Nicolas Clementy

Statin therapy and atrial fibrillation: systematic review and updated meta-analysis of published randomized controlled trials.

Purpose of review Whether statins may prevent atrial fibrillation remains a subject of debate. An updated systematic review of randomized controlled trials with statins that collected data on the incidence or recurrence of atrial fibrillation was performed. Recent findings Thirty-two published studies with 71 005 patients were included in the analysis. Overall, the use of statins was significantly associated with a decreased risk of atrial fibrillation compared with controls [odds ratio (OR) 0.69, 95% confidence interval (CI) 0.57–0.83, P < 0.0001] with heterogeneous results. The benefit of statin therapy appeared highly significant for the prevention of postoperative atrial fibrillation (homogeneous OR 0.37, 95% CI 0.28–0.51, P < 0.00001). Benefit was not apparent for the prevention of new-onset atrial fibrillation (OR 1.00, 95% CI 0.86–1.15, P = 0.95) but was significant for secondary prevention of atrial fibrillation (OR 0.57, 95% CI 0.36–0.91, P = 0.02 with significant heterogeneity). There was no reduction in the risk of atrial fibrillation with more intensive vs. standard statin regimens (OR 1.01, 95% CI 0.77–1.32, P = 0.96). Summary The use of statins was significantly associated with a decreased risk of atrial fibrillation in patients with sinus rhythm. The highest benefit was seen for the prevention of postoperative atrial fibrillation and in secondary prevention of atrial fibrillation, with a heterogeneity that deserves further clarification.

Stroke and Major Bleeding Risk in Elderly Patients Aged ≥75 Years With Atrial Fibrillation The Loire Valley Atrial Fibrillation Project

Background and Purpose— Atrial fibrillation (AF) is increasingly prevalent in the elderly, but such patients tend to be under-represented in clinical trials. Increasing age confers a higher risk of stroke and bleeding when antithrombotic therapy is used. We examined risk factors for stroke and bleeding among elderly (age, >75 years) patients within a real world hospitalized cohort from the Loire Valley AF project. Methods— We identified elderly (age, >75 years) patients with AF, assessed their risk factors, and followed up for stroke, thromboembolism, death, or major bleeding. The effect of vitamin K antagonist (VKA) use on these end points was assessed. Results— We studied 8962 patients with AF, and we identified 4130 elderly (age, ≥75 years) patients. Using Kaplan–Meier analyses, event rates of death, stroke/thromboembolism, the composite of stroke/thromboembolism/death, and major bleeding increased with increasing age. For mortality, VKA-treated patients did better than non-VKA–treated patients. The risk of death and stroke/thromboembolism/death increased with increasing age. The risk of major bleeding did not increase with increasing age strata. VKA treatment was associated with lower mortality in those aged <75 years (adjusted hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.45–0.72), and the effect size was maintained with increasing age strata (Pint=0.67). For stroke/thromboembolism/death, VKA also has a significant benefit in those aged <75 years (adjusted HR, 0.69; [0.57–0.83]), and the effect size was maintained with increasing age strata (Pint=0.58). For major bleeding, there was no statistically significant difference between age strata (Pint=0.67). In elderly patients, age and previous stroke emerged as the main predictors of stroke and thromboembolism. Renal impairment and VKA use were predictors of major bleeding. Conclusions— Elderly patients with AF have a higher risk of stroke and bleeding, but the benefits of VKA therapy for stroke/thromboembolism or mortality were present regardless of increasing age.

Anticoagulation in patients with atrial fibrillation undergoing coronary stent implantation

In patients with atrial fibrillation (AF) undergoing coronary stent implantation, the optimal antithrombotic strategy is unclear. We evaluated whether use of oral anticoagulation (OAC) was associated with any benefit in morbidity or mortality in patients with AF, high risk of thromboembolism (TE) (CHA2DS2-VASC score ≥ 2) and coronary stent implantation. Among 8,962 unselected patients with AF seen between 2000 and 2010, a total of 2,709 (30%) had coronary artery disease and 417/2,709 (15%) underwent stent implantation while having CHA2DS2-VASC score ≥ 2. During follow-up (median=650 days), all TE, bleeding episodes, and major adverse cardiac events (i.e. death, acute myocardial infarction, target lesion revascularisation) were recorded. At discharge, 97/417 patients (23%) received OAC, which was more likely to be prescribed in patients with permanent AF and in those treated for elective stent implantation. The incidence of outcome event rates was not significantly different in patients treated and those not treated with OAC. However, in multivariate analysis, the lack of OAC at discharge was independently associated with increased risk of death/stroke/systemic TE (relative risk [RR] =2.18, 95% confidence interval [CI] 1.02-4.67, p=0.04), with older age (RR =1.12, 1.04-1.20, p=0.003), heart failure (RR =3.26, 1.18-9.01, p=0.02), and history of stroke (RR =18.87, 3.11-111.11, p=0.001). In conclusion, in patients with AF and high thromboembolic risk after stent implantation, use of OAC was independently associated with decreased risk of subsequent death/stroke/systemic TE, suggesting that OAC should be systematically used in this patient population.

Effects of remote monitoring on clinical outcomes and use of healthcare resources in heart failure patients with biventricular defibrillators: results of the MORE‐CARE multicentre randomized controlled trial

The aim of this study was to evaluate the clinical efficacy and safety of remote monitoring in patients with heart failure implanted with a biventricular defibrillator (CRT‐D) with advanced diagnostics.

Should Atrial Fibrillation Patients With Only 1 Nongender-Related CHA2DS2-VASc Risk Factor Be Anticoagulated?

Background and Purpose— There is some uncertainty about treating patients with atrial fibrillation (AF) with 1 nongender-related (NGR) stroke risk factor (CHA2DS2-VASc [ie, congestive heart failure, hypertension, age (≥75 years; 2 points), diabetes, stroke/transient ischemic attack (2 points), vascular disease, age (65–74 years), sex (female)] score of 1 in males and 2 in females) with oral anticoagulation (OAC). Methods— We investigated adverse outcomes and calculated the net clinical benefit of OAC use in a community-based cohort of unselected AF patients with 0 compared with 1 NGR stroke risk factor (CHA2DS2-VASc 0 versus 1 in males; and 1 versus 2 in females). Among 8962 patients with AF, 2208 (25%) had 0 or 1 NGR stroke risk factors, of which 45% were not prescribed OAC. Results— During a follow-up of 1028±1189 days (median, 495; interquartile range, 5–1882 days), the yearly rate of the combined end point of stroke/systemic embolism in nonanticoagulated AF patients with 1 NGR stroke risk factor was 2.09% (95% confidence interval, 1.37–3.18). This corresponded to an adjusted hazard ratio of 2.82 (95% confidence interval, 1.32–6.04) relative to the group with 0 NGR stroke risk factor. When the benefit of ischemic stroke reduction was balanced against the increased risk of intracranial hemorrhage among patients with 1 NGR stroke risk factor, the net clinical benefit was positive in favor of OAC use versus no antithrombotic therapy or antiplatelet therapy use. The net clinical benefit was negative for antiplatelet therapy use versus no antithrombotic therapy. Conclusions— Among AF patients with 1 NGR stroke risk factor (ie, CHA2DS2-VASc 1 in males or 2 in females), OAC use as indicated according to the guidelines was associated with a positive net clinical benefit for the prevention of stroke and thromboembolic events.

Long-term follow-up on high-rate cut-off programming for implantable cardioverter defibrillators in primary prevention patients with left ventricular systolic dysfunction.

AIMS Implantable cardioverter defibrillators (ICDs) are efficient in reducing mortality in patients with left ventricular systolic dysfunction. High-rate cut-off programming may be effective in reducing appropriate and inappropriate therapies, but as the long-term consequences on morbidity and mortality remain unclear, it is underutilized. METHODS AND RESULTS We prospectively studied 365 consecutive patients (mean age 60 ± 10 years), with ischaemic (63%) or non-ischaemic cardiomyopathy and left ventricular dysfunction (mean ejection fraction 25 ± 7%), who were implanted with an ICD in primary prevention of sudden cardiac death (41% single chamber, 31% dual chamber, and 28% biventricular). All devices were programmed with a shock-only zone over 220 beats per minute (b.p.m.) and a monitoring zone between 170 and 220 b.p.m. During a median follow-up of 40 months, 41 patients received appropriate shocks (11.2%) and 24 inappropriate shocks (6.6%). Then, 306 patients never experienced any ICD shock (84%). Inappropriate discharges were related to supraventricular tachyarrhythmia in 10 patients, and noise/oversensing in 14 patients. Ventricular tachycardia episodes, sustained or not, were recorded in the monitoring zone in 43 patients (11.8%). Seven of these patients were symptomatic (1.9%), without lethal consequence. Sixty-two patients (17%) died: 35 from end-stage heart failure, 1 from unexplained sudden death, and 26 from a documented non-cardiac cause. CONCLUSION High-rate cut-off (220 b.p.m.) shock-only ICD programming, in primary prevention patients with reduced left ventricular ejection fraction, appeared to be safe during a long-term follow-up. It also resulted in a very low rate of discharges, which are known to be deleterious in this population.

Prognostic value of CHA2DS2-VASc score in patients with ‘non-valvular atrial fibrillation’ and valvular heart disease: the Loire Valley Atrial Fibrillation Project

AIMS The CHA2DS2VASc score is a clinical risk stratification tool which estimates the risk of stroke and thromboembolism in non-valvular atrial fibrillation (AF). We aimed to establish the value of this score for risk evaluation in patients with non-valvular AF and valvular heart disease. METHODS AND RESULTS Among 8053 patients with non-valvular AF (ESC guidelines definition), patients were categorized into Group 1 (no valve disease, n = 6851; 85%) and Group 2 (valve disease with neither rheumatic mitral stenosis nor valve prothesis, n = 1202; 15%). After follow-up of 868 ± 1043 days, 627 stroke/ thromboembolic (TE) events were recorded. Group 2 was significantly older, had a higher CHA2DS2VASc score and had a higher risk of thromboembolic events [hazard ratio (HR) 1.39; 95% CI 1.14-1.69, P = 0.001] compared with Group 1. Severe valve disease was not associated with worse prognosis for stroke/TE events. In the two groups, stroke/TE risk increased with a higher CHA2DS2VASc score. Factors independently associated with increased risk of stroke/TE events were older age (HR 1.25, 95% CI 1.14-1.36 per 10-year increase, P < 0.0001) and higher CHA2DS2VASc score (HR 1.33, 95% CI 1.23-1.45, P < 0.0001). The predictive value (c-statistic) of the CHA2DS2VASc score was similar in the two groups. CONCLUSION In patients with non-valvular AF, left-sided valvular heart disease (excluding mitral stenosis and protheses) was associated with an increased risk of stroke/TE events. A higher CHA2DS2VASc score in these patients is likely to explain these results.

Patients With Ischemic Stroke and Incident Atrial Fibrillation A Nationwide Cohort Study

Background and Purpose— A substantial part of ischemic strokes is attributed to atrial fibrillation (AF). We hypothesized that patients with ischemic stroke without prior diagnosed AF were at higher risk of having a subsequent diagnosis of AF, and this was associated with multiple risk factors. Methods— This French longitudinal cohort study was based on the national database covering hospital care from 2008 to 2012 for the entire population. Results— Of 65 807 patients with ischemic stroke in 2009, 48 992 did not have AF at baseline. A total of 4828 of these patients were diagnosed as having AF during a follow-up of 15±15 months (incidence rate 7.9 per 100 person-years). By comparison, the yearly rate of new-onset AF for the 826 416 patients with a cardiac hospitalization was 5.9%. CHADS2 (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack) and CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack [doubled], vascular disease, age 65–75 years, and sex category [female]) scores were both associated with the risk of new-onset AF during follow-up (CHADS2: hazard ratio [HR] 1.70, 95% confidence interval [CI] 1.66–1.75; CHA2DS2-VASc: HR 1.45, 95% CI 1.42–1.48). The c statistics were 0.700 (95% CI 0.696–0.706) for CHADS2 and 0.706 (95% CI 0.702–0.710) with CHA2DS2-VASc (P=0.003 for comparison of the 2 scores). Independent predictors of subsequent diagnosis of AF were age 65 to 74 years (HR 2.29, 95% CI 2.06–2.54), age ≥75 years (HR 3.31, 95% CI 3.02–3.64), hypertension (HR 1.22, 95% CI 1.13–1.32), heart failure (HR 2.56, 95% CI 2.41–2.72), and vascular disease (HR 1.10, 95% CI 1.04–1.17). Conclusions— Ischemic stroke was associated with a substantially increased risk of incident AF, particularly among individuals with higher CHADS2 or CHA2DS2-VASc scores. These risk scores seem to be simple tools for identifying patients at higher risk of incident AF after ischemic stroke.

Incidence and predictors of sudden death, major conduction defects and sustained ventricular tachyarrhythmias in 1388 patients with myotonic dystrophy type 1

Aims To describe the incidence and identify predictors of sudden death (SD), major conduction defects and sustained ventricular tachyarrhythmias (VTA) in myotonic dystrophy type 1 (DM1). Methods and results We retrospectively enrolled 1388 adults with DM1 referred to six French medical centres between January 2000 and October 2013. We confirmed their vital status, classified all deaths, and determined the incidence of major conduction defects requiring permanent pacing and sustained VTA. We searched for predictors of overall survival, SD, major conduction defects, and sustained VTA by Cox regression analysis. Over a median 10-year follow-up, 253 (18.2%) patients died, 39 (3.6%) suddenly. Analysis of the cardiac rhythm at the time of the 39 SD revealed sustained VTA in 9, asystole in 5, complete atrioventricular block in 1 and electromechanical dissociation in two patients. Non-cardiac causes were identified in the five patients with SD who underwent autopsies. Major conduction defects developed in 143 (19.3%) and sustained VTA in 26 (2.3%) patients. By Cox regression analysis, age, family history of SD and left bundle branch block were independent predictors of SD, while age, male sex, electrocardiographic conduction abnormalities, syncope, and atrial fibrillation were independent predictors of major conduction defects; non-sustained VTA was the only predictor of sustained VTA. Conclusions SD was a frequent mode of death in DM1, with multiple mechanisms involved. Major conduction defects were by far more frequent than sustained VTA, whose only independent predictor was a personal history of non-sustained VTA. ClinicalTrials.gov no: NCT01136330.Aims To describe the incidence and identify predictors of sudden death (SD), major conduction defects and sustained ventricular tachyarrhythmias (VTA) in myotonic dystrophy type 1 (DM1). Methods and results We retrospectively enrolled 1388 adults with DM1 referred to six French medical centres between January 2000 and October 2013. We confirmed their vital status, classified all deaths, and determined the incidence of major conduction defects requiring permanent pacing and sustained VTA. We searched for predictors of overall survival, SD, major conduction defects, and sustained VTA by Cox regression analysis. Over a median 10-year follow-up, 253 (18.2%) patients died, 39 (3.6%) suddenly. Analysis of the cardiac rhythm at the time of the 39 SD revealed sustained VTA in 9, asystole in 5, complete atrioventricular block in 1 and electromechanical dissociation in two patients. Non-cardiac causes were identified in the five patients with SD who underwent autopsies. Major conduction defects developed in 143 (19.3%) and sustained VTA in 26 (2.3%) patients. By Cox regression analysis, age, family history of SD and left bundle branch block were independent predictors of SD, while age, male sex, electrocardiographic conduction abnormalities, syncope, and atrial fibrillation were independent predictors of major conduction defects; non-sustained VTA was the only predictor of sustained VTA. Conclusions SD was a frequent mode of death in DM1, with multiple mechanisms involved. Major conduction defects were by far more frequent than sustained VTA, whose only independent predictor was a personal history of non-sustained VTA. ClinicalTrials.gov no: NCT01136330.

The evolution of infrahissian conduction time in myotonic dystrophy patients: clinical implications

Background Myotonic dystrophy (MD1) is a hereditary autosomal dominant disease with variable penetrance. Cardiac conduction disturbances are frequent and may be responsible for sudden death, but its progression was heretofore unknown. Aims The aim of the study was to analyse the natural history of infrahissian conduction time in patients with a normal first electrophysiological test, and to identify the predictive value of the clinical and ECG factors accompanying an alteration of infrahissian conduction. Methods Among 127 consecutive screened MD patients, 25 were enrolled and underwent a second electrophysiological testing. The second electrophysiological test was carried out on patients showing new symptoms, new atrioventricular conduction disturbances on ECG, or significant modifications of signal-averaged (SA)-ECG, and on asymptomatic patients with a follow-up of at least 60 months since the first electrophysiological test. Results Among the 25 patients, four had new clinical symptoms, four others developed new atrioventricular conduction abnormalities on ECG and six had significant modifications of the SA-ECG. The mean His-ventricle (HV) interval increased significantly between the two electrophysiological studies (initial HV interval 52.1 ms±1.6 ms, final HV interval 61.4 ms±2.2 ms, p<0.005), with a mean increase of 1.2 ms/year. The five patients with HV interval of 70 ms or greater were implanted with a prophylactic dual-chamber pacemaker. Modifications of resting ECG and SA-ECG were strongly associated with HV interval prolongation. Conclusion In patients with a normal initial electrophysiological study, modifications on the resting ECG and/or SA-ECG, on annual check-up, were associated with an alteration of infrahissian conduction.