Chronic Nonvalvular Atrial Fibrillation Research Articles

The Relationship between Hyperuricemia and Echocardiographic Parameters in Patients with Chronic Atrial Fibrillation.

Purpose Uric acid serves as a marker for cardiovascular risk and is often linked to inflammation and oxidative stress. There is evidence suggesting an association between uric acid and atrial fibrillation (AF), including its severity and occurrence of crises, as well as its involvement in cardiovascular mechanisms. The objective of this study was to assess the correlation between hyperuricemia and echocardiographic features in patients with chronic AF lasting for more than 5 years. Methods This case-control study involved 107 patients diagnosed with chronic non-valvular AF. Uric acid levels were measured in all patients, and they were divided into two groups: the first group consisted of 66 patients with hyperuricemia (>7.2 mg/dL), while the second group included 41 patients with normal uric acid levels. Echocardiography (TTE) was performed to evaluate each patient. Various clinical and echocardiographic parameters, such as left ventricle telediastolic (LVTDD) and telesystolic (LVTSD) diameters, left atrial diameter (LAD), aortic diameter (AoD), ejection fraction (EF), and pulmonary artery pressure (PAP), were analyzed. Results Binary logistic regression analysis revealed a statistically significant relationship between uric acid levels (>7.2 mg/dL) and LAD. For each unit increase in LAD, the probability of having hyperuricemia increased by 9% [odds ratio (OD): 0.91, 95% confidence interval (CI): 0.84-0.99]. A significant relationship was found between uric acid levels (>8 mg/dL) and LVESD (p = 0.045) as well as PAP (p = 0.006). For every unit increase in LVESD, the likelihood of having uric acid levels greater than 8 mg/dL increased by 22% [OD: 0.82, 95% CI: 0.67-0.99, b = -0.2]. Likewise, for each unit increase in PAP, the probability of having uric acid levels greater than 8 mg/dL was 9.4% [OD: 0.91, 95% CI: 0.86-0.97, b = -0.09]. Conclusions This study demonstrates that hyperuricemia has a significant relationship with the development of atrial remodeling, with an important association observed between hyperuricemia and an increase in left atrial diameter. Hyperuricemia is also correlated with an enlargement of the left ventricle end-systolic diameter and pulmonary artery pressure, showing a possible influence that hyperuricemia might have also left ventricle morphology and right ventricle function.

A case of cardioembloic stroke with wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome

Here, we report a case of an 85-year-old man who presented sudden onset of diplopia, dysarthria, and gait disturbance. On admission, he exhibited bilateral adduction palsy, convergence palsy, and binocular exotropia in the forward gaze showing wall-eyed bilateral internuclear ophthalmoplegia (WEBINO) syndrome. He had a history of chronic nonvalvular atrial fibrillation. DWI-MRI revealed acute ischemic lesions in the paramedian pontine tegmentum, lower midbrain, both cerebellar hemispheres, and left frontal cortex. He was thus diagnosed with an acute phase of cardioembolic stroke. Subsequently, the right eye adduction palsy in the forward gaze was slightly improved, but other eye movement disorders persisted during discharge from the hospital. The pathology was suspected to involve bilateral damages to both medial longitudinal fasciculus and the paramedian pontine reticular formation. WEBINO syndrome was not only ascribed to lacunar infarction and large artery atherosclerosis but also cardioembolic stroke. The presence of other non-eye symptoms and multiple ischemic lesions could be the characteristics of WEBINO syndrome following cardioembolic stroke.

Relation of apixaban bleeding rates to dose in patients with chronic kidney disease

The objective of this study was to evaluate the safety and efficacy of apixaban 5 mg twice daily vs 2.5 mg twice daily for nonvalvular atrial fibrillation or venous thromboembolism in patients with chronic kidney disease stage 4 and 5, including those on hemodialysis. Data were collected retrospectively on patients with advanced chronic kidney disease and nonvalvular atrial fibrillation and/or venous thromboembolism who received apixaban while hospitalized at our institution between January 2013 and August 2018. The 5 mg twice daily group included 22 patients, and the 2.5 mg twice daily group included 73 patients. There was no difference between groups in major bleeding events (9.1% vs. 12.3%, P = 1.00), any bleeding event (45.4% vs. 67.1%, P = 0.08), ischemic stroke (0% vs. 2.7%, P = 1.00), or venous thromboembolism (4.5% vs. 0%, P = 0.23). Subgroup analyses of patients with a serum creatinine >2.5 mg/dL or creatinine clearance <25 mL/min and patients on hemodialysis produced similar results. Until larger trials are conducted, clinicians should make patient-specific decisions about the optimal dose of apixaban in patients with severe renal impairment.

Beat-to-beat blood pressure measurement in patients with atrial fibrillation: a step towards personalized managemen

Aim. Blood pressure (BP) determination in atrial fibrillation (AF) patients remains challenging due to its high inter-measurement variability. The novel methodology of precise beat-to-beat BP determination may be used to guide the hypotensive therapy selection and adjustment, but along with that provides additional opportunity for the investigation of hemodynamics in patients with chronic AF.Material and method. The study sample consisted of 60 patients with the main diagnosis of grade II-III arterial hypertension; 30 of those were on sinus rhythm and 30 had chronic non-valvular AF. In all patients HR was within the limits recommended for left ventricular ejection fraction of &gt;40%. Beat-to-beat systolic, diastolic, and pulse BP (SBP, DBP, and PBP, respectively) assessment at each heart beat within 15 minute interval was performed with “Kardiotekhnika-SAKR” system (NAO “Incart”, St.Petersburg, Russia).

Hyperuricemia in patients with chronic atrial fibrillation

Uric acid is a cardiovascular risk marker, often associated with inflammation & oxidative stress. There is evidence that associate it with atrial fibrillation (AF), its severity and crisis and showing its association with mechanisms of heart. The aim of this study was to evaluate the relationship between hyperuricemia & echocardiogaphic features in patients with chronic AF for more than 5 years. This was a case-control study which included 107 patients with chronic non-valvular AF. Uricemia was measured in all patients and they were divided into 2 groups: the first consisted in 66 patients with hyperuricemia (> 7.2 mg/dL) and the second in 41 patients with normal uricemia. Every patient was evaluated through echocardiography (TTE). All clinical data (age, disease duration, sex), echocardiographic parameters left ventricle telediastolic (LVTDD) and telesystolic (LVTSD) diameter, left atrial diameter (LAD), aortic diameter (AoD), ejection fraction (EF) and pulmonary pressure (PAP) were analysed. Through binary logistic regression, in backwards conditional method, it results a casual relationship statistically significant between uricemia (7.2 mg/dL) and LAD: for every elevation of LAD with 1 unit, the probability to have hyperuricemia increases by 9% [OD: 0.91, 95% CI: 0.84–0.99]. It exists a significant casual relation between uricemia (> 8 mg/dL) and TSLVD ( P = 0.045) and PAP ( P = 0.006). For every elevation of TSLVD with 1 unit, the chances of having a uricemia > 8 mg/dL increase with 22% [OD: 0.82, 95% CI: 0.67–0.99, b = −0.2]. For every elevation of PAP with 1 unit, the probability of having a uricemia greater than > 8 mg/dL is 9.4% [OD: 0.91, 95% CI: 0.86–0.97, b = −0.09]. In this study, it resulted that hyperuricemia is an important factor in the development of atrial remodelling, associated casually with an increase in left atrial diameter. Hyperuricemia is related with a greater left ventricle telesystolic diameter and pulmonary artery pressure.

Abstract 13927: Advanced Age and Preferential Use of Vitamin K Antagonists in Severe Renal Impairment: First Results of the XARENO Registry in Patients With Non-valvular Atrial Fibrillation and Non-dialysis Dependent Advanced Chronic Kidney Disease

Introduction: Patients with chronic kidney disease (CKD) and non-valvular atrial fibrillation (NVAF) are at increased risk for both ischemic stroke and hemorrhage. In addition, treatment with vitamin K antagonists (VKA) has been associated with worsening of renal function compared to direct oral anticoagulants (DOACs). XARENO (Factor XA -inhibition in RENal patients with non-valvular atrial fibrillation Observational registry) is an ongoing prospective, non-interventional, observational study conducted in Europe. XARENO evaluates the effectiveness of rivaroxaban in preserving renal function and preventing thromboembolic events as compared to VKA in NVAF patients with CKD in clinical practice. Methods: XARENO included male and female NVAF patients ≥18 years old with an estimated glomerular filtration rate (eGFR) between 15 and 49 mL/min per 1.73 m 2 and an indication for anticoagulation. Enrolment took place from April 2016 until January 2020. Patients treated with either rivaroxaban or VKA were included, while patients in whom physicians were withholding any anticoagulation could be also enrolled. Minimal planned follow-up is one year. Primary observational outcomes include efficacy and safety outcomes (progression of CKD, stroke, other thromboembolic events, major cardiovascular events, major bleeding, and all-cause mortality). First results on outcomes in the full cohort are expected in 2021. Results: In this analysis of a first set of 1485 patients (56.1% males), 731 and 666 patients received rivaroxaban and VKA, while 88 patients did not receive any anticoagulation. Mean age at baseline was 77.3 years (67.5% older than 75 years) with a mean eGFR of 38.9 mL/min per 1.73 m 2 . Overall 74.7% of patients had eGFR values below 45 mL/min per 1.73 m 2 and 28.0% below 30 mL/min per 1.73 m 2 . In the latter group, use of a VKA was about twofold more frequent compared to rivaroxaban. Conclusions: This first analysis of XARENO patients reveals the very high age of NVAF patients with concomitant non-dialysis dependent advanced CKD and a preferential use of VKA in stage 4 CKD. XARENO aims to provide important information on the real-world effectiveness and safety of rivaroxaban compared with VKA for this vulnerable patient group.

Association of arterial thromboembolism location with presence of nonvalvular atrial fibrillation.

Since nonvalvular atrial fibrillation is persistent in nature, patients with chronic nonvalvular atrial fibrillation are at life-time risk for development of thromboembolic events. Several novel oral anticoagulants have entered the market and there has been a growing body of evidence regarding their efficacy in prevention of ischemic stroke and arterial thromboembolism. The present study sought to compare the baseline characteristics between patients presenting with upper and lower extremity arterial thromboembolism developed secondary to nonvalvular atrial fibrillation. This retrospective study was made up of patients presenting with acute upper or lower extremity arterial thromboembolism as the first presentation of atrial fibrillation. Patients were included if they had acute upper or lower critical limb ischemia symptoms lasting for less than one week. Patients in whom chronic peripheral artery disease was diagnosed were also excluded to prevent potential confounding. Overall, 46.9% of patients presented with upper extremity arterial thromboembolism and 53.1% of patients presented with lower extremity arterial thromboembolism. None of the baseline characteristics showed significant difference between patients with upper and lower extremity arterial thrombosis. It was observed that there was no significant difference in the incidence of extremity involvement of acute arterial thromboembolism occurring in patients with nonvalvular atrial fibrillation in our study, and we think that acute arterial thromboembolism must be taken into consideration as one of the first signs and symptoms of atrial fibrillation.

Novel Models for the Prediction of Left Atrial Appendage Thrombus in Patients with Chronic Nonvalvular Atrial Fibrillation.

Predicting left atrial appendage thrombus (LAAT) in chronic nonvalvular atrial fibrillation remains challenging despite the fact that several predictive models have been proposed to date. In this study, we sought to develop new and simpler models for LAAT prediction in chronic nonvalvular atrial fibrillation. The study enrolled 144 patients with chronic nonvalvular atrial fibrillation who underwent transesophageal echocardiography for LAAT detection. We examined the association of LAAT incidence with the CHA2DS2-VASc score and echocardiographic parameters pertaining to the left atrium (LA), including diameter, volume index, strain, and strain rate measured on speckle tracking echocardiography. LAAT was found in 24.3% of patients (39/144). The following parameters had good diagnostic performance for LAAT: LA volume index >57 mL (area under the curve (AUC), 0.72; sensitivity, 77.1%; specificity, 64.2%), LA positive strain ≤6.7% in the four-chamber view (AUC, 0.84; sensitivity, 77.1%; specificity, 77.1%), and LA negative strain rate >−0.73 s−1 in the four-chamber view (AUC, 0.83; sensitivity, 85.7%; specificity, 70.6%). The CHA2DS2-VASc score alone had a low predictive value for LAAT in this population (χ2 = 3.53), whereas the combination of CHA2DS2-VASc score with LA volume index had significant association and better predictive value (χ2 = 12.03), and the combination of CHA2DS2-VASc score with LA volume index and LA positive strain or negative strain rate in the four-chamber view had the best predictive ability for LAAT (χ2: 33.47 and 33.48, respectively). We propose two novel and simple models for noninvasive LAAT prediction in patients with chronic nonvalvular atrial fibrillation. These models combine the CHA2DS2-VASc score with LA volume index and LA longitudinal strain parameters measured on speckle tracking echocardiography in the four-chamber view. We hope these simple models can help with decision-making in managing the antithrombotic treatment of such patients, whose risk of stroke cannot be determined solely based on the CHA2DS2-VASc score.

Stroke Severity in Patients on Non-Vitamin K Antagonist Oral Anticoagulants with a Standard or Insufficient Dose.

The stroke severity or functional outcomes could differ because the efficacy of non-vitamin K antagonist oral anticoagulants (NOACs) could be different according to the dose. We investigated whether there was any difference in the stroke outcomes in patients with non-valvular atrial fibrillation (NVAF) by their prior medication status, including standard-dosed versus under-dosed NOACs. We enrolled 858 patients with acute ischaemic stroke with chronic NVAF admitted at six hospitals in Korea. We categorized their prior medication status as follows: (1) no anti-thrombotics (n = 219), (2) only anti-platelet (n = 347), (3) warfarin with a sub-therapeutic intensity (n = 185), (4) warfarin with a therapeutic intensity (n = 37), (5) under-dosed NOAC (n = 27) and (6) standard-dosed NOAC (n = 43). We compared the initial stroke severity between groups. Among the 858 patients, the patients on standard-dosed NOACs had the lowest initial National Institute of Health Stroke Scale (NIHSS) score, followed by those on warfarin with a therapeutic intensity and those on only anti-platelet (p < 0.05). Multivariate analysis demonstrated that the NIHSS score was significantly low in the patients on warfarin with a therapeutic intensity (B, -5.602; 95% confidence interval [CI], -8.636 to -2.568; p < 0.001) or those on standard-dosed NOACs (B, -3.588; 95% CI, -6.405 to -0.771; p = 0.013), while there was no difference in the NIHSS score between the patients not taking any anti-thrombotics and those on warfarin with a sub-therapeutic intensity or under-dosed NOACs. Use of warfarin with a therapeutic intensity or standard-dosed NOACs was associated with a relatively mild stroke in the patients with NVAF.

Pretreatment with intravenous amiodarone improves the efficacy of ibutilide treatment on cardioversion rate and maintenance time of sinus rhythm in patients with persistent atrial fibrillation.

The aim of the present study was to assess the efficacy and safety of the pharmacological conversion of persistent atrial fibrillation (AF) using amiodarone or/and ibutilide. Seventy-nine consecutive patients (48 males and 31 females; mean age, 64.6±11.2 years; range, 40-80 years) with non-valvular chronic AF lasting >7 days (range, 7-97 days) that were admitted to hospital for elective pharmacological cardioversion were randomly assigned to receive treatment with intravenous ibutilide (1 mg plus an additional 1 mg if required; n=39) or intravenous amiodarone (300 mg) plus intravenous ibutilide (1 mg; n=40). Success rates of cardioversion were 51.3% (20/39 patients) for ibutilide alone and 71.8% (28/39 patients) for amiodarone + ibutilide (P<0.05). A comparable increase in the QTc interval was observed in the two groups. It was observed that the co-administration of amiodarone and ibutilide was safer than ibutilide alone with regard to the risk of ventricular arrhythmia. Forty-eight patients of successful cardioversion were personally contacted for follow-up. The result indicated that the sinus rhythm maintenance time of the amiodarone + ibutilide group (4.36±2.44 months) was significantly higher than that of the ibutilide group (2.34±1.75 months; P<0.01). In conclusion, pretreatment with intravenous amiodarone + ibutilide for pharmacological cardioversion of persistent AF is considered to be more effective and safer than treatment with ibutilide alone.

Bridging anticoagulation for interruption of warfarin in a patient with atrial fibrillation

A 78-year-old man with chronic nonvalvular atrial fibrillation presents to his family physician three weeks before a transurethral resection of the prostate for benign prostatic hypertrophy. His history includes hypertension and type 2 diabetes. He has no history of congestive heart failure, stroke

The Related Factors and Clinical Predictive Value of Left Atrial Spontaneous Echo Contrast in Patient with Nonvalvular Chronic Atrial Fibrillation

Background: To investigate left atrial or left atrial appendage spontaneous echo by transesophageal echocardiography for clinical risk assessment, providing an important basis for guiding treatment and so on. Methods: Select 113 atrial fibrillation patients who did not have formal warfarin treatment in 2011-2014 and did transesophageal echocardiography, after excluding substandard patients, 92 patients were divided into LASEC positive group (n=63) and negative group (n=29). Analyses the clinical features and echocardiographic parameters. Evaluate the diagnostic value with results of multivariate analysis. Results: The study found a significant difference (P 40 mm and hypertension have a extremely significant difference (P<0.01). CHA2DS2-VASC score, D-dimer in plasma have a predictive value for LASEC patients with atrial fibrillation. Conclusion: Patients with persistent AF have a higher LASEC incidence, LASEC has clinical predictive value, there are certain guiding significance in clinical practice.

Assessment of left atrium mechanical function by deformation imaging in atrial fibrillation and its correlation with CHA2DS2-VASc risk score

Abstract Objectives Evaluation of left atrium (LA) mechanical function by speckle tracking based strain (SPTS) in patients with chronic non-valvular atrial fibrillation (AF) and its correlation with CHA 2 DS 2 -VASc risk score. Background AF is a progressive condition that begins with increased hemodynamic load or structural remodeling of the atria, understanding atrial function could lead to better ability to predict the risk of developing stroke and the response to treatment. SPTS is a recently emerged modality that accurately estimates myocardial function. Methods Sixty patients with chronic AF and 20 age and sex matched normal control individuals underwent conventional echo where LV dimensions, wall thickness, EF, LA diameter and volumes were measured. Peak left atrial longitudinal strain (PALS) was measured in apical four (AP4) and two chamber view (AP2) and its correlation with CHA 2 DS 2 -VASc risk score in the AF group was evaluated. Results LA diameter and volumes were greater in AF patients ( P -value 2 DS 2 -VASc score. Also, there was no significant difference between PALS in patients with CHA 2 DS 2 -VASc score less than and more than two points. Conclusion AF leads to impairment of LA mechanical function as evidenced by low PALS but PALS was not significantly correlated with CHA 2 DS 2 -VASc score. Also, there was no significantly statistical difference between PALS in patients with low and high CHA 2 DS 2 -VASc scores.

GISE/AIAC position paper on percutaneous left atrial appendage occlusion in patients with nonvalvular atrial fibrillation: recommendations for patient selection, facilities, competences, organizing and training requirements

Thromboembolism from the left atrial appendage is the most feared complication in patients with atrial fibrillation (AF). The cornerstone for the management of chronic nonvalvular AF is stroke reduction with oral anticoagulation (OAC). However, poor compliance, maintaining a narrow therapeutic window, and major side effects such as bleeding have severely limited its use, creating a therapeutic dilemma. About 20% of AF patients do not receive OAC due to contraindications and less than half of AF patients are not on OAC due to reluctance of the prescribing physician and/or patient non-compliance. Fortunately, over the past decade, the introduction of percutaneous approaches for left atrial appendage occlusion has offered a viable alternative to the management of nonvalvular AF in patients with OAC contraindication. Occlusion devices such as the Amplatzer Cardiac Plug and Watch man device have shown their noninferiority to OAC for stroke prophylaxis with less bleeding complications, while more recently some new devices have been introduced. The aim of this position paper is to review the most relevant clinical aspects of left atrial appendage occlusion from patient selection to periprocedural and follow-up management. In addition, the importance of a medical team and an organizational environment adequate to optimize all the steps of this procedure is discussed.

Mean platelet volume in patients with nonvalvular atrial fibrillation

The procoagulant and prothrombotic states in patients with chronic atrial fibrillation are higher than those in patients with normal sinus rhythm. Mean platelet volume (MPV) which is a marker of platelet function and activation can reflect changes either in the level of platelet stimulation or the rate of platelet production. In this study, we aimed to assess and compare the hematologic parameters of routine complete blood count analysis in elderly patients with nonvalvular atrial fibrillation and control individuals with normal sinus rhythm. One hundred and seven consecutive patients with nonvalvular chronic atrial fibrillation and 112 age and sex-matched control individuals with normal sinus rhythm were retrospectively included in the study from the outpatient cardiology clinic. Hematological variables, including MPV, platelet count, red blood cell and white blood cell count were measured in all patients and control individuals. Presence of coronary artery disease, hypertension, sex, hyperlipidemia, diabetes mellitus, smoking status, hematocrit and platelet count were comparable between two groups (P>0.05 for all). However, MPV and white blood cell count were significantly higher in patients with atrial fibrillation compared to those without atrial fibrillation. Logistic regression analysis revealed that white blood cell count and MPV significantly and independently associated with atrial fibrillation. We have shown that MPV and white blood cell count is independently associated with chronic nonvalvular atrial fibrillation. To improve the clinical utility of MPV and role of inflammation in the pathogenesis of atrial fibrillation, further studies are needed to be carried out.

The Relationship Between Serum Bilirubin Concentration and Atrial Fibrillation.

BackgroundSeveral studies have demonstrated that higher serum bilirubin inhibits the inflammation and proliferation of vascular smooth muscle cells; also there is a relationship between serum bilirubin and cardiovascular disease. However, the relationship between bilirubin and atrial fibrillation (AF) is still unknown. In our study, we compared serum bilirubin, between nonvalvular AF patients and controls.Materials and MethodOne hundred and two patients with nonvalvular chronic AF without any other cardiovascular disease (mean age 62.51 ± 5.88) were included in our study. One hundred age-matched healthy people with sinus rhythm were accepted as control groups (mean age 61.35 ± 5.44). Routine biochemical parameters and serum bilirubin levels were performed.ResultsNo statistically significant difference was found between two groups in terms of basic characteristics. Total, direct and indirect serum bilirubin levels were significantly lower among persons with AF compared to controls (0.82 ± 0.8 vs. 0.48 ± 0.5, 0.30 ± 0.2 vs. 0.19 ± 0.1 and 0.52 ± 0.5 vs. 0.29 ± 0.3 mg/dL; all P < 0.001, respectively).ConclusionAs a result, our study revealed a relationship between serum bilirubin and nonvalvular AF.

The Effects of Vitamin D Deficiency on Atrial Fibrillation

Vitamin D deficiency is associated with cardiovascular disease such as coronary artery disease, heart failure, and hypertension. Vitamin D deficiency activates the renin-angiotensin-aldosterone system, which affects the cardiovascular system. For this reason, it could be suggested that there is a relationship between vitamin D deficiency and atrial fibrillation (AF). In our study, we compared 25-hydroxyvitamin D (25-OHD) levels between nonvalvular AF, valvular AF, and control groups in sinus rhythm. A total of 102 patients with nonvalvular chronic AF without any other cardiovascular disease (mean age 62.51 ± 5.88; group I) and 96 patients with AF, which is associated with mitral valve disease (mean age 61.51 ± 5; group II) were included in our study. Of all, 100 age-matched healthy people with sinus rhythm were accepted as control groups (mean age 61.35 ± 5.44). Routine biochemical parameters, 25-OHD and parathormone levels were performed. Baseline characteristics of the study groups were comparable. Group I patients had a lower vitamin D level than group II and the control group (6.51 ± 4.89, 9.24 ± 7.39, and 11.18 ± 6.98 ng/mL, P < .001, respectively). In groups I and II, the patients' left atrium diameter and systolic pulmonary artery pressure are higher than the control group. As a result, our study revealed a relationship between vitamin D deficiency and nonvalvular AF.

Serum γ-Glutamyltransferase Activity in Patients With Nonvalvular Atrial Fibrillation

Procoagulant and prothrombotic states in patients with chronic atrial fibrillation (AF) are higher than those in patients with normal sinus rhythm. We assessed and compared serum γ-glutamyltranferase (GGT) activity in elderly patients with nonvalvular AF and control participants with normal sinus rhythm. Consecutive patients (n = 81) with nonvalvular chronic AF and 210 age- and gender-matched control participants with normal sinus rhythm were retrospectively included in the study from the outpatient cardiology clinic. Presence of coronary artery disease, hypertension, gender, hyperlipidemia, diabetes mellitus, smoking status, glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and ejection fraction were comparable between the 2 groups (P > .05 for all). However, serum γ-GGT activity was significantly higher (P = .003) in patients with AF compared with those without AF. We have shown that serum γ-GGT activity is independently associated with chronic nonvalvular AF.

Plasma proteomics of patients with non-valvular atrial fibrillation on chronic anti-coagulation with warfarin or a direct factor Xa inhibitor

Plasma proteins mediate thrombogenesis, inflammation, endocardial injury and structural remodelling in atrial fibrillation (AF). We hypothesised that anti-coagulation with rivaroxaban, a direct factor Xa inhibitor, would differentially modulate biologically-relevant plasma proteins, compared with warfarin, a multi-coagulation protein antagonist. We performed unbiased liquid chromatography/tandem mass spectroscopy and candidate multiplexed protein immunoassays among Japanese subjects with non-valvular chronic AF who were randomly assigned to treatment with 24 weeks of rivaroxaban (n=93) or warfarin (n=94). Nine metaproteins, including fibulin-1 (p=0.0033), vitronectin (p=0.0010), haemoglobin α (p=0.0012), apolipoproteins C-II (p=0.0017) and H (p=0.0023), complement C5 precursor (p=0.0026), coagulation factor XIIIA (p=0.0026) and XIIIB (p=0.0032) subunits, and 10 candidate proteins, including thrombomodulin (p=0.0004), intercellular adhesion molecule-3 (p=0.0064), interleukin-8 (p=0.0007) and matrix metalloproteinase-3 (p=0.0003), were differentially expressed among patients with and without known clinical risk factors for stroke and bleeding in AF. Compared with warfarin, rivaroxaban treatment was associated with a greater increase in thrombomodulin (Δ 0.1 vs. 0.3 pg/ml, p=0.0026) and a trend towards a reduction in matrix metalloproteinase-9 (Δ 2.2 vs. -4.9 pg/ml, p=0.0757) over 24 weeks. Only modest correlations were observed between protein levels and prothrombin time, factor Xa activity and prothrombinase-induced clotting time. Plasma proteomics can identify distinct functional patterns of protein expression that report on known stroke and bleeding risk phenotypes in an ethnically-homogeneous AF population. The greater upregulation of thrombomodulin among patients randomised to rivaroxaban represents a proof-of-principle that pharmacoproteomics can be employed to discern novel effects of factor Xa inhibition beyond standard pharmacodynamic measures.

Long-Term Oral Anticoagulant Management Associated with Routine Medical Care (RMC) In Patients with Non-Valvular Atrial Fibrillation (NVAF) In Canada,

Abstract 4192 Introduction:There are no prospective, long-term studies describing the process and quality of care, resource utilization (RU), and quality of life (QoL) associated with being on oral anticoagulant therapy for non-valvular atrial fibrillation (NVAF) patients managed through routine medical care (RMC) in Canada. Methods:Resource utilization associated with Oral Anticoagulant Management (ROAM) is a prospective cohort study being conducted across 9 Canadian provinces whose objective is to describe the process and quality of care, RU, clinical events and health utility scores associated with long-term oral anticoagulant (warfarin) therapy in patients with new onset or chronic NVAF. Eligible, consenting patients are followed for 48 weeks and complete a weekly study diary providing data on international normalized ratio (INR) test dates and values, RU associated with warfarin monitoring, and all physician visits, procedures and hospitalizations. Health utility scores, representing the patient's health state, measured using the EuroQol-5D (EQ-5D) standardized QoL instrument are collected every 4 weeks. INR test values and dates and source documentation around patient reported clinical events are also collected from the participating physicians. Results:497 out of a planned enrolment of 600 patients have been recruited. 180 patients with completed 48 week follow-up and physician-provided INR values are included in this analysis, 98% from primary care physicians and specialists (RMC) and 2% from anticoagulant clinics. Median age [range] was 75 [39, 90] years with 67% males. Common co-morbidities were hypertension (60%) and ischemic heart disease (27%). Estimated median [range] time since NVAF diagnosis was 4 [0, 32] years. Physicians reported a total of 2484 INR tests over the study duration (a mean of 13.8 tests per patient) while patients recorded 2711 tests being completed in their diaries over the same time period (a mean of 15.06 tests per patient). Of the 2711 patient reported tests only 1914 INR results (71%) were communicated back to patients via telephone (70%) or in person (15%). Median [quartile] time between the INR test and the patient acquiring the results was 1.4 [1.0, 2.5] days. The INR test dates provided by physicians matched the dates recorded by patients in the diary 67% of the time. 51 (28%) of patients recorded no INR values. Of the 129 patients with at least one recorded INR value, physician and patient INR values matched completely for only 8 (4%) patients and matched on average 62% of the time (range 30% to 98%) for the rest. Mean [95% CI] time in therapeutic range (TTR) by the Rosendaal method was 67% [64%, 71%] using physician reported values and 67% [62%, 72%] based on patient reported values. Mean INR testing frequency was 30 days following an INR in the therapeutic range, 25 days following an INR of less than 2 and 22 days following an INR greater than 3. Three strokes and 3 bleeds were self-reported in 5 patients (9%) that are being adjudicated. The initial mean [95% CI] health utility score was 0.85 [0.83, 0.88]. A decrease in health utility score was observed in 133 (74%) of the patients based on a random effects regression model. Fixed effect estimate of the mean [95% CI] change in health utility scores per 6 months was −0.01 [0, −0.02]. Covariates (age, gender and time since diagnosis) were investigated but had limited effect on the health utility score. Conclusions:This is the first prospective cohort study of NVAF patients on long-term warfarin therapy being monitored primarily through RMC in Canada. The majority of patients are monitored via telephone with frequent miscommunication between health care providers and patients about INR results and delays in getting results to patients. TTR is higher than previously reported for RMC, which may suggest a self-selection bias for better quality physician-patient combinations. Although frequency of testing was appropriate for in-range INRs, the times to testing after out-of-range results appear delayed. Analysis of health utility scores showed a small decrease in health status over time in this cohort of patients with generally high health utility scores. Relationship between TTR and clinical events will be presented. Disclosures:Selby:Boehringer Ingelheim: Honoraria, Research Funding. Mittmann:Boehringer Ingelheim: Research Funding. Isogai:Boehringer Ingelheim: Research Funding. Kaus:Boehringer Ingelheim: Research Funding. Koo:Boehringer Ingelheim: Research Funding. Sealey:Boehringer Ingelheim: Research Funding.