Comparative study of atrial vulnerability in patients with unexplained ischemic stroke or lone atrial paroxysmal fibrillation

Strokes have a high prevalence, with a high rate of recurrence, and about 30-40% remain of unknown cause. Some patients might have asymptomatic paroxysmal atrial fibrillation (AF) which remains the main cause of embolic events. A latent atrial arrhythmogenic substrate may induce recurrent arrhythmias, including functional abnormalities such as nonuniform refractoriness and/or anatomic abnormalities such as atrial septum aneurysm (ASA) and patent foramen ovale (PFO). In 175 patients divided into three groups (Group I: 103 patients with unexplained ischemic stroke, Group II: 48 patients with paroxysmal AF and Group III or control group: 24 patients explored for another cause), such an atrial arrhythmogenic substrate was assessed by electrophysiological study. Groups I and II had a similar high rate of inducible atrial arrhythmias compared to control group III where no arrhythmia was induced. An induced atrial arrhythmia was observed in more than 50% of patients of Group I and in more than 70% of patients of Group II without any significant difference according to age. However, in 26 young patients of Group I who had a transesophageal echocardiography, both a high rate (46%) of ASA and/or PFO and a frequent latent atrial vulnerability (LAV) were observed, compared to older patients where an atrial septum abnormality was observed in only 21% of cases. Thus, among patients with stroke of unknown cause, a high percentage of them might have asymptomatic atrial paroxysmal arrhythmia. The predictive value of the electrophysiological study for spontaneous arrhythmias and recurrence of stroke remains to be demonstrated.     

Anticoagulation remains underused in prevention of stroke associated with atrial fibrillation: Insights from two consecutive national surveys

Background

Atrial fibrillation (AF) is a major risk factor of ischemic stroke. We tested whether the adoption of the CHADS₂ score in clinical guidelines has impacted treatment strategies for stroke prevention, and examined how AF affects stroke outcome.

Methods

In the setting of two national surveys [National Acute Stroke Israeli Surveys; all patients hospitalized for stroke in Israel during February-March 2004, and March-April 2007] data of patients with and without AF were analyzed with respect to patient characteristics, use of anticoagulation, stroke severity, clinical course, and long-term outcome.

Results

Of 3040 patients with acute ischemic stroke, 586 patients (19%) had a history of AF. Severe strokes on admission were significantly more frequent in patients with AF, as was the proportion of total anterior circulation strokes. Ischemic stroke associated with AF predicted poor outcome at discharge (adjusted OR 1.56; 95%CI 1.24-1.96) and higher mortality rates throughout follow-up. Among patients with a CHADS₂ score ≥ 2 prior to the index stroke and without known contraindications, 41% received anticoagulation. This proportion increased to only 62% after the index stroke, even after excluding patients with severe disability and no significant increase between 2004 and 2007 was detectable. Increasing age, in-hospital infectious complications, and unfavorable functional status at discharge were independently associated with decreased likelihood of receiving anticoagulation.

Conclusions

In deviation from current recommendations and in spite of the introduction of CHADS₂ criteria, anticoagulation for stroke prevention remains underutilized, despite the particularly poor outcome of strokes associated with AF.     

Catheter ablation for atrial fibrillation is associated with reduced risk of mortality in the elderly: a prospective cohort study and propensity score analysis

BackgroundIt is unclear whether catheter ablation (CA) for atrial fibrillation (AF) affects the long-term prognosis in the elderly. This study aims to evaluate the relationship between CA and long-term outcomes in elderly patients with AF.MethodsPatients more than 75 years old with non-valvular AF were prospectively enrolled between August 2011 and December 2017 in the Chinese Atrial Fibrillation Registry Study. Participants who underwent CA at baseline were propensity score matched (1:1) with those who did not receive CA. The outcome events included all-cause mortality, cardiovascular mortality, stroke/transient ischemic attack (TIA), and cardiovascular hospitalization.ResultsOverall, this cohort included 571 ablated patients and 571 non-ablated patients with similar characteristics on 18 dimensions. During a mean follow-up of 39.75 ± 19.98 months (minimum six months), 24 patients died in the ablation group, compared with 60 deaths in the non-ablation group [hazard ratio (HR) = 0.49, 95% confidence interval (CI): 0.30-0.79, P = 0.0024]. Besides, 6 ablated and 29 non-ablated subjects died of cardiovascular disease (HR = 0.25, 95% CI: 0.11–0.61, P = 0.0022). A total of 27 ablated and 40 non-ablated patients suffered stroke/TIA (HR = 0.79, 95% CI: 0.48–1.28, P = 0.3431). In addition, 140 ablated and 194 non-ablated participants suffered cardiovascular hospitalization (HR = 0.84, 95% CI: 0.67–1.04, P = 0.1084). Subgroup analyses according to gender, type of AF, time since onset of AF, and anticoagulants exposure in initiation did not show significant heterogeneity.ConclusionsIn elderly patients with AF, CA may be associated with a lower incidence of all-cause and cardiovascular mortality.     

非瓣膜性心房颤动患者的卒中危险因素分析

卒中是非瓣膜性心房颤动(以下简称为房颤)的主要并发症。心力衰竭、高龄、高血压、糖尿病及卒中或短暂性脑缺血发作史与房颤患者卒中的风险相关,此外,临床上其他原因所致的缺血性卒中的危险因素也与房颤患者的卒中风险相关。筛选房颤患者并发卒中的危险因素,并采取有效方法评估其卒中的危险性,无论是对于抗凝治疗预防卒中事件,还是对于减少抗凝治疗引起的出血风险,都具有十分重要的意义。     

缺血性卒中防治中的抗凝治疗

凝血系统的激活在缺血性卒中,尤其是心源性脑栓塞的发生和发展过程中起着重要作用.作为缺血性卒中的主要预防措施之一,抗凝治疗愈来愈受到广泛关注.同时,针对凝血途径中的不同环节进行干预的抗凝药研究也取得了重大进展.     

Prevalence of risk factors for atrial fibrillation and stroke among 1210 patients with sleep disordered breathing

Aims

This study sought to identify the prevalence of risk factors for atrial fibrillation and stroke in a sleep apnea population.

Methods

Study participants included 1210 consecutive adults who were referred with suspicion of sleep apnea. Statistical analysis was used to determine the relationship between sleep apnea syndrome and risk factors for atrial fibrillation and stroke.

Results

Among 1210 enrolled patients, 65.8% had severe sleep apnea (Apnea/hypopnea Index — AHI > 30), 25.2% had mild to moderate sleep apnea (AHI 5 to 30), and 8.8% had no sleep apnea (AHI < 5). At baseline, the mean apnea–hypopnea index in patients with sleep apnea syndrome was 35. Compared to patients with an AHI < 5, those with an AHI > 30 were older (47.3 ± 11.4 vs. 52.74 ± 12.4, p < 0.001) and had a higher body mass index (BMI) (30.7 ± 7.3 vs. 33.83 ± 10.1, p < 0.001), a higher prevalence of hypertension (38 vs. 16%, p < 0.001), and a higher CHADS₂ (congestive heart failure, hypertension, age, diabetes and prior stroke) score (0.59 ± 0.8 vs. 0.28 ± 0.64, p < 0.001).

Conclusions

Patients with severe sleep apnea have a higher prevalence of risk factors for atrial fibrillation and stroke when compared with subjects without sleep apnea.     

Statin therapy in the prevention of atrial fibrillation in the early postoperative period after coronary artery bypass grafting: A meta-analysis

BackgroundPostoperative atrial fibrillation (POAF) is observed in the early postoperative period in approximately every third patient after coronary artery bypass grafting (CABG). The pathogenesis of POAF is multifactorial and is not yet fully studied. In many studies, postoperative inflammatory response has been extensively investigated as a potential basic factor of POAF. It is known that statins have anti-inflammatory properties. In some studies, pre- and perioperative use of statins has shown the decrease of incidence of POAF after CABG.ObjectiveWe conducted meta-analysis of randomized and observational studies of efficiency of statin therapy for the prevention of POAF after CABG.Material and methodsThe meta-analysis included 15 clinical trials of statins in 9369 patients with performed CABG during the past 10 years. 5598 patients (59.75%) were taking statins and 3771 patients (40.25%) were not taking statins. The following outcomes observed in the early postoperative period were studied: incidence of POAF, total mortality rate, total stroke rate, and total rate of myocardial infarction. The duration of hospitalization and levels of inflammatory markers before and after CABG were also assessed.ResultsThe statin therapy reduced the incidence of POAF after CABG (OR = 0.48, 95% CI: 0.35–0.67, P < 0.001). Moreover, the statin therapy decreased the total length of hospital stay and levels of inflammatory markers in the blood serum.ConclusionThe results of our meta-analysis leave no doubt in the presence of anti-inflammatory and anti-arrhythmic effect of statin therapy. We confirmed the overall positive role of using statins before CABG for POAF prevention.     

Recurrent Stroke Incidence and Etiology in Patients with Embolic Stroke of Undetermined Source and Other Stroke Subtypes

Aims: This study aimed at clarifying the incidence of recurrent stroke and its etiology in patients with embolic stroke of undetermined source (ESUS) and other stroke subtypes in both the acute and chronic periods. Methods: A total of 645 patients who were admitted with acute ischemic stroke (IS) between March 2015 and August 2019 were enrolled. Among them, 511 patients with ESUS, cardioembolism (CE), large artery atherosclerosis (LAA), or small vessel disease (SVD) were analyzed in this study. After discharge, 391 patients who visited the outpatient clinic were followed up until August 2020. The outcome was stroke recurrence. Results: In the acute admission, recurrence rates were 7.6%, 8.1%, 18.8%, and 2.2% in patients with ESUS, CE, LAA, and SVD, respectively, and there were significant differences between the groups. The subtype of recurrence was almost identical to that of the index stroke. In the outpatient clinic, the annual recurrence rates were 4.4%, 4.3%, 6.0%, and 2.9% in ESUS, CE, LAA, and SVD, respectively, and no difference was observed. Subtypes of recurrence in outpatients with ESUS included ESUS, intracerebral hemorrhage (ICH), and SVD. Patients with ESUS and SVD had a higher risk of ICH during follow-up. Conclusions: Although the risk of recurrence was comparable between patients with ESUS and CE and intermediate between patients with LAA and SVD, in the acute admission unit, the risk in outpatients was similar among all subtypes. ESUS was the most recurrent stroke subtype in outpatients with ESUS. The risk of hemorrhagic stroke was significant in patients with SVD and ESUS.     

SAMe-TT2R2 Score,Time in Therapeutic Range,and Outcomes in Anticoagulated Patients with Atrial Fibrillation

BackgroundOral anticoagulation is highly effective in preventing stroke and mortality in nonvalvular atrial fibrillation patients. However, the efficacy and safety of vitamin K antagonists (the main oral anticoagulation drug used) strongly depends upon the quantity of anticoagulation control, as reflected by the average percentage of the time in therapeutic range of international normalized ratio 2.0-3.0. An easy, simple prediction of which atrial fibrillation patients are likely to do well on vitamin K antagonists (with good average time in therapeutic range) could guide decision-making between using vitamin K antagonists (eg, warfarin) and non-vitamin K antagonist oral anticoagulants.Methods and ResultsIn a consecutive cohort of nonvalvular atrial fibrillation patients attending our anticoagulation clinic, we tested the hypothesis that the new Sex, Race, Medical history, Tobacco use, Race (SAMe-TT₂R₂) score was a predictor for good average time in therapeutic range, and second, this would translate into adverse events in a “real world” cohort of patients with nonvalvular atrial fibrillation. The incidence of bleeding, adverse cardiovascular events (including stroke/thromboembolism), and mortality during the follow-up was higher with increasing SAMe-TT₂R₂ score. The SAMe-TT₂R₂ score was predictive for the composite of all adverse events (hazard ratio 1.32 [95% Confidence Interval 1.17-1.50]; P <.001), adverse cardiovascular events (1.52 [1.28-1.83]; P <.001), and all-cause mortality (1.41 [1.16-1.67]; P = .001). A trend was also observed for major bleeding events (1.23 [0.99-1.53]; P = .059).ConclusionIn a “real world” cohort of consecutive patients with nonvalvular atrial fibrillation, a high SAMe-TT₂R₂ score (reflecting poor anticoagulation control with poor time in therapeutic range) was associated with more bleeding, adverse cardiovascular events, and mortality during follow-up.     

Sequential changes in renal function and the risk of stroke and death in patients with atrial fibrillation

Background

Renal dysfunction has been proposed for the risk factor for stroke and bleeding in atrial fibrillation (AF). The impact of changes in renal dysfunction over time and the relationship to stroke and bleeding risk in these patients remain unknown. We investigated sequential change in renal function (estimated glomerular filtration rate, eGFR) and the risk for clinical events (ischaemic stroke, death and major bleeding) over time in a cohort of 617 AF patients followed up for 2 years.

Methods

eGFR was estimated at baseline, 6 months and 12 months using three formulas (Modification of Diet in Renal Disease equation, MDRD, Chronic Kidney Disease Epidemiology Collaboration, CKD-EPI, and Cockcroft–Gault equation). Changes in eGFR and the risk for clinical events were analysed by Cox models, receiver operating curves (ROC), and Kaplan–Meier survival curves.

Results

When patients with eGFR ≤ 60 ml/min/1.73 m² were compared to patients with eGFR > 60 ml/min/1.73 m², there was an increase over time in stroke or death, or death, with impaired renal function (all p < 0.05). An absolute decrease in eGFR ≥ 15 ml/min/1.73 m² on Cockcroft–Gault and CKD-EPI and ≥ 25 ml/min/1.73 m² on MDRD were associated with an increased risk for stroke or death, death, and ischaemic stroke at 6 months (all p < 0.05), but not major bleeding. A relative reduction (decline of ≥ 25%) in eGFR was also an independent risk. ROC analysis showed that a relative reduction in eGFR ≥ 25% at 6 months and 12 months modestly predicted the occurrence of stroke or death in patients with AF (c-indexes: 0.57 to 0.61, p < 0.05).

Conclusion

In patients with AF, an absolute decrease in eGFR ≥ 15 ml/min/1.73 m² on Cockcroft–Gault and CKD-EPI, and ≥ 25 ml/min/1.73 m² on MDRD, or a relative reduction (≥ 25%) in eGFR, independently predicted the risk for the endpoints ‘stroke or death’, ‘death’ or (at 6 months) ischaemic stroke. Deteriorating renal function increases the risk of death in AF patients.     

Trends in the rates of hospitalizations for acute stroke among patients over 90 years of age with atrial fibrillation in the United States: from 2005 to 2014

Background Acute stroke (AS) rates in patients over 90 years of age (very elderly) with atrial fibrillation (AF) in the United States (US) are not known. We assessed trends in hospitalizations for AS among very elderly with AF in the US from 2005 to 2014. Methods We used the nationwide inpatient sample (NIS) from the USA; 2005–2014. AF and AS diagnoses were abstracted using international classification of diseases, 9^th Revision, clinical modification (ICD-9-CM) codes. Results From 2005–2014, 3,606,073 hospitalizations of very elderly with AF were reported. Of these, 188,948 hospitalizations (141,822 hospitalizations in women and 47,126 hospitalizations in men) had AS as the primary diagnosis. Age adjusted AS hospitalizations increased in the total cohort (3217/million in 2005 to 3871/million in 2014), in women (3540/million in 2005 to 4487/million in 2014) and in men (2490/million in 2005 to 3173/million in 2014) (P < 0.001). Anticoagulation rates increased in women (8% in 2005 to 19.9% in 2014) and in men (8.9% in 2005 to 21.6% in 2014). AS rates, though numerically lower than the total cohort, showed an increasing trend in anticoagulated patients as well (all anticoagulated patients: 212/million in 2005 to 513/million in 2014; anticoagulated women: 224/million in 2005 to 529/million in 2014, anticoagulated men: 184/million in 2005 to 518/million in 2014). Conclusions There is an increasing trend in AS hospitalizations among nonagenarians with AF in the US despite improving utilization of anticoagulants in this patient population. The etiologies driving this alarming trend are unclear and require fur?ther study.     

Mortality in patients with atrial fibrillation has significantly decreased during the last three decades: 35 years of follow-up in 1627 pacemaker patients

Aim: The impact of atrial fibrillation (AF) on mortality is not fullyunderstood. We therefore sought to investigate long-term effectsof AF on mortality in patients with the need for pacemaker (PM)therapy. Methods and results: A total of 1627 PM recipients with AF at implantation were followedin a single-centre, longitudinal study for up to 35 years. Baselinefactors affecting survival and long-term follow-up were analysed.A total of 7362 patient-years of follow-up (PM implanted between1971 and 2000, followed until 31 December 31 2005) were analysed.Female PM recipients lived significantly longer than male (P= 0.025; mean survival 91.9 vs. 72.1 months) despite older ageat time of inclusion. Mean survival times almost doubled forpatients implanted in the last decade, with 139.8 months inthe nineties vs. 66.8 months in the seventies and 75.7 monthsin the eighties (P < 0.001). Male gender, age at implantation,non-syncopal bradycardia, and decade of implantation influencedsurvival. Conclusion: Life expectancy in AF patients after PM implantation has doubledwithin the last three decades, with a mean survival in the overallpopulation of 7.6 years for women and 6.0 years for men. Survivalis influenced by several simple baseline characteristics, whichmay help to identify patients with very long survival times.     

Validation of contemporary stroke and bleeding risk stratification scores in non-anticoagulated Chinese patients with atrial fibrillation

Background

Risk stratification schemes assessing stroke and thromboembolism (stroke/TE) and bleeding relating to atrial fibrillation (AF) have largely been derived and validated in Western populations. We assessed risk factors that constitute scores for assessing stroke/TE (CHADS₂, CHA₂DS₂-VASc) and bleeding (HAS-BLED), and the predictive value of these scores in a large cohort of Chinese patients with AF.

Methods and results

We studied 1034 AF patients (27.1% female, median age 75; 85.6% non-anticoagulated) with mean follow-up of 1.9 years. On multivariate analysis, vascular disease was independently associated with stroke/TE in non-anticoagulated patients (p = 0.04). In patients with a CHADS₂ or CHA₂DS₂-VASc score = 1, the rate of stroke/TE was 2.9% and 0.9% respectively, but in patients at “high risk” (scores ≥ 2), this rate was 4.6% and 4.5%, respectively. The c-statistics for predicting stroke/TE with CHADS₂ and CHA₂DS₂-VASc were 0.58 (p = 0.109) and 0.72 (p < 0.001), respectively. Compared to CHADS₂, the use of CHA₂DS₂-VASc would result in a Net Reclassification Improvement (NRI) of 16.6% (p = 0.009) and an Integrated Discrimination Improvement (IDI) of 1.1% (p = 0.002). Cumulative survival of the patients with a CHA₂DS₂-VASc score ≥ 2 was decreased compared to those with a CHA₂DS₂-VASc score 0–1 (p < 0.001), but the CHADS₂ was not predictive of mortality. There was an increased risk of major bleeding with increasing HAS-BLED score (c-statistic 0.61, 95% CI: 0.51–0.71, p = 0.042).

Conclusions

Vascular disease was a strong independent predictor of stroke/TE in Chinese patients with AF. The CHA₂DS₂-VASc score performed better than CHADS₂ in predicting stroke/TE in this Chinese AF population. Cumulative survival of the patients at high risk with the CHA₂DS₂-VASc score (but not using CHADS₂) was significantly decreased.     

Embolic stroke, sinus rhythm and left atrial mechanical function.

A 64-year-old man manifested a stroke two years after restoration of sinus rhythm through a radiofrequency catheter ablation. Transesophageal echocardiography demonstrated the presence of a thrombus in the left atrial appendage. Left atrial volumes and different parameters of atrial emptying showed that, despite the persistence of the sinus rhythm, atrial mechanical function was severely impaired. After atrial ablation procedures echocardiography can be useful to stratify patients according to their risk of developing embolic events and hence be of help in deciding whether or not discontinuation of anticoagulant therapy is the appropriate choice.