Patient Acceptance and Adherence to the COMPASS Trial Drug Recommendations Following Symptomatic Carotid Endarterectomy.

BACKGROUND: The COMPASS trial demonstrated that in patients with atherosclerotic diseases, low-dose rivaroxaban and aspirin provides greater protection against subsequent major adverse cardiovascular events (MACEs) than mono-antiplatelet therapy (MAPT) alone. Drug acceptance and adherence maximizes this benefit. We have assessed drug acceptance and adherence to the COMPASS drug regime in patients following carotid endarterectomy (CEA) for symptomatic carotid artery stenosis. METHODS: Following CEA, the views of 63 patients on the COMPASS drug regime were assessed using the Beliefs about Medicine Questionnaire and drug adherence was determined using the Sidorkiewicz scoring system. These views were compared with those of 54 patients on MAPT. Side effects (bleeding and drug reactions) and new MACE were recorded. RESULTS: Post-CEA patients on the COMPASS drug regimen had strong positive views on the necessity to take these drugs (necessity scale 19.6 ± 3.6). Although there were some concerns about the COMPASS drug regimen, these were not strongly held (concern cscale 11.8 ± 4.9) and the necessity-concerns differential was positive (7.8 ± 6.2). The Drug Adherence Score was "High" to "Good" (level of drug adherence 1.7 ± 1.0). The Beliefs about Medicine Questionnaire scales and Drug Adherence Score of post-CEA patients on the COMPASS drug regimen were similar to those on MAPT. The incidence of post-CEA MACE and side effects were similar for those on the COMPASS drug regimen and MAPT. CONCLUSIONS: Post-CEA patients on the COMPASS drug regimen had positive views on taking the drugs and drug adherence was high. We did not identify any patient-related barriers to the use of the COMPASS drug regimen to further reduce cardiovascular events.

Validation of a deep-learning-based retinal biomarker (Reti-CVD) in the prediction of cardiovascular disease: data from UK Biobank.

BACKGROUND: Currently in the United Kingdom, cardiovascular disease (CVD) risk assessment is based on the QRISK3 score, in which 10% 10-year CVD risk indicates clinical intervention. However, this benchmark has limited efficacy in clinical practice and the need for a more simple, non-invasive risk stratification tool is necessary. Retinal photography is becoming increasingly acceptable as a non-invasive imaging tool for CVD. Previously, we developed a novel CVD risk stratification system based on retinal photographs predicting future CVD risk. This study aims to further validate our biomarker, Reti-CVD, (1) to detect risk group of ≥ 10% in 10-year CVD risk and (2) enhance risk assessment in individuals with QRISK3 of 7.5-10% (termed as borderline-QRISK3 group) using the UK Biobank. METHODS: Reti-CVD scores were calculated and stratified into three risk groups based on optimized cut-off values from the UK Biobank. We used Cox proportional-hazards models to evaluate the ability of Reti-CVD to predict CVD events in the general population. C-statistics was used to assess the prognostic value of adding Reti-CVD to QRISK3 in borderline-QRISK3 group and three vulnerable subgroups. RESULTS: Among 48,260 participants with no history of CVD, 6.3% had CVD events during the 11-year follow-up. Reti-CVD was associated with an increased risk of CVD (adjusted hazard ratio [HR] 1.41; 95% confidence interval [CI], 1.30-1.52) with a 13.1% (95% CI, 11.7-14.6%) 10-year CVD risk in Reti-CVD-high-risk group. The 10-year CVD risk of the borderline-QRISK3 group was greater than 10% in Reti-CVD-high-risk group (11.5% in non-statin cohort [n = 45,473], 11.5% in stage 1 hypertension cohort [n = 11,966], and 14.2% in middle-aged cohort [n = 38,941]). C statistics increased by 0.014 (0.010-0.017) in non-statin cohort, 0.013 (0.007-0.019) in stage 1 hypertension cohort, and 0.023 (0.018-0.029) in middle-aged cohort for CVD event prediction after adding Reti-CVD to QRISK3. CONCLUSIONS: Reti-CVD has the potential to identify individuals with ≥ 10% 10-year CVD risk who are likely to benefit from earlier preventative CVD interventions. For borderline-QRISK3 individuals with 10-year CVD risk between 7.5 and 10%, Reti-CVD could be used as a risk enhancer tool to help improve discernment accuracy, especially in adult groups that may be pre-disposed to CVD.

Perceived vs. objective frailty in patients with atrial fibrillation and impact on anticoagulant dosing: an ETNA-AF-Europe sub-analysis.

AIMS: Frailty is common in patients with atrial fibrillation (AF), with possible impact on therapies and outcomes. However, definitions of frailty are variable, and may not overlap with frailty perception among physicians. We evaluated the prevalence of frailty as perceived by enrolling physicians in the Edoxaban Treatment in Routine Clinical Practice for Patients With Non-Valvular AF (ETNA-AF)-Europe registry (NCT02944019), and compared it with an objective frailty assessment. METHODS AND RESULTS: ETNA-AF-Europe is a prospective, multi-centre, post-authorization, observational study. There we assessed the presence of frailty according to (i) a binary subjective investigators' judgement and (ii) an objective measure, the Modified Frailty Index. Baseline data on frailty were available in 13 621/13 980 patients. Prevalence of perceived frailty was 10.6%, with high variability among participating countries and healthcare settings (range 5.9-19.6%). Conversely, only 5.0% of patients had objective frailty, with minimal variability (range 4.5-6.7%); and only <1% of patients were identified as frail by both approaches. Compared with non-frailty-perceived, perceived frail patients were older, more frequently female, and with lower body weight; conversely, objectively frail patients had more comorbidities. Non-recommended edoxaban dose regimens were more frequently prescribed in both frail patient categories. CONCLUSIONS: Physicians' perception of frailty in AF patients is variable, mainly driven by age, sex, and weight, and quite different compared with the results of an objective frailty assessment. Whatever the approach, frailty appears to be associated with non-recommended anticoagulant dosages. Whether this apparent inappropriateness influences hard outcomes remains to be assessed.

Characteristics of patients initiated on edoxaban in Europe: baseline data from edoxaban treatment in routine clinical practice for patients with atrial fibrillation (AF) in Europe (ETNA-AF-Europe).

BACKGROUND: Non-vitamin K antagonist (VKA) oral anticoagulants (NOACs) have substantially improved anticoagulation therapy for prevention of stroke and systemic embolism in patients with atrial fibrillation (AF). The available routine care data have demonstrated the safety of different NOACs; however, such data for edoxaban are scarce. Here, we report baseline characteristics of 13,638 edoxaban-treated patients with AF enrolled between November 2016 and February 2018. METHODS: ETNA-AF-Europe is a multinational, multi-centre, post-authorisation, observational study conducted in 825 sites in 10 European countries. Patients will be followed up for four years. RESULTS: Overall, 13,980 patients were enrolled of which 342 patients were excluded from the analysis. Mean patient age was 73.6 years with an average creatinine clearance of 69.4 mL/min. 56.6% were male. The calculated CHA2DS2-VASc and HAS-BLED mean scores were 3.1 and 2.6, respectively. Overall, 3.3, 14.6 and 82.0% of patients had low (CHA2DS2-VASc = 0), intermediate (CHA2DS2-VASc = 1) and high (CHA2DS2-VASc≥2) risks of stroke, respectively. High-risk patients (those with prior stroke, prior major bleeding, prior intracranial bleed or CHA2DS2-VASc ≥4) comprised 38.4% of the overall population. For 75.1% of patients edoxaban was their first anticoagulant prescription, whilst 16.9% switched from a VKA and 8.0% from another NOAC. A total of 23.4% of patients in ETNA-AF-Europe received the reduced dose of edoxaban 30 mg. Overall, 83.8% of patients received an edoxaban dose in line with the criteria outlined in the label. CONCLUSION: Edoxaban was predominantly initiated in older, often anticoagulation-naïve, unselected European patients with AF, with a good overall adherence to the approved label. TRIAL REGISTRATION: NCT02944019; Date of registration: October 24, 2016.

Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for cardiogenic pulmonary oedema.

BACKGROUND: Non-invasive positive pressure ventilation (NPPV) has been used to treat respiratory distress due to acute cardiogenic pulmonary oedema (ACPE). We performed a systematic review and meta-analysis update on NPPV for adults presenting with ACPE. OBJECTIVES: To evaluate the safety and effectiveness of NPPV compared to standard medical care (SMC) for adults with ACPE. The primary outcome was hospital mortality. Important secondary outcomes were endotracheal intubation, treatment intolerance, hospital and intensive care unit length of stay, rates of acute myocardial infarction, and adverse event rates. SEARCH METHODS: We searched CENTRAL (CRS Web, 20 September 2018), MEDLINE (Ovid, 1946 to 19 September 2018), Embase (Ovid, 1974 to 19 September 2018), CINAHL Plus (EBSCO, 1937 to 19 September 2018), LILACS, WHO ICTRP, and clinicaltrials.gov. We also reviewed reference lists of included studies. We applied no language restrictions. SELECTION CRITERIA: We included blinded or unblinded randomised controlled trials in adults with ACPE. Participants had to be randomised to NPPV (continuous positive airway pressure (CPAP) or bilevel NPPV) plus standard medical care (SMC) compared with SMC alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected articles for inclusion. We extracted data with a standardised data collection form. We evaluated the risks of bias of each study using the Cochrane 'Risk of bias' tool. We assessed evidence quality for each outcome using the GRADE recommendations. MAIN RESULTS: We included 24 studies (2664 participants) of adult participants (older than 18 years of age) with respiratory distress due to ACPE, not requiring immediate mechanical ventilation. People with ACPE presented either to an Emergency Department or were inpatients. ACPE treatment was provided in an intensive care or Emergency Department setting. There was a median follow-up of 13 days for hospital mortality, one day for endotracheal intubation, and three days for acute myocardial infarction. Compared with SMC, NPPV may reduce hospital mortality (risk ratio (RR) 0.65, 95% confidence interval (CI) 0.51 to 0.82; participants = 2484; studies = 21; I2 = 6%; low quality of evidence) with a number needed to treat for an additional beneficial outcome (NNTB) of 17 (NNTB 12 to 32). NPPV probably reduces endotracheal intubation rates (RR 0.49, 95% CI 0.38 to 0.62; participants = 2449; studies = 20; I2 = 0%; moderate quality of evidence) with a NNTB of 13 (NNTB 11 to 18). There is probably little or no difference in acute myocardial infarction (AMI) incidence with NPPV compared to SMC for ACPE (RR 1.03, 95% CI 0.91 to 1.16; participants = 1313; studies = 5; I2 = 0%; moderate quality of evidence). We are uncertain as to whether NPPV increases hospital length of stay (mean difference (MD) -0.31 days, 95% CI -1.23 to 0.61; participants = 1714; studies = 11; I2 = 55%; very low quality of evidence). Adverse events were generally similar between NPPV and SMC groups, but evidence was of low quality. AUTHORS' CONCLUSIONS: Our review provides support for continued clinical application of NPPV for ACPE, to improve outcomes such as hospital mortality and intubation rates. NPPV is a safe intervention with similar adverse event rates to SMC alone. Additional research is needed to determine if specific subgroups of people with ACPE have greater benefit of NPPV compared to SMC. Future research should explore the benefit of NPPV for ACPE patients with hypercapnia.

The value of maintaining normokalaemia and enabling RAASi therapy in chronic kidney disease.

BACKGROUND: People with chronic kidney disease (CKD) are at an increased risk of developing hyperkalaemia due to their declining kidney function. In addition, these patients are often required to reduce or discontinue guideline-recommended renin-angiotensin-aldosterone system inhibitor (RAASi) therapy due to increased risk of hyperkalaemia. This original research developed a model to quantify the health and economic benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD. METHODS: A patient-level simulation model was designed to fully characterise the natural history of CKD over a lifetime horizon, and predict the associations between serum potassium levels, RAASi use and long-term outcomes based on published literature. The clinical and economic benefits of maintaining sustained potassium levels and therefore avoiding RAASi discontinuation in CKD patients were demonstrated using illustrative, sensitivity and scenario analyses. RESULTS: Internal and external validation exercises confirmed the predictive capability of the model. Sustained potassium management and ongoing RAASi therapy were associated with longer life expectancy (+ 2.36 years), delayed onset of end stage renal disease (+ 5.4 years), quality-adjusted life-year gains (+ 1.02 QALYs), cost savings (£3135) and associated net monetary benefit (£23,446 at £20,000 per QALY gained) compared to an absence of RAASi to prevent hyperkalaemia. CONCLUSION: This model represents a novel approach to predicting the long-term benefits of maintaining normokalaemia and enabling optimal RAASi therapy in patients with CKD, irrespective of the strategy used to achieve this target, which may support decision making in healthcare.

Serum potassium as a predictor of adverse clinical outcomes in patients with chronic kidney disease: new risk equations using the UK clinical practice research datalink.

BACKGROUND: To address a current paucity of European data, this study developed equations to predict risks of mortality, major adverse cardiac events (MACE) and renin angiotensin-aldosterone system inhibitor (RAASi) discontinuation using time-varying serum potassium and other covariates, in a UK cohort of chronic kidney disease (CKD) patients. METHODS: This was a retrospective observational study of adult CKD patients listed on the Clinical Practice Research Datalink, with a first record of CKD (stage 3a-5, pre-dialysis) between 2006 and 2015. Patients with heart failure at index were excluded. Risk equations developed using Poisson Generalized Estimating Equations were utilised to estimate adjusted incident rate ratios (IRRs) between serum potassium and adverse outcomes, and identify other predictive clinical factors. RESULTS: Among 191,964 eligible CKD patients, 86,691 (45.16%), 30,629 (15.96%) and 9440 (4.92%) experienced at least one hyperkalaemia episode, when defined using serum potassium concentrations 5.0-< 5.5 mmol/L, 5.5-< 6.0 mmol/L and ≥ 6.0 mmol/L, respectively. Relative to the reference category (4.5 to < 5.0 mmol/L), adjusted IRRs for mortality and MACE exhibited U-shaped associations with serum potassium, with age being the most important predictor of both outcomes (P < 0.0001). A J-shaped association between serum potassium and RAASi discontinuation was observed; estimated glomerular filtration rate was most predictive of RAASi discontinuation (P < 0.0001). CONCLUSIONS: Hyperkalaemia was associated with increased mortality and RAASi discontinuation risk. These risk equations represent a valuable tool to predict clinical outcomes among CKD patients; and identify those likely to benefit from strategies that treat hyperkalaemia, prevent RAASi discontinuation, and effectively manage serum potassium levels.

Comparison of Digital 12-Lead ECG and Digital 12-Lead Holter ECG Recordings in Healthy Male Subjects: Results from a Randomized, Double-Blinded, Placebo-Controlled Clinical Trial.

BACKGROUND: Electrocardiogram (ECG) variability is greatly affected by the ECG recording method. This study aims to compare Holter and standard ECG recording methods in terms of central locations and variations of ECG data. METHODS: We used the ECG data from a double-blinded, placebo-controlled, randomized clinical trial and used a mixed model approach to assess the agreement between two methods in central locations and variations of eight ECG parameters (Heart Rate, PR, QRS, QT, RR, QTcB, QTcF, and QTcI intervals). RESULTS: A total of 34 heathy male subjects with mean age of 25.7 ± 4.78 years were randomized to receive either active drug or placebo. Digital 12-lead ECG and digital 12-lead Holter ECG recordings were performed to assess ECG variability. There are no significant differences in least square mean between the Holter and the standard method for all ECG parameters. The total variance is consistently higher for the Holter method than the standard method for all ECG parameters except for QRS. The intraclass correlation coefficient (ICC) values for the Holter method are consistently lower than those for the standard method for all ECG parameters except for QRS, in particular, the ICC for QTcF is reduced from 0.86 for the standard method to 0.67 for the Holter method. CONCLUSIONS: This study suggests that Holter ECGs recorded in a controlled environment are not significantly different but more variable than those from the standard method.

Development of delivery indicators and delivery enablers for cardiovascular disease in the UK: a modified Delphi study.

INTRODUCTION: Standards to define and measure quality in healthcare for cardiovascular disease risk reduction and secondary prevention are available, but there is a paucity of indicators that could serve as facilitators of structural change at a system level. This research study aimed to develop a range of delivery indicators to help cardiac clinical networks assess delivery of and progress towards cardiovascular disease objectives. METHODS: This study used an adapted version of the European Society of Cardiology's four-step process for the development of quality indicators. The four steps in this study were as follows: identify critical factors of enablement, construct a list of candidate indicators, select a final set of indicators and assess availability of national data for each indicator. In this iterative process, a core project group of six members was supported by a wider review group of 21 people from the National Health Service (NHS) clinical and management personnel database. RESULTS: The core project group identified six relevant cardiovascular disease priorities in the NHS Long Term Plan and used an iterative process to identify 21 critical factors that impact on their implementation. A total of 57 potential indicators that could be measures of implementation were developed. The core project group agreed on a set of 38 candidate indicators that were circulated to the review group for rating. Based on these scores, the core project group excluded 5 indicators to arrive at a final set of 33 delivery indicators. National datasets were available for 22 of the final indicators, which were designated as delivery indicators. The remaining 11, for which national datasets were not available but locally available datasets could be used, were designated as delivery enablers. CONCLUSION: The suite of delivery indicators and delivery enablers for cardiovascular disease could allow a more focused evaluation of factors that impact on delivery of healthcare for cardiovascular disease.

Behavioral Science: Enhancing Our Approach to the Development of Effective Additional Risk Minimization Strategies.

Additional risk minimization strategies may be required to assure a positive benefit-risk balance for some therapeutic products associated with serious adverse drug reactions/risks of use, without which these products may be otherwise unavailable to patients. The goals of risk minimization strategies are often fundamentally to influence the behavior of healthcare professionals (HCPs) and/or patients and can include appropriate patient selection, provision of education and counselling, appropriate medication use, adverse drug reaction monitoring, and adoption of other elements to assure safe use, such as pregnancy prevention. Current approaches to additional risk minimization strategy development rely heavily on information provision, without full consideration of the contextual factors and multi-level influences on patient and HCP behaviors that impact adoption and long-term adherence to these interventions. Application of evidence-based behavioral science methods are urgently needed to improve the quality and effectiveness of these strategies. Evidence from the fields of adherence, health promotion, and drug utilization research underscores the value and necessity for using established behavioral science frameworks and methods if we are to achieve clinical safety goals for patients. The current paper aims to enhance additional risk minimization strategy development and effectiveness by considering how a behavioral science approach can be applied, drawing from evidence in understanding of engagement with pharmaceutical medicines as well as wider public health interventions for patients and HCPs.

Long-term effectiveness and safety of edoxaban in patients with atrial fibrillation: 4-year data from the ETNA-AF-Europe study.

BACKGROUND: To assess long-term effectiveness and safety of edoxaban in Europe. METHODS AND RESULTS: ETNA-AF-Europe, a prospective, multinational, multi-centre, post-authorisation, observational study was conducted in agreement with the European Medicines Agency. The primary and secondary objectives assessed real-world safety (including bleeding and deaths) and effectiveness (including stroke, systemic embolic events and clinical edoxaban use), respectively. Median (interquartile range) age of the 13,164 patients was 75.0 (68.0-80.0) years; CHA2DS2-VASc and HAS-BLED scores were 3.0 (2.0-4.0) and 2.0 (1.0-2.0), respectively. Follow-up duration was 3.98 (3.21-4.05) years. Patients on edoxaban 30 mg (n = 3042) at baseline were older (80.0 vs 73.0 years), more likely assessed as frail by investigators (27.0% vs 6.6%) and had more comorbidities than those on edoxaban 60 mg (n = 9617; missing dosing information for n = 505). Annualised event rates of all-cause and cardiovascular death in the overall population, edoxaban 60 mg and edoxaban 30 mg groups were 4.1%, 2.8% and 8.4%, and 1.0%, 0.7% and 2.0%, respectively. Annualised rates of stroke were relatively constant throughout the follow-up, transient ischaemic attack and systemic embolism were < 1% in the overall population. Rates of any major and major gastrointestinal bleeding were low, with slightly higher rates for edoxaban 30 vs 60 mg group. Intracranial haemorrhage was uncommon (0.2%). CONCLUSIONS: In European patients with AF, long-term therapy with edoxaban is associated with low and relatively constant annualised rates of stroke and major bleeding. Differences in outcomes between the two approved doses are attributable to differences in clinical characteristics.

Postoperative B-type natriuretic peptide for prediction of major cardiac events in patients undergoing noncardiac surgery: systematic review and individual patient meta-analysis.

BACKGROUND: It is unclear whether postoperative B-type natriuretic peptides (i.e., BNP and N-terminal proBNP) can predict cardiovascular complications in noncardiac surgery. METHODS: The authors undertook a systematic review and individual patient data meta-analysis to determine whether postoperative BNPs predict postoperative cardiovascular complications at 30 and 180 days or more. RESULTS: The authors identified 18 eligible studies (n = 2,051). For the primary outcome of 30-day mortality or nonfatal myocardial infarction, BNP of 245 pg/ml had an area under the curve of 0.71 (95% CI, 0.64-0.78), and N-terminal proBNP of 718 pg/ml had an area under the curve of 0.80 (95% CI, 0.77-0.84). These thresholds independently predicted 30-day mortality or nonfatal myocardial infarction (adjusted odds ratio [AOR] 4.5; 95% CI, 2.74-7.4; P < 0.001), mortality (AOR, 4.2; 95% CI, 2.29-7.69; P < 0.001), cardiac mortality (AOR, 9.4; 95% CI, 0.32-254.34; P < 0.001), and cardiac failure (AOR, 18.5; 95% CI, 4.55-75.29; P < 0.001). For greater than or equal to 180-day outcomes, natriuretic peptides independently predicted mortality or nonfatal myocardial infarction (AOR, 3.3; 95% CI, 2.58-4.3; P < 0.001), mortality (AOR, 2.2; 95% CI, 1.67-86; P < 0.001), cardiac mortality (AOR, 2.1; 95% CI, 0.05-1,385.17; P < 0.001), and cardiac failure (AOR, 3.5; 95% CI, 1.0-9.34; P = 0.022). Patients with BNP values of 0-250, greater than 250-400, and greater than 400 pg/ml suffered the primary outcome at a rate of 6.6, 15.7, and 29.5%, respectively. Patients with N-terminal proBNP values of 0-300, greater than 300-900, and greater than 900 pg/ml suffered the primary outcome at a rate of 1.8, 8.7, and 27%, respectively. CONCLUSIONS: Increased postoperative BNPs are independently associated with adverse cardiac events after noncardiac surgery.

Comparison of standard and modified transvenous techniques for complex pacemaker lead extractions in the context of cardiac implantable electronic device-related infections: a 10-year experience.

AIMS: Complete lead extraction of cardiac implantable electronic devices (CIED) for device-related infections remains a complex procedure for chronically implantated leads. We present data from a single-centre registry of consecutive patients with extractions over 10 years. METHOD AND RESULTS: Patients were identified from the centre's electronic database with CIED-related infections who underwent lead extraction using either the standard technique and equipment or a modified innovative transvenous lead technique extraction using an ablation catheter. Of 151 patients with CIED-related infections, not responding to simple manual traction to effect lead extraction, average age 65 ± 8 years (range 45-82), 64% being male, 75 underwent standard (S) extraction, and 76 underwent modified (M) extraction. Procedural, lead extraction, and fluoroscopy exposure times with S and M methods, respectively, were 65 ± 14 vs. 52 ± 6 min (P < 0.01), 56 ± 12 vs. 36 ± 8 min (P < 0.001), and 48 ± 12 vs. 31 ± 7 min (P < 0.001). Retrieval rates were numerically lower with the standard technique at 92 vs. 96% but did not achieve significance, with respective complication rates of 6.7 and 5.3%. CONCLUSION: In our single-centre study, a modified extraction technique to retrieve leads for infections of CIEDs using a steerable ablation catheter has improved procedural parameters over the standard technique, without compromising clinical lead extraction success rates. This may be a promising approach for a future, prospective trial.

Patient perspective on the management of atrial fibrillation in five European countries.

BACKGROUND: Long-term management of chronic conditions, such as atrial fibrillation (AF), require frequent interactions with the healthcare systems. The multinational EUropean Patient Survey in Atrial Fibrillation (EUPS-AF) was conducted to investigate patient satisfaction with AF management in different of five European healthcare systems at a time of changing treatment paradigms for stroke prophylaxis, prior to the advent of newer oral anticoagulants. METHODS: Adults (>18 years) were recruited at random from the total populations of France, Germany, Italy, Spain and the UK using a randomized telephone dialling system. At least 300 respondents per country reporting to have a diagnosis of AF or receiving oral anticoagulation therapy for suspected AF or to have a heart rhythm disturbance completed a structured telephone interview. RESULTS: Most respondents were satisfied with their treatment for AF over the previous 12 months, with 85.5% (n = 1289) rating their care as good or better. Suboptimal clinical practices, however, were identified in several key areas. Coordination of primary and secondary care and a lack of patient engagement and support were particular issues, especially for those patients likely to have extensive contact with their healthcare system. CONCLUSIONS: In the context of Europe-wide guidelines for management of AF, most patients with AF were satisfied with their care, but for a greater proportion of patients, some aspects are unsatisfactory. Patient-centred surveys, such as the EUPS-AF, are crucial for understanding the factors that contribute to patient satisfaction and compliance with long-term treatment for chronic conditions.

Clinical outcomes by supplemental oxygen use in remdesivir-treated, hospitalised adults with COVID-19.

BACKGROUND: Clinical trials show different effects of remdesivir on clinical outcomes relative to COVID-19 severity at hospital admission; in Europe, there are few real-world data. METHODS: A multicentre, multinational retrospective cohort study in adult patients hospitalised with PCR-confirmed COVID-19 was conducted to understand remdesivir clinical use in different countries and to describe outcomes for patients receiving remdesivir stratified by oxygen use. Primary endpoints were all-cause mortality at day 28 and hospitalisation duration. Patients were categorised by baseline disease severity: no supplemental oxygen (NSO); low flow oxygen ≤ 6 litres (l)/minute (LFO); high flow oxygen > 6 l/minute (HFO). RESULTS: Four hundred and forty-eight (448) patients (72 [16.1%] HFO; 295 [65.8%] LFO; 81 (18.1%] NSO) were included; median age was 65 years and 64% were male. Mortality was higher in patients on HFO (rate 23.6%) compared to LFO (10.2%; p = 0.001) or NSO (6.2%; p = 0.002). Duration of hospitalisation was longer in patients on HFO (13 days) compared to LFO (9 days; p = 0.003) and NSO (9 days; p = 0.021). Patients who initiated remdesivir ≥ 2 days compared to within a day of hospitalisation had a 4.2 times higher risk of death, irrespective of age, sex, comorbidities, and oxygen support at baseline. Requirement for mechanical ventilation/ECMO and readmission within 28 days of discharge was similar across groups. Remdesivir use and outcomes differed by country. CONCLUSIONS: A higher mortality rate and duration of hospitalisation was seen in remdesivir-treated COVID-19 patients on HFO compared to LFO and NSO. Initiation of remdesivir upon admission as opposed to delayed initiation has a mortality benefit. CLINICAL TRIALS REGISTRATION: NCT04847622.

Cardiovascular disease risk assessment using a deep-learning-based retinal biomarker: a comparison with existing risk scores.

Aims: This study aims to evaluate the ability of a deep-learning-based cardiovascular disease (CVD) retinal biomarker, Reti-CVD, to identify individuals with intermediate- and high-risk for CVD. Methods and results: We defined the intermediate- and high-risk groups according to Pooled Cohort Equation (PCE), QRISK3, and modified Framingham Risk Score (FRS). Reti-CVD's prediction was compared to the number of individuals identified as intermediate- and high-risk according to standard CVD risk assessment tools, and sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated to assess the results. In the UK Biobank, among 48 260 participants, 20 643 (42.8%) and 7192 (14.9%) were classified into the intermediate- and high-risk groups according to PCE, and QRISK3, respectively. In the Singapore Epidemiology of Eye Diseases study, among 6810 participants, 3799 (55.8%) were classified as intermediate- and high-risk group according to modified FRS. Reti-CVD identified PCE-based intermediate- and high-risk groups with a sensitivity, specificity, PPV, and NPV of 82.7%, 87.6%, 86.5%, and 84.0%, respectively. Reti-CVD identified QRISK3-based intermediate- and high-risk groups with a sensitivity, specificity, PPV, and NPV of 82.6%, 85.5%, 49.9%, and 96.6%, respectively. Reti-CVD identified intermediate- and high-risk groups according to the modified FRS with a sensitivity, specificity, PPV, and NPV of 82.1%, 80.6%, 76.4%, and 85.5%, respectively. Conclusion: The retinal photograph biomarker (Reti-CVD) was able to identify individuals with intermediate and high-risk for CVD, in accordance with existing risk assessment tools.

Nebulized Recombinant Tissue Plasminogen Activator (rt-PA) for Acute COVID-19-Induced Respiratory Failure: An Exploratory Proof-of-Concept Trial.

Acute lung injury in COVID-19 results in diffuse alveolar damage with disruption of the alveolar-capillary barrier, coagulation activation, alveolar fibrin deposition and pulmonary capillary thrombi. Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to facilitate localized thrombolysis in the alveolar compartment and improve oxygenation. In this proof-of-concept safety study, adults with COVID-19-induced respiratory failure and a <300 mmHg PaO2/FiO2 (P/F) ratio requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care, between 23 April-30 July 2020 and 21 January-19 February 2021, respectively. Matched historical controls (MHC; n = 18) were used in C1 to explore efficacy. Safety co-primary endpoints were treatment-related bleeds and <1.0-1.5 g/L fibrinogen reduction. A variable dosing strategy with clinical efficacy endpoint and minimal safety concerns was determined in C1 for use in C2; patients were stratified by ventilation type to receive 40-60 mg rt-PA daily for ≤14 days. Nine patients in C1 (IMV, 6/9; NIRS, 3/9) and 26 in C2 (IMV, 12/26; NIRS, 14/26) received nebulized rt-PA for a mean (SD) of 6.7 (4.6) and 9.1(4.6) days, respectively. Four bleeds (one severe, three mild) in three patients were considered treatment related. There were no significant fibrinogen reductions. Greater improvements in mean P/F ratio from baseline to study end were observed in C1 compared with MHC (C1; 154 to 299 vs. MHC; 154 to 212). In C2, there was no difference in the baseline P/F ratio of NIRS and IMV patients. However, a larger improvement in the P/F ratio occurred in NIRS patients (NIRS; 126 to 240 vs. IMV; 120 to 188) and fewer treatment days were required (NIRS; 7.86 vs. IMV; 10.5). Nebulized rt-PA appears to be well-tolerated, with a trend towards improved oxygenation, particularly in the NIRS group. Randomized clinical trials are required to demonstrate the clinical effect significance and magnitude.