Project description:ImportanceThere is a genetic predisposition to early-onset atrial fibrillation (EOAF) in European American individuals. However, the role of family history in the pathogenesis of EOAF in racial and ethnic minorities remains unclear.ObjectiveTo determine whether probands with EOAF across racial and ethnic groups have a higher rate of AF in first-degree family members than racially and ethnically matched control patients with non-early-onset AF (non-EOAF).Design, setting, and participantsIn this cohort study, patients prospectively enrolled in a clinical and genetic biorepository were administered baseline questionnaires that included questions about family history of AF. Early-onset AF was defined as AF occurring in probands aged 60 years or younger in the absence of structural heart disease. All other forms were categorized as non-EOAF. Recruitment took place from July 2015 to December 2017. Analysis was performed in January 2018.Main outcomes and measuresPrimary analysis of reported family history of AF in first-degree relatives with sensitivity analysis restricted to those in whom a family history was confirmed by medical record review and electrocardiogram.ResultsOf 664 patients enrolled (mean [SD] age, 62 [12] years; 407 [61%] male), 267 (40%) were European American; 258 (39%), African American; and 139 (21%), Hispanic/Latino. There was a family history of AF in 36 probands with EOAF (49%) compared with 128 patients with non-EOAF (22%) (difference, 27%; 95% CI, 14%-40%; P < .001). On multivariable analysis, the adjusted odds of a proband with EOAF who was of African descent (odds ratio [OR], 2.69; 95% CI, 1.06-6.91; P < .001) or Hispanic descent (OR, 9.25; 95% CI, 2.37-36.23; P = .002) having a first-degree relative with AF were greater than those of European descent (OR, 2.51; 95% CI, 1.29-4.87; P = .006). Overall, probands with EOAF were more likely to have a first-degree relative with AF compared with patients with non-EOAF (adjusted OR, 3.02; 95% CI, 1.82-4.95; P < .001) across the 3 racial and ethnic groups. Atrial fibrillation in a first-degree family member was confirmed in 32% of probands with EOAF vs 11% of those with non-EOAF (difference, 21%; 95% CI, 11%-33%; P < .001). Furthermore, African American (28% vs 5%; difference, 23%; 95% CI, 4%-43%; P = .001), European American (35% vs 20%; difference, 15%; 95% CI, 1%-30%; P = .03), and Hispanic/Latino (30% vs 5%; difference, 25%; 95% CI, 4%-54%; P = .02) probands with EOAF were more likely to have a first-degree relative with confirmed AF vs racially and ethnically matched control patients with non-EOAF. The positive and negative predictive values for a family history of confirmed AF were both 89%.Conclusions and relevanceProbands of African or Hispanic/Latino descent with EOAF were more likely to have a first-degree relative with AF when compared with European American individuals. These findings support genetic predisposition to EOAF across all 3 races.

Project description:BACKGROUND:Ablation is a widely used therapy for atrial fibrillation (AF); however, arrhythmia recurrence and repeat procedures are common. Studies examining surrogate markers of genetic susceptibility to AF, such as family history and individual AF susceptibility alleles, suggest these may be associated with recurrence outcomes. Accordingly, the aim of this study was to test the association between AF genetic susceptibility and recurrence after ablation using a comprehensive polygenic risk score for AF. METHODS:Ten centers from the AF Genetics Consortium identified patients who had undergone de novo AF ablation. AF genetic susceptibility was measured using a previously described polygenic risk score (N=929 single-nucleotide polymorphisms) and tested for an association with clinical characteristics and time-to-recurrence with a 3 month blanking period. Recurrence was defined as >30 seconds of AF, atrial flutter, or atrial tachycardia. Multivariable analysis adjusted for age, sex, height, body mass index, persistent AF, hypertension, coronary disease, left atrial size, left ventricular ejection fraction, and year of ablation. RESULTS:Four thousand two hundred seventy-six patients were eligible for analysis of baseline characteristics and 3259 for recurrence outcomes. The overall arrhythmia recurrence rate between 3 and 12 months was 44% (1443/3259). Patients with higher AF genetic susceptibility were younger (P<0.001) and had fewer clinical risk factors for AF (P=0.001). Persistent AF (hazard ratio [HR], 1.39 [95% CI, 1.22-1.58]; P<0.001), left atrial size (per cm: HR, 1.32 [95% CI, 1.19-1.46]; P<0.001), and left ventricular ejection fraction (per 10%: HR, 0.88 [95% CI, 0.80-0.97]; P=0.008) were associated with increased risk of recurrence. In univariate analysis, higher AF genetic susceptibility trended towards a higher risk of recurrence (HR, 1.08 [95% CI, 0.99-1.18]; P=0.07), which became less significant in multivariable analysis (HR, 1.06 [95% CI, 0.98-1.15]; P=0.13). CONCLUSIONS:Higher AF genetic susceptibility was associated with younger age and fewer clinical risk factors but not recurrence. Arrhythmia recurrence after AF ablation may represent a genetically different phenotype compared to AF susceptibility.

Project description:ImportanceIn patients with paroxysmal atrial fibrillation (AF), rhythm control with either antiarrhythmic drugs (AADs) or catheter ablation has been associated with decreased symptoms, prevention of adverse remodeling, and improved cardiovascular outcomes. Adoption of advanced cardiovascular therapeutics, however, is often slower among patients from racial/ethnic minority groups and those with lower income.ObjectiveTo ascertain the cumulative rates of AAD and catheter ablation use for the management of paroxysmal AF and to investigate for the presence of inequities in AF management by evaluating the association of race/ethnicity and socioeconomic status with their use in the United States.Design, setting, and participantsThis cohort study obtained inpatient, outpatient, and pharmacy claims data from the Optum Clinformatics Data Mart between October 1, 2015, and June 30, 2019. Adult patients (aged ≥18 years) in the database with a diagnosis of incident paroxysmal AF were identified. Patients were excluded if they did not have continuous insurance enrollment for at least 1 year before and at least 6 months after study entry.ExposuresRace/ethnicity and zip code-linked median household income.Main outcomes and measuresTreatment with a rhythm control strategy, and catheter ablation specifically, among those who received rhythm control. Multivariable logistic regression models were used to assess the association of race/ethnicity and zip code-linked median household income with a rhythm control strategy (AADs or catheter ablation) vs a rate control strategy as well as with catheter ablation vs AADs among those receiving rhythm control.ResultsOf the 109 221 patients who met the inclusion criteria, 55 185 were men (50.5%) and 73 523 were White (67.3%), with a median (interquartile range) age of 75 (68-82) years. A total of 86 359 patients (79.1%) were treated with rate control, 19 362 patients (17.7%) with AADs, and 3500 (3.2%) with catheter ablation. Between 2016 and 2019, the cumulative percentage of patients treated with catheter ablation increased from 1.6% to 3.8%. In multivariable analyses, Black race (adjusted odds ratio [aOR], 0.89; 95% CI, 0.83-0.94; P < .001) and lower zip code-linked median household income (aOR for <$50 000: 0.83 [95% CI, 0.79-0.87; P < .001]; aOR for $50 000-$99 999: 0.92 [95% CI, 0.88-0.96; P = <.001] compared with ≥$100 000) were independently associated with lower use of rhythm control. Latinx ethnicity (aOR, 0.73; 95% CI, 0.60-0.89; P = .002) and lower zip code-linked median household income (aOR for <$50 000: 0.61 [95% CI, 0.54-0.69; P < .001]; aOR for $50 000-$99 999: 0.81 [95% CI, 0.72-0.90; P < .001] compared with ≥$100 000) were independently associated with lower catheter ablation use among those receiving rhythm control.Conclusions and relevanceThis study found that despite increased use of rhythm control strategies for treatment of paroxysmal AF, catheter ablation use remained low and patients from racial/ethnic minority groups and those with lower income were less likely to receive rhythm control treatment, especially catheter ablation. These findings highlight inequities in paroxysmal AF management based on race/ethnicity and socioeconomic status.

Project description:BackgroundRhythm control strategies for atrial fibrillation (AF), including catheter ablation, are substantially underused in racial/ethnic minorities in North America.ObjectivesThis study sought to describe outcomes in the CABANA trial as a function of race/ethnicity.MethodsCABANA randomized 2,204 symptomatic participants with AF to ablation or drug therapy including rate and/or rhythm control drugs. Only participants in North America were included in the present analysis, and participants were subgrouped as racial/ethnic minority or nonminority with the use of National Institutes of Health definitions. The primary endpoint was a composite of death, disabling stroke, serious bleeding, or cardiac arrest.ResultsOf 1,280 participants enrolled in CABANA in North America, 127 (9.9%) were racial and ethnic minorities. Compared with nonminorities, racial and ethnic minorities were younger with median age 65.6 versus 68.5 years, respectively, and had more symptomatic heart failure (37.0% vs 22.0%), hypertension (92.1% vs 76.8%, respectively), and ejection fraction <40% (20.8% vs 7.1%). Racial/ethnic minorities treated with ablation had a 68% relative reduction in the primary endpoint (adjusted hazard ratio [aHR]: 0.32; 95% confidence interval [CI]: 0.13-0.78) and a 72% relative reduction in all-cause mortality (aHR: 0.28; 95% CI: 0.10-0.79). Primary event rates in racial/ethnic minority and nonminority participants were similar in the ablation arm (4-year Kaplan-Meier event rates 12.3% vs 9.9%); however, racial and ethnic minorities randomized to drug therapy had a much higher event rate than nonminority participants (27.4% vs. 9.4%).ConclusionAmong racial or ethnic minorities enrolled in the North American CABANA cohort, catheter ablation significantly improved major clinical outcomes compared with drug therapy. These benefits, which were not seen in nonminority participants, appear to be due to worse outcomes with drug therapy. (Catheter Ablation vs Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial [CABANA]; NCT00911508).

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Genetic heterogeneity of atrial fibrillation susceptibility loci across racial or ethnic groups.

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