Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p <.001. Over 24 months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10 ml/min/1.73 m2 decrease), that was most notable in patients with eGFR <30 ml/min/1.73 m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90 ml/min/1.73 m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients

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

Probe Footprint Estimation in Eddy-Current Imaging

Eddy-current imaging has been described in detail in previous publications [1,2,3]. As with other imaging systems, the image of an object represents blurring of the structures of the object by the system point spread function (PSF). Differing from other imaging systems, the PSF is very large and causes great spatial blurring of the object. This is because the eddy-current probe is a coil; its active area is much greater than the size of a beam of light, sound, or x-rays</p

A Val85Met mutation in melanocortin-1 receptor is associated with reductions in eumelanic pigmentation and cell surface expression in domestic rock pigeons (Columba livia).

Variation in the melanocortin-1 receptor (Mc1r) is associated with pigmentation diversity in wild and domesticated populations of vertebrates, including several species of birds. Among domestic bird species, pigmentation variation in the rock pigeon (Columbalivia) is particularly diverse. To determine the potential contribution of Mc1r variants to pigment diversity in pigeons, we sequenced Mc1r in a wide range of pigeon breeds and identified several single nucleotide polymorphisms, including a variant that codes for an amino acid substitution (Val85Met). In contrast to the association between Val85Met and eumelanism in other avian species, this change was associated with pheomelanism in pigeons. In vitro cAMP accumulation and protein expression assays revealed that Val85Met leads to decreased receptor function and reduced cell surface expression of the mutant protein. The reduced in vitro function is consistent with the observed association with reduced eumelanic pigmentation. Comparative genetic and cellular studies provide important insights about the range of mechanisms underlying diversity among vertebrates, including different phenotypic associations with similar mutations in different species

Examples of plumage pigment variation in domestic rock pigeons.

<p>All birds are show homer breed unless otherwise noted. <b>A</b>–<b>C</b>. Eumelanic phenotypes: <b>A</b>, black check; <b>B</b>, blue bar (same color as <b>A</b>, but different pattern); <b>C</b>, brown (Mookee). <b>D</b>–<b>G</b>. Pheomelanic phenotypes: <b>D</b>, ash-red check; <b>E</b>, ash-red bar (same color as <b>D</b>, but different pattern); <b>F</b>, yellow check (dilute form of phenotype in <b>D</b>); <b>G</b>, <i>recessive red</i> (Chinese owl). <b>H</b>. White (white carneau). <b>I</b>. Fantail, a breed examined in subset of association tests. Panels <b>H</b> and <b>I</b> modified after [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074475#B27" target="_blank">27</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074475#B48" target="_blank">48</a>], respectively; photos courtesy of Eric Domyan (<b>A</b>–<b>F</b>) and Sydney Stringham (<b>H</b>).</p

Amino acid sequence variation among avian orthologs of Mc1r.

<p>Several variants have been implicated in pigment variation within avian species. The Val85Met mutation found in domestic pigeons is associated with eumelanism in the lesser snow goose and red-footed booby. Functional studies of Mc1r protein variants have been conducted for chicken [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074475#B14" target="_blank">14</a>] and pigeon (this study). Additional mutations in chicken have been identified on the E92K background [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074475#B13" target="_blank">13</a>] but are not shown here. Figure based on previous review of avian Mc1r diversity [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0074475#B2" target="_blank">2</a>].</p

Functional differences between Val85 and Met85 alleles of Mc1r.

<p><b>A</b>. cAMP production in response to αMSH stimulation is reduced in cells transfected with the Met85 allele relative to the Val85 allele (p < 0.02, paired t-test). Error bars, ± SEM. <b>B</b>. Total cellular protein expression of HA/FLAG-tagged Mc1r is equivalent in COS-7 cells transfected with pigeon Val85 and Met85 alleles. The non-specific OD_{492/620 nm} value (GFP) was 0.008 ± 0.001 (0% set point) and the OD_{492/620 nm} value of the Val85 allele was 0.415 ± 0.070 (100% set point). <b>C</b>. Surface protein expression of the Met85 allele is reduced relative to Val85 allele (p < 0.007, one-sample t-test). Non-specific OD_{492/620 nm} value (GFP) was 0.053 ± 0.050 (0%) and the OD_{492/620 nm} value of the Val85 allele was 0.501 ± 0.049 (100%). </p