Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Structural characterization of the hemoglobin of **Gasterophilus intestinalis**

Background Current animal models of human cardiac disease may be similar in anatomy and physiology but are often expensive and tedious to work with. The current need is for a model organism that is more efficient to work with in the lab but that still provides an accurate model of human cardiac disease. Drosophila melanogaster (D. mel) is such a candidate. While 74% of the genes coding for protein are conserved between D. mel and human hearts, it is unknown if cardiac medication used in humans, such as atropine and propranolol hydrochloride, similarly affect heart rate. I hypothesized that administration of atropine and propranolol hydrochloride to third instar larvae would cause an increase and decrease respectively in the heart rates of D. mel. Methods After larvae hatched and reached the second instar larval phase, they were moved to fresh vials. The control group larvae were transferred to vials containing no medication, and the experimental group larvae were transferred to vials with 1mM atropine or 1mM propranolol hydrochloride. The larvae inhabited the new vials for twenty-four hours to reach the third instar larvae stage. Larvae were removed, placed individually on a microscope slide, and observed using the 4X objective lens of a Leica compound microscope. Heart rates of fifty larvae per group were recorded in triplicate over fifteen second intervals. Results We observed elevated heart rates of 406 ± 3.18 beats per minute in atropine treated larvae when compared to rates of 388 ± 2.07 in control larvae, a 4.83% increase. Moreover, heart rates were slowed to an average of 274 ± 2.70 beats per minute in propranolol hydrochloride treated hearts, a 29.18% decrease. Both changes in heart rate when compared to the control were found to be statistically significant (p\u3c0.001). Conclusion Administration of propranolol hydrochloride and atropine increased and decreased the heart rates of D. mel respectively. This data supports the hypothesis that D. mel can serve as an experimental model for human cardiovascular disease. Future work should build on this study and focus on the use of D. mel in preliminary pharmaceutical testing for new medication treating cardiovascular conditions