Background: Atrial fibrillation (AF) is a common cardiac arrhythmia that increases the risk of stroke. Medical therapy for decreasing stroke risk involves anticoagulation, which may increase bleeding risk for certain patients. In determining optimal therapy for stroke prevention for patients with AF, clinicians use tools with various clinical, imaging, and patient characteristics to weigh stroke risk against therapy-associated bleeding risk. Aim: Review published literature and summarize available risk stratification tools for stroke and bleeding prediction in patients with AF. Methods: We searched for English-language studies in PubMed®, Embase®, and the Cochrane Database of Systematic Reviews published between January 1, 2000, and February 14, 2018. Two reviewers screened citations for studies that examined tools for predicting thromboembolic and bleeding risks in patients with AF. Data regarding study design, patient characteristics, interventions, outcomes, quality and applicability were extracted. Results: 61 studies were relevant to predicting thromboembolic risk and 38 to predicting bleeding risk. Data suggest that CHADS2, CHA2DS2-VASc, and ABC risk scores have the best evidence predicting thromboembolic risk (moderate strength of evidence for limited prediction ability of each score) and that HAS-BLED has the best evidence for predicting bleeding risk (moderate strength of evidence). Limitations: Studies were heterogeneous in methodology and populations of interest, setting, interventions, and outcomes analyzed. Conclusion: CHADS2, CHA2DS2-VASc, and ABC stroke have the best prediction for stroke events, and HAS-BLED provides the best prediction for bleeding risk. Future studies should define the role of imaging tools and biomarkers in enhancing the accuracy of risk prediction tools. Primary Funding Source: Patient-Centered Outcomes Research Institute (PROSPERO #CRD42017069999)

The incidence of diabetes mellitus is increasing. Cardiac dysfunction often develops, resulting in diverse arrhythmias. These arise from ion channel remodeling or from altered speed and pattern of impulse propagation. Few studies have investigated impulse propagation in the diabetic heart. We previously showed a reduced conduction reserve in the diabetic heart, with associated changes in intercellular gap junctions. The present study investigated whether these effects are sex specific. Hearts from control and streptozotocin-diabetic male and female rats were used. Optical mapping was performed with the voltage-sensitive dye di-4-ANEPPS, using Langendorff-perfused hearts. Isolated ventricular cells and tissue sections were used for immunofluorescent labeling of the gap junction protein connexin43 (Cx43). The gap junction uncoupler heptanol (0.75 mM) or elevated K+ (9 mM, to reduce cell excitability) produced significantly greater slowing of propagation in diabetic males than females. In ovariectomized diabetic females, 9 mM K+ slowed conduction significantly more than in nonovariectomized females. The subcellular redistribution (lateralization) of the gap junction protein Cx43 was smaller in diabetic females. Pretreatment of diabetic males with the angiotensin-converting enzyme inhibitor quinapril reduced Cx43 lateralization and the effects of 9 mM K+ on propagation. In conclusion, the slowing of cardiac impulse propagation in type 1 diabetes is smaller in female rats, partly due to the presence of female sex hormones. This difference is (partly) mediated by sex differences in activation of the cardiac renin-angiotensin system.

Agency for Healthcare Research and Quality (PROSPERO: CRD42016047032).