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).

Background: The comparative safety and effectiveness of treatments to prevent thromboembolic complications in atrial fibrillation (AF) remains uncertain. Purpose: To compare the available treatment strategies in patients with AF. Data Sources: English-language studies in multiple databases from January 1, 2000, to February 14, 2018. Study Selection: Two reviewers independently screened citations for studies examining treatments for stroke prevention in patients with AF. Data Extraction: Two reviewers independently abstracted data and assessed study quality and applicability. Data Synthesis: Data from 220 articles were included. Dabigatran and apixaban were superior while rivaroxaban and edoxaban were similar to warfarin in the prevention of stroke or systemic embolism. Apixaban and edoxaban were superior while rivaroxaban and dabigatran were similar to warfarin in reducing the risk of major bleeding. Treatment effects with dabigatran were similar in patients with renal dysfunction (interaction p>0.05) and patients less than 75 years old had lower rates of bleeding with dabigatran (interaction p<0.001). The benefit of treatment with apixaban was consistent in many subgroups including those with renal impairment, diabetes and prior stroke (interaction p>0.05 for all). The greatest bleeding risk reduction was observed in patients with GFR<50mL/min (p=0.003). Similar treatment effects of rivaroxaban and edoxaban were observed in patients with prior stroke, diabetes, or heart failure (interaction p>0.05 for all). Limitations: Heterogeneous study populations, interventions and outcomes. Conclusion: The available DOACs are at least as effective and safe when compared to warfarin. Similar benefits of treatment with DOACs were observed across multiple patient subgroups of interest, giving assurance to the safe and efficacious use of DOACs for a wide range of patients with AF. Primary Funding Source: Patient-Centered Outcomes Research Institute (PROSPERO #CRD42017069999)

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Optical mapping has become an important technique in the study of cardiac electrophysiology, especially in terms of investigating the mechanisms of cardiac arrhythmias. The increasing availability of transgenic mice as models for cardiovascular disease is driving the need for instrumentation suitable for the study of electrical activity in the mouse heart. In this paper we evaluate our optical mapping system's ability to clearly record induced arrhythmic activity in an isolated mouse atrial preparation. Preliminary results indicate that the signal quality is high enough that individual optically recorded action potentials can be discerned in many pixels, even without post-processing for noise removal. The optical mapping video is clear enough for general observations regarding the patterns of electrical propagation during arrhythmic behaviour. The induced arrhythmias appear to have a regular pattern of activity, and are likely best classified as atrial tachycardias.

This paper discusses the development of an algorithm to mask poor quality data in fluorescence videos of cardiac tissue stained with voltage-sensitive dye. The aim was to simplify further analysis by eliminating the step of manually masking areas of poor signal quality and areas outside the preparation of interest. Our algorithm estimates signal to noise ratio (SNR) from the power spectral density (PSD) for each pixel. This information is combined with information about the fluorescence intensity in each pixel, according to a user-selectable weighting factor. A threshold is then applied to the resulting combined measure. This approach resulted in an effective algorithm that is capable of automatically creating a "mask" that can be applied to the data to exclude parts of the data from further analysis. The algorithm is sufficiently efficient to allow interactive use, allowing the user to adjust the parameters of the algorithm and instantly view the resulting mask. This tool will be useful as a technique to simplify further analysis of voltage-sensitive dye imaging data.