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ObjectivePulmonary vein isolation (PVI) guided by a standardised CLOSE (contiguous optimised lesions) protocol has been shown to increase clinical success after catheter ablation for paroxysmal atrial fibrillation (PAF). This study analysed healthcare utilisation and quality of life (QOL) outcomes from a large multicentre prospective study, measured association between QOL and atrial fibrillation (AF) burden and identified factors associated with lack of QOL improvement.MethodsCLOSE-guided ablation was performed in 329 consecutive patients (age 61.4 years, 60.8% male) with drug-refractory PAF in 17 European centres. QOL was measured at baseline and 12 months post-ablation via Atrial Fibrillation Effect on QualiTy of Life Survey (AFEQT) and EuroQoL EQ-5D-5L questionnaires. All-cause and cardiovascular hospitalisations and cardioversions over 12 months pre-ablation and post-ablation were recorded. Rhythm monitoring included weekly and symptom-driven trans-telephonic monitoring, plus ECG and Holter monitoring at 3, 6 and 12 months. AF burden was defined as the percentage of postblanking tracings with an atrial tachyarrhythmia ≥30 s. Continuous measures across multiple time points were analysed using paired t-tests, and associations between various continuous measures were analysed using independent sample t-tests. Each statistical test used two-sided p values with a significance level of 0.05.ResultsBoth QOL instruments showed significant 12-month improvements across all domains: AFEQT score increased 25.1–37.5 points and 33.3%–50.8% fewer patients reporting any problem across EuroQoL EQ-5D-5L domains. Overall, AFEQT improvement was highly associated with AF burden (p=0.009 for 2DS2-VASc scores at baseline, and higher AF burden following PVI.ConclusionsQOL improved and healthcare utilisation decreased significantly after ablation with a standardised CLOSE protocol. QOL improvement was significantly associated with impairment at baseline and AF burden after ablation.Trial registration numberNCT03062046.

ObjectivesThis study evaluated the comparative effectiveness of vitamin K antagonists (VKAs), direct thrombin inhibitors (DTIs) and factor Xa inhibitors (FXaI) in patients with atrial fibrillation (AF) at risk of stroke in everyday practice.MethodsData from patients with AF and Congestive heart failure, Hypertension, Age 75 years, Diabetes mellitus, prior Stroke, TIA, or thromboembolism, Vascular disease, Age 65-74 years, Sex category (CHA2DS2-VASc) score ≥2 (excluding gender) in the Global Anticoagulant Registry in the FIELD–Atrial Fibrillation registry were analysed using an improved method of propensity weighting, overlap weights and Cox proportional hazards models.ResultsAll-cause mortality, non-haemorrhagic stroke/systemic embolism (SE) and major bleeding over 2 years were compared in 25 551 patients, 7162 (28.0%) not treated with oral anticoagulant (OAC) and 18 389 (72.0%) treated with OAC (FXaI (41.8%), DTI (11.4%) and VKA (46.8%)). OAC treatment compared with no OAC treatment was associated with decreased risk of all-cause mortality (HR 0.82 (95% CI 0.74 to 0.91)) and non-haemorrhagic stroke/SE (HR 0.71 (95% CI 0.57 to 0.88)) but increased risk of major bleeding (HR 1.46 (95% CI 1.15 to 1.86)). Non-vitamin K antagonist oral anticoagulant (NOAC) use compared with no OAC treatment was associated with lower risks of all-cause mortality and non-haemorrhagic stroke/SE (HR 0.67 (95% CI 0.59 to 0.77)) and 0.65 (95% CI 0.50 to 0.86)) respectively, with no increase in major bleeding (HR 1.10 (95% CI 0.82 to 1.47)). NOAC use compared with VKA use was associated with lower risk of all-cause mortality and major bleeding (rates/100 patient-years 3.6 (95% CI 3.3 to 3.9) vs 4.8 (95% CI 4.5 to 5.2) and 1.0 (95% CI 0.9 to 1.1) vs 1.4 (95% CI 1.2 to 1.6); HR 0.79 (95% CI 0.70 to 0.89) and 0.77 (95% CI 0.61 to 0.98) respectively), with similar risk of non-haemorrhagic stroke/SE (rates/100 patient-years 0.8 (95% CI 0.7 to 0.9) versus 1.0 (95% CI 0.8 to 1.1); HR 0.96 (95% CI 0.73 to 1.25).ConclusionImportant benefits in terms of mortality and major bleeding were observed with NOAC versus VKA with no difference among NOAC subtypes.Trial registration numberNCT01090362.

Background and purposeThe diagnostic benefit of using continuous ECG (cECG) for poststroke atrial fibrillation (AF) screening in a primary care setting is unclear. We aimed to assess the diagnostic yield from screening patients who previously had a stroke with a 7-day Holter monitor.MethodsPatients older than 49 years, naive to AF, with an ischaemic stroke over 1 year before enrolment were included. In a primary care setting, all patients were screened for AF using pulse palpation, 12-lead ECG and 7-day Holter monitoring. Further, NT-proBNP was determined at baseline.Results7-day Holter monitoring uncovered AF in 17 of 366 patients (4.6% (95% CI 2.7 to 7.3)). The number needed to screen was 22 patients (14–37). 12-lead ECG uncovered AF in 3 patients (0.82% (95% CI 0.17 to 2.4)), and 122 patients had irregular pulse during pulse palpation (33.5% (95% CI 28.7 to 38.2)). When using 7-day Holter monitoring as reference standard, the sensitivity of pulse palpation and 12-lead ECG was 47% (95% CI 23% to 72%) and 18% (95% CI 4% to 43%). High levels (≥400 pg/mL) of NT-proBNP versus low levels (≤200 pg/mL) were not associated with AF in the univariate analysis nor when adjusted for age (OR 2.4 (95% CI 0.5 to 8.4) and 1.6 (95% CI 0.3 to 6.0)).ConclusionsA relevant proportion of patients with stroke more than 1 year before inclusion were diagnosed with AF through 7-day Holter monitoring. Given the low sensitivities of pulse palpation and 12-lead ECG, additional cECG may be considered during poststroke primary care follow-up.

​ObjectiveCardiopulmonary resuscitation (CPR) performed before the arrival of emergency medical services (EMS) is associated with increased survival after out-of-hospital cardiac arrest (OHCA). The aim of this study was to determine whether patients who receive bystander CPR have a different comorbidity compared with patients who do not, and to determine the association between bystander CPR and 30-day survival when adjusting for such a possible difference.​MethodsPatients with witnessed OHCA in the Swedish Registry for Cardiopulmonary Resuscitation between 2011 and 2015 were included, and merged with the National Patient Registry. The Charlson Comorbidity Index (CCI) was used to measure comorbidity. Multiple logistic regression was used to examine the effect of CCI on the association between bystander CPR and outcome.​ResultsIn total, 11 955 patients with OHCA were included, 71% of whom received bystander CPR. Patients who received bystander CPR had somewhat lower comorbidity (CCI) than those who did not (mean±SD: 2.2±2.3 vs 2.5±2.4; p​ConclusionPatients who undergo CPR before the arrival of EMS have a somewhat lower degree of comorbidity than those who do not. Taking this difference into account, bystander CPR is still associated with a marked increase in 30-day survival after OHCA.

Aim This study aimed to determine whether patients suffering from out-of-hospital cardiac arrest (OHCA) with a pre-OHCA diagnosis of heart disease have higher survival chances than patients without such a diagnosis and to explore possible underlying mechanisms. Methods A retrospective cohort study in 3760 OHCA patients from the Netherlands (2010–2016) was performed. Information from emergency medical services, treating hospitals, general practitioner, resuscitation ECGs and civil registry was used to assess medical histories and the presence of pre-OHCA diagnosis of heart disease. We used multivariable regression analysis to calculate associations with survival to hospital admission or discharge, immediate causes of OHCA (acute myocardial infarction (AMI) vs non-AMI) and initial recorded rhythm. Results Overall, 48.1% of OHCA patients had pre-OHCA heart disease. These patients had higher odds to survive to hospital admission than patients without pre-OHCA heart disease (OR 1.25 (95%CI 1.05 to 1.47)), despite being older and more often having cardiovascular risk factors and some non-cardiac comorbidities. These patients also had higher odds of shockable initial rhythm (SIR) (OR 1.60 (1. 36 to 1.89)) and a lower odds of AMI as immediate cause of OHCA (OR 0.33 (0.25 to 0.42)). Their chances of survival to hospital discharge were not significantly larger (OR 1.16 (0.95 to 1.42)). Conclusion Having pre-OHCA diagnosed heart disease is associated with better odds to survive to hospital admission, but not to hospital discharge. This is associated with higher odds of a SIR and in a subgroup with available diagnosis a lower proportion of AMI as immediate cause of OHCA.

AimsIt is unknown whether screen-detected atrial fibrillation (AF) carries cardiovascular risks similar to clinically detected AF. We aimed to compare clinical outcomes between individuals with screen-detected and clinically detected incident AF.MethodsWe studied 8265 participants (age 49 ± 13 years, 50% women) without prevalent AF from the community-based Prevention of Renal and Vascular End-stage Disease (PREVEND) study. By design of the PREVEND study, 70% of participants had a urinary albumin concentration >10 mg/L. Participants underwent 12-lead ECG screening at baseline and every 3 years. AF was considered screen-detected when first diagnosed during a study visit and clinically detected when first diagnosed during a hospital visit. We analysed data from the baseline visit (1997–1998) up to the third follow-up visit (2008). We used Cox regression with screen-detected and clinically detected AF as time-varying covariates to study the association of screen-detected and clinically detected AF with all-cause mortality, incident heart failure (HF) and vascular events.ResultsDuring a follow-up of 9.8 ± 2.3 years, 265 participants (3.2%) developed incident AF, of whom 60 (23%) had screen-detected AF. The majority of baseline characteristics were comparable between individuals with screen-detected and clinically detected AF. Unadjusted, both screen-detected and clinically detected AF were strongly associated with mortality, incident HF, and vascular events. After multivariable adjustment, screen-detected and clinically detected AF remained significantly associated with mortality (HR 2.21 (95% CI 1.09 to 4.47) vs 2.95 (2.18 to 4.00), p for difference=0.447) and incident HF (4.90 (2.28 to 10.57) vs 3.98 (2.49 to 6.34), p for difference=0.635). After adjustment, screen-detected AF was not significantly associated with vascular events, whereas clinically detected AF was (1.12 (0.46 to 2.71) vs 1.92 (1.21 to 3.06), p for difference=0.283).ConclusionScreen-detected incident AF was associated with an increased risk of adverse outcomes, especially all-cause mortality and incident HF. The risk of outcomes was not significantly different between screen-detected AF and clinically detected AF.

IntroductionPulmonary vein isolation (PVI) is an important treatment for atrial fibrillation (AF). However, many patients need more than one procedure to maintain long-term sinus rhythm. Even after two PVIs some may suffer from AF recurrences. We aimed to identify characteristics of patients who fail after two PVI procedures.Methods and resultsWe included 557 consecutive patients undergoing a first PVI procedure with a second-generation 28 mm cryoballoon. Follow-up procedures were performed using radiofrequency ablation targeting reconnected PVs only. Recurrent AF was defined as any episode of AF lasting >30 s on ECG or 24 hour Holter monitoring performed at 3, 6 and 12 months post procedure. Mean age was 59.1±10.2 years, 383 (68.8%) were male, 448 (80.4%) had paroxysmal AF and the most common underlying condition was hypertension (36.6%). A total of 140/557 (25.1%) patients underwent redo procedure with PVI only. Of these patients 45 (32.4%) had recurrence of AF. These patients were comparable regarding age and sex to those in sinus rhythm after one or two procedures. Multivariate logistic regression showed that non-paroxysmal AF (OR 1.08 (95% CI 1.01 to 1.15), estimated glomerular filtration rate (OR 0.96, 95% CI 0.94 to 0.99), bundle branch block (OR 4.17, 95% CI 1.38 to 12.58), heart failure (OR 4.17, 95% CI 1.38 to 12.58) and Left Atrium Volume Index (OR 1.04, 95% CI 1.01 to 1.08) were associated with AF recurrence after two PVIs. The area under the curve for the identified risk factors was 0.74.ConclusionsUsing a PVI-only approach, recurrence of AF after two AF ablation procedures is associated with more advanced underlying disease and persistent types of AF.

IntroductionAtrial fibrillation (AF) is the most common sustained arrhythmia worldwide. Direct current cardioversion is commonly used to restore sinus rhythm in patients with AF. Chest pressure may improve cardioversion success through decreasing transthoracic impedance and increasing cardiac energy delivery. We aim to assess the efficacy and safety of routine chest pressure with direct current cardioversion for AF.Methods and analysisMulticentre, double blind (patient and outcome assessment), randomised clinical trial based in New South Wales, Australia. Patients will be randomised 1:1 to control and interventional arms. The control group will receive four sequential biphasic shocks of 150 J, 200 J, 360 J and 360 J with chest pressure on the last shock, until cardioversion success. The intervention group will receive the same shocks with chest pressure from the first defibrillation. Pads will be placed in an anteroposterior position. Success of cardioversion will be defined as sinus rhythm at 1 min after shock. The primary outcome will be total energy provided. Secondary outcomes will be success of first shock to achieve cardioversion, transthoracic impedance and sinus rhythm at post cardioversion ECG.Ethics and disseminationEthics approval has been confirmed at all participating sites via the Research Ethics Governance Information System. The trial has been registered on the Australia New Zealand Clinical Trials Registry (ACTRN12620001028998). De-identified patient level data will be available to reputable researchers who provide sound analysis proposals.

BackgroundIn long QT syndrome (LQTS), beta blockers prevent arrhythmias. As a supplement, means to increase potassium has been suggested. We set to investigate the effect of moderate potassium elevation on cardiac repolarisation.MethodsPatients with LQTS with a disease-causing KCNQ1 or KCNH2 variant were included. In addition to usual beta-blocker treatment, patients were prescribed (1) 50 mg spironolactone (low dose) or (2) 100 mg spironolactone and 3 g potassium chloride per day (high dose+). Electrocardiographic measures were obtained at baseline and after 7 days of treatment.ResultsTwenty patients were enrolled (10 low dose and 10 high dose+). One patient was excluded due to severe influenza-like symptoms, and 5 of 19 patients completing the study had mild side effects. Plasma potassium in low dose did not increase in response to treatment (4.26±0.22 to 4.05±0.19 mmol/L, p=0.07). Also, no change was observed in resting QTcF (QT interval corrected using Fridericia's formula) before versus after treatment (478±7 vs 479±7 ms, p=0.9). In high dose+, potassium increased significantly from 4.08±0.29 to 4.48±0.54 mmol/L (p=0.001). However, no difference in QTcF was observed comparing before (472±8 ms) versus after (469±8 ms) (p=0.66) high dose+ treatment. No patients developed hyperkalaemia.ConclusionIn patients with LQTS, high dose+ treatment increased plasma potassium by 0.4 mmol/L without cases of hyperkalaemia. However, the potassium increase did not shorten the QT interval and several patients had side effects. Considering the QT interval as a proxy for arrhythmic risk, our data do not support that potassium-elevating treatment has a role as antiarrhythmic prophylaxis in patients with LQTS with normal-range potassium levels.Trial registration numberNCT03291145.

ObjectivePatients with heart disease are at increased risk for sudden cardiac death. Guidelines recommend an implantable loop recorder (ILR) for symptomatic patients when symptoms are sporadic and possibly arrhythmia-related. In clinical practice, an ILR is mainly used in patients with unexplained syncope. We aimed to compare the clinical value of an ILR in patients with heart disease and a history of syncope versus those with non-syncopal symptoms.MethodsIn this observational single-centre study, we included symptomatic patients with heart disease who received an ILR. The primary endpoint was an actionable event which was defined as an arrhythmic event leading to a change in clinical management. The secondary endpoint was an event leading to device implantation.ResultsOne hundred and twenty patients (mean age 47±17 years, 49% men) were included. The underlying disease substrate was inherited cardiomyopathy (31%), congenital heart disease (28%), channelopathy (23%) and other (18%). Group A consisted of 43 patients with prior syncope and group B consisted of 77 patients with palpitations and/or near-syncope. The median follow-up duration was 19 months (IQR 8–36). The 3-year cumulative event rate was similar between groups with regard to the primary endpoint (38% vs 39% for group A and B, respectively, logrank p=0.54). There was also no difference in the 3-year cumulative rate of device implantation (21% vs 13% for group A and B, respectively, logrank p=0.65).ConclusionIn symptomatic patients with heart disease, there is no difference in the yield of an ILR in patients presenting with or without syncope.

ObjectiveIncidence and severity of acute myocarditis vary significantly in previous reports and there is a lack of epidemiological studies on the short-term risks of mortality, heart failure and ventricular arrhythmias in patients with acute myocarditis. Therefore, study aims were to examine 90-day risks of mortality, heart failure (HF) and ventricular arrhythmias in patients with acute myocarditis in comparison to age-matched and sex-matched background population controls.MethodsIn this nationwide register-based follow-up study of patients hospitalised with myocarditis between 2002 and 2018 in Denmark, 90-day risks of all-cause mortality, HF, ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation (VF)), cardiac arrest and implantable cardioverter-defibrillator (ICD) implantation were compared with age-matched and sex-matched controls from the background population (1:5 matching). Absolute risks standardised to the age, sex and comorbidity distribution of the entire study population were derived from multivariable Cox regression.ResultsA total of 2523 patients hospitalised with myocarditis were included. Median age was 48 years (Q1–Q3: 30–69) and 67.7% were men. Comorbidity burden was more pronounced among patients with myocarditis relative to controls. Standardised 90-day all-cause mortality risk was 4.9% for patients with acute myocarditis versus 0.3% for controls (pConclusionsIn this large nationwide register-based follow-up study, patients hospitalised with myocarditis had significantly higher 90-day risks of all-cause mortality, HF, ventricular arrhythmias, cardiac arrest and ICD implantation compared with background population controls.

Funder: Wellcome Trust, ObjectiveTo describe patterns of anticoagulation prescription and persistence for those aged ≥65 years with atrial fibrillation (AF).MethodsDescriptive cohort study using electronic general practice records of patients in England, who attended an influenza vaccination aged ≥65 years and were diagnosed with AF between 2008 and 2018. Patients were stratified by 10-year age group and year of diagnosis. Proportion anticoagulated, type of anticoagulation (direct oral anticoagulant (DOAC) or warfarin) initiated at diagnosis and persistence with anticoagulation over time are reported.Results42 290 patients (49% female), aged 65-74 (n=11 722), 75-84 (n=19 055) and 85+ (n=11 513) years at AF diagnosis are included. Prescription of anticoagulation at diagnosis increased over the time period from 55% to 86% in people aged 65-74 years, from 54% to 86% in people aged 75-84 years and from 27% to 75% in people aged 85 years and over. By 2018, 92% of patients with newly diagnosed AF were started on a DOAC. Survivor function for 5-year persistence in patients prescribed DOAC was 0.80 (95% CI 0.77 to 0.82) and for warfarin 0.71 (95% CI 0.70 to 0.72). Survivor function for any anticoagulation at 5 years was 0.79 (95% CI 0.78 to 0.81), 0.73 (95% CI 0.72 to 0.75) and 0.58 (95% CI 0.59 to 0.64) for people aged 65-74, 75-84 and 85+ years, respectively.ConclusionsRates of anticoagulation in AF in those aged ≥65 years have increased from 2008 to 2018, over which time period there has been a shift from initiating anticoagulation with warfarin to DOAC. Persistence with anticoagulation is higher in people on DOACs than on warfarin and in people aged

Background/Introduction Most patients with atrial fibrillation (AF) report symptoms, while around one-third are asymptomatic. We hypothesized that sensory processing, in particular pain, differs in patients with symptomatic and asymptomatic AF. Purpose To assess differences in pain sensitisation in patients with symptomatic and asymptomatic AF. Methods Thirty individuals with permanent AF (15 symptomatic, 15 asymptomatic) completed the AF6 and SF-36 questionnaires and underwent quantitative pain sensitisation testing using pressure algometry at the sternum (referred pain area) and the tibialis anterior muscle (generalized pain area). The primary objective was to assess differences in pressure pain thresholds (PPT), temporal summation of pain (TSP), and conditioned pain modulation (CPM) in the two groups. The secondary objective was to determine association of demographic and clinical parameters to quantitative measures of pain sensitisation. Results The symptomatic group had lower PPTs at both tibialis (p=0.004) and sternum (p=0.01), as well as impaired CPM (p=0.025) and facilitated TSP (p=0.008) at the tibialis but not sternum, compared to the asymptomatic group. The AF6 sum score was negatively correlated to PPT on both tibialis (r=−0.50, p=0.005) and sternum (r=−0.42, p=0.02) and positively correlated to TSP of both tibialis (r=0.57, p=0.001) and sternum (r=0.45, p=0.01), but not to CPM. The physical component summary score was positively correlated to the PPT on both tibialis (r=0.52, p=0.003) and sternum (r=0.40, p=0.03) and negatively to TSP on the tibialis (r=−0.53, p=0.003) but not sternum. Conclusions Patients with symptomatic AF exhibit lower pain tolerance than patients with asymptomatic AF, as well as impaired pain inhibitory control and facilitated summation of pain, indicating that pain sensitisation may be of importance in symptomatic AF. Funding Acknowledgement Type of funding sources: Public hospital(s). Main funding source(s): Department of Cardiology, Örebro University, Sweden PPTs tibialis anterior musclePPTs sternum

ObjectiveThe purpose of this study was to develop a non-invasive and convenient nomogram based on speckle tracking echocardiography, left atrial appendage function and clinical factors to predict the risk of atrial fibrillation (AF) recurrence after catheter ablation.MethodsA total of 124 prospectively consecutive patients with AF treated with catheter ablation in our hospital was retrospectively analysis. Baseline echocardiographic parameters were measured by using transthoracic and transesophageal echocardiography before ablation. Multivariate analysis was performed for selecting predictors for a nomogram and internal validation and calibration were evaluated by the bootstep method.ResultsDuring the follow-up of 12±3 months, 41 patients (33.1%) occurred AF recurrence after catheter ablation, while 83 patients (66.9%) had maintained sinus rhythm. Four predictors (AF type, left atrial appendage emptying flow velocity, left Atrial maximal volumes index and global longitudinal strain) with the PConclusionsNomogram based on echocardiography and clinical characteristics had good predictive performance for the possibility of AF recurrence, which providing practical guidance for individualised management of patients with AF after catheter ablation.

ObjectiveTo evaluate associations between oral anticoagulant (OAC) discontinuation and risk of ischaemic stroke (IS) among patients with atrial fibrillation (AF).MethodsWe undertook a population-based cohort study with nested case–control analysis using UK primary care electronic health records (IQVIA Medical Research Data-UK) and linked registries from the Region of Southern Denmark (RSD). Patients with AF (76 882 UK, 41 526 RSD) were followed to identify incident IS cases during 2016–2018. Incident IS cases were matched by age and sex to controls. Adjusted ORs for OAC discontinuation (vs current OAC use) were calculated using logistic regression.ResultsWe identified 616 incident IS cases in the UK and 643 in the RSD. ORs for IS with any OAC discontinuation were 2.99 (95% CI 2.31 to 3.86, UK) and 2.30 (95% CI 1.79 to 2.95, RSD), for vitamin K antagonist discontinuation they were 2.38 (95% CI 1.72 to 3.30, UK) and 1.83 (95% CI 1.34 to 2.49, RSD), and for non-vitamin K antagonist oral anticoagulant discontinuation they were 4.59 (95% CI 2.97 to 7.08, UK) and 3.37 (95% CI 2.35 to 4.85, RSD). ORs were unaffected by time since discontinuation and duration of use. Annually, up to 987 IS cases in the UK and 132 in Denmark could be preventable if OAC therapy is not discontinued.ConclusionsOur results suggest that patients with AF who discontinue OAC therapy have a significant twofold to threefold higher risk of IS compared with those who continue therapy. Addressing OAC discontinuation could potentially result in a significant reduction in AF-attributed IS.

IntroductionEarly recognition of individuals with increased risk of sudden cardiac arrest (SCA) remains challenging. SCA research so far has used data from cardiologist care, but missed most SCA victims, since they were only in general practitioner (GP) care prior to SCA. Studying individuals with type 2 diabetes (T2D) in GP care may help solve this problem, as they have increased risk for SCA, and rich clinical datasets, since they regularly visit their GP for check-up measurements. This information can be further enriched with extensive genetic and metabolic information.AimTo describe the study protocol of the REcognition of Sudden Cardiac arrest vUlnErability in Diabetes (RESCUED) project, which aims at identifying clinical, genetic and metabolic factors contributing to SCA risk in individuals with T2D, and to develop a prognostic model for the risk of SCA.MethodsThe RESCUED project combines data from dedicated SCA and T2D cohorts, and GP data, from the same region in the Netherlands. Clinical data, genetic data (common and rare variant analysis) and metabolic data (metabolomics) will be analysed (using classical analysis techniques and machine learning methods) and combined into a prognostic model for risk of SCA.ConclusionThe RESCUED project is designed to increase our ability at early recognition of elevated SCA risk through an innovative strategy of focusing on GP data and a multidimensional methodology including clinical, genetic and metabolic analyses.

Objective The optimal target heart rate in patients with prevalent atrial fibrillation (AF) is not well defined. The aim of this study was to analyse the associations between heart rate and adverse outcomes in a large contemporary cohort of patients with prevalent AF. Methods From two prospective cohort studies, we included stable AF outpatients who were in AF on the baseline ECG. The main outcome events assessed during prospective follow-up were heart failure hospitalisation, stroke or systemic embolism and death. The associations between heart rate and adverse outcomes were evaluated using multivariable Cox regression models. Results The study population consisted of 1679 patients who had prevalent AF at baseline. Mean age was 74 years, and 24.6% were women. The mean heart rate on the baseline ECG was 78 (±19) beats per minute (bpm). The median follow-up was 3.9 years (IQR 2.2–5.0). Heart rate was not significantly associated with heart failure hospitalisation (adjusted HR (aHR) per 10 bpm increase, 1.00, 95% CI 0.94 to 1.07, p=0.95), stroke or systemic embolism (aHR 0.95, 95% CI 0.84 to 1.07, p=0.38) or death (aHR 1.02, 95% CI 0.95 to 1.09, p=0.66). There was no evidence of a threshold effect for heart rates 100 bpm. Conclusions In this large contemporary cohort of outpatients with prevalent AF, we found no association between heart rate and adverse outcome events. These data are in line with recommendations that strict heart rate control is not needed in otherwise stable outpatients with AF.

ObjectiveThe sudden cardiac death (SCD) of a young person is a devastating event for any parent. Inherited heart disease is often either identified or assumed to be the cause. Few studies have explored the psychosocial impact to the surviving at-risk family members. We sought to investigate the needs of parents who have experienced the SCD of their child (≤45 years).MethodsA quantitative needs analysis questionnaire was developed based on semistructured interviews, including one focus group and a review of relevant literature. Eligible participants were invited to participate in this cross-sectional survey study.ResultsThere were 38 parents who completed a quantitative survey. Parents’ perceived needs for information and support spanned medical, psychosocial, spiritual and financial domains. Of the support and information needs assessed, medical needs were identified as the most important domain, followed by psychosocial, spiritual and financial. Importantly, psychosocial information and support needs were reported as the most unmet need, endorsed by 54% of parents. Medical information and support needs were reported as unmet by almost one third of parents. The two most endorsed needs were ‘To have the option of whether or not you would pursue genetic testing for yourself or family members’ and ‘To understand what happened’.ConclusionsThis work demonstrates for the first time, the multifactorial needs of parents after SCD in the young. With the greatest unmet need reported as psychosocial needs, there is clear necessity to find ways of integrating psychological support in to the care of families after SCD in the young.

ObjectiveTo investigate changes in quality of life (QoL), cognition and functional status according to arrhythmia recurrence after atrial fibrillation (AF) ablation.MethodsWe compared QoL, cognition and functional status in patients with recurrent atrial tachycardia (AT)/AF versus those without recurrent AT/AF in the AXAFA–AFNET 5 clinical trial. We also sought to identify factors associated with improvement in QoL and functional status following AF ablation by overall change scores with and without analysis of covariance (ANCOVA).ResultsAmong 518 patients who underwent AF ablation, 154 (29.7%) experienced recurrent AT/AF at 3 months. Patients with recurrent AT/AF had higher mean CHA2DS2-VASc scores (2.8 vs 2.3, pConclusionsPatients without recurrent AT/AF appear to experience greater improvement in functional status but similar QoL as those with recurrent AT/AF after AF ablation.

Background and purposeReal-world data about treatment convenience and satisfaction in Asian non-valvular atrial fibrillation (NVAF) patients after switching from vitamin K antagonists (VKAs) to non-VKA oral anticoagulants were evaluated.MethodsIn this non-interventional study involving 49 sites across five countries in Southeast Asia and South Korea, 379 stable NVAF patients who switched from VKA therapy to dabigatran during routine clinical practice were recruited and followed up for 6 months. Treatment convenience and satisfaction were evaluated using Perception on Anticoagulant Treatment Questionnaire-2 (PACT-Q2). Through post hoc analysis, factors associated with improved treatment convenience scores at visit 2 were described.ResultsTreatment convenience and satisfaction significantly improved after switching from VKAs to dabigatran at visit 2 and visit 3 (convenience: p80th percentile) response on treatment convenience were female sex, younger age (ConclusionDabigatran was associated with a significant improvement in treatment convenience and satisfaction after switching from VKAs when used for stroke prevention in NVAF patients from Southeast Asia and South Korea.

ObjectivesBrugada syndrome (BrS) is an ion channelopathy that predisposes affected patients to spontaneous ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death. The aim of this study is to examine the predictive factors of spontaneous VT/VF.MethodsThis was a territory-wide retrospective cohort study of patients diagnosed with BrS between 1997 and 2019. The primary outcome was spontaneous VT/VF. Cox regression was used to identify significant risk predictors. Non-linear interactions between variables (latent patterns) were extracted using non-negative matrix factorisation (NMF) and used as inputs into the random survival forest (RSF) model.ResultsThis study included 516 consecutive BrS patients (mean age of initial presentation=50±16 years, male=92%) with a median follow-up of 86 (IQR: 45–118) months. The cohort was divided into subgroups based on initial disease manifestation: asymptomatic (n=314), syncope (n=159) or VT/VF (n=41). Annualised event rates per person-year were 1.70%, 0.05% and 0.01% for the VT/VF, syncope and asymptomatic subgroups, respectively. Multivariate Cox regression analysis revealed initial presentation of VT/VF (HR=24.0, 95% CI=1.21 to 479, p=0.037) and SD of P-wave duration (HR=1.07, 95% CI=1.00 to 1.13, p=0.044) were significant predictors. The NMF-RSF showed the best predictive performance compared with RSF and Cox regression models (precision: 0.87 vs 0.83 vs. 0.76, recall: 0.89 vs. 0.85 vs 0.73, F1-score: 0.88 vs 0.84 vs 0.74).ConclusionsClinical history, electrocardiographic markers and investigation results provide important information for risk stratification. Machine learning techniques using NMF and RSF significantly improves overall risk stratification performance.

ObjectiveTo determine AF prevalence and gaps in atrial fibrillation (AF) awareness and management in China.MethodsWe conducted a community-based survey of 47 841 adults (age ≥45 years) in seven geographic regions of China between 2014 and 2016. Participants underwent a structured questionnaire, a standard 12-lead ECG, physical examination and blood sampling. AF prevalence, defined by either ECG detection or self-report, was estimated according to sampling weights, non-response and age and sex distribution of the population. We used multivariable logistic regression to estimate associations among sociodemographic, clinical and geographic factors with the AF prevalence, awareness and treatment.ResultsThe weighted AF prevalence was 1.8% (95% CI 1.7% to 1.9%), but varied from 0.9% to 2.4% across geographical regions and equates to being present in an estimated 7.9 (95% CI 7.4 to 8.4) million people in China. Among men and women, the AF prevalence increased from 0.8% and 0.6% in the age group 45–54 years to 5.4% and 4.9% in the age group ≥75 years, respectively. Proportions of people who were aware of having AF decreased overall from 65.3% in 45–54 year-olds to 53.9% in ≥75 year-olds and varied between sex (men 58.5%, women 68.8%) and residency status (urban 78.3%, rural 35.3%). Only 6.0% of patients with high-risk AF received anticoagulation therapy.ConclusionsAF prevalence is higher than previously reported in China, with low awareness and large treatment gaps. Large-scale efforts are urgently needed to reduce AF adverse consequences.

Objectives To investigate timing and age distribution of atrial fibrillation (AF) in selected oncology patients, and the impact of AF timing, CHA2DS2-VASc score and cancer therapeutics on mortality. Methods This is a retrospective cohort study of oncology patients referred to the cardio-oncology service from 2011 to 2018 for echocardiographic cardiosurveillance and/or pre-existing cardiovascular risk factor/disease management. Rates of first AF diagnosis was assessed using a parametric multiphase hazard model (predictive modelling) and non-parametrically by Kaplan-Meier with transformations tested using a bootstrap methodology. Results Among 6754 patients identified, 174 patients had their first AF diagnosis before cancer while 609 patients had their first diagnosis of AF after cancer. Most first AF diagnosis occurred at/early after cancer diagnosis. Increasing AF prevalence at time of cancer diagnosis was seen across older age groups ranges. Diagnosis of cancer at an older age and exposure to cardiotoxic treatment (anthracyclines, HER2-neu inhibitors, tyrosine kinase inhibitors including ibrutinib and radiation) were associated with an increased risk of AF. Modelling of the hazard function of AF identified a high left-skewed peak within 3 years after cancer diagnosis (‘early phase’), followed by a gradual late slight rise 3 years after cancer diagnosis (‘late phase’). AF diagnosis was only associated with death in the early phase (p

ObjectivePrevious studies have postulated a causal role of patent foramen ovale (PFO) in the aetiology of embolic stroke in the general population. We hypothesised that the presence of concomitant PFO and atrial fibrillation (AF) will add incremental risk of ischaemic stroke to that linked to AF alone.MethodsWe analysed data on 3069 consecutive patients (mean age 69.4±12.2 years; 67.1% men) undergoing transoesophageal echocardiography-guided electrical cardioversion (ECV) for AF between May 2000 and March 2012. PFO was identified by colour Doppler and agitated saline contrast study. All patients were followed up after ECV for first documentation of ischaemic stroke. Outcomes were compared using Cox regression models.ResultsThe prevalence of PFO was 20.0% and the shunt direction was left-to-right in the majority of patients (71.4%). Patients with PFO had a higher frequency of obstructive sleep apnoea (21.7% vs 17.1%, p=0.01) and higher mean peak left atrial appendage emptying velocity (38.3±21.8 vs 36.1±20.4 cm/s; p=0.04) compared with those without PFO. Otherwise, baseline characteristics were similar between groups. During a mean follow-up period of 7.3±4.6 years, 214 patients (7.0%) had ischaemic stroke. Multivariable analysis showed no significant association between PFO and ischaemic stroke (HR, 0.82 (95% CI 0.57 to 1.18)). PFO shunt direction was strongly associated with stroke: HR, 1.91 (95% CI 1.16 to 3.16) for right-to-left shunt and HR, 0.58 (95% CI 0.36 to 0.93) for left-to-right shunt.ConclusionsThe presence of concurrent PFO in this largely anticoagulated group of patients with AF was not associated with increased risk of ischaemic stroke.

ObjectiveElectrical cardioversion is frequently performed to restore sinus rhythm in patients with persistent atrial fibrillation (AF). However, AF recurs in many patients and identifying the patients who benefit from electrical cardioversion is difficult. The objective was to develop sex-specific prediction models for successful electrical cardioversion and assess the potential of machine learning methods in comparison with traditional logistic regression.MethodsIn a retrospective cohort study, we examined several candidate predictors, including comorbidities, biochemistry, echocardiographic data, and medication. The outcome was successful cardioversion, defined as normal sinus rhythm immediately after the electrical cardioversion and no documented recurrence of AF within 3 months after. We used random forest and logistic regression models for sex-specific prediction.ResultsThe cohort comprised 332 female and 790 male patients with persistent AF who underwent electrical cardioversion. Cardioversion was successful in 44.9% of the women and 49.9% of the men. The prediction errors of the models were high for both women (41.0% for machine learning and 48.8% for logistic regression) and men (46.0% for machine learning and 44.8% for logistic regression). Discrimination was modest for both machine learning (0.59 for women and 0.56 for men) and logistic regression models (0.60 for women and 0.59 for men), although the models were well calibrated.ConclusionsSex-specific machine learning and logistic regression models showed modest predictive performance for successful electrical cardioversion. Identifying patients who will benefit from cardioversion remains challenging in clinical practice. The high recurrence rate calls for thoroughly informed shared decision-making for electrical cardioversion.

ObjectiveWe evaluated atrial fibrillation (AF) patients’ perceptions of anticoagulation treatment with dabigatran or a vitamin K antagonist (VKA) for stroke prevention, according to accepted indications.MethodsThe RE-SONANCE observational, prospective, multicentre, international study used the validated Perception on Anticoagulant Treatment Questionnaire (PACT-Q) to assess patients with AF already taking a VKA who were switched to dabigatran (cohort A), and newly diagnosed patients initiated on either dabigatran or a VKA (cohort B). Visit 1 (V1) was at baseline, and visit 2 (V2) and visit 3 (V3) were at 30–45 and 150–210 days after baseline, respectively. Primary outcomes were treatment satisfaction and convenience in cohort A at V2 and V3 versus baseline, and in cohort B for dabigatran and a VKA at V2 and V3.ResultsThe main analysis set comprised 4100 patients in cohort A and 5365 in cohort B (dabigatran: 3179; VKA: 2186). In cohort A, PACT-Q2 improved significantly (pConclusionsSwitching to dabigatran from long-term VKA therapy or newly initiated dabigatran is associated with improved patient treatment convenience and satisfaction compared with VKA therapy.

AimsBody composition (BC) is known to alter in heart failure. Cardiac resynchronisation therapy (CRT) improves left ventricular geometry but the impact on BC is unknown. Our aim was to evaluate BC in these patients before and after CRT implantation.MethodsProspective proof-of-concept pilot study of heart failure patients undergoing CRT between September 2014 and December 2015. Assessments performed pre-CRT and post-CRT (6 weeks and 6 months) were: BC parameters (using air-displacement plethysmography), New York Heart Failure classification for assessing symptom severity, echocardiography to assess left ventricular geometry, electrocardiography, Minnesota Heart Failure Questionnaire and N-terminal probrain natriuretic peptide (NT-pro-BNP). Repeated measures analysis of variance was performed to assess relative change over time and potential correlations.ResultsTwenty-five patients were recruited; mean-age (±SD) was 73.4±10.0 years, 23 males, 18 CRT defibrillators (remainder CRT pacemakers), 16 had ischaemic aetiology, 6 diabetics, 17 with left bundle-branch morphology on ECG and 10 had atrial fibrillation. Significant inverse correlations were observed in the first 6 weeks following CRT between fat mass and left ventricular end-diastolic volume (r=−0.69, pConclusionThis is the first study to observe interplay between BC and cardiac geometry/function following CRT; a trend in overall fat mass reduction was noted following CRT and merits further study.

ObjectiveCritically ill patients admitted to the intensive care unit (ICU) often develop atrial fibrillation (AF), with an incidence of around 5%. Stroke prevention in AF is well described in clinical guidelines. The extent to which stroke prevention is prescribed to ICU patients with AF is unknown. We aimed to determine the incidence of new-onset AF and describe stroke prevention strategies initiated on the ICU of our teaching hospital. Also, we compared mortality in patients with new-onset AF to critically ill patients with previously diagnosed AF and patients without any AF.MethodsThis study was a retrospective cohort study including all admissions to the ICU of the Martini Hospital (Groningen, The Netherlands) in the period 2011 to 2016. Survival analyses were performed using these real-world data.ResultsIn total, 3334 patients were admitted to the ICU, of whom 213 patients (6.4%) developed new-onset AF. 583 patients (17.5%) had a previous AF diagnosis, the other patients were in sinus rhythm. In-hospital mortality and 1-year mortality after hospital discharge were significantly higher for new-onset AF patients compared with patients with no history of AF or previously diagnosed AF. At hospital discharge, only 56.3% of the new-onset AF-patients eligible for stroke prevention received an anticoagulant. Anticoagulation was not dependent on CHA2DS2-VASc score or other patient characteristics. An effect of anticoagulative status on mortality was not significant.ConclusionAF is associated with increased mortality in critically ill patients admitted to the ICU. More guidance is needed to optimise anticoagulant treatment in critically ill new-onset AF patients.

BackgroundPublic access defibrillators (PADs) represent unique life-saving medical devices as they may be used by untrained lay rescuers. Collecting representative clinical data on these devices can be challenging. Here, we present results from a retrospective observational cohort study, describing real-world PAD utilisation over a 5-year period.MethodsData were collected between October 2012 and October 2017. Responders voluntarily submitted electronic data downloaded from HeartSine PADs, and patient demographics and other details using a case report form in exchange for a replacement battery and electrode pack.ResultsData were collected for 977 patients (692 males, 70.8%; 255 females, 26.1%; 30 unknown, 3.1%). The mean age (SD) was 59 (18) years (range ConclusionThis is the first study to report global PAD usage in voluntarily submitted, unselected real-world cases and demonstrates the real-world effectiveness of PADs, as confirmed by first shock success.

BackgroundSudden cardiac death (SCD) is a major global health problem, accounting for up to 20% of deaths in Western societies. Clinical quality registries have been shown in a range of disease conditions to improve clinical management, reduce variation in care and improve outcomes.AimTo identify existing cardiac arrest (CA) and SCD registries, characterising global coverage and methods of data capture and validation.MethodsBiomedical and public search engines were searched with the terms ‘registry cardio*’; ‘sudden cardiac death registry’ and ‘cardiac arrest registry’. Registries were categorised as either CA, SCD registries or ‘other’ according to prespecified criteria. SCD registry coordinators were contacted for contemporaneous data regarding registry details.ResultsOur search strategy identified 49 CA registries, 15 SCD registries and 9 other registries (ie, epistries). Population coverage of contemporary CA and SCD registries is highly variable with registries densely concentrated in North America and Western Europe. Existing SCD registries (n=15) cover a variety of age ranges and subpopulations, with some enrolling surviving patients (n=8) and family members (n=5). Genetic data are collected by nine registries, with the majority of these (n=7) offering indefinite storage in a biorepository.ConclusionsMany CA registries exist globally, although with inequitable population coverage. Comprehensive multisource surveillance SCD registries are fewer in number and more challenging to design and maintain. Challenges identified include maximising case identification and case verification.Trial registration numberCRD42019118910.

Objective To study time trends in incidence of atrial fibrillation (AF) in the entire Norwegian population from 2004 to 2014, by age and sex, and to estimate the prevalence of AF at the end of the study period. Methods A national cohort of patients with AF (≥18 years) was identified from inpatient admissions with AF and deaths with AF as underlying cause (1994– 2014), and AF outpatient visits (2008–2014) in the Cardiovascular Disease in Norway (CVDNOR) project. AF admissions or out-of-hospital death from AF, with no AF admission the previous 10 years defined incident AF. Age-standardised incidence rates (IR) and incidence rate ratios (IRR) were calculated. All AF cases identified through inpatient admissions and outpatient visits and alive as of 31 December 2014 defined AF prevalence. Results We identified 175 979 incident AF cases (30% primary diagnosis, 69% secondary diagnosis, 0.6% outof-hospital deaths). AF IRs (95% confidence intervals) per 100 000 person years were stable from 2004 (433 (426–440)) to 2014 (440 (433–447)). IRs were stable or declining across strata of sex and age with the exception of an average yearly increase of 2.4% in 18–44 yearolds: IRR 1.024 (1.014–1.034). In 2014, the prevalence of AF in the adult population was 3.4%. Conclusions We found overall stable IRs of AF for the adult Norwegian population from 2004 to 2014. The prevalence of AF was 3.4% at the end of 2014, which is higher than reported in previous studies. Signs of an increasing incidence of early-onset AF (

AimsOral anticoagulants (OACs) are crucial for treating atrial fibrillation (AF) patients at high thromboembolic risk. However, in AF patients at intermediate thromboembolic risk with a single non-sex-related stroke risk factor (CHA2DS2-VASc score 1 in men, 2 in women), guidelines advise to consider starting anticoagulation, which may result in OAC non-initiation due to underestimation of the thromboembolic risk of a single stroke risk factor and overestimation of the OAC-related bleeding risk. A critical appraisal of the role of OACs and the benefit–risk profile of non-vitamin K antagonist oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in this patient subgroup are needed.Methods and resultsThis systematic review provides an overview of literature on the effectiveness and safety of OACs in AF patients with a single non-sex-related stroke risk factor after searching Medline and Embase. Differences between individual stroke risk factors regarding the ischaemic stroke risk in non-anticoagulated AF patients are identified in a meta-analysis, demonstrating the highest increased risk in patients aged 65–74 years old or with diabetes mellitus, followed by heart failure, hypertension and vascular disease. Furthermore, meta-analysis results favour NOACs over VKAs, given their equal effectiveness and superior safety in AF patients at intermediate thromboembolic risk (HR 0.93, 95% CI 0.65 to 1.34 for stroke or systemic embolism; HR 0.60, 95% CI 0.45 to 0.80 for major bleeding; HR 0.48, 95% CI 0.14 to 1.59 for intracranial bleeding; HR 0.58, 95% CI 0.47 to 0.71 for mortality).ConclusionOur systematic review with meta-analysis favours the use of anticoagulation in AF patients with a single non-sex-related stroke risk factor, especially when age ≥65 years or diabetes mellitus is present, with a preference for NOACs over VKAs.

BackgroundCardiac arrhythmias have been observed among patients hospitalised with acute COVID-19 infection, and palpitations remain a common symptom among the much larger outpatient population of COVID-19 survivors in the convalescent stage of the disease.ObjectiveTo determine arrhythmia prevalence among outpatients after a COVID-19 diagnosis.MethodsAdults with a positive COVID-19 test and without a history of arrhythmia were prospectively evaluated with 14-day ambulatory electrocardiographic monitoring. Participants were instructed to trigger the monitor for palpitations.ResultsA total of 51 individuals (mean age 42±11 years, 65% women) underwent monitoring at a median 75 (IQR 34–126) days after a positive COVID-19 test. Median monitoring duration was 13.2 (IQR 10.5–13.8) days. No participant demonstrated atrial fibrillation, atrial flutter, sustained supraventricular tachycardia (SVT), sustained ventricular tachycardia or infranodal atrioventricular block. Nearly all participants (96%) had an ectopic burden of ConclusionsWe did not find evidence of malignant or sustained arrhythmias in outpatients after a positive COVID-19 diagnosis. While palpitations were common, symptoms frequently corresponded to sinus rhythm/sinus tachycardia or non-malignant arrhythmias such as isolated ectopy or non-sustained SVT. While these findings cannot exclude the possibility of serious arrhythmias in select individuals, they do not support a strong or widespread proarrhythmic effect of COVID-19 infection after resolution of acute illness.

BackgroundThe limited availability of balloon sizes for cryoballoon leads to anatomical limitations for pulmonary vein (PV) isolation. We conducted a comprehensive systematic analysis on procedural success rate, atrial fibrillation (AF) recurrence rate and complications of cryoballoon ablation in association with the anatomy of the left atrium and PV based on preprocedural CT to gain insights into proper treatments of patients with AF using cryoballoon.MethodA systematic search of literature databases, including PubMed, Web of Science and Cochrane Library, from the inception of each database through February 2021 was conducted. Search keywords included ‘atrial fibrillation’, ‘cryoballoon ablation’ and ‘anatomy’.ResultsOverall, 243 articles were identified. After screening, 16 articles comprising 1396 patients were included (3, 5 and 8 for acute success, AF recurrence and complications, respectively). Regarding acute success and AF recurrences, thinner width of the left lateral ridge, higher PV ovality, PV ostium-bifurcation distance, shorter distance from the non-coronary cusp to inferior PVs, shallower angle of right PVs against the atrial septum and larger right superior PV (RSPV) were associated with poor outcomes. Regarding complications, shorter distance between the RSPV ostium and the right phrenic nerve, larger RSPV-left atrium angle, larger RSPV area and smaller right carina width were associated with incidences of phrenic nerve injury.ConclusionThis study elucidated several key anatomical features of PVs possibly affecting acute success, AF recurrence and complications in patients with AF using cryoballoon ablation. CT analysis has helped to describe benefits and anatomical limitations for cryoballoon ablation.

BackgroundOptions for patients with ventricular tachycardia (VT) refractory to antiarrhythmic drugs and/or catheter ablation remain limited. Stereotactic radiotherapy has been described as a novel treatment option.MethodsSeven patients with recurrent refractory VT, deemed high risk for either first time or redo invasive catheter ablation, were treated across three UK centres with non-invasive cardiac stereotactic ablative radiotherapy (SABR). Prior catheter ablation data and non-invasive mapping were combined with cross-sectional imaging to generate radiotherapy plans with aim to deliver a single 25 Gy treatment. Shared planning and treatment guidelines and prospective peer review were used.ResultsAcute suppression of VT was seen in all seven patients. For five patients with at least 6 months follow-up, overall reduction in VT burden was 85%. No high-grade radiotherapy treatment-related side effects were documented. Three deaths (two early, one late) occurred due to heart failure.ConclusionsCardiac SABR showed reasonable VT suppression in a high-risk population where conventional treatment had failed.

Objective Plasma cancer antigen (CA)-125 is a tumour marker recently shown to be associated with systolic heart failure and new-onset atrial fibrillation (AF) after myocardial infarction. However, no reports have described the relationship between CA-125 and new-onset AF in healthy postmenopausal women. The aim of the present study was to evaluate the relationship between CA-125 and new-onset AF in postmenopausal women. Methods Between 2005 and 2015, 2086 women, including 1012 postmenopausal women, visited our hospital for annual health check-ups. We excluded patients with systolic dysfunction, chronic inflammatory disease, chronic obstructive pulmonary disease, histories of AF or neoplastic diseases. A total of 746 postmenopausal women underwent thorough physical examinations, including those for biomarkers such as brain natriuretic peptide, high-sensitivity C-reactive protein (hs-CRP) and CA-125. Results During the 10-year observation period, AF was documented in 31 participants (4.2%). The mean age of participants developing AF (75±6 years) was higher than that of those without AF (68±8 years). Participants developing AF showed significantly higher CA-125 (11.4±6.3 U/mL) and hs-CRP (0.10±0.11 mg/dL) levels than did those without AF (7.7±3.2 U/mL, p

Objective Atrial fibrillation (AF) is the most common arrhythmia and associated with increased morbidity and mortality. Its increasing prevalence calls for novel biomarkers to identify underlying pathophysiological mechanisms as well as patients at risk. Methods Plasma samples from 1694 individuals from the Swedish population-based Malmö Preventive Project (mean age 69.5 years; 29.3% female; mean follow-up time 9.7±3.1 years) were analysed with the Olink proximity extension assay CVD III panel consisting of 92 proteins to identify proteins associated with incident AF or atrial flutter, referred to as incident AF. Incident cases of AF (n=278) were retrieved by linkage to the registers. Participants were followed until the first episode of AF or until censoring by death or emigration. Bonferroni-corrected multivariable Cox regression models adjusted for known risk factors were used to explore possible associations of the 92 proteins and incidence of AF. Results Multivariable Cox regression analyses of 11 proteins associated with incident AF (mean follow-up time 9.7±3.1 years) after Bonferroni correction confirmed N-terminal pro-B-type natriuretic peptide (HR per 1 SD increment (95% CI) 1.80 (1.58 to 2.04); p=1.2×10−19) as risk marker of incident AF. Further, matrix metalloproteinase-2 (1.22 (1.07 to 1.39); p=0.002) and osteopontin (1.27 (1.12 to 1.44); p=2.7×10−4) were associated with incident AF at follow-up independently of traditional risk markers and NT-proBNP. Conclusion In a general Swedish population, we confirmed the well-known association of NT-proBNP with incident AF and also identified matrix metalloproteinase-2 and osteopontin as novel risk markers for incident AF, independently of traditional risk factors and NT-proBNP.

ObjectiveAtrial fibrillation (AF) is a growing problem internationally and a recognised cause of cardiovascular morbidity and mortality. The London borough of Hounslow has a lower than expected prevalence of AF, suggesting poor detection and associated undertreatment. To improve AF diagnosis and management, a quality improvement (QI) initiative was set up in 48 general practices in Hounslow. We aimed to study whether there was evidence of a change in AF diagnosis and management in Hounslow following implementation of interventions in this QI initiative.MethodsUsing the general practice information system (SystmOne), data were retrospectively collected for 415 626 patients, who were actively registered at a Hounslow practice between 1 January 2011 and 31 August 2018. Process, outcome and balancing measures were analysed using statistical process control and interrupted time series regression methods. The baseline period was from 1 January 2011 to 30 September 2014 and the intervention period was from 1 October 2014 to 31 August 2018.ResultsWhen comparing the baseline to the intervention period, (1) the rate of new AF diagnoses increased by 27% (relative risk 1.27; 95% CI 1.05 to 1.52; p2DS2-VASc and HAS-BLED risk assessments within 30 days of AF diagnosis increased from 1.7% to 19% and 0.2% to 8.1%, respectively; (4) among those at higher risk of stroke, anticoagulation prescription within 30 days of AF diagnosis increased from 31% to 63% while prescription of antiplatelet monotherapy within the same time period decreased from 17% to 7.1%; and (5) average CHA2DS2-VASc and HAS-BLED risk scores did not change.ConclusionImplementation of interventions in the Hounslow QI initiative coincided with improved AF diagnosis and management. Areas with perceived underdetection of AF should consider similar interventions and methodology.

ObjectivesProlonged ECG monitoring is clinically useful to detect unknown atrial fibrillation (AF) in stroke survivors. The diagnostic yield of prolonged ECG monitoring in other patient populations is less well characterised. We therefore studied the diagnostic yield of prolonged Holter ECG monitoring for AF in an unselected patient cohort referred from primary care or seen in a teaching hospital.MethodsWe analysed consecutive 7-day ECG recordings in unselected patients referred from different medical specialities and assessed AF detection rates by indication, age and comorbidities.ResultsSeven-day Holter ECGs (median monitoring 127.5 hours, IQR 116 to 152) were recorded in 476 patients (mean age 54.6 (SD 17.0) years, 55.9% female) without previously known AF, requested to evaluate palpitations (n=241), syncope (n=99), stroke or transient ischaemic attack (n=75), dizziness (n=29) or episodic chest pain (n=32). AF was newly detected in 42/476 (8.8%) patients. Oral anticoagulation was initiated in 40/42 (95.2%) patients with newly detected AF. Multivariate logistic regression, adjusted for age, sex and monitoring duration found four clinical parameters to be associated with newly detected AF: hypertension OR=2.54, (1.08 to 8.61) (adjusted OR (95% CI)), p=0.034; previous stroke or TIA OR=4.14 (1.81 to 13.01), p=0.001; left-sided valvular heart disease OR=5.07 (2.48 to 18.70), pConclusionsOpen multispeciality access to prolonged ECG monitoring, for example, as part of integrated, cross-sector AF care, can accelerate diagnosis of AF and increase adequate use of oral anticoagulation, especially in older and symptomatic patients with comorbidities.

BackgroundIn recent Danish nationwide register-based study, adults with small, unrepaired atrial septal defects (ASD) have increased risk of pneumonia, atrial fibrillation (AF) and stroke. Moreover, they revealed higher mortality than the background population.ObjectiveIn this nationwide study, we evaluate the hidden burden of atrial and ventricular arrhythmias in adult patients with a small, unrepaired ASD without a previous diagnosis of AF.MethodsAll Danish patients, aged 18–65, diagnosed between 1953 and 2011 with an unrepaired ASD and no documented AF were invited for 7 days Holter-recording, echocardiography and 6 min walk test. The first 48 hours Holter-recording was completely analysed, while only AF was screened for throughout all 7 days. Furthermore, the entire patient group were characterised using the unique Danish registries.ResultsA total of 151 patients (mean age 32 years) were included. Approximately 80% of the patients had spontaneous closure of their defect. Despite this, occult arrhythmias were frequent. The most common arrhythmia was supraventricular tachycardia (n=24, 16%) with non-sustained atrial arrhythmias in 21 patients and AF in two patients. A considerable number of patients had non-sustained ventricular tachycardia (n=12, 8%). Patients with ASD and tachyarrhythmias had increased right ventricular to left ventricular diastolic area in echocardiography and higher age when compared with ASD patients without arrhythmias.ConclusionAdult patients with small, unrepaired ASD have a hidden burden of both atrial and ventricular tachyarrhythmias. The mechanism likely relates to the residua of previous right-heart volume overload and incomplete reverse remodelling. Our results support guidelines recommending continued follow-up of patients with small, unrepaired ASD.

ObjectiveAtrial fibrillation (AF) is one of the most common side effects of ibrutinib, a drug that has dramatically improved the prognosis of chronic B-cell malignancies such as chronic lymphocytic leukaemia (CLL). The true incidence of ibrutinib-related AF (IRAF) is not well known and its therapeutic management poses unique challenges especially due to the inherent risk of bleeding. We aimed to determine the incidence and predictors of IRAF, and to analyse its management and outcome.MethodsA standardised monitoring was applied at two cardio-oncology clinics in consecutive patients referred before and during ibrutinib therapy. The primary endpoint was the incidence of IRAF. The excess of AF incidence with ibrutinib was studied by comparing the incidence of IRAF with the expected incidence of AF in general population and in patients with CLL not exposed to ibrutinib.Results53 patients were included. The incidence of IRAF was 38% at 2 years and the risk was 15-fold higher than the AF risk in both the general population and patients with CLL not exposed to ibrutinib (p2 at treatment initiation identified patients at high risk of developing IRAF. No major bleeding events occurred in patients on ibrutinib, although the majority of patients with IRAF were treated with anticoagulants.ConclusionsThis cardio-oncology study showed that the risk of IRAF was much higher than previously reported. The majority of cases occurred in asymptomatic patients justifying close monitoring.

ObjectivePacemaker (PM) therapy is effective when syncope is associated with bradycardia, but syncope recurrences and fall injuries after PM implantation may occur. We aimed to survey indications and outcomes of PM implantation, following evaluation of unexplained syncope.MethodsAmong 1666 consecutive unpaced patients investigated in a tertiary syncope unit by carotid-sinus massage (CSM), head-up tilt test (HUT) and ECG monitoring, 106 (6.4%; age, 65 ± 17 years) received a PM. We assessed bradycardia detection methods, PM implantation indications, and explored incidence of recurrent syncope, fall-related fractures and mortality.ResultsIndications for PM therapy were met in 32/106 patients (30%) by CSM, in 41/106 (39%) by HUT, in 14/106 patients (13%) by implantable loop-recorder (ILR) and in 19/106 (18%) by standard ECG. Sinus arrest with asystole was the predominant PM indication during CSM/HUT and external ECG monitoring, whereas ILR detected proportionally the same numbers o f asystole due to sinus arrest and atrioventricular block. During follow-up (median, 4.3 years), 15 patients (14%) had syncope recurrence, 15 suffered fall-related fractures and 9 died. Neither syncope recurrence nor fall-related fractures were dependent on initial PM indication. The composite endpoint of recurrent syncope/fall-related fracture was associated with treated hypertension (OR 2.45; 95% CI 1.00 to 6.0), reduced glomerular filtration rate (OR 1.63 per 10 mL/min↓; 95% CI 1.22 to 2.19) and atrial fibrillation (OR 3.98; 95% CI 1.11 to 14.3). Recurrent syncope predicted increased mortality (OR 9.20; 95% CI 1.89 to 44.8).ConclusionsCardiovascular autonomic testing and ECG monitoring effectively identify pacing indications in patients with unexplained syncope. After PM implantation, treated hypertension, renal failure and atrial fibrillation predict syncope recurrence and fall-related injury. Recurrent syncope predicts increased mortality.

ObjectiveTo evaluate the cost-effectiveness of insertable cardiac monitors (ICMs) compared with standard of care (SoC) for detecting atrial fibrillation (AF) in patients at high risk of stroke (CHADS2 >2), using a UK National Health Service (NHS) perspective.MethodsUsing patient characteristics and clinical data from the REVEAL AF trial, a Markov model assessed the cost-effectiveness of detecting AF with an ICM compared with SoC. Costs and benefits were extrapolated across modelled patient lifetime. Ischaemic and haemorrhagic strokes, intracranial and extracranial haemorrhages and minor bleeds were modelled. Diagnostic and device costs were included, plus costs of treating stroke and bleeding events and costs of oral anticoagulants (OACs). Costs and health outcomes, measured as quality-adjusted life years (QALYs), were discounted at 3.5% per annum. One-way deterministic and probabilistic sensitivity analyses (PSA) were undertaken.ResultsThe total per-patient cost for ICM was £13 360 versus £11 936 for SoC (namely, annual 24 hours Holter monitoring). ICMs generated a total of 6.50 QALYs versus 6.30 for SoC. The incremental cost-effectiveness ratio (ICER) was £7140/QALY gained, below the £20 000/QALY acceptability threshold. ICMs were cost-effective in 77.4% of PSA simulations. The number of ICMs needed to prevent one stroke was 21 and to cause a major bleed was 37. ICERs were sensitive to assumed proportions of patients initiating or discontinuing OAC after AF diagnosis, type of OAC used and how intense the traditional monitoring was assumed to be under SoC.ConclusionsThe use of ICMs to identify AF in a high-risk population is cost-effective for the UK NHS.

ObjectiveSudden cardiac death (SCD) in families with premature atherosclerosis (PAS) is generally attributed to lethal arrhythmias during myocardial infarction. Yet, such arrhythmias may also arise from non-ischaemic inherited susceptibility. We aimed to test the hypothesis that Brugada syndrome is prevalent among families with PAS in which SCD occurred.MethodsWe investigated all patients who underwent Ajmaline testing to screen them for Brugada syndrome because of unexplained familial SCD in the Amsterdam University Medical Centers between 2004 and 2017. We divided the cohort into two groups based on a positive family history for PAS. All individuals with a positive Ajmaline test were screened for SCN5A-mutation.ResultsIn families with SCD and PAS, the prevalence of positive Ajmaline test was similar to families with SCD alone (22% vs 19%). The number of SCD cases in families with SCD and PAS was higher (2.34 vs 1.63, pConclusionsBrugada syndrome has a similar prevalence in families with SCD and PAS as in families with SCD alone, although SCD in families with SCD and PAS occurs in more family members and at older age, while SCN5A mutations in these families are rare. This suggests that the SCD occurring in families with PAS could be related to an underlying genetic predisposition of arrhythmias, with a different genetic origin. It could be considered to screen families with SCD and PAS for Brugada syndrome.

BackgroundVentricular tachycardia (VT) is associated with increased morbidity and mortality. There is growing evidence for the effectiveness of catheter ablation in improving outcomes in patients with recurrent VT. Consequently the threshold for referral for VT ablation has fallen over recent years, resulting in increased number of procedures.ObjectiveTo evaluate the effectiveness and safety of VT ablation in a real-world tertiary centre setting.MethodsThis is a prospective analysis of all VT ablation cases performed at University Hospital Coventry. Follow-up data were obtained from review of electronic medical records and patient interview. The primary endpoint for normal heart VT was death, cardiovascular hospitalisation and VT recurrence, and for structural heart VT was arrhythmic death, VT storm (>3 episodes within 24 hours) or appropriate shock.ResultsForty-seven patients underwent 53 procedures from January 2012 to January 2018. The mean age ±SD was 57±15 years, 68% were male, 81% were Caucasian and 66% were elective cases. The aetiology of VT included normal heart (49%), ischaemic cardiomyopathy (ICM, 36%), dilated cardiomyopathy (9%), hypertrophic cardiomyopathy (4%) and valvular heart disease (2%). Procedural success occurred in 83%, with six major complications. After a median follow-up of 231 days (lower quartile 133, upper quartile 631), the primary outcome occurred in 28% of patients. There were two non-arrhythmic deaths (4%). At a median follow-up of 193 days (129–468), the primary outcome occurred in 19% of patients with ICM, while VT storm/appropriate shocks occurred in three patients (17%).ConclusionsOur real-world registry confirms that VT ablation is safe, and is associated with high acute procedural success and long-term outcomes comparable with randomised controlled studies.

BackgroundAtrial fibrillation (AF) is associated with left ventricular (LV) systolic dysfunction which may improve after AF ablation. We hypothesised that increased ventricular irregularity, as measured by R-R dispersion on the baseline ECG, would predict improvement in the left ventricular ejection fraction (LVEF) after AF ablation.MethodsPatients with LVEF 7.5%. Multivariable logistic regression (restricted to echocardiographic/ECG variables) was performed to evaluate predictors of LVEF improvement.ResultsFifty-two patients were included in this study. LVEF improved in 30 patients (58%) and was unchanged/worsened in 22 patients (42%). Those with versus without LVEF improvement had an increased baseline R-R dispersion (645±155 ms vs 537±154 ms, p=0.02, respectively). The average baseline heart rate in all patients was 93 beats per minute. After multivariable logistic regression, increased R-R dispersion (OR 1.59, 95% CI 1.00 to 2.55, p=0.03) predicted LVEF improvement.ConclusionsIncreased R-R dispersion on ECG was independently associated with improved systolic function after AF ablation. This broadens the existing knowledge of arrhythmia-induced cardiomyopathy, demonstrating that irregular electrical activation (as measured by increased R-R dispersion on ECG) is associated with a cardiomyopathy capable of improving after AF ablation.

OBJECTIVES: Compare the effect of apixaban and warfarin on coagulation and primary haemostasis biomarkers in atrial fibrillation (AF). METHODS: The biomarker substudy from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation trial included 4850 patients with AF randomised to treatment with apixaban or warfarin. Sixty per cent of patients used vitamin K antagonist (VKA) within 7 days before randomisation. Prothrombin fragment 1+2 (F1+2), D-dimer, soluble CD40 ligand (sCD40L) and von Willebrand factor (vWF) antigen were analysed at randomisation and after 2 months of study treatment. RESULTS: In patients not on VKA treatment at randomisation, F1+2 and D-dimer levels were decreased by 25% and 23%, respectively, with apixaban, and by 59% and 38%, respectively, with warfarin (p

ObjectivesGrowth differentiation factor 15 (GDF-15) is a biomarker independently associated with bleeding and death in anticoagulated patients with atrial fibrillation (AF). GDF-15 is also used as one component in the more precise biomarker-based ABC (age, biomarkers, clinical history)-AF-bleeding and ABC-AF-death risk scores. Data from large trials indicate a geographic variability in regard to overall outcomes, including bleeding and mortality risk. Our aim was to assess the consistency of the association between GDF-15, ABC-AF-bleeding score and ABC-AF-death score, with major bleeding and death, across world geographic regions.MethodsData were available from 14 767 patients with AF from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial and 8651 patients with AF from the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) trial in this cohort study. GDF-15 was analysed from plasma samples obtained at randomisation. The geographical consistency of the associations between outcomes and GDF-15, ABC-AF-bleeding score and ABC-AF-death scores were assessed by Cox-regression models including interactions with predefined geographical region.ResultsGDF-15 and the ABC-AF-bleeding score were associated with major bleeding in both trials across regions (pConclusionsIn patients with AF on anticoagulation, GDF-15 and the biomarker-based ABC-AF-bleeding and ABC-AF-death risk scores are consistently associated with respectively increased risk of major bleeding and death and have similar prognostic value across world geographic regions.Trial registration numberClinicalTrials.gov Registry NCT00412984 and NCT00262600.

ObjectiveCavo-tricuspid isthmus atrial flutter (CTI-AFL) is an important arrhythmia to recognise because there is a highly effective and relatively low-risk ablation strategy. However, clinical experience has demonstrated that providers often have difficulty distinguishing AFL from atrial fibrillation.MethodsWe developed a novel ECG-based three-step algorithm to identify CTI-AFL based on established CTI flutter characteristics and verified on consecutive ablation cases of typical flutter, atypical flutter and atrial fibrillation. The algorithm assesses V1/inferior lead F-wave concordance, consistency of P-wave morphology and the presence of isoelectric intervals in the inferior leads. In this observation study, the algorithm was validated on a cohort of 50 second-year medical students. Students were paired in a control and experimental group, and each pair received 10 randomly selected ECGs (from a pool of 50 intracardiac electrogram-proven CTI-AFL and 50 AF or atypical AFL cases). The experimental group received a cover sheet with the CTI algorithm, and the control group received no additional guidance.ResultsThere was a statistically significant difference in the mean number of correctly identified ECGs among the students in the experimental and control groups (8.12 vs 5.68, pConclusionWe developed a three-step ECG algorithm that provides a simple, sensitive, specific and accurate tool to identify CTI-AFL.

AimsThe clinical outcome and threshold of oral anticoagulation differs between patients with solitary atrial flutter (AFL) and those with AFL developing atrial fibrillation (AF) (AFL-DAF). We therefore investigated previously unevaluated predictors of AF development in patients with AFL, and also the predictive values of risk scores in predicting the occurrence of AF and ischaemic stroke.Methods and resultsParticipants were those diagnosed with AFL between 1 January 2001 and 31 December 2013. Patients were classified into solitary AFL and AFL-DAF groups during follow-up. Finally, 4101 patients with solitary AFL and 4101 patients with AFL-DAF were included after 1:1 propensity score matching with CHA2DS2-VASc scores and their components, AFL diagnosis year and other comorbidities. The group difference in the prevalence of ischaemic stroke/transient ischaemic attack (TIA) and congestive heart failure (CHF) was substantial, that of vascular disease was moderate, and that of diabetes and hypertension was negligible. Therefore, we reweighted the component of heart failure as 2 (the same with stroke/TIA) and vascular disease as 1 in the proposed A2C2S2-VASc score. The proposed A2C2S2-VASc and CHA2DS2-VASCscores showed patients with AFL who had higher delta scores and follow-up scores had higher risk of AF development. The delta score outperformed the follow-up score in both scoring systems in predicting ischaemic stroke.ConclusionThis study showed that new-onset CHF, stroke/TIA and vascular disease were predictors of AF development in patients with AFL. The dynamic score and changes in both CHA2DS2-VASCand the proposed A2C2S2-VASc score could predict the development of AF and ischaemic stroke.