Impact of anticoagulation therapy on the cognitive decline and dementia in patients with non-valvular atrial fibrillation (cognitive decline and dementia in patients with non-valvular atrial fibrillation [CAF] trial).

Background: Atrial fibrillation (AF) is associated with a risk for cognitive impairment and dementia, which is more pronounced in patients with a history of clinical stroke. Anticoagulation use and efficacy impact long-term risk of dementia in AF patients in observational trials. Methods: The cognitive decline and dementia in patients with non-valvular atrial fibrillation (CAF) Trial was a randomized, prospective, open-label vanguard clinical study with blinded endpoint assessment involving patients with moderate- to high-risk (CHADS2 or CHA2DS2-Vasc scores of ≥2) non-valvular AF assigned to dabigatran etexilate or warfarin. The primary endpoint was incident dementia or moderate cognitive decline at 24 months. Results: A total of 101 patients were enrolled [mean age:73.7 ± 6.0 years, male: 54(53.5%)]. Prior stroke and stroke risk factors were similar between groups. Average INR over the study was 2.41 ± 0.68 in the warfarin group. No patient experienced a stroke or developed dementia. Mini-Mental Status Evaluation, Hachinski Ischemic scale, cognitive subscale of the Alzheimer's Disease Assessment Scale, Disability Assessment for Dementia, Quality of Life Improvement as assessed by Minnesota Living with Heart Failure Scale and the Anti-Clot Treatment Scale Quality of Life Survey scores did not vary at baseline or change over 2 years. Biomarker analysis indicated a similar efficacy of anticoagulation strategies. Conclusion: Use of dabigatran and well-managed warfarin therapy were associated with similar risks of stroke, cognitive decline, and dementia at 2 years, suggestive that either strategy is acceptable. The results of this Vanguard study did not support the pursuit of a larger formally powered study.

Discovery of TITIN Gene Truncating Variant Mutations and 5-Year Outcomes in Patients With Nonischemic Dilated Cardiomyopathy.

Genetic factors play an important role in nonischemic dilated cardiomyopathy (NIDC). However, prime opportunities remain for genetic discovery and prognostic understanding. TITIN gene truncating variant mutations (TTNtv) are of interest because of their frequent appearance in NIDC series. We sought to discover known and novel TTNtv mutations in a NIDC cohort and assess 5-year outcomes. Patients with NIDC entered into the INSPIRE Registry with ≥3 years of follow-up were studied. Whole exome sequencing (WES) was performed using an Illumina Novaseq platform. Genetic analysis used Sentieon software and the GRCh38 human reference genome. Variant calls were annotated with ClinVar. Five-year outcomes were determined by functional assessment and ejection fraction (EF) as recovered (EF ≥50%), persistent (EF 21% to 49%), or progressive (left ventricular assist device, transplant, heart failure [HF] or arrhythmic death, or EF ≤20%). The study comprised 229 NIDC patients (age = 50 ± 15 years, 58% men). TTNtv's were discovered in 27 patients with 22 unique mutations; (7 known, 15 novel). TTNtv+ patients more frequently presented with severe NIDC (EF ≤20%) (p = 0.032). By 5-year, outcomes were worse in TTNtv+ patients (p = 0.027), and patients less often recovered (11% vs. 30%). Prognosis was similar with known and novel mutations. Nongenetic (e.g., environmental) cocausal risk factors for HF were frequently present, and these factors frequently appeared to act in concert with genetic variants to precipitate clinical HF. In conclusion, our study expands the library of likely pathogenic TTN mutations and increases our understanding of their clinical impact in association with other HF risk factors.

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.

Biomarkers in the risk assessment for stroke and dementia in atrial fibrillation.

PURPOSE OF REVIEW: Atrial fibrillation is one of the most common clinically encountered arrhythmias exhibiting a strong association with a spectrum of cerebral injuries from the occurrence of clinical stroke, subclinical stroke, dementia, and cognitive decline. Dynamic noninvasive specific and sensitive diagnostic tests may allow a personalized approach to the atrial fibrillation patient's treatment based upon quantitative parameters, aiming to prevent or delay stroke, dementia, progressive cognitive decline, or to assess responses to these therapies. This review will explore molecular markers that have been shown to have an association with atrial fibrillation, and have a potential to be predictive for the risk for stroke, cognitive dysfunction, and dementia in these patients. RECENT FINDINGS: Circulating biomarkers of vascular disease, fibrosis, thrombosis, and inflammation are associated with risk of stroke in patients with atrial fibrillation. These biomarkers are additive to the predictive utility of the CHADS2 and CHA2DS2-VASc scores, and in some cases allow for additional risk prognostication of the broad categories allocated by CHADS2 and CHA2DS2-VASc scores of low, medium, and high. SUMMARY: Across the spectrum of cerebral injuries in patients with atrial fibrillation, biomarkers hold the promise of personalized risk stratification and management to minimize risks of disease.

Free thyroxine within the normal reference range predicts risk of atrial fibrillation.

INTRODUCTION: Hyperthyroidism is a known precipitating factor for atrial fibrillation (AF). However, recent reports have suggested an increased risk of AF with free thyroxine (fT4) levels even within the upper reference (normal) range. We sought to test whether higher fT4 levels within the reference range are associated with an increased risk of AF. METHODS AND RESULTS: All patients in the Intermountain Healthcare electronic medical record database with an fT4 level not on thyroid medication were included. The reference range of fT4 was divided into quartiles (Q), and associations with prevalent and incident AF were assessed by multivariable regression. Similar analyses were performed for thyroid stimulating hormone (TSH) and total and free T3. A total of 174 914 patients were included and followed for 7.0 ± 4.9 years. Of these, 7.4%, 88.4%, and 4.2% had fT4 levels below, within, and above the reference range. As expected, prevalent AF was greater with elevated fT4. However, gradients also were noted within the reference range, comparing Q4 to Q1, for prevalent AF (adjusted odds ratio 1.4, P < .0001) and incident AF (adjusted hazard ratio 1.16, P < .0001). In contrast, no relationship with AF prevalence and incidence was noted for total and free T3 within their reference ranges, and the pattern for TSH was uninformative. CONCLUSION: Higher fT4 levels within the reference range were associated with an increased prevalence and incidence of AF. These findings in a large dataset prospectively validate earlier reports and may have important implications, including a redefinition of the normal range and fT4 targets for replacement therapy.

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.

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.

The Impact of Repeated Cardioversions for Atrial Fibrillation on Stroke, Hospitalizations, and Catheter Ablation Outcomes.

BACKGROUND: Long-term outcomes after direct current cardioversion (DCCV) in patients that receive anticoagulation have demonstrated to have no adverse sequela. Less is known about the impact on atrial fibrillation (AF) outcomes and resource utilization of repeated DCCVs that are often required for long-term rhythm control. METHODS: A total of 4,135 AF patients >18 years of age that underwent DCCV with long-term system follow-up were evaluated. Patients were stratified by the number of DCCVs received: 1 (n=2,201), 2-4 (n=1,748), and ≥5 (n=186). Multivariable Cox hazard regression was used to determine the association of DCCV categories to the outcomes of death, AF hospitalization, AF ablation, DCCVs, and stroke/transient ischemic attack. RESULTS: The average follow-up of the patient population was 1,633.1±1,232.9 (median: 1,438.0) days. Patients who underwent 2-4 and ≥5 DCCVs had more comorbidities, namely hypertension, hyperlipidemia and heart failure. Anticoagulation use was common at the time of DCCV in all groups (89.1%, 91.2%, 91.9%, p=0.06) and amiodarone use increased with increasing DCCV category (30.1%, 43.4%, 52.2, p<0.0001). At 5 years, patients that received more DCCVs had higher rates of repeat DCCVs, AF hospitalizations, and ablations. Stroke rates were not increased. Though not statistically significant, 5-year death was increased when comparing DCCV >5 vs. 1, (HR=1.32 [0.89-1.94], p=0.17). CONCLUSIONS: This study found that the increasing number of DCCVs, despite escalation of other pharmacologic and nonpharmacologic therapies, is a long-term independent risk factor for repeat DCCVs, ablations, and AF hospitalizations among AF patients.

Stroke-independent contribution of atrial fibrillation to dementia: a meta-analysis.

Background: Atrial fibrillation (AF) is associated with an increased risk of dementia. It is presently unknown to what extent AF contributes to dementia onset independently from prevalent and incident cerebrovascular accidents (CVAs)/transient ischaemic attacks (TIAs). Methods: MEDLINE/PubMed and Embase databases were searched for prospective observational results, which produced risk estimates for dementia in AF patients, adjusted for prevalent and incident CVAs/TIAs. Results: Five prospective observational studies were included, comprising 61 008 patients, having a median follow-up of 12.5 years. Meta-analysis of observational results indicates an increased risk of dementia in AF, adjusted for cerebrovascular clinical events (HR 1.28, 95% CI 1.17 to 1.41, I2=0%). Funnel plot analysis did not reveal a statistically significant asymmetry. Meta-regression analysis did not indicate statistically significant associations between baseline study-level covariates and risk estimates. Conclusion: AF confers a nearly 30% increased risk of dementia, independently from CVAs/TIAs. Screening for AF and subsequent optimised management to lower risk of cranial injury could help in preventing dementia, a condition characterised by high social and healthcare costs.

Augmented intelligence decision tool for stroke prediction combines factors from CHA2 DS2 -VASc and the intermountain risk score for patients with atrial fibrillation.

INTRODUCTION: CHA2 DS2 -VASc and CHADS2 are computationally simple risk prediction tools used to guide anticoagulation decisions for stroke prophylaxis, but they have modest risk discrimination ability and use static dichotomous variables. The Intermountain Mortality Risk Scores (IMRS) are dynamic decision tools using standard clinical laboratory tests. This study derived new stroke prediction scores using variables from both CHA2 DS2 -VASc and IMRS. METHODS AND RESULTS: In outpatients with first atrial fibrillation (AF) diagnosis at the Intermountain Healthcare (females, n = 26 063 males, n = 29 807), sex-specific "IMRS-VASc" scores were derived using variables from CHA2 DS2 -VASc, warfarin use, the complete blood count, and the comprehensive metabolic profile. Validation was performed in an independent Intermountain outpatient AF cohort (females, n = 11 021; males, n = 12 641). Stroke occurred among 3.1% and 3.1% of females and 2.3% and 2.5% of males in derivation and validation groups, respectively. IMRS-VASc stratified stroke with similar ability in derivation (c-statistics, females: c = 0.703, males: c = 0.697) and validation groups (females: c = 0.681, males: c = 0.685). CHA2 DS2 -VASc (females: c = 0.581 and c = 0.605; males: c = 0.616 and c = 0.613 in derivation and validation, respectively) and CHADS2 (females: c = 0.581 and c = 0.608; males: c = 0.620 and c = 0.621 in derivation and validation, respectively) were substantially weaker stroke predictors. IMRS was the strongest mortality predictor (females: c = 0.783 and c = 0.782; males: c = 0.796 and c = 0.794 in derivation and validation, respectively) and all scores were poor at predicting bleeding risk. CONCLUSIONS: A temporally dynamic risk score, IMRS-VASc was derived and validated as a predictor of stroke in outpatients with AF. IMRS-VASc requires further validation and the evaluation of its use in guiding care and treatment decisions for patients with AF.

Rationale and design of the impact of anticoagulation therapy on the Cognitive Decline and Dementia in Patients with Nonvalvular Atrial Fibrillation (CAF) Trial: A Vanguard study.

Atrial fibrillation (AF) is associated with a risk for cognitive impairment and dementia, which is more pronounced in patients with a history of clinical stroke. Observational trials suggest that the implementation and quality of long-term anticoagulation impact dementia risk. Emerging evidence suggests that direct oral anticoagulants may improve long-term risk of dementia in AF patients. This manuscript describes the rational and trial design of the the Cognitive Decline and Dementia in Atrial Fibrillation Patients (CAF) Trial. CAF investigates if AF patients randomized to dabigatran etexilate will have long-term higher cognition scores and lower rates of dementia compared in the long term to dose-adjusted warfarin (International Normalized Ratio [INR]: 2.0-3.0). As of 27 February 2019, a total of 120 subjects will be enrolled at one investigational site in the United States and will be followed for 2 years after study enrollment. To date, 97 have been enrolled. The average age is 74.2 years, 53% are male, and 9% had a prior stroke. In this Vanguard study, patients will be followed for 2 years after study enrollment. These prospective, randomized data will inform the understanding of two anticoagulants in AF patients as it relates to risk of cognitive decline and dementia. Cranial imaging and biomarkers collected will assist in understanding mechanisms of brain injury.

Atrial Fibrillation and Dementia: Exploring the Association, Defining Risks and Improving Outcomes.

AF is strongly associated with a spectrum of cranial injuries including stroke and dementia. Dementia risk is seen in patients with and without a prior stroke and includes idiopathic forms of dementia, such as Alzheimer's disease. The initiation, use and efficacy of anticoagulation have been shown in multiple observational trials to have an impact on dementia risk. Cerebral hypoperfusion during AF can result in cognitive decline and patients with cranial atherosclerosis may have unique susceptibility. Therapies to carefully control the ventricular rate and catheter ablation have been shown in observational trials to lower dementia risk. There is a need for further research in multiple areas and the observational trials will require prospective trials confirmation. Recent guidelines for AF have advocated the initiation of effective anticoagulation, the treatment of associated disease conditions that may influence the progression of AF and catheter ablation, with long-term management of risk factors to lower risk of dementia.

CHA2DS2-VASc scores and Intermountain Mortality Risk Scores for the joint risk stratification of dementia among patients with atrial fibrillation.

BACKGROUND: High CHA2DS2-VASc scores in atrial fibrillation (AF) patients are generally associated with increased risks of stroke and dementia. At lower CHA2DS2-VASc scores, there remains an unquantifiable cranial injury risk, necessitating an improved risk assessment method within these lower-risk groups. OBJECTIVE: The purpose of this study was to determine whether sex-specific Intermountain Mortality Risk Scores (IMRS), a dynamic measures of systemic health that comprises commonly performed blood tests, can stratify dementia risk overall and among CHA2DS2-VASc score strata in AF patients. METHODS: Female (n = 34,083) and male (n = 39,998) AF patients with no history of dementia were studied. CHA2DS2-VASc scores were assessed at the time of AF diagnosis and were stratified into scores of 0-1, 2, and ≥3. Within each CHA2DS2-VASc score stratum, patients were further stratified by IMRS categories of low, moderate, and high. Multivariable Cox hazard regression was used to determine dementia risk. RESULTS: High-risk IMRS patients were generally older and had higher rates of hypertension, diabetes, heart failure, and prior stroke. Higher CHA2DS2-VASc score strata (≥3 vs ≤1: women, hazard ratio [HR] 7.77, 95% confidence interval [CI] 5.94-10.17, P < .001; men: HR 4.75, 95% CI 4.15-5.44, P < .001) and IMRS categories (high vs low: women, HR 3.09, 95% CI 2.71-3.51, P < .001; men, HR 2.70, 95% CI 2.39-3.06, P < .001) were predictive of dementia. When stratified by CHA2DS2-VASc scores, IMRS further identified risk in each stratum. CONCLUSION: Both CHA2DS2-VASc scores and IMRS were independently associated with dementia incidence among AF patients. IMRS further stratified dementia risk among CHA2DS2-VASc score strata, particularly among those with lower CHA2DS2-VASc scores.

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.

Improving CHA2DS2-VASc stratification of non-fatal stroke and mortality risk using the Intermountain Mortality Risk Score among patients with atrial fibrillation.

Background: Oral anticoagulation (OAC) therapy guidelines recommend using CHA2DS2-VASc to determine OAC need in atrial fibrillation (AF). A usable tool, CHA2DS2-VASc is challenged by its predictive ability. Applying components of the complete blood count and basic metabolic profile, the Intermountain Mortality Risk Score (IMRS) has been extensively validated. This study evaluated whether use of IMRS with CHA2DS2-VASc in patients with AF improves prediction. Methods: Patients with AF undergoing cardiac catheterisation (N=10 077) were followed for non-fatal stroke and mortality (mean 5.8±4.1 years, maximum 19 years). CHA2DS2-VASc and IMRS were calculated at baseline. IMRS categories were defined based on previously defined criteria. Cox regression was adjusted for demographic, clinical and treatment variables not included in IMRS or CHA2DS2-VASc. Results: In women (n=4122, mean age 71±12 years), the composite of non-fatal stroke/mortality was stratified (all p-trend <0.001) by CHA2DS2-VASc (1: 12.6%, 2: 22.8%, >2: 48.1%) and IMRS (low: 17.8%, moderate: 40.9%, high risk: 64.5%), as it was for men (n=5955, mean age 68±12 years) by CHA2DS2-VASc (<2: 15.7%, 2: 30.3%, >2: 51.8%) and IMRS (low: 19.0%, moderate: 42.0%, high risk: 65.9%). IMRS stratified stroke/mortality (all p-trend <0.001) in each CHA2DS2-VASc category. Conclusions: Using IMRS jointly with CHA2DS2-VASc in patients with AF improved the prediction of stroke and mortality. For example, in patients at the OAC treatment threshold (CHA2DS2 -VASc = 2), IMRS provided ≈4-fold separation between low and high risk. IMRS provides an enhancing marker for risk in patients with AF that reflects the underlying systemic nature of this disease that may be considered in combination with the CHA2DS2-VASc score.

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.

Vagus nerve injury symptoms after catheter ablation for atrial fibrillation.

BACKGROUND: Vagus nerve injury during catheter ablation for atrial fibrillation can significantly impact quality of life and result in lingering gastrointestinal symptoms. This study was designed to define risk factors of vagus nerve injury, symptoms, prevalence, and temporal resolution. METHODS: A total of 100 patients undergoing radiofrequency catheter ablation (RFCA) were enrolled and consented to participate in the study. Patients completed a 22-item questionnaire that included questions specific to vagus nerve injury symptomatology during their baseline visit and at 1 and 3 months post-RFCA. RESULTS: The average age of the population was 63 ± 10.6 years and 68% were male. A total of 100 patients completed their baseline questionnaire (90 patients completed the 1-month questionnaires and 85 patients completed the 3-month questionnaires). Symptoms rated as moderate were prevalent at baseline (trouble swallowing 13%, bloating 26%, feeling full 20%), and increased in all categories analyzed at 1 month and with the exception of trouble swallowing returned to the preablation percentages at 3 months (heartburn 22.4%, trouble swallowing 18.8%, bloating 16.5%, nausea 8.2%, vomiting 3.5%, constipation 18.8%, diarrhea 16.4%, feeling full 15.3%). Severe rated symptoms of trouble swallowing (2-5.5%), bloating (5-7.6%), and early satiety (5-9.8%) increased at 1 month and bloating and early satiety percentages remained approximately two times higher at 3 months (trouble swallowing 2.4%, bloating 8.2%, early satiety 7.1%). CONCLUSION: The majority of symptoms were resolved by 3 months, although those patients who rate bloating and early satiety at a severe rating may have persistent symptoms.

Atrial Fibrillation Ablation and its Impact on Stroke.

Atrial fibrillation (AF) is a commonly encountered arrhythmia, which is not yet fully understood. Catheter ablation has shown to be an effective strategy for rhythm management and several small or retrospective studies have shown that stroke rates are decreased in ablated AF patients compared to those medically managed. Several studies even show that ablation returns stroke risk to that of non-AF patients. Large scale, prospective trials will further illuminate this connection and provide mechanistic understanding of the role of the procedure versus the process of selection for the procedure and peri- and post-procedural therapy and management. Furthermore, modification of risk factors associated with AF show a significant increase in the sustained success of AF ablation and can also moderate the progression of AF.

Five-year impact of catheter ablation for atrial fibrillation in patients with a prior history of stroke.

BACKGROUND: Catheter ablation of atrial fibrillation (AF) is an established therapeutic rhythm approach. Patients with a prior history of a stroke (CVA) represent a unique high-risk population for recurrent thromboembolic events. The role of antiarrhythmic treatment on the natural history of stroke recurrence in these patients is not fully understood. METHODS: Three patient groups with a prior CVA and 5 years of follow-up were matched 1:3:3 by propensity score (±0.01): AF ablation patients receiving their first ablation (n  =  139), AF patients that did not receive an ablation (n  =  416), and CVA patients without clinical AF (n  =  416). Prior CVA was determined by medical chart review. Patients were followed for outcomes of recurrent CVA, heart failure, and death. RESULTS: The average age of the population was 69 ± 11 years and 51% male. AF ablation patients had higher rates of hypertension and heart failure (P < 0.0001), but diabetes prevalence was similar between the groups (P  =  0.5). Note that 5-year risk of CVA (HR  =  2.26, P < 0.0001) and death (HR  =  2.43, P < 0.0001) were higher in the AF, no ablation group compared those that were ablated. When comparing AF, ablation to no AF patients, there was not a significant difference in 5-year risk of for CVA (HR  =  0.82, P  =  0.39) and death (HR  =  0.92, P  =  0.70); however, heart failure risk was increased (HR  =  3.08, P  =  0.001). CONCLUSION: In patients with AF and a prior CVA, patients undergoing ablation have lower rates of recurrent stroke compared to AF patients not ablated. Although the full mechanisms of benefit are unknown, as CVA rates are similar to patients without AF these data are suggestive of a potential altering of the natural history of disease progression.