Validating the predictive ability of the 2MACE score for major adverse cardiovascular events in patients with atrial fibrillation: results from phase II/III of the GLORIA-AF registry.

The 2MACE score was specifically developed as a risk-stratification tool in atrial fibrillation (AF) to predict cardiovascular outcomes. We evaluated the predictive ability of the 2MACE score in the GLORIA-AF registry. All eligible patients from phase II/III of the prospective global GLORIA-AF registry were included. Major adverse cardiac events (MACEs) were defined as the composite outcome of stroke, myocardial infarction and cardiovascular death. Cox proportional hazards were used to examine the relationship between the 2MACE score and study outcomes. Predictive capability of the 2MACE score was investigated using receiver-operating characteristic curves. A total of 25,696 patients were included (mean age 71 years, female 44.9%). Over 3 years, 1583 MACEs were recorded. Patients who had MACE were older, with more cardiovascular risk factors and were less likely to be managed using a rhythm-control strategy. The median 2MACE score in the MACE and non-MACE groups were 2 (IQR 1-3) and 1 (IQR 0-2), respectively (p < 0.001). The 2MACE score was positively associated with an increase in the risk of MACE, with a score of ≥ 2 providing the best combination of sensitivity (69.6%) and specificity (51.6%), HR 2.47 (95% CI, 2.21-2.77). The 2MACE score had modest predictive performance for MACE in patients with AF (AUC 0.655 (95% CI, 0.641-0.669)). Our analysis in this prospective global registry demonstrates that the 2MACE score can adequately predict the risk of MACE (defined as myocardial infarction, CV death and stroke) in patients with AF. Clinical trial registration: http://www.clinicaltrials.gov . Unique identifiers: NCT01468701, NCT01671007 and NCT01937377.

Contemporary management of atrial fibrillation and the predicted vs. absolute risk of ischaemic stroke despite treatment: a report from ESC-EHRA EORP-AF Long-Term General Registry.

BACKGROUND: Risk stratification in patients with atrial fibrillation (AF) is important to facilitate guideline-directed therapies. The Calculator of Absolute Stroke Risk (CARS) scheme enables an individualized estimation of 1-year absolute risk of stroke in AF. We aimed to investigate the predicted and absolute risks of ischaemic stroke, and evaluate whether CARS (and CHA2DS2-VASc score) may be useful for identifying high risk patients with AF despite contemporary treatment. METHODS: We utilized the EORP-AF General Long-Term Registry which prospectively enrolled patients with AF from 250 centres across 27 participating European countries. Patients with sufficient data to determine CARS and CHA2DS2-VASc score, and reported outcomes of ischaemic stroke were included in this analysis. The primary outcome of ischaemic stroke was recorded over a 2-year follow-up period. RESULTS: A total of 9444 patients were included (mean age 69.1 [±11.4] years; 3776 [40.0%] females). There was a high uptake (87.9%) of anticoagulation therapy, predominantly with vitamin K antagonist (50.0%). Over a mean follow-up period of 24 months, there were a total of 101 (1.1%) ischaemic stroke events. In the entire cohort, the median CARS and absolute annual risks of ischaemic stroke were 2.60 (IQR 1.60-4.00) and 0.53% (95%CI 0.43-0.64%), respectively. There was no statistical difference between the predictive performance of CARS and CHA2DS2-VASc score (0.621 [95%CI 0.563-0.678] vs. 0.626 [95%CI 0.573-0.680], P = 0.725). CONCLUSION: Contemporary management of AF was associated with a low risk of ischaemic stroke. CARS and CHA2DS2-VASc score may be useful to identify high risk patients despite treatment who may benefit from more aggressive treatment and follow-up.

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry.

BACKGROUND: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The 'Atrial fibrillation Better Care' (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. METHODS: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. RESULTS: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58-0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52-0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58-0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56-0.98) and composite outcome (aHR: 0.76, 95%CI 0.60-0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. CONCLUSIONS: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients.

Local impedance for the optimization of radiofrequency lesion delivery: A review of bench and clinical data.

INTRODUCTION: Radiofrequency catheter ablation is a cornerstone of treatment for many cardiac arrhythmias. Progression in three-dimensional mapping and contact-force sensing technologies have improved our capability to achieve success, but challenges still remain. METHODS: In this article, we discuss the importance of overall circuit impedance in radiofrequency lesion formation. This is followed by a review of the literature regarding recently developed "local impedance" technology and its current and future potential applications and limitations, in the context of established surrogate markers currently used to infer effective ablation. RESULTS: We discuss the role of local impedance in assessing myocardial substrate, as well as its role in clinical studies of ablation. We also discuss safety considerations, limitations and ongoing research. CONCLUSION: Local impedance is a novel tool which has the potential to tailor ablation in a manner distinct from other established metrics.

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry.

BACKGROUND: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. METHODS: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. RESULTS: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p < .001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01-1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23-3.99] compared to eGFR ≥90 ml/min/1.73 m2 ). CONCLUSION: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF.

Social determinants of health and cardiovascular outcomes in patients with heart failure.

BACKGROUND: We examined the associations between family income and educational attainment with incident atrial fibrillation (AF), myocardial infarction (MI), stroke and cardiovascular (CV) death among patients with newly-diagnosed heart failure (HF). METHODS: In a nationwide Danish registry of HF patients diagnosed between 2008 and 2018, we established a cohort for each outcome. When examining AF, MI and stroke, respectively, patients with a history of these outcomes at diagnosis of HF were excluded. We used cause-specific proportional hazard models to estimate hazard ratios for tertile groups of family income and three levels of educational attainment. RESULTS: Among 27,947 AF-free patients, we found no association between income or education and incident AF. Among 27,309 MI-free patients, we found that lower income (hazard ratio 1.28 [95% CI 1.11-1.48] and 1.11 [0.96-1.28] for lower and medium vs. higher income) and education (1.23 [1.04-1.45] and 1.15 [0.97-1.36] for lower and medium vs. higher education) were associated with MI. Among 36,801 stroke-free patients, lower income was associated with stroke (1.38 [1.23-1.56] and 1.27 [1.12-1.44] for lower and medium vs. higher income) but not education. Lower income (1.56 [1.46-1.67] and 1.32 [1.23-1.42] for lower and medium vs. higher income) and education (1.20 [1.11-1.29] and 1.07 [0.99-1.15] for lower and medium vs. higher education) were associated with CV death. CONCLUSIONS: In patients with newly-diagnosed HF, lower family income was associated with higher rates of acute MI, stroke and cardiovascular death. Lower educational attainment was associated with higher rates of acute MI and cardiovascular death. There was no evidence of associations between income and education with incident AF.

Number needed to treat for net effect of anticoagulation in atrial fibrillation: Real-world vs. clinical-trial evidence.

AIMS: The net benefit of oral anticoagulants (OACs) in atrial fibrillation (AF) is poorly understood. We aimed to determine the NNT for net effect (NNTnet ) using calculator of absolute stroke risk (CARS) in anticoagulated patients with AF in real-world and clinical trial cohorts. METHODS: Post-hoc analysis of patient-level data from the real-world Murcia AF Project and AMADEUS clinical trial. Baseline risk of stroke was determined using CARS. The risk of stroke and major bleeding events with OAC were determined using the number of respective events at 1-year. NNTnet was calculated as a reciprocal of the net effect of absolute risk reduction with OAC (NNTnet  = 1/(absolute risk reduction of stroke[ARRstroke ] - absolute risk increase of major bleeding[ARIbleeding ])). RESULTS: In total, 3511 patients were included (1306 [37.2%] real-world patients and 2205 [62.8%] clinical trial participants). The absolute 1-year stroke risk was similar across both cohorts. In the real-world cohort, OAC was associated with a 4.0% ARRstroke , 25 NNTbenefit , 1.0% ARIbleeding , 100 NNTharm and 34 NNTnet . In the clinical trial cohort, OAC was associated with a 3.8% ARRstroke , 27 NNTbenefit , 1.6% ARIbleeding , 63 NNTharm and 46 NNTnet . In both cohorts, the NNTnet was significantly lower in patients with an excess stroke risk of ≥2% by CARS. CONCLUSION: Overall, the NNTnet approach in AF incorporates information regarding baseline risk of stroke and major bleeding, and relative effects of OAC with the potential to include multiple additional outcomes and weighting of events based on their perceived effects by individual patients.

Relationship between Chronic Kidney Disease, Time-in-Therapeutic Range, and Adverse Outcomes in Atrial Fibrillation: A post hoc Analysis from the AMADEUS Trial.

BACKGROUND: The benefit of anticoagulation therapy in atrial fibrillation (AF) and chronic kidney disease (CKD) remains controversial. We aimed to evaluate the impact of renal function on the quality of anticoagulation control, and the effects of both these factors on outcomes in AF. METHODS: Post hoc analysis of the AMADEUS trial. Trial-related outcomes were adjudicated and we studied the composite of first stroke/major bleeding/all-cause mortality, ischaemic stroke, major bleeding, all-cause mortality, and cardiovascular mortality. RESULTS: We included 2,282 vitamin K antagonist (VKA)-treated patients {n = 787 (34.5%) females; median age 72 (interquartile ranges [IQR] 64-77) years}. Median follow-up was 365 (IQR 189-460) days. There were 1,922 (84.2%) non-CKD and 360 (15.8%) CKD patients. Renal function was inversely correlated with time-in-therapeutic range (r = -0.047, p = 0.025). There was no statistical difference in terms of crude study outcomes based on renal function. Multivariable regression analysis demonstrated that moderate renal failure with estimated glomerular filtration rate of less than 60 mL/min/1.73 m2 (p = 0.032) and percentage of time-in-therapeutic range (p = 0.011) were independent predictors for the composite outcome of stroke, major bleeding, and all-cause mortality. CONCLUSION: Deteriorated renal function has a small negative impact on the quality of anticoagulation control with VKA which is linked to poor outcomes in AF. However, moderate renal failure itself was an independent risk factor for increased risk of stroke, major bleeding, and all-cause mortality amongst patients with AF.

Clinical utility and prognostic implications of the novel 4S-AF scheme to characterize and evaluate patients with atrial fibrillation: a report from ESC-EHRA EORP-AF Long-Term General Registry.

AIMS: The 4S-AF classification scheme comprises of four domains: stroke risk (St), symptoms (Sy), severity of atrial fibrillation (AF) burden (Sb), and substrate (Su). We sought to examine the implementation of the 4S-AF scheme in the EORP-AF General Long-Term Registry and compare outcomes in AF patients according to the 4S-AF-led decision-making process. METHODS AND RESULTS: Atrial fibrillation patients from 250 centres across 27 European countries were included. A 4S-AF score was calculated as the sum of each domain with a maximum score of 9. Of 6321 patients, 8.4% had low (St), 47.5% EHRA I (Sy), 40.5% newly diagnosed or paroxysmal AF (Sb), and 5.1% no cardiovascular risk factors or left atrial enlargement (Su). Median follow-up was 24 months. Using multivariable Cox regression analysis, independent predictors of all-cause mortality were (St) [adjusted hazard ratio (aHR) 8.21, 95% confidence interval (CI): 2.60-25.9], (Sb) (aHR 1.21, 95% CI: 1.08-1.35), and (Su) (aHR 1.27, 95% CI: 1.14-1.41). For CV mortality and any thromboembolic event, only (Su) (aHR 1.73, 95% CI: 1.45-2.06) and (Sy) (aHR 1.29, 95% CI: 1.00-1.66) were statistically significant, respectively. None of the domains were independently linked to ischaemic stroke or major bleeding. Higher 4S-AF score was related to a significant increase in all-cause mortality, CV mortality, any thromboembolic event, and ischaemic stroke but not major bleeding. Treatment of all 4S-AF domains was associated with an independent decrease in all-cause mortality (aHR 0.71, 95% CI: 0.55-0.92). For each 4S-AF domain left untreated, the risk of all-cause mortality increased substantially (aHR 1.35, 95% CI: 1.16-1.56). CONCLUSION: Implementation of the novel 4S-AF scheme is feasible, and treatment decisions based on this scheme improve mortality rates in AF.

Relationship between temporal rhythm-based classification of atrial fibrillation and stroke: real-world vs. clinical trial.

BACKGROUND: The risk of stroke according to clinical classification of atrial fibrillation (AF) remains poorly defined. Here, we assessed the impact of AF type on stroke risk in vitamin K antagonist-treated patients with AF in 'real-world' and 'clinical trial' cohorts. METHODS: Post-hoc analysis of patient-level data from the Murcia AF Project and AMADEUS trial. Clinical classification of AF was based on contemporary recommendations from international guidelines. Study endpoint was the incidence rate of ischaemic stroke. Stroke risk was determined using CHA2DS2-VASc score and CARS. A modified CHA2DS2-VAS'c' score that applied one additional point for a 'c' criterion of continuous AF (i.e. non-paroxysmal AF) was calculated. RESULTS: We included 5,917 patients: 1,361 (23.0%) real-world and 4,556 (77.0%) clinical trial. Baseline demographics were balanced in the real-world cohort but clinical trial participants with non-pAF (vs. pAF) were older, male-predominant and had more comorbidities. Crude stroke rates were comparable between the groups in real-world patients (IRR 0.72 [95% CI,0.37-1.28], p = 0.259) though clinical trial participants with non-pAF had a significantly higher crude rate of stroke events (IRR 4.66 [95%,CI,2.41-9.48], p < 0.001). Using multivariable analysis, AF type was not independently associated with stroke risk in the real-world (adjusted HR 1.41 [95% CI,0.80-2.50], p = 0.239) and clinical trial (adjusted HR 1.16 [95% CI,0.62-2.20], p = 0.646) cohorts, after accounting for other risk factors. There was no significant improvement in the CHA2DS2-VAS'c' compared to CHA2DS2-VASc score in either cohorts (p > 0.05). CONCLUSIONS: Overall, our results support the need for anticoagulation based on thromboembolic risk profile rather than AF type.

Ablation index-guided 50W radiofrequency ablation for left atrial posterior wall isolation in atrial fibrillation.

BACKGROUND: Ablation index (AI)-guided ablation for posterior wall isolation (PWI) using high-power, short-duration remains untested. We sought to evaluate the acute outcomes of AI-guided 50 W ablation vs. conventional ablation, and investigate the differences in relationship between contact force (CF), time and AI in both groups. METHODS: Consecutive patients undergoing first-time AI-guided ablation with PWI using either 50 W or 35-40 W ablation were enrolled. Acute procedural metrics and individual lesion level ablation data were compared between groups. RESULTS: 40 patients (50 W: n = 20, 35-40 W: n = 20) with atrial fibrillation were included. Total procedure time was significantly reduced with 50 W (120 vs. 143 mins, p = 0.004) and there was a trend toward decreased ablation time (22 vs. 28 mins, p = 0.052). First pass and acute success of PWI were comparable between the 50 W and 35-40 W groups (10 vs. 8 patients, p = 0.525 and 20 vs. 19 patients, p = 1.000, respectively). Individual lesion analysis of all 959 RF applications (50 W: n = 458, 35-40 W: n = 501) demonstrated that 50 W ablation led to lower ablation time per lesion (10.4 vs. 13.0s, p < 0.001), and increased AI (471 vs. 461, p < 0.001) and impedance drop (7.4 vs. 6.9ohms, p = 0.007). Excessive ablations (AI>600 for roof line; AI>500 elsewhere) were more frequently observed in the 50 W group (9.0% vs. 4.6%, p = 0.007). CF had very good discriminative capability for excessive ablation in both groups. At 50 W, limiting the CF to <10 g reduced the number of excessive ablations on the floor line and within the posterior box to 12% and 4%,respectively. Recurrence of atrial arrhythmias at 12 months were comparable between the groups. CONCLUSION: AI-guided 50 W RF ablation reduces the ablation time of individual lesions and total procedure time without compromising first pass and acute success rates of PWI or 12-month outcomes compared to conventional powers.

Procedural efficiencies, lesion metrics, and 12-month clinical outcomes for Ablation Index-guided 50 W ablation for atrial fibrillation.

AIMS: The safety of Ablation Index (AI)-guided 50 W ablation for atrial fibrillation (AF) remains uncertain, and mid-term clinical outcomes have not been described. The interplay between AI and its components at 50 W has not been reported. METHODS AND RESULTS: Eighty-eight consecutive AF patients (44% paroxysmal) underwent AI-guided 50 W ablation. Procedural and 12-month clinical outcomes were compared with 93 consecutive controls (65% paroxysmal) who underwent AI-guided ablation using 35-40 W. Posterior wall isolation (PWI) was performed in 44 (50%) and 23 (25%) patients in the 50 and 35-40 W groups, respectively, P < 0.001. The last 10 patients from each group underwent analysis of individual lesions (n = 1230) to explore relationships between different powers and the AI components. Pulmonary vein isolation was successful in all patients. Posterior wall isolation was successful in 41/44 (93.2%) and 22/23 (95.7%) in the 50 and 35-40 W groups, respectively (P = 0.685). Radiofrequency times (20 vs. 26 min, P < 0.001) and total procedure times (130 vs. 156 min, P = 0.002) were significantly lower in the 50 W group. No complication or steam pop was seen in either group. Twelve-month freedom from arrhythmia was similar (80.2% vs. 82.8%, P = 0.918). A higher proportion of lesions in the 50 W group were associated with impedance drop >7 Ω (54.6% vs. 45.5%, P < 0.001). Excessive ablation (AI >600 anteriorly, >500 posteriorly) was more frequent in the 50 W group (9.7% vs. 4.3%, P < 0.001). CONCLUSION: Ablation Index-guided 50 W AF ablation is as safe and effective as lower powers and results in reduced ablation and procedure times. Radiofrequency lesions are more likely to be therapeutic, but there is a higher risk of delivering excessive ablation.

Safety, effectiveness, and quality of life following pulmonary vein isolation with a multi-electrode radiofrequency balloon catheter in paroxysmal atrial fibrillation: 1-year outcomes from SHINE.

AIMS: To evaluate the safety and effectiveness of a compliant multi-electrode radiofrequency balloon catheter (RFB) used with a multi-electrode diagnostic catheter for pulmonary vein isolation (PVI). METHODS AND RESULTS: This prospective, multicentre, single-arm study was conducted at six European sites and enrolled patients with symptomatic paroxysmal atrial fibrillation. The primary effectiveness endpoint was entrance block in treated pulmonary veins (PVs) after adenosine/isoproterenol challenge. The primary safety endpoint was the occurrence of primary adverse events (PAEs) within 7 days. Cerebral magnetic resonance imaging and neurological assessments were performed pre- and post-ablation in a subset of patients. Atrial arrhythmia recurrence was assessed over 12 months via transtelephonic and Holter monitoring. Quality of life was assessed by the Atrial Fibrillation Effect on Quality of Life (AFEQT) questionnaire. Of 85 patients undergoing ablation per study protocol, PV entrance block was achieved in all (one PV required touch-up with a focal catheter). Acute reconnection of ≥1 PVs after adenosine/isoproterenol challenge was observed in 9.3% (30/324) of PVs ablated. Post-ablation, silent cerebral lesions were detected in 9.7% (3/31) of patients assessed, all of which was resolved at 1-month follow-up. One patient experienced a PAE (retroperitoneal bleed). Freedom from documented symptomatic and all arrhythmia was 72.2% and 65.8% at 12 months. Four patients (4.7%) underwent repeat ablation. Significant improvements in all AFEQT subscale scores were seen at 6 and 12 months. CONCLUSION: PVI with the novel RFB demonstrated favourable safety and effectiveness, with low repeat ablation rate and clinically meaningful improvement in quality of life. CLINICALTRIALS.GOV REGISTRATION NUMBER: NCT03437733.

Primary percutaneous coronary intervention in nonagenarians: is it worthwhile?

BACKGROUND: Previous studies have demonstrated the feasibility of primary percutaneous coronary intervention (PPCI) in carefully selected nonagenarians. Although current guidelines recommend immediate revascularization in patients with ST elevation myocardial infarction (STEMI) it remains unclear whether PPCI reduces mortality in nonagenarians. The objective of this study is to compare mortality in nonagenarians presenting via the PPCI pathway who undergo coronary intervention, versus those who are managed medically. METHODS AND RESULTS: A total of 111 consecutive nonagenarians who presented to our tertiary center via the PPCI pathway between July 2013 and December 2018 with myocardial infarction were included. Clinical and angiographic details were collected alongside data on all-cause mortality. The final diagnosis was STEMI in 98 (88.3%) and NSTEMI in 13 (11.7%). PPCI was performed in 42 (37.8%), while 69 (62.2%) were medically managed. A significant number of the medically managed cohort had atrial fibrillation (23.2% vs 2.4% p = 0.003) and presented with a completed infarct (43.5% vs 4.8% p = 0.001). Other baseline and clinical variables were well matched in both groups. There was a trend towards increased 30-day mortality in the medically managed group (40.6% vs 23.8% p = 0.07). Kaplan Meier survival analysis demonstrated a significant difference in survival by 3 years (48.1% vs 21.7% p = 0.01). This was the case even when those with completed infarcts were excluded (44.3% vs 14.6%, p = 0.01). CONCLUSION: In this series of selected nonagenarians presenting with acute myocardial infarction, those undergoing PPCI appeared to have a lower mortality compared to those managed medically.

Long-term outcomes of left atrial appendage occlusion in high-risk atrial fibrillation patients: 4-year follow up data.

Long-term follow-up data of left atrial appendage (LAA) occlusion in patients with atrial fibrillation (AF) are sparse. To address these data gaps, we analysed the 4-year outcomes of AF patients following LAA occlusion. The was a retrospective cohort study of high-risk patients with AF who underwent successful implantation of the Amulet device at our center between 2014 and 2017. Study endpoints were the rate of stroke, major bleeding and all-cause mortality. We included 71 patients (35.2% females) with a median age of 78 (IQR 73-82) years. Over a median follow-up period of 46 (IQR 19-56) months, the annual rate of ischemic stroke was 1.06 events/100 patient-years (95% CI 0-2.35), hemorrhagic stroke was 1.06 events/100 patient-years (95% CI 0-2.35) and major extracranial bleeding that required unplanned hospital admission was 1.84 events/100 patient-years (95% CI 0.25-3.43). A total of 28 (39.4%) patients died during this period with an annual mortality rate of 10.29 events/100 patient-years (95% CI 7.25-13.32). Our experience suggests that LAA occlusion using the Amulet device appears to be associated with a low risk of ischemic stroke in high-risk AF patients who are deemed unsuitable for oral anticoagulation; however, these patients have a high rate of mortality over the medium to long-term follow-up, and an ongoing significant risk of bleeding and thrombotic events.

Outcomes in VKA-treated patients with atrial fibrillation and chronic kidney disease: Clinical trials vs 'real-world'.

BACKGROUND: Our objectives were to evaluate the risk of adverse events in a 'real-world' vs 'clinical trial' cohort of atrial fibrillation (AF) patients with chronic kidney disease (CKD). METHODS: We studied patient-level data for vitamin K antagonist-treated AF patients with a creatinine clearance <60 mL/min from the Murcia AF Project and AMADEUS trial. The study end-points were ischaemic stroke, major bleeding, all-cause mortality, myocardial infarction and intracranial haemorrhage. RESULTS: This study included 1,108 AF patients with CKD. The annual rate of the composite study outcome of ischaemic stroke, major bleeding and all-cause mortality was higher in the real-world (13.4%) vs AMADEUS (6.6%) cohort with an IRR of 2.04 (95% CI,1.34-3.09), P < .001. Individual annual rates of major bleeding, all-cause mortality and non-cardiovascular mortality were significantly greater in the real-world cohort. Similar findings were demonstrated even after multivariable adjustment, with the composite outcome HR of 2.85 (95% CI,1.74-4.66), P < .001. In a propensity score matched cohort, this risk remained significantly higher in the real-world cohort (IRR 2.95 [95% CI,1.03-10.28], P = .027), as did the risk of major bleeding and all-cause mortality. CONCLUSION: Vitamin K antagonist-treated AF patients with CKD are exposed to significant annual rates of major adverse events including all-cause mortality. This risk may be under-appreciated in the idealised environment of randomised controlled trials.

Impact of abdominal obesity on outcomes of catheter ablation in Korean patients with atrial fibrillation.

BACKGROUND: Effects of abdominal obesity on outcomes of atrial fibrillation (AF) ablation remains ill-defined. Here, we evaluated the impact of abdominal obesity on the long-term efficacy and safety of catheter AF ablation among Korean patients. METHODS: We utilised the Korean National Health Insurance Service database to identify patients who underwent AF ablation. Abdominal obesity was defined as waist circumference ≥90 cm (males) and ≥85 cm (females). The primary endpoint was AF recurrence and secondary endpoints were ischaemic stroke, intracranial haemorrhage and death. Additionally, safety endpoints of peri-procedural complications were studied. RESULTS: Among 5397 patients (median age 58 [IQR 51-65] years; 23.6% females), abdominal obesity was present in 1759 (32.6%). The rate of AF recurrence was not statistically different between the groups at 1-year (10.3 vs 8.7 events/100-PYs, P = .078), though abdominal obesity was associated with significantly higher rates of AF recurrence at 3-year (7.6 vs 6.3 events/100-PYs, P = .008) and 6-year (6.3 vs 5.2 events/100-PYs, P = .004) follow-ups. Kaplan-Meier survival analysis found significantly higher rates of AF recurrence in patients with obesity based on body mass index (BMI) and waist circumference (log-rank for trend P = .006). Using multivariable regression analysis, obesity by both BMI and waist circumference was an independent predictor for AF recurrence (HR 1.21 [95% CI, 1.05-1.40]), after accounting for other risk factors. There was a trend for increased rates of ischaemic stroke at 3-year and 6-year follow-ups in patients with abdominal obesity. Furthermore, this group of patients had a greater rate of intracranial haemorrhage. All-cause death was comparable between both groups. Total peri-procedural complications were not associated with abdominal obesity. CONCLUSION: Abdominal obesity as indicated by waist circumference was associated with a greater burden of concomitant diseases and an independent risk factor for long-term redo AF intervention following catheter ablation but had no effects on total peri-procedural complications.

Smart Wearables for Cardiac Monitoring-Real-World Use beyond Atrial Fibrillation.

The possibilities and implementation of wearable cardiac monitoring beyond atrial fibrillation are increasing continuously. This review focuses on the real-world use and evolution of these devices for other arrhythmias, cardiovascular diseases and some of their risk factors beyond atrial fibrillation. The management of nonatrial fibrillation arrhythmias represents a broad field of wearable technologies in cardiology using Holter, event recorder, electrocardiogram (ECG) patches, wristbands and textiles. Implementation in other patient cohorts, such as ST-elevation myocardial infarction (STEMI), heart failure or sleep apnea, is feasible and expanding. In addition to appropriate accuracy, clinical studies must address the validation of clinical pathways including the appropriate device and clinical decisions resulting from the surrogate assessed.

Practice-derived data on non-vitamin K antagonist oral anticoagulant therapy to complement observations from randomized trials.

Anticoagulation is fundamental in the management of patients with atrial fibrillation (AF). The study aims to provide a comparative review of the major phase III randomized clinical trials (RCTs) and real-world data (RWD) from reliable, high-grade Phase IV studies that assess the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) vs. vitamin K antagonists (VKAs). Observational studies based on nationwide or health insurance database records on the use of NOACs vs. VKAs in patients with AF were included. We performed a comparison of the efficacy and safety characteristics associated with NOACs vs. VKAs in RCTs and RWD. Although RCTs provide strong support for evidence-based practice, RWD may be used to reflect the broader picture of various clinical settings, provide supplementary insight and fulfil knowledge gaps. Both study types confirmed the safety and efficacy of NOACs in preventing stroke and thromboembolism in patients with AF. In comparison to VKAs, NOACs were associated with reduced risk of ischaemic events and lower rates of adverse events such as major bleeding or intracranial haemorrhage. Administration of NOACs might be associated with increased risk of dose-related gastrointestinal bleeding and myocardial ischaemic events, especially in the early treatment period after switching from VKAs. Special care should be taken in challenging clinical situations like severe renal or hepatic impairment when the treatment regimen needs to be considered individually. Randomized clinical trial and RWD studies are complementary and present comparable findings, affirming that NOACs are safe and effective for anticoagulation of patients with AF in daily clinical practice.

Systematic re-evaluation of SCN5A variants associated with Brugada syndrome.

BACKGROUND: A large number of SCN5A variants have been reported to underlie Brugada syndrome (BrS). However, the evidence supporting individual variants is highly heterogeneous. OBJECTIVE: We systematically re-evaluated all SCN5A variants reported in BrS using the 2015 American college of medical genetics and genomics and the association for molecular pathology (ACMG-AMP) guidelines. METHODS: A PubMed/Embase search was performed to identify all reported SCN5A variants in BrS. Standardized bioinformatic re-analysis (SIFT, PolyPhen, Mutation Taster, Mutation assessor, FATHMM, GERP, PhyloP, and SiPhy) and re-evaluation of frequency in the gnomAD database were performed. Fourteen ACMG-AMP rules were deemed applicable for SCN5A variant analysis. RESULTS: Four hundred and eighty unique SCN5A variants were identified, the majority of which 425 (88%) were coding variants. One hundred and fifty-six of 425 (37%) variants were classified as pathogenic/likely pathogenic. Two hundred and fifty-eight (60%) were classified as variants of uncertain significance, while a further 11 (3%) were classified as benign/likely benign. When considering the subset of variants that were considered "null" variants separately, 95% fulfilled criteria for pathogenicity/likely pathogenicity. In contrast, only 17% of missense variants fulfilled criteria for pathogenicity/likely pathogenicity. Importantly, however, only 25% of missense variants had available functional data, which was a major score driver for pathogenic classification. CONCLUSION: Based on contemporary ACMG-AMP guidelines, only a minority of SCN5A variants implicated in BrS fulfill the criteria for pathogenicity or likely pathogenicity.