Exercise-based cardiac rehabilitation for adults with atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF), the most prevalent cardiac arrhythmia, disrupts the heart's rhythm through numerous small re-entry circuits in the atrial tissue, leading to irregular atrial contractions. The condition poses significant health risks, including increased stroke risk, heart failure, and reduced quality of life. Given the complexity of AF and its growing incidence globally, exercise-based cardiac rehabilitation (ExCR) may provide additional benefits for people with AF or those undergoing routine treatment for the condition. OBJECTIVES: To assess the benefits and harms of ExCR compared with non-exercise controls for people who currently have AF or who have been treated for AF. SEARCH METHODS: We searched the following electronic databases: CENTRAL in the Cochrane Library, MEDLINE Ovid, Embase Ovid, PsycINFO Ovid, Web of Science Core Collection Thomson Reuters, CINAHL EBSCO, LILACS BIREME, and two clinical trial registers on 24 March 2024. We imposed no language restrictions. SELECTION CRITERIA: We included randomised clinical trials (RCTs) that investigated ExCR interventions compared with any type of non-exercise control. We included adults 18 years of age or older with any subtype of AF or those who had received treatment for AF. DATA COLLECTION AND ANALYSIS: Five review authors independently screened and extracted data in duplicate. We assessed risk of bias using Cochrane's RoB 1 tool as outlined in the Cochrane Handbook for Systematic Reviews of Interventions. We assessed clinical and statistical heterogeneity by visual inspection of the forest plots and by using standard Chi² and I² statistics. We performed meta-analyses using random-effects models for continuous and dichotomised outcomes. We calculated standardised mean differences where different scales were used for the same outcome. We used the GRADE approach to assess the certainty of the evidence. MAIN RESULTS: We included 20 RCTs involving a total of 2039 participants with AF. All trials were conducted between 2006 and 2024, with a follow-up period ranging from eight weeks to five years. We assessed the certainty of evidence as moderate to very low. Five trials assessed comprehensive ExCR programmes, which included educational or psychological interventions, or both; the remaining 15 trials compared exercise-only cardiac rehabilitation with controls. The overall risk of bias in the included studies was mixed. Details on random sequence generation, allocation concealment, and use of intention-to-treat analysis were typically poorly reported. Evidence from nine trials (n = 1173) suggested little to no difference in mortality between ExCR and non-exercise controls (risk ratio (RR) 1.06, 95% confidence interval (CI) 0.76 to 1.49; I² = 0%; 101 deaths; low-certainty evidence). Based on evidence from 10 trials (n = 825), ExCR may have little to no effect on SAEs (RR 1.30, 95% CI 0.63 to 2.67; I² = 0%; 28 events; low-certainty evidence). Evidence from four trials (n = 378) showed that ExCR likely reduced AF recurrence (measured via Holter monitoring) compared to controls (RR 0.70, 95% CI 0.56 to 0.88; I² = 2%; moderate-certainty evidence). ExCR may reduce AF symptom severity (mean difference (MD) -1.59, 95% CI -2.98 to -0.20; I² = 61%; n = 600; low-certainty evidence); likely reduces AF symptom burden (MD -1.61, 95% CI -2.76 to -0.45; I² = 0%; n = 317; moderate-certainty evidence); may reduce AF episode frequency (MD -1.29, 95% CI -2.50 to -0.07; I² = 75%; n = 368; low-certainty evidence); and likely reduces AF episode duration (MD -0.58, 95% CI -1.14 to -0.03; I² = 0%; n = 317; moderate-certainty evidence), measured via the AF Severity Scale (AFSS) questionnaire. Moderate-certainty evidence from six trials (n = 504) showed that ExCR likely improved the mental component summary measure in health-related quality of life (HRQoL) of the 36-item Short Form Health Survey (SF-36) (MD 2.66, 95% CI 1.22 to 4.11; I² = 2%), but the effect of ExCR on the physical component summary measure was very uncertain (MD 1.75, 95% CI -0.31 to 3.81; I² = 52%; very low-certainty evidence). ExCR also may improve individual components of HRQoL (general health, vitality, emotional role functioning, and mental health) and exercise capacity (peak oxygen uptake (VO2peak) and 6-minute walk test) following ExCR. The effects of ExCR on serious adverse events and exercise capacity were consistent across different models of ExCR delivery: centre compared to home-based, exercise dose, exercise only compared to comprehensive programmes, and aerobic training alone compared to aerobic plus resistance programmes. Using univariate meta-regression, there was evidence of significant association between location of trial and length of longest follow-up on exercise capacity. AUTHORS' CONCLUSIONS: Due to few randomised participants and typically short-term follow-up, the impact of ExCR on all-cause mortality or serious adverse events for people with AF is uncertain. ExCR likely improves AF-specific measures including reduced AF recurrence, symptom burden, and episode duration, as well as the mental components of HRQoL. ExCR may improve AF symptom severity, episode frequency, and VO2peak. Future high-quality RCTs are needed to assess the benefits of ExCR for people with AF on patient-relevant outcomes including AF symptom severity and burden, AF recurrence, AF-specific quality of life, and clinical events such as mortality, readmissions, and serious adverse events. High-quality trials are needed to investigate how AF subtype and clinical setting (i.e. primary and secondary care) may influence ExCR effectiveness.

Early statin use is associated with improved survival and cardiovascular outcomes in patients with atrial fibrillation and recent ischaemic stroke: A propensity-matched analysis of a global federated health database.

INTRODUCTION: Statins reduce recurrent stroke and cardiovascular events in patients with non-cardioembolic stroke. The benefits of statins in patients with AF and recent IS remain unclear. We aimed to investigate the benefits of statins in patients with AF and recent IS. PATIENTS AND METHODS: This retrospective, cohort study was conducted using deidentified electronic medical records within TriNetX platform. Patients with AF and recent IS, who received statins within 28 days of their index stroke were propensity score-matched with those who did not. Patients were followed up for up to 2 years. Primary outcomes were the 2-year risk of recurrent IS, all-cause mortality and the composite outcome of all-cause mortality, recurrent IS, transient ischaemic attack (TIA), and acute myocardial infarction (MI). Secondary outcomes were the 2-year risk of TIA, intracranial haemorrhage (ICH), acute MI, and hospital readmission. Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals (95%CI). RESULTS: Of 20,902 patients with AF and recent IS, 7500 (35.9%) received statins within 28 days of their stroke and 13,402 (64.1%) did not. 11,182 patients (mean age 73.7 ± 11.5; 5277 (47.2%) female) remained after propensity score matching. Patients who received early statins had significantly lower risk of recurrent IS (HR: 0.45, 95%CI: 0.41-0.48, p < 0.001), mortality (HR: 0.75, 95%CI: 0.66-0.84, p < 0.001), the composite outcome (HR: 0.48, 95%CI: 0.45-0.52, p < 0.001), TIA (HR: 0.37, 95%CI: 0.30-0.44, p < 0.001), ICH (HR: 0.59, 95%CI: 0.47-0.72, p < 0.001 ), acute MI (HR: 0.35, 95%CI: 0.30-0.42, p < 0.001) and hospital readmission (HR: 0.46, 95%CI: 0.42-0.50, <0.001). Beneficial effects of early statins were evident in the elderly, different ethnic groups, statin dose intensity, and AF subtypes, large vessel occlusion and embolic strokes and within the context of statin lipophilicity, optimal LDL-cholesterol levels, various cardiovascular comorbidities, treatment with intravenous thrombolysis or endovascular thrombectomy, and NIHSS 0-5 and NIHSS > 5 subgroups. DISCUSSION AND CONCLUSION: Patients with AF and recent IS, who received early statins, had a lower risk of recurrent stroke, death, and other cardiovascular outcomes including ICH, compared to those who did not.

Stroke-heart syndrome: Incidence and clinical outcomes of cardiac complications following intracerebral haemorrhage.

INTRODUCTION: Newly diagnosed cardiovascular complications following an ischaemic stroke, termed stroke-heart syndrome, are common and associated with worse outcomes. Little is known regarding stroke-heart syndrome in relation to intracerebral haemorrhage (ICH). This study aimed to investigate the incidence and 5-year major adverse cardiovascular events (MACE; acute myocardial infarction, ischaemic stroke, all-cause mortality and recurrent ICH) of newly diagnosed cardiovascular complications following incident ICH, using a global federated database. PATIENTS AND METHODS: A retrospective cohort study was conducted using anonymised electronic medical records. Patients aged ⩾ 18 years with non-traumatic ICH and 5-year follow-up were included. Patients with newly diagnosed cardiovascular complications within 4-weeks following the initial ICH were 1:1 propensity score-matched with patients without new-onset cardiovascular complications. Each cardiovascular complications were investigated as a composite stroke-heart syndrome cohort and separately for associated MACE. Cox hazard regression models were used to determine 5-year incidence of MACE. RESULTS: Before propensity score matching, 171,489 patients with non-traumatic ICH, 15% (n = 26,449) experienced ⩾1 newly diagnosed cardiovascular complication within 4 weeks. After matching, patients with ICH and cardiovascular complications were associated with a significantly higher risk of 5-year MACE (HR 1.35 [95% CI 1.32-1.38]), and in each composite compared to matched controls. There was no significant risk of rehospitalisation over 5-year follow-up [HR 0.90 [0.73-1.13]). The risk of MACE was significantly higher in patients with newly diagnosed cardiovascular complications. DISCUSSION AND CONCLUSIONS: Newly diagnosed cardiovascular complications following ICH (i.e. stroke-heart syndrome) were common and associated with a significantly worsened 5-year prognosis.

Clinical trial evaluation: the EDOSURE clinical trial program.

EDOSURE is a trial program of the direct oral anticoagulant drug edoxaban, comprising ten randomized clinical trials of which eight are currently published. They evaluate the use of edoxaban in the treatment of nonvalvular atrial fibrillation and acute venous thromboembolism, including in special circumstances such as patients undergoing cardiac procedures, cancer-associated venous thromboembolism, and elderly patients whose bleeding risk precludes conventional anticoagulation strategies. As a result of the collective evidence generated by EDOSURE, edoxaban is now recommended as a treatment option by numerous international guidelines. This review summarizes the context, rationale, and key findings of the studies.

EDOSURE is a collection of clinical trials of the medication edoxaban ­ a blood thinner used to treat or prevent clotting. It encompasses ten trials, eight of which are complete and two are ongoing. Edoxaban's main uses are in patients with atrial fibrillation, or venous clots (e.g., deep vein thrombosis). Trials of blood thinners need to assess the balance of effectiveness (how well the drug treats or prevents clotting) against risk (causing bleeding). These trials collectively demonstrate first that edoxaban is an effective treatment in these conditions and is at least as safe as traditional options like warfarin. Second, in patients with atrial fibrillation who are undergoing procedures like cardiac stenting or ablations, edoxaban is as effective as the previous standard treatments. Finally, in higher-risk populations, such as frail and/or elderly patients, edoxaban can represent a relatively safe option at lower doses. This article is a review of the individual trials, their important findings, and potential limiting factors.

Regular use of fish oil supplements and course of cardiovascular diseases: prospective cohort study.

Objective: To examine the effects of fish oil supplements on the clinical course of cardiovascular disease, from a healthy state to atrial fibrillation, major adverse cardiovascular events, and subsequently death. Design: Prospective cohort study. Setting: UK Biobank study, 1 January 2006 to 31 December 2010, with follow-up to 31 March 2021 (median follow-up 11.9 years). Participants: 415 737 participants, aged 40-69 years, enrolled in the UK Biobank study. Main outcome measures: Incident cases of atrial fibrillation, major adverse cardiovascular events, and death, identified by linkage to hospital inpatient records and death registries. Role of fish oil supplements in different progressive stages of cardiovascular diseases, from healthy status (primary stage), to atrial fibrillation (secondary stage), major adverse cardiovascular events (tertiary stage), and death (end stage). Results: Among 415 737 participants free of cardiovascular diseases, 18 367 patients with incident atrial fibrillation, 22 636 with major adverse cardiovascular events, and 22 140 deaths during follow-up were identified. Regular use of fish oil supplements had different roles in the transitions from healthy status to atrial fibrillation, to major adverse cardiovascular events, and then to death. For people without cardiovascular disease, hazard ratios were 1.13 (95% confidence interval 1.10 to 1.17) for the transition from healthy status to atrial fibrillation and 1.05 (1.00 to 1.11) from healthy status to stroke. For participants with a diagnosis of a known cardiovascular disease, regular use of fish oil supplements was beneficial for transitions from atrial fibrillation to major adverse cardiovascular events (hazard ratio 0.92, 0.87 to 0.98), atrial fibrillation to myocardial infarction (0.85, 0.76 to 0.96), and heart failure to death (0.91, 0.84 to 0.99). Conclusions: Regular use of fish oil supplements might be a risk factor for atrial fibrillation and stroke among the general population but could be beneficial for progression of cardiovascular disease from atrial fibrillation to major adverse cardiovascular events, and from atrial fibrillation to death. Further studies are needed to determine the precise mechanisms for the development and prognosis of cardiovascular disease events with regular use of fish oil supplements.

Continuous infusion versus bolus injection of loop diuretics for acute heart failure.

BACKGROUND: Acute heart failure (AHF) is new onset of, or a sudden worsening of, chronic heart failure characterised by congestion in about 95% of cases or end-organ hypoperfusion in 5% of cases. Treatment often requires urgent escalation of diuretic therapy, mainly through hospitalisation. This Cochrane review evaluated the efficacy of intravenous loop diuretics strategies in treating AHF in individuals with New York Heart Association (NYHA) classification III or IV and fluid overload. OBJECTIVES: To assess the effects of intravenous continuous infusion versus bolus injection of loop diuretics for the initial treatment of acute heart failure in adults. SEARCH METHODS: We identified trials through systematic searches of bibliographic databases and in clinical trials registers including CENTRAL, MEDLINE, Embase, CPCI-S on the Web of Science, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry platform (ICTRP), and the European Union Trials register. We conducted reference checking and citation searching, and contacted study authors to identify additional studies. The latest search was performed on 29 February 2024. SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving adults with AHF, NYHA classification III or IV, regardless of aetiology or ejection fraction, where trials compared intravenous continuous infusion of loop diuretics with intermittent bolus injection in AHF. We excluded trials with chronic stable heart failure, cardiogenic shock, renal artery stenosis, or end-stage renal disease. Additionally, we excluded studies combining loop diuretics with hypertonic saline, inotropes, vasoactive medications, or renal replacement therapy and trials where diuretic dosing was protocol-driven to achieve a target urine output, due to confounding factors. DATA COLLECTION AND ANALYSIS: Two review authors independently screened papers for inclusion and reviewed full-texts. Outcomes included weight loss, all-cause mortality, length of hospital stay, readmission following discharge, and occurrence of acute kidney injury. We performed risk of bias assessment and meta-analysis where data permitted and assessed certainty of the evidence. MAIN RESULTS: The review included seven RCTs, spanning 32 hospitals in seven countries in North America, Europe, and Asia. Data collection ranged from eight months to six years. Following exclusion of participants in subgroups with confounding treatments and different clinical settings, 681 participants were eligible for review. These additional study characteristics, coupled with our strict inclusion and exclusion criteria, improve the applicability of the body of the evidence as they reflect real-world clinical practice. Meta-analysis was feasible for net weight loss, all-cause mortality, length of hospital stay, readmission, and acute kidney injury. Literature review and narrative analysis explored daily fluid balance; cardiovascular mortality; B-type natriuretic peptide (BNP) change; N-terminal-proBNP change; and adverse incidents such as ototoxicity, hypotension, and electrolyte imbalances. Risk of bias assessment revealed two studies with low overall risk, four with some concerns, and one with high risk. All sensitivity analyses excluded trials at high risk of bias. Only narrative analysis was conducted for 'daily fluid balance' due to diverse data presentation methods across two studies (169 participants, the evidence was very uncertain about the effect). Results of narrative analysis varied. For instance, one study reported higher daily fluid balance within the first 24 hours in the continuous infusion group compared to the bolus injection group, whereas there was no difference in fluid balance beyond this time point. Continuous intravenous infusion of loop diuretics may result in mean net weight loss of 0.86 kg more than bolus injection of loop diuretics, but the evidence is very uncertain (mean difference (MD) 0.86 kg, 95% confidence interval (CI) 0.44 to 1.28; 5 trials, 497 participants; P < 0.001, I2 = 21%; very low-certainty evidence). Importantly, sensitivity analysis excluding trials with high risk of bias showed there was insufficient evidence for a difference in bodyweight loss between groups (MD 0.70 kg, 95% CI -0.06 to 1.46; 3 trials, 378 participants; P = 0.07, I2 = 0%). There may be little to no difference in all-cause mortality between continuous infusion and bolus injection (risk ratio (RR) 1.53, 95% CI 0.81 to 2.90; 5 trials, 530 participants; P = 0.19, I2 = 4%; low-certainty evidence). Despite sensitivity analysis, the direction of the evidence remained unchanged. No trials measured cardiovascular mortality. There may be little to no difference in the length of hospital stay between continuous infusion and bolus injection of loop diuretics, but the evidence is very uncertain (MD -1.10 days, 95% CI -4.84 to 2.64; 4 trials, 211 participants; P = 0.57, I2 = 88%; very low-certainty evidence). Sensitivity analysis improved heterogeneity; however, the direction of the evidence remained unchanged. There may be little to no difference in the readmission to hospital between continuous infusion and bolus injection of loop diuretics (RR 0.85, 95% CI 0.63 to 1.16; 3 trials, 400 participants; P = 0.31, I2 = 0%; low-certainty evidence). Sensitivity analysis continued to show insufficient evidence for a difference in the readmission to hospital between groups. There may be little to no difference in the occurrence of acute kidney injury as an adverse event between continuous infusion and bolus injection of intravenous loop diuretics (RR 1.02, 95% CI 0.70 to 1.49; 3 trials, 491 participants; P = 0.92, I2 = 0%; low-certainty evidence). Sensitivity analysis continued to show that continuous infusion may make little to no difference on the occurrence of acute kidney injury as an adverse events compared to the bolus injection of intravenous loop diuretics. AUTHORS' CONCLUSIONS: Analysis of available data comparing two delivery methods of diuretics in acute heart failure found that the current data are insufficient to show superiority of one strategy intervention over the other. Our findings were based on trials meeting stringent inclusion and exclusion criteria to ensure validity. Despite previous reviews suggesting advantages of continuous infusion over bolus injections, our review found insufficient evidence to support or refute this. However, our review, which excluded trials with clinical confounders and RCTs with high risk of bias, offers the most robust conclusion to date.

Asymptomatic vs. symptomatic atrial fibrillation: Clinical outcomes in heart failure patients.

BACKGROUND: The outcome implications of asymptomatic vs. symptomatic atrial fibrillation (AF) in specific groups of patients according to clinical heart failure (HF) and left ventricular ejection fraction (LVEF) need to be clarified. METHODS: In a prospective observational study, patients were categorized according to overt HF with LVEF≤40 %, or with LVEF>40 %, or without overt HF with LVEF40 %≤ or > 40 %, as well as according to the presence of asymptomatic or symptomatic AF. RESULTS: A total of 8096 patients, divided into 8 groups according to HF and LVEF, were included with similar proportions of asymptomatic AF (ranging from 43 to 48 %). After a median follow-up of 730 [699 -748] days, the composite outcome (all-cause death and MACE) was significantly worse for patients with asymptomatic AF associated with HF and reduced LVEF vs. symptomatic AF patients of the same group (p = 0.004). On adjusted Cox regression analysis, asymptomatic AF patients with HF and reduced LVEF were independently associated with a higher risk for the composite outcome (aHR 1.32, 95 % CI 1.04-1.69) and all-cause death (aHR 1.33, 95 % CI 1.02-1.73) compared to symptomatic AF patients with HF and reduced LVEF. Kaplan-Meier curves showed that HF-LVEF≤40 % asymptomatic patients had the highest cumulative incidence of all-cause death and MACE (p < 0.001 for both). CONCLUSIONS: In a large European cohort of AF patients, the risk of the composite outcome at 2 years was not different between asymptomatic and symptomatic AF in the whole cohort but adverse implications for poor outcomes were found for asymptomatic AF in HF with LVEF≤40 %.

Risk of Atrial Fibrillation and Adverse Outcomes in Patients With Cardiac Implantable Electronic Devices.

BACKGROUND AND OBJECTIVES: Comprehensive epidemiological data are lacking on the incident atrial fibrillation (AF) in patients with cardiac implantable electronic devices (CIEDs). This study aimed to examine the incidence, risk factors, and AF-related adverse outcomes of patients with CIEDs. METHODS: This was an observational cohort study that analyzed patients without prevalent AF who underwent CIED implantation in 2009-2018 using a Korean nationwide claims database. The subjects were divided into three groups by CIED type and indication: pacemaker (n=21,438), implantable cardioverter defibrillator (ICD)/cardiac resynchronization therapy (CRT) with heart failure (HF) (n=3,450), and ICD for secondary prevention without HF (n=2,146). The incidence of AF, AF-associated predictors, and adverse outcomes were evaluated. RESULTS: During follow-up, the incidence of AF was 4.3, 7.3, and 5.1 per 100 person-years in the pacemaker, ICD/CRT with HF, and ICD without HF cohorts, respectively. Across the three cohorts, older age and valvular heart disease were commonly associated with incident AF. Incident AF was consistently associated with an increased risk of ischemic stroke (3.8-11.4-fold), admission for HF (2.6-10.5-fold), hospitalization for any cause (2.4-2.7-fold), all-cause death (4.1-5.0-fold), and composite outcomes (3.4-5.7-fold). Oral anticoagulation rates were suboptimal in patients with incident AF (pacemaker, 51.3%; ICD/CRT with HF, 51.7%; and ICD without HF, 33.8%, respectively). CONCLUSIONS: A substantial proportion of patients implanted CIED developed newly diagnosed AF. Incident AF was associated with a higher risk of adverse events. The importance of awareness, early detection, and appropriate management of AF in patients with CIED should be emphasized.

Effects of glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors on cardiovascular and kidney outcomes in Asian versus White patients with type 2 diabetes mellitus.

BACKGROUND: The study aimed to assess the treatment effects of the two medications on cardiovascular and kidney outcomes in Asian compared with White patients with type 2 diabetes mellitus (T2DM). METHODS: MEDLINE, EMBASE, and CENTRAL were searched up to October 31, 2022. We included the trials that assessed the effects of glucagon-like peptide-1 receptor agonists (GLP-1 RA) or sodium-glucose cotransporter-2 inhibitors (SGLT2i) versus placebo in Asian and White patients with T2DM on major adverse cardiovascular events (MACE) and kidney outcomes. The Bucher method was used to perform an indirect comparison for estimating the differences in treatment effects of GLP-1 RA and SGLT2i between Asian versus White patients. Interaction tests were also performed for treatment-by-race to assess the potential effect modification by race. RESULTS: We included 22 publications from 13 randomized trials. For MACE, there were no differences in treatment effects of GLP-1 RA (HR = 0.84, 95% CI: 0.68-1.04) or SGLT2i (HR = 0.90, 95% CI: 0.72-1.13) in Asian versus White patients. No differences in treatment effects of SGLT2i on kidney outcomes in Asian versus White patients were found (HR = 1.01, 95% CI: 0.75-1.36). There was no significant effect modification by race on cardiovascular and kidney outcomes. CONCLUSIONS: There were no significant differences in treatment effects of GLP-1 RA or SGLT2i for MACE between Asian and White patients with T2DM. Likewise, no significant differences in treatment effects of SGLT2i on kidney outcomes were found between Asian and White patients.

Molecular biomarkers predicting newly detected atrial fibrillation after ischaemic stroke or TIA: A systematic review.

Background: Several molecular biomarkers are available that predict newly detected atrial fibrillation (NDAF). We aimed to identify such biomarkers that predict NDAF after an Ischaemic stroke (IS)/Transient Ischaemic Attack (TIA) and evaluate their performance. Methods: A systematic review was undertaken in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Studies of patients with IS, TIA, or both, who underwent ECG monitoring for ⩾24 h, which reported molecular biomarkers and frequency of NDAF after electronic searches of multiple databases were included. Results: Twenty-one studies (76% IS, 24% IS and TIA) involving 4640 patients were included. Twelve biomarkers were identified, with cardiac biomarkers evaluated in the majority (75%) of patients. Performance measures were inconsistently reported. Among cohorts selecting high-risk individuals (12 studies), the most studied biomarkers were N-Terminal-Pro Brain Natriuretic Peptide (NT-ProBNP, five studies; C-statistics reported by three studies, 0.69-0.88) and Brain Natriuretic Peptide (BNP, two studies; C-statistics reported in two studies, 0.68-0.77). Among unselected cohorts (nine studies), the most studied biomarker was BNP (six studies; C-statistics reported in five studies, 0.75-0.88). Only BNP was externally validated (two studies) but using different thresholds to categorise risk of NDAF. Conclusion: Cardiac biomarkers appear to have modest to good discrimination for predicting NDAF, although most analyses were limited by small, heterogeneous study populations. Their clinical utility should be explored further, and this review supports the need to assess the role of molecular biomarkers in large prospective studies with standardised selection criteria, definition of clinically significant NDAF and laboratory assays.

Transient ischemic attack events and incident cardiovascular and non-cardiovascular complications: Observations from a large diversified multimorbid cohort.

Background: Transient ischemic attack (TIA) is a strong signal prompting the incidence of future cardiovascular and non-cardiovascular complications, in light of recent debate on the so-called "stroke-heart syndrome." We aimed to investigate the relation of TIAs to incident clinical events. Methods: Patients were drawn from three health plans with a wide spectrum of age groups and a wide mix of socio-economic/disability status. Two TIA cohorts in a retrospective design were used to achieve the study specific aims: (i) to investigate the incidence of TIA and associated cardiovascular and non-cardiovascular complications within 30 and 90 days from the onset of incident TIA events; and (ii) to examine the potential risk factors for developing incident TIA events in the general population with/without a history of prior stroke. Results: The incident TIA cohort consisted of 53,716 patients with an average age of 64.2 years (SD 15.2) and 46.1% male. Following TIA, the incidence proportions of ischemic stroke within 30 and 90 days were 2.7% and 3.8%, respectively, and for incident acute coronary syndrome being 0.94 and 1.84, respectively. Ventricular arrhythmia had proportions of 1.2 and 2.14, respectively within 30 and 90 days, with acute heart failure having values of 0.49 and 0.923. About 45% or more of the cardiovascular and non-cardiovascular complications occurred in the first 30 days following the incident TIA cases. About one-third of the recurrent TIA cases followed the incident TIA cases within a span of 30 days. Amongst comorbidities with stroke in the comorbid history, prior stroke provided the strongest risk factor in terms of odds ratio (OR = 8.34, 95% CI 7.21-9.66) for incident TIA events. Age was strongly associated with incident TIA events. Without a prior history of stroke (ischemic stroke/transient ischemic attack/thrombo-embolic events), valvular disease was the strongest risk factor from among the comorbidities (OR-1.87, 95% CI 1.51-2.32). Age also provided strong associations with incident TIA events. Conclusions: Following a TIA, there was a high risk of stroke, acute coronary syndrome, ventricular arrhythmia, acute heart failure, and non-cardiovascular complications.

Three-year outcomes of patients with non-valvular atrial fibrillation: the COOL-AF registry.

BACKGROUND: Clinical outcomes of patients with non-valvular atrial fibrillation (AF) in Asian populations may be different from non-Asians. In this study, we aimed to determine the incidence of ischemic stroke/systemic embolism (SSE), major bleeding, and death, and the predictors for clinical outcomes in a contemporary Asian cohort of newly diagnosed AF patients. METHODS: This is a prospective multicenter nationwide registry of patients with AF from 27 hospitals in Thailand. Baseline data and follow-up data were collected every 6 months until 3 years. Data collections included demographic, medical history, laboratory, and medication details. Clinical outcomes were SSE, major bleeding, and all-cause mortality. Incidence rates for each clinical outcome were calculated and presented as rate per 100 person-years. Univariate and multivariate analysis was performed to determine the independent predictors for clinical outcomes. RESULTS: There was a total of 3405 patients: mean age was 67.8 ± 11.3 years, 1981 (58.2%) were male. During 30.8 ± 9.7 months follow-up, there was a total of 132 SSE (3.9%), 191 major bleeding (5.6%), and 357 all-cause deaths (10.5%). The incidence rates of SSE, major bleeding, and death were 1.56 (1.30-1.84), 2.26 (1.96-2.61), and 4.17 (3.33-4.25), per 100 person-years respectively. Independent predictors for clinical outcomes were age, type of AF, and the presence of comorbid conditions. CONCLUSION: The incidence rate of SSE, major bleeding, and death remains high reflecting the unmet needs in AF management.

Heightened risks of cardiovascular disease in South Asian populations: causes and consequences.

INTRODUCTION: South Asian individuals comprise almost a quarter of the world's population and have an excess risk of atherosclerotic cardiovascular disease (ASCVD) compared to other ethnicities. In part, this can be explained by higher prevalence, earlier onset, and suboptimal control of traditional cardiovascular risk factors, such as insulin resistance, metabolic syndrome, and dyslipidaemia. However, there remains a significant residual excess risk associated with South Asian ethnicity after controlling for traditional risk factors. AREAS COVERED: In this review, we describe the epidemiology of ASCVD in both native and diaspora South Asian populations. We explore how traditional cardiovascular risk factors, novel cardiovascular risk factors, and social determinants of health may contribute to the excess ASCVD risk seen in South Asian populations. EXPERT OPINION: There should be increased awareness of the relative importance of South Asian ethnicity and related social determinants of health, as risk factors for ASCVD. Systematic screening processes should be tailored to this population, and modifiable risk factors should be treated aggressively. Further research is required to quantify determinants of the excess ASCVD risk seen in South Asian populations and to develop targeted interventions to address these factors.

Anticoagulation in older people with atrial fibrillation moving to care homes: a data linkage study.

BACKGROUND: Treatment decisions about oral anticoagulants (OACs) for atrial fibrillation (AF) are complex in older care home residents. AIM: To explore factors associated with OAC prescription. DESIGN AND SETTING: Retrospective cohort study set in care homes in Wales, UK, listed in the Care Inspectorate Wales Registry 2017/18. METHOD: Analysis of anonymised individual-level electronic health and administrative data was carried out on people aged ≥65 years entering a care home between 1 January 2003 and 31 December 2018, provisioned from the Secure Anonymised Information Linkage Databank. RESULTS: Between 2003 and 2018, 14 493 people with AF aged ≥65 years became new residents in care homes in Wales and 7057 (48.7%) were prescribed OACs (32.7% in 2003 compared with 72.7% in 2018) within 6 months before care home entry. Increasing age and prescription of antiplatelet therapy were associated with lower odds of OAC prescription (adjusted odds ratio [aOR] 0.96 per 1-year age increase, 95% confidence interval [CI] = 0.95 to 0.96 and aOR 0.91, 95% CI = 0.84 to 0.98, respectively). Conversely, prior venous thromboembolism (aOR 4.06, 95% CI = 3.17 to 5.20), advancing frailty (mild: aOR 4.61, 95% CI = 3.95 to 5.38; moderate: aOR 6.69, 95% CI = 5.74 to 7.80; and severe: aOR 8.42, 95% CI = 7.16 to 9.90), and year of care home entry from 2011 onwards (aOR 1.91, 95% CI = 1.76 to 2.06) were associated with higher odds of an OAC prescription. CONCLUSION: There has been an increase in OAC prescribing in older people newly admitted to care homes with AF. This study provides an insight into the factors influencing OAC prescribing in this population.

Mobile health-technology integrated care in atrial fibrillation patients with heart failure: A report from the mAFA-II randomized clinical trial.

BACKGROUND: To assess the effect of mobile health (mHealth) technology-implemented 'Atrial fibrillation Better Care' (ABC) pathway-approach (mAFA intervention) in AF patients with Heart Failure (HF). METHODS: From the Mobile Health Technology for Improved Screening and Optimized Integrated Care in AF (mAFA-II) cluster randomized trial, we evaluated the effect of mAFA intervention on the risk of major outcomes in patients with HF using Inverse Probability of Treatment Weighting. Primary outcome was the composite outcome of stroke/thromboembolism, all-cause death, and rehospitalization. The effect of mAFA and the interaction with HF at baseline was assessed through Cox-regressions. RESULTS: Among the 3,324 patients originally enrolled in the trial, 714 (21.5%; mean age: 72.7±13.1 years; 39.9% females) had HF. The effect of mAFA intervention on the primary outcome was consistent in patients with and without HF (Hazard Ratio, (HR): 0.59, 95% Confidence Interval (CI): 0.29-1.22 vs. HR: 0.40, 95%CI: 0.21-0.76, p for interaction=0.438); similar findings were found for rehospitalisations and bleeding events. A trend towards lower efficacy of mAFA in HF patients was observed for all-cause death, while the risk of the composite outcome of 'recurrent AF, HF and acute coronary syndrome' was higher among AF-HF patients allocated to mAFA (p for interaction: <0.001). CONCLUSION: A mHealth-technology implemented ABC pathway provides consistent effects on the risks of primary outcome, rehospitalisation and bleeding, in AF patients both with and without HF. However, AF-HF patients may need tailored approaches to improve their overall prognosis, specifically to reduce the risk of recurrent AF, HF and acute coronary syndrome.

Men who live alone have worse anticoagulation control: A Danish registry study.

Men living alone may have particular difficulty in managing chronic medical conditions. Anticoagulation control, a sensitive indicator of self-management, was significantly worse among men living alone.

Clinical Features Associated with 'Normal Range' Fibrin D-Dimer Levels in Atrial Fibrillation Patients with Left Atrial Thrombus.

BACKGROUND: Left atrial thrombus (LAT) often complicates with atrial fibrillation (AF). The evidence whether fibrin D-dimer levels could be used as a predictive biomarker for LAT is contradictory. This study firstly investigated the relationship between 'normal range' D-dimer and prevalent LAT. Second, we explored factors contributing to normal D-dimer levels in the presence of LAT. METHODS: We studied 244 AF patients with LAT (mean age: 59.9 years, SD:11.7; 53.3% female): of these, 103 (42.2%) had normal D-dimer, 25 (10.2%) had atrial thrombus exclusion score (ATE score) of 0 19 (16.7%) males had CHA2DS2-VASc score of 0, 21(16.2%) females had CHA2DS2-VASc score of 1 and 16 had overlapped ATE score of 0 and CHA2DS2-VASc score of 0 (N = 8 if male) or CHA2DS2-VASc score of 1(N = 8 if female). Using multivariate binary analysis, larger left atrial diameter (LAD; adjusted OR: 1.06, 1.03-1.10, p = 0.001) were associated with increased D-dimer. Patients with high body mass index (BMI), hypertension history and previous anticoagulation were more likely to show normal range D-dimer levels in the presence of LAT. CONCLUSIONS: A high prevalence (42.2%) of 'normal range' D-dimer levels was found in AF patients with LAT, especially in those with hypertension, high BMI and prior anticoagulation. D-dimer levels of those patients with larger LAD were more likely to be increased.