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·wk -1 of high-intensity 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 (28%) low lifetime hours of activity patients ( 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 seems 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.

Rate control in atrial fibrillation, calcium channel blockers versus beta-blockers.

OBJECTIVE: To investigate heart rate differences between non-dihydropyridine calcium channel blockers and beta-blockers in patients with non-permanent atrial fibrillation (AF). METHODS: Using data from 'A Comparison of Rate Control and Rhythm Control in Patients with Atrial Fibrillation' (AFFIRM), where patients were randomised 1:1 rate or rhythm control, we compared the effect of rate control drugs on heart rate during AF as well as during sinus rhythm. Multivariable logistic regression was used to adjust for baseline characteristics. RESULTS: A total of 4060 patients were enrolled in the AFFIRM trial, mean age was 70±9 years, 39% were women. Out of the total, 1112 patients were in sinus rhythm at baseline and used either non-dihydropyridine channel blockers or beta-blockers. Of them, 474 had AF during follow-up while remaining on the same rate control drugs, 218 (46%) on calcium channel blockers and 256 (54%) on beta-blockers. Mean age of calcium channel blocker patients was 70±8 years and 68±8 for beta-blocker patients (p=0.003), 42% were women. A resting heart rate <110 beats per min during AF was achieved in 92% of patients using calcium channel blockers and 92% of patients using beta-blockers (p=1.00). Bradycardia during sinus rhythm occurred in 17% of patients using calcium channel blockers vs 32% using beta-blockers (p<0.001). After adjusting for patient characteristics, calcium channel blockers were associated with a reduction in bradycardia during sinus rhythm (OR 0.41, 95% CI 0.19 to 0.90). CONCLUSION: In patients with non-permanent AF, calcium channel blockers instituted for rate control were associated with less bradycardia during sinus rhythm compared with beta-blockers.

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.

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.

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.

Rate control drugs differ in the prevention of progression of atrial fibrillation.

AIMS: We hypothesize that in patients with paroxysmal atrial fibrillation (AF), verapamil is associated with lower AF progression compared to beta blockers or no rate control. METHODS AND RESULTS: In this pre-specified post hoc analysis of the RACE 4 randomized trial, the effect of rate control medication on AF progression in paroxysmal AF was analysed. Patients using Vaughan-Williams Class I or III antiarrhythmic drugs were excluded. The primary outcome was a composite of first electrical cardioversion (ECV), chemical cardioversion (CCV), or atrial ablation. Event rates are displayed using Kaplan-Meier curves and multivariable Cox regression analyses are used to adjust for baseline differences. Out of 666 patients with paroxysmal AF, 47 used verapamil, 383 used beta blockers, and 236 did not use rate control drugs. The verapamil group was significantly younger than the beta blocker group and contained more men than the no rate control group. Over a mean follow-up of 37 months, the primary outcome occurred in 17% in the verapamil group, 33% in the beta blocker group, and 33% in the no rate control group (P = 0.038). After adjusting for baseline characteristics, patients using verapamil have a significantly lower chance of receiving ECV, CCV, or atrial ablation compared to patients using beta blockers [hazard ratio (HR) 0.40, 95% confidence interval (CI) 0.19-0.83] and no rate control (HR 0.64, 95% CI 0.44-0.93). CONCLUSION: In patients with newly diagnosed paroxysmal AF, verapamil was associated with less AF progression, as compared to beta blockers and no rate control.