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The interruption of oral anticoagulation therapy (OAC) after CA of atrial fibrillation (AF) is controversial. The purpose of this study was to evaluate the relationship between successful long-term outcomes of catheter resection and SR maintenance and ischemic stroke risk in Korea. We studied 1,548 consecutive patients who were followed up for more than 2 years after CA of AF. We investigated the incidence of ischemic stroke during long-term follow-up. Compared to the AF recurrence group (n = 619), the sinus rhythm (SR) maintenance group (n = 929) had more paroxysmal AF (74.6% versus 44.4%, p<0.001), smaller LA size (39.9±5.7mm versus 42.3±6.0mm, p<0.001), and younger age (54.2±10.9 years versus 56.4±10.6 years, p<0.001). However, CHA2DS2-VASc scores were not significantly different between the two groups (0.9 vs. 1.1, p = 0.053). The overall incidence of ischemic stroke during the mean follow-up period of 54 months after CA was 0.6%, and was significantly lower in the SR group than the AF recurrence group (0.3% vs. 1.1%, log-rank test p<0.001). However, in sub-analysis in the SR group, the rate of ischemic stroke was significantly increasing in patients with a CHA2DS2-VASc score ≥ 4 compared to those with a CHA2DS2-VASc score < 4 (4.3% vs. 0.2%, log-rank test p<0.001). In conclusion, this long-term follow-up data in patients with AF who underwent successful CA showed that SR maintenance was correlated with a lower rate of ischemic stroke in Korea. However, it was only observed in patients with CHA2DS2-VASc score ≤3. [ABSTRACT FROM AUTHOR]

Background and objectives: High monocyte counts are related to adverse outcomes in cardiovascular disease. Their role in prognostication in patients with atrial fibrillation (AF) is unknown. We investigated whether monocyte counts are useful as a marker of prognosis in patients with AF. Methods: Monocyte counts were obtained from blood samples in 881 AF patients. Study outcomes were (i) all-cause death; (ii) major adverse cardiovascular events; (iii) stroke, TIA or other systemic embolism (SSE); and (iv) major bleeding. Results: Median follow up was 7.2 years; 44% of patients died, 48% developed MACE; 9% had SSE and 5% had major bleeding. On Cox regression, after adjustment for CHA2DS2-VASc score, the highest quartile of monocyte counts (i.e., ≥580 μL vs. other quartiles) was associated with increased risk of death (hazard ratio [HR] 1.64, 95% confidence interval [CI] 1.31–2.05, p<0.001) and MACE (HR 1.58, 95% CI 1.28–1.96, p<0.001). Persistent monocyte levels ≥580 per μL during follow up were associated with further increase in risk of death (HR 1.52, 95% CI 1.10–2.11, p = 0.01) and MACE (HR 1.54, 95% CI 1.13–2.09, p = 0.006). Persistent monocyte levels ≥580 per μL during were associated with a significant increase in major bleeding events (HR 2.77, 95% CI 1.36–5.67, p = 0.005, after adjustment for HAS-BLED score). Conclusion: High monocyte counts independently predict the occurrence of MACE, major bleeding and mortality, but not SSE. Understanding the pathophysiological mechanisms involved would help understand the relationships between monocytes, and adverse thrombotic and bleeding outcomes in AF patients. [ABSTRACT FROM AUTHOR]

Background: Patients with end-stage renal disease have very high mortality. In individuals on hemodialysis, cardiovascular deaths account for ~50% of all deaths in this population, mostly due to arrhythmia. To determine the causes of these arrhythmic deaths is essential in order to adopt preventive strategies. The main objective of this study was to investigate whether, the presence of QTc interval alterations, from electrolyte abnormalities or presence of rare genetic variants, could have a relationship with sudden arrhythmogenic deaths in end-stage renal disease patients. Methods: We recorded the pre- and post-dialysis QTc interval in 111 patients undergoing hemodialysis. In 47 of them, we analyzed 24 SCD-related genes including the most prevalent genes associated with long QT syndrome using a custom resequencing panel. Results: We found a positive although not significant association between the presence of long QTc and mortality in a subset of end-stage renal disease patients. In addition, in five patients with long QTc only after dialysis (21.7%) we detected rare potentially pathogenic genetic variants. Three out of these five carriers subsequently died suddenly. Conclusions: Genetic background may be determinant in the risk of sudden cardiac death in these patients. We recommend evaluating the QTc interval before and after hemodialysis, and performing a genetic analysis of individuals with long QTc after hemodialysis. [ABSTRACT FROM AUTHOR]

Background: Fetal heart rate variability (fHRV) of normal-to-normal (NN) beat intervals provides high-temporal resolution access to assess the functioning of the autonomic nervous system (ANS). Aim: To determine critical periods of fetal autonomic maturation. The developmental pace is hypothesized to change with gestational age (GA). Study design: Prospective longitudinal observational study. Subjects: 60 healthy singleton fetuses were followed up by fetal magnetocardiographic heart rate monitoring 4–11 times (median 6) during the second half of gestation. Outcome measure: FHRV parameters, accounting for differential aspects of the ANS, were studied applying linear mixed models over four predefined pregnancy segments of interest (SoI: <27; 27+0–31+0; 31+1–35+0; >35+1 weeks GA). Periods of fetal active sleep and quiescence were accounted for separately. Results: Skewness of the NN interval distribution VLF/LF band power ratio and complexity describe a saturation function throughout the period of interest. A decreasing LF/HF ratio and an increase in pNN5 indicate a concurrent shift in sympathovagal balance. Fluctuation amplitude and parameters of short-term variability (RMSSD, HF band) mark a second acceleration towards term. In contrast, fetal quiescence is characterized by sequential, but low-margin transformations; ascending overall variability followed by an increase of complexity and superseded by fluctuation amplitude. Conclusions: An increase in sympathetic activation, connected with by a higher ability of parasympathetic modulation and baseline stabilization, is reached during the transition from the late 2nd into the early 3rd trimester. Pattern characteristics indicating fetal well-being saturate at 35 weeks GA. Pronounced fetal breathing efforts near-term mirror in fHRV as respiratory sinus arrhythmia. [ABSTRACT FROM AUTHOR]

Risk stratification in secondary prevention has emerged as an unmet clinical need in order to mitigate the Number-Needed-to-Treat and make expensive therapies both clinically relevant and cost-effective. P wave indices reflect atrial conduction, which is a sensitive marker for inflammatory, metabolic, and pressure overload myocardial cell remodeling; the three stimuli are traditional mechanisms for adverse clinical evolution. Accordingly, we sought to investigate the predictive role of P-wave indices to estimate residual risk in patients with chronic coronary artery disease (CAD). The cohort included 520 post-Coronary Artery Bypass Grafting patients with a median age of 60 years who were followed for a median period of 1025 days. The primary endpoint was long-term all-cause death. Cubic spline model demonstrated a linear association between P-wave duration and incidence rate of long-term all-cause death (p = 0.023). P-wave >110ms was a marker for an average of 425 days shorter survival as compared with P-wave under 80ms (Logrank p = 0.020). The Cox stepwise regression models retained P-wave duration as independent marker (HR:1.37; 95%CI:1.05–1.79,p = 0.023). In conclusion, the present study suggests that P-wave measurement may constitute a simple, inexpensive and accessible prognostic tool to be added in the bedside risk estimation in CAD patients. [ABSTRACT FROM AUTHOR]

Background: Anticoagulation decreases a patient’s risk of ischemic stroke and increases the risk of hemorrhage. Decision analyses regarding anticoagulation therefore require that different outcomes be weighted in comparison to one another. Most decision analyses to date have weighted intracranial hemorrhage (ICH) as 1.5 times worse than ischemic stroke, but because death and disability have lifelong impact, the expected impact should vary by life expectancy. Therefore, a fixed weighting ratio leads to age-related bias decision analyses of anticoagulation. We aimed to quantify the relative impact of ICH and ischemic stroke and derive a ratio that allows decision analysis without microsimulation. Methods: We created a microsimulation model to predict QALYs lost due to ICH and ischemic stroke. We then applied a meta-model to predict the ratio of QALYs lost from ICH relative to ischemic stroke. Results: Previously-used weighting ratios (1.5) are close to our derived mean weighting ratio (1.60). However, the weighting ratio of QALYs lost from ICH relative to ischemic stroke is sensitive to age and discount rate. Patients at younger ages have higher mean weighting ratios, as do patients with higher discount rates. Conclusions: The ratio of QALYs lost to ICH relative to ischemic stroke varies with age and discount rate. We present a set of such ratios here for use in decision analyses that do not incorporate full microsimulation models. Use of weighting ratios that vary with age, rather than the current fixed ratios, has the potential to reduce age-based bias in decision-making regarding events with lifelong implications. In this case, use of dynamic ratios may change anticoagulation recommendations for patients with nonvalvular atrial fibrillation at relatively low stroke risk. [ABSTRACT FROM AUTHOR]

Acoustocerebrography is a novel, non-invasive, transcranial ultrasonic diagnostic method based on the transmission of multispectral ultrasound signals propagating through the brain tissue. Dedicated signal processing enables the estimation of absorption coefficient, frequency-dependent attenuation, speed of sound and tissue elasticity. Hypertension and atrial fibrillation are well known factors correlated with white matter lesions, intracerebral hemorrhage and cryptogenic stroke numbers. The aim of this study was to compare the acoustocerebrography signal in the brains of asymptomatic atrial fibrillation patients with and without hypertension. The study included 97 asymptomatic patients (40 female and 57 male, age 66.26 ± 6.54 years) who were clinically monitored for atrial fibrillation. The patients were divided into two groups: group I (patients with hypertension) n = 75, and group II (patients without hypertension) n = 22. Phase and amplitude of all spectral components for the received signals from the brain path were extracted and compared to the phase and amplitude of the transmitted pulse. Next, the time of flight and the attenuation of each frequency component were calculated. Additionally, a fast Fourier transformation was performed and its features were extracted. After introducing a machine learning technique, the ROC plot of differentiations between group I and group II with an AUC of 0.958 (sensitivity 0.99 and specificity 0.968) was obtained. It can be assumed that the significant difference in the acoustocerebrography signals in patients with hypertension is due to changes in the brain tissue, and it allows for the differentiating of high-risk patients with asymptomatic atrial fibrillation and hypertension. [ABSTRACT FROM AUTHOR]

Background: T-wave alternans (TWA), a marker of electrical instability, can be modulated by cardiac resynchronization therapy (CRT). The relationship between TWA and heart failure response to CRT has not been clearly defined. Methods and results: In 40-patients (age 65±11 years, left ventricular ejection-fraction [LVEF] 23±7%), TWA was evaluated prospectively at median of 2 months (baseline) and 8 months (follow-up) post-CRT implant. TWA-magnitude (Valt >0μV, k≥3), its duration (d), and burden (Valt ·d) were quantified in moving 128-beat segments during incremental atrial (AAI, native-TWA) and atrio-biventricular (DDD-CRT) pacing. The immediate and long-term effect of CRT on TWA was examined. Clinical response to CRT was defined as an increase in LVEF of ≥5%. Native-TWA was clinically significant (Valt ≥1.9μV, k≥3) in 68% of subjects at baseline. Compared to native-TWA at baseline, DDD-CRT pacing at baseline and follow-up reduced the number of positive TWA segments, peak-magnitude, longest-duration and peak-burden of TWA (44±5 to 33±5 to 28±4%, p = 0.02 and 0.002; 5.9±0.8 to 4.1±0.7 to 3.8±0.7μV, p = 0.01 and 0.01; 97±9 to 76±8 to 67±8sec, p = 0.004 and <0.001; and 334±65 to 178±58 to 146±54μV.sec, p = 0.01 and 0.004). In addition, the number of positive segments and longest-duration of native-TWA diminished during follow-up (44±5 to 35±6%, p = 0.044; and 97±9 to 81±9sec, p = 0.02). Clinical response to CRT was observed in 71% of patients; the reduction in DDD-CRT paced TWA both at baseline and follow-up was present only in responders (interaction p-values <0.1). Conclusion: Long-term CRT reduces the prevalence and magnitude of TWA. This CRT induced beneficial electrical remodeling is a marker of clinical response after CRT. [ABSTRACT FROM AUTHOR]

A recent analysis showed an association with new onset atrial fibrillation (NOAF) and incident cancer among women. We aimed to examine the risk of cancer among patients with NOAF in general population. A retrospective cohort of 5130 patients with NOAF was identified from a random sample of one million subjects between 2005 and 2010 from Taiwan National Health Insurance Research Database. The standard incidence ratio of incident cancer and hazard ratios were calculated by modeling cumulative incidence with competing risk of death. During a mean follow-up duration of 3.4 years, 330 patients developed cancer. The standard incidence ratio of all malignancies was 1.41 (95% confidence interval 1.26–1.57), suggesting a 41% increase in cancer risk compared with the general population. The risk of cancer was higher among men or the elderly with NOAF after adjusting for confounding factors and after considering the competing risk of death. The risk of cancer was not associated with CHA2DS2–VASc score (p = 0.32) among patients with NOAF. In conclusion, patients with NOAF were associated with a higher risk of cancer. Within this group, the risk of ischemic stroke (in terms of CHADS2-VASc score) did not reflect the risk of incident cancer. [ABSTRACT FROM AUTHOR]

Background: The optimal antithrombotic therapy for atrial fibrillation (AF) patients undergoing coronary stenting is unknown. The present meta-analysis sought to investigate the efficacy and safety of triple therapy (TT; warfarin, clopidogrel and aspirin) vs dual antiplatelet therapy (DAPT; clopidogrel plus aspirin) in those patients. Methods: PubMed and Cochrane Library were searched for studies enrolling AF patients undergoing coronary stenting on TT and DAPT up to September 2016, and fourteen studies were included. Efficacy outcomes included ischemic stroke, stent thrombosis, major adverse cardiovascular event (MACE), all-cause mortality and myocardial infarction (MI); safety outcome was major bleeding. We conducted meta-analysis and used odds ratio (OR) with 95% confidence intervals (CI) to compare TT and DAPT. Meta-regression, sensitivity and subgroup analysis were taken to investigate the source of heterogeneity in the outcome of major bleeding. Results: 14 eligible observational studies with 11,697 subjects were identified. Compared with DAPT, TT had decreased the risk of ischemic stroke [OR = 0.74, 95% CI (0.59, 0.93), P = 0.009] and stent thrombosis [OR = 0.40, 95% CI (0.18, 0.93), P = 0.033]. While, there was an increased risk of major bleeding [OR = 1.55, 95% CI (1.16, 2.09), P = 0.004] associated with TT. The risk of MACE, all-cause mortality and MI had no significant statistical difference between TT and DAPT. Furthermore, the results of univariate and multivariate meta-regression analysis implicated that there were no obvious correlations between certain baseline characteristics (age, gender, race, hypertension, study design) and risk of major bleeding. Also of major bleeding, the findings of sensitivity analysis were generally robust, and a prespecified subgroup analysis of race demonstrated that the source of heterogeneity might attribute to Asian studies mostly. Conclusions: TT reduced the risk of ischemic stroke and stent thrombosis with an acceptable major bleeding risk compared with DAPT, and TT was considered as a valid alternative in AF patients undergoing coronary stenting. Further prospective randomized trials are needed to ensure the reliability of these data and find the optimal therapeutic strategy in this setting of patients. [ABSTRACT FROM AUTHOR]

Dispersion of ventricular repolarization due to abnormal activation contributes to the susceptibility to cardiac arrhythmias. However, the global pattern of repolarization is difficult to assess clinically. Activation recovery interval (ARI) has been used to understand the properties of ventricular repolarization. In this study, we developed an ARI imaging technique to noninvasively reconstruct three-dimensional (3D) ARI maps in 10 premature ventricular contraction (PVC) patients and evaluated the results with the endocardial ARI maps recorded by a clinical navigation system (CARTO). From the analysis results of a total of 100 PVC beats in 10 patients, the average correlation coefficient is 0.86±0.05 and the average relative error is 0.06±0.03. The average localization error is 4.5±2.3 mm between the longest ARI sites in 3D ARI maps and those in CARTO endocardial ARI maps. The present results suggest that ARI imaging could serve as an alternative of evaluating global pattern of ventricular repolarization noninvasively and could assist in the future investigation of the relationship between global repolarization dispersion and the susceptibility to cardiac arrhythmias. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common arrhythmia. The most common diagnostic method, 12-lead electrocardiogram (ECG), can record episodes of arrhythmia from which the type and severity can be determined. The Heart Spectrum Blood Pressure Monitor (P2; OSTAR Meditech Corp., New Taipei City, Taiwan) is used to measure cardiovascular pressure change with fast Fourier transform (FFT) analysis to obtain heart rate frequency variability and accurate blood pressure data. We compared the diagnostic efficacy of the Heart Spectrum Blood Pressure Monitor to a 12-lead ECG (gold standard) for patients with AF. Three measurement methods were used in this study to analyze the heart index and compare the results with simultaneous 12-lead ECG: blood pressure; mean arterial pressure, which was calculated from individual blood pressure as a constant pressure; and a constant pressure of 60 mmHg. The physician used a 12-lead ECG and the Heart Spectrum Blood Pressure Monitor simultaneously. The Heart Spectrum Blood Pressure Monitor used FFT analysis to diagnose AF, and the findings were compared to the 12-lead ECG readings. This unblinded clinical trial was conducted in the emergency department of Taipei Medical University Hospital. Twenty-nine subjects with AF and 33 without AF aged 25 to 97 y (mean, 63.5 y) were included. Subjects who were exposed to high-frequency surgical equipment during testing, those with cardiac pacemakers or implantable defibrillators, and pregnant women were excluded. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 97%, 97%, 97%, and 97%, respectively, for method 1; 90%, 100%, 100%, and 91%, respectively, for method 2; and 100%, 94%, 94%, and 100%, respectively, for method 3. The sensitivity, specificity, PPV, and NPV for both methods ranged between 90% and 100%, indicating that the Heart Spectrum Blood Pressure Monitor can be effectively applied for AF detection. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the prevalence and risk factors of acquired long QT syndrome (LQTS) on admission to a general Intensive Care Unit (ICU), and to assess the risk of LQTS associated with prescribed medications. Methods: Prospective observational, cross-sectional study approved by the Institutional Review Board. Between May 2014 and July 2016, 412 patients >18 years-old consecutively admitted to the ICU of a university hospital were included. LQTS was defined as a QT interval on the admission electrocardiogram corrected using Bazett’s formula (QTc) >460 ms for men and >470 ms for women. All medications administered within 24 hours before admission were recorded. Logistic regression was used. Results: LQTS prevalence was 27.9%. In LQTS patients, 70.4% had ≥ 1 LQTS-inducing drug prescribed in the 24 hours prior to ICU admission versus 70.4% in non-LQTS patients (p = 0.99). Bradycardia and Charlson morbidity index score are independent risk factors for LQTS. Haloperidol (OR 4.416), amiodarone (OR 2.509) and furosemide (OR 1.895) were associated with LQTS, as well as another drug not yet described, namely clopidogrel (OR 2.241). Conclusions: The LQTS is highly prevalent in critically ill patients, ICU patients are often admitted with LQTS-inducing medications, and patients with slow heart rate or with high Charlson comorbidity index should be evaluated for LQTS. [ABSTRACT FROM AUTHOR]

Introduction: Postoperative atrial fibrillation (POAF) is a common complication following cardiac surgery associated with increased morbidity and mortality. Although sustained hyperglycemia is a known risk factor of AF and poor ICU outcomes, emerging in-vitro studies reveal acute glycemic fluctuations to be an additional independent predictor of AF. The effect of acute glycemic fluctuations on the incidence of POAF in the clinical setting remains unclear. We aim to investigate the effect of the magnitude of acute perioperative glycemic fluctuations on the incidence of POAF in a multi-ethnic Southeast-Asian population. Methods: We obtained data from1743 patients who underwent elective CABG in a tertiary heart centre from 2009–2011. Patients were kept to a tight baseline glycemic control in accordance with hospital protocol. The magnitude of the difference between the highest and lowest perioperative glucose levels up till the first 48 postoperative hours was employed as a measure of glycemic fluctuation. Patients were divided into 4 groups for analysis based on the magnitude of glycemic fluctuation:A)0-2mmol/L(N = 147); B)>2-4mmol/L(N = 426); C)>4-6mmol/L(N = 513); D)>6mmol/L(N = 657).Our primary outcome was the incidence of POAF. Secondary outcomes included ICU and 30-day mortality and length of stay. Results: The overall incidence of POAF was 14.7%. This increased as the magnitude of glycemic fluctuation increased, and was statistically highest in Group D(16.4%) as compared with the other 3 sub-groups. Multivariate logistic regression revealed the magnitude of perioperative glycemic fluctuation to be an independent risk factor of POAF(O.R.1.06, 95% C.I.1.01–1.11, p = 0.014).ICU length of stay was statistically highest in Group D(63.1 hours, p = < .001). However, ICU and 30 day mortality rates were similar among the 4 groups. Conclusion: Increased magnitudes of acute perioperative glycemic fluctuations are associated with a significantly increased risk of POAF and length of ICU stay; and should therefore be minimised but balanced against the risks of hypoglycemia so as to avoid POAF and optimise patient outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Direct oral anticoagulants (DOAC) have gained an increased share over warfarin for prevention and treatment of thromboembolic disease. We studied DOAC adoption across providers and medical specialties. Methods: Retrospective, cross-sectional analysis of Medicare Part D public use files (PUF), 2013 to 2015. We summarized prescription data for claims and drug payment, stratified by drug class, specialty and calendar year. We treated DOAC claims as a count outcome and explored patterns of expansion across prescribers via a truncated negative binomial regression. We described dispersion and spread in DOAC prescribing, across hospital referral regions (HRRs), including the p90/p10 ratios, and the median absolute deviation from the median. Results: In 2015 part D PUF, oral anticoagulant claims have climbed to approximately 24.4 million with a payment cost of approximately $3.3 billion. DOAC claims comprised 31.0% of oral anticoagulant claims, showing a relative increase of approximately 127% compared to 2013. The upper decile of prescribers accounted for half of the oral anticoagulant prescriptions and the resulting cost. The median cost per DOAC claim in 2015 was $367.4 (interquartile range 323.9 to 445.9), as opposed to $12.3 (interquartile range 9.2 to 16.5) for warfarin. The median cost per standardized (30-day supply) prescription was $317.0 (interquartile range 303.8 to 324.3) and $8.0 (6.7 to 9.8) for DOACs and warfarin, respectively. DOAC adoption differs by specialty. Cardiologists, cardiac electrophysiologists and orthopedics had the highest predicted DOAC share per 100 claims (53.8, 72.9 and 71.5, respectively in 2015); nephrologists, family practitioners and geriatricians the lowest (22.3, 21.5 and 20.7, respectively in 2015). The p90/p10 ratio and the median absolute deviation from the median varied across HRRs and correlated positively with the prevalence of stroke and atrial fibrillation in the Medicare population. Conclusions: DOACs have been increasing their share year-over-year, but adoption varies across specialties. In prevalent areas for stroke and atrial fibrillation, prescription dispersion magnifies, and this may signify a rapid adoption by top providers. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) is a major risk factor for ischemic stroke unless treated with an anticoagulant. Detecting AF can be difficult because AF is often paroxysmal and asymptomatic. The aims of this study were to develop a screening model to detect AF in a primary healthcare setting and to initiate oral anticoagulant therapy in high-risk patients to prevent stroke. Methods: This was a cross-sectional study. All 70- to 74-year-old individuals registered at a single primary healthcare center in Stockholm were invited to participate in AF screening upon visiting the center during a ten-month period. Those who did not have contact with the center during this period were invited to participate by letter. Thirty-second intermittent ECG recordings were made twice a day using a handheld Zenicor device over a 2-week period in participants without AF. Oral anticoagulant therapy was offered to patients with newly detected AF. Findings: Of the 415 eligible individuals, a total of 324 (78.1%) patients participated in the study. The mean age of the participants was 72 years, 52.2% were female, and the median CHA2DS2-VASc score of the participants was 3. In the target population, 34 (8.2%) individuals had previously diagnosed AF. Among participants without previously known AF, 16 (5.5%) cases of AF were detected. The final AF prevalence in the target population was 12%. Oral anticoagulant therapy was successfully initiated in 88% of these patients with newly detected AF. Conclusions: The AF screening project exhibited a high participation rate and resulted in a high rate of newly discovered AF; of these newly diagnosed patients, 88% could be treated with an oral anticoagulant. [ABSTRACT FROM AUTHOR]

The relative efficacy of antiarrhythmic drugs (AADs) after electrical cardioversion are not well established. This study aimed to investigate the efficacies of different AADs for maintaining sinus rhythm (SR) after electrical cardioversion for atrial fibrillation (AF). We selected patients from a retrospective registry including patients admitted for cardioversion between January 2012 and June 2016. The primary outcome was time to AF recurrence during the first year after cardioversion. The secondary outcomes included AF recurrence within 1 month, and first readmission due to heart failure, stroke, or additional non-pharmacological rhythm control. A total of 265 patients were divided into the 4 groups according to AAD type: flecainide (n = 33), propafenone (n = 64), amiodarone (n = 128), and dronedarone (n = 40). During the first year after cardioversion, the AF recurrence-free survival was similar between all AAD groups (69.7% vs. 67.2% vs. 71.9% vs. 80.0%, p = 0.439). About half of all recurrences occurred during the first month. There was no difference in any of the secondary outcomes, although the amiodarone group showed a trend toward more non-pharmacological rhythm control. AAD type was not associated with recurrence in multivariate analysis. In this study, half of all patients received amiodarone after electrical cardioversion. Flecainide, propafenone, amiodarone, and dronedarone showed similar efficacies for maintaining SR after electrical cardioversion. Thus, it might be reasonable to reconsider amiodarone use after cardioversion, since it did not show superior efficacy to the other drugs considered and is associated with potential side effects. [ABSTRACT FROM AUTHOR]

Ventricular arrhythmias in Brugada syndrome (BS) typically occur at rest and especially during sleep, suggesting that changes in the autonomic modulation may play an important role in arrhythmogenesis. The autonomic response to exercise and subsequent recovery was evaluated on 105 patients diagnosed with BS (twenty-four were symptomatic), by means of a time-frequency heart rate variability (HRV) analysis, so as to propose a novel predictive model capable of distinguishing symptomatic and asymptomatic BS populations. During incremental exercise, symptomatic patients showed higher HFnu values, probably related to an increased parasympathetic modulation, with respect to asymptomatic subjects. In addition, those extracted HRV features best distinguishing between populations were selected using a two-step feature selection approach, so as to build a linear discriminant analysis (LDA) classifier. The final features subset included one third of the total amount of extracted autonomic markers, mostly acquired during incremental exercise and active recovery, thus evidencing the relevance of these test segments in BS patients classification. The derived predictive model showed an improved performance with respect to previous works in the field (AUC = 0.92 ± 0.01; Se = 0.91 ± 0.06; Sp = 0.90 ± 0.05). Therefore, based on these findings, some of the analyzed HRV markers and the proposed model could be useful for risk stratification in Brugada syndrome. [ABSTRACT FROM AUTHOR]

Admissions of Standardbred racehorses (Std) to the Ontario Veterinary College Teaching Hospital (OVCTH) for treatment of atrial fibrillation (AF) began to increase in the early 1990s. The arrhythmia has been shown to have a modest heritability (h2 ≃ 0.15), with some stallions appearing as sires or sires of mares used in breeding (broodmares) of affected horses more frequently than others. The objective of this study was to determine the marginal genetic contributions of ancestors to cohorts of Std affected with AF and their contemporary control groups, and whether these ancestors contribute significantly more to the affected cohorts than to controls. All Std admitted to OVCTH for treatment of AF that were born between 1993 and 2007 comprised the affected case group (n = 168). Five randomly selected racing contemporaries for each Std admitted, assumed to not suffer from the arrhythmia, comprised the control group (n = 840). Three-year overlapping cohorts were created for case and control horses, determined according to year of birth, for a total of 26 cohorts. Marginal genetic contributions of ancestors to each cohort were determined and differences analyzed for statistical significance using a two-tailed paired t-test, with P ≤ 0.05 considered significant. The marginal contributions of 26 ancestors were significant, with 11 contributing significantly more to affected cohorts than the corresponding controls, and 15 contributing significantly more to controls than the corresponding affected cohorts. One stallion and one broodmare were very highly significant to affected cohorts at P ≤ 0.001, and nine stallions and three broodmares were very highly significant to control cohorts at P ≤ 0.001. Therefore, a number of stallions have statistically significant contributions to the genetics of Std affected with AF, while many others have statistically significant contributions to healthy Std. The arrhythmia appears to be particularly prevalent in the descendants of one sire family. [ABSTRACT FROM AUTHOR]

Background: There was a paucity of data on the magnitude of potentially inappropriate prescriptions (PIPs) among Ethiopian elderly cardiovascular patients. Objective: The aim of this study was to assess PIPs and associated factors in the elderly population with cardiovascular disorders using the START/STOPP screening criteria. Methods: A hospital-based cross-sectional study was conducted at medical wards of a teaching hospital in Ethiopia from 1 December 2016–30 May 2017. Included patients were hospitalized elderly patients aged 65 years or older with cardiovascular disorders; their medications were evaluated using the START/STOPP screening criteria from admission to discharge. Multivariable logistic regression was applied to identify factors associated with inappropriate medications. One Way Analysis Of Variance (ANOVA) was carried out to test significant differences on the number of PIPs per individual diagnosis. Results: Two hundred thirty-nine patients were included in the analysis. More-than a third of the patients were diagnosed with heart failure, 88 (36.82%). A total of 221 PIPs were identified in 147 patients, resulting in PIP prevalence of 61.5% in the elderly population. Of the total number of PIPs, occurrence of one, two and three PIPs accounted for 83 (56.4%), 52(35.4%), and 12(8.2%) respectively. One way ANOVA test showed significant differences on the mean number of PIPs per individual diagnosis (f = 5.718, p<0.001). Angiotensin Converting Enzyme Inhibitors (ACEIs) were the most common inappropriately prescribed medications, 32(14.5%). Hospital stay, AOR: 1.086 (1.016–1.160), number of medications at discharge, AOR: 1.924 (1.217–3.041) and the presence of co-morbidities, AOR: 3.127 (1.706–5.733) increased the likelihood of PIP. Conclusion: Approximately, two-thirds of elderly cardiovascular patients encountered potentially inappropriate prescriptions. ACEIs were the most commonly mis-prescribed medications. Longer hospital stay, presence of comorbidities and prescription of large number of medications at discharge have been correlated with the occurrence of inappropriate medication. It is essential to evaluate patients’ medications during hospital stay using the STOPP and START tool to reduce PIPs. [ABSTRACT FROM AUTHOR]

Background: Among the potential factors which may contribute to the development and perpetuation of atrial fibrillation, dysregulation of miRNAs has been suggested. Thus in this study, we have quantified the basal expressions of 662 mature human miRNAs in left atrium (LA) from patients undergoing cardiac surgery for valve repair, suffering or not from atrial fibrillation (AF) by using TaqMan® Low Density arrays (v2.0). Results: Among the 299 miRNAs expressed in all patients, 42 miRNAs had altered basal expressions in patients with AF. Binding-site predictions with Targetscan (conserved sites among species) indicated that the up- and down-regulated miRNAs controlled respectively 3,310 and 5,868 genes. To identify the most relevant cellular functions under the control of the altered miRNAs, we focused on the 100 most targeted genes of each list and identified 5 functional protein-protein networks among these genes. Up-regulated networks were involved in synchronisation of circadian rythmicity and in the control of the AKT/PKC signaling pathway (i.e., proliferation/adhesion). Down-regulated networks were the IGF-1 pathway and TGF-beta signaling pathway and a network involved in RNA-mediated gene silencing, suggesting for the first time that alteration of miRNAs in AF would also perturbate the whole miRNA machinery. Then we crossed the list of miRNA predicted genes, and the list of mRNAs altered in similar patients suffering from AF and we found that respectively 44.5% and 55% of the up- and down-regulated mRNA are predicted to be conserved targets of the altered miRNAs (at least one binding site in 3’-UTR). As they were involved in the same biological processes mentioned above, these data demonstrated that a great part of the transcriptional defects previously published in LA from AF patients are likely due to defects at the post-transcriptional level and involved the miRNAs. Conclusions: Our stringent analysis permitted us to identify highly targeted protein-protein networks under the control of miRNAs in LA and, among them, to highlight those specifically affected in AF patients with altered miRNA signature. Further studies are now required to determine whether alterations of miRNA levels in AF pathology are causal or represent an adaptation to prevent cardiac electrical and structural remodeling. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and its incidence is increasing worldwide. One method used to restore sinus rhythm is direct current cardioversion (DCCV). Despite the high success rate of DCCV, AF typically recurs within the first 2 weeks. However, our understanding of the pathophysiology of AF recurrence, incidence, and progression are highly limited. Lipidomic profiling was applied to identify altered lipids in plasma from patients with AF using ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry coupled with multivariate statistical analysis. Partial least-squares discriminant analysis revealed a clear separation between AF patients and healthy controls. The levels of several lipid species, including fatty acids and phospholipids, were different between AF patients and healthy controls, indicating that oxidative stress and inflammation are associated with the pathogenesis of AF. Similar patterns were also detected between recurrent and non-recurrent AF patients. These results suggest that the elevated saturated fatty acid and reduced polyunsaturated fatty acid levels in AF patients may be associated with enhanced inflammation and that free fatty acid levels may play a crucial role in the development and progression of AF. [ABSTRACT FROM AUTHOR]

Introduction: Warfarin and new oral anticoagulants are effective in reducing stroke in atrial fibrillation; however, the benefits and risks rates in clinical trials show heterogeneity for each anticoagulant, and is unknown the cost influence on a model considering most of the treatment consequences. We designed a benefit-risk and cost assessment of oral anticoagulants. Design: We followed the roadmap proposed by IMI-PROTECT and the considerations of emerged good practice to perform Multi-Criteria Decision Analysis (MCDA). The roadmap defines the following steps: (1) planning, (2) evidence gathering and data preparation, (3) analyses, (4) explorations, and (5) conclusions. We defined two reference points (0–100) to allocate numerical values for scores and weights, and used an analogue numeric scale to assess physicians’ preferences. As benefits of the anticoagulant therapy, we included reductions in stroke and all-cause mortality; intracranial haemorrhage, gastrointestinal haemorrhage, minor bleeding and myocardial infarction were considered risks. We also made an estimation of the annual drug cost per person. Main results: The scores were: Apixaban 33, Dabigatrán 25, warfarin 18 and Rivaroxaban 14 this score reveals the most preferred up to the less preferred option, considering the benefit-risk ratio and drug costs altogether. The relative model weights were: 51.1% for risks, 40.4% for benefits and 8.5% for cost. The sensitivity analysis confirms the model robustness. Conclusions: From this analysis, apixaban should be considered as the preferred anticoagulant option -due to a better benefit-risk balance and a minor cost influence- followed by dabigatran, warfarin and rivaroxaban. [ABSTRACT FROM AUTHOR]

Aim: Acute and subacute cardiotoxicity are characterized by prolongation of the corrected QT interval (QTc) and other measures derived from the QTc interval, such as QTc dispersion (QTdc) and transmural dispersion of repolarization (DTpTe). Although anthracyclines prolong the QTc interval, it is unclear whether breast cancer patients who undergo the ACT chemotherapy regimen of anthracycline (doxorubicin: A), cyclophosphamide (C) and taxane (T) may present with QTc, QTdc and DTpTe prolongation. Methods: Twenty-three consecutive patients with breast cancer were followed prospectively during ACT chemotherapy and were analyzed according to their QT measurements. QTc, QTdc and DTpTe measurements were determined by a 12-lead electrocardiogram (EKG) prior to chemotherapy (baseline), immediately after the first phase of anthracycline and cyclophosphamide (AC) treatment, and immediately after T treatment. Serum troponin and B-type natriuretic peptide (BNP) levels were also measured. Results: Compared to baseline values, the QTc interval was significantly prolonged after the AC phase (439.7 ± 33.2 ms vs. 472.5 ± 36.3 ms, p = 0.001) and after T treatment (439.7 ± 33.2 ms vs. 467.9 ± 42.6 ms, p < 0.001). Troponin levels were elevated after the AC phase (23.0 pg/mL [min-max: 6.0–85.0] vs. 6.0 pg/mL [min-max: 6.0–22.0], p < 0.001) and after T treatment (25.0 pg/mL [min-max: 6.0–80.0] vs. 6.0 pg/mL [min-max: 6.0–22.0], p < 0.001) compared to baseline values. Conclusion: In this prospective study of patients with non-metastatic breast cancer who underwent ACT chemotherapy, significant QTc prolongation and an elevation in serum troponin levels were observed. [ABSTRACT FROM AUTHOR]

Introduction: The role of implantable cardioverter-defibrillator (ICD) placement in the primary prevention of sudden cardiac death (SCD) in all consecutive patients with left ventricular ejection fraction (LVEF) ≤ 35% is still a matter of hot debate due to the fact that the population of these patients is highly heterogeneous in terms of the SCD risk. Nevertheless, reduced LVEF is still the only established criterion during qualification of patients for ICD implantation in the primary prevention of SCD, therefore identification of persons with particularly high risk among patients with LVEF ≤35% is currently of lesser importance. More important seems to be the selection of individuals with relatively low risk of SCD in whom ICD implantation can be safely postponed. The aim of the study was to determine whether well-known, non-invasive parameters, such as microvolt T-wave alternans (MTWA), baroreflex sensitivity (BRS) and short-term heart rate variability (HRV), can be helpful in the identification of low-arrhythmic risk patients with left ventricular systolic dysfunction. Methods: In 141 patients with coronary artery disease and LVEF ≤ 35%, MTWA testing, as well as BRS and short-term HRV parameters, were analysed. During 34 ± 13 months of follow-up 37 patients had arrhythmic episode (EVENT): SCD, non-fatal sustained ventricular arrhythmia (ventricular tachycardia [VT] or ventricular fibrillation [VF]), or adequate high-voltage ICD intervention (shock) due to a rapid ventricular arrhythmia ≥200/min. LVEF, non-negative MTWA (MTWA_non-neg), BRS and low frequency power in normalized units (LFnu) turned out to be associated with the incidence of EVENT in univariate Cox analysis. The cut-off values for BRS and LFnu that most accurately distinguished between patients with and without EVENT were 3 ms/mmHg and 23, respectively. The only variable that provided 100% negative predictive value (NPV) for EVENT was negative MTWA result (MTWA_neg), but solely for initial 12 months of the follow-up; the NPVs for other potential predictors of the EVENT were lower. The cut-off values for BRS and LFnu that provide 100% NPV for EVENT during 12 and 24 months were higher: 6.0 ms/mmHg and 73 respectively, but the gain in the NPV occurred at an expense of the number of identified patients. However, the number of identified non-risk patients turned out to be higher when the predictive model included MTWA_neg and the lower cut-off values for ANS parameters: 100% NPV for 12 and 24 months of follow-up was obtained for combination MTWA_neg and BRS ≥ 3 ms/mmHg, for combination MTWA_neg and LFnu ≥ 23 100% NPV was obtained for 12 months. Conclusion: Well-known, non-invasive parameters, such as MTWA, BRS and short-term HRV indices may be helpful in the identification of individuals with a relatively low risk of malignant ventricular arrhythmias among patients with ischemic left ventricular systolic dysfunction; in such persons, implantation of ICD could be safely postponed. [ABSTRACT FROM AUTHOR]

In year 2016, the American Society of Echocardiography (ASE) and the European Association of Cardiovascular Imaging (EACVI) updated Recommendations for the assessment and grading of diastolic dysfunction (DD). We aimed to assess the applicability of this DD grading method and its association with prognosis in patients with severe aortic stenosis (AS) who underwent transcatheter aortic valve implantation (TAVI). We retrospectively identified 237 consecutive patients with severe AS who underwent trans-femoral TAVI. Baseline transthoracic echocardiography was evaluated to assess pre- and post-TAVI diastolic function according to the current ASE/EACVI Recommendations. Prior to TAVI, 41 (17%) patients were diagnosed as having grade I DD, 111 (47%) patients had grade II DD, 80 (34%) had grade III DD. DD grade after TAVI decreased (p < 0.001) with 75 patients (32%) reclassified to a lower DD grade. During the median follow-up of 1,320 days, 136 (57%) patients died. In univariable Cox proportional hazards model analysis, neither pre- nor post-TAVI DD grade were associated with prognosis. However, patients with grade III DD detected before TAVI and AR≥ 2 after TAVI had poorer survival (p<0.008). Patients with grade III DD detected after TAVI and AR≥ 2 after TAVI had poorer prognosis (p = 0.002). TAVI improves DD grade. While poor DD grade was not associated with mortality after treatment of AS by TAVI, concomitant presence of DD and post-procedural AR carried a poor prognosis. [ABSTRACT FROM AUTHOR]

Discontinuation of oral anticoagulants may expose non-valvular atrial fibrillation (NVAF) patients to an increased risk of stroke. This study describes the real-world discontinuation rates and compared the risk of drug discontinuation among NVAF patients initiating apixaban, warfarin, dabigatran, or rivaroxaban. This retrospective cohort study evaluated newly-anticoagulated NVAF patients in the MarketScan® data population from 01/01/2012 through 12/31/2014. Discontinuation was defined as a lack of subsequent prescription of the index drug within 30 days after the last supply day of the last prescription. A Cox model was used to estimate the hazard ratio (HR) of discontinuation, adjusted for age, sex, and comorbidities. Among 45,361 eligible NVAF patients, 15,461 (34.1%) initiated warfarin; 7,438 (16.4%) apixaban; 4,661 (10.3%) dabigatran; and 17,801 (39.2%) initiated rivaroxaban treatment. Compared to warfarin, patients who initiated dabigatran (adjusted HR [aHR]: 0.84, 95% confidence interval [CI]: 0.80–0.87, P<0.001), rivaroxaban (aHR: 0.70, 95% CI: 0.68–0.73, P<0.001), or apixaban (aHR: 0.57, 95% CI: 0.55–0.60, P<0.001) were 16%, 30%, and 43% less likely to discontinue treatment, respectively. When compared to apixaban, patients who initiated dabigatran (aHR: 1.46, 95% CI: 1.38–1.54, P<0.001) or rivaroxaban (aHR: 1.23, 95% CI: 1.17–1.28, P<0.001) were more likely to discontinue treatment. Among newly-anticoagulated NVAF patients in the real-world setting, initiation on rivaroxaban, dabigatran, or apixaban was associated with a significantly lower risk of discontinuation compared to warfarin. When compared to apixaban, patients who initiated treatment with warfarin, dabigatran, or rivaroxaban were more likely to discontinue treatment. [ABSTRACT FROM AUTHOR]

Background: Many studies have investigated the use of clinical decision support systems as a means to improve care, but have thus far failed to show significant effects on patient-related outcomes. We developed a clinical decision support system that attempted to address issues that were identified in these studies. The system was implemented in Dutch general practice and was designed to be both unobtrusive and to respond in real time. Despite our efforts, usage of the system was low. In the current study we perform a mixed methods evaluation to identify remediable barriers which led to disappointing usage rates for our system. Methods: A mixed methods evaluation employing an online questionnaire and focus group. The focus group was organized to clarify free text comments and receive more detailed feedback from general practitioners. Topics consisted of items based on results from the survey and additional open questions. Results: The response rate for the questionnaire was 94%. Results from the questionnaire and focus group can be summarized as follows: The system was perceived as interruptive, despite its design. Participants felt that there were too many recommendations and that the relevance of the recommendations varied. Demographic based recommendations (e.g. age) were often irrelevant, while specific risk-based recommendations (e.g. diagnosis) were more relevant. The other main barrier to use was lack of time during the patient visit. Conclusion: These results are likely to be useful to other researchers who are attempting to address the problems of interruption and alert fatigue in decision support. [ABSTRACT FROM AUTHOR]

Introduction: As atrial fibrillation (AF) is often asymptomatic, it may remain undiagnosed until or even after development of complications, such as stroke. Consequently the observed prevalence of AF may underestimate total disease burden. Methods: To estimate the prevalence of undiagnosed AF in the United States, we performed a retrospective cohort modeling study in working age (18–64) and elderly (≥65) people using commercial and Medicare administrative claims databases. We identified patients in years 2004–2010 with incident AF following an ischemic stroke. Using a back-calculation methodology, we estimated the prevalence of undiagnosed AF as the ratio of the number of post-stroke AF patients and the CHADS2-specific stroke probability for each patient, adjusting for age and gender composition based on United States census data. Results: The estimated prevalence of AF (diagnosed and undiagnosed) was 3,873,900 (95%CI: 3,675,200–4,702,600) elderly and 1,457,100 (95%CI: 1,218,500–1,695,800) working age adults, representing 10.0% and 0.92% of the respective populations. Of these, 698,900 were undiagnosed: 535,400 (95%CI: 331,900–804,400) elderly and 163,500 (95%CI: 17,700–400,000) working age adults, representing 1.3% and 0.09% of the respective populations. Among all undiagnosed cases, 77% had a CHADS2 score ≥1, and 56% had CHADS2 score ≥2. Conclusions: Using a back-calculation approach, we estimate that the total AF prevalence in 2009 was 5.3 million of which 0.7 million (13.1% of AF cases) were undiagnosed. Over half of the modeled population with undiagnosed AF was at moderate to high risk of stroke. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the most prevalent cardiac rhythm disorder worldwide but the underlying genetic and molecular mechanisms and the response to therapies is not fully understood. Despite a greater burden of AF risk factors in Hispanics/Latinos the prevalence of AF remains low. Over the last decade, genome-wide association studies have identified numerous AF susceptibility loci in mostly whites of European descent. The goal of this study was to determine if the top 9 single nucleotide polymorphisms (SNPs) associated with AF in patients of European descent also increase susceptibility to AF in Hispanics/Latinos. AF cases were prospectively enrolled in the University of Illinois at Chicago (UIC) AF Registry and control subjects were identified from the UIC Cohort of Patients, Family and Friends. AF cases and controls were genotyped for 9 AF risk SNPs at chromosome 1q21: rs13376333, rs6666258; chr1q24: rs3903239; chr4q25: rs2200733; rs10033464; chr10q22: rs10824026; chr14q23: rs1152591; chr16q22: rs2106261 and rs7193343. The study sample consisted of 713 Hispanic/Latino subjects including 103 AF cases and 610 controls. Among the 8 AF risk SNPs genotyped, only rs10033464 SNP at chromosome (chr) 4q25 (near PITX2) was significantly associated with development of AF after multiple risk factor adjustment and multiple testing (adj. odds ratio [OR] 2.27, 95% confidence interval [CI] 1.31–3.94; P = 3.3 x 10−3). Furthermore, the association remained significant when the analysis was restricted to Hispanics of Mexican descent (adj. OR 2.32, 95% CI 1.35–3.99; P = 0.002. We confirm for the first time the association between a chromosome 4q25 SNP and increased susceptibility to AF in Hispanics/Latinos. While the underlying molecular mechanisms by which the chr4q25 SNP modulates AF risk remains unclear, this study supports a genetic basis for non-familial AF in patients of Hispanic descent. [ABSTRACT FROM AUTHOR]

Background: Medication non-adherence can result in poor health outcomes. Understanding differences in adherence rates to non-vitamin K oral anticoagulants (NOACs) could guide treatment decisions and improve clinical outcomes among patients with non-valvular atrial fibrillation (NVAF). Objective: To compare adherence to rivaroxaban and apixaban among the overall NVAF population and subgroups of prior oral anticoagulant (OAC) users (e.g., multiple comorbidities, non-adherence risk factors). Methods: Using healthcare claims from the Truven Health Analytics MarketScan (7/2012-7/2015), adult patients with ≥2 dispensings of rivaroxaban or apixaban ≥ 180 days apart with > 60 days of supply, ≥ 6 months of pre- and post-index eligibility, ≥ 1 atrial fibrillation diagnosis pre- or on the index date, and without valvular involvement were identified. Propensity-score methods adjusting for potential baseline confounders were used to create matched cohorts of rivaroxaban and apixaban patients. Adherence was assessed during the implementation phase using the percentage of patients with proportion of days covered (PDC) ≥0.8 at 6 months. Subgroups of patients with prior OAC use were evaluated; additional subgroups were identified and evaluated by Quan-Charlson Comorbidity index ≥2 and presence of non-adherence risk factors (i.e., mental disorders, stress, isolation, and rheumatoid arthritis). Results: A total of 13,890 NVAF subjects were included in each of the 2 matched cohorts. All baseline characteristics were balanced between cohorts. At 6 months, significantly more rivaroxaban users were adherent to treatment compared to apixaban users (81.8% vs. 78.0%; absolute difference of 3.8%; p<.001). Rivaroxaban users had significantly higher adherence rates in all subgroups examined. Conclusion: Rivaroxaban users had consistently higher adherence rates than apixaban users overall and among all NVAF subgroups examined. [ABSTRACT FROM AUTHOR]

Background: Different outcomes among patients hospitalized for bleeding after starting anticoagulation could influence choice of anticoagulant. We compared length of hospitalization, proportion of Intensive Care Unit (ICU) admissions, ICU length of stay, and 30- and 90-day mortality for adults with atrial fibrillation hospitalized for bleeding after starting warfarin, dabigatran, or rivaroxaban. Methods: An US commercial database of 38 million members from 1 November 2010 to 31 March 2014 was used to examine adults with atrial fibrillation hospitalized for bleeding after starting warfarin (2,446), dabigatran (442), or rivaroxaban (256). Outcomes included difference in mean total length of hospitalization, proportion of ICU admissions, mean length of ICU stay, and all-cause 30- and 90-day mortality. Results: Warfarin users were older and had more comorbidities. Multivariable regression modeling with propensity score weighting showed warfarin users were hospitalized 2.0 days longer (95% CI 1.8–2.3; p < 0.001) than dabigatran users and 2.6 days longer (95% CI 2.4–2.9; p < 0.001) than rivaroxaban users. Dabigatran users were hospitalized 0.6 days longer (95% CI 0.2–1.0; p = 0.001) than rivaroxaban users. There were no differences in the proportion of ICU admissions. Among ICU admissions, warfarin users stayed 3.0 days (95% CI 1.9–3.9; p < 0.001) longer than dabigatran users and 2.4 days longer (95% CI 0.9–3.7; p = 0.003) than rivaroxaban users. There was no difference in ICU stay between dabigatran and rivaroxaban users. There were no differences in 30- and 90-day all-cause mortality. Conclusions: Rivaroxaban and dabigatran were associated with shorter hospitalizations; however, there were no differences in 30- and 90-day mortality. These findings suggest bleeding associated with the newer agents is not more dangerous than bleeding associated with warfarin. [ABSTRACT FROM AUTHOR]

Background: The management of patients with non-valvular atrial fibrillation (NVAF) with rate-lowering or anti-arrhythmic drugs has markedly changed over the last decade, but it is unknown how these changes have affected patients with NVAF with a permanent pacemaker (PPM). Methods: Through Danish nationwide registries, patients with NVAF and a PPM were identified from 2001 to 2012. Changes in concomitant pharmacotherapy and comorbidities were tested using the Cochran–Armitage trend test and linear regression. Patients with NVAF were identified to calculate the proportional amount of PPM implants. Results: A total of 12,231 NVAF patients with a PPM were included in the study, 55.6% of which were men. Median age was 78 years (interquartile range 70–84). From 2001 to 2012, the number of NVAF patients with a PPM increased from 850 to 1344, while the number of NVAF patients increased from 67,478 to 127,261. Thus, the proportional amount of NVAF patients with a PPM decreased from 1.3% to 1.1% (p = 0.015). Overall 45.9% had atrial fibrillation (AF) duration less than one year and the proportion declined from 55.5% to 42.4% (p <0.001). Diabetes mellitus increased from 7.2% to 16.8% (p <0.001). Heart failure (HF) decreased from 36.7% to 29.3% (p = 0.010) and ischemic heart disease (IHD) decreased from 32.4% to 26.1% (p <0.001). Beta-blocker use increased from 38.1% to 58.0% (p <0.001), while digoxin and anti-arrhythmic drug use decreased over time. Conclusion: From 2001 to 2012, the absolute number of NVAF patients with a PPM increased while the proportional amount decreased. The number of NVAF patients receiving a PPM within one year of AF diagnosis decreased. The prevalence of DM increased, while the prevalence of HF and IHD was high but decreasing. The use of beta-blockers increased markedly, while use of digoxin and anti-arrhythmic drugs decreased over time. [ABSTRACT FROM AUTHOR]

Background: We sought to determine the leading causes of cardiovascular (CV) hospitalization, and to describe and compare national rates of CV hospitalization by age, gender, race, ethnicity, region, and year, among U.S. veterans. Methods: We evaluated the electronic health records of all veterans aged ≥18 years who had accessed any healthcare services at either a VA healthcare facility or a non-VA healthcare facility that was reimbursed by the VA, between January 1 2010 and December 31 2014. Among these 8,452,912 patients, we identified the 5 leading causes of CV hospitalization and compared rates of hospitalization by age, gender, race, ethnicity, region, year and type of VA healthcare user. Results: The top 5 causes of CV hospitalization were: coronary atherosclerosis, heart failure, acute myocardial infarction, stroke and atrial fibrillation. Overall, 297,373 (3.5%) veterans were hospitalized for one or more of these cardiovascular conditions. The percentage of veterans hospitalized for one or more of these CV conditions decreased over time, from 1.23% in 2010 to 1.18% in 2013, followed by a slight increase to 1.20% in 2014. There was significant variation in rates of CV hospitalization by gender, race, ethnicity, geographic region, and urban vs. rural zip code. In particular, older, male, Black, non-Hispanic, urban and Continental region veterans experienced the highest rates of CV hospitalizations. Conclusions: Among 8.5 million patients enrolled in the VA healthcare system from 2010 to 2014, there was substantial variation in rates of CV hospitalization by age, gender, race, geographical distribution, year, and use of non-VA (vs. VA only) healthcare care facilities. [ABSTRACT FROM AUTHOR]

Background: Patients with cardiac sarcoidosis are at increased risk of ventricular tachycardia/fibrillation. Objective: We tested the hypothesis that the wearable cardioverter defibrillator can be used to mitigate the risk of sudden cardiac death among cardiac sarcoidosis patients. Methods: A retrospective review of the commercial database identified cardiac sarcoidosis patients who wore the wearable cardioverter defibrillator. Evidence for cardiac sarcoidosis diagnosis as well as demographic, co-morbidity and left ventricular ejection fraction were provided by patient clinical records. Clinical data also included daily wearable cardioverter defibrillator wear, shock treatment and survival information. Results: The wearable cardioverter defibrillator was worn by 46 cardiac sarcoidosis patients, 24 (52%) male. The median age was 48 years and median left ventricular ejection fraction was 30%. The wearable cardioverter defibrillator was worn a median of 23.6 hours each day. There were 11 ventricular tachycardia/fibrillation episodes occurring in 10 (22%) patients. Ventricular tachycardia/fibrillation occurred over a range of 1 to 79 days, median 24 days. First-shock success for conversion of ventricular tachycardia/fibrillation was 100%. Patient survival 24 hours after shock treatment was 100%. Follow up to determine the reason for discontinuing wearable cardioverter defibrillator use indicated that among shocked patients 7 received an implantable cardioverter defibrillator, 1 patient was admitted to the hospital ending in death 2 weeks after discontinuing wearable cardioverter defibrillator use, and 2 patients were lost to follow up. Among the not shocked patients, there were 16 who received an implantable cardioverter defibrillator while 7 achieved improved left ventricular ejection fraction. Conclusion: Management of sudden cardiac death among cardiac sarcoidosis patients was aided by the wearable cardioverter defibrillator resulting in successful termination of ventricular tachycardia/fibrillation upon delivery of shock. [ABSTRACT FROM AUTHOR]

Background: Human Immunodeficiency Virus-Infected (HIV+) persons have elevated risks for various manifestations of cardiovascular disease (CVD). No studies to our knowledge have compared atrial fibrillation (AF) and atrial flutter (AFL) prevalence and associated characteristics for HIV+ persons and matched uninfected controls. Methods and findings: Persons with diagnoses of HIV receiving care at a large urban academic medical center were frequency-matched 1:2 on age, sex, race, zip code, and clinic location with uninfected persons. Possible AF/AFL was screened for using administrative codes and diagnoses of AF/AFL were subsequently adjudicated using electrocardiography and physician notes; adjudication was performed given the inconsistent validity of administrative code-derived AF diagnoses found in previous studies. There were 101 confirmed AF/AFL cases (2.00%) among 5,052 HIV+ patients and 159 confirmed AF/AFL cases (1.57%) among 10,121 uninfected controls [Odds Ratio (OR) 1.27, 95% Confidence Interval (CI) 0.99–1.64; p = 0.056]. The association between HIV serostatus and AF/AFL was attenuated after adjustment for demographics and CVD risk factors. Among HIV+ persons, nadir CD4+ T cell count <200 cells/mm3 was associated with approximately twofold elevated odds of AF/AFL even after adjustment for demographics and CVD risk factors (Multivariable-adjusted OR 1.98, 95% CI 1.21–3.25). There was no significant association between log10 of peak HIV viral load and AF/AFL (Multivariable-adjusted OR 1.03, 95% CI 0.86–1.24). Older age, diabetes, hypertension, and chronic obstructive pulmonary disease were associated with similarly elevated odds of AF/AFL for HIV+ persons and uninfected controls. Conclusion: HIV-related immunosuppression (nadir CD4 T cell count <200 cells/mm3) and traditional CVD risk factors are associated with significantly elevated odds of AF/AFL among HIV+ persons. Although atrial fibrillation and flutter was more common among HIV+ versus uninfected persons in this cohort, this difference was attenuated by adjustment for demographics and CVD risk factors. [ABSTRACT FROM AUTHOR]

Aim: Warfarin is a cornerstone for the prevention of thromboembolism in atrial fibrillation (AF), and several efforts have been taken to increase its usage and safety, including risk stratification schemes. Our aim was to investigate the temporal trends in initiation of warfarin and its effects on incidence of bleeding and thromboembolism in patients with new-onset atrial fibrillation 1996–2011. Methods: All patients with a first-time diagnosis of non-valvular atrial fibrillation were identified from nationwide administrative registries. Trends were determined by linear regression. Results: In total 153,682 patients were included. Initiation of warfarin increased from 14% to 41% (p<0.0001). Events of thromboembolism decreased from 3.9% to 2.6% annually (p<0.0001). The greatest decline in thromboembolic events was observed for patients with a CHA2DS2VASc score >1, where the annual decline was -0.12% (95%CI: -0.161; -0.084)) for those treated with warfarin and -0.073% (95%CI: -0.116;-0.030)) for those not treated with warfarin. Bleeding increased from 3.3% to 3.9% (p = 0.043). For those with a CHA2DS2VASc score >1 annual bleeding rates increased by 0.095% (95%CI: -0.025; -0.165) in warfarin treated and by 0.056% (95%CI: -0.013; -0.100) in patients not treated with warfarin. Conclusion: Warfarin use increased by nearly a 3-fold between 1996 and 2011. During the same period, thromboembolic events declined by a third and bleeding increased by a fifth, suggesting a beneficial effect associated with higher warfarin use. Notably, a small decline in thromboembolic events and increase in bleeding events was observed for the untreated population, suggesting a changing risk profile of AF patients. [ABSTRACT FROM AUTHOR]

Patients with primary biliary cholangitis (PBC) can have extrahepatic manifestations. However, data about cardiac involvement of PBC is limited. We aimed in this study to analyze the clinical characteristics in patients with PBC complicated with and without cardiac involvement, and the risk factors of cardiac involvement in PBC. PBC patients admitted to Peking Union Medical College Hospital between January 2002 and February 2016 were consecutively enrolled. Structured interview, systemic rheumatologic examination, and laboratory tests were conducted for each patient, and risk factors of cardiac involvement were analyzed by comparing patients with and without cardiac involvement. In total, 580 PBC patients were enrolled, and cardiac involvement was identified in 24 patients (4%), with 11 male (46%) and a mean age of 57±8 year. Cardiomyopathy and arrhythmias were presented in 17 (70.8%) and 21 (87.5%) patients, respectively. Patients with cardiac involvement were more frequently male (46% vs. 11%, P<0.01), complicated with inflammatory myopathy (IM) (58% vs. 1%, P<0.01), and had a longer disease course (median, 72 vs 24 month, P<0.01). Furthermore, concomitant IM was the independent risk factor of cardiac involvement in PBC (OR = 77.333, 95% CI: 23.704–252.294). Cardiac involvement was a rare complication of PBC, which was more frequently observed in male or long-course patients. Importantly, concomitant IM was the strong independent risk factor of cardiac involvement in PBC. Given cardiac involvement is a serious complication, thorough evaluation of cardiac manifestation in high-risk PBC patients is highly recommended. [ABSTRACT FROM AUTHOR]

Background: Vitamin K antagonist (VKA) therapy is safer and more effective when patients have a high time within the therapeutic range and low international normalised ratio variability. The SAMe-TT2R2 score aims to identify those at risk for poor VKA control. Objectives: To evaluate the predictive value and clinical usefulness of the SAMe-TT2R2 score to identify those at risk for poor VKA control. Methods: We performed a systematic review in MEDLINE and Embase for original research papers assessing the SAMe-TT2R2’s relation to poor TTR. We performed a meta-analysis where scores ≥ 2 and ≥ 3 predicting TTR < 70%. When studies evaluated other cutoffs for TTR or SAMe-TT2R2, they were harmonised by multiple simulations with patient characteristics from the individual studies, if the data were available. Results: 16 studies were identified and used in the meta-analysis: 4 and 2 times directly, 8 and 8 times harmonised for scores ≥ 2 and ≥ 3, respectively (not all studies provided information about both cutoffs). The sensitivities and specificities were too heterogeneous to pool. The positive likelihood ratios were 1.25 (1.14-1.38) for a score ≥ 2, and 1.24 (1.09-1.40) for a score ≥ 3; the negative ones were 0.87 (0.82-0.93) and 0.96 (0.91-1.02), respectively. This shows that the post-test probabilities hardly differ from the prior probability (prevalence). Conclusion: The SAMe-TT2R2 score does predict low TTR, but the effect is small. Its effect on individual patients is too limited to be clinically useful. [ABSTRACT FROM AUTHOR]

The risk of atrial fibrillation (AF)-related stroke is usually assessed by calculating the CHA2DS2-VASc score, the components of which are various risk factors, including prior stroke. Although prior stroke is considered the strongest risk factor, the associated risk is actually inferred. Nevertheless, it implies a “freedom-from-event effect” (FEE)—the longer a patient is stroke-free, the lower the stroke risk. Although dynamic prognostication has been applied to cancer, the FEE has been ignored in AF, probably because of methodological difficulties. We conducted a simulation study to evaluate the FEE in the risk of AF-related stroke. We modeled various populations of AF patients and simulated the development of stroke assuming a nonhomogeneous Poisson process, where the hazard depends on age, comorbidities, and individual variability. Parameters were set so that the model respects the CHA2DS2-VASc scoring scheme and reproduces the 1-year CHA2DS2-VASc score-wise stroke risk and relative risk conferred by real-world risk factors. We tracked stroke risk over 0 to 15 years of freedom-from-stroke time (FST), both prospective FST (pFST), which begins at the time of diagnosis and continues to the future, and retrospective FST (rFST), which begins at the present and looks backward to the time of diagnosis. The pFST counterbalanced the increase in stroke risk conferred by aging; in patients with a CHA2DS2-VASc score of 1, the pFST offset 62% of the age-conferred risk increase. The rFST reduced the stroke risk; in patients with a CHA2DS2-VASc score of 2 and without prior stroke, an rFST of 6.8 years reduced the stroke risk to the midpoint between CHA2DS2-VASc scores 1 and 2. The study results suggest that the FEE should be considered in evaluating stroke risk in patients with AF. The FEE may be important in other recurrent diseases for which a prior event is a risk factor for a future event. [ABSTRACT FROM AUTHOR]

Exercising horses uniquely accommodate 7–8-fold increases in heart rate (HR). The present experiments for the first time analysed the related adaptations in action potential (AP) restitution properties recorded by in vivo telemetric electrocardiography from Thoroughbred horses. The horses were subjected to a period of acceleration from walk to canter. The QRS durations, and QT and TQ intervals yielded AP conduction velocities, AP durations (APDs) and diastolic intervals respectively. From these, indices of active, λ = QT/(QRS duration), and resting, λ0 = TQ/(QRS duration), AP wavelengths were calculated. Critical values of QT and TQ intervals, and of λ and λ0 at which plots of these respective pairs of functions showed unity slope, were obtained. These were reduced by 38.9±2.7% and 86.2±1.8%, and 34.1±3.3% and 85.9±1.2%, relative to their resting values respectively. The changes in λ were attributable to falls in QT interval rather than QRS duration. These findings both suggested large differences between the corresponding critical (129.1±10.8 or 117.4±5.6 bpm respectively) and baseline HRs (32.9±2.1 (n = 7) bpm). These restitution analyses thus separately identified concordant parameters whose adaptations ensure the wide range of HRs over which electrophysiological activation takes place in an absence of heart block or arrhythmias in equine hearts. Since the horse is amenable to this in vivo electrophysiological analysis and displays a unique wide range of heart rates, it could be a novel cardiac electrophysiology animal model for the study of sudden cardiac death in human athletes. [ABSTRACT FROM AUTHOR]

Background: During recent years, systematic reviews of observational studies have compared digoxin to no digoxin in patients with atrial fibrillation or atrial flutter, and the results of these reviews suggested that digoxin seems to increase the risk of all-cause mortality regardless of concomitant heart failure. Our objective was to assess the benefits and harms of digoxin for atrial fibrillation and atrial flutter based on randomized clinical trials. Methods: We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-Expanded, BIOSIS for eligible trials comparing digoxin versus placebo, no intervention, or other medical interventions in patients with atrial fibrillation or atrial flutter in October 2016. Our primary outcomes were all-cause mortality, serious adverse events, and quality of life. Our secondary outcomes were heart failure, stroke, heart rate control, and conversion to sinus rhythm. We performed both random-effects and fixed-effect meta-analyses and chose the more conservative result as our primary result. We used Trial Sequential Analysis (TSA) to control for random errors. We used GRADE to assess the quality of the body of evidence. Results: 28 trials (n = 2223 participants) were included. All were at high risk of bias and reported only short-term follow-up. When digoxin was compared with all control interventions in one analysis, we found no evidence of a difference on all-cause mortality (risk ratio (RR), 0.82; TSA-adjusted confidence interval (CI), 0.02 to 31.2; I2 = 0%); serious adverse events (RR, 1.65; TSA-adjusted CI, 0.24 to 11.5; I2 = 0%); quality of life; heart failure (RR, 1.05; TSA-adjusted CI, 0.00 to 1141.8; I2 = 51%); and stroke (RR, 2.27; TSA-adjusted CI, 0.00 to 7887.3; I2 = 17%). Our analyses on acute heart rate control (within 6 hours of treatment onset) showed firm evidence of digoxin being superior compared with placebo (mean difference (MD), -12.0 beats per minute (bpm); TSA-adjusted CI, -17.2 to -6.76; I2 = 0%) and inferior compared with beta blockers (MD, 20.7 bpm; TSA-adjusted CI, 14.2 to 27.2; I2 = 0%). Meta-analyses on acute heart rate control showed that digoxin was inferior compared with both calcium antagonists (MD, 21.0 bpm; TSA-adjusted CI, -30.3 to 72.3) and with amiodarone (MD, 14.7 bpm; TSA-adjusted CI, -0.58 to 30.0; I2 = 42%), but in both comparisons TSAs showed that we lacked information. Meta-analysis on acute conversion to sinus rhythm showed that digoxin compared with amiodarone reduced the probability of converting atrial fibrillation to sinus rhythm, but TSA showed that we lacked information (RR, 0.54; TSA-adjusted CI, 0.13 to 2.21; I2 = 0%). Conclusions: The clinical effects of digoxin on all-cause mortality, serious adverse events, quality of life, heart failure, and stroke are unclear based on current evidence. Digoxin seems to be superior compared with placebo in reducing the heart rate, but inferior compared with beta blockers. The long-term effect of digoxin is unclear, as no trials reported long-term follow-up. More trials at low risk of bias and low risk of random errors assessing the clinical effects of digoxin are needed. Systematic review registration: PROSPERO CRD42016052935 [ABSTRACT FROM AUTHOR]

Electrical restitution (ER) is a major determinant of repolarization stability and, under fast pacing rate, it reveals memory properties of the cardiac action potential (AP), whose dynamics have never been fully elucidated, nor their ionic mechanisms. Previous studies have looked at ER mainly in terms of changes in AP duration (APD) when the preceding diastolic interval (DI) changes and described dynamic conditions where this relationship shows hysteresis which, in turn, has been proposed as a marker of short-term AP memory and repolarization stability. By means of numerical simulations of a non-propagated human ventricular AP, we show here that measuring ER as APD versus the preceding cycle length (CL) provides additional information on repolarization dynamics which is not contained in the companion formulation. We focus particularly on fast pacing rate conditions with a beat-to-beat variable CL, where memory properties emerge from APD vs CL and not from APD vs DI and should thus be stored in APD and not in DI. We provide an ion-currents characterization of such conditions under periodic and random CL variability, and show that the memory stored in APD plays a stabilizing role on AP repolarization under pacing rate perturbations. The gating kinetics of L-type calcium current seems to be the main determinant of this safety mechanism. We also show that, at fast pacing rate and under otherwise identical pacing conditions, a periodically beat-to-beat changing CL is more effective than a random one in stabilizing repolarization. In summary, we propose a novel view of short-term AP memory, differentially stored between systole and diastole, which opens a number of methodological and theoretical implications for the understanding of arrhythmia development. [ABSTRACT FROM AUTHOR]

Background: Cardiac surgery patients often experience several types of tachyarrhythmias after admission to the intensive care unit (ICU), which increases mortality and morbidity. Dexmedetomidine (DEX) is a popular medicine used for sedation in the ICU, and its other pharmacological characteristics are gradually being uncovered. Purpose: To determine whether DEX has an antiarrhythmic effect after cardiac surgery. Methods: The three primary databases MEDLINE, Embase (OVID SP) and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched, and all English-language and randomized control-designed clinical publications comparing DEX to control medicines for sedation after elective cardiac surgery were included. Two colleagues independently extracted the data and performed other quality assessments. A subgroup analysis was performed according to the different medicines used and whether cardiopulmonary bypass (CPB) was applied. All tachyarrhythmias that occurred in the atria and ventricles were analyzed. Results: A total of 1295 patients in 9 studies met the selection criteria among 2587 studies that were screened. After quantitative synthesis, our results revealed that the DEX group was associated with a lower incidence of ventricular arrhythmia (VA, OR 0.24, 95% CI 0.09–0.64, I2 = 0%, P = 0.005) than the control group. Subgroup analysis did not reveal a significant difference between the DEX and propofol subgroups (OR 0.13, 95% CI 0.03–0.56, I2 = 0%, P = 0.007). Additionally, no difference in the incidence of atrial fibrillation (AF) was observed regardless of the different control medicines (OR 0.82, 95% CI 0.60–1.10, I2 = 25%, P = 0.19) or whether CPB was applied. Conclusions: This meta-analysis revealed that DEX has an antiarrhythmic effect that decreases the incidence of VA compared to other drugs used for sedation following cardiac surgery. DEX may not have an effect on AF, but cautious interpretation should be exercised due to high heterogeneity. [ABSTRACT FROM AUTHOR]

Background: Rheumatic heart disease (RHD) is a major cause of premature death in low and middle-income countries. The greatest barrier to RHD control is neglect of the disease in national health policies and a lack of prevalence data that might inform control efforts. Myanmar is making remarkable progress against many infectious diseases, but there are almost no data to define the clinical burden of RHD in the country. This prospective audit was performed in an adult medical ward of a tertiary-referral hospital in Yangon, to gain an insight into the prevalence of RHD in Myanmar. Principal findings: All patients admitted to the ward between May 1, 2016 and April 30, 2017 were eligible for enrolment. RHD was confirmed in 96 patients who were admitted on 134 occasions, representing 1.1% of the 12,172 adult medical admissions during the study period. This compared with 410 (3.4%) admissions with HIV and 14 (0.1%) with malaria. Patients with RHD had a median age of 44 years (interquartile range: 35–59); 70 (73%) were female. Only one patient had ever had surgery despite 79 (82%) meeting criteria for intervention; 54 (56%) patients were not receiving any regular clinician review. Prior to hospitalisation only 18 (19%) patients were receiving regular penicillin. Only 8 (19%) of the 42 women <50 years were using contraception. Of 49 patients who had been hospitalised previously, 22 (45%) were receiving no regular therapy. During the study three (3.1%) patients died, and 28 (29%) were lost to follow-up. Of the 65 (68%) alive and retained in care, 21 (32%) were still experiencing moderate-severe RHD-related symptoms at the study’s end. Conclusions: There is a significant and unmet clinical burden of RHD in Myanmar. A national RHD programme would improve patient care, reducing morbidity and mortality from this preventable disease. [ABSTRACT FROM AUTHOR]

Background: Patients with atrial fibrillation (AF) have an increased risk for the development of heart failure (HF). In this study, we aimed to detect predictors of HF hospitalizations in an unselected AF population. Methods: The Basel Atrial Fibrillation Cohort Study is an ongoing observational multicenter cohort study in Switzerland. For this analysis, 1193 patients with documented AF underwent clinical examination, venous blood sampling and resting 12-lead ECG at baseline. Questionnaires about lifestyle and medical history were obtained in person at baseline and during yearly follow-up phone calls. HF hospitalizations were validated by two independent physicians. Cox regression analyses were performed using a forward selection strategy. Results: Overall, 29.8% of all patients were female and mean age was 69 ±12 years. Mean follow-up time was 3.7 ±1.5 years. Hospitalization for HF occurred in 110 patients, corresponding to an incidence of 2.5 events per 100 person years of follow-up. Independent predictors for HF were body mass index (HR 1.40 [95%CI 1.17; 1.66], p = 0.0002), chronic kidney disease (2.27 [1.49; 3.45], p = 0.0001), diabetes mellitus (2.13 [1.41; 3.24], p = 0.0004), QTc interval (1.25 [1.04; 1.49], p = 0.02), brain natriuretic peptide (2.19 [1.73; 2.77], p<0.0001), diastolic blood pressure (0.79 [0.65; 0.96], p = 0.02), history of pulmonary vein isolation or electrical cardioversion (0.54 [0.36; 0.80], p = 0.003) and serum chloride (0.82 [0.70; 0.96], p = 0.02). Conclusions: In this unselected AF population, several traditional cardiovascular risk factors and arrhythmia interventions predicted HF hospitalizations, providing potential opportunities for the implementation of strategies to reduce HF among AF patients. [ABSTRACT FROM AUTHOR]

Prior real-world studies have shown that apixaban is associated with a reduced risk of stroke/systemic embolism (stroke/SE) and major bleeding versus warfarin. However, few studies evaluated the effectiveness and safety of apixaban according to its dosage, and most studies contained limited numbers of patients prescribed 2.5 mg twice-daily (BID) apixaban. Using pooled data from 4 American claims database sources, baseline characteristics and outcomes for patients prescribed 5 mg BID and 2.5 mg BID apixaban versus warfarin were compared. After 1:1 propensity-score matching, 31,827 5 mg BID apixaban-matched warfarin patients and 6600 2.5 mg BID apixaban-matched warfarin patients were identified. Patients prescribed 2.5 mg BID apixaban were older, had clinically more severe comorbidities, and were more likely to have a history of stroke and bleeding compared with 5 mg BID apixaban patients. Compared with warfarin, 5 mg BID apixaban was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.60–0.81) and major bleeding (HR: 0.59, 95% CI: 0.53–0.66). Compared with warfarin, 2.5 mg BID apixaban was also associated with a lower risk of stroke/SE (HR: 0.63, 95% CI: 0.49–0.81) and major bleeding (HR: 0.59, 95% CI: 0.49–0.71). In this real-world study, both apixaban doses were assessed in 2 patient groups differing in age and clinical characteristics. Each apixaban dose was associated with a lower risk of stroke/SE and major bleeding compared with warfarin in the distinct population for which it is being prescribed in United States clinical practice. Trial registration: Clinicaltrials.Gov Identifier: . [ABSTRACT FROM AUTHOR]

Background: While oral anticoagulants (OACs) are highly effective for ischemic stroke prevention in atrial fibrillation, intracerebral hemorrhage (ICH) remains the most feared complication of OAC. Clinical controversy remains regarding OAC resumption and its timing for ICH survivors with atrial fibrillation because the balance between risks and benefits has not been investigated in randomized trials. Aims/Hypothesis: To survey the practice of stroke neurologists, thrombosis experts and neurosurgeons on OAC re-initiation following OAC-associated ICH. Methods: An online survey was distributed to members of the International Society for Thrombosis and Haemostasis, Canadian Stroke Consortium, NAVIGATE-ESUS trial investigators (Clinicatrials.gov identifier NCT02313909) and American Association of Neurological Surgeons. Demographic factors and 11 clinical scenarios were included. Results: Two hundred twenty-eight participants from 38 countries completed the survey. Majority of participants were affiliated with academic centers, and >20% managed more than 15 OAC-associated ICH patients/year. Proportion of respondents suggesting OAC anticoagulant resumption varied from 30% (for cerebral amyloid angiopathy) to 98% (for traumatic ICH). Within this group, there was wide distribution in response for timing of resumption: 21.4% preferred to re-start OACs after 1–3 weeks of incident ICH, while 25.3% opted to start after 1–3 months. Neurosurgery respondents preferred earlier OAC resumption compared to stroke neurologists or thrombosis experts in 5 scenarios (p<0.05 by Kendall’s tau). Conclusions: Wide variations in current practice exist among management of OAC-associated ICH, with decisions influenced by patient- and provider-related factors. As these variations likely reflect the lack of high quality evidence, randomized trials are direly needed in this population. [ABSTRACT FROM AUTHOR]

Background: The factors influencing three major outcomes–death, stroke/systemic embolism (SE), and major bleeding–have not been investigated in a large international cohort of unselected patients with newly diagnosed atrial fibrillation (AF). Methods and results: In 28,628 patients prospectively enrolled in the GARFIELD-AF registry with 2-year follow-up, we aimed at analysing: (1) the variables influencing outcomes; (2) the extent of implementation of guideline-recommended therapies in comorbidities that strongly affect outcomes. Median (IQR) age was 71.0 (63.0 to 78.0) years, 44.4% of patients were female, median (IQR) CHA2DS2-VASc score was 3.0 (2.0 to 4.0); 63.3% of patients were on anticoagulants (ACs) with or without antiplatelet (AP) therapy, 24.5% AP monotherapy, and 12.2% no antithrombotic therapy. At 2 years, rates (95% CI) of death, stroke/SE, and major bleeding were 3.84 (3.68; 4.02), 1.27 (1.18; 1.38), and 0.71 (0.64; 0.79) per 100 person-years. Age, history of stroke/SE, vascular disease (VascD), and chronic kidney disease (CKD) were associated with the risks of all three outcomes. Congestive heart failure (CHF) was associated with the risks of death and stroke/SE. Smoking, non-paroxysmal forms of AF, and history of bleeding were associated with the risk of death, female sex and heavy drinking with the risk of stroke/SE. Asian race was associated with lower risks of death and major bleeding versus other races. AC treatment was associated with 30% and 28% lower risks of death and stroke/SE, respectively, compared with no AC treatment. Rates of prescription of guideline-recommended drugs were suboptimal in patients with CHF, VascD, or CKD. Conclusions: Our data show that several variables are associated with the risk of one or more outcomes, in terms of death, stroke/SE, and major bleeding. Comprehensive management of AF should encompass, besides anticoagulation, improved implementation of guideline-recommended therapies for comorbidities strongly associated with outcomes, namely CHF, VascD, and CKD. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: Compared with left atrial (LA) dimension, LA emptying fraction (LAEF) has received less emphasis as a predictor of atrial fibrillation (AF) recurrence after radiofrequency catheter ablation (RFCA). In addition, patients experiencing post-RFCA AF recurrence may respond to previously ineffective antiarrhythmic drugs (AADs). Classifying these patients into a third RFCA outcome category is recommended. Objective: To identify predictors of RFCA outcome classified into three categories, and to build proportional odds logistic regression models for clinical applicability to predict AF recurrence. Methods: Data were retrospectively collected from 483 consecutive patients with drug-refractory AF undergoing RFCA (328 men; age 58.4 ± 11.5 years; 383 paroxysmal). Patients were classified into 3 groups based on the last RFCA outcome: group 1, free from AF without AADs; group 2, free from AF with AADs; and group 3, recurrence of AADs-refractory atrial tachyarrhythmia. Results: After a mean follow-up duration of 64.5 ± 43.2 months and mean ablation procedure number of 1.37 ± 0.68, the RFCA outcome showed 76.0%, 9.5% and 14.5% of patients in groups 1, 2, and 3, respectively. In multivariate analysis, LAEF was the most stable and important predictor of AF recurrence, followed by body mass index, stroke, AF duration, mitral regurgitation, and LA linear ablation. For patients undergoing repeat RFCA, LAEF was the only independent predictor (cutoffs: 43% and 35% for groups 1 and 3, respectively). Conclusion: LAEF provides optimal prognostic information regarding the risk stratification of AF patients undergoing RFCA. [ABSTRACT FROM AUTHOR]