What determines the optimal pharmacological treatment of atrial fibrillation? Insights from in silico trials in 800 virtual atria

The best pharmacological treatment for each atrial fibrillation (AF) patient is unclear. We aim to exploit AF simulations in 800 virtual atria to identify key patient characteristics that guide the optimal selection of anti-arrhythmic drugs. The virtual cohort considered variability in electrophysiology and low voltage areas (LVA) and was developed and validated against experimental and clinical data from ionic currents to ECG. AF sustained in 494 (62%) atria, with large inward rectifier K+ current (IK1) and Na+/K+ pump (INaK) densities (IK1 0.11 ± 0.03 vs. 0.07 ± 0.03 S mF–1; INaK 0.68 ± 0.15 vs. 0.38 ± 26 S mF–1; sustained vs. un-sustained AF). In severely remodelled left atrium, with LVA extensions of more than 40% in the posterior wall, higher IK1 (median density 0.12 ± 0.02 S mF–1) was required for AF maintenance, and rotors localized in healthy right atrium. For lower LVA extensions, rotors could also anchor to LVA, in atria presenting short refractoriness (median L-type Ca2+ current, ICaL, density 0.08 ± 0.03 S mF–1). This atrial refractoriness, modulated by ICaL and fast Na+ current (INa), determined pharmacological treatment success for both small and large LVA. Vernakalant was effective in atria presenting long refractoriness (median ICaL density 0.13 ± 0.05 S mF–1). For short refractoriness, atria with high INa (median density 8.92 ± 2.59 S mF–1) responded more favourably to amiodarone than flecainide, and the opposite was found in atria with low INa (median density 5.33 ± 1.41 S mF–1). In silico drug trials in 800 human atria identify inward currents as critical for optimal stratification of AF patient to pharmacological treatment and, together with the left atrial LVA extension, for accurately phenotyping AF dynamics

In Silico TRials guide optimal stratification of ATrIal FIbrillation patients to Catheter Ablation and pharmacological medicaTION: the i-STRATIFICATION study

Aims: Patients with persistent atrial fibrillation (AF) experience 50% recurrence despite pulmonary vein isolation (PVI), and no consensus is established for secondary treatments. The aim of our i-STRATIFICATION study is to provide evidence for stratifying patients with AF recurrence after PVI to optimal pharmacological and ablation therapies, through in silico trials. Methods and results: A cohort of 800 virtual patients, with variability in atrial anatomy, electrophysiology, and tissue structure (low-voltage areas, LVAs), was developed and validated against clinical data from ionic currents to electrocardiogram. Virtual patients presenting AF post-PVI underwent 12 secondary treatments. Sustained AF developed in 522 virtual patients after PVI. Second ablation procedures involving left atrial ablation alone showed 55% efficacy, only succeeding in the small right atria (<60 mL). When additional cavo-tricuspid isthmus ablation was considered, Marshall-PLAN sufficed (66% efficacy) for the small left atria (<90 mL). For the bigger left atria, a more aggressive ablation approach was required, such as anterior mitral line (75% efficacy) or posterior wall isolation plus mitral isthmus ablation (77% efficacy). Virtual patients with LVAs greatly benefited from LVA ablation in the left and right atria (100% efficacy). Conversely, in the absence of LVAs, synergistic ablation and pharmacotherapy could terminate AF. In the absence of ablation, the patient’s ionic current substrate modulated the response to antiarrhythmic drugs, being the inward currents critical for optimal stratification to amiodarone or vernakalant. Conclusion: In silico trials identify optimal strategies for AF treatment based on virtual patient characteristics, evidencing the power of human modelling and simulation as a clinical assisting tool

Changes in the investigation and management of suspected myocardial infarction and injury during COVID-19: a multi-centre study using routinely collected healthcare data

Objective: The COVID-19 pandemic was associated with a reduction in the incidence of myocardial infarction (MI) diagnosis, in part because patients were less likely to present to hospital. Whether changes in clinical decision making with respect to the investigation and management of patients with suspected MI also contributed to this phenomenon is unknown. Methods: Multicentre retrospective cohort study in three UK centres contributing data to the National Institute for Health Research Health Informatics Collaborative. Patients presenting to the Emergency Department (ED) of these centres between 1st January 2020 and 1st September 2020 were included. Three time epochs within this period were defined based on the course of the first wave of the COVID-19 pandemic: pre-pandemic (epoch 1), lockdown (epoch 2), post-lockdown (epoch 3). Results: During the study period, 10,670 unique patients attended the ED with chest pain or dyspnoea, of whom 6,928 were admitted. Despite fewer total ED attendances in epoch 2, patient presentations with dyspnoea were increased (p < 0.001), with greater likelihood of troponin testing in both chest pain (p = 0.001) and dyspnoea (p < 0.001). There was a dramatic reduction in elective and emergency cardiac procedures (both p < 0.001), and greater overall mortality of patients (p < 0.001), compared to the pre-pandemic period. Positive COVID-19 and/or troponin test results were associated with increased mortality (p < 0.001), though the temporal risk profile differed. Conclusions: The first wave of the COVID-19 pandemic was associated with significant changes not just in presentation, but also the investigation, management, and outcomes of patients presenting with suspected myocardial injury or MI

ART DEMONSTRATES THAT FOOTBALL IS METASTASIZED, AND GIVES IT REFUGE

U ovom se radu problemski analiziraju obilježja nogometa u hit-romanu Alena Bovića Metastaze (2006) te u dvjema kasnijim obradama tog književnog djela – u kazališnoj predstavi Metastaze i istoimenom igranom filmu. Otuda ideja da se ondje zatečen, devijantnim pojavama obilježen nogomet, koji više baš i nema puno dodirnih točaka s igrom koja mu leži u korijenima, nazove metastaziralim. Umjetnička se stvarnost pritom promatra kao korespondentna društvenoj stvarnosti pa se za takvo etiketiranje nogometa prepoznaju razlozi na objema razinama. Na temelju takvog pristupa Metastazama, ali i na osnovi prethodno ponuđenog komparativnog uvida u nogometnu tematiku u nekim drugim književnim, kazališnim i filmskim ostvarenjima u Hrvatskoj i izvan nje, postavlja se teza o umjetnosti kao dokazu metastaziralog nogometa. No, još je izazovnije utvrditi može li umjetnost istodobno poslužiti i kao utočište metastaziralom nogometu tako da se njome revitalizira ponajprije estetska, ali istodobno i etička dimenzija tog sporta. Iz tih pobuda argumentacija u ovome radu uključuje tekstove i autore u širokom rasponu od književne kritike, antropologije igara i sociologije sporta do semiotike, kulturalnih studija i estetike. U ovom se radu problemski analiziraju obilježja nogometa u hit-romanu Alena Bovića Metastaze (2006) te u dvjema kasnijim obradama tog književnog djela – u kazališnoj predstavi Metastaze i istoimenom igranom filmu. Otuda ideja da se ondje zatečen, devijantnim pojavama obilježen nogomet, koji više baš i nema puno dodirnih točaka s igrom koja mu leži u korijenima, nazove metastaziralim. Umjetnička se stvarnost pritom promatra kao korespondentna društvenoj stvarnosti pa se za takvo etiketiranje nogometa prepoznaju razlozi na objema razinama. Na temelju takvog pristupa Metastazama, ali i na osnovi prethodno ponuđenog komparativnog uvida u nogometnu tematiku u nekim drugim književnim, kazališnim i filmskim ostvarenjima u Hrvatskoj i izvan nje, postavlja se teza o umjetnosti kao dokazu metastaziralog nogometa. No, još je izazovnije utvrditi može li umjetnost istodobno poslužiti i kao utočište metastaziralom nogometu tako da se njome revitalizira ponajprije estetska, ali istodobno i etička dimenzija tog sporta. Iz tih pobuda argumentacija u ovome radu uključuje tekstove i autore u širokom rasponu od književne kritike, antropologije igara i sociologije sporta do semiotike, kulturalnih studija i estetike.This article presents an analysis of the characteristics of football as depicted in the bestselling novel Metastaze (Metastases) (2006) by Alen Bović and in its two subsequent adaptations – the play Metastaze (Metastases) directed by Boris Svrtan and the film Metastaze (Metastases) directed by Branko Schmidt. Football as it appears in these three pieces is metastasized: it is deviant and in fact undergoes so many significant changes that it no longer has much in common with the original game. Artistic reality is seen as corresponding to social reality, and reasons for the metastasized nature of football are found on both levels. Based on the proposed analysis of Metastaze and a comparative analysis of descriptions of football in other books, plays and films in Croatia and abroad a hypothesis is put forward whereby art offers evidence as to the metastasized nature of football. A greater challenge still is to establish whether art might, at the same time, provide refuge to the metastasized football, revitalizing its aesthetic and ethical dimension. Given the scope of these claims, the arguments in the article are based on a wide array of texts and authors ranging from literary criticism, anthropology of games and sociology of sport to semiotics, cultural studies and aesthetics

Adenosine stress CMR T1-mapping detects early microvascular dysfunction in patients with type 2 diabetes mellitus without obstructive coronary artery disease

Background Type 2 diabetes mellitus (T2DM) is associated with coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD). Cardiovascular magnetic resonance (CMR) T1-mapping at rest and during adenosine stress can assess coronary vascular reactivity. We hypothesised that the non-contrast T1 response to vasodilator stress will be altered in patients with T2DM without CAD compared to controls due to coronary microvascular dysfunction. Methods Thirty-one patients with T2DM and sixteen matched healthy controls underwent CMR (3 T) for cine, rest and adenosine stress non-contrast T1-mapping (ShMOLLI), first-pass perfusion and late gadolinium enhancement (LGE) imaging. Significant CAD (>50% coronary luminal stenosis) was excluded in all patients by coronary computed tomographic angiography. Results All subjects had normal left ventricular (LV) ejection and LV mass index, with no LGE. Myocardial perfusion reserve index (MPRI) was lower in T2DM than in controls (1.60 ± 0.44 vs 2.01 ± 0.42; p = 0.008). There was no difference in rest native T1 values (p = 0.59). During adenosine stress, T1 values increased significantly in both T2DM patients (from 1196 ± 32 ms to 1244 ± 44 ms, p < 0.001) and controls (from 1194 ± 26 ms to 1273 ± 44 ms, p < 0.001). T2DM patients showed blunted relative stress non-contrast T1 response (T2DM: ΔT1 = 4.1 ± 2.9% vs. controls: ΔT1 = 6.6 ± 2.6%, p = 0.007) due to a blunted maximal T1 during adenosine stress (T2DM 1244 ± 44 ms vs. controls 1273 ± 44 ms, p = 0.045). Conclusions Patients with well controlled T2DM, even in the absence of arterial hypertension and significant CAD, exhibit blunted maximal non-contrast T1 response during adenosine vasodilatory stress, likely reflecting coronary microvascular dysfunction. Adenosine stress and rest T1 mapping can detect subclinical abnormalities of the coronary microvasculature, without the need for gadolinium contrast agents. CMR may identify early features of the diabetic heart phenotype and subclinical cardiac risk markers in patients with T2DM, providing an opportunity for early therapeutic intervention