Blood groups and Rhesus status as potential predictors of outcomes in patients with cardiac resynchronisation therapy.

Cardiac resynchronisation therapy (CRT) improves prognosis in patients with heart failure (HF) however the role of ABO blood groups and Rhesus factor are poorly understood. We hypothesise that blood groups may influence clinical and survival outcomes in HF patients undergoing CRT. A total of 499 patients with HF who fulfilled the criteria for CRT implantation were included. Primary outcome of all-cause mortality and/or heart transplant/left ventricular assist device was assessed over a median follow-up of 4.6 years (IQR 2.3-7.5). Online repositories were searched to provide biological context to the identified associations. Patients were divided into blood (O, A, B, and AB) and Rhesus factor (Rh-positive and Rh-negative) groups. Mean patient age was 66.4 ± 12.8 years with a left ventricular ejection fraction of 29 ± 11%. There were no baseline differences in age, gender, and cardioprotective medication. In a Cox proportional hazard multivariate model, only Rh-negative blood group was associated with a significant survival benefit (HR 0.68 [0.47-0.98], p = 0.040). No association was observed for the ABO blood group (HR 0.97 [0.76-1.23], p = 0.778). No significant interaction was observed with prevention, disease aetiology, and presence of defibrillator. Rhesus-related genes were associated with erythrocyte and platelet function, and cholesterol and glycated haemoglobin levels. Four drugs under development targeting RHD were identified (Rozrolimupab, Roledumab, Atorolimumab, and Morolimumab). Rhesus blood type was associated with better survival in HF patients with CRT. Further research into Rhesus-associated pathways and related drugs, namely whether there is a cardiac signal, is required.

The BLISTER Score: A Novel, Externally Validated Tool for Predicting Cardiac Implantable Electronic Device Infections, and Its Cost-Utility Implications for Antimicrobial Envelope Use.

BACKGROUND: Antimicrobial envelopes reduce the incidence of cardiac implantable electronic device infections, but their cost restricts routine use in the United Kingdom. Risk scoring could help to identify which patients would most benefit from this technology. METHODS: A novel risk score (BLISTER [Blood results, Long procedure time, Immunosuppressed, Sixty years old (or younger), Type of procedure, Early re-intervention, Repeat procedure]) was derived from multivariate analysis of factors associated with cardiac implantable electronic device infection. Diagnostic utility was assessed against the existing PADIT score (Prior procedure, Age, Depressed renal function, Immunocompromised, Type of procedure) in both standard and high-risk external validation cohorts, and cost-utility models examined different BLISTER and PADIT score thresholds for TYRX (Medtronic; Minneapolis, MN) antimicrobial envelope allocation. RESULTS: In a derivation cohort (n=7383), cardiac implantable electronic device infection occurred in 59 individuals within 12 months of a procedure (event rate, 0.8%). In addition to the PADIT score constituents, lead extraction (hazard ratio, 3.3 [95% CI, 1.9-6.1]; P<0.0001), C-reactive protein >50 mg/L (hazard ratio, 3.0 [95% CI, 1.4-6.4]; P=0.005), reintervention within 2 years (hazard ratio, 10.1 [95% CI, 5.6-17.9]; P<0.0001), and top-quartile procedure duration (hazard ratio, 2.6 [95% CI, 1.6-4.1]; P=0.001) were independent predictors of infection. The BLISTER score demonstrated superior discriminative performance versus PADIT in the standard risk (n=2854, event rate: 0.8%, area under the curve, 0.82 versus 0.71; P=0.001) and high-risk validation cohorts (n=1961, event rate: 2.0%, area under the curve, 0.77 versus 0.69; P=0.001), and in all patients (n=12 198, event rate: 1%, area under the curve, 0.8 versus 0.75, P=0.002). In decision-analytic modeling, the optimum scenario assigned antimicrobial envelopes to patients with BLISTER scores ≥6 (10.8%), delivering a significant reduction in infections (relative risk reduction, 30%; P=0.036) within the National Institute for Health and Care Excellence cost-utility thresholds (incremental cost-effectiveness ratio, £18 446). CONCLUSIONS: The BLISTER score (https://qxmd.com/calculate/calculator_876/the-blister-score-for-cied-infection) was a valid predictor of cardiac implantable electronic device infection, and could facilitate cost-effective antimicrobial envelope allocation to high-risk patients.

The frequency of gene variant reclassification and its impact on clinical management in the inherited arrhythmia clinic.

BACKGROUND: Genetic testing in the inherited arrhythmia clinic informs risk stratification, clinical management, and family screening. Periodic review of variant classification is recommended as supporting evidence accrues over time. However, there is limited reporting of real-world data on the frequency and impact of variant reclassification. OBJECTIVE: The purpose of this study was to determine the burden of variant reclassification in our inherited arrhythmia clinic and the impact on clinical management. METHODS: Genetic testing reports for patients referred to our clinic from 2004-2020 were reviewed. Reported variants were reinvestigated using ClinVar, VarSome, and a literature review. Classification was updated using the American College of Medical Genetics and Genomics (ACMG) criteria and tested for association with arrhythmic events and modification of medical management. RESULTS: We identified 517 patients (median age 37 years) who underwent gene panel testing. A variant of uncertain significance (VUS) was reported for 94 patients (18.2%) and more commonly identified when using large gene panels (P <.001). A total of 28 of 87 unique VUSs (32.2%) were reclassified to pathogenic/likely pathogenic (n = 11) or benign/likely benign (n = 17). Of 138 originally reported pathogenic variants, 7 (5.1%) lacked support using ACMG criteria. Variant reclassification was not associated with arrhythmic events; however, it did impact genotype-specific counseling and future therapeutic options. CONCLUSION: In our large real-world patient cohort, we identify a clinically important proportion of both pathogenic variants and VUSs with evidence for reclassification. These findings highlight the need for informed pretest counseling, a regular structured review of variants reported in genetic testing, and the potential benefits to patients for supporting genotype-guided therapy.

DOACs vs Vitamin K Antagonists During Cardiac Rhythm Device Surgery: A Multicenter Propensity-Matched Study.

BACKGROUND: There is a paucity of data comparing vitamin K antagonists (VKAs) to direct oral anticoagulants (DOACs) at the time of cardiac implantable electronic device (CIED) surgery. Furthermore, the best management of DOACs (interruption vs continuation) is yet to be determined. OBJECTIVES: This study aimed to compare the incidence of device-related bleeds and thrombotic events based on anticoagulant type (DOAC vs VKA) and regimen (interrupted vs uninterrupted). METHODS: This was an observational multicenter study. We included patients on chronic oral anticoagulation undergoing CIED surgery. Patients were matched using propensity scoring. RESULTS: We included 1,975 patients (age 73.8 ± 12.4 years). Among 1,326 patients on DOAC, this was interrupted presurgery in 78.2% (n = 1,039) and continued in 21.8% (n = 287). There were 649 patients on continued VKA. The matched population included 861 patients. The rate of any major bleeding was higher with continued DOAC (5.2%) compared to interrupted DOAC (1.7%) and continued VKA (2.1%) (P = 0.03). The rate of perioperative thromboembolism was 1.4% with interrupted DOAC, whereas no thromboembolic events occurred with DOAC or VKA continuation (P = 0.04). The use of dual antiplatelet therapy, DOAC continuation, and male sex were independent predictors of major bleeding on a multivariable analysis. CONCLUSIONS: In this large real-world cohort, a continued DOAC strategy was associated with a higher bleeding risk compared to DOAC interruption or VKA continuation in patients undergoing CIED surgery. However, DOAC interruption was associated with increased thromboembolic risk. Concomitant dual antiplatelet therapy should be avoided whenever clinically possible. A bespoke approach is necessary, with a strategy of minimal DOAC interruption likely to represent the best compromise.

Right coronary artery compromise following radiofrequency catheter ablation for supraventricular tachycardia: cases reports.

Background: Coronary compromise is a serious potential complication following catheter ablation; however, procedural details in the literature are often lacking, preventing the identification of learning opportunities. Case summary: We report two cases of right coronary compromise following catheter ablation for symptomatic supraventricular tachycardia. After radiofrequency energy delivery at the coronary sinus ostium in both cases, inferior lead ST-elevation was observed. Diagnostic coronary angiography identified an occluded posterior left ventricular branch of the coronary artery, and optical coherence tomography demonstrated a high thrombus burden at this location. Electrocardiographic ST-segments settled with implantation of a drug-eluting stent. Discussion: Coronary compromise was likely secondary to energy delivery during catheter ablation. This case series highlights the need for electrophysiologist to understand coronary anatomy relative to anatomical landmarks, to anticipate the risk of vascular injury as physical distance from the site of ablation is likely important. Risk for coronary compromise, while a rare complication, needs to be discussed with patients during the consenting process. We also demonstrate the importance of an efficient multi-disciplinary team process for managing acute procedural complications.

Atrial fibrillation cryoablation is an effective day case treatment: the UK PolarX vs. Arctic Front Advance experience.

AIMS: Pulmonary vein isolation (PVI) is the cornerstone of catheter ablation for atrial fibrillation (AF). There are limited data on the PolarX Cryoballoon. The study aimed to establish the safety, efficacy, and feasibility of same day discharge for Cryoballoon PVI. METHODS AND RESULTS: Multi-centre study across 12 centres. Procedural metrics, safety profile, and procedural efficacy of the PolarX Cryoballoon with the Arctic Front Advance (AFA) Cryoballoon were compared in a cohort large enough to provide definitive comparative data. A total of 1688 patients underwent PVI with cryoablation (50% PolarX and 50% AFA). Successful PVI was achieved with 1677 (99.3%) patients with 97.2% (n = 1641) performed as day case procedures with a complication rate of <1%. Safety, procedural metrics, and efficacy of the PolarX Cryoballoon were comparable with the AFA cohort. The PolarX Cryoballoon demonstrated a nadir temperature of -54.6 ± 7.6°C, temperature at 30 s of -38.6 ± 7.2°C, time to -40°C of 34.1 ± 13.7 s, and time to isolation of 49.8 ± 33.2 s. Independent predictors for achieving PVI included time to reach -40°C [odds ratio (OR) 1.34; P < 0.001] and nadir temperature (OR 1.24; P < 0.001) with an optimal cut-off of ≤34 s [area under the curve (AUC) 0.73; P < 0.001] and nadir temperature of ≤-54.0°C (AUC 0.71; P < 0.001), respectively. CONCLUSIONS: This large-scale UK multi-centre study has shown that Cryoballoon PVI is a safe, effective day case procedure. PVI using the PolarX Cryoballoon was similarly safe and effective as the AFA Cryoballoon. The cryoablation metrics achieved with the PolarX Cryoballoon were different to that reported with the AFA Cryoballoon. Modified cryoablation targets are required when utilizing the PolarX Cryoballoon.

Hypoxia Promotes Atrial Tachyarrhythmias via Opening of ATP-Sensitive Potassium Channels.

BACKGROUND: Hypoxia-ischemia predisposes to atrial arrhythmia. Atrial ATP-sensitive potassium channel (KATP) modulation during hypoxia has not been explored. We investigated the effects of hypoxia on atrial electrophysiology in mice with global deletion of KATP pore-forming subunits. METHODS: Whole heart KATP RNA expression was probed. Whole-cell KATP current and action potentials were recorded in isolated wild-type (WT), Kir6.1 global knockout (6.1-gKO), and Kir6.2 global knockout (6.2-gKO) murine atrial myocytes. Langendorff-perfused hearts were assessed for atrial effective refractory period (ERP), conduction velocity, wavefront path length (WFPL), and arrhymogenicity under normoxia/hypoxia using a microelectrode array and programmed electrical stimulation. Heart histology was assessed. RESULTS: Expression patterns were essentially identical for all KATP subunit RNA across human heart, whereas in mouse, Kir6.1 and SUR2 (sulphonylurea receptor subunit) were higher in ventricle than atrium, and Kir6.2 and SUR1 were higher in atrium. Compared with WT, 6.2-gKO atrial myocytes had reduced tolbutamide-sensitive current and action potentials were more depolarized with slower upstroke and reduced peak amplitude. Action potential duration was prolonged in 6.1-gKO atrial myocytes, absent of changes in other ion channel gene expression or atrial myocyte hypertrophy. In Langendorff-perfused hearts, baseline atrial ERP was prolonged and conduction velocity reduced in both KATP knockout mice compared with WT, without histological fibrosis. Compared with baseline, hypoxia led to conduction velocity slowing, stable ERP, and WFPL shortening in WT and 6.1-gKO hearts, whereas WFPL was stable in 6.2-gKO hearts due to ERP prolongation with conduction velocity slowing. Tolbutamide reversed hypoxia-induced WFPL shortening in WT and 6.1-gKO hearts through ERP prolongation. Atrial tachyarrhythmias inducible with programmed electrical stimulation during hypoxia in WT and 6.1-gKO mice correlated with WFPL shortening. Spontaneous arrhythmia was not seen. CONCLUSIONS: KATP block/absence leads to cellular and tissue level atrial electrophysiological modification. Kir6.2 global knockout prevents hypoxia-induced atrial WFPL shortening and atrial arrhythmogenicity to programmed electrical stimulation. This mechanism could be explored translationally to treat ischemically driven atrial arrhythmia.

Amplified sinus-P-wave analysis predicts outcomes of cryoballoon ablation in patients with persistent and long-standing persistent atrial fibrillation: A multicentre study.

Introduction: Outcomes of catheter ablation for non-paroxysmal atrial fibrillation (AF) remain suboptimal. Non-invasive stratification of patients based on the presence of atrial cardiomyopathy (ACM) could allow to identify the best responders to pulmonary vein isolation (PVI). Methods: Observational multicentre retrospective study in patients undergoing cryoballoon-PVI for non-paroxysmal AF. The duration of amplified P-wave (APW) was measured from a digitally recorded 12-lead electrocardiogram during the procedure. If patients were in AF, direct-current cardioversion was performed to allow APW measurement in sinus rhythm. An APW cut-off of 150 ms was used to identify patients with significant ACM. We assessed freedom from arrhythmia recurrence at long-term follow-up in patients with APW ≥ 150 ms vs. APW < 150 ms. Results: We included 295 patients (mean age 62.3 ± 10.6), of whom 193 (65.4%) suffered from persistent AF and the remaining 102 (34.6%) from long-standing persistent AF. One-hundred-forty-two patients (50.2%) experienced arrhythmia recurrence during a mean follow-up of 793 ± 604 days. Patients with APW ≥ 150 ms had a significantly higher recurrence rate post ablation compared to those with APW < 150 ms (57.0% vs. 41.6%; log-rank p < 0.001). On a multivariable Cox-regression analysis, APW≥150 ms was the only independent predictor of arrhythmia recurrence post ablation (HR 2.03 CI95% 1.28-3.21; p = 0.002). Conclusion: APW duration predicts arrhythmia recurrence post cryoballoon-PVI in persistent and long-standing persistent AF. An APW cut-off of 150 ms allows to identify patients with significant ACM who have worse outcomes post PVI. Analysis of APW represents an easy, non-invasive and highly reproducible diagnostic tool which allows to identify patients who are the most likely to benefit from PVI-only approach.

Long-term outcomes following catheter ablation versus medical therapy in patients with persistent atrial fibrillation and heart failure with reduced ejection fraction.

AIMS: The ARC-HF and CAMTAF trials randomized patients with persistent atrial fibrillation (AF) and heart failure (HF) to early routine catheter ablation (ER-CA) versus pharmacological rate control (RC). After trial completion, delayed selective catheter ablation (DS-CA) was performed where clinically indicated in the RC group. We hypothesized that ER-CA would result in a lower risk of cardiovascular hospitalization and death versus DS-CA in this population. METHODS AND RESULTS: Overall, 102 patients were randomized (age 60 ± 11 years, left ventricular ejection fraction [LVEF] 31 ± 11%): 52 to ER-CA and 50 to RC. After 12 months, patients undergoing ER-CA had improved self-reported symptom scores, lower New York Heart Association class (i.e. better functional capacity), and higher LVEF compared to patients receiving RC alone. During a median follow-up of 7.8 (interquartile range 3.9-9.9) years, 27 (54%) patients in the RC group underwent DS-CA and 34 (33.3%) patients died, including 17 (32.7%) randomized to ER-CA and 17 (34.0%) randomized to RC. Compared with DS-CA, a strategy of ER-CA exhibited similar risk of all-cause mortality (adjusted hazard ratio [aHR] 0.89, 95% confidence interval [CI] 0.44-1.77, p = 0.731) and combined all-cause mortality or cardiovascular hospitalization (aHR 0.80, 95% CI 0.43-1.47, p = 0.467). However, analyses according to treatment received suggested an association between CA and improved outcomes versus RC (all-cause mortality: aHR 0.43, 95% CI 0.20-0.91, p = 0.028; all-cause mortality/cardiovascular hospitalization: aHR 0.48, 95% CI 0.24-0.94, p = 0.031). CONCLUSIONS: In patients with persistent AF and HF, ER-CA produces similar long-term outcomes to a DS-CA strategy. The association between CA as a treatment received and improved outcomes means there is still a lack of clarity regarding the role of early CA in selected patients. Randomized trials are needed to clarify this question.

ECG-I phenotyping of persistent AF based on driver burden and distribution to predict response to pulmonary vein isolation (PHENOTYPE-AF).

BACKGROUND: This prospective trial sought to phenotype persistent atrial fibrillation (AF) based on AF mechanisms using electrocardiographic imaging (ECGI) mapping to determine whether this would predict long-term freedom from arrhythmia after pulmonary vein isolation (PVI). METHODS: Patients with persistent AF of <2 years duration underwent cryoballoon PVI. ECGI mapping was performed before PVI to determine potential drivers (PDs) defined as rotational activations completing ≥1.5 revolutions or focal activations. The coprimary endpoint was the association between (1) PD burden (defined as the number of PD occurrences) and (2) PD distribution (defined as the number of segments on an 18-segment model of the atria harboring PDs) with freedom from arrhythmia at 1-year follow up. RESULTS: Of 100 patients, 97 completed follow up and 52 (53.6%) remained in sinus rhythm off antiarrhythmic drugs. Neither PD burden nor PD distribution predicted freedom from arrhythmia (hazard ratio [HR]: 1.01, 95% confidence interval [CI]: 0.99-1.03, p = .164; and HR: 1.04, 95% CI: 0.91-1.17, p = .591, respectively). Otherwise, the burden of rotational PDs, rotational stability, and the burden of PDs occurring at the pulmonary veins and posterior wall all failed to predict arrhythmia recurrence (all p > .10). CONCLUSIONS: AF mechanisms as determined using ECGI mapping do not predict outcomes after PVI for persistent AF. Further studies using different methodologies to characterize AF mechanisms are warranted (NCT03394404).

Coronary sinus electrogram characteristics predict termination of AF with ablation and long-term clinical outcome.

INTRODUCTION: Markers predicting atrial fibrillation (AF) termination and freedom from AF/atrial tachycardia (AT) has been proposed. This study aimed to evaluate the role of novel coronary sinus (CS) electrogram characteristics in predicting the acute ablation response and freedom from AF/AT during follow-up. METHODS: Patients undergoing ablation for persistent AF as part of the Stochastic Trajectory Analysis of Ranked signals mapping study were included. Novel CS electrogram characteristics including CS cycle length variability (CLV) and CS activation pattern stability (APS) and proportion of low voltage zones (LVZs) were reviewed as potential predictors for AF termination on ablation and freedom from AF/AT during follow-up. The relationship between localized driver characteristics and CS electrogram characteristics was also assessed. RESULTS: Sixty-five patients were included. AF termination was achieved in 51 patients and 80% of patients were free from AF/AT during a follow-up of 29.5 ± 3.7 months. CS CLV of <30 ms, CS APS of ≥30% and proportion of LVZ < 30% showed high diagnostic accuracy in predicting AF termination on ablation and freedom from AF/AT during follow-up (CS CLV odds ratio [OR] 25.6, area under the curve [AUC] 0.91; CS APS OR 15.9, AUC 0.94; proportion of LVZs OR 21.4, AUC 0.88). These markers were independent predictors of AF termination on ablation and AF/AT recurrence during follow-up. Ablation of a smaller number of drivers that demonstrate greater dominance strongly correlate with greater CS organization. CONCLUSION: Novel CS electrogram characteristics were independent predictors of AF termination and AF/AT recurrence during follow-up. These markers can potentially aid in predicting outcomes and guide ablation and follow-up strategies.

PolarX Cryoballoon metrics predicting successful pulmonary vein isolation: targets for ablation of atrial fibrillation.

AIM: Evaluate the novel PolarX Cryoballoon in atrial fibrillation (AF) catheter ablation through a propensity-matched comparison with the Arctic Front Advance (AFA). The aim was also to identify cryoablation metrics that are predictive of successful pulmonary vein isolation (PVI) with the PolarX Cryoballoon. METHODS AND RESULTS: This prospective multi-centre study included patients that underwent cryoablation for AF. All patients underwent PVI with reconnection assessed after a 30-min waiting period and adenosine. Safety, efficacy, and cryoablation metrics were compared between PolarX and a propensity-matched AFA cohort. Seventy patients were included with 278 veins treated. In total, 359 cryoablations were performed (1.3 ± 0.6 per vein) to achieve initial PVI with 205 (73.7%) veins isolating with a single cryoablation. Independent predictors for achieving initial PVI included temperature at 30 s [odds ratio (OR) 1.26; P = 0.003] and time to reach -40°C (OR 1.88; P < 0.001) with an optimal cut-off of ≤-38.5°C at 30 s [area under the curve (AUC) 0.79; P < 0.001] and ≤-40°C at ≤32.5 s (AUC 0.77; P < 0.001), respectively. Of the 278 veins, 46 (16.5%) veins showed acute reconnection. Temperature at 30 s (≤-39.5°C, OR 1.24; P = 0.002), nadir temperature (≤-53.5°C, OR 1.35; P = 0.003), and time to isolation (≤38.0 s, OR 1.18; P = 0.009) were independent predictors of sustained PVI. Combining two of these three targets was associated with reconnection in only 2-5% of PVs. Efficacy and safety of the PolarX Cryoballoon were comparable to AFA Cryoballoon, however, cryoablation metrics were significantly different. CONCLUSIONS: The PolarX Cryoballoon has a different cryoablation profile to AFA Cryoballoon. Prospective testing of these proposed targets in large outcomes studies is required.

Contemporary Practice and Optimising Referral Pathways for Implantable Cardiac Monitoring for Atrial Fibrillation after Cryptogenic Stroke.

OBJECTIVES: Diagnosing atrial fibrillation (AF) in patients following Cryptogenic stroke (CS) has therapeutic implications that can reduce the risk of further strokes. However, it's indolent and paroxysmal nature makes this challenging. Prolonged rhythm monitoring using implantable loop recorders (ILRs) can significantly increase the AF detection rate in the clinical trial paradigm. Whether this can be translated to real-world practice is unknown. An evaluation of referral pathways, workload and real-world efficacy may help select patients and inform service development. MATERIALS AND METHODS: Retrospective review of all patients with CS referred to a tertiary electrophysiology referral hospital for ILR implantation between February 2017 and October 2020 for AF detection was conducted. The electronic health record was used to determine demographic and mortality data. Remote monitoring was used to identify AF occurrence. RESULTS: 107 patients were included. The average time from stroke to ILR implantation was 10.5 (5.9-18.6) months. The average monitoring duration was 18.1 ± 11.2 months with 15 (14.0%) patients diagnosed with AF and commenced on anticoagulation. One diagnosis were made in the first 30 days whereas 11 (73%) were made within 12 months. Paroxysmal AF episodes ranged from 6 min to 13 h. Patients with CHA2DS2-VASc >3 were more likely to have AF (20.3% vs 4.7%, p = 0.02). Age was independently associated with AF detection after multi-variate regression. 352 ± 1171 unique events were recorded per patient, 75% of which were for suspected AF. External manufacturer-led triage of transmissions reduced transmission volume by 33%. CONCLUSIONS: ILR-based AF detection rate was high among referred CS patients, despite implantation occurring relatively late. Older patients may be less likely to be referred despite positive correlation between age and AF detection. Although recording algorithms and external triage reduced transmission volume, specialist analysis was required to manage the ILR event burden.

Assessing Noninvasive Delineation of Low-Voltage Zones Using ECG Imaging in Patients With Structural Heart Disease.

OBJECTIVES: This study sought to assess the association between electrocardiographic imaging (ECGI) parameters and voltage from simultaneous electroanatomic mapping (EAM). BACKGROUND: ECGI offers noninvasive assessment of electrophysiologic features relevant for mapping ventricular arrhythmia and its substrate, but the accuracy of ECGI in the delineation of scar is unclear. METHODS: Sixteen patients with structural heart disease underwent simultaneous ECGI (CardioInsight, Medtronic) and contact EAM (CARTO, Biosense-Webster) during ventricular tachycardia catheter ablation, with 7 mapped epicardially. ECGI and EAM geometries were coregistered using anatomic landmarks. ECGI points were paired to the closest site on the EAM within 10 mm. The association between EAM voltage and ECGI features from reconstructed epicardial unipolar electrograms was assessed by mixed-effects regression models. The classification of low-voltage regions was performed using receiver-operating characteristic analysis. RESULTS: A total of 9,541 ECGI points (median: 596; interquartile range: 377-737 across patients) were paired to an EAM site. Epicardial EAM voltage was associated with ECGI features of signal fractionation and local repolarization dispersion (N = 7; P < 0.05), but they poorly classified sites with bipolar voltage of <1.5 mV or <0.5 mV thresholds (median area under the curve across patients: 0.50-0.62). No association was found between bipolar EAM voltage and low-amplitude reconstructed epicardial unipolar electrograms or ECGI-derived bipolar electrograms. Similar results were found in the combined cohort (n = 16), including endocardial EAM voltage compared to epicardial ECGI features (n = 9). CONCLUSIONS: Despite a statistically significant association between ECGI features and EAM voltage, the accuracy of the delineation of low-voltage zones was modest. This may limit ECGI use for pr-procedural substrate analysis in ventricular tachycardia ablation, but it could provide value in risk assessment for ventricular arrhythmias.

Risk factors for developing pacing induced LV dysfunction: Experience from a tertiary center in the UK.

BACKGROUND: The risk factors for developing pacing induced left ventricular dysfunction (LVD) in patients with high burden of right ventricular pacing (RVP) is poorly understood. Therefore, in the present study, we aimed to assess the determinants of pacing induced LVD. METHODS: Our data were retrospectively collected from 146 patients with RVP > 40% who underwent generator change (GC) or cardiac resynchronization therapy (CRT) upgrade between 2016 and 2019 who had left ventricular ejection fraction (EF) ≥50% at initial implant. RESULTS: A total of 75 patients had CRT upgrade due to pacing induced LVD (EF < 50%) and 71 patients with preserved LV function (EF ≥ 50%) had a GC. Primary indication for pacing in both groups was complete heart block. Male predominance (p = .008), prior myocardial infarction (MI) (p = .001), atrial fibrillation (AF) (p = .009), chronic kidney disease (CKD) (p = .005), and borderline low systolic function (BLSF) (EF 50%-55%) (p = .04) were more prevalent in the CRT upgrade group. Presence of AF (odds ratio [OR] = 3.05, 95% confidence interval [CI] 1.42-6.58; p = .004), BLSF (OR = 3.8, 95% CI 1.22-11.8; p = .02), and male gender (OR = 2.41, 95% CI 1.14-5.08; p = .02) were independent predictors for RVP induced LVD. Age (OR = 1.08, 95% CI 1.02-1.14; p = .005) and BLSF (OR = 5.33, 95% CI 1.26-22.5; p = .023) were independent predictors of earlier development of LVD after implant. CONCLUSIONS: Our results suggested that AF, BLSF, and male gender are predictors for development of pacing induced LVD in patients with high RVP burden. LVD can occur at any time after pacemaker implant with BLSF and increasing age associated with earlier development of LVD.

Driver characteristics associated with structurally and electrically remodeled atria in persistent atrial fibrillation.

Background: Recent studies suggest persistent atrial fibrillation (AF) is maintained by localized focal or rotational electrical activations termed drivers. Objective: The purpose of this study was to evaluate how left atrial (LA) dilation and time in AF impact persistent AF mechanisms. Methods: Patients with persistent AF <2 years underwent electrocardiographic image mapping. Potential drivers (PDs) were defined as rotational wavefront activity ≥1.5 revolutions or focal activations. Distribution of PDs was recorded using an 18-segment model. Results: One hundred patients were enrolled (age 61.3 ± 12.1 years). Of these patients, 47 were hypertensive, 14 had diabetes mellitus, and 10 had ischemic heart disease. AF duration was 8 [5-15] months. Median LA diameter was 39 [33-43] mm. Although LA dimensions did not correlate with overall PD burden or distribution, there was a modest correlation between increasing LA area (r = 0.235; P = .024) and LA volume (r = 0.216; P = .039) with proportion of PDs that were rotational. Although time in AF did not correlate with overall PD burden or distribution, there was a correlation between time in AF and the number of focal PDs (r = 0.203; P = .044). Female gender, increasing age, and hypertension also were associated with an increase in focal PDs. Conclusion: This is the first study to demonstrate different AF mechanisms in patient subgroups. Greater understanding of patient-specific AF mechanisms may facilitate a tailored approach to AF mapping and ablation.

Ethanol ablation for ventricular arrhythmias: A systematic review and meta-analysis.

INTRODUCTION: Ethanol ablation (EA) is an alternative option for subjects with ventricular arrhythmias (VAs) refractory to conventional medical and ablative treatment. However, data on the efficacy and safety of EA remain sparse. METHODS: A systematic literature search was conducted. The primary outcomes were 1) freedom from the targeted VA and 2) freedom from any VAs post-EA. Additional safety outcomes were also analyzed. RESULTS: Ten studies were selected accounting for a population of 174 patients (62.3 ± 12.5 years, 94% male) undergoing 185 procedures. The overall acute success rate of EA was 72.4% (confidence interval [CI95% ]: 65.6-78.4). After a mean follow-up of 11.3 ± 5.5 months, the incidence of relapse of the targeted VA was 24.4% (CI95% : 17.1-32.8), while any VAs post-EA occurred in 41.3% (CI95% : 33.7-49.1). The overall incidence of procedural complications was 14.1% (CI95% : 9.8-19.8), with pericardial complications and complete atrioventricular block being the most frequent. An anterograde transarterial approach was associated with a higher rate of VA recurrences and complications compared to a retrograde transvenous route; however, differences in the baseline population characteristics and in the targeted ventricular areas should be accounted. CONCLUSION: EA is a valuable therapeutic option for VAs refractory to conventional treatment and can result in 1-year freedom from VA recurrence in 60%-75% of the patients. However, anatomical or technical challenges preclude acute success in almost 30% of the candidates and the rate of complication is not insignificant, highlighting the importance of well-informed patient selection. The certainty of the evidence is low, and further research is necessary.

The utility of implantable loop recorders in patient management: an age- and indication-stratified study in the outpatient-implant era.

AIM: Implantable loop recorders (ILRs) are now routinely implanted for long-term cardiac monitoring in the clinical setting. The aim of this study was to examine the real-world performance of these devices focusing on the management changes made in response to ILR-recorded data. METHODS AND RESULTS: This was a single-centre, prospective observational study of consecutive patients undergoing ILR implantation. All patients who underwent implantation of a Medtronic Reveal LINQ device from September 2017 to June 2019 at Barts Heart Centre were included. Five hundred and one patients were included. Three hundred and two (60%) patients underwent ILR implantation for an indication of pre-syncope/syncope, 96 (19%) for palpitations, 72 (14%) for atrial fibrillation (AF) detection with a history of cryptogenic stroke, and 31 (6%) for high risk of serious cardiac arrhythmia. The primary outcome of this study was that an ILR-derived diagnosis altered management in 110 patients (22%). Secondary outcomes concerned subgroup analyses by indication: in patients who presented with syncope/pre-syncope, a change in management resulting from ILR data was positively associated with age [hazard ratio (HR) 1.04, 95% confidence interval 1.02-1.06; P < 0.001] and negatively associated with a normal electrocardiogram at baseline (HR 0.54 [0.31-0.93]; P = 0.03). Few patients (1/57, 2%) aged <40 years in this group underwent device implantation, compared to 19/62 patients (31%) aged 75 years and over (P = 0.0024). Out of 183 (12%) patients, 22 in the 40-74 age range had a device implanted. Among patients who underwent ILR insertion following cryptogenic stroke, 13/72 (18%) had AF detected, leading to a decision to commence anticoagulation. CONCLUSION: These results inform the utility of ILR in the clinical setting. Diagnoses provided by ILR that lead to changes in management are rare in patients under age 40, particularly following syncope, pre-syncope, or palpitations. In older patients, new diagnoses are frequently made and trigger important changes in treatment.

The Use of Electrocardiographic Imaging in Localising the Origin of Arrhythmias During Catheter Ablation of Ventricular Tachycardia.

Non-invasive electrocardiographic imaging (ECGI) is a novel clinical tool for mapping ventricular arrhythmia. Using multiple body surface electrodes to collect unipolar electrograms and conventional medical imaging of the heart, an epicardial shell can be created to display calculated electrograms. This calculation is achieved by solving the inverse problem and allows activation times to be calculated from a single beat. The technology was initially pioneered in the US using an experimental torso-shaped tank. Accuracy from studies in humans has varied. Early data was promising, with more recent work suggesting only moderate accuracy when reproducing cardiac activation. Despite these limitations, the system has been successfully used in pioneering work with non-invasive cardiac radioablation to treat ventricular arrhythmia. This suggests that the resolution may be sufficient for treatment of large target areas. Although untested in a well conducted clinical study it is likely that it would not be accurate enough to guide more discreet radiofrequency ablation.

Dynamic spatial dispersion of repolarization is present in regions critical for ischemic ventricular tachycardia ablation.

BACKGROUND: The presence of dynamic substrate changes may facilitate functional block and reentry in ventricular tachycardia (VT). OBJECTIVE: We aimed to study dynamic ventricular repolarization changes in critical regions of the VT circuit during sensed single extrastimulus pacing known as the Sense Protocol (SP). METHODS: Twenty patients (aged 67 ± 9 years, 17 male) underwent VT ablation. A bipolar voltage map was obtained during sinus rhythm (SR) and right ventricular SP pacing at 20 ms above ventricular effective refractory period. Ventricular repolarization maps were constructed. Ventricular repolarization time (RT) was calculated from unipolar electrogram T waves, using the Wyatt method, as the dV/dtmax of the unipolar T wave. Entrainment or pace mapping confirmed critical sites for ablation. RESULTS: The median global repolarization range (max-min RT per patient) was 166 ms (interquartile range [IQR] 143-181 ms) during SR mapping vs 208 ms (IQR 182-234) during SP mapping (P = .0003 vs intrinsic rhythm). Regions of late potentials (LP) had a longer RT during SP mapping compared to regions without LP (mean 394 ± 40 ms vs 342 ± 25 ms, P < .001). In paired regions of normal myocardium there was no significant spatial dispersion of repolarization (SDR)/10 mm2 during SP mapping vs SR mapping (SDR 11 ± 6 ms vs 10 ± 6 ms, P = .54). SDR/10 mm2 was greater in critical areas of the VT circuit during SP mapping 63 ± 29 ms vs SR mapping 16 ± 9 ms (P < .001). CONCLUSION: Ventricular repolarization is prolonged in regions of LP and increases dynamically, resulting in dynamic SDR in critical areas of the VT circuit. These dynamic substrate changes may be an important factor that facilitates VT circuits.