Feasibility of Patient-Managed ECG Recordings to Detect the Time of Atrial Fibrillation Recurrence after Electrical Cardioversion: Results from the PRE-ELECTRIC Study.

BACKGROUND: Electrical cardioversion (ECV) is a common procedure to terminate persistent atrial fibrillation (AF). The recurrence rate is high, and the patients often fail to recognize AF recurrence. OBJECTIVES: The aim of the study was to evaluate the feasibility of patient-managed electrocardiography (ECG) to detect the time to AF recurrence after ECV. METHODS: PRE-ELECTRIC (predictors for recurrence of atrial fibrillation after electrical cardioversion) is a prospective, observational study. Patients ≥18 years of age scheduled for ECV of persistent AF at Bærum Hospital were eligible for inclusion in the study. Time to recurrence of AF was detected by thumb ECG, recorded twice daily and whenever experiencing symptoms. The observation period was 28 days. We defined adherence as the observed number of days with ECG recordings divided by the expected number of days with ECG recordings. Study personnel contacted the participants by phone to assess their awareness of AF recurrence after a recurrence was detected in the thumb ECG. RESULTS: The study enrolled 200 patients scheduled for ECV of persistent AF at Bærum Hospital between 2018 and 2022. The mean age was 66.2 ± 9.3 years, and 21.0% (42/200) were women. The most frequent comorbidities were hypertension (n = 94, 47.0%) and heart failure (n = 51, 25.5%). A total of 164 participants underwent ECV of AF. The procedure was initially successful in 90.9%, of which 50.3% had a recurrence of AF within 4 weeks. The median time to recurrence was 5 days. Among the cardioverted participants, 123 (75.0%) had no missing days of thumb ECG recording during the observation period, and 97.0% had ≤3 missing days. More than a third (37.3%) of the participants with AF recurrence were unaware of the recurrence at the time of contact. Women were older and more symptomatic than men but had similar outcomes after ECV. CONCLUSIONS: Recurrence of AF after ECV was common. Using patient-managed thumb ECG was a feasible method to detect AF recurrence following ECV. Further studies are needed to investigate whether patient-managed ECG after ECV can optimize AF treatment.

Sex differences in early-onset atrial fibrillation in Norwegian primary care: a retrospective national database analysis.

BACKGROUND: Individual variation in the need for healthcare constitutes knowledge gaps for young atrial fibrillation (AF) patients. We aimed to estimate the prevalence and primary care burden of early-onset AF in Norway, emphasising sex differences, in a nationwide healthcare database. METHODS: We used data from the Norwegian Control and Payment of Health Reimbursement database to identify all Norwegian residents ≥18 years of age registered with a primary care physician (PCP) in 2019, with onset of AF at ≤50 years of age (early-onset AF) in the period 2006-2019. From the accumulated number of early-onset AF cases among current residents, we calculated the prevalence in 2019. The group-level primary care burden was calculated as the total number of annual AF consultations divided by the annual number of AF patients (2014-2018), and individual burden as the mean number of consultations per AF patient per year within the study period. We analysed the distribution of AF consultations between PCP and primary care emergency room (ER) services in total and by sex. RESULTS: We identified 10 925 Norwegian residents with early-onset AF in 2019 (26.3% women, mean age 48.4 years). The prevalence of early-onset AF was 0.34% (women: 0.19%, men: 0.50%). The early-onset AF population had on average one annual primary care consultation for AF. The individual burden of annual AF consultations varied widely; <1: 66% of women and 54% of men, (1-5]: 25% of women and 36% of men, (5-10]: 6% of women and 8% of men, ≥10: 2% of women and 2% of men. A higher proportion of men (71%) than women (38%) attended both PCP and ER services due to AF. CONCLUSIONS: The study confirmed a low prevalence of early-onset AF, with substantial sex differences and individual variation in primary healthcare needs. Our results signal a need for a higher resolution with regard to age groups in future research on burden and sex differences in early-onset AF.

Prevalence and incidence rates of atrial fibrillation in Norway 2004-2014.

OBJECTIVE: To study time trends in incidence of atrial fibrillation (AF) in the entire Norwegian population from 2004 to 2014, by age and sex, and to estimate the prevalence of AF at the end of the study period. METHODS: A national cohort of patients with AF (≥18 years) was identified from inpatient admissions with AF and deaths with AF as underlying cause (1994-2014), and AF outpatient visits (2008-2014) in the Cardiovascular Disease in Norway (CVDNOR) project. AF admissions or out-of-hospital death from AF, with no AF admission the previous 10 years defined incident AF. Age-standardised incidence rates (IR) and incidence rate ratios (IRR) were calculated. All AF cases identified through inpatient admissions and outpatient visits and alive as of 31 December 2014 defined AF prevalence. RESULTS: We identified 175 979 incident AF cases (30% primary diagnosis, 69% secondary diagnosis, 0.6% out-of-hospital deaths). AF IRs (95% confidence intervals) per 100 000 person years were stable from 2004 (433 (426-440)) to 2014 (440 (433-447)). IRs were stable or declining across strata of sex and age with the exception of an average yearly increase of 2.4% in 18-44 year-olds: IRR 1.024 (1.014-1.034). In 2014, the prevalence of AF in the adult population was 3.4%. CONCLUSIONS: We found overall stable IRs of AF for the adult Norwegian population from 2004 to 2014. The prevalence of AF was 3.4% at the end of 2014, which is higher than reported in previous studies. Signs of an increasing incidence of early-onset AF (<45 years) are worrying and need further investigation.

Loss-of-Function Variants in Cytoskeletal Genes Are Associated with Early-Onset Atrial Fibrillation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and it is associated with an increased risk of heart failure, stroke, dementia, and death. Recently, titin-truncating variants (TTNtv), which are predominantly associated with dilated cardiomyopathy (DCM), were associated with early-onset AF. Furthermore, genome-wide association studies (GWAS) associated AF with other structural genes. In this study, we investigated whether early-onset AF was associated with loss-of-function variants in DCM-associated genes encoding cytoskeletal proteins. Using targeted sequencing, we examined a cohort of 527 Scandinavian individuals with early-onset AF and a control group of individuals free of AF (n = 383). The patients had onset of AF before 50 years of age, normal echocardiogram, and no other cardiovascular disease at onset of AF. We identified six individuals with rare loss-of-function variants in three different genes (dystrophin (DMD), actin-associated LIM protein (PDLIM3), and fukutin (FKTN)), of which two variants were novel. Loss-of-function variants in cytoskeletal genes were significantly associated with early-onset AF when patients were compared with controls (p = 0.044). Using publicly available GWAS data, we performed genetic correlation analyses between AF and 13 other traits, e.g., showing genetic correlation between AF and non-ischemic cardiomyopathy (p = 0.0003). Our data suggest that rare loss-of-function variants in cytoskeletal genes previously associated with DCM may have a role in early-onset AF, perhaps through the development of an atrial cardiomyopathy.

Prevalence of atrial fibrillation and cardiovascular risk factors in a 63-65 years old general population cohort: the Akershus Cardiac Examination (ACE) 1950 Study.

OBJECTIVES: To investigate the sex-specific prevalence of atrial fibrillation (AF), including subclinical AF found by screening in a general population aged 63-65 years. The prevalence of cardiovascular risk factors and their association with AF will also be investigated. DESIGN: Cross-sectional analysis of an observational, prospective, longitudinal, population-based cohort study. SETTING: General population in Akershus county, Norway. PARTICIPANTS: Women and men born in 1950. We included 3706 of 5827 eligible individuals (63.6%); 48.8% were women. METHODS: All participants underwent extensive cardiovascular examinations, including 12-lead ECG. History of AF and other cardiovascular diseases were self-reported. Subsequent validation of all reported or detected AF diagnoses was performed. RESULTS: Mean age was 63.9±0.7 years. Prevalence of ECG-verified AF was 4.5% (women 2.4%, men 6.4%; p<0.001), including screen-detected AF in 0.3% (women 0.1%, men 0.6%; p<0.01). Hypertension was found in 62.0% (women 57.8%, men 66.0%; p<0.001). Overweight or obesity was found in 67.6% (women 59.8%, men 74.9%; p<0.001). By multivariate logistic regression, risk factors associated with AF were height (OR 1.67 per 10 cm; 95% CI 1.26 to 2.22; p<0.001), weight (OR 1.15 per 10 kg; 95% CI 1.01 to 1.30; p=0.03), hypertension (OR 2.49; 95% CI 1.61 to 3.86; p<0.001), heart failure (OR 3.51; 95% CI 1.71 to 7.24; p=0.001), reduced estimated glomerular filtration rate (OR 2.56; 95% CI 1.42 to 4.60; p<0.01) and at least one first-degree relative with AF (OR 2.32; 95% CI 1.63 to 3.31; p<0.001), whereas male sex was not significantly associated (OR 1.00; 95% CI 0.59 to 1.68; p=0.99). CONCLUSION: In this cohort from the general population aged 63-65 years, we found a higher prevalence of known AF than previously reported below the age of 65 years. The additional yield of single time point screening for AF was low. Body size and comorbidity may explain most of the sex difference in AF prevalence at this age. TRIAL REGISTRATION NUMBER: NCT01555411; Results.

Familial atrial fibrillation predicts increased risk of mortality: a study in Danish twins.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia. Several studies have shown association of genetic variants with AF and that familial AF increases the risk of AF. We have previously shown a substantial heritability of AF in a twin study. The objective of this study was to determine whether having a co-twin with AF influences mortality. METHODS AND RESULTS: We identified all Danish twins with AF born during and after 1912 in the Danish Twin Registry, the National Patient Registry, and the Central Office of Civil Registration. For each twin, we randomly identified 4 twins without AF, matched on sex, zygosity, and age. We compared survival among the co-twins of the affected twins (co-cases, n=2164) and the co-twins of the unaffected twins (co-controls, n=8626). The co-cases showed increased death rates compared with the co-controls (hazard ratio, 1.20; 95% confidence interval, 1.11-1.30; P<0.0001), and this effect was more pronounced in monozygotic twins (hazard ratio, 1.30; 95% confidence interval, 1.09-1.55; P=0.003), compared with dizygotic same sex (hazard ratio, 1.16; 95% confidence interval, 1.04-1.29; P=0.006) and opposite sex twins (hazard ratio, 1.20; 95% confidence interval, 0.97-1.47; P=0.093). CONCLUSIONS: The mortality rate was 20% higher in twins who had a co-twin with AF than in twins without familial AF. This effect was almost doubled in monozygotic twins compared with dizygotic twins, suggesting the influence of genetic factors.

Familial aggregation of atrial fibrillation: a study in Danish twins.

BACKGROUND: Heritability may play a role in nonfamilial atrial fibrillation (AF). We hypothesized that a monozygotic (MZ) twin whose co-twin was diagnosed with AF would have an increased risk of the disease compared with a dizygotic (DZ) twin in the same situation. METHODS AND RESULTS: A sample of 1137 same-sex twin pairs (356 MZ and 781 DZ pairs) in which one or both members were diagnosed with AF were identified in The Danish Twin Registry. Concordance rates were twice as high for MZ pairs than for DZ pairs regardless of sex (22.0% versus 11.6%, P<0.0001). In a Cox regression of event-free survival times, we compared the time span between occurrences of disease in MZ and DZ twins. The unaffected twin was included when his or her twin-sibling (the index twin) was diagnosed with AF. After adjustment for age at entry, MZ twins had a significantly shorter event-free survival time (hazard ratio, 2.0; 95% CI, 1.3 to 3.0), thereby indicating a genetic component. Using biometric models, we estimated the heritability of AF to be 62% (55% to 68%), due to additive genetics. There were no significant differences across sexes. CONCLUSIONS: All the analyses of twin similarities in the present study indicate that genetic factors play a substantial role in the risk of AF for both sexes. The recurrence risk for co-twins (12% to 22%) is clinically relevant and suggests that co-twins of AF-affected twins belong to a high-risk group for AF.