Clinical phenotype classification to predict risk and optimize the management of patients with atrial fibrillation using the Atrial Fibrillation Better Care (ABC) pathway: a report from the COOL-AF registry.

BACKGROUND: Phenotypic classification is a method of grouping patients with similar phenotypes. AIM: We aimed to use phenotype classification based on a clustering process for risk stratification of patients with non-valvular atrial fibrillation (AF) and second, to assess the benefit of the Atrial Fibrillation Better Care (ABC) pathway. METHODS: Patients with AF were prospectively enrolled from 27 hospitals in Thailand from 2014 to 2017, and followed up every 6 months for 3 years. Cluster analysis was performed from 46 variables using the hierarchical clustering using the Ward minimum variance method. Outcomes were a composite of all-cause death, ischemic stroke/systemic embolism, acute myocardial infarction and heart failure. RESULTS: A total of 3405 patients were enrolled (mean age 67.8 ± 11.3 years, 58.2% male). During the mean follow-up of 31.8 ± 8.7 months. Three clusters were identified: Cluster 1 had the highest risk followed by Cluster 3 and Cluster 2 with a hazard ratio (HR) and 95% confidence interval (CI) of composite outcomes of 2.78 (2.25, 3.43), P < 0.001 for Cluster 1 and 1.99 (1.63, 2.42), P < 0.001 for Cluster 3 compared with Cluster 2. Management according to the ABC pathway was associated with reductions in adverse clinical outcomes especially those who belonged to Clusters 1 and 3 with HR and 95%CI of the composite outcome of 0.54 (0.40, 073), P < 0.001 for Cluster 1 and 0.49 (0.38, 0.63), P < 0.001 for Cluster 3. CONCLUSION: Phenotypic classification helps in risk stratification and prognostication. Compliance with the ABC pathway was associated with improved clinical outcomes.

Pharmacokinetics and pharmacodynamics of direct oral anticoagulants.

INTRODUCTION: Direct oral anticoagulants (DOACs) have overtaken vitamin K antagonists to become the most widely used method of anticoagulation for most indications. Their stable and predictable pharmacokinetics combined with relatively simple dosing, and the absence of routine monitoring has made them an attractive proposition for healthcare providers. Despite the benefits of DOACs as a class, important differences exist between individual DOAC drugs in respect of their pharmacokinetic and pharmacodynamic profiles with implications for dosing and reversal in cases of major bleeding. AREAS COVERED: This review summarizes the state of knowledge relating to the pharmacokinetics of dabigatran (factor IIa/thrombin inhibitor) and apixaban, edoxaban and rivaroxaban (factor Xa) inhibitors. We focus on pharmacokinetic differences between the drugs which may have clinically significant implications. EXPERT OPINION: Patient-centered care necessitates a careful consideration of the pharmacokinetic and pharmacodynamic differences between DOACs, and how these relate to individual patient circumstances. Prescribers should be aware of the potential for pharmacokinetic drug interactions with DOACs which may influence prescribing decisions in patients with multiple comorbidities. In order to give an appropriate dose of DOAC drugs, accurate estimation of renal function using the Cockcroft-Gault formula using actual body weight is necessary. An increasing body of evidence supports the use of DOACs in patients who are obese, and this is becoming more routine in clinical practice.

Cerebrovascular risk factors and their time-dependent effects on stroke survival in the EMMA cohort study.

To investigate the time-dependent effects of traditional risk factors on functional disability in all-cause mortality post-stroke, we evaluated data from a long-term stroke cohort. Baseline cerebrovascular risk factors (CVRF) and functionality at 1 and 6 months were evaluated in survivors from a prospective stroke cohort using the modified Rankin scale (m-RS), which classifies participants as improvement of disability, unchanged disability (at least moderate), and worsening disability. Cox regression models considering baseline risk factors, medication use, and functionality 6 months after stroke were fitted to identify their time-dependent effects up to 12 years of follow-up. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) are presented. Among 632 survivors (median age 68, 54% male, 71% first-ever episode), age and functional disability (unchanged and worsening) 6 months after ischemic stroke had time-dependent effects on all-cause mortality risk up to 12 years of follow-up. The most impacting risk factors were unchanged (at least moderate) (HR, 2.99; 95%CI: 1.98-4.52) and worsening disability (HR, 2.85; 95%CI: 1.26-6.44), particularly in the first two years after a stroke event (Time 1: ≥6 mo to <2.5 y). Worsening disability also impacted mortality in the period from ≥2.5 to <7.5 years (Time 2) of follow-up (HR, 2.43 (95%CI: 1.03-5.73). Other baseline factors had a fixed high-risk effect on mortality during follow-up. Post-stroke and continuous medication use had a fixed protective effect on mortality. Functional disability was the main contributor with differential risks of mortality up to 12 years of follow-up.

Effectiveness of out-patient based acute heart failure care: a pilot randomised controlled trial.

OBJECTIVES: Acute heart failure (AHF) hospitalisation is associated with 10% mortality. Outpatient based management (OPM) of AHF appeared effective in observational studies. We conducted a pilot randomised controlled trial (RCT) comparing OPM with standard inpatient care (IPM). METHODS: We randomised patients with AHF, considered to need IV diuretic treatment for ≥2 days, to IPM or OPM. We recorded all-cause mortality, and the number of days alive and out-of-hospital (DAOH). Quality of life, mental well-being and Hope scores were assessed. Mean NHS cost savings and 95% central range (CR) were calculated from bootstrap analysis. Follow-up: 60 days. RESULTS: Eleven patients were randomised to IPM and 13 to OPM. There was no statistically significant difference in all-cause mortality during the index episode (1/11 vs 0/13) and up to 60 days follow-up (2/11 vs 2/13) [p = .86]. The OPM group accrued more DAOH {47 [36,51] vs 59 [41,60], p = .13}. Two patients randomised to IPM (vs 6 OPM) were readmitted [p = .31]. Hope scores increased more with OPM within 30 days but dropped to lower levels than IPM by 60 days. More out-patients had increased total well-being scores by 60 days (p = .04). OPM was associated with mean cost savings of £2658 (95% CR 460-4857) per patient. CONCLUSIONS: Patients with acute HF randomised to OPM accrued more days alive out of hospital (albeit not statistically significantly in this small pilot study). OPM is favoured by patients and carers and is associated with improved mental well-being and cost savings.

Artificial intelligence in radiology: trainees want more.

AIM: To understand the attitudes of UK radiology trainees towards artificial intelligence (AI) in Radiology, in particular, assessing the demand for AI education. MATERIALS AND METHODS: A survey, which ran over a period of 2 months, was created using the Google Forms platform and distributed via email to all UK training programmes. RESULTS: The survey was completed by 149 trainee radiologists with at least one response from all UK training programmes. Of the responses, 83.7% were interested in AI use in radiology but 71.4% had no experience of working with AI and 79.9% would like to be involved in AI-based projects. Almost all (98.7%) felt that AI should be taught during their training, yet only one respondent stated that their training programme had implemented AI teaching. Respondents indicated that basic understanding, implementation, and critical appraisal of AI software should be prioritized in teaching. Of the trainees, 74.2% agreed that AI would enhance the job of diagnostic radiologists over the next 20 years. The main concerns raised were information technology/implementation and ethical/regulatory issues. CONCLUSION: Despite the current limited availability of AI-based activities and teaching within UK training programmes, UK trainees' attitudes towards AI are mostly positive with many showing interest in being involved with AI-based projects, activities, and teaching.

Cerebrovascular risk factors and their time-dependent effects on stroke survival in the EMMA cohort study

To investigate the time-dependent effects of traditional risk factors on functional disability in all-cause mortality post-stroke, we evaluated data from a long-term stroke cohort. Baseline cerebrovascular risk factors (CVRF) and functionality at 1 and 6 months were evaluated in survivors from a prospective stroke cohort using the modified Rankin scale (m-RS), which classifies participants as improvement of disability, unchanged disability (at least moderate), and worsening disability. Cox regression models considering baseline risk factors, medication use, and functionality 6 months after stroke were fitted to identify their time-dependent effects up to 12 years of follow-up. Adjusted hazard ratios (HR) with 95% confidence intervals (CI) are presented. Among 632 survivors (median age 68, 54% male, 71% first-ever episode), age and functional disability (unchanged and worsening) 6 months after ischemic stroke had time-dependent effects on all-cause mortality risk up to 12 years of follow-up. The most impacting risk factors were unchanged (at least moderate) (HR, 2.99; 95%CI: 1.98-4.52) and worsening disability (HR, 2.85; 95%CI: 1.26-6.44), particularly in the first two years after a stroke event (Time 1: ≥6 mo to <2.5 y). Worsening disability also impacted mortality in the period from ≥2.5 to <7.5 years (Time 2) of follow-up (HR, 2.43 (95%CI: 1.03-5.73). Other baseline factors had a fixed high-risk effect on mortality during follow-up. Post-stroke and continuous medication use had a fixed protective effect on mortality. Functional disability was the main contributor with differential risks of mortality up to 12 years of follow-up.

Patient and Public Involvement and Engagement (PPIE): first steps in the process of the engagement in research projects in Brazil.

Patient and Public Involvement and Engagement (PPIE) - sometimes called Community Engagement and Involvement (CEI) - comes as a big challenge but one that can be very helpful for health care professionals and stakeholders in planning better health policies for attending to the main needs of the community. PPIE involves three pillars: public involvement, public engagement, and participation. Public involvement occurs when members of the general population are actively involved in developing the research question, designing, and conducting the research. Public engagement tells people about new studies, why they are important, the impact of results, the possible implication of the main findings for the community, and the possible impact of these new findings in society, as well as, in the dissemination of knowledge to the general population. Participation is being a volunteer in the study. Our experience with PPIE, to the best of our knowledge the first initiative in Brazil, is a partnership with the University of Birmingham, the University of Liverpool, and the NIHR Global Health Group on Atrial Fibrillation (AF) Management focusing on the AF care pathway exploring the important aspects of diagnosis and treatment in the primary care system from a low-middle income area in São Paulo. The involvement of patients/public in the research represents a new step in the process of inclusion of all segments of our society based on patient illness and the gaps in knowledge aiming to open new horizons for continuous improvement and better acceptance of research projects.

Patient and Public Involvement and Engagement (PPIE): first steps in the process of the engagement in research projects in Brazil

Patient and Public Involvement and Engagement (PPIE) - sometimes called Community Engagement and Involvement (CEI) - comes as a big challenge but one that can be very helpful for health care professionals and stakeholders in planning better health policies for attending to the main needs of the community. PPIE involves three pillars: public involvement, public engagement, and participation. Public involvement occurs when members of the general population are actively involved in developing the research question, designing, and conducting the research. Public engagement tells people about new studies, why they are important, the impact of results, the possible implication of the main findings for the community, and the possible impact of these new findings in society, as well as, in the dissemination of knowledge to the general population. Participation is being a volunteer in the study. Our experience with PPIE, to the best of our knowledge the first initiative in Brazil, is a partnership with the University of Birmingham, the University of Liverpool, and the NIHR Global Health Group on Atrial Fibrillation (AF) Management focusing on the AF care pathway exploring the important aspects of diagnosis and treatment in the primary care system from a low-middle income area in São Paulo. The involvement of patients/public in the research represents a new step in the process of inclusion of all segments of our society based on patient illness and the gaps in knowledge aiming to open new horizons for continuous improvement and better acceptance of research projects.

Contemporary management of patients with atrial fibrillation in the Netherlands and Belgium: a report from the EORP-AF long-term general registry.

BACKGROUND: Contemporary data regarding the characteristics, treatment and outcomes of patients with atrial fibrillation (AF) are needed. We aimed to assess these data and guideline adherence in the EURObservational Research Programme on Atrial Fibrillation (EORP-AF) long-term general registry. METHODS: We analysed 967 patients from the EORP-AF long-term general registry included in the Netherlands and Belgium from 2013 to 2016. Baseline and 1­year follow-up data were gathered. RESULTS: At baseline, 887 patients (92%) received anticoagulant treatment. In 88 (10%) of these patients, no indication for chronic anticoagulant treatment was present. A rhythm intervention was performed or planned in 52 of these patients, meaning that the remaining 36 (41%) were anticoagulated without indication. Forty patients were not anticoagulated, even though they had an indication for chronic anticoagulation. Additionally, 63 of the 371 patients (17%) treated with a non-vitamin K antagonist oral anticoagulant (NOAC) were incorrectly dosed. In total, 50 patients (5%) were overtreated and 89 patients (9%) were undertreated. However, the occurrence of major adverse cardiac and cerebrovascular events (MACCE) was still low with 4.2% (37 patients). CONCLUSIONS: Overtreatment and undertreatment with anticoagulants are still observable in 14% of this contemporary, West-European AF population. Still, MACCE occurred in only 4% of the patients after 1 year of follow-up.

Oral anticoagulants for nonvalvular atrial fibrillation in frail elderly patients: insights from the ARISTOPHANES study.

BACKGROUND: Patient frailty amongst patients with nonvalvular atrial fibrillation (NVAF) is associated with adverse health outcomes and increased risk of mortality. Additional evidence is needed to evaluate effective and safe NVAF treatment in this patient population. OBJECTIVES: This subgroup analysis of the ARISTOPHANES study compared the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) amongst frail NVAF patients prescribed nonvitamin K antagonist oral anticoagulants (NOACs) or warfarin. METHODS: This comparative retrospective observational study of frail, older NVAF patients who initiated apixaban, dabigatran, rivaroxaban or warfarin from 01JAN2013-30SEP2015 was conducted using Medicare and 3 US commercial claims databases. To compare each drug, 6 propensity score-matched (PSM) cohorts were created. Patient cohorts were pooled from 4 databases after PSM. Cox models were used to estimate hazard ratios (HR) of S/SE and MB. RESULTS: Amongst NVAF patients, 34% (N = 150 487) met frailty criteria. Apixaban and rivaroxaban were associated with a lower risk of S/SE vs warfarin (apixaban: HR: 0.61, 95% CI: 0.55-0.69; rivaroxaban: HR: 0.79, 95% CI: 0.72-0.87). For MB, apixaban (HR: 0.62, 95% CI: 0.57-0.66) and dabigatran (HR: 0.79, 95% CI: 0.70-0.89) were associated with a lower risk and rivaroxaban (HR: 1.14, 95% CI: 1.08-1.21) was associated with a higher risk vs warfarin. CONCLUSION: Amongst this cohort of frail NVAF patients, NOACs were associated with varying rates of stroke/SE and MB compared with warfarin. Due to the lack of real-world data regarding OAC treatment in frail patients, these results may inform clinical practice in the treatment of this patient population.

Baseline factors associated with early and late death in intracerebral haemorrhage survivors.

BACKGROUND AND PURPOSE: The aim of this study was to determine whether early and late death are associated with different baseline factors in intracerebral haemorrhage (ICH) survivors. METHODS: This was a secondary analysis of the multicentre prospective observational CROMIS-2 ICH study. Death was defined as 'early' if occurring within 6 months of study entry and 'late' if occurring after this time point. RESULTS: In our cohort (n = 1094), there were 306 deaths (per 100 patient-years: absolute event rate, 11.7; 95% confidence intervals, 10.5-13.1); 156 were 'early' and 150 'late'. In multivariable analyses, early death was independently associated with age [per year increase; hazard ratio (HR), 1.05, P = 0.003], history of hypertension (HR, 1.89, P = 0.038), pre-event modified Rankin scale score (per point increase; HR, 1.41, P < 0.0001), admission National Institutes of Health Stroke Scale score (per point increase; HR, 1.11, P < 0.0001) and haemorrhage volume >60 mL (HR, 4.08, P < 0.0001). Late death showed independent associations with age (per year increase; HR, 1.04, P = 0.003), pre-event modified Rankin scale score (per point increase; HR, 1.42, P = 0.001), prior anticoagulant use (HR, 2.13, P = 0.028) and the presence of intraventricular extension (HR, 1.73, P = 0.033) in multivariable analyses. In further analyses where time was treated as continuous (rather than dichotomized), the HR of previous cerebral ischaemic events increased with time, whereas HRs for Glasgow Coma Scale score, National Institutes of Health Stroke Scale score and ICH volume decreased over time. CONCLUSIONS: We provide new evidence that not all baseline factors associated with early mortality after ICH are associated with mortality after 6 months and that the effects of baseline variables change over time. Our findings could help design better prognostic scores for later death after ICH.

Mon2 predicts poor outcome in ST-elevation myocardial infarction.

AIMS: There are limited data on the role of human monocyte subsets in ST-elevation myocardial infarction (STEMI). The study aimed to establish the relationship between monocyte subsets, their phagocytic and nuclear factor κB (NFκB) activity and outcomes in STEMI. METHODS: Monocyte subsets and their phagocytic activity and intracellular levels of inhibitory κB kinase ß (IKKß, marker of NFκB activity) were measured by flow cytometry in 245 patients with STEMI, median follow-up of 46 months. RESULTS: Mon2 (CD14++CD16+CCR2+) counts were independently predictive of major adverse cardiovascular events (MACE) [4th quartile HR 3.42 (95% CI 1.43-8.16), P = 0.006 and 3rd quartile HR 2.88 (95% CI 1.19-7.00), P = 0.02 vs. 1st quartile]. Mon2 subset was the only subset associated with higher occurrence of heart failure (4th quartile vs. 1st quartile, sevenfold, P = 0.001 on univariate analysis; fivefold, P = 0.04 on multivariable analysis). On receiver operating characteristic, analysis including of Mon2 improved prognostic value of troponin T and creatine kinase for MACE and heart failure (HF). Higher intracellular Mon2 IKKß levels were associated with 10-fold lower occurrence of HF on multivariable analysis (4th vs. 1st quartiles, P = 0.03). Abnormal Mon1 and Mon2 phagocytic capacities were related to HF development, but the association was dependent on the infarct size and other prognosticators. High Mon2 levels were associated with lower ejection fraction after STEMI onset (P = 0.001) and at 6-month follow-up (P < 0.001). CONCLUSIONS: Abnormal Mon2 characteristics have a unique association with poor outcome in patients with STEMI. The relation of Mon2 with occurrence of HF is strongly and independently related to their functional status, which may have potential therapeutic implications.

State of play and future direction with NOACs: An expert consensus.

Atrial fibrillation (AF) and venous thromboembolism (VTE) are cardiovascular conditions significant in contemporary practice. In both, the use of anticoagulation with vitamin K antagonists (VKAs) has been traditionally used to prevent adverse events. However, VKA therapy is associated with challenges relating to dose maintenance, the need to monitor anticoagulation, and bleeding risks. The non-vitamin K oral anticoagulants (NOACs) are becoming accepted as a clear alternative to VKA therapy for both AF and VTE management. The aim of this paper was to review contemporary evidence on the safety of NOACs in both conditions. A comprehensive literature review was conducted to explore key safety issues and expert consensus was achieved from eight professionals specialised in AF and VTE care. Consensus-based statements were formulated where available evidence was weak or contradictory. The expert statements in this paper form a key overview of the safety of NOACs compared with VKA therapy, and the comparative safety of different NOACs. It is apparent that a detailed patient work-up is required in order to identify and manage individual risk factors for bleeding and thrombosis prior to NOAC therapy. Additional measures, such as dose reductions, may also be used to maintain the safety of NOACs in practice.

Editor's Choice - Frailty and the management of patients with acute cardiovascular disease: A position paper from the Acute Cardiovascular Care Association.

Frailty is increasingly seen among patients with acute cardiovascular disease. A combination of an ageing population, improved disease survival, treatable long-term conditions as well as a greater recognition of the syndrome has accelerated the prevalence of frailty in the modern world. Yet, this has not been matched by an expansion of research. National and international bodies have identified acute cardiovascular disease in the frail as a priority area for care and an entity that requires careful clinical decisions, but there remains a paucity of guidance on treatment efficacy and safety, and how to manage this complex group. This position paper from the Acute Cardiovascular Care Association presents the latest evidence about frailty and the management of frail patients with acute cardiovascular disease, and suggests avenues for future research.