Step Count, Self-reported Physical Activity, and Predicted 5-Year Risk of Atrial Fibrillation: Cross-sectional Analysis.

BACKGROUND: Physical inactivity is a known risk factor for atrial fibrillation (AF). Wearable devices, such as smartwatches, present an opportunity to investigate the relation between daily step count and AF risk. OBJECTIVE: The objective of this study was to investigate the association between daily step count and the predicted 5-year risk of AF. METHODS: Participants from the electronic Framingham Heart Study used an Apple smartwatch. Individuals with diagnosed AF were excluded. Daily step count, watch wear time (hours and days), and self-reported physical activity data were collected. Individuals' 5-year risk of AF was estimated, using the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE)-AF score. The relation between daily step count and predicted 5-year AF risk was examined via linear regression, adjusting for age, sex, and wear time. Secondary analyses examined effect modification by sex and obesity (BMI≥30 kg/m2), as well as the relation between self-reported physical activity and predicted 5-year AF risk. RESULTS: We examined 923 electronic Framingham Heart Study participants (age: mean 53, SD 9 years; female: n=563, 61%) who had a median daily step count of 7227 (IQR 5699-8970). Most participants (n=823, 89.2%) had a <2.5% CHARGE-AF risk. Every 1000 steps were associated with a 0.08% lower CHARGE-AF risk (P<.001). A stronger association was observed in men and individuals with obesity. In contrast, self-reported physical activity was not associated with CHARGE-AF risk. CONCLUSIONS: Higher daily step counts were associated with a lower predicted 5-year risk of AF, and this relation was stronger in men and participants with obesity. The utility of a wearable daily step counter for AF risk reduction merits further investigation.

Epigenetic Age and the Risk of Incident Atrial Fibrillation.

BACKGROUND: The most prominent risk factor for atrial fibrillation (AF) is chronological age; however, underlying mechanisms are unexplained. Algorithms using epigenetic modifications to the human genome effectively predict chronological age. Chronological and epigenetic predicted ages may diverge in a phenomenon referred to as epigenetic age acceleration (EAA), which may reflect accelerated biological aging. We sought to evaluate for associations between epigenetic age measures and incident AF. METHODS: Measures for 4 epigenetic clocks (Horvath, Hannum, DNA methylation [DNAm] PhenoAge, and DNAm GrimAge) and an epigenetic predictor of PAI-1 (plasminogen activator inhibitor-1) levels (ie, DNAm PAI-1) were determined for study participants from 3 population-based cohort studies. Cox models evaluated for associations with incident AF and results were combined via random-effects meta-analyses. Two-sample summary-level Mendelian randomization analyses evaluated for associations between genetic instruments of the EAA measures and AF. RESULTS: Among 5600 participants (mean age, 65.5 years; female, 60.1%; Black, 50.7%), there were 905 incident AF cases during a mean follow-up of 12.9 years. Unadjusted analyses revealed all 4 epigenetic clocks and the DNAm PAI-1 predictor were associated with statistically significant higher hazards of incident AF, though the magnitudes of their point estimates were smaller relative to the associations observed for chronological age. The pooled EAA estimates for each epigenetic measure, with the exception of Horvath EAA, were associated with incident AF in models adjusted for chronological age, race, sex, and smoking variables. After multivariable adjustment for additional known AF risk factors that could also potentially function as mediators, pooled EAA measures for 2 clocks remained statistically significant. Five-year increases in EAA measures for DNAm GrimAge and DNAm PhenoAge were associated with 19% (adjusted hazard ratio [HR], 1.19 [95% CI, 1.09-1.31]; P<0.01) and 15% (adjusted HR, 1.15 [95% CI, 1.05-1.25]; P<0.01) higher hazards of incident AF, respectively. Mendelian randomization analyses for the 5 EAA measures did not reveal statistically significant associations with AF. CONCLUSIONS: Our study identified adjusted associations between EAA measures and incident AF, suggesting that biological aging plays an important role independent of chronological age, though a potential underlying causal relationship remains unclear. These aging processes may be modifiable and not constrained by the immutable factor of time.

Epidemiology of Atrial Fibrillation in the 21st Century: Novel Methods and New Insights.

Accompanying the aging of populations worldwide, and increased survival with chronic diseases, the incidence and prevalence of atrial fibrillation (AF) are rising, justifying the term global epidemic. This multifactorial arrhythmia is intertwined with common concomitant cardiovascular diseases, which share classical cardiovascular risk factors. Targeted prevention programs are largely missing. Prevention needs to start at an early age with primordial interventions at the population level. The public health dimension of AF motivates research in modifiable AF risk factors and improved precision in AF prediction and management. In this review, we summarize current knowledge in an attempt to untangle these multifaceted associations from an epidemiological perspective. We discuss disease trends, preventive opportunities offered by underlying risk factors and concomitant disorders, current developments in diagnosis and risk prediction, and prognostic implications of AF and its complications. Finally, we review current technological (eg, eHealth) and methodological (artificial intelligence) advances and their relevance for future prevention and disease management.

Association of Habitual Physical Activity With Cardiovascular Disease Risk.

RATIONALE: A sedentary lifestyle is associated with increased risk for cardiovascular disease (CVD). Smartwatches enable accurate daily activity monitoring for physical activity measurement and intervention. Few studies, however, have examined physical activity measures from smartwatches in relation to traditional risk factors associated with future risk for CVD. OBJECTIVE: To investigate the association of habitual physical activity measured by smartwatch with predicted CVD risk in adults. METHODS AND RESULTS: We enrolled consenting FHS (Framingham Heart Study) participants in an ongoing eFHS (electronic Framingham Heart Study) at the time of their FHS research center examination. We provided participants with a smartwatch (Apple Watch Series 0) and instructed them to wear it daily, which measured their habitual physical activity as the average daily step count. We estimated the 10-year predicted risk of CVD using the American College of Cardiology/American Heart Association 2013 pooled cohort risk equation. We estimated the association between physical activity and predicted risk of CVD using linear mixed effects models adjusting for age, sex, wear time, and familial structure. Our study included 903 eFHS participants (mean age 53±9 years, 61% women, 9% non-White) who wore the smartwatch ≥5 hours per day for ≥30 days. Median daily step count was similar among men (7202 with interquartile range 3619) and women (7260 with interquartile range 3068; P=0.52). Average 10-year predicted CVD risk was 4.5% (interquartile range, 6.1%) for men and 1.2% (interquartile range, 2.2%) for women (P=1.3×10-26). Every 1000 steps higher habitual physical activity was associated with 0.18% lower predicted CVD risk (P=3.2×10-4). The association was attenuated but remained significant after further adjustment for body mass index (P=0.01). CONCLUSIONS: In this community-based sample of adults, higher daily physical activity measured by a study smartwatch was associated with lower predicted risk of CVD. Future research should examine the longitudinal association of prospectively measured daily activity and incident CVD.

Anti-inflammatory HDL effects are impaired in atrial fibrillation.

High-density lipoprotein (HDL), best known for cholesterol transport, also has anti-inflammatory effects. Previous studies suggest involvement of myeloperoxidase (MPO) in modification of HDL. HDL bound Sphingosine-1-phosphate (S1P) has been implied to be an essential protein regarding beneficial HDL effects. In this study, we analyzed anti-inflammatory HDL properties in patients with atrial fibrillation (AF), a disease involving atrial inflammation, compared to non-AF controls and whether anti-inflammatory properties improve upon catheter ablation. Additionally, association with serum concentrations of MPO and S1P were assessed. We isolated HDL from 25 AF patients, 13 non-AF individuals and 14 AF patients at follow-up (FU) after catheter ablation. S1P was measured in a cohort of 141 AF and 21 FU patients. Following preincubation with HDL from either group, bovine aortic endothelial cells were stimulated using tumor necrosis factor α and expression of pro-inflammatory genes intercellular adhesion molecule 1 (ICAM1), vascular cell adhesion molecule 1 (VCAM1), E-selectin (SELE) and P-selectin (SELP) was assessed using qPCR. Concentrations of circulating protein of these genes as well as MPO and S1P were measured in serum samples. Compared to non-AF individuals HDL from AF patients suppressed gene expression of the pro-inflammatory adhesion molecules ICAM1, VCAM1, SELE and SELP 27%, 18%, 21% and 57% less, respectively (p < 0.05 for all except SELE p = 0.06). In FU patients, the anti-inflammatory HDL activity was improved (suppression of ICAM1 + 22%, VCAM1 + 10%, SELE + 38% and SELP + 75%, p < 0.05 for all except VCAM1 p = 0.08). AF patients using angiotensin converting enzyme inhibitors or angiotensin receptor blockers had better anti-inflammatory HDL properties than non-users (gene expression suppression at least 28% more, p < 0.05 for all except ICAM1 p = 0.051). Circulating protein concentrations were not correlated with in vitro gene-expression, but circulating P-selectin was generally elevated in AF and FU patients compared to non-AF patients. MPO plasma concentration was positively associated with gene-expression of ICAM1, VCAM1 and SELP (r2 > 0.4, p < 0.05). Serum concentrations of S1P were increased in FU patients {1.201 µM [1.077-1.543]} compared to AF patients {0.953 µM [0.807-1.135], p < 0.01} but not correlated with ICAM1, VCAM1 and SELP gene expression. We conclude that the anti-inflammatory activity of HDL is impaired in AF patients, which might promote AF progression and AF-associated complications.

Temporal trends in cause-specific mortality among individuals with newly diagnosed atrial fibrillation in the Framingham Heart Study.

BACKGROUND: All-cause mortality following atrial fibrillation (AF) has decreased over time. Data regarding temporal trends in causes of death among individuals with AF are scarce. The aim of our study was to analyze temporal trends in cause-specific mortality and predictors for cardiovascular (CVD) and non-CVD deaths among participants with incident AF in the Framingham Heart Study. METHODS: We categorized all newly diagnosed AF cases according to age at AF diagnosis (< 70, 70 to < 80, and ≥ 80 years) and epoch of AF diagnosis (< 1990, 1990-2002, and ≥ 2003). We followed participants until death or the last follow-up. We categorized death causes into CVD, non-CVD, and unknown causes. For each age group, we tested for trends in the cumulative incidence of cause-specific death across epochs. We fit multivariable Fine-Gray models to assess subdistribution hazard ratios (HR) between clinical risk factors at AF diagnosis and cause-specific mortality. RESULTS: We included 2125 newly diagnosed AF cases (mean age 75.5 years, 47.8% women). During a median follow-up of 4.8 years, 1657 individuals with AF died. There was evidence of decreasing CVD mortality among AF cases diagnosed < 70 years and 70 to < 80 years (ptrend < 0.001) but not ≥ 80 years (p = 0.76). Among the cases diagnosed < 70 years, the cumulative incidence of CVD death at 75 years was 67.7% in epoch 1 and 13.9% in epoch 3; among those 70 to < 80 years, the incidence at 85 years was 58.9% in epoch 1 and 18.9% in epoch 3. Advancing age (HR per 1 SD increase 6.33, 95% CI 5.44 to 7.37), prior heart failure (HR 1.49, 95% CI 1.14-1.94), and prior myocardial infarction (HR 1.44, 95% CI 1.15-1.80) were associated with increased rate of CVD death. CONCLUSIONS: In this community-based cohort, CVD mortality among AF cases decreased over time. Most deaths in individuals with AF are no longer CVD-related, regardless of age at AF diagnosis.

Prediction of low-voltage areas using modified APPLE score.

AIMS: The presence of low-voltage areas (LVAs) in patients with atrial fibrillation (AF) reflects left atrial (LA) electroanatomical substrate, which is essential for individualized AF management. However, echocardiographic anteroposterior LA diameter included into previous LVAs prediction scores does not mirror LA size accurately and impaired left ventricular ejection fraction (LV-EF) is not directly associated with atrial myopathy. Therefore, we aimed to compare a modified (m)APPLE score, which included LA volume (LAV) and LA emptying fraction (LA-EF) with the regular APPLE score for the prediction of LVAs. METHODS AND RESULTS: In patients undergoing first AF catheter ablation, LVAs were determined peri-interventionally using high-density maps and defined as signal amplitude <0.5 mV. All patients underwent cardiovascular magnetic resonance imaging before intervention. The APPLE (one point for Age ≥ 65 years, Persistent AF, imPaired eGFR ≤ 60 mL/min/1.73 m2, LA diameter ≥ 43 mm, and LVEF < 50%) and (m)APPLE (last two variables changed by LAV ≥ 39 mL/m2, and LA-EF < 31%) scores were calculated at baseline. The study population included 219 patients [median age 65 (interquartile range 57-72) years, 41% females, 59% persistent AF, 25% LVAs]. Both scores were significantly associated with LVAs [OR 1.817, 95% CI 1.376-2.399 for APPLE and 2.288, 95% CI 1.650-3.172 for (m)APPLE]. Using receiver operating characteristic curves analysis, the (m)APPLE score [area under the curve (AUC) 0.779, 95% CI 0.702-0.855] showed better LVAs prediction than the APPLE score (AUC 0.704, 95% CI 0.623-0.784), however, without statistically significant difference (P = 0.233). CONCLUSION: The modified (m)APPLE score demonstrated good prognostic value for LVAs prediction and was comparable with the regular APPLE score.

Adherence of Mobile App-Based Surveys and Comparison With Traditional Surveys: eCohort Study.

BACKGROUND: eCohort studies offer an efficient approach for data collection. However, eCohort studies are challenged by volunteer bias and low adherence. We designed an eCohort embedded in the Framingham Heart Study (eFHS) to address these challenges and to compare the digital data to traditional data collection. OBJECTIVE: The aim of this study was to evaluate adherence of the eFHS app-based surveys deployed at baseline (time of enrollment in the eCohort) and every 3 months up to 1 year, and to compare baseline digital surveys with surveys collected at the research center. METHODS: We defined adherence rates as the proportion of participants who completed at least one survey at a given 3-month period and computed adherence rates for each 3-month period. To evaluate agreement, we compared several baseline measures obtained in the eFHS app survey to those obtained at the in-person research center exam using the concordance correlation coefficient (CCC). RESULTS: Among the 1948 eFHS participants (mean age 53, SD 9 years; 57% women), we found high adherence to baseline surveys (89%) and a decrease in adherence over time (58% at 3 months, 52% at 6 months, 41% at 9 months, and 40% at 12 months). eFHS participants who returned surveys were more likely to be women (adjusted odds ratio [aOR] 1.58, 95% CI 1.18-2.11) and less likely to be smokers (aOR 0.53, 95% CI 0.32-0.90). Compared to in-person exam data, we observed moderate agreement for baseline app-based surveys of the Physical Activity Index (mean difference 2.27, CCC=0.56), and high agreement for average drinks per week (mean difference 0.54, CCC=0.82) and depressive symptoms scores (mean difference 0.03, CCC=0.77). CONCLUSIONS: We observed that eFHS participants had a high survey return at baseline and each 3-month survey period over the 12 months of follow up. We observed moderate to high agreement between digital and research center measures for several types of surveys, including physical activity, depressive symptoms, and alcohol use. Thus, this digital data collection mechanism is a promising tool to collect data related to cardiovascular disease and its risk factors.

Association of Habitual Physical Activity With Home Blood Pressure in the Electronic Framingham Heart Study (eFHS): Cross-sectional Study.

BACKGROUND: When studied in community-based samples, the association of physical activity with blood pressure (BP) remains controversial and is perhaps dependent on the intensity of physical activity. Prior studies have not explored the association of smartwatch-measured physical activity with home BP. OBJECTIVE: We aimed to study the association of habitual physical activity with home BP. METHODS: Consenting electronic Framingham Heart Study (eFHS) participants were provided with a study smartwatch (Apple Watch Series 0) and Bluetooth-enabled home BP cuff. Participants were instructed to wear the watch daily and transmit BP values weekly. We measured habitual physical activity as the average daily step count determined by the smartwatch. We estimated the cross-sectional association between physical activity and average home BP using linear mixed effects models adjusting for age, sex, wear time, antihypertensive drug use, and familial structure. RESULTS: We studied 660 eFHS participants (mean age 53 years, SD 9 years; 387 [58.6%] women; 602 [91.2%] White) who wore the smartwatch 5 or more hours per day for 30 or more days and transmitted three or more BP readings. The mean daily step count was 7595 (SD 2718). The mean home systolic and diastolic BP (mmHg) were 122 (SD 12) and 76 (SD 8). Every 1000 increase in the step count was associated with a 0.49 mmHg lower home systolic BP (P=.004) and 0.36 mmHg lower home diastolic BP (P=.003). The association, however, was attenuated and became statistically nonsignificant with further adjustment for BMI. CONCLUSIONS: In this community-based sample of adults, higher daily habitual physical activity measured by a smartwatch was associated with a moderate, but statistically significant, reduction in home BP. Differences in BMI among study participants accounted for the majority of the observed association.

Relevance of esophageal position and temperature on thermal injuries and rhythm outcome in atrial fibrillation ablations.

BACKGROUND: Thermolesions are a dangerous complication of atrial fibrillation (AF) ablation. We aimed to assess the reasons for thermolesions and the effect of esophageal position on recurrences. METHODS: The study included consecutive patients undergoing AF catheter ablation at Heart Center Leipzig between January and September 2014. We collected data of esophagus localization, temperature, endoscopy, and follow-up. RESULTS: The study included 645 patients into analyses. A total of 626 (97.2%) received a temperature probe. Esophageal position was categorized: (A) behind left pulmonary veins, (B) left ostial, (C) in the middle of left atrium, (D) right ostial, and (E) behind right pulmonary veins. The most frequent esophageal position was B-C (n = 201, 32.1%), followed by B (n = 161, 25.7%), and C (n = 147, 23.5%). The temperature was highest in A-B positions (42.04°C) and in D-E positions (41.70°C). There was a significant correlation between the endoscopically detected esophageal lesions (EDEL) and the esophageal position (r² = -.115, P = .004) and the esophageal temperature (r² = .162, P = .000), but not with body mass index (BMI) (r² = -.016, P = .688). Additional substrate modification in the left atrium resulted in significantly higher esophageal temperatures (P < .001) and more frequent EDEL (P = .049). An EDEL was found in 15 patients (2.3% of all patients, 5.6% of patients receiving endoscopy). Of those, the median esophageal temperature was 41.8°C (interquartile range [IQR]: 41.2-42.4). Neither esophageal position nor temperature during ablation was associated with arrhythmia recurrences (both P > .400). CONCLUSIONS: EDEL depended on the esophageal position and temperature, but not on BMI. Esophageal position and intraluminal temperature during ablation had no effect on recurrences.

Atrial fibrillation is associated with alterations in HDL function, metabolism, and particle number.

Increased morbidity and mortality in atrial fibrillation (AF) are related to the pro-fibrotic, pro-thrombotic, and pro-inflammatory processes that underpin the disease. High-density lipoproteins (HDL) have anti-inflammatory, anti-oxidative, and anti-thrombotic properties. Functional impairment of HDL may, therefore, associate with AF initiation or progression. We studied indices of HDL quality and quantity of AF patients and healthy controls, including HDL-particle number, HDL cholesterol, apolipoprotein (apo) A-I levels, serum amyloid A (SAA) content and HDL-cholesterol efflux capacity, and paraoxonase activity of apoB-depleted serum. Serum samples were collected from AF patients (n = 91) before catheter ablation and from age- and sex-matched control subjects (n = 54). HDL-cholesterol efflux capacity was assessed in a validated assay using [3H]-cholesterol-labeled J774 macrophages. Lecithin-cholesterol acyltransferase (LCAT) and paraoxonase activities were assessed using fluorometric assays, SAA levels were determined by ELISA, and total and subclass HDL-particle number was assessed by nuclear magnetic resonance spectroscopy. ApoA-I levels were determined by immunoturbidimetry. HDL-cholesterol efflux capacity, HDL-particle number, apoA-I levels, and LCAT activity were markedly reduced in AF patients when compared to healthy individuals (all p < 0.001), whereas HDL-associated paraoxonase activity and SAA content were not altered (p = 0.578, p = 0.681). Notably, cholesterol efflux capacity, HDL-particle number, apoA-I levels as well as LCAT activity recovered following restoration of sinus rhythm (all p < 0.001). We identified marked alterations in HDL function, HDL maturation, and HDL-particle number in AF patients. Assessing HDL-particle number and function in AF may be used as a surrogate marker of AF onset and progression and may help identifying patients at high risk.

Prediction of electro-anatomical substrate using APPLE score and biomarkers.

AIMS: Low voltage areas (LVAs) represent advanced remodelling processes in left atrium in patients with atrial fibrillation (AF) and are associated with higher rates of arrhythmia recurrences. However, the prediction of LVA based on clinical parameters is understudied. Recently, we introduced APPLE score to predict rhythm outcomes after catheter ablation. The aim of this study was to analyse (i) LVA prediction using APPLE score and (ii) differences in biomarker profiles according to APPLE score in AF patients. METHODS AND RESULTS: Patients undergoing first AF ablation were included. The APPLE score (one point for Age >65 years, Persistent AF, imPaired eGFR <60 mL/min/1.73 m2, LA diameter ≥43 mm, EF <50%) was calculated before ablation. Blood plasma samples from femoral vein were collected before ablation. Low voltage area were determined using high-density maps and defined as <0.5 mV. NT-proANP, NT-proBNP, L-Selectin, and vascular cell adhesion protein 1 (VCAM-1) were studied using commercially available assays. We studied 214 patients [age median (interquartile range) 65 (57-72) years, 59% males, 59% persistent AF, 27% LVA]. There were 42% patients with APPLE ≥3. The levels of NT-proANP (P < 0.001), NT-proBNP (P = 0.016), and VCAM-1 (P = 0.040) increased with each APPLE point. In the univariable analysis, APPLE score [odds ratio (OR) 1.921, 95% confidence interval (CI) 1.453-2.538; P < 0.001], female gender (OR 2.283, 95% CI 1.280-4.071; P = 0.005), and NT-proANP (OR 1.031, 95% CI 1.008-1.054; P = 0.007) were significant predictors for LVA. On the multivariable analysis, only APPLE score and female gender remained associated with LVA. CONCLUSION: The APPLE score can be used for prediction of LVA before AF ablation. There was a positive correlation between biomarker levels and APPLE score.

Very late arrhythmia recurrences in patients with sinus rhythm within the first year after catheter ablation: The Leipzig Heart Center AF Ablation Registry.

AIMS: Arrhythmia recurrences after catheter ablation of atrial fibrillation (AF) still remain an important management issue. Recently, the APPLE score had been introduced to predict rhythm outcomes within 12 months after catheter ablation, while the simple MB-LATER score was developed for the prediction of very late recurrence of AF (VLRAF) occurring after 12 months. The aim of this study was to compare APPLE and MB-LATER scores in predicting VLRAF. METHODS AND RESULTS: The study population included arrhythmia-free patients within first 12 months after first radiofrequency catheter ablation from The Heart Center Leipzig AF Ablation Registry. The APPLE [one point for Age >65 years, Persistent AF, imPaired eGFR <60 mL/min/1.73 m2, Left atrial (LA) diameter ≥43 mm, EF <50%] and MB-LATER scores [one point for Male gender, Bundle branch block or QRS >120 ms, LA diameter ≥47 mm, AF Type (persistent AF), Early Recurrence <3 months] were calculated before and 3 months after ablation, respectively. We followed 482 patients {age 61 [interquartile range (IQR) 54-68] years, 66% males, 32% persistent AF} for median 40 (IQR 35-50) months. There were 184 patients (38.3%) with arrhythmia recurrences within 13-60 months after ablation. On multivariate analysis, APPLE [odds ratio (OR) 1.517, 95% confidence interval (CI) 1.244-1.850, P < 0.001] and MB-LATER (OR 1.437, 95% CI 1.211-1.705, P < 0.001) scores and diabetes mellitus (OR 2.214, 95% CI 1.353-3.625, P = 0.002) were significantly associated with arrhythmia recurrences. Receiver operating characteristic curve analyses demonstrated moderate prediction for both scores [area under the curve (AUC) 0.607, P < 0.001 for APPLE score, AUC 0.604, P < 0.001 for MB-LATER]. CONCLUSION: Prediction of VLRAF is similar for both APPLE and MB-LATER scores. A better score remains still a clinical unmet need.

Heart Failure and Stroke.

PURPOSE: Ischemic stroke significantly contributes to morbidity and mortality in heart failure (HF). The risk of stroke increases significantly, with coexisting atrial fibrillation (AF). An aggravating factor could be asymptomatic paroxysms of AF (so-called silent AF), and therefore, the risk stratification in these patients remains difficult. This review provides an overview of stroke risk in HF, its risk stratification, and stroke prevention in these patients. RECENT FINDINGS: Stroke risk stratification in HF patients remains an important issue. Recently, the CHA2DS2-VASc score, originally developed to predict stroke risk in AF patients, had been reported to be a predictive for strokes in HF patients regardless of AF being present. Furthermore, there are several independent risk factors (e.g., hypertension, diabetes mellitus, prior stroke) described. Based on the current evidence, HF should be considered as an independent risk factor for stroke. The CHA2DS2-VASc score might be useful to predict stroke risk in HF patients with or without AF in clinical routine. However, there is only a recommendation for the oral anticoagulation use in patients with concomitant HF and AF, while in patients with HF and no AF, individualized risk stratification is preferred. Current guidelines recommend to prefer non-vitamin Kantagonist anticoagulants over warfarin.

Cardiogenic Stroke Despite Low CHA2 DS2 -VASc Score: Assessing Stroke risk by Left Atrial Appendage Anatomy (ASK LAA).

INTRODUCTION: In patients with atrial fibrillation (AF), LAA morphology has been suggested to modify thromboembolic event (TE) risk. We tested the hypothesis that TE in low-risk patients is associated with LAA characteristics. METHODS: Of 2,069 patients who underwent AF ablation, 25 (1.2%) had a prior TE and a low CHA2 DS2 -VASc score (≤1). Those patients were matched for the CHA2 DS2 -VASc criteria with 75 event-free patients and CT data were compared. LAA measurements, morphology (Cactus, Chicken-Wing, Windsock, Cauliflower), and takeoff of the superior and inferior edge in relation (higher or lower) to the respective takeoff of the adjacent pulmonary vein (PV) were determined. LAA flow in relation to heart rate was also compared. RESULTS: Univariate analysis showed that TE patients had a higher incidence of superior LAA takeoff (i.e., higher than the left superior PV; 28% vs. 4%, P = 0.002) and a higher incidence of hyperlipidemia (40% vs. 17%, P = 0.028), while LAA morphologies, inferior takeoff, and other LAA characteristics were similar between groups. Logistic regression revealed that a superior LAA takeoff (OR: 9.1, 95% CI: 2.1-38.6, P = 0.003) was the only independent predictor of TE. There was a negative correlation between heart rate and LAA flow (r = -0.2 cm/s pro bpm, P = 0.048), that was even more pronounced for the superior LAA takeoff (r = -0.67 cm/s pro bpm, P = 0.035). CONCLUSION: A higher LAA takeoff is associated with a tachycardia-mediated thrombogenic flow and an increased thromboembolic risk. These findings may have implications for anticoagulation management of AF patients with low CHA2 DS2 -VASc scores and higher LAA takeoff.

J wave pattern in unexplained syncope.

J wave pattern (JWP), characterized by J-point elevation in the anterolateral or inferior leads of the 12-lead electrocardiogram, has been associated with increased risk for idiopathic ventricular fibrillation and mortality. However, its prevalence in syncope of different etiologies is unknown and was evaluated in this study. The study sample comprised 170 consecutive patients with vasovagal syncope or syncope that remained unexplained after complete work-up. JWP in inferior leads and with a horizontal/descending ST-segment is more frequently found in subjects with unexplained syncope than in subjects with vasovagal syncope. This finding may be linked with worse prognosis of unexplained syncope.

The predictive value of echocardiographic parameters associated with left ventricular diastolic dysfunction on short- and long-term outcomes of catheter ablation of atrial fibrillation.

AIMS: Recurrence of atrial fibrillation (AF) is frequently observed after AF catheter ablation. However, the predictive value of echocardiographic parameters associated with left ventricular diastolic dysfunction (LVDD) has not been well studied. METHODS AND RESULTS: In 124 consecutive patients (mean age 61 ± 10 years, 60% male) with paroxysmal (n = 70) or persistent AF (n = 54) undergoing AF catheter ablation, mitral early diastolic peak (E-wave) and late peak (A-wave) velocities, E/A ratio, deceleration time (DT) of mitral early velocity, early diastolic mitral annulus peak velocity (e'), and E/e' ratio were determined by transthoracic echocardiography. Early (ERAF) and late AF recurrence (LRAF) were monitored with 7-day Holter electrocardiograms directly after catheter ablation and after 6 and 12 months. Early AF recurrence occurred in 34% of the patients, while LRAF was observed in 27% of the patients. Patients with ERAF had higher E-wave (0.9 ± 0.2 vs. 0.8 ± 0.2 m/s, P = 0.035) and lower A-wave velocity (0.5 ± 0.2 vs. 0.6 ± 0.2 m/s, P = 0.038), higher E/A ratio (1.8 ± 0.9 vs. 1.5 ± 0.9, P = 0.089), and slower DT (214 ± 67 vs. 243 ± 68 ms, P = 0.073), while E/e', left atrial diameter, and left ventricular ejection fraction were similar. In multivariable regression analysis, the E/A ratio was the only independent predictor of ERAF (odds ratio 2.905, 95% confidence interval 1.072-7.870, P = 0.036). None of the echocardiographic parameters influenced the late therapy outcome. CONCLUSION: Early results of the catheter ablation, but not the late rhythm outcome, are influenced by an impaired mitral inflow pattern, which is associated with LVDD.

Bidirectional Association Between Atrial Fibrillation and Myocardial Infarction, and Relation to Mortality in the Framingham Heart Study.

BACKGROUND: Individuals with both atrial fibrillation (AF) and myocardial infarction (MI) have higher mortality compared with individuals with only 1 condition. Whether mortality differs according to the temporal order of AF and MI is unclear. METHODS AND RESULTS: We included participants from the FHS (Framingham Heart Study) from 1960 and onwards. We assessed the hazard ratio (HR) of new-onset AF and MI, and mortality according to MI and AF status (prevalent and interim) using multivariable-adjusted Cox proportional hazards models. Interim diseases were modeled as time-varying variables. For the analysis of new-onset AF, 10 923 participants (55% women; mean±SD age, 54±8 years) were included. For new-onset MI, 10 804 participants (55% women; mean±SD age, 54±8 years) were included. Compared with no MI, the hazard of new-onset AF was higher in participants with prevalent (HR, 1.60 [95% CI, 1.32-1.94]) and interim MI (HR, 3.96 [95% CI, 3.18-4.91]). Both ST-segment-elevation MI and non-ST-segment-elevation MI were associated with new-onset AF. Interim AF, not prevalent AF, was associated with higher hazard rate of new-onset MI (HR, 2.21 [95% CI, 1.67-2.92]). Interim AF was associated with both ST-segment-elevation MI and non-ST-segment-elevation MI. Mortality was significantly greater among participants with AF and MI compared with participants with 1 of the 2, regardless of temporal order. CONCLUSIONS: We report a bidirectional association between AF and MI, which was observed for both non-ST-segment-elevation MI and ST-segment-elevation MI. Participants with both AF and MI had considerably higher mortality compared with participants with only 1 of the 2 conditions, regardless of order.

Response of circulating heat shock protein 70 and anti-heat shock protein 70 antibodies to catheter ablation of atrial fibrillation.

BACKGROUND: This pilot study investigated the association between heat shock protein 70 (HSP70) and anti-HSP70 antibodies as well as their changes and rhythm outcome after atrial fibrillation (AF) catheter ablation. METHODS: We studied 67 patients with AF (59±11 years, 66% male, 66% lone AF) undergoing catheter ablation. Circulating HSP70 and anti-HSP70 antibody levels were quantified using commercially available assays before and 6 months after catheter ablation. Serial 7-day Holter ECGs were used to detect AF recurrences. RESULTS: At baseline, HSP70 was detectable in 14 patients (21%), but there was no correlation between clinical or echocardiographic variables and the presence or the level of HSP70. In contrast, patients with paroxysmal AF (n=39) showed lower anti-HSP70 antibodies (median [IQR] of 43 [28 - 62] µg/ml) than patients with persistent AF (n=28; 53 [41 - 85] µg/ml, p=0.035). Using multivariable regression analysis, AF type was the only variable associated with anti-HSP70 antibodies (Beta=0.342, p=0.008). At 6 months, HSP70 was present in 27 patients (41%, p<0.001 vs. baseline). Similarly, there was an increase of anti-HSP70 antibodies (48 [36 - 72] vs. 57 [43 - 87] µg/ml, p<0.001). AF recurrence rates were higher in patients with HSP70 increase ≥0.025 ng/ml (32 vs. 11%, p=0.038) or anti-HSP70 increase ≥2.5 µg/ml (26 vs. 4%, p=0.033). CONCLUSIONS: HSP70 and anti-HSP70 antibodies may - at least in part - be associated in the progression of AF and AF recurrence after catheter ablation.