Non-valvular Atrial Fibrillation Risk Research Articles

Abstract TP379: Antithrombotic Bridging in Patients With Acute Ischemic Stroke and Atrial Fibrillation

Introduction: Atrial fibrillation (AF) is the most common cardiac arrhythmia, with a prevalence of 5.9% in those over age 65. AF increases stroke risk 5-fold, causing 1 in 6 acute ischemic strokes (AIS). Stroke from AF carries a higher early mortality and poorer functional outcome, and a risk of recurrent AIS, when compared to ischemic stroke patients in sinus rhythm, of approximately 5% in the first 2-4 weeks. The CHADS2 score is used to estimate stroke risk of non-valvular AF. Anticoagulation is recommended for a score of > 2 unless contraindicated. Controversy exists regarding whether AF patients with AIS should receive parenteral anticoagulation or antiplatelet therapy as a bridging method to oral anticoagulation. Methods: We conducted a single center retrospective chart review of patients admitted between 6/2011 and 3/2014, with diagnosis of AIS and AF (n=354), as part of quality improvement. Bleeding complications related to bridging therapy and incidence of recurrent stroke were reviewed. Results: Complications were seen in 24 (13.3%) patients receiving parenteral bridging anticoagulation (n=180, 50.8%), including 14 intracranial and 14 extracranial bleeding events (7.7% each). Multiple bleeding complications were seen in 2.2% (n=4). Bleeding complications were seen in 5.5% (n=9) of patients receiving antiplatelet bridging (n=161, 45.4%), with 4.3% intracranial (n=7) and 1.2% extracranial (n=2) bleeding events. None had more than one bleeding complication. Relative risk for bleeding complications with parenteral anticoagulation versus antiplatelet bridging was 2.38 (CI 1.1426 to 4.9793, p=0.02). Thirteen patients (3.6%) received no bridging and had no bleeding complications. Two patients of 354 (0.5%) had recurrent ischemic events, one each in the parenteral anticoagulation and antiplatelet groups. Conclusions: Preliminary data does not support bridging with parenteral anticoagulation in AIS and AF due to higher incidence of bleeding complications and low incidence of recurrent AIS. These findings may be related to the limited number of patients included in this study. A future goal is to increase the number of patients reviewed to strengthen the validity of these results.

Gender differences and management of stroke risk of nonvalvular atrial fibrillation in an upper middle-income country: Insights from the CARMEN-AF registry

BackgroundAtrial Fibrillation (AF) is associated with an increased risk of stroke and systemic embolism. Several studies have suggested that female AF patients could have a greater risk for stroke. There is scarce information about clinical characteristics and use of antithrombotic therapies in Latin American patients with nonvalvular AF. ObjectiveTo describe the gender differences in clinical characteristics, thromboembolic risk, and antithrombotic therapy of patients with nonvalvular AF recruited in Mexico, an upper middle-income country, into the prospective national CARMEN-AF Registry. MethodsA total of 1423 consecutive patients, with at least one thromboembolic risk factor were enrolled in CARMEN-AF Registry during a three-year period (2014–2017). They were categorized according to Gender. ResultsOverall, 48.6% were women, mean age 70 ± 12 years. Diabetes, smoking, alcoholism, non-ischemic cardiomyopathy, coronary artery disease, and obstructive sleep apnea were higher in men. Most women were found with paroxysmal AF (40.6%), and most men with permanent AF (44.0%). No gender differences were found in the use of vitamin K antagonists (VKA) (30.5% in women vs. 28.0% in men). No gender differences were found in the use of direct oral anticoagulants (DOAC) (33.8% women vs 35.4% men). ConclusionsCARMEN-AF Registry demonstrates that in Mexico, regardless of gender, a large proportion of patients remain undertreated. No gender differences were found in the use of VKA or DOAC.

Depression, antidepressants, and the risk of non-valvular atrial fibrillation: A nationwide Danish matched cohort study.

Depression is associated with an increased risk of a series of cardiovascular diseases and with increased symptom burden in patients with atrial fibrillation. The aim of this study was to determine the association between depression as well as antidepressant treatment and the risk of incident atrial fibrillation. A nationwide register-based study comparing the atrial fibrillation risk in all Danes initiating antidepressant treatment from 2000 to 2013 ( N = 785,254) with that in a 1:5-matched sample from the general population. Cox regression was used to estimate adjusted hazard ratios (aHRs) and associated 95% confidence intervals (95% CIs), both after initiation of treatment and in the month before when patients were assumed to have medically untreated depression. Antidepressant treatment was associated with a three-fold higher risk of atrial fibrillation during the first month (aHR = 3.18 (95% CI: 2.98-3.39)). This association gradually attenuated over the following year (aHR = 1.37 (95% CI: 1.31-1.44) 2-6 months after antidepressant therapy initiation, and aHR = 1.11 (95% CI: 1.06-1.16) 6-12 months after). However, the associated atrial fibrillation risk was even higher in the month before starting antidepressant treatment (aHR = 7.65 (95% CI: 7.05-8.30) from 30 to 15 days before, and aHR = 4.29 (95% CI: 3.94-4.67) the last 15 days before). Overall, 0.4% of patients were diagnosed with atrial fibrillation from 30 days before to 30 days after antidepressant treatment. Antidepressant users had a substantially increased atrial fibrillation risk, particularly before treatment initiation. Whether this mirrors a causal relation between depression and atrial fibrillation may have large consequences for public health and should be discussed.

Use of neutrophil-lymphocyte ratio for risk stratification and relationship with time in therapeutic range in patients with nonvalvular atrial fibrillation: A pilot study.

Atrial fibrillation is one of the most common abnormal heart rhythms. Neutrophil-lymphocyte ratio (NLR) has emerged as a potential marker for the level of inflammation in cardiac disorders. NLR might be associated with thrombosis and bleeding risk scores and might predict cardioembolic risk in nonvalvular atrial fibrillation (NVAF) patients within the therapeutic international normalized ratio (INR). We enrolled 272 patients taking warfarin for NVAF and classified them into 2 groups: Group A consisted of patients (n = 132) whose time in therapeutic range (TTR) was ≥65%, and Group B comprised patients (n = 139) whose TTR was <65%. NLR values were higher in group B than in group A (P < 0.0001). Patients classified as high risk according to CHA2 DS2 -VASc score had significantly higher NLR levels (P = 0.002) than those classified as low and intermediate risk. Furthermore, NLR levels were significantly correlated with CHA2 DS2 -VASc and HAS-BLED scores (P < 0.001 and P < 0.0001, respectively). NLR predicted patients within therapeutic INR range (TTR ≥65%) with sensitivity of 81% and specificity of 71% in a receiver operator characteristic curve analysis, using a cutoff value of 2.17. Area under the curve for NLR was 0.81 (P < 0.0001). To our knowledge, this is the first study showing correlation of NLR with both CHA2 DS2 -VASc and HAS-BLED risk scores. NLR might represent a useful marker to identify patients with high risks of stroke and bleeding and may have predictive value in identifying patients within the therapeutic INR range.

Adherence to oral anticoagulant therapy in patients with atrial fibrillation. Focus on non-vitamin K antagonist oral anticoagulants.

Oral anticoagulation is pivotal in the management of thromboembolic risk in non-valvular atrial fibrillation (NVAF) patients. Effective anticoagulation is important to avoid major adverse events and medication adherence is central to achieve good anticoagulation control. Non-vitamin K antagonist oral anticoagulants (NOACs) are as effective and safe as vitamin K antagonist (VKAs) in NVAF patients. Due to the absence of routine anticoagulation monitoring with NOACs treatment, concerns have been raised about patient's adherence to NOACs and real-life data demonstrates variability in adherence and persistence. A multi-level approach, including patients' preferences, factors determining physicians' prescribing habits and healthcare system infrastructure and support, is warranted to improve initiation and adherence of anticoagulants. Adherence to NOACs is paramount to achieve a clinical benefit. Implementation of educational programs and easy-to-use tools to identify patients most likely to be non-adherent to NOACs, are central issues in improving the quality of NVAF anticoagulation management.

Should All Patients With Atrial Fibrillation Receive an Oral Anticoagulant in the Era of Non-Vitamin K Anticoagulants?

Oral anticoagulants (OAC) decrease the thromboembolic risk of non-valvular atrial fibrillation (AF) at the expense of increased bleeding. Over the years, several risk stratification schemes for both stroke and bleeding risk have been devised, among which lately the respective CHA2DS2-VASc and HAS-BLED scores predominate. However, even when the bleeding risk score is high, the guidelines recommend not to withhold OAC at least for patients with high stroke risk, but to attempt to concomitantly modify the conditions contributing to the high bleeding risk. The CHA2DS2-VASc score has been considered more reliable than other scores in identifying “truly low-risk” patients who do not require OAC, in whom the risk of bleeding may negate the protective effect of OAC. Some have suggested more complex schemes to better identify very low risk patients, but these schemes may lead to more extensive and costly assessments to decide on a relatively simple question, i.e. the need or not for anticoagulation therapy. In the era of non-vitamin K oral anticoagulants (NOACs), this may not be necessary any more, and a simple recommendation of providing every AF patient with OAC therapy may turn out to be a more practical and realistic approach, as long as these newer agents remain safe and effective.

Novel nonpharmacologic approaches for stroke prevention in atrial fibrillation: results from clinical trials

Atrial fibrillation (AF), the most common cardiac arrhythmia, confers a 5-fold risk of stroke that increases to 17-fold when associated with mitral stenosis. At this time, the most effective long-term solution to protect patients from stroke and thromboembolism is oral anticoagulation, either with vitamin K antagonists (VKAs) or a novel oral anticoagulant (NOAC). Despite the significant benefits they confer, both VKAs and NOACs are underused because of their increased potential for bleeding, and VKAs are underused because of their narrow therapeutic range, need for regular international normalized ratio checks, and interactions with food or medications. In patients with nonvalvular AF, approximately 90% of strokes originate from the left atrial appendage (LAA); in patients with rheumatic mitral valve disease, many patients (60%) have strokes that originate from the left atrium itself. Surgical LAA amputation or closure, although widely used to reduce stroke risk in association with cardiac surgery, is not currently performed as a stand-alone operation for stroke risk reduction because of its invasiveness. Percutaneous LAA closure, as an alternative to anticoagulation, has been increasingly used during the last decade in an effort to reduce stroke risk in nonvalvular AF. Several devices have been introduced during this time, of which one has demonstrated noninferiority compared with warfarin in a randomized controlled trial. This review describes the available technologies for percutaneous LAA closure, as well as a summary of the published trials concerning their safety and efficacy in reducing stroke risk in AF.

Left Atrial Appendage: Physiology, Pathology, and Role as a Therapeutic Target.

Atrial fibrillation (AF) is the most common clinically relevant cardiac arrhythmia. AF poses patients at increased risk of thromboembolism, in particular ischemic stroke. The CHADS2 and CHA2DS2-VASc scores are useful in the assessment of thromboembolic risk in nonvalvular AF and are utilized in decision-making about treatment with oral anticoagulation (OAC). However, OAC is underutilized due to poor patient compliance and contraindications, especially major bleedings. The Virchow triad synthesizes the pathogenesis of thrombogenesis in AF: endocardial dysfunction, abnormal blood stasis, and altered hemostasis. This is especially prominent in the left atrial appendage (LAA), where the low flow reaches its minimum. The LAA is the remnant of the embryonic left atrium, with a complex and variable morphology predisposing to stasis, especially during AF. In patients with nonvalvular AF, 90% of thrombi are located in the LAA. So, left atrial appendage occlusion could be an interesting and effective procedure in thromboembolism prevention in AF. After exclusion of LAA as an embolic source, the remaining risk of thromboembolism does not longer justify the use of oral anticoagulants. Various surgical and catheter-based methods have been developed to exclude the LAA. This paper reviews the physiological and pathophysiological role of the LAA and catheter-based methods of LAA exclusion.

Efficacy and Safety of Novel Oral Anticoagulants in Patients with Cervical Artery Dissections

Background: American and European guidelines support antiplatelet agents and anticoagulants as reasonable treatments of cervical artery dissection (CAD), though randomized clinical trials are lacking. The utility of novel oral anticoagulants (NOAC), effective in reducing embolic stroke risk in non-valvular atrial fibrillation (NVAF), has not been reported in patients with CAD. We report on the use, safety, and efficacy of NOACs in the treatment of CAD. Methods: We retrospectively identified patients diagnosed with CAD at a single academic center between January 2010 and August 2013. Patients were categorized by their antithrombotic treatment at hospital discharge with a NOAC (dabigatran, rivaroxaban, or apixaban), traditional anticoagulant (AC: warfarin or treatment dose low-molecular weight heparin), or antiplatelet agent (AP: aspirin, clopidogrel, or aspirin/extended-release dypyridamole). Using appropriate tests, we compared the baseline medical history, presenting clinical symptoms and initial radiographic characteristics among patients in the 3 treatment groups. We then evaluated for the following outcomes: recurrent stroke, vessel recanalization, and bleeding complications. p values <0.05 were considered significant. Results: Of the 149 included patients (mean age 43.4 years; 63.1% female; 70.5% vertebral artery CAD), 39 (26.2%), 70 (47.0%), and 40 (26.8%) were treated with a NOAC, AC, and AP, respectively. More patients with severe stenosis or occlusion were treated with NOAC than with AC or AP (61.8 vs. 60.0 vs. 22.5%, p = 0.002). Other baseline clinical and radiographic findings, including the presence of acute infarction and hematoma, did not differ between the 3 treatment groups. One hundred and thirty-five (90.6%) patients had clinical follow-up (median time 7.5 months) and 125 (83.9%) had radiographic follow-up (median time 5 months) information. There were 2 recurrent strokes in the NOAC group and 1 in each of the AC and AP groups (p = 0.822). There were more major hemorrhagic events in the AC group (11.4%) compared to the NOAC (0.0%) and AP (2.5%) groups (p = 0.034). Three patients treated with NOAC and none treated with AC or AP had a worsened degree of stenosis on follow-up imaging (8.6 vs. 0.0 vs. 0.0%, p = 0.019). Conclusion: Compared to traditional anticoagulants for CAD, treatment with NOACs is associated with similar rates of recurrent stroke, fewer hemorrhagic complications, but greater rates of radiographic worsening. These data suggest that NOACs may be a reasonable alternative in the management of CAD. Prospective validation of these findings is needed.

The Atrial Fibrillation in Turkey: Epidemiologic Registry (AFTER)

AFTER (Atrial Fibrillation in Turkey: Epidemiologic Registry) is a prospective, multicenter study designed with the aim of describing the prevalence and epidemiology of AF practice in Turkey. This study aims to evaluate stroke risk in non-valvular atrial fibrillation (AF) and anticoagulant drug utilization within conformity to AF guidelines. Patients were recruited in 17 referral hospitals reflecting all the population of 7 geographical regions of Turkey. 2242 consecutive patients who had been admitted with AF on ECG were included in the study. 1745 of these patients, who had non-valvular AF, were included in the statistical evaluation. Stroke risk was evaluated with the CHA2DS2-VASc score. The average age of participants was determined to be 69.2 ± 11.5 years (56% female). Persistent-permanent AF was found to be the most common type of non-valvular AF (78%). The most common comorbid disorder was hypertension (73%). It was found that oral anticoagulant therapy was used by 40% of all patients, 37% of whom had effective INR (2.0-3.0). Upon multivariate analysis, age was found to be the only independent predictor of stroke among the variables' effects on thromboembolic events that created CHA2DS2-VASc abbreviations (OR 1.026, p < 0.001). These results suggest that stroke risk scores should be thoroughly heeded based on guidelines, and that anticoagulation must be applied according to their guidance.

Circulation: Clinical Summaries

<i>Circulation:</i> Clinical Summaries

Abstract WP333: A Simplified Score to Predict Stroke Risk in Nonvalvular Atrial Fibrillation

The widely used CHADS2 score has been validated to predict the annual stroke risk (SR) in patients with non-valvular atrial fibrillation (AF). The CHA2DS2-VASc score incorporates 5 more risk factors including female gender, age 65 to 74 years, and peripheral arterial disease (PAD), prior myocardial infarct or aortic plaque. The two schemes have different SR and require separate tables to calculate SR (Table 1) . Table 1 An acronym (AFIB)2S4 + PaF2 (Table 2) is presented to predict SR that increases with higher scores, simplifies memorization of the score, incorporates all known risk factors and more accurately predicts SR without the use of tables. Table 2 The SR per 100 patient-years is calculated by adding (AFIB)2S4 + PaF2 scores. For example if all are positive including age 75 years then the SR is 15%, while if all are negative, including age &lt;65 and male gender, then the SR is 0. To determine the predictive accuracy of the three scores, we reviewed the records of 100 consecutive patients admitted with acute cerebrovascular events and AF. The results showed 83% would have been classified as moderate to high risk (score&gt;1) by CHADS2 , 95% by CHA2DS2-VASc , and 99% by (AFIB)2S4 + PaF2. (P &lt;0.012). Conclusion: Compared to the CHADS2 , and CHA2DS2-VASc , (AFIB)2S4 + PaF2 more accurately predicts risk of acute cerebrovascular events in patients with AF. It is easy to remember and does not require the use of tables to assess SR in AF. Further studies are needed for validation. PEN ©

Genetic Polymorphisms Conferring Risk of Non-Valvular Atrial Fibrillation in Korean Population: Chromosome 4q25, PITX2, and 16q22 ZFHX3

Background: GWAS revealed several genomes related with atrial fibrillation (AF), such as genetic variants on chromosome 4q22, PITX2, or chromosome 16q22 (ZFHX3). We evaluated those genetic polymorphisms in Korean patients with non-familial non-valvular AF. Methods and Results: We evaluated and compared the allelic frequencies of genetic polymorphisms of chromosome 4q22, PITX2, or 16q22 (ZFHX3) in 454 patients with non-valvular AF (296 paroxysmal AF [PAF], 158 persistent AF [PeAF]) and 422 sex-matched healthy controls by direct DNA sequencing and SNaPshotTM assay. Results: 1. The 4q25 rs2200733 (OR 0.368 (0.246–0.549), p<0.0001), the PITX2 rs17042171 (OR 0.368 (0.246–0.551), p<0.0001), the PITX2 rs6843082 (OR 0.234 (0.15–0.366), p<0.0001), and the 16q22 rs2106261 (OR 2.439 (1.62–3.672), p<0.0001) genotypes were more prevalent in patients with AF than control group. 2. In the haplotype analyses, the 4q25 rs17042171–rs2200733–rs6843082–rs10033464 A–T–G–G (OR 3.3421 (1.867–5.982), p<0.0001) and 4q25 without C–C–A–G (OR 4.630 (2.924–7.299), p<0.0001) were more predisposed in AF than in control group. 3. The 16q22 rs7193343–rs210626116q22 A–G haplotype was more prevalent in patients with AF (OR 0.477 (0.242–0.939), p=0.0322) than control group. Conclusion: This study demonstrates the Chromosom 4q25, PITX2, and 16q22 ZFHX3 polymorphisms were associated with non-familial non-valvular AF in Korean population. The 4q25 and PITX2 were closely related with Korean non-valvular AF in haplotype analyses.

Individualized Medical Decision Making

The need is urgent to provide older persons with individualized information about the benefits and harms of different diagnostic and treatment strategies. This need results from the growing recognition of the heterogeneity in outcomes in older persons with differing comorbidity profiles. The heterogeneity of benefits and harms resulting from treatment is not yet as well appreciated. Warfarin vs aspirin therapy for the reduction of stroke risk in nonvalvular atrial fibrillation provides an example of a treatment for which the benefit-to-harm ratio may actually reverse according to an older person's comorbidities, thus highlighting the importance of basing this treatment decision on individualized outcome data. Despite the wealth of studies in nonvalvular atrial fibrillation, many assumptions are necessary to calculate patient-specific outcomes, and these assumptions may lead to substantial overestimation or underestimation of benefits and harms. Improving care for patients with comorbidities will require substantive increases in the efforts and resources allocated to the collection and dissemination of outcome data for patients with varying comorbidities.

Predicting Embolic Events in Patients With Nonvalvular Atrial Fibrillation: Evaluation of the CHADS 2 Score in a Mediterranean Population

A new index for predicting embolic risk in nonvalvular atrial fibrillation has been proposed, the CHADS2 score, which is calculated by adding 1 point each for the presence of congestive heart failure, hypertension, age 75 years or older, and diabetes, and by adding 2 points for a history of stroke or transient ischemic attack (TIA). Our objective was to evaluate the use of this score in a Mediterranean population. Between February 1st, 2000 and December 20th, 2006, all patients with permanent nonvalvular atrial fibrillation being treated at two outpatient cardiology clinics in a university hospital in the south of Spain were offered antithrombotic therapy in accordance with scientific society recommendations and were prospectively monitored for embolic events (i.e., stroke, TIA or peripheral embolism). A CHADS2 score was derived for each of the 296 patients who did not receive anticoagulation. The CHADS2 score was 0 in 69 (23.3%) patients, 1 in 81 (27.4%), 2 in 99 (33.4%), 3 in 30 (10.1%), and 4 or more in 17 (5.7%). After 21 (17) months of follow-up, the embolic event rates for CHADS2 scores of 0, 1, 2, 3, and > or =4 were 2.88, 5.80, 5.16, 14.78 and 22.02 per 100 patient-years, respectively (P=.0016). Patients with a CHADS2 score from 0-2 had an embolic rate of 4.63 per 100 patient-years, compared with 17.31 per 100 patient-years in those with a score > or =3 (P=.00087). The CHADS2 score proved useful for quantifying the risk of an embolic event in Mediterranean patients with nonvalvular atrial fibrillation. In our series, the risk of embolism in patients with a low score was not negligible.

A Cautionary Note on Data Sources for Evidence-Based Clinical Decisions: Warfarin and Stroke Prevention

Stroke risk in nonvalvular atrial fibrillation can be reduced by warfarin or aspirin; the choice of therapy requires the assessment of risks and benefits. The authors compared methods of risk assessment and their implications for risk communication and treatment. Stroke risk was compared in 193 patients with atrial fibrillation using the Framingham equation; an atrial fibrillation-specific Framingham equation; the Congestive heart failure, Hypertension, Age, Diabetes and Stroke (CHADS(2)) score; the Stroke Prevention and Atrial Fibrillation (SPAF) scheme; and the Scottish Intercollegiate Guidelines Network (SIGN) guidelines. Treatment guidance from SIGN, a simple prediction rule, and a decision analytical approach was compared. In the latter, patients were classified as risk too low to benefit from warfarin if the risk of cerebral bleeding on warfarin approximated to, or exceeded, thromboembolic stroke risk reduction. Framingham equations gave lower stroke risks overall than SIGN or SPAF. CHADS(2) was intermediate. Using SIGN, warfarin would be given to all 103 patients without a history of stroke/transient ischemic attack and for whom warfarin was not contraindicated but only to 73 patients using the simple prediction rule and 48 patients using the decision analysis. Community-based cohorts give lower stroke risk estimates than CHADS(2); both give lower estimates than schemes from control groups from randomized controlled trials. Using community-derived risks would lead to fewer patients being treated with warfarin than guidance derived from randomized controlled trial controls, which may lead to many low-risk patients being treated with high-risk therapy. This raises the debate about appropriate sources of data for risk assessment to support risk communication and effective clinical decisions.

Left ventricular diastolic dysfunction as a predictor of the first diagnosed nonvalvular atrial fibrillation in 840 elderly men and women

ObjectivesThe objective of this study was to determine whether diastolic dysfunction is associated with increased risk of nonvalvular atrial fibrillation (NVAF) in older adults with no history of atrial arrhythmia. BackgroundFew data exist regarding the relationship between diastolic function and NVAF. MethodsThe clinical and echocardiographic characteristics of patients age ≥65 years who had an echocardiogram performed between 1990 and 1998 were reviewed. Exclusion criteria were history of atrial arrhythmia, stroke, valvular or congenital heart disease, or pacemaker implantation. Patients were followed up in their medical records to the last clinical visit or death for documentation of first AF. ResultsOf 840 patients (39% men; mean [± SD] age, 75 ± 7 years), 80 (9.5%) developed NVAF over a mean (± SD) follow-up of 4.1 ± 2.7 years. Abnormal relaxation, pseudonormal, and restrictive left ventricular diastolic filling were associated with hazard ratios of 3.33 (95% confidence interval [CI], 1.5 to 7.4; p = 0.003), 4.84 (95% CI, 2.05 to 11.4; p < 0.001), and 5.26 (95% CI, 2.3 to 12.03; p < 0.001), respectively, when compared with normal diastolic function. After a number of adjustments, diastolic function profile remained incremental to history of congestive heart failure and previous myocardial infarction for prediction of NVAF. Age-adjusted Kaplan-Meier five-year risks of NVAF were 1%, 12%, 14%, and 21% for normal, abnormal relaxation, pseudonormal, and restrictive diastolic filling, respectively. ConclusionsThe presence and severity of diastolic dysfunction are independently predictive of first documented NVAF in the elderly.

Influence of age on left atrial appendage function in patients with nonvalvular atrial fibrillation.

Age is an independent risk factor for thromboembolism in nonvalvular atrial fibrillation (NVAF). An association between low left atrial appendage (LAA) Doppler velocities and thromboembolic risk in NVAF has been reported. The study was undertaken to identify age-related differences in LAA function that may explain the higher thromboembolic rates in older patients with NVAF. Forty-two consecutive patients (age 69+/-2 years [range 42-92], 24 [57%] men) with NVAF underwent transthoracic and transesophageal echocardiography. The following were compared in 22 patients younger and 20 older than 70 years: left ventricular (LV) diameter, mass and ejection fraction, left atrial (LA) diameter and volume, LAA area and volume, LAA peak emptying (PE) and peak filling (PF) velocities, presence and severity of spontaneous echo contrast (SEC) and mitral regurgitation (MR). Left atrial diameter (4.6+/-0.1 vs. 4.5+/-0.2 cm), LA volume (105+/-10 vs. 92+/-8 ml), LAA area (6.8+/-0.6 vs. 5.2+/-0.8 cm2), and LAA volume (5.6+/-0.9 vs. 3.9+/-1.0 ml) were similar (p>0.05) in both groups. Older patients had lower LAA PE (26+/-2 vs. 34+/-3 cm/s, p = 0.02) and PF (32+/-2 vs. 41+/-4 cm/s, p = 0.04) velocities, lower LV mass (175+/-13 vs. 234+/-21 gm, p = 0.02), higher relative wall thickness (0.52+/-0.02 vs. 0.43+/-0.03, p = 0.02), smaller LV diastolic diameter (4.3+/-0.1 vs. 5.2+/-0.2 cm, p < 0.001), and higher LV ejection fraction (62+/-2 vs. 55+/-2%, p = 0.025). Frequency and severity of SEC and MR were similar in both groups. Multivariate analysis identified older age as the only significant predictor of reduced LAA velocities. Compared with younger patients, older patients with NVAF have lower LAA velocities despite higher LV ejection fraction, smaller LV size, and similar LA and LAA volumes. These findings may explain the higher thromboembolic rates in older patients with NVAF.

Prophylaxis and treatment of stroke. The state of the art in 1993.

The most significant impact on cerebral infarction comes from the primary prevention of the processes that lead to stroke in at-risk individuals prior to the development of symptoms. Antithrombotic therapy with warfarin or aspirin significantly reduces thromboembolic risk in non-valvular atrial fibrillation. The failure of primary preventive measures and the progression of disease is heralded by the development of cerebral or retinal ischaemic events; the majority of clinical trials investigating stroke prevention have targeted the secondary prevention of stroke in patients with ischaemic symptoms. A 25% risk reduction has been demonstrated with antiplatelet therapy. This was typically aspirin 1000 to 1300 mg/day, but more recently even lower doses have been beneficial, with lower rates of minor and major bleeding. Ticlopidine has demonstrated efficacy in the secondary prevention of stroke after transient ischaemic attacks and completed stroke, with a 2% risk of significant neutropenia. The benefits of carotid endarterectomy have been demonstrated in patients with symptomatic internal carotid artery stenosis involving 70 to 99% of the arterial diameter. Surgery is not indicated in patients with less than 30% internal carotid artery stenosis; 30 to 69% continues to be studied. When primary and secondary preventive measures have failed, strategies directed at managing acute focal cerebral ischaemia include re-establishing cerebral blood flow and limiting ischaemic neuronal injury. Advances in basic research that have identified components of the ischaemic cascade have been translated clinically into numerous clinical trials, each targeted to one or sometimes two steps in the hope of improving neuronal salvage.(ABSTRACT TRUNCATED AT 250 WORDS)