SummaryBackground Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest antiischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT).

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic has affected more than 100 million people and clinics are being established for diagnosing and treating lingering symptoms, so called long-COVID. A key concern are neurological and long-term cognitive complications. At the same time, the prevalence and nature of the cognitive sequalae of COVID-19 are unclear. The present study aimed to investigate the frequency, pattern and severity of cognitive impairments 3-4 months after COVID-19 hospital discharge, their relation to subjective cognitive complaints, quality of life and illness variables. We recruited patients at their follow-up visit at the respiratory outpatient clinic, Copenhagen University Hospital, Bispebjerg, approximately four months after hospitalisation with COVID-19. Patients underwent pulmonary, functional and cognitive assessments. Twenty-nine patients were included. The percentage of patients with clinically significant cognitive impairment ranged from 59-65% depending on the applied cut-off for clinical relevance of cognitive impairment, with verbal learning and executive functions being most affected. Objective cognitive impairment scaled with subjective cognitive complaints, lower work function and poorer quality of life. Cognitive impairments were associated with d-dimer levels during acute illness and residual pulmonary dysfunction. In conclusion, these findings provide new evidence for frequent cognitive sequelae of COVID-19 and indicate an association with the severity of the lung affection and potentially restricted cerebral oxygen delivery. Further, the associations with quality of life and functioning call for systematic cognitive screening of patients after recovery from severe COVID-19 illness and implementation of targeted treatments for patients with persistent cognitive impairments.

BackgroundThere is emerging data of long-term effects of COVID-19 comprising a diversity of symptoms. The aim of this study was to systematically describe and measure pulmonary and extra- pulmonary post COVID-19 complications in relation to acute COVID-19 severity.MethodsPatients attending a standard of care 3-months post-hospitalisation follow-up visit, and those referred by their general practitioner because of persistent post-COVID-19 symptoms were included. Patients underwent symptomatic, quality of life, pulmonary (lung function and HRCT), cardiac (high resolution ECG), physical (1-MSTST, handgrip strength, CPET) and cognitive evaluations.ResultsAll 34 hospitalised and 22 out of 23 non-hospitalised patients had≥1 complaint or abnormal finding at follow-up. 67% of patients were symptomatic (MRC ≥2 or CAT ≥10), with no difference between hospitalised versus non-hospitalised patients. Pulmonary function (FEV1 or DLCO) <80% of predicted) was impaired in 68% of patients. DLCO was significantly lower in those hospitalised compared to non-hospitalised (70.1±18.0 versus 80.2±11.2% predicted, p=0.02). 53% had an abnormal HRCT (predominantly groundglass opacities) with higher composite CT-scores in hospitalised versus non-hospitalised patients (2.3 [0.1, 4.8] and 0.0 [0.0, 0.3], p<0.001). 1-MSTST was below the 25th percentile in almost half of patients, but no signs of cardiac dysfunction were found. Cognitive impairments were present in 59–66% of hospitalised and 31–44% of non-hospitalised patients (p=0.08).ConclusionThree months after COVID-19 infection, patients were still symptomatic and demonstrated objective respiratory, functional, radiological and cognitive abnormalities, which were more prominent in hospitalised patients. Our study underlines the importance of multidimensional management strategies in these patients.

Cellulose nanocrystals (CNCs) are topical in materials science but their full potential is yet to be fulfilled because of bottlenecks in the production: the process consumes huge amounts of water, recycling the strong acid catalyst is difficult, and purification steps are cumbersome, particularly with lengthy dialysis. Production of CNCs with HCl vapour overcomes many of these difficulties but the dispersion of CNCs from the already hydrolysed fibre matrix is a formidable challenge. This study is a fundamental effort to explore very basic means to facilitate CNC dispersion from cotton linter fibres (filter paper), hydrolysed to levelling off degree of polymerization by HCl vapour. The introduction of carboxylic groups on the cellulose crystal surface proved the most efficient method to alleviate dispersion with good yields (ca. 50%) and a provisional possibility to tune the CNC length. By contrast, attempts to directly disperse untreated hydrolysed fibres in various organic solvents and aqueous surfactant solutions were unsuccessful. The results showed that hydrolysis of native cellulose fibres by HCl vapour is indeed a viable method for producing CNCs but it has more potential as a pre-treatment step rather than a full-fledged process on its own.

Ventricular arrhythmia and subsequent sudden cardiac death (SCD) due to acute myocardial infarction (AMI) is one of the most frequent causes of death in humans. Lethal ventricular arrhythmias like ventricular fibrillation (VF) prior to hospitalization have been reported to occur in more than 10% of all AMI cases and survival in these patients is poor. Identification of risk factors and mechanisms for VF following AMI as well as implementing new risk stratification models and therapeutic approaches is therefore an important step to reduce mortality in people with high cardiovascular risk. Studying spontaneous VF following AMI in humans is challenging as it often occurs unexpectedly in a low risk subgroup. Large animal models of AMI can help to bridge this knowledge gap and are utilized to investigate occurrence of arrhythmias, involved mechanisms and therapeutic options. Comparable anatomy and physiology allow for this translational approach. Through experimental focus, using state-of-the-art technologies, including refined electrical mapping equipment and novel pharmacological investigations, valuable insights into arrhythmia mechanisms and possible interventions for arrhythmia-induced SCD during the early phase of AMI are now beginning to emerge. This review describes large experimental animal models of AMI with focus on first AMI-associated ventricular arrhythmias. In this context, epidemiology of first AMI, arrhythmogenic mechanisms and various potential therapeutic pharmacological targets will be discussed.

Background and Purpose Inhibition of the G‐protein gated ACh‐activated inward rectifier potassium current, IK,ACh may be an effective atrial selective treatment strategy for atrial fibrillation (AF). Therefore, the anti‐arrhythmic and electrophysiological properties of a novel putatively potent and highly specific IK,ACh inhibitor, XAF‐1407 (3‐methyl‐1‐[5‐phenyl‐4‐[4‐(2‐pyrrolidin‐1‐ylethoxymethyl)‐1‐piperidyl]thieno[2,3‐d]pyrimidin‐6‐yl]azetidin‐3‐ol), were characterised for the first time in vitro and investigated in horses with persistent AF. Experimental Approach The pharmacological ion channel profile of XAF‐1407 was investigated using cell lines expressing relevant ion channels. In addition, eleven horses were implanted with implantable cardioverter defibrillators enabling atrial tachypacing into self‐sustained AF. The electrophysiological effects of XAF‐1407 were investigated after serial cardioversions over a period of 1 month. Cardioversion success, drug‐induced changes of atrial tissue refractoriness, and ventricular electrophysiology were assessed at baseline (day 0) and days 3, 5, 11, 17, and 29 after AF induction. Key Results XAF‐1407 potently and selectively inhibited Kir3.1/3.4 and Kir3.4/3.4, underlying the IK,ACh current. XAF‐1407 treatment in horses prolonged atrial effective refractory period as well as decreased atrial fibrillatory rate significantly (~20%) and successfully cardioverted AF, although with a decreasing efficacy over time. XAF‐1407 shortened atrioventricular‐nodal refractoriness, without effect on QRS duration. QTc prolongation (4%) within 15 min of drug infusion was observed, however, without any evidence of ventricular arrhythmia. Conclusion and Implications XAF‐1407 efficiently cardioverted sustained tachypacing‐induced AF of short duration in horses without notable side effects. This supports IK,ACh inhibition as a potentially safe treatment of paroxysmal AF in horses, suggesting potential clinical value for other species including humans.

BackgroundLarge animal models are important in atrial fibrillation (AF) research, as they can be used to study the pathophysiology of AF and new therapeutic approaches. Unlike other animal models, horses spontaneously develop AF and could therefore serve as a bona fide model in AF research. We therefore aimed to study the electrical, functional and structural remodelling caused by chronic AF in a horse model.MethodNine female horses were included in the study, with six horses tachypaced into self-sustained AF and three that served as a time-matched sham-operated control group. Acceleration in atrial fibrillatory rate (AFR), changes in electrocardiographic and echocardiographic variables and response to medical treatment (flecainide 2 mg/kg) were recorded over a period of 2 months. At the end of the study, changes in ion channel expression and fibrosis were measured and compared between the two groups.ResultsAFR increased from 299 ± 33 fibrillations per minute (fpm) to 376 ± 12 fpm (p < 0.05) and atrial function (active left atrial fractional area change) decreased significantly during the study (p < 0.05). No changes were observed in heart rate or ventricular function. The AF group had more atrial fibrosis compared to the control group (p < 0.05). No differences in ion channel expression were observed.ConclusionHorses with induced AF show signs of atrial remodelling that are similar to humans and other animal models.

Due to the evolution of transportable ECLS systems and percutaneous techniques implantation on scene is feasible. Extracorporeal life support may serve as a bridge-to-decision and bridge-to-treatment device. Neurological evaluation before ventricular assist device implantation and PCI under stable conditions are possible. Despite substantial mortality, ECLS implantation in selected patients by an experienced team offers additional support to conventional therapy as well as CPR and allows survival in patients that otherwise most likely would have died. This concept has to be implemented in cardiac survival networks in the future.