Anticoagulation for post-operative atrial fibrillation after isolated coronary artery bypass grafting: a meta-analysis.

BACKGROUND AND AIMS: This study aimed to evaluate clinical outcomes in patients developing post-operative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) and characterize variations in oral anticoagulation (OAC) use, benefits, and complications. METHODS: A systematic search identified studies on new-onset POAF after CABG and OAC initiation. Outcomes included risks of thromboembolic events, bleeding, and mortality. Furthermore, a meta-analysis was conducted on these outcomes, stratified by the use or non-use of OAC. RESULTS: The identified studies were all non-randomized. Among 1 698 307 CABG patients, POAF incidence ranged from 7.9% to 37.6%. Of all POAF patients, 15.5% received OAC. Within 30 days, thromboembolic events occurred at rates of 1.0% (POAF: 0.3%; non-POAF: 0.8%) with 2.0% mortality (POAF: 1.0%; non-POAF: 0.5%). Bleeding rates were 1.1% for POAF patients and 2.7% for non-POAF patients. Over a median of 4.6 years, POAF patients had 1.73 thromboembolic events, 3.39 mortality, and 2.00 bleeding events per 100 person-years; non-POAF patients had 1.14, 2.19, and 1.60, respectively. No significant differences in thromboembolic risks [effect size -0.11 (-0.36 to 0.13)] and mortality [effect size -0.07 (-0.21 to 0.07)] were observed between OAC users and non-users. However, OAC use was associated with higher bleeding risk [effect size 0.32 (0.06-0.58)]. CONCLUSIONS: In multiple timeframes following CABG, the incidence of complications in patients who develop POAF is low. The use of OAC in patients with POAF after CABG is associated with increased bleeding risk.

Safety and efficacy of long-term Sodium Channel Blocker therapy for Early Rhythm Control: The EAST-AFNET 4 trial.

BACKGROUND AND AIMS: Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers flecainide and propafenone (SCB) in patients with cardiovascular disease. SCB were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4. METHODS: 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 or acute coronary syndrome) during SCB-intake for ERC patients (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. RESULTS: Flecainide or propafenone was given to 689 patients (age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with heart failure; 41 with prior myocardial infarction, CABG or PCI; 26 with left ventricular hypertrophy >15 mm; median therapy duration 1,153 [237, 1,828] days). The primary efficacy outcome occurred less often in patients treated with SCB (3/100 (99/3,316) patient-years) than in patients who never received SCB (SCBnever 4.9/100 (150/3,083) patient-years, p < 0.001). There were numerically fewer primary safety outcomes in patients receiving SCB (2.9/100 (96/3,359) patient-years) than in SCBnever patients (4.2/100 (135/3,220) 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 heart failure. CLINICAL TRIAL REGISTRATION: ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org.

Prognosis of patients in end-stage heart failure with atrial fibrillation treated with ablation: Insights from CASTLE-HTx.

BACKGROUND: The CASTLE-HTx trial demonstrated the benefit of atrial fibrillation (AF) ablation compared with medical therapy in decreasing mortality, need for left ventricular assist device implantation, or heart transplantation (HTx) in patients with end-stage heart failure (HF). OBJECTIVE: This analysis aimed to identify risk factors related to adverse outcomes in patients with end-stage HF and to assess the impact of ablation. METHODS: The CASTLE-HTx protocol randomized 194 patients with end-stage HF and AF to ablation vs medical therapy. We identified left ventricular ejection fraction <30%, New York Heart Association class ≥III, and AF burden >50% as predictors for the primary end point. The CASTLE-HTx risk score assigned weights to these risk factors. Patients with a risk score ≥3 were identified as high risk. RESULTS: The patients were assigned to low-risk (89 [45.9%]) and high-risk (105 [54.1%]) groups. After a median follow-up of 18 months, a primary end point event occurred in 6 and 31 patients of the low- and high-risk groups (hazard ratio, 4.98; 95% confidence interval, 2.08-11.9). The incidence rate (IR) difference between ablation and medical therapy was much larger in high-risk patients (8/49 [IR, 11.4] vs 23/56 [IR, 36.1]) compared with low-risk patients (2/48 [IR, 2.6] vs 4/41 [IR, 6.3]). The IR difference for ablation was significantly higher in high-risk patients (24.69) compared with low-risk patients (3.70). CONCLUSION: The absolute benefit of ablation is more pronounced in high-risk patients, but low-risk patients may also benefit. The CASTLE-HTx risk score identifies patients with end-stage HF who will particularly benefit from ablation.

Previous Exercise Levels and Outcome in Patients with New Atrial Fibrillation: 'Past Achievements Do Not Predict the Future'.

INTRODUCTION: Long-term endurance exercise is suspect to elevate the risk of atrial fibrillation (AF),but little is known about cardiovascular outcome and disease progression in this subgroup of AF patients. We investigated whether previous exercise level determines cardiovascular outcome. METHODS: In this post hoc analysis of the RACE 4 randomized trial, we analyzed all patients with a completed questionnaire on sports participation. Three subgroups were made based on lifetime sports hours up to randomization and previous compliance to the international physical activity guidelines. High lifetime hours of high dynamic activity patients were defined as more than 150 min/week of high intense physical exercise. The primary endpoint was a composite of cardiovascular death and hospital admissions. RESULTS: A total of 879 patients were analyzed, divided in 203 high lifetime hours of high dynamic activity -, 192 high lifetime hours of activity- and 484 low lifetime hours of activity patients. Over a mean follow up of 36 months (±14), the primary endpoint occurred in 61 out of 203 (30%) high lifetime hours of high dynamic activity -, 53 out of 192 (27%) high lifetime hours of activity- and 135 out of 484 low lifetime hours of activity patients (28%) (p = 0.74). During follow up 42 high lifetime hours of high dynamic activity- (35%), 43 high lifetime hours of activity- (32%) and 104 low lifetime hours of activity patients (34%) with paroxysmal AF received electrical or chemical cardioversion or atrial ablation (p = 0.90). CONCLUSIONS: In patients included in the RACE 4, there appears to be no relation between previous activity levels and cardiovascular outcome and the need for electrical or chemical cardioversion or atrial ablation. Cardiovascular outcome was driven by AF related arrhythmic events.

Blood-based cardiometabolic phenotypes in atrial fibrillation and their associated risk: EAST-AFNET 4 biomolecule study.

BACKGROUND: Atrial fibrillation (AF) and concomitant cardiometabolic disease processes interact and combine to lead to adverse events such as stroke, heart failure, myocardial infarction, and cardiovascular death. Circulating biomolecules provide quantifiable proxies for cardiometabolic disease processes. Their role in defining subphenotypes of AF is not known. METHODS AND RESULTS: This prespecified analysis of the EAST-AFNET4 biomolecule study assigned patients to clusters using polytomous variable latent class analysis (poLCA) based on baseline concentrations of thirteen precisely-quantified biomolecules potentially reflecting ageing, cardiac fibrosis, metabolic dysfunction, oxidative stress, cardiac load, endothelial dysfunction, and inflammation. In each cluster, rates of cardiovascular death, stroke, or hospitalization for heart failure or acute coronary syndrome, the primary outcome of EAST-AFNET 4, were calculated and compared between clusters over median 5.1 years follow-up. Findings were independently validated in a prospective cohort of 748 patients with AF (BBC-AF; median follow up 2.9 years).Unsupervised biomolecule analysis assigned 1586 patients (71 years old, 46% women) into four clusters. The highest-risk cluster was dominated by elevated BMP10, IGFBP7, NT-proBNP, ANGPT2 and GDF15. Patients in the lowest-risk cluster showed low concentrations of these biomolecules. Two intermediate-risk clusters differed by high or low concentrations of hsCRP, IL-6, and D-dimer. Patients in the highest-risk cluster had a 5-fold higher cardiovascular event rate than patients in the low-risk cluster. Early rhythm control was effective across clusters (pinteraction = 0.63). Sensitivity analyses and external validation in BBC-AF replicated clusters and risk gradients. CONCLUSIONS: Biomolecule concentrations identify cardiometabolic subphenotypes in patients with atrial fibrillation at high and low cardiovascular risk.

Orally Inhaled Flecainide for Conversion of Atrial Fibrillation to Sinus Rhythm: INSTANT Phase 2 Trial.

BACKGROUND: INSTANT (INhalation of flecainide to convert recent-onset SympTomatic Atrial fibrillatioN to sinus rhyThm) was a multicenter, open-label, single-arm study of flecainide acetate oral inhalation solution (FlecIH) for acute conversion of recent-onset (≤48 hours) symptomatic atrial fibrillation (AF) to sinus rhythm. OBJECTIVES: This study investigated the efficacy and safety in 98 patients receiving a single dose of FlecIH delivered via oral inhalation. METHODS: Patients self-administered FlecIH over 8 minutes in a supervised medical setting using a breath-actuated nebulizer and were continuously monitored for 90 minutes using a 12-lead Holter. RESULTS: Mean age was 60.5 years, mean body mass index was 27.0 kg/m2, and 34.7% of the patients were women. All patients had ≥1 AF-related symptoms at baseline, and 87.8% had AF symptoms for ≤24 hours. The conversion rate was 42.6% (95% CI: 33.0%-52.6%) with a median time to conversion of 14.6 minutes. The conversion rate was 46.9% (95% CI: 36.4%-57.7%) in a subpopulation that excluded predose flecainide exposure for the current AF episode. Median time to discharge among patients who converted was 2.5 hours, and only 2 patients had experienced AF recurrence by day 5. In the conversion-no group, 44 (81.5%) patients underwent electrical cardioversion by day 5. The most common adverse events were related to oral inhalation of flecainide (eg, cough, oropharyngeal irritation/pain), which were mostly of mild intensity and limited duration. CONCLUSIONS: The risk-benefit of orally inhaled FlecIH for acute cardioversion of recent-onset AF appears favorable. FlecIH could provide a safe, effective, and convenient first-line therapeutic option. (INhalation of Flecainide to Convert Recent Onset SympTomatic Atrial Fibrillation to siNus rhyThm [INSTANT]; NCT03539302).

Adherence to a handheld device-based atrial fibrillation screening protocol is associated with clinical outcomes.

OBJECTIVE: To evaluate adherence and adherence consistency to the handheld ECG device-based screening protocol and their association with adverse cerebral and cardiovascular outcomes in two systematic atrial fibrillation (AF) screening programmes. METHODS: In 2012 (Systematic ECG Screening for Atrial Fibrillation Among 75-Year Old Subjects in the Region of Stockholm and Halland, Sweden (STROKESTOP) study) and 2016 (Stepwise mass screening for atrial fibrillation using N-terminal pro b-type natriuretic peptide (STROKESTOP II) study), half of all 75- and 76-year-old inhabitants of up to two Swedish regions were invited to participate in a systematic AF screening programme. Participants were instructed to perform 30-second measurements twice daily in STROKESTOP and four times daily in STROKESTOP II for 2 weeks. Adherence was defined as the number of measurements performed divided by the number of measurements asked, whereas adherence consistency was defined as the number of days with complete registrations. RESULTS: In total, 6436 participants (55.7% female) from STROKESTOP and 3712 (59.8% female) from STROKESTOP II were included. Median adherence and adherence consistency were 100 (92-100)% and 12 (11-13) days in STROKESTOP and 90 (75-98)% and 8 (3-11) days in STROKESTOP II. Female sex and lower education were factors associated with both optimal adherence and adherence consistency in both studies. In STROKESTOP, low adherence and adherence consistency were associated with higher risk of adverse cerebral and cardiovascular outcomes (HR for composite primary endpoint 1.30 (1.11 to 1.51), p=0.001), including stroke (HR 1.68 (1.22 to 2.32), p=0.001) and dementia (1.67 (1.27 to 2.19), p<0.001). CONCLUSIONS: Adherence to twice daily handheld ECG measurements in STROKESTOP was higher than to four times daily measurements in STROKESTOP II. Female sex and lower educational attainment were associated with ≥100% adherence and adherence consistency. Low adherence and adherence consistency were associated with a higher risk of adverse outcomes.

Cardioversion strategy impacts rate control during recurrences in patients with paroxysmal atrial fibrillation: A subanalysis of the RACE 7 ACWAS trial.

BACKGROUND: In the Rate Control versus Electrical Cardioversion Trial 7-Acute Cardioversion versus Wait and See, patients with recent-onset atrial fibrillation (AF) were randomized to either early or delayed cardioversion. AIM: This prespecified sub-analysis aimed to evaluate heart rate during AF recurrences after an emergency department (ED) visit identified by an electrocardiogram (ECG)-based handheld device. METHODS: After the ED visit, included patients (n = 437) were asked to use an ECG-based handheld device to monitor for recurrences during the 4-week follow-up period. 335 patients used the handheld device and were included in this analysis. Recordings from the device were collected and assessed for heart rhythm and rate. Optimal rate control was defined as a target resting heart rate of <110 beats per minute (bpm). RESULTS: In 99 patients (29.6%, mean age 67 ± 10 years, 39.4% female, median 6 [3-12] AF recordings) a total of 314 AF recurrences (median 2 [1-3] per patient) were identified during follow-up. The average median resting heart rate at recurrence was 100 ± 21 bpm in the delayed vs 112 ± 25 bpm in the early cardioversion group (p = .011). Optimal rate control was seen in 68.4% [21.3%-100%] and 33.3% [0%-77.5%] of recordings (p = .01), respectively. Randomization group [coefficient -12.09 (-20.55 to -3.63, p = .006) for delayed vs. early cardioversion] and heart rate on index ECG [coefficient 0.46 (0.29-0.63, p < .001) per bpm increase] were identified on multivariable analysis as factors associated with lower median heart rate during AF recurrences. CONCLUSION: A delayed cardioversion strategy translated into a favorable heart rate profile during AF recurrences.

An angiopoietin 2, FGF23, and BMP10 biomarker signature differentiates atrial fibrillation from other concomitant cardiovascular conditions.

Early detection of atrial fibrillation (AF) enables initiation of anticoagulation and early rhythm control therapy to reduce stroke, cardiovascular death, and heart failure. In a cross-sectional, observational study, we aimed to identify a combination of circulating biomolecules reflecting different biological processes to detect prevalent AF in patients with cardiovascular conditions presenting to hospital. Twelve biomarkers identified by reviewing literature and patents were quantified on a high-precision, high-throughput platform in 1485 consecutive patients with cardiovascular conditions (median age 69 years [Q1, Q3 60, 78]; 60% male). Patients had either known AF (45%) or AF ruled out by 7-day ECG-monitoring. Logistic regression with backward elimination and a neural network approach considering 7 key clinical characteristics and 12 biomarker concentrations were applied to a randomly sampled discovery cohort (n = 933) and validated in the remaining patients (n = 552). In addition to age, sex, and body mass index (BMI), BMP10, ANGPT2, and FGF23 identified patients with prevalent AF (AUC 0.743 [95% CI 0.712, 0.775]). These circulating biomolecules represent distinct pathways associated with atrial cardiomyopathy and AF. Neural networks identified the same variables as the regression-based approach. The validation using regression yielded an AUC of 0.719 (95% CI 0.677, 0.762), corroborated using deep neural networks (AUC 0.784 [95% CI 0.745, 0.822]). Age, sex, BMI and three circulating biomolecules (BMP10, ANGPT2, FGF23) are associated with prevalent AF in unselected patients presenting to hospital. Findings should be externally validated. Results suggest that age and different disease processes approximated by these three biomolecules contribute to AF in patients. Our findings have the potential to improve screening programs for AF after external validation.

Catheter Ablation in End-Stage Heart Failure with Atrial Fibrillation.

BACKGROUND: The role of catheter ablation in patients with symptomatic atrial fibrillation and end-stage heart failure is unknown. METHODS: We conducted a single-center, open-label trial in Germany that involved patients with symptomatic atrial fibrillation and end-stage heart failure who were referred for heart transplantation evaluation. Patients were assigned to receive catheter ablation and guideline-directed medical therapy or medical therapy alone. The primary end point was a composite of death from any cause, implantation of a left ventricular assist device, or urgent heart transplantation. RESULTS: A total of 97 patients were assigned to the ablation group and 97 to the medical-therapy group. The trial was stopped for efficacy by the data and safety monitoring board 1 year after randomization was completed. Catheter ablation was performed in 81 of 97 patients (84%) in the ablation group and in 16 of 97 patients (16%) in the medical-therapy group. After a median follow-up of 18.0 months (interquartile range, 14.6 to 22.6), a primary end-point event had occurred in 8 patients (8%) in the ablation group and in 29 patients (30%) in the medical-therapy group (hazard ratio, 0.24; 95% confidence interval [CI], 0.11 to 0.52; P<0.001). Death from any cause occurred in 6 patients (6%) in the ablation group and in 19 patients (20%) in the medical-therapy group (hazard ratio, 0.29; 95% CI, 0.12 to 0.72). Procedure-related complications occurred in 3 patients in the ablation group and in 1 patient in the medical-therapy group. CONCLUSIONS: Among patients with atrial fibrillation and end-stage heart failure, the combination of catheter ablation and guideline-directed medical therapy was associated with a lower likelihood of a composite of death from any cause, implantation of a left ventricular assist device, or urgent heart transplantation than medical therapy alone. (Funded by Else Kröner-Fresenius-Stiftung; CASTLE-HTx ClinicalTrials.gov number, NCT04649801.).

BMI is not independently associated with coronary artery calcification in a large single-center CT cohort.

Objective: Obesity is associated with cardiovascular disease (CVD) and CVD mortality. However, previous reports showed a paradoxical protective effect in patients with known CVD referred as "obesity paradox". Therefore, the aim of the present study was to investigate the association of body mass index (BMI) with coronary artery calcification (CAC) in a large outpatient cardiac CT cohort. Methods: 4.079 patients who underwent cardiac CT between December 2007-May 2014 were analyzed. BMI and clinical risk factors (current smoking, diabetes mellitus type 2, family history, systolic blood pressure, lipid spectrum) were assessed. Missing values were imputed using multiple imputation. CAC extent was categorized as absent (0), mild (>0-100), moderate (>100-400) and severe (>400). Results: Multivariable multinomial logistic regression analysis, including all risk factors as independent variables, showed no association between BMI and CAC. Using absence of calcification as reference category, the odds ratios per unit increase in BMI were 1.01 for mild; 1.02 for moderate; and 1.00 for severe CAC (p-values ≥0.103). Conclusions: No statistically significant association was observed between BMI and CAC after adjustment for other risk factors.

Evaluating subclinical left ventricular and left atrial dysfunction in idiopathic atrial fibrillation: A speckle-tracking based strain-analysis.

OBJECTIVE: A subset of patients with atrial fibrillation (AF) presents without established AF risk factors and normal left ventricular (LV) systolic function, called idiopathic AF (IAF). Traditionally, echocardiography derived LV dimensions and ejection fraction (EF) are used to exclude LV dysfunction in IAF, but their sensitivity is limited. Our objective is to evaluate the presence of subtle alterations in LV function despite normal LVEF in patients with IAF compared to healthy controls, using speckle-tracking echocardiography (STE) based global longitudinal strain (GLS). METHODS: Standard transthoracic echocardiography was performed in 80 patients with IAF and 129 healthy controls. Patients with overt cardiac disease as well as known established AF risk factors were excluded. STE analysis was performed to assess GLS of the LV, and left atrial strain (LAS). RESULTS: LVEF was normal and comparable between patients with IAF and healthy controls (63 ± 4% for both groups; p = 0.801). Mean GLS was within normal limits for both groups but statistically significantly more negative in patients with IAF (-20.6 ± 2.5% vs. -19.7 ± 2.5%; p = 0.016), however not when indexed for ventricular cycle length (p = 0.784). No differences in LA volume or non-indexed LAS were seen in patients with IAF compared to healthy controls. CONCLUSIONS: In this selected group of IAF patients, STE did not detect any overt LV or LA dysfunction compared to healthy controls. Thus, IAF occurred in these patients not only in the absence of established AF risk factors but also without evidence of ventricular or atrial dysfunction.

Clinical utility of the 4S-AF scheme in predicting progression of atrial fibrillation: data from the RACE V study.

AIMS: The recent 4S-AF (scheme proposed by the 2020 ESC AF guidelines to address stroke risk, symptom severity, severity of AF burden and substrate of AF to provide a structured phenotyping of AF patients in clinical practice to guide therapy and assess prognosis) scheme has been proposed as a structured scheme to characterize patients with atrial fibrillation (AF). We aimed to assess whether the 4S-AF scheme predicts AF progression in patients with self-terminating AF. METHODS AND RESULTS: We analysed 341 patients with self-terminating AF included in the well-phenotyped Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilization in the Progression of AF (RACE V) study. Patients had continuous monitoring with implantable loop recorders or pacemakers. AF progression was defined as progression to persistent or permanent AF or progression of self-terminating AF with >3% burden increase. Progression of AF was observed in 42 patients (12.3%, 5.9% per year). Patients were given a score based on the components of the 4S-AF scheme. Mean age was 65 [interquartile range (IQR) 58-71] years, 149 (44%) were women, 103 (49%) had heart failure, 276 (81%) had hypertension, and 38 (11%) had coronary artery disease. Median CHA2DS2-VASc (the CHA2DS2-VASc score assesses thromboembolic risk. C, congestive heart failure/left ventricular dysfunction; H, hypertension; A2, age ≥ 75 years; D, diabetes mellitus; S2, stroke/transient ischaemic attack/systemic embolism; V, vascular disease; A, age 65-74 years; Sc, sex category (female sex)) score was 2 (IQR 2-3), and median follow-up was 2.1 (1.5-2.6) years. The average score of the 4S-AF scheme was 4.6 ± 1.4. The score points from the 4S-AF scheme did not predict the risk of AF progression [odds ratio (OR) 1.1 95% CI 0.88-1.41, C-statistic 0.53]. However, excluding the symptoms domain, resulting in the 3S-AF (4S-AF scheme without the domain symptom severity, only including stroke risk, severity of AF burden and substrate of AF) scheme, predicted the risk of progression (OR 1.59 95% CI 1.15-2.27, C-statistic 0.62) even after adjusting for sex and age. CONCLUSIONS: In self-terminating AF patients, the 4S-AF scheme does not predict AF progression. The 3S-AF scheme, excluding the symptom domain, may be a more appropriate score to predict AF progression. TRIAL REGISTRATION NUMBERS: Clinicaltrials.gov NCT02726698 for RACE V.

Time of onset of atrial fibrillation and atrial fibrillation progression data from the RACE V study.

AIMS: Atrial fibrillation (AF) progression is associated with adverse outcome, but the role of the circadian or diurnal pattern of AF onset remains unclear. We aim to assess the association between the time of onset of AF episodes with the clinical phenotype and AF progression in patients with self-terminating AF. METHODS AND RESULTS: The Reappraisal of AF: Interaction Between Hypercoagulability, Electrical Remodelling, and Vascular Destabilization in the Progression of AF study included patients with self-terminating AF who underwent extensive phenotyping at baseline and continuous rhythm monitoring with an implantable loop recorder (ILR). In this subanalysis, ILR data were used to assess the development of AF progression and the diurnal pattern of AF onset: predominant (>80%) nocturnal AF, predominant daytime AF, or mixed AF without a predominant diurnal AF pattern. The median follow-up was 2.2 (1.6-2.8) years. The median age was 66 (59-71) years, and 117 (42%) were women. Predominant nocturnal (n = 40) and daytime (n = 43) AF onset patients had less comorbidities compared to that of mixed (n = 195) AF patients (median 2 vs. 2 vs. 3, respectively, P = 0.012). Diabetes was more common in the mixed group (12% vs. 5% vs. 0%, respectively, P = 0.031), whilst obesity was more frequent in the nocturnal group (38% vs. 12% vs. 27%, respectively, P = 0.028). Progression rates in the nocturnal vs. daytime vs. mixed groups were 5% vs. 5% vs. 24%, respectively (P = 0.013 nocturnal vs. mixed and P = 0.008 daytime vs. mixed group, respectively). CONCLUSION: In self-terminating AF, patients with either predominant nocturnal or daytime onset of AF episodes had less associated comorbidities and less AF progression compared to that of patients with mixed onset of AF. CLINICAL TRIAL REGISTRATION: NCT02726698.

Brady- and tachyarrhythmias detected by continuous rhythm monitoring in paroxysmal atrial fibrillation.

OBJECTIVE: Atrial fibrillation (AF) is associated with adverse events including conduction disturbances, ventricular arrhythmias and sudden death. The aim of this study was to examine brady- and tachyarrhythmias using continuous rhythm monitoring in patients with paroxysmal self-terminating AF (PAF). METHODS: In this multicentre observational substudy to the Reappraisal of Atrial Fibrillation: interaction between hyperCoagulability, Electrical remodelling and Vascular destabilisation in the progression of AF (RACE V), we included 392 patients with PAF and at least 2 years of continuous rhythm monitoring. All patients received an implantable loop recorder, and all detected episodes of tachycardia ≥182 beats per minute (BPM), bradycardia ≤30 BPM or pauses ≥5 s were adjudicated by three physicians. RESULTS: Over 1272 patient-years of continuous rhythm monitoring, we adjudicated 1940 episodes in 175 patients (45%): 106 (27%) patients experienced rapid AF or atrial flutter (AFL), pauses ≥5 s or bradycardias ≤30 BPM occurred in 47 (12%) patients and in 22 (6%) patients, we observed both episode types. No sustained ventricular tachycardias occurred. In the multivariable analysis, age >70 years (HR 2.3, 95% CI 1.4 to 3.9), longer PR interval (HR 1.9, 1.1-3.1), CHA2DS2-VASc score ≥2 (HR 2.2, 1.1-4.5) and treatment with verapamil or diltiazem (HR 0.4, 0.2-1.0) were significantly associated with bradyarrhythmia episodes. Age >70 years was associated with lower rates of tachyarrhythmias. CONCLUSIONS: In a cohort exclusive to patients with PAF, almost half experienced severe bradyarrhythmias or AF/AFL with rapid ventricular rates. Our data highlight a higher than anticipated bradyarrhythmia risk in PAF. TRIAL REGISTRATION NUMBER: NCT02726698.

Hybrid Ablation Versus Repeated Catheter Ablation in Persistent Atrial Fibrillation: A Randomized Controlled Trial.

BACKGROUND: Although catheter ablation (CA) is successful for the treatment of paroxysmal atrial fibrillation (AF), results are less satisfactory in persistent AF. Hybrid ablation (HA) results in better outcomes in patients with persistent atrial fibrillation (persAF), as it combines a thoracoscopic epicardial and transvenous endocardial approach in a single procedure. OBJECTIVES: The purpose of this study was to compare the effectiveness and safety of HA with CA in a prospective, superiority, unblinded, randomized controlled trial. METHODS: Forty-one ablation-naive patients with (long-standing)-persAF were randomized to HA (n = 19) or CA (n = 22) and received pulmonary vein isolation, posterior left atrial wall isolation and, if needed, a cavotricuspid isthmus ablation. The primary efficacy endpoint was freedom from any atrial tachyarrhythmia >5 minutes off antiarrhythmic drugs after 12 months. The primary and secondary safety endpoints included major and minor complications and the total number of serious adverse events. RESULTS: After 12 months, the freedom of atrial tachyarrhythmias off antiarrhythmic drugs was higher in the HA group compared with the CA group (89% vs 41%, P = 0.002). There was 1 pericarditis requiring pericardiocentesis and 1 femoral arteriovenous-fistula in the HA group. In the CA arm, 1 bleeding from the femoral artery occurred. There were no deaths, strokes, need for pacemaker implantation, or conversions to sternotomy, and the number of (serious) adverse events was comparable between groups (21% vs 14%, P = 0.685). CONCLUSIONS: Hybrid AF ablation is an efficacious and safe procedure and results in better outcomes than catheter ablation for the treatment of patients with persistent AF. (Hybrid Versus Catheter Ablation in Persistent AF [HARTCAP-AF]; NCT02441738).

Healthcare Utilization and Outcomes in Atrial Fibrillation Patients Treated by Drug Therapy versus a Catheter Ablation Strategy-A Middle European Propensity Score Matched Cohort Study.

BACKGROUND AND AIMS: Atrial fibrillation (AF) is the most prevalent arrhythmia, associated with increased mortality and morbidity and causing relevant costs. Treatment options consist of catheter ablation (PVI) and rate or rhythm control drugs (non-PVI). METHODS: We analyze inpatient and outpatient data from the Upper Austrian Health Insurance Fund. Data of patients with a first hospitalization for AF in the years 2005 to 2018 were examined, using propensity score matching (PSM) including all CHA2DS2-VASc variables and working "collar". RESULTS: Out of 21,791 AF patients, PSM identified 1013 well-matching pairs (PVI and non-PVI). Over a ten-year period, the PVI treatment strategy group reveals significantly higher inpatient and outpatient expenditures (€2200/year). Positive economic effects can be demonstrated by a 5.1 percentage points (pp) higher employment rate and fewer retirements (7.6pp). Of utmost important is the 5.8pp all-cause mortality reduction over 10 years in the PVI treatment strategy. CONCLUSIONS: A PVI based treatment strategy results in higher healthcare expenditures vs. drug therapy alone. Most of these higher costs were caused by the PVI procedures during this period. Thus, more effective and efficient methods are needed to further reduce costs for the intervention and prevent repeat procedures. The benefit of a PVI treatment strategy is seen in higher employment rates, which are crucial from a societal perspective and should be a strong argument for caregivers. We show a significant reduction in all-cause mortality, which we partly attribute to the PVI procedure itself, to a stricter risk factor assessment and treatment, and a tighter medical adherence.