Kazuo Miyazawa

Left atrial thrombus resolution in non-valvular atrial fibrillation or flutter: Biomarker substudy results from a prospective study with rivaroxaban (X-TRA)

Abstract Background: Non-vitamin K antagonist oral anticoagulants including rivaroxaban are widely used for stroke prevention in patients with atrial fibrillation (AF). We investigated the relationship between plasma biomarkers (indicative of thrombogenesis, fibrinolysis and inflammation) and left atrial thrombus resolution after rivaroxaban treatment. Methods: This was an ancillary analysis of the X-TRA study, which was a prospective interventional study evaluating the use of rivaroxaban for left atrial/left atrial appendage (LA/LAA) thrombus resolution in AF patients. We assessed various biomarkers of thrombogenesis/fibrinolysis [D-dimer, plasminogen activator inhibitor-1 (PAI-1), prothrombin fragment 1u2009+u20092 (F1,2), thrombin–antithrombin (TAT) complexes, von Willebrand factor (vWF)] and inflammation [high-sensitivity interleukin-6 (hsIL-6), and high-sensitivity C-reactive protein (hsCRP)], measured at baseline and after 6 weeks’ of rivaroxaban treatment. Results: There was a significant decrease in the mean levels of hsCRP, D-dimer, vWF, and TAT from baseline to end of treatment with rivaroxaban. Although none of the thrombogenesis/fibrinolysis biomarkers showed a significant relationship with thrombus resolution, high inflammatory biomarkers at baseline were significantly associated with an increased chance of the thrombus being completely resolved (hsIL-6) or reduced/resolved (hsCRP). Conclusions: Biomarkers of inflammation are significantly associated with LA/LAA thrombus outcomes in AF patients prospectively treated with rivaroxaban. KEY MESSAGES Changes in the thrombogenesis/fibrinolysis biomarker levels reflected the expected pharmacodynamics of rivaroxaban. Higher levels of inflammation biomarkers were significantly associated with thrombus being completely resolved or reduced.

Quantifying Time in Atrial Fibrillation and the Need for Anticoagulation

Atrial fibrillation (AF) is one of the major cardiovascular diseases, and the number of patients with AF is predicted to increase markedly in the coming years. Despite recent advance in management of patients with AF, AF remains one of the main causes of stroke or systemic embolism. Application of simple stroke risk-stratification schemes, such as the CHA2DS2-VASc score has been introduced to identify patients who mostly benefit from oral anticoagulants (OACs) for stroke prevention. Current medical devices allow the detection of short and asymptomatic episodes of AF, termed atrial high rate episodes (AHREs), which are also associated with an increased risk of thromboembolism. Early diagnosis of AF has clinical importance for a timely initiation of OAC, while strokes often occur without AHRE detected within 30days before the event. Consequently, it is unclear whether any AHRE imply the same therapeutic requirements as clinical AF. The exact estimation of AF burden and correct risk stratification in patients with asymptomatic AF and AHRE remains a challenge in clinical practice.

Atrial fibrillation and hypertrophic cardiomyopathy: co-existing conditions with additive risks

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One-year risks of stroke and mortality in patients with atrial fibrillation from different clinical settings: The Gulf SAFE registry and Darlington AF registry

BACKGROUNDnDifferences exist in oral anticoagulation (OAC) use between different populations with atrial fibrillation (AF), which may be associated with varying outcomes.nnnPURPOSEnWe aimed to provide patient level comparisons of two cohorts of patients with AF, from the United Kingdom (UK) and Middle East (ME).nnnMETHODSnThe clinical characteristics, prescription of OAC, one-year risk of stroke and mortality were compared between individual patients with AF included into the Darlington AF registry (UK, nu202f=u202f2258) and the Gulf SAFE (Survey of atrial fibrillation events) registry (ME, nu202f=u202f1740).nnnRESULTSnA high percentage of patients from the Darlington registry were candidates for OAC (i.e., CHA2DS2-VASc score ≥2 in males or ≥3 in females; 82.0% in Darlington and 57.1% in Gulf SAFE). OAC use was suboptimal (52.0% in Darlington vs 58.4% in Gulf SAFE). One-year rates of stroke and mortality were high in both populations, especially in those with CHA2DS2-VASc score ≥2 in males and ≥3 in females (Darlington vs. Gulf SAFE: 3.51% vs. 5.63 for stroke; 11.4% vs. 16.8% for mortality). On multivariate analyses, female sex and previous stroke were independently associated with stroke events; while elderly age, female sex, vascular disease and heart failure were independent risk factors for mortality (all pu202f<u202f0.05). Patients from Gulf SAFE registry had higher risk of stroke (odds ratio, 2.18 [1.47-3.23]) and mortality (odds ratio, 1.67 [1.31-2.14]) compared with those from Darlington registry. The CHA2DS2-VASc score showed good discrimination in predicting one-year risk of stroke (area under curve, 0.71 [0.65-0.76] in non-anticoagulated patients) and mortality (area under curve, 0.70 [0.68-0.72]) in the whole study population, as well as in Darlington or Gulf SAFE registry separately.nnnCONCLUSIONSnStroke prevention was generally suboptimal in patient cohorts from the two registries, which was associated with high one-year risks of stroke and mortality, particularly so among patients from the Gulf SAFE registry. The higher risks for stroke and mortality in AF patients from the Gulf SAFE registry (compared to a UK cohort) merit further implementation of cardiovascular prevention strategies.

Secondary stroke prevention and guideline adherent antithrombotic treatment in patients with atrial fibrillation: Insights from the Gulf Survey of atrial fibrillation events (Gulf SAFE)

BACKGROUNDnAnticoagulation therapy in patients with atrial fibrillation (AF) is well established as effective thromboprophylaxis. However, AF patients with prior stroke are often treated with suboptimal antithrombotic treatment (ATT). In the present study, we investigated clinical characteristics and outcomes in AF patients with versus without prior stoke, in relation to guideline adherence in ATT.nnnMETHODSnWe used data from the Gulf SAFE registry, which included patients with AF who presented to hospitals in Gulf countries of the Middle East. Adherence to guideline recommended ATT was assessed against the European Society of Cardiology guidelines.nnnRESULTSnOf 1860 patients, 15.4% had a history of stroke (secondary stroke prevention). For secondary stroke prevention, 62.0% of patients were prescribed oral anticoagulants, while 27.9% were still prescribed antiplatelet therapy alone and 10.1% received no ATT. Overall, 49.0% were treated with guideline adherent ATT, 25.5% were undertreated, and 25.4% were overtreated. On multivariable logistic regression analysis, undertreatment (OR; 2.763, 95% CI; 1.426-5.352, pu202f=u202f0.003) was significantly associated with an increased risk of 1-year stroke. On the other hand, overtreatment was significantly associated with an increased risk of 1-year bleeding (OR; 3.294, 95% CI; 1.517-7.152, pu202f=u202f0.003).nnnCONCLUSIONSnOnly half of the AF patients received optimal ATT for stroke prevention if we apply guideline recommendations. Guideline adherent ATT significantly reduced the risk of stroke and bleeding compared with non-guideline adherent ATT.

Current and emerging pharmacotherapy for ischemic stroke prevention in patients with atrial fibrillation

ABSTRACT Introduction: Atrial fibrillation (AF) is associated with high morbidity and mortality rates due to thromboembolic complications, and anticoagulation is central to the management of this common arrhythmia to prevent acute thromboembolic events. The traditional anticoagulants: heparin, fondaparinux, and vitamin K antagonists (VKA, e.g. warfarin, acenocoumarol or phenprocoumin) have long served as pharmacotherapy for ischemic stroke prophylaxis. Areas covered: In this review article, the authors provide an overview on current and emerging pharmacotherapy for ischemic stroke prevention. Furthermore, they review the data from novel therapeutic targets in the coagulation cascade, and investigational anticoagulant drugs currently assessed in preclinical and clinical studies. Expert opinion: The introduction of nonvitamin K antagonist oral anticoagulants (NOACs) was an important milestone, as these drugs show relative efficacy, safety, and convenience compared to the VKAs. Nevertheless, their clinical use still has some limitations with, for example, patients with severe renal impairment and those with mechanical heart valves, high bleeding risks, lack of standard laboratory monitoring and (some) reversal agents. To overcome some of these limitations, various attempts are now underway to discover new strategies and targets via the hemostatic pathway in order to develop new coagulation inhibiting drugs.

Risk factors for the development of incident atrial fibrillation in patients with cardiac implantable electronic devices

INTRODUCTIONnCardiac implantable electronic devices (CIEDs) can detect atrial fibrillation (AF) early and accurately. Risk factors for the development of new-onset AF in patients with CIEDs remains uncertain.nnnMETHODSnPatients with CIEDs who visited Chiba University Hospital between January 2016 and December 2016 were enrolled. We only included patients without single chamber CIEDs or a known history of AF.nnnRESULTSnOf 371 patients with CIEDs, 78 (21.0%; median age 61.0u202fyears, 65.5% male) developed new-onset AF. Multivariate analysis demonstrated that independent predictors for the development of new or incident AF were age ≥65u202fyears (odd ratio [OR] 2.76, 95% confidence interval [CI] 1.54-4.96, Pu202f=u202f0.001), diabetes mellitus (OR 2.24, 95% CI 1.20-4.19, Pu202f=u202f0.011), congestive heart failure (OR 1.94, 95% CI 1.06-3.54, Pu202f=u202f0.031), and left atrial volume index >34u202fml/m2 (OR 3.51, 95% CI 1.96-6.25, Pu202f<u202f0.001). Based on these 4 clinical factors (ageu202f≥u202f65, diabetes mellitus, congestive heart failure, left atrial volume indexu202f>u202f34u202fml/m2) there was a good predictive ability for new AF development (AUC 0.728) and clinically usefulness using decision curve analysis.nnnCONCLUSIONSnA substantial number of patients with CIEDs develop new-onset AF. Four clinical factors (ageu202f≥u202f65, diabetes mellitus, congestive heart failure, left atrial volume indexu202f>u202f34u202fml/m2) independently predicted new-onset AF and may provide an approach to clinically useful risk assessment for incident AF.

Inflammation and the risk of atrial high-rate episodes (AHREs) in patients with cardiac implantable electronic devices

IntroductionAtrial high-rate episodes (AHREs) are associated with an increased risk of developing atrial fibrillation and thromboembolism. The characteristics of ‘real world’ patients developing AHREs are poorly known.MethodsWe included 496 consecutive patients with cardiac implantable electronic devices (CIEDs). Primary endpoint was occurrence of AHREs, defined as >u2009175xa0bpm and lastingu2009>u20095xa0min, in a median follow-up of 16.5 (IQR 3.9–38.6) months (1082.4 patient-years). We also tested the predictive value of clinical risk scores for AHREs.ResultsMean age was 68.8u2009±u200914.0xa0years, and 35.5% were women; AHREs were recorded in 173xa0patients [34.7%, 16.0%/year, 95% confidence interval (CI) 13.7–18.6]. Multivariable Cox regression analysis showed that age [hazard ratio (HR) 1.020, 95% CI 1.004–1.035, pu2009=u20090.011], prior AF (HR 3.521, 95% CI 2.831–5.206, pu2009<u20090.001), white cell count (HR 1.039, 95% CI 1.007–1.072, pu2009=u20090.016) and high C reactive protein (CRP; HR 1.039, 95% CI 1.021–2.056, pu2009=u20090.038) were independently associated with AHREs. ROC curve analysis showed that the APPLE score (C statistic 0.53, 95% CI 0.48–0.59; pu2009=u20090.296) ALARMEc score (C statistic 0.51, 95% CI 0.44–0.57; pu2009=u20090.810) were non-significantly associated with AHRE. Similar results were obtained for CHADS2 and CHA2DS2VASc scoreConclusionAHREs are common in CIEDs patients, with age, prior AF, inflammatory markers (high CRP, white cell count) being factors associated with AHREs onset. Clinical risk scores showed limited value for AHREs prediction in this cohort.

Changes in renal function in patients with atrial fibrillation: efficacy and safety of the non-vitamin K antagonist oral anticoagulants

American Heart Journal - In Press.Proof corrected by the author Available online since mercredi 31 janvier 2018