scholarly journals The RACE to the EAST. In pursuit of rhythm control therapy for atrial fibrillation—a dedication to Harry Crijns

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_2) ◽  
pp. ii34-ii39
Author(s):  
Bruno Reissmann ◽  
Günter Breithardt ◽  
A John Camm ◽  
Isabelle C Van Gelder ◽  
Andreas Metzner ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Sinus Rhythm ◽  
Clinical Decision Making ◽  
Clinical Decision ◽  
Cardiovascular Death ◽  
Rhythm Control ◽  
Related Factors ◽  
Antiarrhythmic Drug Therapy ◽  
Coronary Syndrome ◽  
Control Therapy

Abstract The RACE trial was one of the first landmark trials to establish whether restoring and maintaining sinus rhythm could reduce morbidity and mortality in patients with atrial fibrillation (AF). Its neutral outcome shaped clinical decision-making for almost 20 years. However, there were two important treatment-related factors associated with mortality of rhythm control therapy at that time: One was safety of antiarrhythmic drug therapy, and the other one withdrawal of anticoagulation after restoration of sinus rhythm. Both concerns have been overcome, and, moreover, important knowledge considering the importance of time for the treatment of AF has been gained. These insights led to the concept of the EAST-AFNET 4 trial, and after more than two decades in the pursuit of ongoing therapeutic improvement, early rhythm control therapy has demonstrated to reduce a composite of cardiovascular death, stroke, and hospitalization for worsening of HF or acute coronary syndrome, by 21% (first primary outcome, absolute reduction 1.1 per 100 patient-years). For this entire period, Harry Crijns characterized the treatment of AF patients, and contributed decisively to realizing the benefit of rhythm control therapy. It is almost easier to list the clinical trials without Harry's involvement than to list those which he co-designed and led.

scholarly journals Recent advances in rhythm control for atrial fibrillation

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1796 ◽  
Author(s):  
Richard Bond ◽  
Brian Olshansky ◽  
Paulus Kirchhof
Keyword(s):  
Atrial Fibrillation ◽  
Catheter Ablation ◽  
Sinus Rhythm ◽  
Pulmonary Vein ◽  
Pulmonary Vein Isolation ◽  
Rate Control ◽  
Rhythm Control ◽  
Management Problem ◽  
Recent Trial ◽  
Control Therapy

Atrial fibrillation (AF) remains a difficult management problem. The restoration and maintenance of sinus rhythm—rhythm control therapy—can markedly improve symptoms and haemodynamics for patients who have paroxysmal or persistent AF, but some patients fare well with rate control alone. Sinus rhythm can be achieved with anti-arrhythmic drugs or electrical cardioversion, but the maintenance of sinus rhythm without recurrence is more challenging. Catheter ablation of the AF triggers is more effective than anti-arrhythmic drugs at maintaining sinus rhythm. Whilst pulmonary vein isolation is an effective strategy, other ablation targets are being evaluated to improve sinus rhythm maintenance, especially in patients with chronic forms of AF. Previously extensive ablation strategies have been used for patients with persistent AF, but a recent trial has shown that pulmonary vein isolation without additional ablation lesions is associated with outcomes similar to those of more extensive ablation. This has led to an increase in catheter-based technology to achieve durable pulmonary vein isolation. Furthermore, a combination of anti-arrhythmic drugs and catheter ablation seems useful to improve the effectiveness of rhythm control therapy. Two large ongoing trials evaluate whether a modern rhythm control therapy can improve prognosis in patients with AF.

scholarly journals Systematic, early rhythm control strategy for atrial fibrillation in patients with or without symptoms: the EAST-AFNET 4 trial

2021 ◽  
Author(s):  
Stephan Willems ◽  
Katrin Borof ◽  
Axel Brandes ◽  
Günter Breithardt ◽  
A John Camm ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Primary Outcome ◽  
Rhythm Control ◽  
Event Analysis ◽  
Time To Event ◽  
Coronary Syndrome ◽  
Asymptomatic Patients ◽  
Control Therapy

Abstract Aims Clinical practice guidelines restrict rhythm control therapy to patients with symptomatic atrial fibrillation (AF). The EAST-AFNET 4 trial demonstrated that early, systematic rhythm control improves clinical outcomes compared to symptom-directed rhythm control. Methods and results This prespecified EAST-AFNET 4 analysis compared the effect of early rhythm control therapy in asymptomatic patients (EHRA score I) to symptomatic patients. Primary outcome was a composite of death from cardiovascular causes, stroke, or hospitalization with worsening of heart failure or acute coronary syndrome, analyzed in a time-to-event analysis. At baseline, 801/2633 (30.4%) patients were asymptomatic [mean age 71.3 years, 37.5% women, mean CHA2DS2-VASc score 3.4, 169/801 (21.1%) heart failure]. Asymptomatic patients randomized to early rhythm control (395/801) received similar rhythm control therapies compared to symptomatic patients [e.g. AF ablation at 24 months: 75/395 (19.0%) in asymptomatic; 176/910 (19.3%) symptomatic patients, P = 0.672]. Anticoagulation and treatment of concomitant cardiovascular conditions was not different between symptomatic and asymptomatic patients. The primary outcome occurred in 79/395 asymptomatic patients randomized to early rhythm control and in 97/406 patients randomized to usual care (hazard ratio 0.76, 95% confidence interval [0.6; 1.03]), almost identical to symptomatic patients. At 24 months follow-up, change in symptom status was not different between randomized groups (P = 0.19). Conclusion The clinical benefit of early, systematic rhythm control was not different between asymptomatic and symptomatic patients in EAST-AFNET 4. These results call for a shared decision discussing the benefits of rhythm control therapy in all patients with recently diagnosed AF and concomitant cardiovascular conditions (EAST-AFNET 4; ISRCTN04708680; NCT01288352; EudraCT2010-021258-20).

scholarly journals Cardiac Sympathetic Activity and Rhythm Control Following Pulmonary Vein Isolation in Patients with Paroxysmal Atrial Fibrillation—A Prospective 123I-mIBG-SPECT/CT Imaging Study

2021 ◽  
Vol 11 (10) ◽  
pp. 995
Author(s):  
Philipp S. Lange ◽  
Christian Wenning ◽  
Nemanja Avramovic ◽  
Patrick Leitz ◽  
Robert Larbig ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Nervous System ◽  
Drug Therapy ◽  
Sinus Rhythm ◽  
Sympathetic Activity ◽  
Sympathetic Innervation ◽  
Rhythm Control ◽  
Antiarrhythmic Drug Therapy ◽  
Cardiac Sympathetic Innervation

Background: Pulmonary vein isolation (PVI) and antiarrhythmic drug therapy are established treatment strategies to preserve sinus rhythm in atrial fibrillation (AF). However, the efficacy of both interventional and pharmaceutical therapy is still limited. Solid evidence suggests an important role of the cardiac sympathetic nervous system in AF. In this blinded, prospective observational study, we studied left ventricular cardiac sympathetic activity in patients treated with PVI and with antiarrhythmic drugs. Prospectively, Iodine-123-benzyl-guanidine single photon emission computer tomography (123I-mIBG-SPECT) was performed in a total of 23 patients with paroxysmal AF, who underwent PVI (n = 20) or received antiarrhythmic drug therapy only (n = 3), respectively. 123I-mIBG planar and SPECT/CT scans were performed before and 4 to 8 weeks after PVI (or initiation of drug therapy, respectively). For semiquantitative SPECT image analysis, attenuation-corrected early/late images were analyzed. Quantitative SPECT analysis was performed using the AHA 17-segment model of the left ventricle. Results: PVI with point-by-point radiofrequency ablation led to a significantly (p < 0.05) higher visual sympathetic innervation defect score when comparing pre-and post PVI. Newly emerging innervation deficits post PVI were localized predominantly in the inferior lateral wall. These findings were corroborated by semiquantitative SPECT analysis identifying inferolateral segments with a reduced tracer uptake in comparison to SPECT before PVI. Following PVI, patients with an AF relapse showed a different sympathetic innervation pattern compared to patients with sufficient rhythm control. Conclusions: PVI results in novel defects of cardiac sympathetic innervation. Differences in cardiac sympathetic innervation remodelling following PVI suggest an important role of the cardiac autonomous nervous system in the maintenance of sinus rhythm following PVI.

scholarly journals Rhythm Control in AF: Have We Reached the Last Frontier?

2019 ◽  
Vol 14 (2) ◽  
pp. 77-81 ◽  
Author(s):  
Gheorghe-Andrei Dan
Keyword(s):  
Sinus Rhythm ◽  
Rhythm Control ◽  
Strategy Management ◽  
Antiarrhythmic Drug Therapy ◽  
First Line Therapy ◽  
Increased Risk ◽  
Proarrhythmic Risk ◽  
Life Improvement ◽  
Ablative Techniques

AF is a worldwide epidemic, affecting approximately 33 million people, and its rising prevalence is expected to account for increasing clinical and public health costs. AF is associated with an increased risk of MI, heart failure, stroke, dementia, chronic kidney disease and mortality. Preserving sinus rhythm is essential for a better outcome. However, because of the inherent limits of both pharmacological and interventional methods, rhythm strategy management is reserved for symptom and quality-of-life improvement. While ‘classical’ antiarrhythmic drug therapy remains the first-line therapy for rhythm control, its efficacy and safety are limited by empirical use, proarrhythmic risk and organ toxicity. Ablative techniques have had an impressive development, but AF ablation still failed to demonstrate a significant impact on hard endpoints. Understanding of the complex mechanisms of AF will help to develop new vulnerable targets to therapy. Promising molecules are under development, intended to fill the gap between the current pharmacological treatment aimed at maintaining sinus rhythm and the expectations from rhythm strategy.

scholarly journals Early Rhythm Control Therapy in Patients with Atrial Fibrillation and Heart Failure

Circulation ◽  
2021 ◽  
Author(s):  
Andreas Rillig ◽  
Christina Magnussen ◽  
Ann-Kathrin Ozga ◽  
Anna Suling ◽  
Axel Brandes ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Ejection Fraction ◽  
Left Ventricular ◽  
Rhythm Control ◽  
Left Ventricular Ejection ◽  
Ventricular Ejection Fraction ◽  
Heart Failure Patients ◽  
Patients With Heart Failure ◽  
Control Therapy

Background: Even on optimal therapy, many patients with heart failure and atrial fibrillation experience cardiovascular complications. Additional treatments are needed to reduce these events, especially in patients with heart failure and preserved left ventricular ejection fraction (HFpEF). Methods: This prespecified subanalysis of the randomized EAST - AFNET 4 trial assessed the effect of systematic, early rhythm control therapy (ERC; using antiarrhythmic drugs or catheter ablation) compared to usual care (UC, allowing rhythm control therapy to improve symptoms) on the two primary outcomes of the trial and on selected secondary outcomes in patients with heart failure, defined as heart failure symptoms NYHA II-III or left ventricular ejection fraction [LVEF] <50%. Results: This analysis included 798 patients (300 (37.6%) female, median age 71.0 [64.0, 76.0] years, 785 with known LVEF). The majority of patients (n=442) had HFpEF (LVEF≥50%; mean LVEF 61% ± 6.3%), the others had heart failure with mid-range ejection fraction (n=211; LVEF40-49%; mean LVEF 44% ± 2.9%) or heart failure with reduced ejection fraction (n=132; LVEF<40%; mean LVEF 31% ± 5.5%). Over the 5.1-year median follow-up, the composite primary outcome of cardiovascular death, stroke or hospitalization for worsening of heart failure or for acute coronary syndrome occurred less often in patients randomized to ERC (94/396; 5.7 per 100 patient-years) compared with patients randomized to UC (130/402; 7.9 per 100 patient-years; hazard ratio 0.74 [0.56-0.97], p=0.03), not altered by heart failure status (interaction p-value=0.63). The primary safety outcome (death, stroke, or serious adverse events related to rhythm control therapy) occurred in 71/396 (17.9%) heart failure patients randomized to ERC and in 87/402 (21.6%) heart failure patients randomized to UC (hazard ratio 0.85 [0.62-1.17], p=0.33). LV ejection fraction improved in both groups (LVEF change at two years: ERC 5.3%±11.6%, UC 4.9%±11.6%, p=0.43). ERC also improved the composite outcome of death or hospitalization for worsening of heart failure. Conclusions: Rhythm control therapy conveys clinical benefit when initiated within one year of diagnosing atrial fibrillation in patients with signs or symptoms of heart failure. Clinical Trial Registration: Unique Identifiers: ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, Study web site www.easttrial.org; URLs: www.controlled-trials.com; https://clinicaltrials.gov; https://www.clinicaltrialsregister.eu

Abstract 16873: Association of Preoperative Cell-Free DNA Levels and Outcome Following Pediatric Cardiopulmonary Bypass

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Justinn Tanem ◽  
John Scott ◽  
George M Hoffman ◽  
Robert A Niebler ◽  
Aoy TOMITA-MITCHELL ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Cardiac Surgery ◽  
Cardiopulmonary Bypass ◽  
Primary Outcome ◽  
Clinical Decision Making ◽  
Treatment Strategies ◽  
Clinical Decision ◽  
Related Factors ◽  
Cell Free Dna ◽  
Free Dna

Introduction: Preoperative risk stratification in congenital cardiac surgery includes patient and procedure related factors, which may be used in clinical decision making as well program performance evaluation. Despite these tools, unidentified factors contribute to wide variation in outcomes both within and between centers. Identification of latent physiologic risk factors may strengthen predictive models. Hypothesis: Total cell-free DNA (TCF) functions as a biomarker for cellular injury as well as a pro-inflammatory cytokine. We hypothesized that elevated preoperative TCF would be associated with poor outcome following pediatric cardiac surgery requiring cardiopulmonary bypass (CPB). Methods: Prospective observational study of children age < 18 yr and wt > 3 kg undergoing planned CPB surgery. The Children’s Wisconsin Institutional Review Board approved the protocol . A serum TCF sample was obtained after induction of anesthesia prior to surgical incision. The primary outcome measure was a composite of postoperative cardiac arrest, ECMO, or death (CAED). Association of outcome to TCF was assessed by logistic regression with a cutpoint chosen by ROC curve exploration. Odds ratios with 95% CI were calculated. Results: Data were available in 117 patients, median age 0.9 years (range 0-17.4), median weight 7.8kg (range 3.2-98). The primary outcome (CAED) was met in 6/117 (5.1%). Table 1 summarizes characteristics of patients with and without CAED. Risk of CAED was 2% with TCF<20 ng/ml, and 27% with TCF>20 ng/ml (OR=18.2, CI 2.2- 212, p<0.01). Elevated TCF was associated to fewer hospital free days (GLM p<0.01). Data in table reported as median [IQR]. Conclusions: Preoperative TCF has an important association with postoperative cardiac arrest, ECMO, and death. Alternative or intensified treatment strategies could be considered in patients with elevated preoperative TCF.

Heart Teams in atrial fibrillation

ESC CardioMed ◽  
2018 ◽  
pp. 3027-3031
Author(s):  
Manuel Castella ◽  
Hans-Christoph Diener ◽  
Gerhard Hindricks ◽  
Paulus Kirchhof
Keyword(s):  
Atrial Fibrillation ◽  
Organizational Structure ◽  
Stroke Prevention ◽  
Potential Role ◽  
Rhythm Control ◽  
Interdisciplinary Teams ◽  
Heart Team ◽  
Management Decisions ◽  
Therapy Options ◽  
Control Therapy

Both stroke prevention and rhythm control therapy of atrial fibrillation (AF) have been shaped by interdisciplinary teams of surgeons and cardiologists. This chapter describes the roles of the AF Heart Team in supporting difficult management decisions in AF patients in need of advanced stroke prevention or rhythm control therapy options. It delineates the organizational structure of such AF Heart Teams and provides an outline of their potential role within integrated AF management.

3153Rate versus rhythm control and mortality in atrial fibrillation patients: a Danish nationwide cohort study

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
F Dalgaard ◽  
S Al-Khatib ◽  
J Pallisgaard ◽  
C Torp-Pedersen ◽  
T B Lindhardt ◽  
...  
Keyword(s):  
Heart Failure ◽  
Atrial Fibrillation ◽  
Heart Disease ◽  
Control Strategy ◽  
Rate Control ◽  
Channel Blocker ◽  
Rhythm Control ◽  
All Cause Mortality ◽  
Control Therapy

Abstract Background Treatment of AF patients with rate or rhythm drug therapy have shown no difference in mortality in clinical trials. However, the generalizability of these trials to real-world populations can be questioned. Purpose We aimed to investigate the all-cause and cardiovascular (CV) mortality risk in a nationwide AF cohort by treatment strategy (rate vs. rhythm) and by individual drug classes. Methods We queried the Danish nationwide registries from 2000 to 2015 to identify patients with AF. A rate control strategy included the use of one or more of the following medications: beta-blocker, digoxin, and a class-4 calcium channel blocker (CCB). A rhythm control strategy included the use of an anti-arrhythmic drug (amiodarone and class-1C). Primary outcome was all-cause mortality. Secondary outcome was CV mortality. Adjusted incidence rate ratios (IRR) were computed using Poisson regression with time-dependent covariates allowing patients to switch treatment during follow-up. Results Of 140,697 AF patients, 131,793 were on rate control therapy and n=8,904 were on rhythm control therapy. At baseline, patients on rhythm control therapy were younger (71 yrs [IQR: 62–78] vs 74 [65–82], p<0.001) more likely male (63.5% vs 51.7% p<0.001), had more prevalent heart failure (31.1% vs 19.4%, p<0.001) and ischemic heart disease (40.1% vs. 23.3%, p<0.001), and had more prior CV-related procedures; PCI (7.4% vs. 4.0% p<0.001) and CABG (15.0% vs. 2.3%, p<0.001). During a median follow up of 4.0 (IQR: 1.7–7.3) years, there were 64,653 (46.0%) deaths from any-cause, of which 27,025 (19.2%) were CVD deaths. After appropriate adjustments and compared to rate control therapy, we found a lower IRR of mortality and CV mortality in those treated with rhythm control therapy (IRR: 0.93 [95% CI: 0.90–0.97] and IRR 0.84 [95% CI: 0.79–0.90]). Compared with beta-blockers, digoxin was associated with increased risk of all-cause and CV mortality (IRR: 1.26 [95% CI: 1.24–1.29] and IRR: 1.32 [95% CI: 1.28–1.36]), so was amiodarone: IRR for all-cause mortality: 1.16 [95% CI: 1.11–1.21] and IRR for CV mortality: 1.12 [95% CI: 1.05–1.19]. Class-1C was associated with lower all-cause (0.43 [95% CI: 0.37–0.49]) and CV mortality (0.35 [95% CI: 0.28–0.44]). Figure 1. Models were adjusted for age, sex, ischemic heart disease, stroke, chronic obstructive pulmonary disease, chronic kidney disease, valvular atrial fibrillation, bleeding, diabetes, ablation, pacemaker, implantable cardioverter defibrillator, hypertension, heart failure, use of loop diuretics, calendar year, and time on treatment. Abbreviations; CCB; calcium channel blocker, PY; person years. Conclusions In a real-world AF cohort, we found that compared with rate control therapy, rhythm control therapy was associated with a lower risk of all-cause and CV mortality. The reduced mortality risk with rhythm therapy could reflect an appropriate patient selection. Acknowledgement/Funding The Danish Heart Foundation

Sign in / Sign up

Export Citation Format

Share Document