The influence of progression of atrial fibrillation on quality of life: a report from the Euro Heart Survey.

Aims: Progression of atrial fibrillation (AF) from paroxysmal to persistent forms is an active field of research. The influence of AF progression on health related quality of life (HRQoL) is currently unknown. We aimed to assess the influence of AF progression on HRQoL, and whether this association is mediated through symptoms, treatment, and major adverse events. Methods and results: In the Euro Heart Survey, 967 patients were included with paroxysmal AF who filled out EuroQoL-5D at baseline and at 1 year follow-up. Those who progressed (n = 132, 13.6%) developed more problems during follow-up than those who did not, on all EuroQoL-5D domains (increase in problems on mobility 20.5% vs. 11.4%; self-care 12.9% vs. 6.2%; usual activities 23.5% vs. 14.0%; pain/discomfort 20.5% vs. 13.7%; and anxiety/depression 22.7% vs. 15.7%; all P < 0.05), leading to a decrease in utility [baseline 0.744 ± 0.26, follow-up 0.674 ± 0.36; difference -0.07 (95% CI [-0.126,-0.013], P = 0.02)]. Multivariate analysis showed that the effect of progression on utility is mediated by a large effect of adverse events [stroke (-0.27 (95% CI [-0.43,-0.11]); P = 0.001], heart failure [-0.12 (95% CI [-0.20,-0.05]); P = 0.001], malignancy (-0.31 (95% CI [-0.56,-0.05]); P = 0.02] or implantation of an implantable cardiac defibrillator [-0.12 (95% CI [-0.23,-0.02]); P = 0.03)], as well as symptomatic AF [-0.04 (95% CI [-0.08,-0.01]); P = 0.008]. Conclusion: AF progression is associated with a decrease in HRQoL. However, multivariate analysis revealed that AF progression itself does not have a negative effect on HRQoL, but that this effect can be attributed to a minor effect of the associated symptoms and a major effect of associated adverse events

Poor anticoagulation relates to extended access times for cardioversion and is associated with long-term major cardiac and cerebrovascular events

AbstractBackgroundPatients undergoing elective electrical cardioversion (ECV) for atrial fibrillation have a temporarily increased risk of thromboembolism. Current guidelines recommend adequate anticoagulation for ≥3 consecutive weeks precardioversion, i.e. consecutive INR values 2.0–3.0 in patients with vitamin K antagonists (VKA). We aimed to evaluate the occurrence and impact of subtherapeutic INRs precardioversion and to study factors associated with these unwanted fluctuations.MethodsWe recruited 346 consecutive patients undergoing elective ECV in the Maastricht University Medical Centre between 2008 and 2013. Predictors of subtherapeutic INR values were identified and incorporated into a logistic regression model.ResultsA subtherapeutic INR precardioversion occurred in 55.2% of patients. The only statistically significant predictor was VKA-naivety (Odds Ratio (OR) 4.78, 95% Confidence Interval (CI) 2.67–8.58, p<0.001). In patients with ≥1 subtherapeutic INR precardioversion, time from referral until cardioversion was 91.1±42.8days, compared to 41.7±26.6days (p<0.001) in patients without subtherapeutic INRs.No thromboembolic events occurred <30days after the ECV. Independent predictors for the combined endpoint of cardiovascular death, ischemic stroke and the need of blood transfusion (n=30, median follow-up of 374days) were coronary artery disease in the history (OR 3.35, 95%CI 1.54–7.25, p=0.002) and subtherapeutic INR precardioversion (OR 3.64, 95%CI 1.43–9.24, p=0.007).ConclusionsThe use of VKA often results in subtherapeutic INRs precardioversion and is associated with a significant delay until cardioversion, especially in patients with recent initiation of VKA therapy. Furthermore, subtherapeutic INR levels prior to ECV are associated with the combined endpoint of cardiovascular death, ischemic stroke and the need of blood transfusion

Adherence to the "Atrial fibrillation Better Care" (ABC) pathway in patients with atrial fibrillation and cancer:A report from the ESC-EHRA EURObservational Research Programme in atrial fibrillation (EORP-AF) General Long-Term Registry

BACKGROUND: Implementation of the Atrial fibrillation Better Care (ABC) pathway is recommended by guidelines on atrial fibrillation (AF), but the impact of adherence to ABC pathway in patients with cancer is unknown. OBJECTIVES: To investigate the adherence to ABC pathway and its impact on adverse outcomes in AF patients with cancer. METHODS: Patients enrolled in the EORP-AF General Long-Term Registry were analyzed according to (i) No Cancer; and (ii) Prior or active cancer and stratified in relation to adherence to the ABC pathway. The composite Net Clinical Outcome (NCO) of all-cause death, major adverse cardiovascular events and major bleeding was the primary endpoint. RESULTS: Among 6550 patients (median age 69 years, females 40.1%), 6005 (91.7%) had no cancer, while 545 (8.3%) had a diagnosis of active or prior cancer at baseline, with the proportions of full adherence to ABC pathway of 30.6% and 25.7%, respectively. Adherence to the ABC pathway was associated with a significantly lower occurrence of the primary outcome vs. non-adherence, both in 'no cancer' and 'cancer' patients [adjusted Hazard Ratio (aHR) 0.78, 95% confidence interval (CI): 0.66-0.92 and aHR 0.59, 95% CI 0.37-0.96, respectively]. Adherence to a higher number of ABC criteria was associated with a lower risk of the primary outcome, being lowest when 3 ABC criteria were fulfilled (no cancer: aHR 0.54, 95%CI: 0.36-0.81; with cancer: aHR 0.32, 95% CI 0.13-0.78). CONCLUSION: In AF patients with cancer enrolled in the EORP-AF General Long-Term Registry, adherence to ABC pathway was sub-optimal. Full adherence to ABC-pathway was associated with a lower risk of adverse events

Temporal patterns and short-term progression of paroxysmal atrial fibrillation: data from RACE V

Aims: Atrial fibrillation (AF) often starts as a paroxysmal self-terminating arrhythmia. Limited information is available on AF patterns and episode duration of paroxysmal AF. In paroxysmal AF patients, we longitudinally studied the temporal AF patterns, the association with clinical characteristics, and prevalence of AF progression. Methods and results: In this interim analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) registry, 202 patients with paroxysmal AF were followed with continuous rhythm monitoring (implantable loop recorder or pacemaker) for 6 months. Mean age was 64 ± 9 years, 42% were women. Atrial fibrillation history was 2.1 (0.5–4.4) years, CHA2DS2-VASc 1.9 ± 1.3, 101 (50%) had hypertension, 69 (34%) heart failure. One-third had no AF during follow-up. Patients with long episodes (>12 hours) were often men with more comorbidities (heart failure, coronary artery disease, higher left ventricular mass). Patients with higher AF burden (>2.5%) were older with more comorbidities (worse renal function, higher calcium score, thicker intima media thickness). In 179 (89%) patients, 1-year rhythm follow-up was available. On a quarterly basis, average daily AF burden increased from 3.2% to 3.8%, 5.2%, and 6.1%. Compared to the first 6 months, 111 (62%) patients remained stable during the second 6 months, 39 (22%) showed progression to longer AF episodes, 8 (3%) developed persistent AF, and 29 (16%) patients showed AF regression. Conclusions: In paroxysmal AF, temporal patterns differ suggesting that paroxysmal AF is not one entity. Atrial fibrillation burden is low and determined by number of comorbidities. Atrial fibrillation progression occurred in a substantial number. Trial registration number: Clinicaltrials.gov identifier NCT02726698

Different circulating biomarkers in women and men with paroxysmal atrial fibrillation:results from the AF-RISK and RACE V studies

AIMS: The clinical risk profile of atrial fibrillation (AF) patients is different in men and women. Our aim was to identify sex differences in blood biomarkers in patients with paroxysmal AF. METHODS AND RESULTS: Sex differences in 92 blood biomarkers were measured in 364 patients included in our discovery cohort, the identification of a risk profile to guide atrial fibrillation therapy (AF-RISK) study, assessed by multivariable logistic regression and enrichment pathway analysis. Findings were subsequently confirmed in 213 patients included in our validation cohort, the Reappraisal of Atrial Fibrillation: Interaction between HyperCoagulability, Electrical remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) study. In the discovery cohort, mean age was 59 ± 12 years, 41% were women. CHA(2)DS(2)-VASc-score was 1.6 ± 1.4. A total of 46% had hypertension, 10% diabetes, and 50% had heart failure, predominantly with preserved ejection fraction (47%). In women, activated leucocyte cell adhesion molecule (ALCAM) and fatty acid binding protein-4 (FABP-4) were higher. In men, matrix metalloproteinase-3 (MMP-3), C-C motif chemokine-16 (CCL-16), and myoglobin were higher. In the validation cohort, four out of five biomarkers could be confirmed: levels of ALCAM (P = 1.73 × 10(–4)) and FABP-4 (P = 2.46 × 10(–7)) and adhesion biological pathways [false discovery rate (FDR) = 1.23 × 10(–8)] were higher in women. In men, levels of MMP-3 (P = 4.31 × 10(–8)) and myoglobin (P = 2.10 × 10(–4)) and markers for extracellular matrix degradation biological pathways (FDR = 3.59 × 10(–9)) were higher. CONCLUSION: In women with paroxysmal AF, inflammatory biomarkers were more often higher, while in men with paroxysmal AF, biomarkers for vascular remodelling were higher. Our data support the clinical notion that pathophysiological mechanisms in women and men with AF may differ. TRIAL REGISTRATION: Clinicaltrials.gov identifier NCT01510210 for AF-RISK; Clinicaltrials.gov NCT02726698 for RACE V

Temporal patterns and short-term progression of paroxysmal atrial fibrillation data from RACE V

Aims Atrial fibrillation (AF) often starts as a paroxysmal self-terminating arrhythmia. Limited information is available on AF patterns and episode duration of paroxysmal AF. In paroxysmal AF patients, we longitudinally studied the temporal AF patterns, the association with clinical characteristics, and prevalence of AF progression. Methods and results In this interim analysis of the Reappraisal of AF: Interaction Between HyperCoagulability, Electrical Remodelling, and Vascular Destabilisation in the Progression of AF (RACE V) registry, 202 patients with paroxysmal AF were followed with continuous rhythm monitoring (implantable loop recorder or pacemaker) for 6 months. Mean age was 64 +/- 9 years, 42% were women. Atrial fibrillation history was 2.1 (0.5-4.4) years, CHA(2)DS(2)-VASc 1.9 +/- 1.3, 101 (50%) had hypertension, 69 (34%) heart failure. One-third had no AF during follow-up. Patients with long episodes (>12 hours) were often men with more comorbidities (heart failure, coronary artery disease, higher left ventricular mass). Patients with higher AF burden (>2.5%) were older with more comorbidities (worse renal function, higher calcium score, thicker intima media thickness). In 179 (89%) patients, 1-year rhythm follow-up was available. On a quarterly basis, average daily AF burden increased from 3.2% to 3.8%, 5.2%, and 6.1%. Compared to the first 6 months, 111 (62%) patients remained stable during the second 6 months, 39 (22%) showed progression to longer AF episodes, 8 (3%) developed persistent AF, and 29 (16%) patients showed AF regression. Conclusion In paroxysmal AF, temporal patterns differ suggesting that paroxysmal AF is not one entity. Atrial fibrillation burden is low and determined by number of comorbidities. Atrial fibrillation progression occurred in a substantial number

Contemporary stroke prevention strategies in 11 096 European patients with atrial fibrillation: A report from the EURObservational Research Programme on Atrial Fibrillation (EORP-AF) Long-Term General Registry

Aims: Contemporary data regarding atrial fibrillation (AF) management and current use of oral anticoagulants (OACs) for stroke prevention are needed. Methods and results: The EURObservational Research Programme on AF (EORP-AF) Long-Term General Registry analysed consecutive AF patients presenting to cardiologists in 250 centres from 27 European countries. From 2013 to 2016, 11 096 patients were enrolled (40.7% female; mean age 69 ± 11 years). At discharge, OACs were used in 9379 patients (84.9%), with non-vitamin K antagonists (NOACs) accounting for 40.9% of OACs. Antiplatelet therapy alone was used by 20% of patients, while no antithrombotic treatment was prescribed in 6.4%. On multivariable analysis, age, hypertension, previous ischaemic stroke, symptomatic AF and planned cardioversion or ablation were independent predictors of OAC use, whereas lone AF, previous haemorrhagic events, chronic kidney disease and admission for acute coronary syndrome (ACS) or non-cardiovascular causes independently predicted OAC non-use. Regarding the OAC type, coronary artery disease, history of heart failure, or valvular heart disease, planned cardioversion and non-AF reasons for admission independently predicted the use of vitamin K antagonists (VKAs). Wide variability among the European regions was observed in the use of NOACs, independently from other clinical factors. Conclusion: The EORP-AF Long-Term General Registry provides a full picture of contemporary use of OAC in European AF patients. The overall rate of OACs use was generally high (84.9%), and a series of factors were associated with the prescription of OAC. A significant geographical heterogeneity in prescription of NOACs vs. VKAs was evident

Atherothrombosis and Thromboembolism: Position Paper from the Second Maastricht Consensus Conference on Thrombosis

Atherothrombosis is a leading cause of cardiovascular mortality and long-term morbidity. Platelets and coagulation proteases, interacting with circulating cells and in different vascular beds, modify several complex pathologies including atherosclerosis. In the second Maastricht Consensus Conference on Thrombosis, this theme was addressed by diverse scientists from bench to bedside. All presentations were discussed with audience members and the results of these discussions were incorporated in the final document that presents a state-of-the-art reflection of expert opinions and consensus recommendations regarding the following five topics:  1. Risk factors, biomarkers and plaque instability: In atherothrombosis research, more focus on the contribution of specific risk factors like ectopic fat needs to be considered; definitions of atherothrombosis are important distinguishing different phases of disease, including plaque (in)stability; proteomic and metabolomics data are to be added to genetic information.  2. Circulating cells including platelets and atherothrombosis: Mechanisms of leukocyte and macrophage plasticity, migration, and transformation in murine atherosclerosis need to be considered; disease mechanism-based biomarkers need to be identified; experimental systems are needed that incorporate whole-blood flow to understand how red blood cells influence thrombus formation and stability; knowledge on platelet heterogeneity and priming conditions needs to be translated toward the in vivo situation.  3. Coagulation proteases, fibrin(ogen) and thrombus formation: The role of factor (F) XI in thrombosis including the lower margins of this factor related to safe and effective antithrombotic therapy needs to be established; FXI is a key regulator in linking platelets, thrombin generation, and inflammatory mechanisms in a renin–angiotensin dependent manner; however, the impact on thrombin-dependent PAR signaling needs further study; the fundamental mechanisms in FXIII biology and biochemistry and its impact on thrombus biophysical characteristics need to be explored; the interactions of red cells and fibrin formation and its consequences for thrombus formation and lysis need to be addressed. Platelet–fibrin interactions are pivotal determinants of clot formation and stability with potential therapeutic consequences.  4. Preventive and acute treatment of atherothrombosis and arterial embolism; novel ways and tailoring? The role of protease-activated receptor (PAR)-4 vis à vis PAR-1 as target for antithrombotic therapy merits study; ongoing trials on platelet function test-based antiplatelet therapy adjustment support development of practically feasible tests; risk scores for patients with atrial fibrillation need refinement, taking new biomarkers including coagulation into account; risk scores that consider organ system differences in bleeding may have added value; all forms of oral anticoagulant treatment require better organization, including education and emergency access; laboratory testing still needs rapidly available sensitive tests with short turnaround time.  5. Pleiotropy of coagulation proteases, thrombus resolution and ischaemia–reperfusion: Biobanks specifically for thrombus storage and analysis are needed; further studies on novel modified activated protein C–based agents are required including its cytoprotective properties; new avenues for optimizing treatment of patients with ischaemic stroke are needed, also including novel agents that modify fibrinolytic activity (aimed at plasminogen activator inhibitor-1 and thrombin activatable fibrinolysis inhibitor