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Background: There is limited knowledge of physicians' antiarrhythmic drug (AAD) treatment practices for patients with atrial fibrillation and adherence to guidelines in European countries.

Methods: An online survey (n = 321) of cardiologists, cardiac electrophysiologists and interventional electrophysiologists was conducted in Germany (DE; n = 83), Italy (IT; n = 95), Sweden (SE; n = 60) and the United Kingdom (UK; n = 83) including 96 questions on treatment practices.

Results: ESC guidelines were the most important non-patient factor influencing treatment practice (55-72 %). However, while amiodarone was frequently (88-93 %) used in heart failure with reduced left ventricular ejection fraction, it was also a typical treatment choice for minimal/no-structural heart disease (SHD) (28 %), particularly in UK. Other deviations from guidelines were the use of class 1C drugs in coronary artery disease (CAD) and other SHD, and use of sotalol in left ventricular hypertrophy and renal impairment. In-hospital initiation of sotalol was low, with the exception of SE. Sotalol (16-41 %) and dronedarone use (10-54 %) in CAD varied among countries. For frequent, symptomatic paroxysmal AF, ablation was generally favoured, but AADs were preferred by 53 % in SE. In asymptomatic or subclinical AF, AADs were used by 41 % (range: 22-60 %), ablation by 11 % (range 2-18 %). In contrast to guidelines that prioritize safety, anticipated efficacy was more important (51 %) than safety (31 %) when selecting AADs.

Conclusions: Despite recognizing the importance of guidelines, deviations in AAD use were common with the potential to compromise patient safety. These findings indicate the need for more educational support for optimal AAD selection in AF management.

BACKGROUND: Data on long-term effects of catheter ablation vs antiarrhythmic drugs (AADs) on health-related quality of life (HRQoL) and atrial fibrillation (AF) burden are limited.

OBJECTIVE: The study aimed to assess long-term HRQoL and rhythm data in patients with symptomatic AF.

METHODS: The 75 patients who underwent ablation and 74 receiving AADs in the Catheter Ablation compared with Pharmacological Therapy for Atrial Fibrillation (CAPTAF) trial were followed for 48 months. The General Health subscale of the 36-Item Short-Form Health Survey, time to first AF episode ≥1 hour, and AF burden, recorded by implantable cardiac monitors, were compared.

RESULTS: One hundred forty-seven patients completed follow-up, with 7 crossovers in the ablation group and 34 crossovers in the AAD group. General Health improved by ablation from a median of 62 points at baseline to 79.2 points at follow-up (P < .001) and by AADfrom a median of 67 to 77 points (P < .001), without treatment differences (P = .77). Time to first AF episode ≥1 hour was longer (median 257 days in the ablation group vs 180 days in the AAD group; P = .025). The cumulative AF burden during follow-up was lower in the ablation group (median 0.3%; interquartile range [IQR] 0%-1.4%) than in the AAD group (1.6%; IQR 0.1%-11.0%); P = .01. The cumulative reduction in AF burden compared with baseline was greater in the ablation group (median -89.5%; IQR -98.4% to -51.3%) than in the AAD group (-52.7%; IQR -92.6% to 263.6%); P < .001.

CONCLUSION: HRQoL improvement in long-term did not differ between ablation and AAD groups despite a larger reduction in AF burden after ablation. The results should be interpreted in the light of a high crossover rate in the AAD group.

  Background

Early identification of individuals at risk of developing heart failure (HF) may improve poor prognosis. A dominant sympathetic activity is common in HF and associated with worse outcomes; however, less is known about the autonomic balance before HF.

Hypothesis

A low frequency/high frequency (L-F/H-F) ratio, index of heart rate variability, and marker of the autonomic balance predict the development of HF and may improve the performance of the HF prediction model when added to traditional cardiovascular (CV) risk factors.

Methods

Individuals in the PIVUS (Prospective Investigation of the Vasculature in Uppsala Seniors) study (n = 1016, all aged 70 years) were included. Exclusion criteria were prevalent HF, electrocardiographic QRS duration ≥130 millisecond, major arrhythmias, or conduction blocks at baseline. The association between the L-F/H-F ratio and incident HF was assessed using Cox proportional hazard analysis. The C-statistic evaluated whether adding the L-F/H-F-ratio to traditional CV risk factors improved the discrimination of incident HF.

Results

HF developed in 107/836 study participants during 15 years of follow-up. A nonlinear, inverse association between the L-F/H-F ratio and incident HF was mainly driven by an L-F/H-F ratio of <30. The association curve was flat for higher values (hazard ratio, HR for the total curve = 0.78 [95% confidence interval, CI: 0.69−0.88, p < .001]; HR = 2 for L-F/H-F ratio = 10). The traditional prediction model improved by 3.3% (p < .03) when the L-F/H-F ratio was added.

Conclusions

An L-F/H-F ratio of <30 was related to incident HF and improved HF prediction when added to traditional CV risk factors.

Background and Aims

The optimal antithrombotic therapy in patients with device-detected atrial fibrillation (DDAF) is unknown. Concomitant vascular disease can modify the benefits and risks of anticoagulation.

Methods

These pre-specified analyses of the NOAH-AFNET 6 (n = 2534 patients) and ARTESiA (n = 4012 patients) trials compared anticoagulation with no anticoagulation in patients with DDAF with or without vascular disease, defined as prior stroke/transient ischaemic attack, coronary or peripheral artery disease. Efficacy outcomes were the primary outcomes of both trials, a composite of stroke, systemic arterial embolism (SE), myocardial infarction, pulmonary embolism or cardiovascular death, and stroke or SE. Safety outcomes were major bleeding or major bleeding and death.

Results

In patients with vascular disease (NOAH-AFNET 6, 56%; ARTESiA, 46%), stroke, myocardial infarction, systemic or pulmonary embolism, or cardiovascular death occurred at 3.9%/patient-year with and 5.0%/patient-year without anticoagulation (NOAH-AFNET 6), and 3.2%/patient-year with and 4.4%/patient-year without anticoagulation (ARTESiA). Without vascular disease, outcomes were equal with and without anticoagulation (NOAH-AFNET 6, 2.7%/patient-year; ARTESiA, 2.3%/patient-year in both randomized groups). Meta-analysis found consistent results across both trials (I²_{heterogeneity} = 6%) with a trend for interaction with randomized therapy (p_interaction = .08). Stroke/SE behaved similarly. Anticoagulation equally increased major bleeding in vascular disease patients [edoxaban, 2.1%/patient-year; no anticoagulation, 1.3%/patient-year; apixaban, 1.7%/patient-years; no anticoagulation, 1.1%/patient-year; incidence rate ratio 1.55 (1.10–2.20)] and without vascular disease [edoxaban, 2.2%/patient-year; no anticoagulation, 0.6%/patient-year; apixaban, 1.4%/patient-year; no anticoagulation, 1.1%/patient-year; incidence rate ratio 1.93 (0.72–5.20)].

Conclusions

Patients with DDAF and vascular disease are at higher risk of stroke and cardiovascular events and may derive a greater benefit from anticoagulation than patients with DDAF without vascular disease.

Background: Short and rare episodes of atrial fibrillation (AF) are commonly detected using implanted devices (device-detected AF) in patients with prior stroke or transient ischemic attack (TIA). The effectiveness and safety of oral anticoagulation in patients with prior stroke or TIA and device-detected AF but with no ECG-documented AF is unclear.

Methods and Results: This prespecified analysis of the NOAH-AFNET 6 (Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial High Rate Episodes) trial with post hoc elements assessed the effect of oral anticoagulation in patients with device-detected AF with and without a prior stroke or TIA in the randomized, double-blind, double-dummy NOAH-AFNET 6 trial. Outcomes were stroke, systemic embolism, and cardiovascular death (primary outcome) and major bleeding and death (safety outcome). A prior stroke or TIA was found in 253 patients with device-detected AF randomized in the NOAH-AFNET 6 (mean age, 78 years; 36.4% women). There was no treatment interaction with prior stroke or TIA for any of the primary and secondary time-to-event outcomes. In patients with a prior stroke or TIA, 14 out of 122 patients experienced a primary outcome event with anticoagulation (5.7% per patient-year). Without anticoagulation, there were 16 out of 131 patients with an event (6.3% per patient-year). The rate of stroke was lower than expected (anticoagulation: 4 out of 122 [1.6% per patient-year]; no anticoagulation: 6 out of 131 [2.3% per patient-year]). Numerically, there were more major bleeding events with anticoagulation in patients with prior stroke or TIA (8 out of 122 patients) than without anticoagulation (2 out of 131 patients).

Conclusions: Anticoagulation appears to have ambiguous effects in patients with device-detected AF and a prior stroke or TIA in this hypothesis-generating analysis of the NOAH-AFNET 6 in the absence of ECG-documented AF, partially due to a low rate of stroke without anticoagulation.

Background and Aims Patients with long atrial high-rate episodes (AHREs) >= 24 h and stroke risk factors are often treated with anticoagulation for stroke prevention. Anticoagulation has never been compared with no anticoagulation in these patients. Methods This secondary pre-specified analysis of the Non-vitamin K antagonist Oral anticoagulants in patients with Atrial High-rate episodes (NOAH-AFNET 6) trial examined interactions between AHRE duration at baseline and anticoagulation with edoxaban compared with placebo in patients with AHRE and stroke risk factors. The primary efficacy outcome was a composite of stroke, systemic embolism, or cardiovascular death. The safety outcome was a composite of major bleeding and death. Key secondary outcomes were components of these outcomes and electrocardiogram (ECG)-diagnosed atrial fibrillation. Results Median follow-up of 2389 patients with core lab-verified AHRE was 1.8 years. AHRE >= 24 h were present at baseline in 259/2389 patients (11%, 78 +/- 7 years old, 28% women, CHA2DS2-VASc 4). Clinical characteristics were not different from patients with shorter AHRE. The primary outcome occurred in 9/132 patients with AHRE >= 24 h (4.3%/patient-year, 2 strokes) treated with anticoagulation and in 14/127 patients treated with placebo (6.9%/patient-year, 2 strokes). Atrial high-rate episode duration did not interact with the efficacy (P-interaction = .65) or safety (P-interaction = .98) of anticoagulation. Analyses including AHRE as a continuous parameter confirmed this. Patients with AHRE >= 24 h developed more ECG-diagnosed atrial fibrillation (17.0%/patient-year) than patients with shorter AHRE (8.2%/patient-year; P < .001). Conclusions This hypothesis-generating analysis does not find an interaction between AHRE duration and anticoagulation therapy in patients with device-detected AHRE and stroke risk factors. Further research is needed to identify patients with long AHRE at high stroke risk.

Introduction: Catheter ablation of atrial fibrillation (AF) is frequently studied in randomized trials, observational and registry studies. The aim of this expert opinion is to provide guidance for clinicians and industry regarding the development of future clinical studies on catheter ablation of AF, implement lessons learned from previous studies, and promote a higher degree of consistency across studies.

Background: Studies on catheter ablation of AF may benefit from well-described definitions of endpoints and consistent methodology and documentation of outcomes related to efficacy, safety and cost-effectiveness. The availably of new, innovative technologies warrants further consideration about their application and impact on study design and the choice of endpoints. Moreover, recent insights gained from AF ablation studies suggest a reconsideration of some methodological aspects. Methods: A panel of clinical experts on catheter ablation of AF and designing and conducting clinical studies developed an expert opinion on the design and endpoints for studies on catheter ablation of AF. Discussions within the expert panel with the aim to reach consensus on predefined topics were based on outcomes reported in the literature and experiences from recent clinical trials.

Results: A comprehensive set of recommendations is presented. Key elements include the documentation of clinical AF, medication during the study, repeated ablations and their effect on endpoint assessments, postablation blanking and the choice of rhythm-related and other endpoints.

Conclusion: This expert opinion provides guidance and promotes consistency regarding design of AF catheter ablation studies and identified aspects requiring further research to optimize study design and methodology.

CONDENSED ABSTRACT: Recent insights from studies on catheter ablation of atrial fibrillation (AF) and the availability of new innovative technologies warrant reconsideration of methodological aspects related to study design and the choice and assessment of endpoints. This expert opinion, developed by clinical experts on catheter ablation of AF provides a comprehensive set of recommendations related to these methodological aspects. The aim of this expert opinion is to provide guidance for clinicians and industry regarding the development of clinical studies, implement lessons learned from previous studies, and promote a higher degree of consistency across studies.

Background: The prevalence and impact of obesity on outcomes of atrial fibrillation (AF) ablation randomized controlled trials (RCTs) have not been well studied.

Objective: To examine the proportion of participants with obesity enrolled in RCTs of AF ablation and outcomes of ablation when subgroup analysis of participants with obesity were available.

Methods: We systematically searched PubMed and EMBASE for AF ablation RCTs published between January 1, 2015 to May 31, 2022. When body mass index (BMI) data were available, normal distribution was assumed and a z score was used to estimate the proportion of obesity. Results categorized by BMI or body weight status were reviewed. Authors were contacted for additional information.

Results: Of 148 eligible RCTs with 30174 participants, 144 (97.30%) RCTs did not report the proportion of participants with obesity, while published information regarding BMI was available in 63.51%. Three trials excluded patients based on BMI. Using reported BMI, we estimated the proportion of participants with obesity varied greatly across these trials, ranging from 5.82%-71.9% (median 38.02%, interquartile 29.64%, 49.10%). Patients with obesity were represented in a greater proportion among trials conducted in North America (50.23%) and Asia (44.72%), compared to others (32.16%), p < .001. Subgroup analysis or analysis adjusting for BMI was reported in only 13 (8.78%) RCTs; four (30.77%) of these suggested that BMI or body weight might negatively affect primary outcomes.

Conclusion: Obesity is a common comorbidity among AF patients. However, most AF ablation RCTs underreported the proportion of participants with obesity and its impact on the primary outcomes.

Aims To allow timely initiation of anticoagulation therapy for the prevention of stroke, the European guidelines on atrial fibrillation (AF) recommend remote monitoring (RM) of device-detected atrial high-rate episodes (AHREs) and progression of arrhythmia duration along pre-specified strata (6 min...<1h, 1 h...<24 h, >= 24h). We used the MATRIX registry data to assess the capability of a single-lead implantable cardioverter-defibrillator (ICD) with atrial sensing dipole (DX ICD system) to follow this recommendation in patients with standard indication for single-chamber ICD. Methods and results In 1841 DX ICD patients with daily automatic RM transmissions, electrograms of first device-detected AHREs per patient in each duration stratum were adjudicated, and the corresponding positive predictive values (PPVs) for the detections to be true atrial arrhythmia were calculated. Moreover, the incidence and progression of new-onset AF was assessed in 1451 patients with no AF history. A total of 610 AHREs >= 6min were adjudicated. The PPV was 95.1% (271 of 285) for episodes 6min...<1h, 99.6% (253/254) for episodes 1 h...<24h, 100% (71/71) for episodes >= 24h, or 97.5% for all episodes (595/610). The incidence of new-onset AF was 8.2% (119/1451), and in 31.1% of them (37/119), new-onset AF progressed to a higher duration stratum. Nearly 80% of new-onset AF patients had high CHA(2)DS(2)-VASc stroke risk, and 70% were not on anticoagulation therapy. Age was the only significant predictor of new-onset AF. Conclusion A 99.7% detection accuracy for AHRE >= 1h in patients with DX ICD systems in combination with daily RM allows a reliable guideline-recommended screening for subclinical AF and monitoring of AF-duration progression. [Graphics] .