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

On the Photophysics of Metallophthalocyanine-based Phototermal Sensitizers: Synergism between Theory and Experiment

A comprehensive understanding of the factors governing the efficiency of metallophthalocyanine-based photothermal sensitizers requires the knowledge of their excited-state dynamics. This can only be properly gained when the nature and energy of the excited states (often spectroscopically silent) lying between the photogenerated state and the ground state are known. Here the excited state deactivation mechanism of two very promising metallophthalocyanine-based photothermal sensitizers, NiPc(OBu)8 and NiNc(OBu)8, is reviewed. It is shown that time dependent density functional theory (TDDFT) methods are capable to provide reliable information on the nature and energies of the low-lying excited states along the relaxation pathways. TDDFT calculations and ultrafast experiments consistently show that benzoannulation of the Pc ring modifies the photodeactivation mechanism of the photogenerated S1(π, π∗) state by inducing substantial changes in the relative energies of the excited states lying between the S1(π, π∗) state and the ground state

The Role of the Metal Ion in the Photophysical Behavior of Co(II), Ni(II), and Cu(II) Octabutoxynaphthalocyanines: Insights from Ultra-fast Time-resolved Spectroscopy and DFT/TDDFT Calculations

The photo-deactivation mechanism of the MNc(OBu)8 (M = Co, Ni, Cu) series of complexes is reviewed, with special emphasis on the role played by the central metal. Ultra-fast transient absorption experiments and Density Functional Theory and time-dependent Density Functional Theory calculations consistently show that the central metal modifies the photo-deactivation mechanism of the investigated complexes by inducing substantial changes in the nature and energy of the excited states lying between the photo-generated state and the ground state

Інтелектуальні системи підтримання прийняття рішень у розвитку інфраструктури мегаполісу

Мегаполіс з точки зору теорії управління являє собою складну нестаціонарну просторову систему. Проблему прийняття інноваційних рішень щодо розвитку їх інфраструктури зумовлено наявністю великого обсягу інформації, її невизначеністю і суперечливістю. У роботі розглянуто принципи побудови інтелектуальних систем підтримання прийняття рішень ситуаційного типу для інноваційного розвитку інфраструктури мегаполісів. Рішення формуються шляхом логіко-аналітичного оброблення даних про ситуацію в цілому і окремих випадках ситуацій для розглянутого суб’єкта інфраструктури мегаполісу. Для практичної реалізації механізму прийняття рішень запропоновано лінгвочисловий метод визначення потенційно кращої альтернативи та нечіткий ситуаційний алгоритм управління суб’єктами інфраструктури мегаполісу, заснований на структурній спільності ситуацій нечіткої ситуаційної мережі. Отримані результати протестовано на двох реальних об’єктах інфраструктури Києва.From the point of view of the management theory, a megapolis is a complex non-stationary spatial system. The problem of making innovative decisions on the development of their infrastructure is caused by the presence of a large amount of information, its uncertainty and inconsistency. This article discusses the principles of building intelligent decision support systems of a situational type for the innovative development of the infrastructure of megacities. Solutions are formed by logico-analytical processing of data on the situation in general and special cases of situations for the considered subject of the megalopolis infrastructure. For the practical implementation of the decision-making mechanism, the article proposes a linguistic- numerical method for determining the potentially best alternative and a fuzzy situational algorithm for managing the subjects of the megalopolis infrastructure, based on the structural generality of the situations of a fuzzy situational network. The obtained results were tested on two real infrastructure subjects of Kyiv

On the flexibility of carboranylalkylthio substituents in porphyrazines and its relevance to the photophysical properties

Ultrafast transient absorption spectrometry and DFT/TDDFT calculations reveal that following photoexcitation, carboranyl- and carboranyl- free alkylthioporphyrazines deactivate by the pathway S1(π,π*)→Sn(Cβ-2pz/Sl.p.,π*)→ground state. The presence of quenching singlet excited states with predominantly Cβ-2pz/Sl.p.,π* character immediately below the primarily photogenerated S1(π,π*) state is a consequence of the electronic structure changes induced by the inherent flexibility of the alkylthio chains

Effects of Benzoaanulation and α-Octabutoxy Substitution on the Photophysical Behavior of Nickel Phthalocyanines: A Combined Experimental and DFT/TDDFT Study

The photophysical properties of a group of Ni(II)-centered tetrapyrroles have been investigated by ultrafast transient absorption spectrometry and DFT/TDDFT methods in order to characterize the impacts of α-octabutoxy substitution and benzoannulation on the deactivation pathways of the S1(π,π*) state. The compounds examined were NiPc, NiNc, NiPc(OBu)8, and NiNc(OBu)8, where Pc = phthalocyanine and Nc = naphthalocyanine. It was found that the S1(π,π*) state of NiNc(OBu)8 deactivated within the time resolution of the instrument (200 fs) to a vibrationally hot T1(π,π*) state. The quasidegeneracy of the S1(π,π*) and 3(dz2,dx2-y2) states allowed for fast intersystem crossing (ISC) to occur. After vibrational relaxation (ca. 2.5 ps), the T1(π,π*) converted rapidly (ca. 19 ps lifetime) and reversibly into the 3LMCT(π,dx2-y2) state. The equilibrium state, so generated, decayed to the ground state with a lifetime of ca. 500 ps. Peripheral substitution of the Pc ring significantly modified the photodeactivation mechanism of the S1(π,π*) by inducing substantial changes in the relative energies of the S1(π,π*), 3(dπ,dx2-y2), 3(dz2,dx2-y2), T1(π,π*), and 1,3LMCT(π,dx2-y2) excited states. The location of the Gouterman LUMOs and the unoccupied metal level (dx2-y2) with respect to the HOMO is crucial for the actual position of these states. In NiPc, the S1(π,π*) state underwent ultrafast (200 fs) ISC into a hot (d,d) state. Vibrational cooling (ca. 20 ps lifetime) resulted in a cold (dz2,dx2-y2) state, which repopulated the ground state with a 300 ps lifetime. In NiPc(OBu)8, the S1(π,π*) state deactivated through the 3(dz2,dx2-y2), which in turn converted to the 3LMCT(π,dx2-y2) state, which finally repopulated the ground state with a lifetime of 640 ps. Insufficient solubility of NiNc in noncoordinating solvents prevented transient absorption data from being obtained for this compound. However, the TDDFT calculations were used to make speculations about the photoproperties