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The purpose of this study was to assess the performance and limitations of low-voltage zones (LVZ) localization by optimized late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) scar imaging in patients with cardiac implantable electronic devices (CIEDs).Scar evaluation by LGE-CMR can assist ventricular tachycardia (VT) ablation, but challenges with electroanatomical maps coregistration and presence of imaging artefacts from CIED limit accuracy.A total of 10 patients underwent VT ablation and preprocedural LGE-CMR using wideband imaging. Scar was segmented from CMR pixel signal intensity maps using commercial software (ADAS-VT, Galgo Medical) with bespoke tools and compared with detailed electroanatomical maps (CARTO). Coregistration of EP and imaging-derived scar was performed using the aorta as a fiducial marker, and the impact of coregistration was determined by assessing intraobserver/interobserver variability and using computer simulations. Spatial smoothing was applied to assess correlation at different spatial resolutions and to reduce noise.Pixel signal intensity maps localized low-voltage zones (V 1.5 mV) with area under the receiver-operating characteristic curve: 0.82 (interquartile range [IQR]: 0.76-0.83), sensitivity 74% (IQR: 71%-77%), and specificity 78% (IQR: 73%-83%) and correlated with bipolar voltage (r = -0.57 [IQR: -0.68 to -0.42]) across patients. In simulations, small random shifts and rotations worsened LVZ localization in at least some cases. The use of the full aortic geometry ensured high reproducibility of LVZ localization (r0.86 for area under the receiver-operating characteristic curve). Spatial smoothing improved localization of LVZ. Results for LVZ with V 0.5 mV were similar.In patients with CIEDs, novel wideband CMR sequences and personalized coregistration strategies can localize LVZ with good accuracy and may assist VT ablation procedures.

Aims Many cardiac pacemakers and defibrillators are not approved by regulators for magnetic resonance imaging (MRI). Even following generator exchange to an approved magnetic resonance (MR)-conditional model, many systems remain classified ‘non-MR conditional’ due to the leads. This classification makes patient access to MRI challenging, but there is no evidence of increased clinical risk. We compared the effect of MRI on non-MR conditional and MR-conditional pacemaker and defibrillator leads. Methods and results Patients undergoing clinical 1.5T MRI with pacemakers and defibrillators in three centres over 5 years were included. Magnetic resonance imaging protocols were similar for MR-conditional and non-MR conditional systems. Devices were interrogated pre- and immediately post-scan, and at follow-up, and adverse clinical events recorded. Lead parameter changes peri-scan were stratified by MR-conditional labelling. A total of 1148 MRI examinations were performed in 970 patients (54% non-MR conditional systems, 39% defibrillators, 15% pacing-dependent) with 2268 leads. There were no lead-related adverse clinical events, and no clinically significant immediate or late lead parameter changes following MRI in either MR-conditional or non-MR conditional leads. Small reductions in atrial and right ventricular sensed amplitudes and impedances were similar between groups, with no difference in the proportion of leads with parameter changes greater than pre-defined thresholds (7.1%, 95% confidence interval: 6.1–8.3). Conclusions There was no increased risk of MRI in patients with non-MR conditional pacemaker or defibrillator leads when following recommended protocols. Standardizing MR conditions for all leads would significantly improve access to MRI by enabling patients to be scanned in non-specialist centres, with no discernible incremental risk.

Obesity is a risk factor for heart failure (HF), but its presence among HF patients may be associated with favorable outcomes. We investigated the long-term outcomes across different body mass index (BMI) groups, after cardiac resynchronization therapy (CRT), and whether defibrillator back-up (CRT-D) confers survival benefit. One thousand two-hundred seventy-seven (1,277) consecutive patients (mean age: 67.0 ± 12.7 years, 44.1% women, and mean BMI: 28.3 ± 5.6 Kg/m2) who underwent CRT implantation in 5 centers between 2000-2014 were followed-up for a median period of 4.9 years (IQR 2.4 to 7.5). More than 10% of patients had follow-up for ≥10 years. Patients were classified according to BMI as normal: 75% of patients, but were used less frequently in obese individuals. The composite endpoint of all-cause mortality or cardiac transplant/left ventricular assist device (LVAD) occurred in 50.9% of patients. At 10-year follow-up, less than a quarter of patients in the lowest and highest BMI categories were still alive and free from heart transplant/LVAD. After adjustment BMI of 25 to 29.9 Kg/m2 (HR = 0.73 [95%CI 0.56 to 0.96], p = 0.023) and use of CRT-D (HR = 0.74 [95% CI 0.55 to 0.98], p = 0.039) were independent predictors of survival free from LVAD/heart transplant. BMI of 25 to 29.9 Kg/m2 at the time of implant was independently associated with favourable long-term 10-year survival. Use of CRT-D was associated with improved survival irrespective of BMI class.

Background The value of antitachycardia pacing (ATP) in the overall cohort of primary prevention patients who receive implantable cardioverter-defibrillators (ICDs) remains uncertain. ATP success reported in prior trials potentially included a large number of patients receiving unnecessary ATP for arrhythmias that may have self-terminated owing to the prematurity of the intervention. Although some patients derive benefit from initial ATP in terminating rapid ventricular arrhythmias and thereby preventing shocks, there are limited data allowing us to identify those patients a priori. Objective The purpose of APPRAISE ATP is to understand the role of ATP in primary prevention patients currently indicated for ICD therapy in a large prospective randomized controlled trial with modern programming parameters. Methods The study is a global, prospective, randomized, multicenter clinical trial conducted at up to 150 sites globally, enrolling approximately 2600 subjects The primary endpoint of the trial is time to first all-cause shock in a 2-arm study with an equivalent study design in which the incidence of all-cause shocks will be compared between primary prevention subjects programmed with shocks only vs subjects programmed to standard therapy (ATP and shock). Results An Electrogram and Device Interrogation Core Laboratory will review interrogation data to determine primary endpoints that occur in APPRAISE ATP. Their decisions are based on independent physician review of the data from device interrogation. Conclusion The ultimate purpose of the study is to aid clinicians in the selection of ICD technologies based on hard endpoint evidence across the spectrum of indications for primary prevention implantation.

Background Inhomogeneity of ventricular contraction is associated with sudden cardiac death, but the underlying mechanisms are unclear. Alterations in cardiac contraction impact electrophysiological parameters through mechanoelectric feedback. This has been shown to promote arrhythmias in experimental studies, but its effect in the in vivo human heart is unclear. Objective The purpose of this study was to quantify the impact of regional myocardial deformation provoked by a sudden increase in ventricular loading (aortic occlusion) on human cardiac electrophysiology. Methods In 10 patients undergoing open heart cardiac surgery, left ventricular (LV) afterload was modified by transient aortic occlusion. Simultaneous assessment of whole-heart electrophysiology and LV deformation was performed using an epicardial sock (240 electrodes) and speckle-tracking transesophageal echocardiography. Parameters were matched to 6 American Heart Association LV model segments. The association between changes in regional myocardial segment length and activation-recovery interval (ARI; a conventional surrogate for action potential duration) was studied using mixed-effect models. Results Increased ventricular loading reduced longitudinal shortening (P = .01) and shortened ARI (P = .02), but changes were heterogeneous between cardiac segments. Increased regional longitudinal shortening was associated with ARI shortening (effect size 0.20 [0.01–0.38] ms/%; P = .04) and increased local ARI dispersion (effect size –0.13 [–0.23 to –0.03] ms/%; P = .04). At the whole organ level, increased mechanical dispersion translated into increased dispersion of repolarization (correlation coefficient r = 0.81; P = .01). Conclusion Mechanoelectric feedback can establish a potentially proarrhythmic substrate in the human heart and should be considered to advance our understanding and prevention of cardiac arrhythmias.

Purpose of the StudyTo characterise the documentation of working diagnoses and their associated level of certainty by clinicians assessing patients referred to the medical team from the emergency department.DesignThis was a single centre retrospective cohort study of non-consultant grade clinicians at the Royal London Hospital, Barts Health NHS Trust between 01/03/19 to 31/03/19. De-identified electronic health record data was collected to include the type of diagnosis documented (clinical, laboratory result or symptom/sign defined) and the certainty adjective used for single diagnoses. Presence or absence of diagnostic uncertainty was collected for multiple diagnoses.Results865 medical assessments were recorded during the study period. 850 were available for further analysis. 420 presented a single diagnosis while 430 presented multiple diagnoses. Of the 420 single diagnoses, 67 (16%) were documented as either a symptom or physical sign, and 16 (4%) were laboratory-result defined diagnoses. No uncertainty was expressed in 309 (74%) of the diagnoses. Of 430 multiple diagnoses, uncertainty was expressed in 346 (80%) compared to 84 (20%) in which no uncertainty was expressed.ConclusionThe documentation of working diagnoses is highly variable amongst non-consultant grade clinicians assessing patients admitted via the emergency department. In nearly three quarters of assessments with single diagnoses, no element of uncertainty was implied or quantified. More uncertainty was expressed in multiple diagnoses than single diagnoses however documentation style was heterogenous. These data have implications for prospective studies examining the quantification of diagnostic certainty and its association with important process or outcome measures.What is already known on this subject-The factors which influence medical decision-making is almost exclusively assessed by vignettes, simulations or retrospective questionnaires. The certainty or confidence level of a clinician in making a decision can be a source of bias which can lead to patient harm if their confidence is miscalibrated with their accuracy.-A recent review assessing real world studies of decision-making found only nine, all of which used a Likert or visual analogue scaleMain messages-The documentation of working diagnoses is highly variable amongst non-consultant grade clinicians-In nearly three quarters of assessments with single diagnoses, no element of uncertainty was implied or quantified-Existing documentation is too heterogeneous to meaningfully analyse in a quantitative manner – increased standardisation will allow leveraging of electronic health record platforms to become better educational and research tools for clinicians and educators.

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., Graphical abstract

The number of patients of reproductive age with inherited and congenital heart disease receiving implantable cardiac defibrillators (ICD) is steadily increasing. Safely and effectively coordinating pregnancy in this high-risk cohort is important to optimise maternal-foetal outcomes. As members of the multidisciplinary team caring for pregnant patients with indications for ICD, cardiologists and electrophysiologists should be aware of the considerations and nuances involved in managing these patients. This article reviews the pathophysiology of arrhythmias, ICD implantation considerations, novel minimal fluoroscopy techniques and subcutaneous ICD. In addition, antenatal and device management during pregnancy and delivery are discussed.Die Zahl der Patientinnen im gebärfähigen Alter mit erblichen und angeborenen Herzerkrankungen sowie mit implantierbaren Defibrillatoren („implantable cardiac defibrillators“ [ICD]) nimmt stetig zu. Die sichere und effektive Begleitung einer Schwangerschaft in dieser Hochrisikokohorte ist notwendig für ein optimales Ergebnis hinsichtlich Mutter und Fetus. Als Mitglieder des multidisziplinären Teams, die schwangere Patientinnen mit Indikationen für ICD betreuen, sollten sich Kardiologen und Elektrophysiologen aller Besonderheiten dieser Patientinnen bewusst sein. Der vorliegende Beitrag befasst sich mit der Pathophysiologie von Arrhythmien, Überlegungen zur ICD-Implantation, neuartigen Techniken der „minimalen Fluoroskopie“ und subkutanen ICD. Darüber hinaus werden die Schwangerschaftsvorsorge sowie die Device-Handhabung während Schwangerschaft und Geburt diskutiert.

Aims Atrial fibrillation (AF) is common in hypertrophic cardiomyopathy (HCM). Data on the efficacy of catheter ablation of AF in HCM patients are sparse. Methods and results Observational multicentre study in 137 HCM patients (mean age 55.0 ± 13.4, 29.1% female; 225 ablation procedures). We investigated (i) the efficacy of catheter ablation for AF beyond the initial 12 months; (ii) the available risk scores, stratification schemes and genotype as potential predictors of arrhythmia relapse, and (iii) the impact of cryoballoon vs. radiofrequency in procedural outcomes. Mean follow-up was 43.8 ± 37.0 months. Recurrences after the initial 12-month period post-ablation were frequent, and 24 months after the index procedure, nearly all patients with persistent AF had relapsed, and only 40% of those with paroxysmal AF remained free from arrhythmia recurrence. The APPLE score demonstrated a modest discriminative capacity for AF relapse post-ablation (c-statistic 0.63, 95% CI 0.52–0.75; P = 0.022), while the risk stratification schemes for sudden death did not. On multivariable analysis, left atrium diameter and LV apical aneurysm were independent predictors of recurrence. Fifty-eight patients were genotyped; arrhythmia-free survival was similar among subjects with different gene mutations. Rate of procedural complications was high (9.3%), although reducing over time. Outcome for cryoballoon and radiofrequency ablation was comparable. Conclusion Very late AF relapses post-ablation is common in HCM patients, especially in those with persistent AF. Left atrium size, LV apical aneurysm, and the APPLE score might contribute to identify subjects at higher risk of arrhythmia recurrence. First-time cryoballoon is comparable with radiofrequency ablation.

A significant proportion of patients undergoing catheter ablation for atrial fibrillation (AF) experience arrhythmia recurrence. This is mostly due to pulmonary vein reconnection (PVR). Whether mapping using High-Density Wave (HDW) technology is superior to standard bipolar (SB) configuration at detecting PVR is unknown. We aimed to evaluate the efficacy of HDW technology compared to SB mapping in identifying PVR. High-Density (HD) multipolar Grid catheters were used to create left atrial geometries and voltage maps in 36 patients undergoing catheter ablation for AF (either due to recurrence of an atrial arrhythmia from previous AF ablation or de novo AF ablation). Nineteen SB maps were also created and compared. Ablation was performed until pulmonary vein isolation was achieved. Median time of mapping with HDW was 22.3 [IQR: 8.2] min. The number of points collected with HDW (13299.6±1362.8 vs 6952.8±841.9, p

Objectives The goal of this study was to evaluate the role of dynamic substrate changes in facilitating conduction delay and re-entry in ventricular tachycardia (VT) circuits. Background The presence of dynamic substrate changes facilitate functional block and re-entry in VT but are rarely studied as part of clinical VT mapping. Methods Thirty patients (age 67 ± 9 years; 27 male subjects) underwent ablation. Mapping was performed with the Advisor HD Grid multipolar catheter. A bipolar voltage map was obtained during sinus rhythm (SR) and right ventricular sense protocol (SP) single extra pacing. SR and SP maps of late potentials (LP) and local abnormal ventricular activity (LAVA) were made and compared with critical sites for ablation, defined as sites of best entrainment or pace mapping. Ablation was then performed to critical sites, and LP/LAVA identified by the SP. Results At a median follow-up of 12 months, 90% of patients were free from antitachycardia pacing (ATP) or implantable cardioverter-defibrillator shocks. SP pacing resulted in a larger area of LP identified for ablation (19.3 mm2 vs. 6.4 mm2) during SR mapping (p = 0.001), with a sensitivity of 87% and a specificity of 96%, compared with 78% and 65%, respectively, in SR. Conclusions LP and LAVA observed during the SP were able to identify regions critical for ablation in VT with a greater accuracy than SR mapping. This may improve substrate characterization in VT ablation. The combination of ablation to critical sites and SP-derived LP/LAVA requires further assessment in a randomized comparator study., Central Illustration

Background The subcutaneous implantable cardioverter-defibrillator (S-ICD) is an alternative to conventional transvenous ICD (TV-ICD) therapy to reduce lead complications. Objective To evaluate outcomes in channelopathy vs patients with structural heart disease in the EFFORTLESS-SICD Registry and with a previously reported TV-ICD meta-analysis in channnelopathies. Methods The EFFORTLESS registry includes 199 patients with channelopathies (Brugada syndrome 83, long QT syndrome 24, idiopathic ventricular fibrillation 78, others 14) and 786 patients with structural heart disease. Results Channelopathy patients were younger (39 ± 14 years vs 51 ± 17 years; P < .001) with left ventricular ejection fraction 59% ± 9% vs 41% ± 18% (P < .001). The complication rate (follow-up: 3.2 ± 1.5 years vs 3.0 ± 1.5 years) was similar: 13.6% vs 11.2% (P = .42). Appropriate shocks rates were 9.5% vs 10.8% (P = .70), with shocks for monomorphic ventricular tachycardia being 2.0% vs 6.9% (P < .02) and for polymorphic ventricular tachycardia/ventricular fibrillation (VT/VF) 8.0% vs 5.7% (P = .30). Conversion effectiveness of VT/VF episodes was similar: 36 of 37 (97.3%) vs 151 of 155 (97.4%, P = .59). VT/VF storm event (2% vs 0.9%, P = .33) and lower inappropriate shock (IAS) (8.5% vs 12.5%, P = .12) rates were statistically similar between channelopathy and non-channelopathy patients, with 45.5% channelopathy vs 31.4% non-channelopathy patients managed with a conditional zone > 200 beats per minute (P = .0002). Annualized appropriate shock, IAS, and complication rates appear to be lower for the S-ICD vs meta-analysis TV-ICD patients, particularly lead complications. Conclusion EFFORTLESS demonstrates similar S-ICD efficacy and a nonsignificant, lower rate of IAS in channelopathy patients as compared to structural heart disease. Comparable IAS rates were achieved with the device programmed to higher rates for channelopathy patients., Graphical abstract

Introduction The frequency of catheter ablation for atrial fibrillation (AF) has increased dramatically, stretching resources. Discharge on the same day as treatment may increase the efficiency and throughput. There are limited data regarding the safety of this strategy. Methods We performed a retrospective analysis of consecutive patients undergoing AF ablation in a tertiary centre and in a district general hospital, and identified those discharged on the same day of treatment. The safety endpoint was any complication and/or presentation to hospital in the 48-hours and at 30 days post discharge. We performed an economic analysis to calculate potential cost saving. Results Among a total population of 2628 patients, we identified 727 subjects (61.1±12.5 years, 69.6% male) undergoing day-case AF ablation. Cryoballoon technique was used in 79.2% of the day-cases, and 91.6% of the procedures were performed under conscious sedation. 1.8% (13) of the participants met the safety composite endpoint at 48-hour, however only 0.7% (5) required at least one day of hospitalisation. Bleeding/haematoma at the femoral access site (0.5%) and pericarditic chest pain (0.5%) were the main reasons for readmission. None experienced cardiac tamponade or other life-threatening complications in the 48-hours post-discharge. Overall rate of complication and/or presentation to hospital at 30 days was 3.7%. Our day-case policy resulted in an annual cost-saving of approximately of £83,927 for our hospital. Conclusion In this large multicentre cohort, same-day discharge in selected patients following AF ablation appears to be safe and cost-effective, with a very low rate of early readmission or post-discharge complication. This article is protected by copyright. All rights reserved.

Atrial Fibrillation (AF) is a growing public health issue, associated with significant morbidity and mortality. In addition to pharmacological therapy, catheter ablation is an effective strategy in restoring and maintaining sinus rhythm. However, ablation is not without risk, and AF recurs in a significant proportion of patients. Non-invasive, easily accessible markers or indices that could stratify patients depending on the likelihood of a successful outcome following ablation would allow us to select the most appropriate patients for the procedure, reducing the AF recurrence rate and exposure to potentially life-threatening risks. : There has been much attention paid to Brain Natriuretic Peptide (BNP) and N-Terminal prohormone of Brain Natriuretic Peptide (NT-proBNP) as possible predictive markers of successful ablation. Several studies have demonstrated an association between higher pre-ablation levels of these peptides, and a greater likelihood of AF recurrence. Therefore, there may be a role for measuring brain natriuretic peptides levels when selecting patients for catheter ablation.

Introduction Patients with hypertrophic cardiomyopathy (HCM) and atrial fibrillation (AF) require chronic anticoagulation due to high thromboembolic risk. Evidence supporting the use of non-vitamin K oral anticoagulants (NOACs) in patients with HCM remains sparse, and there are no data regarding the use of NOACs in patients with HCM undergoing catheter ablation of AF. Methods Observational nonrandomized study in four European centers. We aimed to investigate the safety and efficacy of NOACs compared with vitamin K antagonists (VKAs) in patients with HCM undergoing catheter ablation for AF. Results A total of 137 patients with HCM (mean age: 55.0 ± 13.4, 29.1% female) underwent 230 catheter ablations for AF (1.7 ± 1.0 per patient). A total of 55 patients (39.4%) underwent 70 procedures (30.4%) on NOAC, while the remaining were on VKA. Warfarin (97.6%) and rivaroxaban (56.4%) were the most frequently used agents in the respective groups. No procedure-related deaths were reported. We observed no significant difference in the rate of thromboembolism (VKA: 0.6%; NOAC: 0%; p = 1.0) or minor bleeding (VKA: 0.6%; NOAC: 1.4%; p = .54). There was a nonsignificant trend towards a lower incidence of major bleeding (VKA: 6.9%; NOAC: 1.4%; p = .09). Conclusion These preliminary data suggest that NOACs are at least as safe and effective as VKAs in patients with HCM undergoing catheter ablation for AF.

BACKGROUND: The long term performance of the Riata family of leads has recently come under increasing scrutiny. We aimed to determine the long term performance of the Riata 1580 leads compared with Endotak 0158 leads. METHODS: All patients with Riata 1580 or Endotak 0158 leads implanted from 2003-2008 at the Heart Hospital, UCLH were analysed. Significant electrical changes were: threshold increase >1V at a set pulse width between pacing checks, persistent R wave fall to 50%, noise, pacing impedance change to 1500 Ω, HV change to 200Ω, HV change ± 15Ω, pacing impedance change > 400Ω over 12 months. RESULTS: 333 Riata and 356 Endotak leads were implanted. Median follow up time + interquartile range, after exclusion of censored events including loss to follow up: Riata 3652 + 655 days, Endotak 3730 + 810 days. A total of 51 (15.9%) Riata leads and 21 (6.3%) Endotak leads were affected. A greater risk of failure was found for the Riata lead compared with the Endotak lead (p = 0.0001). An additional time-dependent effect was found, with the Riata lead 1.9 times more likely to fail in the first 6 years following lead implantation and 5.3 times more likely to fail after 6 years. CONCLUSIONS: Riata leads have a higher risk of failure compared to Endotak leads over time. The importance of careful ongoing performance surveillance late in the leads' lifetime is reflected in this ten year follow up study. This article is protected by copyright. All rights reserved.

Background Infection is a well‐recognized complication of cardiovascular implantable electronic device (CIED) implantation, including the more recently available subcutaneous implantable cardioverter‐defibrillator (S‐ICD). Although the AHA/ACC/HRS guidelines include recommendations for S‐ICD use, currently there are no clinical trial data that address the diagnosis and management of S‐ICD infections. Therefore, an expert panel was convened to develop consensus on these topics. Methods A process mapping methodology was used to achieve a primary goal – the development of consensus on the diagnosis and management of S‐ICD infections. Two face‐to‐face meetings of panel experts were conducted to recommend useful information to clinicians in individual patient management of S‐ICD infections. Results Panel consensus of a stepwise approach in the diagnosis and management was developed to provide guidance in individual patient management. Conclusion Achieving expert panel consensus by process mapping methodology in S‐ICD infection diagnosis and management was attainable, and the results should be helpful in individual patient management.

Introduction Use of non-vitamin K oral anticoagulants (NOACs) has rapidly increased worldwide. We aimed to systematically assess the available evidence regarding the safety and efficacy of NOACs in patients undergoing cardiac implantable electronic device (CIED) surgery. Methods We performed a systematic literature search. Eligible randomised controlled trials and cohort studies were included. The primary outcome measures were clinically significant device-pocket haematoma and thromboembolic events. Results A total of 12 studies were included, equating to 2120 patients. The separate pooling of rate of events showed a low incidence of clinically significant device-pocket haematoma, although numerically higher in patients on continued (1.5%; CI95%0.8–3.0) versus interrupted NOAC (0.9%; CI95%0.5–1.7). The rate of any device-pocket haematoma was numerically higher in the continued versus interrupted NOAC group (5.4%; CI95%3.8–7.7 versus 2.4%; CI95%1.8–3.3). The incidence of thromboembolic events (0.4%; CI95%0.2–0.8) was low and comparable. From a meta-analysis of 3 studies (equating to 773 subjects) allowing for a comparison of continued versus interrupted NOAC, we found no significant difference between the 2 strategies in terms of clinically significant pocket haematoma (RR1.14; CI95%0.43–3.06, p = 0.79), thromboembolic complications (RR1.03; CI95%0.06–16.37, p = 0.98), and any pocket haematoma (RR1.19; CI95%0.65–2.20, p = 0.57). Conclusion Use of NOACs at the time of CIEDs surgery appears to be safe, and either strategy of peri-procedure continuation or interruption might be reasonable. However, continuation of NOAC seems to be associated with a numerically higher rate of bleeding complications. Certainty of the evidence is low, and further studies are required to confirm these findings.

Background Noninvasive mapping identifies potential drivers (PDs) in atrial fibrillation (AF). We analyzed the impact of pulmonary vein isolation (PVI) on PDs and whether baseline PD pattern predicted termination of AF. Methods Patients with persistent AF less than 2 years underwent electrocardiographic imaging mapping before and after cryoballoon PVI. We recorded the number of PD occurrences, characteristics (rotational wavefronts ≥ 1.5 revolutions or focal activations), and distribution using an 18-segment atrial model. Results Of 100 patients recruited, PVI terminated AF in 15 patients; 21.3% ± 9.1% (8.7 ± 4.8) of PDs occurred at the pulmonary veins (PVs) and posterior wall. PVI had no impact on PD occurrences outside the PVs and posterior wall (33.2 ± 12.9 vs 31.6 ± 12.5; P = .164), distribution over the remaining 13 segments (9 [8-11] vs 9 [8-10]; P = .634), the proportion of PDs that was rotational (82.9% ± 9.7% vs 83.6% ± 10.1%; P = .496), or temporal stability (2.4 ± 0.4 vs 2.4 ± 0.5 rotations; P = .541). Fewer focal PDs (area under the curve, 0.683; 95% CI, 0.528-0.839; P = .024) but not rotational PDs (P = .626) predicted AF termination with PVI. Conclusions PVI did not have a global impact on PDs outside the PVs and posterior wall. Although fewer focal PDs predicted termination of AF with PVI, the burden of rotational PDs did not. It is accepted though not all PDs are necessarily real or important. Outcome data are needed to confirm whether noninvasive mapping can predict patients likely to respond to PVI.

The aim of this systematic review was to evaluate randomized clinical trials (RCTs) of cardiac catheter ablation (CCA) and to assess the prevalence, characteristics and reporting standards of clinically relevant patient-reported outcome measures (PROMs). Electronic database searches of Medline, Embase, CENTRAL, and the WHO Trial Registry were conducted in March 2019. The study protocol was registered on PROSPERO (CRD42019133086). Of 7125 records identified, 237 RCTs were included for analysis, representing 35 427 patients with a mean age of 59 years. Only 43 RCTs (18%) reported PROMs of which 27 included a generic PROM that measured health-related quality of life (HRQL) necessary to conduct comparative effectiveness research. There was notable under-representation of certain patient groups—only 31% were women and only 8% were of non-Caucasian ethnicity, in trials which reported such data. The reporting standard of PROMs was highly variable with 8–62% adherence against CONSORT PRO-specific items. In summary, PROMs play a crucial role in determining the clinical and cost-effectiveness of treatments which primarily offer symptomatic improvement, such as CCA. Their underuse significantly limits evaluation of the comparative effectiveness of treatments. Using CCA as an exemplar, there are additional issues of infrequent assessment, poor reporting and under-representation of many population groups. Greater use of PROMs, and specifically validated HRQL questionnaires, is paramount in giving patients a voice in studies, generating more meaningful comparisons between treatments and driving better patient-centred clinical and policy-level decision-making.

Background Maintenance of sinus rhythm is challenging in patients with longstanding persistent atrial fibrillation (PeAF). Minimally invasive surgical AF ablation may improve outcomes when combined with catheter ablation (the ‘convergent’ procedure). This study evaluates the safety and efficacy of the convergent procedure versus catheter ablation alone in longstanding PeAF. Methods 43 consecutive patients with longstanding PeAF underwent subxiphoid endoscopic ablation of the posterior left atrium followed by catheter ablation from 2013 to 2018. The primary outcome was AF-free survival at 12 months; secondary outcomes included change in EHRA class, echocardiographic data, procedural complications, freedom from anti-arrhythmic drugs (AADs), and long term arrhythmia-free survival. Outcomes were compared with a matched group of 43 patients who underwent catheter ablation alone. Both groups underwent multiple catheter ablations as required. Baseline characteristics were similar between groups. Results After 12 months, the convergent procedure was associated with increased AF-free survival on AADs (60.5% versus 25.6%, p = .002) and off AADs (37.2% versus 13.9%, p = .025), versus catheter ablation. Allowing for multiple procedures, after 30.5 ± 13.3 months' follow-up the convergent procedure was associated with increased arrhythmia-free survival on AADs (58.1% versus 30.2%, p = .016) and off AADs (32.5% versus 11.6%, p = .036) versus catheter ablation. There were more complications in the convergent procedure group (11.6% versus 2.3%, p = .2). Multivariate analysis identified only the convergent procedure (OR 3.06 (1.23–7.6), p = .017) as predictive of arrhythmia-free survival long term. Conclusions In longstanding PeAF, the convergent procedure is associated with improved arrhythmia-free survival versus catheter ablation alone. Complication rates are significant but have been shown to depreciate with experience.

Type-2 diabetes mellitus (DM) is associated with an increased risk of atrial fibrillation (AF). It is unclear whether DM is a risk factor for arrhythmia recurrence following catheter ablation of AF. We performed a nonrandomised, observational study in 7 high-volume European centres. A total of 2,504 patients who underwent catheter ablation of AF were included, and procedural outcomes were compared among patients with or without DM. Patients with DM (234) accounted for 9.3% of the sample, and were significantly older, had a higher BMI and suffered more frequently from persistent AF. Arrhythmia relapses at 12 months after AF ablation occurred more frequently in the DM group (32.0% vs 25.3%, p = 0.031). After adjusting for type of AF (i.e., paroxysmal vs persistent), during a median follow-up of 17 ± 16 months, atrial arrhythmia free-survival was lower in the diabetics with persistent AF (log-rank p = 0.003), and comparable for paroxysmal AF (log-rank p = 0.554). These results were confirmed in a propensity-matched analysis, and DM was also an independent predictor of AF recurrence on the multivariate analysis (hazard ratio 1.39; 95% confidence interval 95%1.07 to 1.88; p = 0.016). There was no significant difference in the rate of periprocedural complications among DM and non-DM patients (3.8% vs 6.3%, p = 0.128). Efficacy and safety of cryoballoon ablation were comparable to radiofrequency ablation in both DM and no-DM groups. In conclusion, catheter ablation of AF appears to be safe in patients with DM. However, DM is associated with higher rate of atrial arrhythmia relapse, particularly for patients with persistent AF.

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Catheter ablation for supraventricular tachycardia (SVT) in adults with congenital heart disease (ACHD) is an important therapeutic option. Cavo-tricuspid isthmus (CTI)-dependent intraatrial re-entrant tachycardia (IART) is common. However, induction of sustained tachycardia at the time of ablation is not always possible. We hypothesised that performing an empiric CTI line in case of non-inducibility leads to good outcomes. Long-term outcomes of empiric versus entrained CTI ablation in ACHD patients were examined. Retrospective, single-centre, case-control study over 7 years. Arrhythmia-free survival after empiric versus entrained CTI ablation was compared. Eighty-seven CTI ablations were performed in 85 ACHD patients between 2010 and 2017. The mean age of the cohort was 43 years and 48% were male. Underlying aetiology included ASD (31%), VSD (11.4%), AVSD (9.1%), AVR (4.8%), Fallot’s (18.4%), Ebstein’s (2.3%), Fontan’s palliation (9.2%) and atrial switch (13.8%). CTI-dependent IART was entrained in 59 patients whereas it was non-inducible in 28. The latter had an empiric CTI ablation. Forty-three percent of procedures were performed under general anaesthesia. There were no reported procedural complications. There was no significant difference in the mean procedure or fluoroscopy times between the groups (empiric vs entrained CTI; 169.1 vs 183.3 and 28.1 vs 19.9 min). Arrhythmia-free survival was 64.3% versus 72.8% (p value 0.44) in the empiric and entrained groups at 21 months follow-up. Long-term outcomes after empiric and entrained CTI ablation for IART in ACHD patients are comparable. This is a safe and effective therapeutic option. In the case of non-inducibility of IART, an empiric CTI line should be considered in this cohort.

Hemodynamically unstable ventricular tachycardia (VT) is a critical cardiac arrhythmia associated with hemodynamic compromise that requires immediate cardioversion to prevent sudden cardiac death. Since unnecessary cardioverter defibrillators shocks damage the heart and increase the risk of mortality, the discrimination between unstable (i.e. requiring cardioversion) and stable (i.e. not requiring cardioversion) VT is of paramount importance. The aim of this study was to propose and assess non-invasive identification of hemodynamically unstable VT using photoplethysmography (PPG). Seventy-five (n = 75) episodes of VT were recorded in 14 patients undergoing invasive electrophysiological studies for VT catheter ablation. Invasive continuous arterial blood pressure (ABP), PPG and electrocardiogram (ECG) were simultaneously recorded. VTs were classified as unstable if during the first 10 seconds from onset, the mean ABP (P̅VT VT) was P̅VT VT dropped more than 30% with respect to a 10 seconds baseline (i.e. ratio RABP VT VT VT ABP ABP

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization (QRS duration) and repolarization (JT interval). Abnormalities of the QT interval are associated with potentially fatal ventricular arrhythmia. We conducted genome-wide multi-ancestry analyses in >250,000 individuals and identified 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identified associations with Mendelian disease genes. Enrichments were observed in established pathways for QT and JT, with new genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast, connective tissue components and processes for cell growth and extracellular matrix interactions were significantly enriched for QRS. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlighted potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.

Background Cardiac implantable electronic device (CIED) implantation rates, as well as the clinical and procedural characteristics and outcomes in patients with known active COVID-19 are unknown. Objective To gather information regarding CIED procedures during active COVID-19, performed with personal protective equipment, based on an international survey. Methods Fifty-three centers from 13 countries across 4 continents provided information on 166 patients with known active COVID-19 who underwent a CIED procedure. Results CIED procedure rate in 133,655 hospitalized COVID-19 patients ranged from 0 to 16.2 per 1000 patients (p, Graphical abstract

A 52-year-old gentleman with a subcutaneous implantable defibrillator (S-ICD) implanted in 2015 for primary prevention and a background of hypertrophic cardiomyopathy presented via remote monitoring alert (Boston Scientific Latitude NXT) with an aborted charge episode. The episode showed myopotential noise with baseline wander, and an urgent outpatient follow up was arranged. Upon investigation the S-ICD lead had retracted to the pocket of the generator via a reel mechanism, wrapping the lead around the can. This was likely to be caused by insufficient suturing of the lead collar at the base of xiphisternum. The device had automatically disabled the SmartPass filter, which does not currently have an alert mechanism. This case highlights the rare occurrence of S-ICD lead displacement and components of the SmartPass system which can provide an early warning to lead problems. This article is protected by copyright. All rights reserved.

Background: We aimed to evaluate atrial fibrillation occurrence, reasons for healthcare visits, mortality, causes of death and examined patterns by relative deprivation in the UK. Methods: To study the atrial fibrillation (AF) incidence, mortality and case-fatality, we implemented a prospective cohort study with the linked electronic health records of 5.6 million population in the United Kingdom Clinical Practice Research Datalink from 1998 to 2016. A matched case-control study was used to investigate causes of hospitalisation and death comparing individuals with and without incident AF. Results: During a median follow-up of 10.3 years, 199,433(3.6%) patients developed incident AF. Increased risk of hospitalisation for heart failure, cardiovascular conditions and infection was present among patients who later developed AF. Following an AF diagnosis, patients were frequently admitted to the hospital for heart failure, lower respiratory tract infection, chronic obstructive pulmonary disease and ischemic heart disease. One in 5 AF patients died during the first year after diagnosis, and the mortality increased to 42.7% at the fifth year. The excess deaths in AF cases compared to controls may result from cardiovascular diseases, infection and metabolic disorders. Individuals from areas with higher deprivation in socioeconomic and living status had both higher AF incidence and fatality. Interpretation: We observed an elevated risk of hospitalisation for cardiovascular or respiratory diseases among incident AF patients, and the considerable disparity in AF burden by socioeconomic deprivation informs priorities for prevention and provision of patient care. Funding: The study was supported by the GlaxoSmithKline, University College London Hospital and National Institute for Health Research. The funders did not have any role in study design, data collection, data analysis, interpretation, and writing of the report.

Background and Significance: Mechanical alternans (MA) is a biomarker associated with mortality and life-threatening arrhythmias in heart failure patients. Despite showing prognostic value, its use is limited by the requirement of measuring the continuous blood pressure (BP), which is costly and impractical. Objective: To develop and test, for the first time, non-invasive MA surrogates based on photoplethysmography (PPG). Methods: Continuous BP and PPG were recorded during clinical procedures and tests in 35 patients. MA was induced either by ventricular pacing (Group A, N = 19) or exercise (Group B, N = 16). MA was categorized as sustained or intermittent if MA episodes were observed in at least 20 or between 12 and 20 consecutive beats, respectively. Eight features characterizing the pulse morphology were derived from the PPG, and MA surrogates were evaluated. Results: Sustained alternans was observed in 9 patients (47%) from Group A, whereas intermittent alternans was observed in 13 patients (68%) from Group A and in 10 patients (63%) from Group B. The PPG-based MA surrogate showing the highest accuracy, $V^{\prime}_{M}$ , was based on the maximum of the first derivative of the PPG pulse. It detected both sustained and intermittent MA with 100% sensitivity and 100% specificity in Group A and intermittent MA with 100% sensitivity and 83% specificity in Group B. Furthermore, the magnitudes of MA and its PPG-based surrogate were linearly correlated ( R 2 = 0.83, p . Conclusion: MA can be accurately identified non-invasively through PPG analysis. This may have important clinical implications for risk stratification and remote monitoring.

Introduction: Implantable loop recorders (ILR) are predominantly implanted by cardiologists in the catheter laboratory. We developed a nurse‐delivered service for the implantation of LINQ (Medtronic; Minnesota) ILRs in the outpatient setting. This study compared the safety and cost‐effectiveness of the introduction of this nurse‐delivered ILR service with contemporaneous physician‐led procedures. / Methods: Consecutive patients undergoing an ILR at our institution between 1st July 2016 and 4th June 2018 were included. Data were prospectively entered into a computerized database, which was retrospectively analyzed. / Results: A total of 475 patients underwent ILR implantation, 271 (57%) of these were implanted by physicians in the catheter laboratory and 204 (43%) by nurses in the outpatient setting. Six complications occurred in physician‐implants and two in nurse‐implants (P = .3). Procedural time for physician‐implants (13.4 ± 8.0 minutes) and nurse‐implants (14.2 ± 10.1 minutes) were comparable (P = .98). The procedural cost was estimated as £576.02 for physician‐implants against £279.95 with nurse‐implants, equating to a 57.3% cost reduction. In our center, the total cost of ILR implantation in the catheter laboratory by physicians was £10 513.13 p.a. vs £6661.55 p.a. with a nurse‐delivered model. When overheads for running, cleaning, and maintaining were accounted for, we estimated a saving of £68 685.75 was performed by moving to a nurse‐delivered model for ILR implants. Over 133 catheter laboratory and implanting physician hours were saved and utilized for other more complex procedures. / Conclusion: ILR implantation in the outpatient setting by suitably trained nurses is safe and leads to significant financial savings.

A murine line haploinsufficient in the cardiac sodium channel has been used to model human Brugada syndrome: a disease causing sudden cardiac death due to lethal ventricular arrhythmias. We explored the effects of cholinergic tone on electrophysiological parameters in wild-type and genetically modified, heterozygous, Scn5a+/− knockout mice. Scn5a+/− ventricular slices showed longer refractory periods than wild-type both at baseline and during isoprenaline challenge. Scn5a+/− hearts also showed lower conduction velocities and increased mean increase in delay than did littermate controls at baseline and blunted responses to isoprenaline challenge. Carbachol exerted limited effects but reversed the effects of isoprenaline with coapplication. Scn5a+/− mice showed a reduction in conduction reserve in that isoprenaline no longer increased conduction velocity, and this was not antagonized by muscarinic agonists.

AimsTo evaluate population-based electronic health record (EHR) definitions of atrial fibrillation (AF) and valvular heart disease (VHD) subtypes, time trends in prevalence and prognosis.Methods and resultsA total of 76 019 individuals with AF were identified in England in 1998–2010 in the CALIBER resource, linking primary and secondary care EHR. An algorithm was created, implemented, and refined to identify 18 VHD subtypes using 406 diagnosis, procedure, and prescription codes. Cox models were used to investigate associations with a composite endpoint of incident stroke (ischaemic, haemorrhagic, and unspecified), systemic embolism (SSE), and all-cause mortality. Among individuals with AF, the prevalence of AF with concomitant VHD increased from 11.4% (527/4613) in 1998 to 17.6% (7014/39 868) in 2010 and also in individuals aged over 65 years. Those with mechanical valves, mitral stenosis (MS), or aortic stenosis had highest risk of clinical events compared to AF patients with no VHD, in relative [hazard ratio (95% confidence interval): 1.13 (1.02–1.24), 1.20 (1.05–1.36), and 1.27 (1.19–1.37), respectively] and absolute (excess risk: 2.04, 4.20, and 6.37 per 100 person-years, respectively) terms. Of the 95.2% of individuals with indication for warfarin (men and women with CHA2DS2-VASc ≥1 and ≥2, respectively), only 21.8% had a prescription 90 days prior to the study.ConclusionPrevalence of VHD among individuals with AF increased from 1998 to 2010. Atrial fibrillation associated with aortic stenosis, MS, or mechanical valves (compared to AF without VHD) was associated with an excess absolute risk of stroke, SSE, and mortality, but anticoagulation was underused in the pre-direct oral anticoagulant (DOAC) era, highlighting need for urgent clarity regarding DOACs in AF and concomitant VHD.

INTRODUCTION: Catheter ablation of atrial fibrillation (AF) has been recently shown to have an impact on the outcome of patients with heart failure and reduced LV ejection fraction (LVEF). We aimed to assess patients with reduced LVEF referred to catheter ablation of AF, and the efficacy and safety of this procedure compared with healthier patients. METHODS: 2083 consecutive procedures of catheter ablation of AF in six centers were divided into two groups on the basis of LVEF (≤ vs >35%) and comparisons were performed regarding procedural safety and efficacy. RESULTS: Only 51 (2.4%) of patients had low LVEF. Complication rate was comparable: 8.0% vs 6.9% (P = .760). Low LVEF patients are more frequently in persistent AF at the time of the procedure, have a higher degree of left atrial dilation, and higher CHA2 DS2 VASc score. The rate of atrial arrhythmia relapse post-blanking period in the first 12 months was higher in the low LVEF group: 58.0% vs 37.6% (P

Obesity is already a major global public health issue, implicated in a vast array of conditions affecting multiple body systems. It is now also firmly established as an independent risk factor in the incidence and progression of AF. The rapidly rising morbidity, mortality and healthcare costs associated with AF despite implementation of the three pillars of AF management – anticoagulation, rate control and rhythm control – suggest other strategies need to be considered. Compelling data has unveiled novel insights into adipose tissue biology and its effect on arrhythmogenesis while secondary prevention strategies targeting obesity as part of a comprehensive risk factor management programme have been demonstrated to be highly effective. Here, the authors review the epidemiological basis of the obesity–AF relationship, consider its underlying pathophysiology and discuss new therapeutic opportunities on the horizon.

Mechanical alternans (MA) is a powerful predictor of adverse prognosis in patients with heart failure and cardiomyopathy, but its use remains limited due to the need of invasive continuous arterial pressure recordings. This study aims to assess novel cardiovascular correlates of MA in the intact human heart to facilitate affordable and non-invasive detection of MA and advance our understanding of the underlying pathophysiology. Arterial pressure, respiration, and ECG were recorded in 12 subjects with healthy ventricles during voluntarily controlled breathing at different respiratory rate, before and after administration of beta-blockers. MA was induced by ventricular pacing. A total of 67 recordings lasting approximately 90 s each were analyzed. Mechanical alternans (MA) was measured in the systolic blood pressure. We studied cardiovascular correlates of MA, including maximum pressure rise during systole (dPdtmax), pulse arrival time (PAT), pulse wave interval (PI), RR interval (RRI), ECG QRS complexes and T-waves. MA was detected in 30% of the analyzed recordings. Beta-blockade significantly reduced MA prevalence (from 50 to 11%, p

The British Heart Rhythm Society’s Clinical Practice Guidelines on the Management of Patients Developing QT Prolongation on Antipsychotic Medication are written for heart rhythm consultants, primary care physicians, specialist registrars, nurses and physiologists who may be requested to review ECGs or advise on cases where antipsychotic-induced QT prolongation is suspected or proven. The guidance is adapted from the latest Maudsley Prescribing Guidelines in Psychiatry, published in 2018.

Background: No periprocedural metric has demonstrated improved cardiac resynchronization therapy (CRT) outcomes in a multicenter setting. Objective: We sought to determine if left ventricular (LV) lead placement targeted to the coronary sinus (CS) branch generating the best acute hemodynamic response (AHR) results in improved outcomes at 6 months. Methods: In this multicenter randomized controlled trial, patients were randomized to guided CRT or conventional CRT. Patients in the guided arm had LV dP/dtmax measured during biventricular (BIV) pacing. Target CS branches were identified and the final LV lead position was the branch with the best AHR and acceptable threshold values. The primary endpoint was the proportion of patients with a reduction in LV end-systolic volume (LVESV) of ≥15% at 6 months. Results: A total of 281 patients were recruited across 12 centers. Mean age was 70.8 ± 10.9 years and 54% had ischemic etiology. Seventy-three percent of patients in the guided arm demonstrated a reduction in LVESV of ≥15% at 6 months vs 60% in the conventional arm (P = .02). Patients with AHR ≥ 10% were more likely to demonstrate a reduction of ESV ≥ 15% (84% of patients with an AHR ≥10% vs 28% with an AHR

Background Recognizing the etiology of sudden cardiac arrest (SCA) has an enormous impact on the management of victims and their immediate families. A significant proportion of SCA survivors with a structurally normal heart are not offered a diagnosis and there is no clear consensus on the type and duration of follow‐up. We aimed to assess the utility of a multidisciplinary approach in optimizing diagnosis of cardiac arrest etiology during follow‐up. Methods and Results We retrospectively assessed 327 consecutive SCA survivors (mean age 61.9±16.2 years, 80% men) who underwent secondary prevention implantable cardioverter defibrillators between May 2015 and November 2018. The initial diagnosis was recorded at the time of admission and follow‐up diagnosis was deduced from subsequent clinic records, investigations, and outcomes of multidisciplinary team meetings. Structural heart disease accounted for 282 (86%) of SCAs. Forty‐five (14%) patients had a structurally normal heart and underwent comprehensive testing and follow‐up (mean duration 93±52 weeks). On initial evaluation, 14/45 (31%) of these received a diagnosis, rising to 29/45 (64%) with serial reviews during follow‐up. Discussion in multidisciplinary team meetings and imaging reassessment accounted for 47% of new diagnoses. No additional diagnoses were made beyond 96 weeks. Nineteen (5.8%) fatalities occurred in the entire cohort, exclusively in patients with structural heart disease. Conclusions Systematic comprehensive testing combined with multidisciplinary expert team review of SCA survivors without structural heart disease improves the yield and time to diagnosis compared with previously published studies. This approach has positive implications in the management of SCA survivors and their families.

The electrocardiogram (ECG) is a commonly used clinical tool that reflects cardiac excitability and disease. Many parameters are can be measured and with the improvement of methodology can now be quantified in an automated fashion, with accuracy and at scale. Furthermore, these measurements can be heritable and thus genome wide association studies inform the underpinning biological mechanisms. In this review we describe how we have used the resources in UK Biobank to undertake such work. In particular, we focus on a substudy uniquely describing the response to exercise performed at scale with accompanying genetic information.

Summary of the progress in arrhythmias in 2020. RACE4 and ALL-IN indicated that integrated nurse-led care improves outcomes in AF patients.3 , 4 The same was reported for early rhythm control therapy15 and cryoablation as initial AF treatment.25 , 26 Subcutaneous ICD was non-inferior to classical transvenous ICD therapy in PRAETORIAN.54 One mechanistic study showed that autoantibodies against misexpressed actin, keratin, and connexin-43 proteins create a blood-borne biomarker profile enhancing diagnosis of Brugada syndrome.50 Another mechanistic study indicated that transseptal LV pacing yields similar improvement in contractility as His bundle pacing whilst being more easy to execute.44 In PRE-DETERMINE a simple-to-use ECG risk score improved risk prediction in patients with ischemic heart disease possibly enhancing appropriate ICD therapy in high risk patients.58

Introduction Electrocardiographic (ECG) markers of ventricular depolarisation and repolarisation are associated with an increased risk of arrhythmia and sudden cardiac death. Our prior work indicated lower serum calcium concentrations are associated with longer QT and JT intervals in the general population. Here, we investigate whether serum calcium is a causal risk factor for changes in ECG measures using Mendelian Randomisation (MR). Methods We performed a new genome-wide association study (GWAS) for serum calcium in >300,000 European-ancestry participants from UK-Biobank. Independent lead variants were extracted to be used as instrumental variables (figure 1). Two-sample MR analyses were performed to approximate the causal effect of serum calcium on QT, JT and QRS intervals using an inverse-weighted method in 76,226 UK-Biobank participants with ECG data, not contributing to the serum calcium GWAS. A secondary analysis wase performed using lead variants from a calcium GWAS corrected for serum albumin. Sensitivity analyses were performed using contemporary methods to test for the presence of horizontal pleiotropy. Results 205 independent lead calcium-associated variants were used as instrumental variables for Mendelian Randomisation. A decrease of 0.1 mmol/L genetically-determined serum calcium, was associated with longer QT (3.01ms (95% CI 2.03, 3.99)) and JT (2.89ms (1.91, 3.87)) intervals. A weak association was observed for QRS duration in secondary analyses only (0.39ms (0.08, 0.69)). Results were concordant in all sensitivity analyses. Conclusion These analyses support a causal effect of serum calcium levels on ventricular repolarisation, in a middle-aged population of European-ancestry where serum calcium concentrations are likely stable and chronic. Modulation of calcium concentration may therefore directly influence cardiovascular disease risk. Further research into the effects of serum calcium concentration on arrhythmogenesis is warranted and calcium variants could be considered for inclusion in genetic risk score models for predictive testing. Conflict of Interest None

Introduction Premature ventricular complexes (PVCs) are frequently detected on routine electrocardiogram monitoring during exercise. The prognostic implications of frequent or repetitive PVCs during exercise are well recognised in individuals with known heart disease, but conflicting results have been reported in individuals without known structural or ischaemic substrates. The aim of this study was to evaluate the relationship between PVC frequency during exercise and the risk of major adverse cardiovascular events (MACE) in a large cohort of ~56,000 individuals without known cardiovascular disease with long-term follow-up. Methods Approximately 77,000 individuals from the UK Biobank study participated in an exercise test using a stationary bicycle in conjunction with a 4-lead electrocardiograph device. We excluded individuals with a known cardiovascular disease or a corrupt/incomplete ECG registration. The number of PVCs in the ECG registration were counted for the remaining individuals (N=56,176) using an in-house developed deep learning algorithm. All registrations with a PVC frequency of ≧5% were reviewed manually and corrected if needed. The study endpoint was MACE, defined as either hospitalization or death due to myocardial infarction, heart failure, or ventricular arrhythmia. The association with MACE was evaluated for a range of PVC counts (up to 30 PVCs during exercise) using uni- and multivariate Cox regression analysis. In the multivariate model we adjusted for established cardiovascular risk factors, including age, sex, body mass index, smoking, diabetes, and heart rate recovery. Results The mean age of all individuals was 56,7 (± 8.2) years and men and women were relatively even numbered (47% men). The median follow-up was 10 years during which N=1,871 (3.3%) individuals reached the study endpoint. The prevalence of PVCs observed during the stress test ranged from N=16,330 (29%) individuals having ≧1 PVC, to N=1758 (x%) and N=856 (1.5%) for >10% and ≧25% PVCs, respectively. Interestingly, having at least 1 PVC was already significantly associated with adverse outcome: hazard ratio (HR) [95% CI]: 1.6 [1.4 – 1.7], p Conclusion Historically, occasional occurrence of PVCs during exercise has been considered benign. However, the results of this study may suggest that also low PVC frequencies may carry relevant prognostic information for cardiovascular disease independent of other cardiovascular risk factors. The mechanisms remain to be investigated, but may include subclinical changes in myocardial functioning. Conflict of Interest None

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Background:\ud A small minority of people with coronavirus disease 2019 (COVID‐19) develop a severe illness, characterised by inflammation, microvascular damage and coagulopathy, potentially leading to myocardial injury, venous thromboembolism (VTE) and arterial occlusive events. People with risk factors for or pre‐existing cardiovascular disease may be at greater risk.\ud \ud Objectives:\ud To assess the prevalence of pre‐existing cardiovascular comorbidities associated with suspected or confirmed cases of COVID‐19 in a variety of settings, including the community, care homes and hospitals. We also assessed the nature and rate of subsequent cardiovascular complications and clinical events in people with suspected or confirmed COVID‐19.\ud \ud Search methods:\ud We conducted an electronic search from December 2019 to 24 July 2020 in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, covid‐19.cochrane.org, ClinicalTrials.gov and EU Clinical Trial Register.\ud \ud Selection criteria:\ud We included prospective and retrospective cohort studies, controlled before‐and‐after, case‐control and cross‐sectional studies, and randomised controlled trials (RCTs). We analysed controlled trials as cohorts, disregarding treatment allocation. We only included peer‐reviewed studies with 100 or more participants, and excluded articles not written in English or only published in pre‐print servers.\ud \ud Data collection and analysis:\ud Two review authors independently screened the search results and extracted data. Given substantial variation in study designs, reported outcomes and outcome metrics, we undertook a narrative synthesis of data, without conducting a meta‐analysis. We critically appraised all included studies using the Joanna Briggs Institute (JBI) checklist for prevalence studies and the JBI checklist for case series.\ud \ud Main results:\ud We included 220 studies. Most of the studies originated from China (47.7%) or the USA (20.9%); 9.5% were from Italy. A large proportion of the studies were retrospective (89.5%), but three (1.4%) were RCTs and 20 (9.1%) were prospective.\ud \ud Using JBI’s critical appraisal checklist tool for prevalence studies, 75 studies attained a full score of 9, 57 studies a score of 8, 31 studies a score of 7, 5 studies a score of 6, three studies a score of 5 and one a score of 3; using JBI’s checklist tool for case series, 30 studies received a full score of 10, six studies a score of 9, 11 studies a score of 8, and one study a score of 5\ud \ud We found that hypertension (189 studies, n = 174,414, weighted mean prevalence (WMP): 36.1%), diabetes (197 studies, n = 569,188, WMP: 22.1%) and ischaemic heart disease (94 studies, n = 100,765, WMP: 10.5%) are highly prevalent in people hospitalised with COVID‐19, and are associated with an increased risk of death. In those admitted to hospital, biomarkers of cardiac stress or injury are often abnormal, and the incidence of a wide range of cardiovascular complications is substantial, particularly arrhythmias (22 studies, n = 13,115, weighted mean incidence (WMI) 9.3%), heart failure (20 studies, n = 29,317, WMI: 6.8%) and thrombotic complications (VTE: 16 studies, n = 7700, WMI: 7.4%).\ud \ud Authors' conclusions:\ud This systematic literature review indicates that cardiometabolic comorbidities are common in people who are hospitalised with a COVID‐19 infection, and cardiovascular complications are frequent. We plan to update this review and to conduct a formal meta‐analysis of outcomes based on a more homogeneous selected subsample of high‐certainty studies.

Background We evaluated the effect of adenosine upon mechanisms sustaining persistent AF through analysis of contact electrograms and ECGI mapping. Methods Persistent AF patients undergoing catheter ablation were included. ECGI maps and cycle length (CL) measurements were recorded in the left and right atrial appendages and repeated following boluses of 18 mg of intravenous adenosine. Potential drivers (PDs) were defined as focal or rotational activations completing ≥ 1.5 revolutions. Distribution of PDs was assessed using an 18 segment biatrial model. Results 46 patients were enrolled. Mean age was 63.4 ± 9.8 years with 33 (72%) being male. There was no significant difference in the number of PDs recorded at baseline compared to adenosine (42.1 ± 15.2 vs 40.4 ± 13.0; p = 0.417), nor in the number of segments harbouring PDs, (13 (11–14) vs 12 (10–14); p = 0.169). There was a significantly higher percentage of PDs that were focal in the adenosine maps (36.2 ± 15.2 vs 32.2 ± 14.4; p < 0.001). There was a significant shortening of CL in the adenosine maps compared to baseline which was more marked in the right atrium than left atrium (176.7 ± 34.7 vs 149.9 ± 27.7 ms; p < 0.001 and 165.6 ± 31.7 vs 148.3 ± 28.4 ms; p = 0.003). Conclusion Adenosine led to a small but significant shortening of CL which was more marked in the right than left atrium and may relate to shortening of refractory periods rather than an increase in driver burden or distribution. Registered on Clinicaltrials.gov: NCT03394404.

Cardiac device infection is a serious complication of implantable cardioverter-defibrillator (ICD) placement and requires complete device removal with accompanying antimicrobial therapy for durable cure. Recent guidelines have highlighted the need to better identify patients at high risk of infection to assist in device selection.To estimate the prevalence of infection in de novo transvenous (TV) ICD implants and assess factors associated with infection risk in a Medicare population.A retrospective cohort study was conducted using 100% Medicare administrative and claims data to identify patients who underwent de novo TV-ICD implantation (July 2016-December 2017). Infection within 720 days of implantation was identified using ICD-10 codes. Baseline factors associated with infection were identified by univariable logistic regression analysis of all variables of interest, including conditions in Charlson and Elixhauser comorbidity indices, followed by stepwise selection criteria with a P ≤ .25 for inclusion in a multivariable model and a backwards, stepwise elimination process with P ≤ .1 to remain in the model. A time-to-event analysis was also conducted.Among 26,742 patients with de novo TV-ICD, 519 (1.9%) developed an infection within 720 days post implant. While more than half (54%) of infections occurred during the first 90 days, 16% of infections occurred after 365 days. Multivariable analysis revealed several significant predictors of infection: age70 years, renal disease with dialysis, and complicated diabetes mellitus.The rate of de novo TV-ICD infection was 1.9%, and identified risk factors associated with infection may be useful in device selection.