Atrial fibrillation burden: a new outcome predictor and therapeutic target.

Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, is not a dichotomous disease trait. Technological innovations enable long-term rhythm monitoring in many patients and can estimate AF burden. These technologies are already used to detect and monitor AF. This review describes the relation between AF burden and outcomes and potential effects of AF burden reduction. A lower AF burden is associated with a lower risk of stroke and heart failure in patients with AF: stroke risk without anticoagulation is lower in patients with device-detected AF and a low AF burden (stroke rate 1%/year) than in patients with persistent and permanent AF (stroke rate 3%/year). Paroxysmal AF shows intermediate stroke rates (2%/year). Atrial fibrillation burden-reducing interventions can reduce cardiovascular outcomes in patients with AF: early rhythm control reduces cardiovascular events including stroke and heart failure in patients with recently diagnosed AF and cardiovascular conditions. In patients with heart failure and AF, early rhythm control and AF ablation, interventions that reduce AF burden, reduce mortality and heart failure events. Recent technological innovations allow to estimate AF burden in clinical care, creating opportunities and challenges. While evidence remains limited, the existing data already suggest that AF burden reduction could be a therapeutic goal. In addition to anticoagulation and treatment of cardiovascular conditions, AF burden reduction emerges as a therapeutic goal. Future research will define the AF burden that constitutes a relevant risk of stroke and heart failure. Technologies quantifying AF burden need careful validation to advance the field.

Ablation of Paroxysmal Atrial Fibrillation: between Present and Future.

Pulmonary vein isolation (PVI) is the established cornerstone for atrial fibrillation (AF) ablation, indeed current guidelines recognize PVI as the gold standard for first-time AF ablation, regardless of if it is paroxysmal or persistent. Since 1998 when Haïssaguerre pioneered AF ablation demonstrating a burden reduction after segmental pulmonary vein (PV) ablation, our approach to PVI was superior in terms of methodology and technology. This review aims to describe how paroxysmal atrial fibrillation ablation has evolved over the last twenty years. We will focus on available techniques, a mechanistic understanding of paroxysmal AF genesis and the possibility of a tailored approach for the treatment of AF, before concluding with a future perspective.

Design and deployment of the STEEER-AF trial to evaluate and improve guideline adherence: a cluster-randomized trial by the European Society of Cardiology and European Heart Rhythm Association.

AIMS: The aim is to describe the rationale, design, delivery, and baseline characteristics of the Stroke prevention and rhythm control Treatment: Evaluation of an Educational programme of the European society of cardiology in a cluster-Randomized trial in patients with Atrial Fibrillation (STEEER-AF) trial. METHODS AND RESULTS: STEEER-AF is a pragmatic trial designed to objectively and robustly determine whether guidelines are adhered to in routine practice and evaluate a targeted educational programme for healthcare professionals. Seventy centres were randomized in six countries (France, Germany, Italy, Poland, Spain, and UK; 2022-23). The STEEER-AF centres recruited 1732 patients with a diagnosis of atrial fibrillation (AF), with a mean age of 68.9 years (SD 11.7), CHA2DS2-VASc score of 3.2 (SD 1.8), and 647 (37%) women. Eight hundred and forty-three patients (49%) were in AF at enrolment and 760 (44%) in sinus rhythm. Oral anticoagulant therapy was prescribed in 1543 patients (89%), with the majority receiving direct oral anticoagulants (1378; 89%). Previous cardioversion, antiarrhythmic drug therapy, or ablation was recorded in 836 patients (48.3%). Five hundred fifty-one patients (31.8%) were currently receiving an antiarrhythmic drug, and 446 (25.8%) were scheduled to receive a future cardioversion or ablation. The educational programme engaged 195 healthcare professionals across centres randomized to the intervention group, consisting of bespoke interactive online learning and reinforcement activities, supported by national expert trainers. CONCLUSION: The STEEER-AF trial was successfully deployed across six European countries to investigate guideline adherence in real-world practice and evaluate if a structured educational programme for healthcare professionals can improve patient-level care. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov, NCT04396418.

Disturbed atrial metabolism, shear stress, and cardiac load contribute to atrial fibrillation after ablation: AXAFA biomolecule study.

AIMS: Different disease processes can combine to cause atrial fibrillation (AF). Their contribution to recurrent AF after ablation in patients is not known. Cardiovascular processes associated with recurrent AF after AF ablation were determined by quantifying biomolecules related to inflammation, metabolism, proliferation, fibrosis, shear stress, atrial pressure, and others in the AXAFA biomolecule study. METHODS AND RESULTS: Twelve circulating cardiovascular biomolecules (ANGPT2, BMP10, CA125, hsCRP, ESM1, FABP3, FGF23, GDF15, IGFBP7, IL6, NT-proBNP, and hsTnT) were quantified in plasma samples obtained prior to a first AF ablation using high-throughput, high-precision assays. Cox regression was used to identify biomolecules associated with recurrent AF during the first 3 months after AF ablation. In 433 patients (64 years [58, 70]; 33% women), baseline concentrations of ANGPT2, BMP10, hsCRP, FGF23, FABP3, GDF15, and NT-proBNP were elevated in patients with recurrent AF (120/433; 28%). After adjustment for 11 clinical features and randomized treatment, elevated NT-proBNP [hazard ratio (HR) 1.58, 95% confidence interval (1.29, 1.94)], ANGPT2 [HR 1.37, (1.12, 1.67)], and BMP10 [HR 1.24 (1.02, 1.51)] remained associated with recurrent AF. Concentrations of ANGPT2, BMP10, and NT-proBNP decreased in patients who remained arrhythmia free, but not in patients with recurrent AF, highlighting their connection to AF. The other eight biomarkers showed unchanged concentrations. CONCLUSION: Elevated concentrations of ANGPT2, BMP10, and NT-proBNP are associated with recurrent AF after a first AF ablation, suggesting that processes linked to disturbed cardiomyocyte metabolism, altered atrial shear stress, and increased load contribute to AF after AF ablation in patients.

Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial.

AIMS: Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers (SCBs) flecainide and propafenone in patients with cardiovascular disease. Sodium channel blockers were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4. METHODS AND RESULTS: We analysed the primary safety outcome (death, stroke, or serious adverse events related to rhythm control therapy) and primary efficacy outcome (cardiovascular death, stroke, and hospitalization for worsening of heart failure (HF) or acute coronary syndrome) during SCB intake for patients with ERC (n = 1395) in EAST-AFNET 4. The protocol discouraged flecainide and propafenone in patients with reduced left ventricular ejection fraction and suggested stopping therapy upon QRS prolongation >25% on therapy. Flecainide or propafenone was given to 689 patients [age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with HF; 41 with prior myocardial infarction, coronary artery bypass graft, or percutaneous coronary intervention; 26 with left ventricular hypertrophy >15 mm; median therapy duration 1153 [237, 1828] days]. The primary efficacy outcome occurred less often in patients treated with SCB [3/100 (99/3316) patient-years] than in patients who never received SCB [SCBnever 4.9/100 (150/3083) patient-years, P < 0.001]. There were numerically fewer primary safety outcomes in patients receiving SCB [2.9/100 (96/3359) patient-years] than in SCBnever patients [4.2/100 (135/3220) patient-years, adjusted P = 0.015]. Sinus rhythm at 2 years was similar between groups [SCB 537/610 (88); SCBnever 472/579 (82)]. CONCLUSION: Long-term therapy with flecainide or propafenone appeared to be safe in the EAST-AFNET 4 trial to deliver effective ERC therapy, including in selected patients with stable cardiovascular disease such as coronary artery disease and stable HF. Clinical Trial Registration ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org.

Economic analyses in cardiac electrophysiology: from clinical efficacy to cost utility.

Cardiac electrophysiology is an evolving field that relies heavily on costly device- and catheter-based technologies. An increasing number of patients with heart rhythm disorders are becoming eligible for cardiac interventions, not least due to the rising prevalence of atrial fibrillation and increased longevity in the population. Meanwhile, the expansive costs of healthcare face finite societal resources, and a cost-conscious approach to new technologies is critical. Cost-effectiveness analyses support rational decision-making in healthcare by evaluating the ratio of healthcare costs to health benefits for competing therapies. They may, however, be subject to significant uncertainty and bias. This paper aims to introduce the basic concepts, framework, and limitations of cost-effectiveness analyses to clinicians including recent examples from clinical electrophysiology and device therapy.

Chinese guidelines for the diagnosis and management of atrial fibrillation.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, significantly impacting patients' quality of life and increasing the risk of death, stroke, heart failure, and dementia. Over the past two decades, there have been significant breakthroughs in AF risk prediction and screening, stroke prevention, rhythm control, catheter ablation, and integrated management. During this period, the scale, quality, and experience of AF management in China have greatly improved, providing a solid foundation for the development of the guidelines for the diagnosis and management of AF. To further promote standardized AF management, and apply new technologies and concepts to clinical practice timely and fully, the Chinese Society of Cardiology of Chinese Medical Association and the Heart Rhythm Committee of Chinese Society of Biomedical Engineering jointly developed the Chinese Guidelines for the Diagnosis and Management of Atrial Fibrillation. The guidelines comprehensively elaborated on various aspects of AF management and proposed the CHA2DS2­VASc­60 stroke risk score based on the characteristics of the Asian AF population. The guidelines also reevaluated the clinical application of AF screening, emphasized the significance of early rhythm control, and highlighted the central role of catheter ablation in rhythm control.

Outcome of tailored therapy in rheumatic heart disease with persistent atrial fibrillation (RHD-AF).

INTRODUCTION: Rheumatic heart disease with persistent atrial fibrillation (RHD-AF) is associated with increased morbidity. However, there is no standardized approach for the maintenance of sinus rhythm (SR) in them. We aimed to determine the utility of a stepwise approach to achieve SR in RHD-AF. METHODS: Consecutive patients with RHD-AF from July 2021 to August 2023 formed the study cohort. The stepwise approach included pharmacological rhythm control and/or electrical cardioversion (Central illustration). In patients with recurrence, additional options included AF ablation or pace and ablate strategy with conduction system pacing or biventricular pacing. Clinical improvement, NT-proBNP, 6-Minute Walk Test (6MWT), heart failure (HF) hospitalizations, and thromboembolic complications were documented during follow-up. RESULTS: Eighty-three patients with RHD-AF (mean age 56.13 ± 9.51 years, women 72.28%) were included. Utilizing this approach, 43 (51.81%) achieved and maintained SR during the study period of 11.04 ± 7.14 months. These patients had improved functional class, lower NT-proBNP, better distance covered for 6MWT, and reduced HF hospitalizations. The duration of AF was shorter in patients who achieved SR, compared to those who remained in AF (3.15 ± 1.29 vs 6.93 ± 5.23, p = 0.041). Thirty-five percent (29) maintained SR after a single cardioversion over the study period. Only one underwent AF ablation. Of the 24 who underwent pace and ablate strategy, atrial lead was implanted in 22 (hybrid approach), and 50% of these achieved and maintained SR. Among these 24, none had HF hospitalizations, but patients who maintained SR had further improvement in clinical and functional parameters. CONCLUSIONS: RHD-AF patients who could achieve SR with a stepwise approach, had better clinical outcomes and lower HF hospitalizations.

Effects of rhythm-control and rate-control strategies on cognitive function and dementia in atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Growing evidence suggests that atrial fibrillation (AF) is an independent risk factor for cognitive impairment and dementia, even in the absence of thromboembolic events and stroke. Whether rhythm-control therapy can protect cognitive function remains unclear. We aimed to evaluate the efficacy of rhythm-control strategies in patients with AF regarding cognitive function and dementia risk. METHODS: We systematically searched the PubMed, Embase and Cochrane Library databases for randomised clinical trials, cohort and case-control studies evaluating the associations between rhythm-control strategies and cognitive function outcomes up to May 2023. We assessed the risk of bias using the ROBINS-I and the Cochrane risk-of-bias tool. Both fixed- and random-effects models were used to create summary estimates of risk. RESULTS: We included a total of 14 studies involving 193,830 AF patients. In the pooled analysis, compared with rate-control, rhythm-control therapy was significantly associated with a lower risk of future dementia (hazard ratio (HR) 0.74; 95% confidence interval (CI) 0.62-0.89; I2 = 62%). Among the rhythm-control strategies, AF ablation is a promising treatment that was related to significantly lower risks of overall dementia (HR 0.62; 95% CI 0.56-0.68; I2 = 42%), Alzheimer's disease (HR 0.78; 95% CI 0.66-0.92; I2 = 0%) and vascular dementia (HR 0.58; 95% CI 0.42-0.80; I2 = 31%). Pooled results also showed that compared with patients without ablation, those who underwent AF ablation had significantly greater improvement in cognitive score (standardized mean difference (SMD) 0.85; 95% CI 0.30-1.40; P = 0.005; I2 = 76%). CONCLUSIONS: Rhythm-control strategies, especially ablation, are effective in protecting cognitive function, reducing dementia risk and thus improving quality of life in AF patients.

Risk Factors for Treatment Transition in Patients with Low-Risk Atrial Fibrillation Patients Undergoing Anticoagulation Monotherapy: A Large Claims Database Study in Japan.

The global prevalence of atrial fibrillation (AF) is rising, paralleling increased life expectancy. Early rhythm control benefits AF management. However, in low-risk, often asymptomatic, AF patients, anticoagulant monotherapy is the selected treatment, aligning with current guidelines. However, early AF progression in these low-risk individuals is not well-understood. Thus, this study aims to: 1) determine the proportion of low-risk AF patients who worsen within a year of initial AF diagnosis and 2) identify risk factors such treatment transitions. We analyzed data from 18623 AF patients, spanning January 2005 to June 2017. Low-risk patients were those on anticoagulant monotherapy ± rate control, following the JCS/JHRS 2020 Guideline on Pharmacotherapy of Cardiac Arrhythmias. We defined 2 patterns of treatment transition for 1) initiating ablation or antiarrhythmic drug therapy and 2) solely using antiarrhythmic drugs. This retrospective cohort study was employed a 12-month study, following a 6-month screening period. We included 1874 patients for all rhythm control (analysis 1) and 1503 for only medication-based control (analysis 2). The primary endpoint, treatment transition of AF under monotherapy, occurred in 28.4% of patients in analysis 1 and 10.8% in analysis 2. Risk factors common to both scenarios were male gender, baseline rate control drug use, and rivaroxaban selection, as identified by multiple logistic regression. These findings suggest a higher AF treatment transition trend in patients starting rivaroxaban, calling for further research. The study highlights the importance of informed early rhythm control initiation decisions in clinical settings.

Efficacy of cryoablation in atrial fibrillation: comparison with antiarrhythmic therapy.

Atrial fibrillation (AF) represents the most common arrhythmia in clinical practice, characterized by irregular atrial electrical activity originating mainly in and around the pulmonary veins. This condition can manifest itself symptomatically or silently but still dangerously. Complications associated with AF include stroke, heart failure, worst clinical outcome in patients with underlying conditions, increased emergency room visits, hospitalizations, and cardiovascular mortality. Currently, according to the main international guidelines, antiarrhythmic therapy is considered the first choice for rhythm control in patients with AF despite modest efficacy and non-negligible side effects. In recent decades, radiofrequency catheter ablation has emerged as an alternative to antiarrhythmic drugs for rhythm control. Cryoablation was developed with the aim of reducing procedural times and reducing complications related to the ablative procedure with radiofrequency without losing efficacy. Recent studies conducted with rigour and scientific solidity have demonstrated on the one hand that the results of this technique are not inferior compare with radiofrequency. This study aims to compare data on the safety and efficacy of cryoablation with those obtained from antiarrhythmic drugs through a review of the most recent scientific evidence.

Atrial fibrillation rhythm management: a matter of timing.

Rhythm control in patients with atrial fibrillation (AF) has evolved dramatically in the last decades. Several studies have informed us of the benefits of an early rhythm control strategy and primary rhythm control by catheter ablation (CA). Similarly, several studies have investigated the effects of CA in patients with longer AF duration and more comorbidities, especially heart failure. In the current review, we summarize the current evidence on rhythm control at different time points during the disease course of AF [Table 1 and Central illustration].

Prevalence and incidence of diastolic dysfunction in atrial fibrillation: clinical implications.

BACKGROUND AND AIMS: Atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF) are intimately associated disorders; HFpEF may be overlooked in AF when symptoms are simply attributed to dysrhythmia, and incident AF may identify patients at risk for developing diastolic dysfunction (DD). This study aimed to investigate the prevalence and incidence of DD in patients with new-onset AF compared with sinus rhythm (SR). METHODS: Adults with new-onset AF (n = 1747) or SR (n = 29 623) and no structural heart disease were identified. Propensity score matching was performed (1:3 ratio) between AF and SR based on age, sex, body mass index, and comorbidities. Severe DD (SDD) was defined by ≥3/four abnormal parameters (medial e', medial E/e', tricuspid regurgitation velocity, and left atrial volume index) and ≥moderate DD (>MDD) by ≥2/4. Annualized changes in DD indices were determined. RESULTS: New-onset AF was independently associated with SDD (8% vs. 3%) and ≥MDD (25% vs. 16%); 62% of patients with AF had high-risk H2FPEF scores, and 5% had clinically recognized HFpEF. Over a median follow-up of 3.2 (interquartile range 1.6-5.8) years, DD progressed two-four-fold more rapidly in those with new-onset AF (P < .001 for all). The risk for incident DD was increased in new-onset AF [hazard ratio (95% confidence interval) 2.69 (2.19-3.32) for SDD and 1.73 (1.49-2.02) for ≥MDD]. CONCLUSIONS: Patients with new-onset AF display high-risk features for HFpEF at diagnosis, emphasizing the importance of evaluating for HFpEF among symptomatic patients with AF. Patients with new-onset AF have accelerated progression in DD over time, which may identify patients with preclinical HFpEF, where preventive therapies may be tested.

Atrial fibrillation inpatient management patterns and clinical outcomes during the conflict in Syria: An observational cohort study.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia worldwide. However, there is no data on AF inpatient management strategies and clinical outcomes in Syria. OBJECTIVES: The study aims were to review the inpatient management of patients with AF and assess cardiovascular (CV) mortality in a tertiary cardiology centre in Latakia, Syria. METHODS: A single-centre retrospective observational cohort study was conducted at Tishreen's University Hospital, Latakia, Syria, from June 2021 to June 2023. Patients ≥16 years of age presenting and being treated for AF as the primary diagnosis with or without a thromboembolic event were included. Medical records were examined for patients' demographics, laboratory results, treatment plans and inpatient details. Studied outcomes include inpatient all-cause and CV mortality, ischemic and bleeding events, and conversion to sinus rhythm (SR). RESULTS: The study included 596 patients. The median age was 58, and 61% were males. 121 patients (20.3%) were known to have AF. A rhythm control strategy was pursued in 39% of patients. Ischemic and bleeding events occurred in 62 (11%) and 12 (2%), respectively. CV and all-cause mortality occurred in 28 (4.7%) and 31 patients (5%), respectively. The presence of valvular heart disease (VHD) (adjusted odds ratio (aOR) = 9.1, 95% confidence interval (CI): 1.7 to 55.1, p < .001), thyroid disease (aOR: 9.7, 95% CI = 1.2 to 91.6, p < .001) and chronic obstructive pulmonary disease (COPD) (aOR: 82, 95% CI: 12.7 to 71, p < .001) were independent risk factors of increased CV inpatient mortality. CONCLUSION: Syrian inpatients admitted with AF in Latakia are relatively younger than those in other countries. Active thyroid disease, COPD and VHD were independent risk factors of inpatient CV mortality with AF.

Exosomal miRNA Changes Associated with Restoration to Sinus Rhythm in Atrial Fibrillation Patients.

We aimed to identify serum exosomal microRNAs (miRNAs) associated with the transition from atrial fibrillation (AF) to sinus rhythm (SR) and investigate their potential as biomarkers for the early recurrence of AF within three months post-treatment. We collected blood samples from eight AF patients at Chang Gung Memorial Hospital in Taiwan both immediately before and within 14 days following rhythm control treatment. Exosomes were isolated from these samples, and small RNA sequencing was performed. Using DESeq2 analysis, we identified nine miRNAs (16-2-3p, 22-3p, 23a-3p, 23b-3p, 125a-5p, 328-3p, 423-5p, 504-5p, and 582-3p) associated with restoration to SR. Further analysis using the DIABLO model revealed a correlation between the decreased expression of miR-125a-5p and miR-328-3p and the early recurrence of AF. Furthermore, early recurrence is associated with a longer duration of AF, presumably indicating a more extensive state of underlying cardiac remodeling. In addition, the reads were mapped to mRNA sequences, leading to the identification of 14 mRNAs (AC005041.1, ARHGEF12, AMT, ANO8, BCL11A, DIO3OS, EIF4ENIF1, G2E3-AS1, HERC3, LARS, NT5E, PITX1, SLC16A12, and ZBTB21) associated with restoration to SR. Monitoring these serum exosomal miRNA and mRNA expression patterns may be beneficial for optimizing treatment outcomes in AF patients.

Lifestyle changes in atrial fibrillation management and intervention.

Atrial fibrillation (AF) is one of the most common arrhythmias in adults, and its continued rise in the United States is complicated by the increased incidence and prevalence of several AF risk factors, such as obesity, physical inactivity, hypertension, obstructive sleep apnea, diabetes mellitus, coronary artery disease, and alcohol, tobacco, or caffeine use. Lifestyle and risk factor modification has been proposed as an additional pillar of AF therapy, added to rhythm control, rate control, and anticoagulation, to reduce AF burden and risk. Although emerging evidence largely supports the integration of lifestyle and risk factor management in clinical practice, randomized clinical trials investigating the long-term sustainability and reproducibility of these benefits remain sparse. The purpose of this review is to discuss potentially reversible risk factors on AF, share evidence for the impact on AF by modification of these risk factors, and then provide an overview of the effects of reversing or managing these risk factors on the success of various AF management strategies, such as antithrombotic, rate control, and rhythm control therapies.

Radiofrequency versus cryoballoon catheter ablation in patients with persistent atrial fibrillation: A randomized trial.

INTRODUCTION: Patients with persistent atrial fibrillation (AF) represent a challenging population for rhythm control therapies. Catheter ablation (CA) with pulmonary vein isolation (PVI) is an effective treatment option for the reduction of the arrhythmic burden. Data regarding the comparability between radiofrequency (RF) and cryoballoon ablation (CRYO) in persistent AF are limited. METHODS: This is a prospective, randomized, single-center study designed to compare the efficacy in terms of rhythm control between RF and CRYO in persistent AF. Eligible participants were randomized 2:1 in two arms: RF and CRYO. The primary endpoint of the study was arrhythmia relapse in the early postprocedural period (first 3 months) and in the middle term follow-up (3 months to 12 months). Secondary endpoints included procedure duration, fluoroscopy time, and complications. RESULTS: A total of 199 patients participated in the study (133 patients in the RF arm, 66 in the CRYO arm). No statistically significant difference occurred between the two groups regarding the primary endpoint (recurrences ≤3 months: 35.5% RF vs. 37.9% CRYO, p .755, recurrences >3 months: 26.3% RF vs. 27.3% CRYO, p .999). From the secondary endpoints, CRYO was a procedure of significantly shorter duration (75.15 ± 17.21 in CRYO vs. 136.6 ± 43.33 in RF group, p < .05). CONCLUSION: CRYO and RF ablation appear to be equally effective for rhythm control in patients with persistent AF. CRYO ablation is advantageous in terms of procedure duration.

Improved prognosis with integrated care management including early rhythm control and healthy lifestyle modification in patients with concurrent atrial fibrillation and diabetes mellitus: a nationwide cohort study.

BACKGROUND: Patients with concurrent atrial fibrillation (AF) and diabetes mellitus (DM) [AF-DM] have a high risk of cardiovascular and diabetes-related complications, but are less engaged in a comprehensive treatment approach. We evaluated the association of early rhythm control (ERC), lifestyle modification (LSM), and a combination of ERC and LSM with cardiovascular or diabetes-related complication risk in patients with AF-DM (type 2). METHODS: From the National Health Information Database, 47,940 patients diagnosed with AF-DM in 2009-2016 were included. We defined ERC as rhythm control therapy within two years of AF diagnosis and LSM as adherence to ≥ 2 of the healthy behaviors among non-current smoking, non-drinking, and regular exercise. We compared the primary (ischemic stroke) and secondary (macro- and microvascular complications, glycemic emergency, and all-cause death) outcomes in four groups: non-ERC and non-LSM (group 1), LSM only (group 2), ERC only (group 3), and both ERC and LSM (group 4). RESULTS: Of total, 10,617 (22%), 26,730 (55.8%), 2,903 (6.1%), and 7,690 (16.0%) were classified into groups 1 to 4, in sequence. The mean duration from AF diagnosis to ERC was 25.6 ± 75.5 days. During 4.0 (interquartile range: 2.5-6.2) years' follow-up, groups 2 and 3 were associated with 23% and 33% lower risks of stroke than group 1, respectively. Group 4 was associated with the lowest risk of stroke: hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.51-0.67, p < 0.001. Regarding secondary outcomes, the lowest risks were also observed in group 4; macro- and microvascular complications, glycemic emergency, and all-cause death had HRs (95% CIs) of 0.63 (0.56-0.70), 0.88 (0.82-0.94), 0.72 (0.62-0.84), and 0.80 (0.73-0.87), respectively, all p < 0.001. CONCLUSIONS: For AF-DM patients, ERC and LSM exert a synergistic effect in preventing cardiovascular and diabetes-related complications with the greatest lowered risk of stroke. A comprehensive treatment approach should be pursued in AF-DM patients.

Detection and modification of biomarkers of inflammation determining successful rhythm control in patients with atrial fibrillation.

INTRODUCTION: Multiple pathophysiological mechanisms are involved in the pathogenesis of atrial fibrillation (AF). Growing evidence suggests that both local and systemic inflammation plays a key role even in early stages and its progression towards persisting and permanent AF. Rhythm control therapy via pulmonary vein isolation or cardioversion is the cornerstone of AF therapy for most symptomatic patients, yet arrhythmia recurrence after treatment is still common, especially in patients with persistent AF. MATERIAL AND METHODS: In this review, we summarize the current state of knowledge of biomarkers of inflammation with prognostic value in patients with atrial fibrillation as well as anti-inflammatory medication with potential benefits after rhythm control therapy. RESULTS AND DISCUSSION: Both onset of AF, progression and arrhythmia recurrence after rhythm control therapy can be caused by local and systemic inflammation. Various inflammatory biomarkers have been established to predict treatment success. Furthermore, additional anti-inflammatory therapy may significantly improve success rates.

Cost-effectiveness of early rhythm control vs. usual care in atrial fibrillation care: an analysis based on data from the EAST-AFNET 4 trial.

AIMS: The randomized, controlled EAST-AFNET 4 trial showed that early rhythm control (ERC) reduces the rate of a composite primary outcome (cardiovascular death, stroke, or hospitalization for worsening heart failure or acute coronary syndrome) by ∼20%. The current study examined the cost-effectiveness of ERC compared to usual care. METHODS AND RESULTS: This within-trial cost-effectiveness analysis was based on data from the German subsample of the EAST-AFNET 4 trial (n = 1664/2789 patients). Over a 6-year time horizon and from a healthcare payer's perspective, ERC was compared to usual care regarding costs (hospitalization and medication) and effects (time to primary outcome; years survived). Incremental cost-effectiveness ratios (ICERs) were calculated. Cost-effectiveness acceptability curves were constructed to visualize uncertainty. Early rhythm control was associated with higher costs [+€1924, 95% CI (-€399, €4246)], resulting in ICERs of €10 638 per additional year without a primary outcome and €22 536 per life year gained. The probability of ERC being cost-effective compared to usual care was ≥95% or ≥80% at a willingness-to-pay value of ≥€55 000 per additional year without a primary outcome or life year gained, respectively. CONCLUSION: From a German healthcare payer's perspective, health benefits of ERC may come at reasonable costs as indicated by the ICER point estimates. Taking statistical uncertainty into account, cost-effectiveness of ERC is highly probable at a willingness-to-pay value of ≥€55 000 per additional life year or year without a primary outcome. Future studies examining the cost-effectiveness of ERC in other countries, subgroups with higher benefit from rhythm control therapy, or cost-effectiveness of different modes of ERC are warranted.