs 300.59 ± 19.22 ms; P = .43), ARI heterogeneity (23.32 ± 11.43 ms vs 24.85 ± 12.99 ms; P = .54), or ARI gradients (6.18 ± 2.09 vs 5.66 ± 2.32 ms/mm; P = .39). Endocardial pacing distance from scar did not affect ARI gradients., Conclusion: 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., (© 2022 Heart Rhythm Society. Published by Elsevier Inc.)

Background: Initiation of anticoagulation therapy in ischemic stroke patients is contingent on a clinical diagnosis of atrial fibrillation (AF). Results from previous studies suggest thromboembolic risk may predate clinical manifestations of AF. Early identification of this cohort of patients may allow early initiation of anticoagulation and reduce the risk of secondary stroke., Objective: This study aims to produce a substrate-based predictive model using cardiac magnetic resonance imaging (CMR) and baseline noninvasive electrocardiographic investigations to improve the identification of patients at risk of future thromboembolism., Methods: CARM-AF is a prospective, multicenter, observational cohort study. Ninety-two patients will be recruited following an embolic stroke of unknown source (ESUS) and undergo atrial CMR followed by insertion of an implantable loop recorder (ILR) as per routine clinical care within 3 months of index stroke. Remote ILR follow-up will be used to allocate patients to a study or control group determined by the presence or absence of AF as defined by ILR monitoring., Results: Baseline data collection, noninvasive electrocardiographic data analysis, and imaging postprocessing will be performed at the time of enrollment. Primary analysis will be performed following 12 months of continuous ILR monitoring, with interim and delayed analyses performed at 6 months and 2 and 3 years, respectively., Conclusion: The CARM-AF Study will use atrial structural and electrocardiographic metrics to identify patients with AF, or at high risk of developing AF, who may benefit from early initiation of anticoagulation., (© 2022 Heart Rhythm Society. Published by Elsevier Inc.)

Patients with atrial fibrillation (AF) were largely excluded from the major clinical trials of cardiac resynchronization therapy (CRT), despite the presence of AF in up to 40% of patients receiving CRT in clinical practice. AF appears to attenuate the response to CRT, by the combination of a reduction in biventricular pacing and the loss of atrioventricular synchrony. In addition, remodeling secondary to CRT may influence the progression of AF. Management options for patients with AF and CRT include rate control, with drugs or atrioventricular node ablation, or rhythm control, with electrical cardioversion and antiarrhythmic therapy, or AF catheter ablation. The evidence for these therapies in patients with CRT is largely limited to observational studies or inferred from randomized studies in the general heart failure population. In this review, we explore the complex interaction between AF, heart failure, and CRT and discuss the evidence for the treatment options in this difficult patient cohort., (© 2021 Heart Rhythm Society. Published by Elsevier Inc.)

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) or late (>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., (© 2021 Heart Rhythm Society. Published by Elsevier Inc.)

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/dt max 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 <10%; P < 0.001). Procedure duration and fluoroscopy times were longer in the pressure wire-guided arm (104 ± 39 minutes vs 142 ± 39 minutes; P < .001 and 20 ±16 minutes vs 28 ± 15 minutes; P = .002)., Conclusions: AHR determined by invasively measuring LV dP/dt max during BIV pacing predicts reverse remodeling 6 months after CRT. Patients in whom LV dP/dt max was used to guide LV lead placement demonstrated better rates of reverse remodeling., (© 2021 Heart Rhythm Society. Published by Elsevier Inc.)

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., (© 2021 The Authors.)

Objectives: This study hypothesized that guided implants, in which the optimal left ventricular endocardial (LV ENDO ) pacing location was identified and targeted, would improve acute markers of contractility and chronic markers of cardiac resynchronization (CRT) response., Background: Biventricular endocardial (BiV ENDO ) pacing may offer a potential benefit over standard CRT; however, the optimal LV ENDO pacing site is highly variable. Indiscriminately delivered BiV ENDO pacing is associated with a reverse remodeling response rate of between 40% and 60%., Methods: Registry of centers implanting a wireless, LV ENDO 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 LV ENDO 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 BiV ENDO . 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., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to characterize direction-dependent and coupling interval-dependent changes in left atrial conduction and electrogram morphology in uniformly classified patients with paroxysmal atrial fibrillation (AF) and normal bipolar voltage mapping., Background: Although AF classifications are based on arrhythmia duration, the clinical course, and treatment response vary between patients within these groups. Electrophysiological mechanisms responsible for this variability are incompletely described., Methods: Intracardiac contact mapping during incremental atrial pacing was used to characterize atrial conduction, activation dispersion, and electrogram morphology in 15 consecutive paroxysmal AF patients undergoing first-time pulmonary vein isolation. Outcome measures were vulnerability to AF induction at electrophysiology study and 2-year follow-up for arrhythmia recurrence., Results: Conduction delay showed a bimodal distribution, occurring at either long (high right atrium pacing: 326 ± 13 ms; coronary sinus pacing: 319 ± 16 ms) or short (high right atrium pacing: 275 ± 11 ms; coronary sinus pacing: 271 ± 11 ms) extrastimulus coupling intervals. Arrhythmia recurrence was found only in patients with conduction delay at long extrastimulus coupling intervals, and patients with inducible AF were characterized by increased activation dispersion (activation dispersion time: 168 ± 29 ms vs. 136 ± 11 ms). Electrogram voltage and duration varied throughout the left atrium, between patients, and with pacing site but were not correlated with AF vulnerability or arrhythmia recurrence., Conclusions: Within the single clinical entity of paroxysmal AF, incremental atrial pacing identified a spectrum of activation patterns correlating with AF vulnerability and arrhythmia recurrence. In contrast, electrogram morphology (characterized by electrogram voltage and duration) was highly variable and not associated with AF vulnerability or recurrence. An improved understanding of the electrical phenotype in AF could lead to improved mechanistic classifications.

Objectives: The purpose of this study was to identify the optimal pacing site for the left ventricular (LV) lead in ischemic patients with poor response to cardiac resynchronization therapy (CRT)., Background: LV endocardial pacing may offer benefit over conventional CRT in ischemic patients., Methods: We performed cardiac magnetic resonance, invasive electroanatomic mapping (EAM), and measured the acute hemodynamic response (AHR) in patients with existing CRT systems., Results: In all, 135 epicardial and endocardial pacing sites were tested in 8 patients. Endocardial pacing was superior to epicardial pacing with respect to mean AHR (% change in dP/dt max vs. baseline) (11.81 [-7.2 to 44.6] vs. 6.55 [-11.0 to 19.7]; p = 0.025). This was associated with a similar first ventricular depolarization (Q-LV) (75 ms [13 to 161 ms] vs. 75 ms [25 to 129 ms]; p = 0.354), shorter stimulation-QRS duration (15 ms [7 to 43 ms] vs. 19 ms [5 to 66 ms]; p = 0.010) and shorter paced QRS duration (149 ms [95 to 218 ms] vs. 171 ms [120 to 235 ms]; p < 0.001). The mean best achievable AHR was higher with endocardial pacing (25.64 ± 14.74% vs. 12.64 ± 6.76%; p = 0.044). Furthermore, AHR was significantly greater pacing the same site endocardially versus epicardially (15.2 ± 10.7% vs. 7.6 ± 6.3%; p = 0.014) with a shorter paced QRS duration (137 ± 22 ms vs. 166 ± 30 ms; p < 0.001) despite a similar Q-LV (70 ± 38 ms vs. 79 ± 34 ms; p = 0.512). Lack of capture due to areas of scar (corroborated by EAM and cardiac magnetic resonance) was associated with a poor AHR., Conclusions: In ischemic patients with poor CRT response, biventricular endocardial pacing is superior to epicardial pacing. This may reflect accessibility to sites that cannot be reached via coronary sinus anatomy and/or by access to more rapidly conducting tissue. Furthermore, guidance to the optimal LV pacing site may be aided by modalities such as cardiac magnetic resonance to target delayed activating sites while avoiding scar.