Nonvalvular Atrial Fibrillation Cases Research Articles

Vitamin D3 Deficiency's Impact on Atrial Fibrillation in Hyperthyroidism Patients

Background: Atrial fibrillation (AFi) is more common as people get older. Additionally, a further indicator of the occurrence of AFi is subclinical hyperthyroidism, which is linked to a 3-fold increased risk. Lack of vitamin D causes the renin-angiotensin-aldosterone pathway to become active, which has an impact on the cardiovascular system. Objective: To examine the association between 25-hydroxyvitamin D3 insufficiency and AFi and hyperthyroidism cases with valvular and nonvalvular AFi that required treatment at our medical center. Patients and Methods: Samples taken from 200 cases of AFi (50-65 years old) divided into: group A cases with nonvalvular AFi and group B cases with valve AFi, and 100 healthy individuals with sinus rhythm who were age-matched chosen as control groups. Standard biochemical measurements, including levels of 25-OHvit.D3,the hormone of the thyroid gland, and parathyroid hormone, were made. Results: Cases in group A had decreased 25-OHvit.D3 levels compare to those in the control and B groups (P ≤ 0.05 ).In comparison to the control group, the patients in groups A and B had larger left atriums and greater systolic pulmonary artery pressures. Conclusion: Thus, the study shows a connection between nonvalvular AFi cases with hyperthyroidism and 25-OHvit D3 deficiency.

Vitamin D3 Deficiency's Impact on Atrial Fibrillation in Hyperthyroidism Patients

Background: Atrial fibrillation (AFi) is more common as people get older. Additionally, a further indicator of the occurrence of AFi is subclinical hyperthyroidism, which is linked to a 3-fold increased risk. Lack of vitamin D causes the renin-angiotensin-aldosterone pathway to become active, which has an impact on the cardiovascular system. Objective: To examine the association between 25-hydroxyvitamin D3 insufficiency and AFi and hyperthyroidism cases with valvular and nonvalvular AFi that required treatment at our medical center. Patients and Methods: Samples taken from 200 cases of AFi (50-65 years old) divided into: group A cases with nonvalvular AFi and group B cases with valve AFi, and 100 healthy individuals with sinus rhythm who were age-matched chosen as control groups. Standard biochemical measurements, including levels of 25-OHvit.D3,the hormone of the thyroid gland, and parathyroid hormone, were made. Results: Cases in group A had decreased 25-OHvit.D3 levels compare to those in the control and B groups (P ≤ 0.05 ).In comparison to the control group, the patients in groups A and B had larger left atriums and greater systolic pulmonary artery pressures. Conclusion: Thus, the study shows a connection between nonvalvular AFi cases with hyperthyroidism and 25-OHvit D3 deficiency. Keywords: 25-hydroxyvitamin D3, Atrial fibrillation, Valvular, Parathyroid hormone, Hyperthyroidism.

Evaluation of medical quality and treatment trends of nonvalvular atrial fibrillation in Beijing inpatients.

The quality of care presented to AF cases in tertiary and non-tertiary hospitals in China remains obscure and needs further investigation. Therefore, we examined the compliance with quality measures (QMs) and clinical performance measures (PMs) that were proposed by the ACC/AHA in 2016 in a Chinese adult population with nonvalvular atrial fibrillation (AF). We also investigated the changes in patients' characteristics, treatment plans, and quality of provided care at different time-points [2011-2016]. We used the datasets from two registry-based studies in Beijing, including the Chinese Atrial Fibrillation Registry (CHINA-AF) investigation. From August 2011 to July 2016, an overall number of 13,439 nonvalvular AF cases were included. Our primary outcome was to determine the compliance rate with two PMs [oral anticoagulant (OAC) use and prothrombin time international normalized ratio (INR)] and six QMs (beta-blocker, ACEI-ARB, and the inappropriate prescription of antiarrhythmic drugs, Sotalol, antiplatelet and OAC, and non-dihydropyridine calcium channel antagonist) over a period of 5 years [2011-2016]. Also, the difference in compliance between tertiary and non-tertiary hospitals was investigated. The compliance with PMs and QMs was variable between tertiary and non-tertiary hospitals. In tertiary hospitals, the total number of inpatient beds was >500, and each bed was equipped with >1.03 health technical personnel and >0.4 nurses. In non-tertiary hospitals, the available beds capacity was <500, and each bed corresponded with 0.7-0.88 health technical personnel and >0.4 nurses. The compliance rates with OAC use steadily increased from 2011-2015 in tertiary hospitals (35%, 35.9%, 37.9%, 45%, and 49%, P<0.001). In non-tertiary hospitals, INR follow-up of warfarin use increased significantly over the years, with rates of 36.2%, 60.5%, 71.6%, 64.3%, and 81.5% (P=0.04), respectively. In terms of QMs, the compliance with the six measure sets was quite similar among tertiary and non-tertiary hospitals avoiding any significant difference over the years (P>0.05). We noted an improvement in medical quality regarding the use of OAC, especially in tertiary hospitals. Meanwhile, the compliance rates of INR follow-up improved in non-tertiary hospitals. However, the compliance rates of other performance and QMs are still low, which are in need of improvement.

Successful WATCHMAN Device Placement Despite Left Atrial Appendage Perforation in Two Cases

The WATCHMAN (Boston Scientific, Marlborough, USA) is a device used to occlude the left atrial appendage (LAA) in patients of non-valvular atrial fibrillation (NVAF) with a high CHA2DS2-VASc score who are poor candidates for oral anticoagulation. LAA perforation is a well-known complication of the WATCHMAN device placement. Here we present two cases of NVAF where oral anticoagulation was not advisable due to recurrent bleeding episodes. They underwent the WATCHMAN procedure for stroke prevention. During the placement of the WATCHMAN device into the left atrial appendage (LAA) in both cases, pericardial staining was noted that worsened over the next few minutes. It was decided to deploy the 27 mm WATCHMAN device into the LAA. In one case, satisfactory hemostasis was achieved with the device deployment eliminating the need for cardiothoracic surgery. However, the second case led to pericardial tamponade and was managed by the placement of a pericardial window. To our knowledge, this is the first case series describing the use of a WATCHMAN device upon detection of LAA perforation.

Diagnostic value of N-terminal pro B-type natriuretic peptide for nonvalvular atrial fibrillation in acute ischemic stroke patients: A retrospective multicenter case-control study

BackgroundThe detection of Nonvalvular atrial fibrillation (NVAF) in AIS patients may be elusive and require further investigation such as electrocardiography (ECG) and Holter monitoring. The objective of this study is to evaluate the N-terminal pro B-type natriuretic peptide (NT-proBNP) diagnostic value for NVAF and the clinical outcome of AIS patients. MethodsWe conducted a retrospective study of AIS patients in ten hospitals of the Shaanxi province. All NVAF patients and matched patients without NVAF admitted within 7 days after stroke onset were included in our study. The admission NT-proBNP receiver operating characteristic curve was drawn to determine the discriminative power of NT-proBNP in NVAF identification. Multivariate logistic regression analysis was used to examine the odds ratios (OR) of NT-proBNP for NVAF and identify the potential factors associated with the clinical outcomes in AIS patients. ResultsA total of 275 NVAF cases and 275-matched controls were included in the current study. NT-proBNP was independently associated with NVAF (OR = 64.047, 95% confidence interval [CI]: 30.298–135.390, p < .001) in AIS patients. The optimal cutoff point for the NT-proBNP level to distinguish the NVAF group from the non-NVAF group was 431.0 pg/ml, with an area under curve [AUC] of 0.910 (95% CI: 0.885–0.935, p < .001). The high NT-proBNP level (OR: 3.284, 95% CI: 1.830–5.896, p < .001) was an independent indicator that was positively related to hospitalization mortality. ConclusionThe rise of the serum NT-proBNP level at first admission added great contributions to the NVAF diagnosis after AIS, and was independently associated with the hospitalization mortality of AIS patients.

Factors related to inappropriate edoxaban use.

The aim of this study was to evaluate the appropriateness and clinical outcomes of edoxaban use, and to determine the role of clinical pharmacists in improving the efficacy and safety of edoxaban use. A retrospective study was performed by using an electronic medical record and anticoagulation clinical data from 600 patients who received edoxaban from 1 March 2016 to 16 July 2017 at a tertiary teaching university hospital. The appropriateness of edoxaban use was assessed using eight criteria based on drug use evaluation criteria developed by the American Society of Health-System Pharmacists drug use evaluation guidelines, details in Korea Food and Drug Administration approval of edoxaban. Clinical outcomes were evaluated between the appropriately prescribed and inappropriately prescribed groups regarding the incidence of thrombosis and bleeding episodes. After excluding 86 patients due to the inability to assess renal function, 514 were eligible. Appropriate use was found in 294 patients (57.2%). The most frequent inappropriate use of edoxaban was dose adjustment (60.8%) in accordance with the dosing recommendation in patients with renal insufficiency (creatinine clearance [CrCl] of 15-50mL/min) and a low body weight of <60kg. Moreover, there were three cases of edoxaban use in patients with prosthetic heart valves and moderate-to-severe mitral stenosis, and 15 cases of non-valvular atrial fibrillation in patients with CrCl >95mL/min in whom edoxaban use is not recommended. Furthermore, we found that the factors related to the appropriateness of edoxaban use were <60kg body weight (adjusted odds ratio [OR]: 0.310; confidence interval [CI]: 0.197-0.488) and CrCl <50mL/min (adjusted OR: 0.629; CI: 0.404-0.980). There were 45 events (8.75%) of any bleeding, 9 (1.8%) of stroke/transient ischaemic attack (TIA) and four events (0.8%) of deep vein thrombosis (DVT)/pulmonary embolism (PE). However, there was no difference between the appropriately prescribed group (294 patients) and inappropriately prescribed group (220 patients) in the incidence of bleeding events (27 [9.2%] vs 18 [8.2%]), stroke/TIA (7 [2.4%] vs 2 [0.9%]) and DVT/PE (2 [0.7%] vs 2 [0.9%]), respectively. Although edoxaban has a broad therapeutic window that does not require routine monitoring, it should be cautiously used in patients with renal insufficiency (CrCl <50mL/min) and body weight <60kg.

Association between P-selectin levels and left atrial blood stasis in patients with nonvalvular atrial fibrillation

BackgroundP-selectin - a biomarker of platelet and endothelial cell activation is elevated in patients with non-valvular atrial fibrillation (NVAF). However, the association between sP-selectin level and thromboembolic complications in NVAF patients remains controversial. We tested the hypothesis that plasma soluble P-selectin (sPSL) level correlates with the measures of left atrial blood stasis in NVAF. MethodsPlasma sPSL concentration was measured using solid-phase ELISA in 103 NVAF patients (age 63 ± 14 years; 26% women) and 48 normal sinus rhythm controls (NSR; age 64 ± 14 years; 41% women) who were not on aspirin. Within the group of NVAF cases, 27 had no spontaneous echocardiographic contrast (SEC) detected by transesophageal echocardiography, 31had mild SEC, 15 moderate, 20 severe, and 10 patients had left atrial appendage thrombus (LAAT). ResultsThe median soluble sPSL level was higher in NVAF cases compared to NSR controls [(interquartile range) 26 (20−32) ng/mL vs 22 (15–29) ng/mL, p = 0.0045]. Only NVAF patients with CHA2DS2-VASc score ≥ 1 had higher sPSL level compared to NSR controls. Patients with severe SEC had significantly higher sPSL levels [32 (24–38) ng/mL] compared to all other NVAF patients (p = 0.0042) and to NSR controls (p < 0.0001). Also NVAF patients with LAAT had higher sPSL level compared to NSR controls. ConclusionsThere is a direct correlation between p-selectin level and severe blood stasis in the left atrium. Only NVAF patients with CHA2DS2-VASc score ≥ 1 or with LAAT had higher sPSL level compared to NSR controls.

Platelet-predominate gene expression and reticulated platelets in nonvalvular atrial fibrillation: Effect of pulmonary veins isolation.

Reticulated platelet (RP) content is increased in nonvalvular atrial fibrillation (NVAF). The purpose of this study was to determine if platelet content, morphology, and RP proportion are modulated by platelet genes. Expression of six platelet-predominate genes impacting platelet formation and release, platelet count, and RP content was assessed in NVAF patients before and 3-4 months after pulmonary veins isolation (PVI) and compared to normal sinus rhythm (NSR) controls. RNA from isolated platelets was reverse-transcribed assayed against selected genes utilizing real-time qPCR, and expressed as mean cycle threshold (ΔCt) using beta-2-microglobulin as endogenous control. RP content was assessed by flow cytometry. A fourfold lower expression of CFL1 gene coding for nonmuscle cofilin (7.8 ± 0.9vs. 5.7 ± 1.6, P<0.001) and twofold lower expression of four other genes were associated with similar platelet counts but fourfold higher (28.7+7.0vs. 6.7+5.4, P<0.001) RP content (%) in 97 NVAF cases compared to 51 NSR controls. Three to 4 months after PVI, RP decreased by 28%, while CFL1 gene expression increased over twofold but TUBA4A gene expression decreased almost twofold; NFE2 and MYL6 gene expression remained unchanged. NVAF is associated with notable downregulation of genes directing platelet production and size but increased RP content. PVI impacts the expression of many of these genes, implying a direct relationship between atrial fibrillation and platelet biogenesis.

Direct Oral Anticoagulants

Non–vitamin K antagonist oral anticoagulants, also known as direct oral anticoagulants, are a relatively recent class of medications introduced into clinical practice. Due to their safety profiles, fixed dosing, and lack of need for frequent laboratory monitoring, they are becoming preferred to traditional anticoagulation with warfarin in many cases of nonvalvular atrial fibrillation and venous thromboembolism. Currently, four drugs are available: dabigatran, a direct thrombin inhibitor, and rivaroxaban, apixaban, and edoxaban, factor Xa inhibitors. This review covers the pharmacology, monitoring, and reversal agents currently available for these medications. The indications for their use are covered through a review of the major clinical trials that led to their US and European approvals for clinical use. Perioperative management of these medications is discussed. Tables list indications, dosing, and monitoring, as well as bleeding risks and efficacy compared with warfarin. This review contains 1 figure, 11 tables, and 70 references. Key words: apixaban, dabigatran, direct oral anticoagulant, edoxaban, rivaroxaban

Association of Soluble CD40 Ligand WithDuration of Atrial Fibrillation andWith Intensity of Spontaneous Echocardiographic Contrast.

The authors tested the hypothesis that the inflammatory response of nonvalvular atrial fibrillation (NVAF) is associated with elevated soluble CD40 ligand (sCD40L). NVAF is generally believed to be an inflammatory disease process. sCD40L represents a sensitive invivo indicator of platelet activation and may serve as an "inflammatory and thrombotic thermometer." Plasma sCD40L was measured using enzyme-linked immunoadsorbent assay in 109 NVAF cases (60.9 ± 15 years of age; 26% women) and 48normal sinus rhythm (NSR) controls (62.3 ± 15 years of age; 44% women). Patients were separated by arrhythmia duration of<1 month (n= 21), 1 to 12 months (n= 18), and >12 months (n= 70). Median sCD40L level was significantly higher in NVAF cases than in NSR controls (321 pg/ml vs. 238 pg/ml, respectively; p= 0.029). This difference was driven by higher levels in patients with NVAF duration for<1 month (552pg/ml) and 1 to 12 months (328 pg/ml). NVAF patients with arrhythmia duration for over 1 year had sCD40L levels not significantly different from those of NSR controls. An sCD40L concentration of 552 pg/ml distinguished NVAF patients with dysrhythmia duration of<1 month (area under the curve [AUC] of 0.72; p= 0.0010) or duration for ≤12months (AUC: 0.69; p= 0.0003) from NSR controls. Circulating sCD40L levels were also significantly higher among patients with mild spontaneous echocardiogram contrast (SEC) (p= 0.0378) and those with moderate SEC (p= 0.007) compared with NSR controls. sCD40L levels are significantly higher in NVAF patients than in NSR controls but only for up to 1 year after development of dysrhythmia. An sCD40L concentration of 552 pg/ml can help to assess development or recurrence of asymptomatic NVAF.

A Comparison of Oral Anticoagulant Use for Atrial Fibrillation in the Pre- and Post-DOAC Eras.

Direct oral anticoagulants (DOACs) have seen rapid uptake for the prevention of stroke associated with non-valvular atrial fibrillation (NVAF). It is unclear whether use of DOACs represents direct therapeutic substitution over warfarin or if this coincides with an increase in overall treatment rates. This study sought to describe the difference in oral anticoagulant (OAC) use in the pre-DOAC and post-DOAC eras. Incident cases of NVAF were identified from the Truven Marketscan database during the years 2005-2009 ('pre-DOAC') and 2013 ('post-DOAC'). Demographic and clinical characteristics were compared for the overall cohorts and among those who did and did not receive OAC in both time periods. OAC treatment was observed by stroke (CHA2DS2-VASc) and bleed risk (HAS-BLED) scores. Logistic regression was used to compare the individual characteristics associated with OAC use between the study periods. During the pre- and post-DOAC eras, 105,610 and 11,992 NVAF patients were identified. OAC treatment increased from 42.2 to 54.0% (absolute change 11.8%, relative change 28.0%) from the pre- to post-DOAC periods without meaningful differences between the populations. Larger relative increases in OAC treatment were observed for those at high risk of stroke (33.9% increase) and for those with moderate (30.4% increase) to high risk (28.6% increase) of bleed. Other than time period of diagnosis, no patient characteristics differed between those treated with OACs in the pre and post periods. There has been an overall increase in OAC use in the NVAF population, attributable to both favorable randomized trial results and aggressive marketing of DOACs in the USA.

Intracerebral Hematoma Occurring During Warfarin Versus Non–Vitamin K Antagonist Oral Anticoagulant Therapy

The neuroradiological findings and its outcomes of intracerebral hemorrhage (ICH) were compared between the non-vitamin K antagonist oral anticoagulant (NOAC) therapy and warfarin therapy. In the latest 3years, 13 cases of nonvalvular atrial fibrillation on NOAC therapy were admitted for ICH. For comparison, 65 age- and gender-comparable patients with ICH on warfarin therapy were recruited. Three NOACs had been prescribed: dabigatran (n= 4), rivaroxaban (n= 2), and apixaban (n= 7). The average ages were 76 ± 9 and 78 ± 8 years in the warfarin (n= 65) and NOAC groups (n= 13), respectively. There was no difference in the clinical features, including the CHADS2 score or HAS-BLED score: 2.62 ± 1.31 versus 2.62 ± 1.33, or 1.09 ± 0.43 versus 1.00 ± 0.41, for the warfarin and NOAC groups, respectively. The volume of ICH <30ml was found in 84.6% of the patients on NOACs, but it was found in 53.8% of the patients on warfarin (p= 0.0106). The expansion of hematoma was limited to 7 patients (10.8%) of the warfarin group. A lower hospital mortality and better modified Rankin Scale were observed in the NOAC group than in the warfarin group: 1 (7.7%) versus 27 (41.5%; p= 0.0105) and 3.2 ± 1.4 versus 4.5 ± 1.6 (p= 0.0057), respectively. In conclusion, ICH on NOAC therapy had smaller volume of hematoma with reduced rate of expansion and decreased mortality compared with its occurrence on warfarin.

Abstract 9664: Utilization Patterns of Anticoagulants in Non-Valvular Atrial Fibrillation after the entry of Novel Oral Anticoagulants in the United States

Introduction: Anticoagulants including warfarin and novel oral anticoagulants (NOACs) are recommended for stroke prevention in non-valvular atrial fibrillation (NVAF) patients. Limited data are available on real-world use of warfarin and NOACs in these patients since the entry of NOACs into the US market in October, 2010. Hypothesis: Warfarin and NOACs are prescribed for stroke prevention differentially based on patient characteristics. Methods: Incident cases of NVAF were identified from GE electronic medical records database between 11/2010 and 08/2011 based on ICD-9 codes 427.31 and 427.32. Baseline characteristics were obtained from medical record history prior to diagnosis. Patients were assessed over 6 months for initiation of warfarin or NOAC (dabigatran or rivaroxaban). Factors associated with anticoagulant initiation and NOAC initiation were examined using multivariate logistic regression analyses. Results: Among 19,730 NVAF patients, mean age was 70.8 years, 45.5% were female, and 36.5% initiated an anticoagulant (31.0% warfarin and 5.5% NOAC). CHADS2 score differed across treatment groups with CHADS2 ≥2 found in 47.9%, 45.6% and 36.3% of patients receiving warfarin, NOACs, and no anticoagulants, respectively (p &lt; 0.001). Age, prescriber type, hypertension, diabetes, CHF, prior stroke/TIA, prior MI, and history of GI or other bleeding were significantly associated with the use of anticoagulants. NOAC use was more likely than warfarin in patients with hypertension (OR=1.19), history of GI bleeding (OR=1.40) and prior aspirin use (OR=1.81) but less likely in those with history of CHF (OR=0.70). Conclusions: Since the entry of NOACs, over 60% of newly diagnosed NVAF patients did not receive anticoagulants despite 36% of those patients having CHADS2 score ≥2. GI bleeding history, CHF, and prior aspirin use were major clinical factors associated with NOAC use. Further research is warranted to examine changes in anticoagulant treatment over time.

Association between KCNE1 (G38S) genetic polymorphism and non-valvular atrial fibrillation in an Uygur population

The relationship between KCNE1 G38S genetic polymorphism and non-valvular atrial fibrillation is different among different populations. The study explored the KCNE1 G38S to understand if the KCNE1 G38S is associated with the Uygur atrial fibrillation patients. KCNE1 G38S genetic polymorphism was determined between 237 non-valvular atrial fibrillation cases and 237 control subjects using PCR-RFLP. In univariate analyses, there was a statistical difference in genotype distribution between the patients and controls, and a significant difference in allele frequency of KCNE1 G38S was observed between the two groups (62.6 vs 52.7 %, p = 0.003). In multivariate analyses, the KCNE1 38G variant was independently associated with a significant predisposing effect on AF after adjusting for related risk factors, and the odds ratio for patients was 1.634 (95 % CI: 1.192-2.240, p = 0.002). The KCNE1 38G is a risk factor for incident AF in an Uygur population. The KCNE1 G38S might have different impact on AF in different ethnicities.

Recurrence of embolic stroke in non-valvular atrial fibrillation (NVAF). An autopsy study.

From 3434 consecutive autopsied cases over 60 years of age, we performed retrospective, clinicopathological examinations on 81 patients with symptomatic embolic stroke and non-valvular atrial fibrillation (NVAF) who had not received anticoagulant therapy during their lives. Twenty-one had recurrent embolic strokes (recurrence rate: 25.9%). In the thrombotic infarction without NVAF, the recurrence rate was 21.4%. Recurrent strokes occurred earlier in the embolic infarction of NVAF than in the thrombotic infarction. Most of the lesions of initial embolic strokes were present in the territory of one middle cerebral artery (MCA), while many lesions of recurrent strokes were found in the territory of the contralateral MCA. Between the NVAF cases with and without recurrent embolic stroke, there was no significant difference in the background condition such as history of hypertension, duration of NVAF, severity of cerebral arterial atherosclerosis, heart weight, intracardiac thrombi, myocardial infarctions and infarctions in other systemic organs.