Women have less progression of paroxysmal atrial fibrillation: data from the RACE V study.

BACKGROUND: Sex differences in atrial fibrillation (AF) are observed in terms of comorbidities, symptoms, therapies received, AF progression and cardiovascular complications. METHODS: We assessed the differences in prevalence and the determinants of AF progression, as well as the clinical characteristics and quality of life (QoL), between women and men with paroxysmal AF included in the RACE V (Reappraisal of Atrial Fibrillation: Interaction between hyperCoagulability, Electrical remodeling, and Vascular Destabilisation in the Progression of AF) study. At baseline, extensive phenotyping was done. To assess AF progression, implantable loop recorder (ILR) monitoring was used throughout follow-up. AF progression was defined as (1) progression to persistent or permanent AF or (2) progression of paroxysmal AF (>3% burden increase). RESULTS: 417 patients were included, 179 (43%) of whom were women. Women were older (median 67 years vs 63 years, p<0.001), less often had coronary artery disease (n=11 (6%) vs n=36 (16%), p=0.003), had more obesity (n=57 (32%) vs n=50 (21%), p=0.013), had less epicardial and pericardial fat (median 144 (interquartile range [IQR] 94-191) mL vs 199 (IQR 146-248) mL, p<0.001; and median 89 (ICQ 61-121) mL vs 105 (IQR 83-133) mL, p<0.001, respectively) and had more impaired left atrial function. The median follow-up was 2.2 (1.6-2.8) years. 51 of 417 patients (5.5% per year) showed AF progression (15/179 (8.4%) women and 36/238 (15.1%) men, p=0.032). Multivariable analysis showed tissue factor pathway inhibitor, N-terminal prohormone brain natriuretic peptide (NT-proBNP) and PR interval being associated with AF progression in women and factor XIIa:C1 esterase, NT-proBNP and proprotein convertase subtilisin/kexin type 9 in men. QoL was not different between sexes. CONCLUSION: Despite older age, the incidence of AF progression was lower in women. Parameters associated with AF progression varied in part between sexes, suggesting different underlying pathophysiological mechanisms.

Long-Term Performance of Epicardial versus Transvenous Left Ventricular Leads for Cardiac Resynchronization Therapy.

Aims: to study the technical performance of epicardial left ventricular (LV) leads placed via video assisted thoracic surgery (VATS), compared to transvenously placed leads for cardiac resynchronization therapy (CRT). Methods: From 2001 until 2013, a total of 644 lead placement procedures were performed for CRT. In the case of unsuccessful transvenous LV lead placement, the patient received an epicardial LV lead. Study groups consist of 578 patients with a transvenous LV lead and 66 with an epicardial LV lead. The primary endpoint was LV-lead failure necessitating a replacement or deactivation. The secondary endpoint was energy consumption. Results: The mean follow up was 5.9 years (epicardial: 5.5 ± 3.1, transvenous: 5.9 ± 3.5). Transvenous leads failed significantly more frequently than epicardial leads with a total of 66 (11%) in the transvenous leads group vs. 2 (3%) in the epicardial lead group (p = 0.037). Lead energy consumption was not significantly different between groups. Conclusions: Epicardial lead placement is feasible, safe and shows excellent long-term performance compared to transvenous leads. Epicardial lead placement should be considered when primary transvenous lead placement fails or as a primary lead placement strategy in challenging cases.

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.