Despite improvements in the management of atrial fibrillation, patients with this condition remain at increased risk for cardiovascular complications. It is unclear whether early rhythm-control ...therapy can reduce this risk.
In this international, investigator-initiated, parallel-group, open, blinded-outcome-assessment trial, we randomly assigned patients who had early atrial fibrillation (diagnosed ≤1 year before enrollment) and cardiovascular conditions to receive either early rhythm control or usual care. Early rhythm control included treatment with antiarrhythmic drugs or atrial fibrillation ablation after randomization. Usual care limited rhythm control to the management of atrial fibrillation-related symptoms. The first primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome; the second primary outcome was the number of nights spent in the hospital per year. The primary safety outcome was a composite of death, stroke, or serious adverse events related to rhythm-control therapy. Secondary outcomes, including symptoms and left ventricular function, were also evaluated.
In 135 centers, 2789 patients with early atrial fibrillation (median time since diagnosis, 36 days) underwent randomization. The trial was stopped for efficacy at the third interim analysis after a median of 5.1 years of follow-up per patient. A first-primary-outcome event occurred in 249 of the patients assigned to early rhythm control (3.9 per 100 person-years) and in 316 patients assigned to usual care (5.0 per 100 person-years) (hazard ratio, 0.79; 96% confidence interval, 0.66 to 0.94; P = 0.005). The mean (±SD) number of nights spent in the hospital did not differ significantly between the groups (5.8±21.9 and 5.1±15.5 days per year, respectively; P = 0.23). The percentage of patients with a primary safety outcome event did not differ significantly between the groups; serious adverse events related to rhythm-control therapy occurred in 4.9% of the patients assigned to early rhythm control and 1.4% of the patients assigned to usual care. Symptoms and left ventricular function at 2 years did not differ significantly between the groups.
Early rhythm-control therapy was associated with a lower risk of adverse cardiovascular outcomes than usual care among patients with early atrial fibrillation and cardiovascular conditions. (Funded by the German Ministry of Education and Research and others; EAST-AFNET 4 ISRCTN number, ISRCTN04708680; ClinicalTrials.gov number, NCT01288352; EudraCT number, 2010-021258-20.).
The benefit of an implantable cardioverter-defibrillator (ICD) in patients with symptomatic systolic heart failure caused by coronary artery disease has been well documented. However, the evidence ...for a benefit of prophylactic ICDs in patients with systolic heart failure that is not due to coronary artery disease has been based primarily on subgroup analyses. The management of heart failure has improved since the landmark ICD trials, and many patients now receive cardiac resynchronization therapy (CRT).
In a randomized, controlled trial, 556 patients with symptomatic systolic heart failure (left ventricular ejection fraction, ≤35%) not caused by coronary artery disease were assigned to receive an ICD, and 560 patients were assigned to receive usual clinical care (control group). In both groups, 58% of the patients received CRT. The primary outcome of the trial was death from any cause. The secondary outcomes were sudden cardiac death and cardiovascular death.
After a median follow-up period of 67.6 months, the primary outcome had occurred in 120 patients (21.6%) in the ICD group and in 131 patients (23.4%) in the control group (hazard ratio, 0.87; 95% confidence interval CI, 0.68 to 1.12; P=0.28). Sudden cardiac death occurred in 24 patients (4.3%) in the ICD group and in 46 patients (8.2%) in the control group (hazard ratio, 0.50; 95% CI, 0.31 to 0.82; P=0.005). Device infection occurred in 27 patients (4.9%) in the ICD group and in 20 patients (3.6%) in the control group (P=0.29).
In this trial, prophylactic ICD implantation in patients with symptomatic systolic heart failure not caused by coronary artery disease was not associated with a significantly lower long-term rate of death from any cause than was usual clinical care. (Funded by Medtronic and others; DANISH ClinicalTrials.gov number, NCT00542945 .).
Cardioversion is widely used in patients with atrial fibrillation (AF) and atrial flutter when a rhythm control strategy is pursued. We sought to summarize the current evidence on this important area ...of clinical management of patients with AF including electrical and pharmacological cardioversion, peri-procedural anticoagulation and thromboembolic complications, success rate, and risk factors for recurrence to give practical guidance.
DANISH (The Danish Study to Assess the Efficacy of Implantable Cardioverter Defibrillators ICDs in Patients With Nonischemic Systolic Heart Failure on Mortality) found that primary-prevention ICD ...implantation was not associated with an overall survival benefit in patients with nonischemic systolic heart failure during a median follow-up of 5.6 years, although there was a beneficial effect on all-cause mortality in patients ≤70 years. This study presents an additional 4 years of follow-up data from DANISH.
In DANISH, 556 patients with nonischemic systolic heart failure were randomized to receive an ICD and 560 to receive usual clinical care and followed until June 30, 2016. In this long-term follow-up study, patients were followed until May 18, 2020. Analyses were conducted for the overall population and according to age (≤70 and >70 years).
During a median follow-up of 9.5 years (25th-75th percentile, 7.9-10.9 years), 208/556 patients (37%) in the ICD group and 226/560 patients (40%) in the control group died. Compared with the control group, the ICD group did not have significantly lower all-cause mortality (hazard ratio HR 0.89, 95% CI, 0.74-1.08;
= 0.24). In patients ≤70 years (n = 829), all-cause mortality was lower in the ICD group than the control group (117/389 30% versus 158/440 36%; HR, 0.78 95% CI, 0.61-0.99;
= 0.04), whereas in patients >70 years (n = 287), all-cause mortality was not significantly different between the ICD and control group (91/167 54% versus 68/120 57%; HR, 0.92 95% CI, 0.67-1.28;
= 0.75). Cardiovascular death showed similar trends (overall, 147/556 26% versus 164/560 29%; HR, 0.87 95% CI, 0.70-1.09;
= 0.20; ≤70 years, 87/389 22% versus 122/440 28%; HR, 0.75 95% CI, 0.57-0.98;
= 0.04; >70 years, 60/167 36% versus 42/120 35%; HR, 0.97 95% CI, 0.65-1.45;
= 0.91). The ICD group had a significantly lower incidence of sudden cardiovascular death in the overall population (35/556 6% versus 57/560 10%; HR, 0.60 95% CI, 0.40-0.92;
= 0.02) and in patients ≤70 years (19/389 5% versus 49/440 11%; HR, 0.42 95% CI, 0.24-0.71;
= 0.0008), but not in patients >70 years (16/167 10% versus 8/120 7%; HR, 1.34 95% CI, 0.56-3.19;
= 0.39).
During a median follow-up of 9.5 years, ICD implantation did not provide an overall survival benefit in patients with nonischemic systolic heart failure. In patients ≤70 years, ICD implantation was associated with a lower incidence of all-cause mortality, cardiovascular death, and sudden cardiovascular death. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00542945.
Abstract
Aims
We aimed to investigate whether left atrial (LA) markers from cardiovascular magnetic resonance (CMR) were able to predict atrial fibrillation (AF) in elderly patients with risk factors ...for stroke.
Methods and results
At baseline, 203 participants with stroke risk factors but without history of AF underwent advanced CMR and received an implantable loop recorder. During a median of 40 (37–42) months of continuous monitoring, incident AF was detected in 79 patients (39%). With regards to CMR markers, a steep increase in incidence rate of AF was seen with LA maximum volume (LAmax) above 55 mL/m2, LA minimum volume (LAmin) above 30 mL/m2, LA total emptying fraction (LA TEF) below 45%, LA active emptying fraction (LA AEF) below 37%, LA strain S below 25%, LA strain A below 17%, and LA strain rate A above −1.7 s−1. After multivariate adjustment, the above-mentioned CMR markers remained associated with AF incidence: hazard ratio (95% confidence interval) 1.25 (1.06–1.48) and 1.51 (1.22–1.87) per 10 mL/m2 increase of LAmax and LAmin, respectively, 1.49 (1.26–1.76) and 1.46 CI (1.25–1.71) per 5% decrease in LA TEF and LA AEF, respectively, 1.23 (1.05–1.44) and 1.56 (1.18–2.06) per 5% decrease in LA strain S and A, respectively, and 2.06 (1.31–3.23) per s−1 increase in LA strain rate A. In prediction analyses, LA functional indices increased area under the receiver operating characteristic curve significantly.
Conclusion
The risk of AF, including asymptomatic AF, increases significantly with increasing LA volumes and worsening LA function.
The effectiveness and safety of antithrombotic therapy (AT) among patients with a history of intracerebral hemorrhage remain uncertain. We therefore determined the prevalence of indication for AT ...among patients hospitalized with first-time intracerebral hemorrhage and examined the impact of subsequent AT use on the long-term clinical outcome.
We performed a population-based cohort study using nationwide Danish medical registries. Patients with risk of thromboembolism surviving the first 30 days after hospitalization because of intracerebral hemorrhage were identified and followed up. We estimated the hazard ratio of all-cause death, thromboembolic events, or major bleeding according to use of AT.
We identified 6369 patients between 2005 and 2013. Among these patients, 2978 (47%) had indication for AT, and during the follow-up, (median: 2.3 year) 1281 (43%) died, 497 (17%) had a thromboembolic event, and 536 (18%) had major bleeding. Postdischarge use of oral anticoagulation therapy among patients with indication for oral anticoagulation therapy was associated with a significant lower risk of death (adjusted hazard ratio, 0.59; 95% confidence interval, 0.43-0.82) and thromboembolic events (adjusted hazard ratio 0.58; 95% confidence interval, 0.35-0.97) and no increased risk of major bleeding (adjusted hazard ratio 0.65; 95% confidence interval, 0.41-1.02). In contrast, use of platelet inhibitors among patients with indication for platelet inhibitors was not related to statistically significantly improved clinical outcome.
Approximately 1 of 2 patients surviving intracerebral hemorrhage had a high risk of thromboembolism. Postdischarge use of oral anticoagulation therapy was associated with a lower risk of all-cause mortality and thromboembolic events and no increased risk of major bleeding.
Pacemakers can automatically identify and catalog atrial high-rate episodes (AHREs). While most AHREs represent true atrial tachyarrhythmia/atrial fibrillation (AT/AF), a review of stored ...electrograms suggests that a substantial proportion do not. As AHREs may lead to the initiation of oral anticoagulation, it is crucial to understand the relationship between AHREs and true AT/AF.
To compare the positive predictive value of AHREs for electrogram-confirmed AT/AF for various atrial rates and episode durations.
By using data from 2580 patients who participated in the ASymptomatic atrial fibrillation and Stroke Evaluation in pacemaker patients and the AF Reduction atrial pacing Trial, all AHREs >6 minutes and >190 beats/min with available electrograms were reviewed to determine whether they represented true AT/AF. The positive predictive value of these AHREs was assessed for episode durations of 6 minutes, 30 minutes, 6 hours, and 24 hours at atrial rates of 190 and 250 beats/min.
Of 5769 AHREs >6 minutes and >190 beats/min, 82.7% were true AT/AF and 17.3% were false positives (predominantly due to repetitive non-re-entrant ventriculoatrial synchrony). False positives dropped to 6.8%, 3.3%, and 1.8% when the threshold duration was increased to 30 minutes, 6 hours, and 24 hours, respectively. Increasing the threshold heart rate to 250 beats/min added little to the positive predictive value when longer threshold durations were used.
By using a cutoff of >6 minutes and >190 beats/min, the rate of false-positive AHREs is 17.3%, making physician review of electrograms essential. For AHREs lasting >6 hours, the rate of false positives is 3.3%, making physician review less crucial.
Atrial fibrillation (AF) is the most common clinical arrhythmia and is associated with increased morbidity and mortality. There is growing evidence that numerous cardiovascular diseases and risk ...factors are associated with incident AF and that lone AF is rare. Beyond oral anticoagulant therapy, rate and rhythm control, therapy targeting risk factors and underlying conditions is an emerging AF management strategy that warrants better implementation in clinical practice. This review describes current evidence regarding the association between known modifiable risk factors and underlying conditions and the development and progression of AF. It discusses evidence for the early management of underlying conditions to improve AF outcomes. It also provides perspective on the implementation of tailored AF management in daily clinical practice.
EQ-5D is a generic instrument to measure health-related quality of life. In 2009, a new version, EQ-5D-5L, was introduced as an attempt to reduce ceiling effects and improve sensitivity to small ...changes over time. The objective of this study was to assess the measurement properties of the EQ-5D-5L instrument compared to the EQ-5D-3L instrument in an elderly general population with a moderate to a high degree of comorbidity. A subgroup of participants in a large clinical trial completed the EQ-5D-3L and the EQ-5D-5L questionnaires. Based on the collected data, we tested for feasibility and ceiling and floor effects. Furthermore, we assessed the redistribution properties of the responses and examined the level of inconsistency, informativity, and convergent validity. A total of 1002 persons diagnosed with hypertension, diabetes, heart failure, and/or previous stroke completed both the EQ-5D-3L and the EQ-5D-5L questionnaires. The overall ceiling effect decreased from 46% with the EQ-5D-3L to 30% with the EQ-5D-5L and absolute and relative informativity were higher for EQ-5D-5L, and there was a stronger correlation between EQ-5D-5L and EQ VAS. The EQ-5D-5L seemed to perform better than the EQ-5D-3L in terms of feasibility, ceiling effect, discriminatory power, and convergent validity. The overall ceiling effect was higher than that found in patient samples in previous studies but lower than the one found in population studies.
IntroductionAtrial fibrillation (AF) is the most common postoperative complication after surgical aortic valve replacement (SAVR) and occurs in up to 50% of the patients. Development of postoperative ...AF (POAF) is associated with a 2–3 fold increased risk of adverse events, including stroke, myocardial infarction and death.Several studies have implied that prophylactic Atorvastatin therapy could prevent POAF in patients undergoing coronary artery bypass graft. These studies suggest that Atorvastatin has rapid and significant pleiotropic actions that reduce the risk of POAF. However, prophylactic treatment with statins has yet to be understood in SAVR. The aim of this study is to investigate whether prophylactic administration of torvastatin reduces POAF in patients undergoing SAVR.Methods and analysisIn this investigator-initiated, prospective, parallel-group, randomised, double-blind, placebo-controlled single-centre trial, 266 patients undergoing elective solitary SAVR with bioprosthetic valve, with no prior history of AF, and statin-naïve will be randomised (1:1) to treatment with Atorvastatin (80 mg once daily) or matching placebo for 1–2 weeks prior to and 30 days after surgery. The primary endpoint is POAF defined as an episode of irregular RR-intervals without a traceable p-wave of at least 30 s duration. After discharge and until day 30 after surgery, POAF will be documented by either rhythm strip or 12-lead ECG.Ethics and disseminationProtocol approval has been obtained from the Regional Scientific Ethical Committee for Southern Denmark (S-20210159), The Danish Medicines Agency (2021103821) and the Data Protection Agency (21/65621).The trial is conducted in accordance with the Declaration of Helsinki, the ICH-GCP (International Conference on Harmonisation Good Clinical Practice) guidelines and the legal regulations of Denmark. Study findings will be shared via peer-reviewed journal publication and conference presentations.Trial registration numberNCT05076019.
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