Implantable cardioverter defibrillator use in arrhythmogenic right ventricular cardiomyopathy in North America and Europe.

BACKGROUND AND AIMS: Implantable cardioverter-defibrillators (ICDs) are critical for preventing sudden cardiac death (SCD) in arrhythmogenic right ventricular cardiomyopathy (ARVC). This study aims to identify cross-continental differences in utilization of primary prevention ICDs and survival free from sustained ventricular arrhythmia (VA) in ARVC. METHODS: This was a retrospective analysis of ARVC patients without prior VA enrolled in clinical registries from 11 countries throughout Europe and North America. Patients were classified according to whether they received treatment in North America or Europe and were further stratified by baseline predicted VA risk into low- (<10%/5 years), intermediate- (10%-25%/5 years), and high-risk (>25%/5 years) groups. Differences in ICD implantation and survival free from sustained VA events (including appropriate ICD therapy) were assessed. RESULTS: One thousand ninety-eight patients were followed for a median of 5.1 years; 554 (50.5%) received a primary prevention ICD, and 286 (26.0%) experienced a first VA event. After adjusting for baseline risk factors, North Americans were more than three times as likely to receive ICDs {hazard ratio (HR) 3.1 [95% confidence interval (CI) 2.5, 3.8]} but had only mildly increased risk for incident sustained VA [HR 1.4 (95% CI 1.1, 1.8)]. North Americans without ICDs were at higher risk for incident sustained VA [HR 2.1 (95% CI 1.3, 3.4)] than Europeans. CONCLUSIONS: North American ARVC patients were substantially more likely than Europeans to receive primary prevention ICDs across all arrhythmic risk strata. A lower rate of ICD implantation in Europe was not associated with a higher rate of VA events in those without ICDs.

Clinical Management of Brugada Syndrome: Commentary From the Experts.

Although there is consensus on the management of patients with Brugada Syndrome with high risk for sudden cardiac arrest, asymptomatic or intermediate-risk patients present clinical management challenges. This document explores the management opinions of experts throughout the world for patients with Brugada Syndrome who do not fit guideline recommendations. Four real-world clinical scenarios were presented with commentary from small expert groups for each case. All authors voted on case-specific questions to evaluate the level of consensus among the entire group in nuanced diagnostic and management decisions relevant to each case. Points of agreement, points of controversy, and gaps in knowledge are highlighted.

Increasing time between first diagnosis of atrial fibrillation and catheter ablation adversely affects long-term outcomes in patients with and without structural heart disease.

INTRODUCTION: Atrial Fibrillation (AF) is a common arrhythmia often comorbid with systolic or diastolic heart failure (HF). Catheter ablation is a more effective treatment for AF with concurrent left ventricular dysfunction, however, the optimal timing of use in these patients is unknown. METHODS: All patients that received a catheter ablation for AF(n = 9979) with 1 year of follow-up within the Intermountain Healthcare system were included. Patients with were identified by the presence of structural disease by ejection fraction (EF): EF ≤ 35% (n = 1024) and EF > 35% (n = 8955). Recursive partitioning categories were used to separate patients into clinically meaningful strata based upon time from initial AF diagnosis until ablation: 30-180(n = 2689), 2:181-545(n = 1747), 3:546-1825(n = 2941), and 4:>1825(n = 2602) days. RESULTS: The mean days from AF diagnosis to first ablation was 3.5 ± 3.8 years (EF > 35%: 3.5 ± 3.8 years, EF ≤ 35%: 3.4 ± 3.8 years, p = .66). In the EF > 35% group, delays in treatment (181-545 vs. 30-180, 546-1825 vs. 30-180, >1825 vs. 30-180 days) increased the risk of death with a hazard ratio (HR) of 2.02(p < .0001), 2.62(p < .0001), and 4.39(p < .0001) respectively with significant risks for HF hospitalization (HR:1.44-3.69), stroke (HR:1.11-2.14), and AF recurrence (HR:1.42-1.81). In patients with an EF ≤ 35%, treatment delays also significantly increased risk of death (HR 2.07-3.77) with similar trends in HF hospitalization (HR:1.63-1.09) and AF recurrence (HR:0.79-1.24). CONCLUSION: Delays in catheter ablation for AF resulted in increased all-cause mortality in all patients with differential impact observed on HF hospitalization, stroke, and AF recurrence risks by baseline EF. These data favor earlier use of ablation for AF in patients with and without structural heart disease.

Atrial fibrillation is a risk factor for major adverse cardiovascular events in COVID-19.

Background: New-onset atrial fibrillation (AF) during COVID-19 infection is associated with worse cardiovascular outcomes and mortality, with new-onset AF being associated with worse clinical outcomes than recurrent AF. However, it is not known whether a prior history of AF is an independent cardiovascular risk factor predicting worse outcomes in COVID-19 patients. The present investigation sought to determine whether AF should be considered a risk factor for worse outcomes in COVID-19 illness. Methods: From March 2020-September 2021 patients testing positive for SARS-CoV-2 with a prior AF diagnosis (n = 3623) were propensity matched to non-AF SARS-CoV-2 positive patients (n = 3610). Multivariable Cox hazard regression was used to determine subsequent MACE (all-cause death, myocardial infarction, HF and stroke) risk among patients with and without AF. Results: COVID-19 patients with a prior history of AF were more likely to be hospitalized, require ICU care, supplemental oxygen, and ventilator support compared COVID-19 patients without a history of AF. There was a 1.40 times higher rate of MACE in the COVID-19 patients with prior AF compared to patients without prior AF (p < 0.0001). The increased rate of MACE in patients with a prior AF was primarily secondary to increases in heart failure hospitalization and death. This finding was confirmed even after controlling for acute AF during COVID-19 illness (HR 1.22, p = 0.0009). Conclusion: AF history was shown to be an independent risk factor for MACE during a COVID-19 illness. Both recurrent and principally new-onset AF were associated with an increased risk of poor clinical outcomes during COVID-19 illness.

Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways.

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization.

Arrhythmic risk prediction in arrhythmogenic right ventricular cardiomyopathy: external validation of the arrhythmogenic right ventricular cardiomyopathy risk calculator.

AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) causes ventricular arrhythmias (VAs) and sudden cardiac death (SCD). In 2019, a risk prediction model that estimates the 5-year risk of incident VAs in ARVC was developed (ARVCrisk.com). This study aimed to externally validate this prediction model in a large international multicentre cohort and to compare its performance with the risk factor approach recommended for implantable cardioverter-defibrillator (ICD) use by published guidelines and expert consensus. METHODS AND RESULTS: In a retrospective cohort of 429 individuals from 29 centres in North America and Europe, 103 (24%) experienced sustained VA during a median follow-up of 5.02 (2.05-7.90) years following diagnosis of ARVC. External validation yielded good discrimination [C-index of 0.70 (95% confidence interval-CI 0.65-0.75)] and calibration slope of 1.01 (95% CI 0.99-1.03). Compared with the three published consensus-based decision algorithms for ICD use in ARVC (Heart Rhythm Society consensus on arrhythmogenic cardiomyopathy, International Task Force consensus statement on the treatment of ARVC, and American Heart Association guidelines for VA and SCD), the risk calculator performed better with a superior net clinical benefit below risk threshold of 35%. CONCLUSION: Using a large independent cohort of patients, this study shows that the ARVC risk model provides good prognostic information and outperforms other published decision algorithms for ICD use. These findings support the use of the model to facilitate shared decision making regarding ICD implantation in the primary prevention of SCD in ARVC.

Low voltage-guided ablation of posterior wall improves 5-year arrhythmia-free survival in persistent atrial fibrillation.

INTRODUCTION: The posterior wall (PW) has been proposed as a standard target for ablation beyond pulmonary vein antral isolation (PVI) in patients with persistent atrial fibrillation (AF). However, studies have shown inconsistent outcomes with the addition of PW ablation. The presence or absence of low voltage on the PW may explain these inconsistencies. We evaluated whether PW ablation based on the presence or absence of low voltage improves long-term arrhythmia-free outcomes. METHODS: We retrospectively reviewed 5-year follow-up in 152 consecutive patients who received either standard ablation (SA) with PVI alone or PVI + PW ablation (PWA) based on physician discretion (n = 77) or voltage-guided ablation (VGA) with PVI and addition of PWA only if low voltage was present on the PW (n = 75). RESULTS: The two groups were well matched for baseline characteristics. At 5-year follow-up, 64% of patients receiving VGA were atrial tachyarrhythmia (AT)/AF free compared to 34% receiving SA (HR 0.358 p < .005). PWA had similar AF recurrence in SA and VGA groups (0.30 vs. 0.27 p = .96) but higher AT recurrence when comparing SA and VGA groups (0.39 vs. 0.15 p = .03). In multivariate analysis, both VGA and PWA predicted AF arrhythmia-free survival (HR 0.33, p = .001 and HR 0.20, p = .008, respectively). For AT, VGA predicted arrhythmia-free survival (HR 0.22, p = .028), while PWA predicted AT recurrence (HR 4.704, p = .0219). CONCLUSION: VGA of the posterior wall ablation beyond PVI in persistent AF significantly improves long-term arrhythmia-free survival when compared with non-voltage-guided ablation. PW ablation without voltage-guidance reduced AF recurrence but at the cost of a higher incidence of AT.

Long-term outcomes in patients treated with flecainide for atrial fibrillation with stable coronary artery disease.

BACKGROUND: Class 1C antiarrhythmic drugs (AAD) have been associated with harm in patients treated for ventricular arrhythmias with a prior myocardial infarction. Consensus guidelines have advocated that these drugs not be used in patients with stable coronary artery disease (CAD). However, long-term data are lacking to know if unique risks exist when these drugs are used for atrial fibrillation (AF) in patients with CAD without a prior myocardial infarction. METHODS: In 24,315 patients treated with the initiation of AADs, two populations were evaluated: (1) propensity-matched AF patients with CAD were created based upon AAD class (flecainide, n = 1,114, vs class-3 AAD, n = 1,114) and (2) AF patients who had undergone a percutaneous coronary intervention or coronary artery bypass graft (flecainide, n = 150, and class-3 AAD, n = 1,453). Outcomes at 3 years for mortality, heart failure (HF) hospitalization, ventricular tachycardia (VT), and MACE were compared between the groups. RESULTS: At 3 years, mortality (9.1% vs 19.3%, P < .0001), HF hospitalization (12.5% vs 18.3%, P < .0001), MACE (22.9% vs 36.6%, P < .0001), and VT (5.8% vs 8.5%, P = .02) rates were significantly lower in the flecainide group for population 1. In population 2, adverse event rates were also lower, although not significantly, in the flecainide compared to the class-3 AAD group for mortality (20.9% vs 25.8%, P = .26), HF hospitalization (24.5% vs 26.1%, P = .73), VT (10.9% vs 14.7%, P = .28) and MACE (44.5% vs 49.5%, P = .32). CONCLUSIONS: Flecainide in select patients with stable CAD for AF has a favorable safety profile compared to class-3 AADs. These data suggest the need for prospective trials of flecainide in AF patients with CAD to determine if the current guideline-recommended exclusion is warranted.

Absent or Mild Coronary Calcium Predicts Low-Risk Stress Test Results and Outcomes in Patients Considered for Flecainide Therapy.

BACKGROUND: Flecainide is a useful antiarrhythmic for atrial fibrillation (AF). However, because of ventricular proarrhythmia risk, a history of myocardial infarction (MI) or coronary artery disease (CAD) is a flecainide exclusion, and stress testing is used to exclude ischemia. We assessed whether absent/mild coronary artery calcium (CAC) can supplement or avoid the need for stress testing. METHODS: We assessed ischemic burden using regadenoson Rb-82 PET/CT in 1372 AF patients ≥50 years old without symptoms or signs of clinical CAD. CAC was determined qualitatively by low dose attenuation computed tomography (CT) (n = 816) or by quantitative CT (n = 556). Ischemic burden and clinical outcomes were compared by CAC burden. RESULTS: Patients with CAC absent or mild (n = 766, 57.2%) were younger, more frequently female, and had higher BMI but lower rates of diabetes, hypertension, and dyslipidemia. Average ischemic burden was lower in CAC-absent/mild patients, and CAC-absent/mild patients showed greater coronary flow reserve, had fewer referrals for coronary angiography, and less often had obstructive CAD. Revascularization at 90 days was lower, and the rate of longer-term major adverse cardiovascular events was favorable. CONCLUSIONS: An easily administered, inexpensive, low radiation CAC scan can identify a subset of flecainide candidates with a low ischemic burden on PET stress testing that rarely needs coronary angiography/intervention and has favorable outcomes. Absent or mild CAC-burden combined with other clinical information may avoid or complement routine stress testing. However, additional, ideally randomized and multicenter trials are indicated to confirm these findings before replacing stress testing with CAC screening in selecting patients for flecainide therapy in clinical practice.

Management of Congenital Long-QT Syndrome: Commentary From the Experts.

While published guidelines are useful in the care of patients with long-QT syndrome, it can be difficult to decide how to apply the guidelines to individual patients, particularly those with intermediate risk. We explored the diversity of opinion among 24 clinicians with expertise in long-QT syndrome. Experts from various regions and institutions were presented with 4 challenging clinical scenarios and asked to provide commentary emphasizing why they would make their treatment recommendations. All 24 authors were asked to vote on case-specific questions so as to demonstrate the degree of consensus or divergence of opinion. Of 24 authors, 23 voted and 1 abstained. Details of voting results with commentary are presented. There was consensus on several key points, particularly on the importance of the diagnostic evaluation and of ß-blocker use. There was diversity of opinion about the appropriate use of other therapeutic measures in intermediate-risk individuals. Significant gaps in knowledge were identified.

Genetic Susceptibility for Atrial Fibrillation in Patients Undergoing Atrial Fibrillation Ablation.

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.

Stroke and dementia risk in patients with and without atrial fibrillation and carotid arterial disease.

BACKGROUND: Patients with carotid arterial disease (CD) with and without atrial fibrillation (AF) are at risk of stroke. Patients with AF are at a higher risk of stroke and dementia. OBJECTIVES: We sought to understand the risks of stroke, transient ischemic attack (TIA), and dementia in patients with and without AF and CD or a combination of both as well as to determine whether therapies for each disease may influence risks. METHODS: A total of 11,572 patients were included in 4 groups, with 2893 patients populating each group (1: no AF or CD; 2: AF, no CD; 3: CD and no AF; 4: AF and CD) and matched for age, sex, and comorbidities. Long-term outcomes of stroke/TIA and dementia were assessed. Subset analyses of these outcomes were performed in patients with CD treated with revascularization and in patients with AF treated with ablation. RESULTS: CD increased the risk of stroke/TIA (hazard ratio [HR] 2.74; P < .0001) and dementia (HR 1.44; P < .0001). Similarly, AF increased the risk of stroke/TIA (HR 2.08; P < .0001) and dementia (HR 1.30; P = .004). The coexistence of AF and CD further augmented the risk of both end points. CD revascularization was associated with a decreased risk of dementia (HR 0.47; P < .0001) but not stroke. Ablation of AF improved outcomes of stroke/TIA (HR 0.55; P = .002), particularly in those with CD (HR 0.36; P < .0001), and was associated with a reduced risk of dementia (HR 0.51; P = .04). CONCLUSION: CD and AF augment risk of stroke/TIA and dementia in the general population, and the coexistence of both diseases is additive in risk. Ablation of AF was associated with lower risk, the magnitude of which was greater in those with CD.

Long-term outcomes after low power, slower movement versus high power, faster movement irrigated-tip catheter ablation for atrial fibrillation.

BACKGROUND: High power, shorter duration (HPSD) ablation strategies have been advocated to increase efficacy and minimize posterior wall deep tissue thermal injury during atrial fibrillation (AF) ablation. OBJECTIVE: The purpose of this study was to determine the long-term outcomes of arrhythmia-free survival from AF and atrial flutter (AFL) between HPSD and low power, longer duration (LPLD) ablation strategies. METHODS: Of a total of 1333 first time AF ablation procedures with 3 years of follow-up, propensity-matched populations for baseline risk factors were created, comprising 402 patients treated with LPLD ablation (30 W for 5 seconds: posterior wall; 30 W for 10-20 seconds: anterior wall) and 402 patients treated with HPSD ablation (50 W for 2-3 seconds: posterior wall; 50 W for 5-15 seconds: anterior wall). AF/AFL outcomes after a 90-day blanking period were assessed. RESULTS: HPSD ablation was associated with shorter procedure and fluoroscopy times (P < .0001 for both). The recurrence of AF at 1 year (12.9% vs 16.2%; P = .19) and 3 years (26.5% vs 30.7%; P = .23) was similar between LPLD and HPSD groups. AFL was higher at 1 year (7.2% vs 11.2%; P = .03) and 3 years (16.1% vs 21.8%; P = .06; P = .04 after multivariate adjustment) with HPSD ablation. Patients who underwent an LPLD approach had lower rates of need for repeat ablation (21% vs 30%; P = .002). CONCLUSION: Long-term freedom from AF rates were not significantly different between both approaches. An HPSD ablation strategy compared with an LPLD approach was associated with an increased risk of AFL and need for repeat ablation but with lowered procedure times.

Spontaneous Atrial Fibrillation in Transgenic Goats With TGF (Transforming Growth Factor)-ß1 Induced Atrial Myopathy With Endurance Exercise.

BACKGROUND: There is increasing evidence that endurance exercise is associated with increased risk of atrial fibrillation (AF). However, it is unknown if the relationship between endurance exercise and AF is dependent on an atrial myopathy. METHODS: Six cardiac-specific TGF (transforming growth factor)-ß1 transgenic and 6 wild-type (WT) goats were utilized for these studies. Pacemakers were implanted in all animals for continuous arrhythmia monitoring and AF inducibility. AF inducibility was evaluated using 5 separate 10 s bursts of atrial pacing (160-200 ms). Three months of progressive endurance exercise (up to 90 minutes at 4.5 mph) was performed. Quantitative assessment of circulating microRNAs and inflammatory biomarkers was performed. RESULTS: Sustained AF (≥30 s) was induced with 10 s of atrial pacing in 4 out of 6 transgenic goats compared with 0 out of 6 WT controls at baseline (P<0.05). No spontaneous AF was observed at baseline. Interestingly, between 2 and 3 months of exercise 3 out of 6 transgenic animals developed self-terminating spontaneous AF compared with 0 out of 6 WT animals (P<0.05). There was an increase in AF inducibility in both transgenic and WT animals during the first 2 months of exercise with partial normalization at 3 months (transgenic 67%; 100%; 83% versus WT 0%; 67%; 17%). These changes in AF susceptibility were associated with a decrease in circulating microRNA-21 and microRNA-29 during the first 2 months of exercise with partial normalization at 3 months in both transgenic and WT animals. Finally, MMP9 (matrix metallopeptidase 9) was increased during the second and third months of exercise training. CONCLUSIONS: This study demonstrates a novel transgenic goat model of cardiac fibrosis (TGF-ß1 overexpression) to demonstrate that endurance exercise in the setting of an underlying atrial myopathy increases the incidence of spontaneous AF. Furthermore, endurance exercise seems to increase inducible AF secondary to altered expression of key profibrotic biomarkers that is independent of the presence of an atrial myopathy.

Circulating Levels of Biomarkers of Cerebral Injury in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is a source of altered brain perfusion and ischemia, potentially leading to cerebral injury and blood brain barrier (BBB) disruption, which may result in the permeation of neurospecific molecules into the bloodstream. We retrospectively analyzed circulating levels of biomarkers of cerebral injury: Astrocyte-specific glial acidic fibrillary protein (GFAP), calcium-binding protein B (S100 b), stress response marker growth differential factor 15 (GDF15), and microtubule associated Tau protein, in patients with AF and non-AF controls. A total of 196 AF cases and 47 non-AF controls were enrolled in this study all without previous clinical stroke or cerebral injury. Plasma samples were obtained from the Intermountain INSPIRE biobank registry. AF status was determined at the time of the sample draw using clinical diagnosis. Assessment of circulating biomarkers was conducted with EIA. Multivariate linear modeling, using natural log, and square root transformation of the biomarkers, was done adjusting for (1) CHA2DS2-VASc and anticoagulation, and (2) age, gender, coronary artery disease and anticoagulation. Circulating Tau, GDF15, and GFAP were elevated in AF cases. After multivariate adjustment, GFAP and Tau remained significantly elevated in the AF, whereas the signal for GDF15 was confounded by age. In conclusion, circulating biomarkers of neuronal and glial injury Tau and GFAP are elevated in patients with AF that are consistent with subclinical cerebral injury and disruption of the BBB, which can predispose these patients to the development of cognitive dysfunction and/or dementia later in life.

Cardiac Implantable Electronic Device Therapy: Permanent Pacemakers, Implantable Cardioverter Defibrillators, and Cardiac Resynchronization Devices.

Cardiac implantable electronic devices (CIEDs) provide lifesaving therapy for the treatment of bradyarrhythmias, ventricular tachyarrhythmias, and advanced systolic heart failure. Advances in CIED therapy have expanded the number of patients receiving permanent pacemakers, implantable cardioverter defibrillators, and cardiac resynchronization therapy devices. These devices improve quality of life and, in many cases, reduce mortality. However, limitations remain in the management of patients who require CIED therapy. This article provides a broad overview of CIED therapy in the management of the cardiac patient.

The role of microRNAs in the development, regulation, and treatment of atrial fibrillation.

BACKGROUND: MicroRNAs (miRNA)s regulate expression of genes involved in various processes including cardiac automaticity, conduction, excitability, and fibrosis and therefore may provide a diagnostic utility to identify high-risk patients for atrial fibrillation (AF). In this study, we tested the hypothesis that specific profiles of circulating miRNAs can identify patients with AF and can also help to identify patients at high risk of AF recurrence after ablation. METHODS: Two patient populations were studied: 140 AF cases (93 paroxysmal and 47 persistent) and 50 healthy controls, and 141 AF ablation cases with (n = 86) and without (n = 55) 1-year recurrence. Assessment of several previously identified AF-associated plasma miRNAs (21, 29a, 133a, 133b, 150, 328) was performed with TaqMan assays, using synthetic miRNAs as standards. RESULTS: The AF cases compared to the healthy controls were older and were more often male and hypertensive. After multivariate adjustment, higher miRNA-21 levels significantly decreased the risk of AF (OR = 0.93 per fmol/µl (95% CI = 0.89-0.98, p = 0.007)). There were no significant differences in circulating miRNAs between the AF subtypes of persistent and paroxysmal. Among the AF ablation cases, miRNA-150 was lower for those with AF recurrences at 1 year (adjusted OR = 0.98 per 500,000 fmol/µl; 95% CI = 0.965, 0.998; p = 0.039). CONCLUSIONS: Decreased circulating miRNA-21 is associated with AF, but not with AF subtypes, suggestive that molecular mechanisms responsible for the onset and progression of the AF may be different. Circulating miRNA-150 was significantly associated with a reduction in 1-year AF recurrence post ablation suggestive of adverse structural and electrical remodeling as recurrence mechanisms.

The Impact of Gender on Atrial Fibrillation Incidence and Progression to Dementia.

There are a paucity of data regarding the role of gender and atrial fibrillation (AF) on cognitive decline and incidence of dementia. Such data may provide insight into the disproportionate incidence of dementia in women and may help identify high-risk characteristics to target for prevention. We examined patients who underwent coronary angiography at an Intermountain Healthcare Medical Center and enrolled in a prospective cardiovascular database. To be included, patients could not have a previous diagnosis of AF or dementia and had to have 5years of follow-up. Endpoints included incident AF and dementia. Study cohort consisted of 35,608 patients without a previous history of AF or dementia, with 14,377 (40.4%) being woman. Women had lower rates of hypertension, diabetes, coronary artery disease, and prior myocardial infarction, but higher rates of prior stroke. Men had a higher incidence of 5-year and long-term AF. However, women trended toward a higher incidence of 5-year and long-term dementia and stroke compared with men. In all groups of patients with and without AF, prior stroke predicted cognitive decline. In patients without a history of or development of AF, diabetes significantly increased risk of dementia. Women have higher rates of dementia over time than men, driven by higher baseline stroke rates and nontraditional cardiovascular risk factors. The higher dementia rates were in the setting of lower AF rates. However, in both men and women who develop AF, dementia rates are increased and do not show gender-based differences in risk.