The year in cardiology: arrhythmias and pacing.

During this last year, there has been much progress with regard to anticoagulant and ablation therapy for atrial fibrillation (AF). Apart from recently issued European Society of Cardiology Guidelines for the management of patients with supraventricular arrhythmias, there has been little progress in research in this field. Ventricular arrhythmias and device therapy have seen modest progress

Electronic health record-wide association study for atrial fibrillation in a British cohort

Background: Atrial fibrillation (AF) confers a major healthcare burden from hospitalisations and AF-related complications, such as stroke and heart failure. We performed an electronic health records-wide association study to identify the most frequent reasons for healthcare utilization, pre and post new-onset AF. Methods: Prospective cohort study with the linked electronic health records of 5.6 million patients in the United Kingdom Clinical Practice Research Datalink (1998–2016). A cohort study with AF patients and their age-and sex matched controls was implemented to compare the top 100 reasons of frequent hospitalisation and primary consultation. Results: Of the 199,433 patients who developed AF, we found the most frequent healthcare interactions to be cardiac, cerebrovascular and peripheral-vascular conditions, both prior to AF diagnosis (41/100 conditions in secondary care, such as cerebral infarction and valve diseases; and 33/100 conditions in primary care), and subsequently (47/100 conditions hospital care and 48 conditions in primary care). There was a high representation of repeated visits for cancer and infection affecting multiple organ systems. We identified 10 novel conditions which have not yet been associated with AF: folic acid deficiency, pancytopenia, idiopathic thrombocytopenic purpura, seborrheic dermatitis, lymphoedema, angioedema, laryngopharyngeal reflux, rib fracture, haemorrhagic gastritis, inflammatory polyneuropathies. Conclusion: Our nationwide data provide knowledge and better understanding of the clinical needs of AF patients suggesting: (i) groups at higher risk of AF, where screening may be more cost-effective, and (ii) potential complications developing following new-onset AF that can be prevented through implementation of comprehensive integrated care management and more personalised, tailored treatment. Clinical trial registration: NCT0478636

Cardiac rehabilitation meta-analysis of trials in patients with coronary heart disease using individual participant data (CaReMATCH): Project protocol

Background: Exercise-based cardiac rehabilitation (CR) has long been a cornerstone in the secondary prevention of coronary heart disease (CHD). Despite meta-analyses of randomised trials demonstrating a positive impact of CR on cardiovascular mortality, hospitalisation, exercise capacity and health related quality of life, the impact of CR on all-cause mortality remains uncertain, especially in the context of contemporary clinical practice. This CR meta-analysis of trials in patients with coronary heart disease using individual participant data (IPD) (CaReMATCH) seeks to (1) provide definitive estimates of the effectiveness of CR in terms of all-cause mortality, cardiovascular mortality, hospitalisation and health-related quality of life, and (2) determine the influence of individual patient characteristics (e.g. age, sex, risk factors) on the effectiveness of CR to inform a personalised CR-approach. Methods: Randomised controlled trials will be identified that were performed in the last decade, to ensure that CR was performed in combination with contemporary medical care (2010–2020). For our first aim, outcomes of interest include all cause- and CVD-related mortality and hospitalisations. To answer our second research question, we will collect data on exercise capacity, health-related quality of life, and patient baseline demographic and clinical data. Original IPD will be requested from the authors of all eligible trials; we will check original data and compile a master dataset. IPD meta-analyses will be conducted using a one-step meta-analysis approach where the IPD from all studies are modelled simultaneously whilst accounting for the clustering of participants within studies. Discussion: Findings from CaReMATCH will inform future (inter)national clinical and policy decision-making on the (personalised) application of exercise-based CR for patients with CHD

The relationship of renal function to outcome: A post hoc analysis from the EdoxabaN versus warfarin in subjectS UndeRgoing cardiovErsion of Atrial Fibrillation (ENSURE-AF) study.

The ENSURE-AF study (NCT 02072434) of anticoagulation for electrical cardioversion in nonvalvular atrial fibrillation (NVAF) showed comparable low rates of bleeding and thromboembolism between the edoxaban and the enoxaparin-warfarin treatment arms. This post hoc analysis investigated the relationship between renal function and clinical outcomes. METHODS: ENSURE-AF was a multicenter, PROBE evaluation trial of edoxaban 60 mg, or dose reduced to 30 mg/d for weight≤60 kg, creatinine clearance (CrCl; Cockcroft-Gault) ≤50 mL/min, or concomitant P-glycoprotein inhibitors compared with therapeutically monitored enoxaparin-warfarin in 2,199 NVAF patients undergoing electrical cardioversion. Efficacy and safety outcomes and time in therapeutic range in the warfarin arm were analyzed in relation to CrCl in prespecified ranges ≥15 and ≤30, >30 and ≤50, >50 and 30 to ≤50 compared with 71.8% in those with CrCl ≥80. The odds ratios for the primary efficacy and safety end points were comparable for the different predefined renal function strata; given the small numbers, the 95% CI included 1.0. In the subset of those with CrCl ≥95, the odds ratios showed consistency with the other CrCl strata. When CrCl was assessed as a continuous variable, there was a nonsignificant trend toward higher major or clinically relevant nonmajor bleeding with reducing CrCl levels, with no significant differences between the 2 treatment arms. When we assessed CrCl at baseline compared with end of treatment, there were no significant differences in CrCl change between the edoxaban and enoxaparin-warfarin arms. The proportions with worsening of renal function (defined as a decrease of >20% from baseline) were similar in the 2 treatment arms. CONCLUSION: Given the small number of events in ENSURE-AF, no effect of renal (dys)function was demonstrated in comparing edoxaban to enoxaparin-warfarin for cardioversion; efficacy and safety of edoxaban remained consistent even in patients with normal or supranormal renal function

Viewpoint Stroke prevention in recent guidelines for the management of patients with atrial fibrillation: An appraisal.

Formal guidelines play an important role in disseminating the best available evidence knowledge and are expected to provide simple and practical recommendations for the most optimal management of patients with various conditions. Such guidelines have important implications for many disease states, which thereby could be more professionally managed in everyday clinical practice by clinicians with divergent educational backgrounds, and also more easily implemented in wards or outpatient clinics eliminating inequalities in health care management. In this brief Viewpoint, we provide an appraisal on the recommendations pertinent to the prevention of atrial fibrillation-related stroke or systemic thromboembolism, as provided in recently published guidelines for the management of this arrhythmia

Cerebrovascular Dysfunction in Atrial Fibrillation

© Copyright © 2020 Junejo, Lip and Fisher. It is now well established that besides being the most common sustained arrhythmia, atrial fibrillation (AF) is a major healthcare burden. Risk of debilitating stroke is increased in AF patients, but even in the absence of stroke, this population is at heightened risk of cognitive decline, depression, and dementia. The reasons for this are complex, multifactorial, and incompletely understood. One potential contributing mechanism is cerebrovascular dysfunction. Cerebral blood flow is regulated by chemical, metabolic, autoregulatory, neurogenic, and systemic factors. The dysfunction in one or more of these mechanisms may contribute to the elevated risk of cognitive decline and cerebrovascular events in AF. This short review presents the evidence for diminished cerebral blood flow, cerebrovascular carbon dioxide reactivity (i.e., cerebrovascular vasodilatory reserve), cerebral autoregulation, and neurovascular coupling in AF patients when compared to control participants in sinus rhythm. Further work is needed to understand the physiological mechanisms underpinning these observations and their clinical significance in atrial fibrillation patients

Optimizing adherence and persistence to non-vitamin K antagonist oral anticoagulant therapy in atrial fibrillation

Atrial fibrillation (AF) is associated with an increased risk of stroke, which can be prevented by the use of oral anticoagulation. Although non-vitamin K antagonist oral anticoagulants (NOACs) have become the first choice for stroke prevention in the majority of patients with non-valvular AF, adherence and persistence to these medications remain suboptimal, which may translate into poor health outcomes and increased healthcare costs. Factors influencing adherence and persistence have been suggested to be patient-related, physician-related, and healthcare system-related. In this review, we discuss factors influencing patient adherence and persistence to NOACs and possible problem solving strategies, especially involving an integrated care management, aiming for the improvement in patient outcomes and treatment satisfaction

Myocardial Strain Imaging in Resistant Hypertension.

PURPOSE OF REVIEW: Resistant hypertension (RH) is a major contributor to cardiovascular diseases and is associated with increased all-cause and cardiovascular mortality. Cardiac changes such as impaired left ventricular (LV) function, left ventricular hypertrophy (LVH), myocardial fibrosis, and enlarged left atrium (LA) are consequences of chronic exposure to an elevated blood pressure. The purpose of this review article is to demonstrate the potential benefits of using STE as a non-invasive imaging technique in the assessment of cardiac remodeling in patients with hypertension and specifically in uncontrolled and RH population. RECENT FINDINGS: It is well-recognized that conventional transthoracic echocardiography is a useful analytic imaging modality to evaluate hypertension-mediated organ damage (HMOD) and in a resistant hypertensive population. More recently two-dimensional speckle tracking echocardiography (STE) has been utilized to provide further risk assessment to this population. Recent data has shown that STE is a new promising echocardiographic marker to evaluate early stage LV dysfunction and myocardial fibrosis over conventional 2D parameters in patients with cardiovascular diseases

Relationship between Renal Function, Fibrin Clot Properties and Lipoproteins in Anticoagulated Patients with Atrial Fibrillation

Background: Mechanisms by which chronic kidney disease (CKD) influences fibrin clot properties in atrial fibrillation (AF) remain ill-defined. We aimed to investigate the effects of AF and CKD on fibrin clot properties and lipoproteins, and determine the relationship between these factors. Methods: Prospective cross-sectional study of patients recruited from cardiology services in Liverpool between September 2019 and October 2021. Primary groups consisted of anticoagulated AF patients with and without CKD in a 1:1 ratio. Control group comprised anticoagulated patients without AF or CKD. Fibrin clot properties were analysed using turbidity and permeation assays. Detailed lipoprotein characteristics, including total cholesterol, low-density lipoprotein cholesterol (LDL-C), small dense LDL and oxidised LDL, were measured. Results: Fifty-six anticoagulated patients were enrolled (median age 72.5; 34% female); 46 with AF (23 with CKD and 23 without CKD) and 10 controls. AF was associated with changes in three indices of fibrin clot properties using PTT (Tlag 314 vs. 358 s, p = 0.047; Abspeak 0.153 vs. 0.111 units, p = 0.031; Tlysis50% 884 vs. 280 s, p = 0.047) and thrombin reagents (Tlag 170 vs. 132 s, p = 0.031; Tmax 590 vs. 462 s, p = 0.047; Tpeak50% 406 vs. 220 s, p = 0.005) while the concomitant presence of CKD led to changes in fibrin clot properties using kaolin (Tlag 1072 vs. 1640 s, p = 0.003; Tmax 1458 vs. 1962 s, p = 0.005; Tpeak50% 1294 vs. 2046, p = 0.008) and PPP reagents (Tlag 566 vs. 748 s, p = 0.044). Neither of these conditions were associated with changes in fibrin clot permeability. Deteriorating eGFR was significantly correlated to the speed of clot formation, and CKD was independently associated with unfavourable clot properties (Tlag −778, p = 0.002; Tmax −867, p = 0.004; Tpeak50% −853, p = 0.004 with kaolin reagent). AF alone was not associated with changes in lipoprotein distribution while AF patients with CKD had lower total cholesterol, LDL-C and small dense LDL due to the presence of other risk factors. No significant relationship was observed between fibrin clot properties and lipoprotein distribution. Conclusions: There are important changes that occur in fibrin clot properties with AF and CKD that may account for the increased risk of thromboembolic complications. However, these changes in fibrin clot properties were not attributable to alterations in lipoprotein distribution

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