Early Rhythm Control Therapy in Patients With Atrial Fibrillation and Heart Failure.

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. METHODS: This prespecified subanalysis of the randomized EAST-AFNET4 trial (Early Treatment of Atrial Fibrillation for Stroke Prevention Trial) assessed the effect of systematic, early rhythm control therapy (ERC; using antiarrhythmic drugs or catheter ablation) compared with usual care (allowing rhythm control therapy to improve symptoms) on the 2 primary outcomes of the trial and on selected secondary outcomes in patients with heart failure, defined as heart failure symptoms New York Heart Association II to 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 heart failure and preserved LVEF (LVEF≥50%; mean LVEF 61±6.3%), the others had heart failure with midrange ejection fraction (n=211; LVEF 40%-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 randomly assigned to ERC (94/396; 5.7 per 100 patient-years) compared with patients randomly assigned to usual care (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 of 396 (17.9%) patients with heart failure randomly assigned to ERC and in 87 of 402 (21.6%) patients with heart failure randomly assigned to usual care (hazard ratio, 0.85 [0.62-1.17]; P=0.33). LVEF improved in both groups (LVEF change at 2 years: ERC 5.3±11.6%, usual care 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 1 year of diagnosing atrial fibrillation in patients with signs or symptoms of heart failure. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01288352. URL: http://www.controlled-trials.com; Unique identifier: ISRCTN04708680. URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2010-021258-20

Safety and efficacy of long-term Sodium Channel Blocker therapy for Early Rhythm Control: The EAST-AFNET 4 trial.

BACKGROUND AND AIMS: Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers flecainide and propafenone (SCB) in patients with cardiovascular disease. SCB were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4. METHODS: We analysed the primary safety outcome (death, stroke, or serious adverse events related to rhythm-control therapy) and primary efficacy outcome (cardiovascular death, stroke and hospitalization for worsening of heart failure or acute coronary syndrome) during SCB-intake for ERC patients (n = 1395) in EAST-AFNET 4. The protocol discouraged flecainide and propafenone in patients with reduced left ventricular ejection fraction and suggested stopping therapy upon QRS prolongation >25% on therapy. RESULTS: Flecainide or propafenone was given to 689 patients (age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with heart failure; 41 with prior myocardial infarction, CABG or PCI; 26 with left ventricular hypertrophy >15 mm; median therapy duration 1,153 [237, 1,828] days). The primary efficacy outcome occurred less often in patients treated with SCB (3/100 (99/3,316) patient-years) than in patients who never received SCB (SCBnever 4.9/100 (150/3,083) patient-years, p < 0.001). There were numerically fewer primary safety outcomes in patients receiving SCB (2.9/100 (96/3,359) patient-years) than in SCBnever patients (4.2/100 (135/3,220) patient-years, adjusted p = 0.015). Sinus rhythm at 2 years was similar between groups (SCB 537/610 (88); SCBnever 472/579 (82)). CONCLUSION: Long-term therapy with flecainide or propafenone appeared to be safe in the EAST-AFNET 4 trial to deliver effective ERC therapy, including in selected patients with stable cardiovascular disease such as coronary artery disease and stable heart failure. CLINICAL TRIAL REGISTRATION: ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org

Nightly sleep apnea severity in patients with atrial fibrillation: Potential applications of long-term sleep apnea monitoring

In patients with atrial fibrillation (AF), the prevalence of moderate-to-severe sleep-disordered breathing (SDB) ranges between 21% and 72% and observational studies have demonstrated that SDB reduces the efficacy of rhythm control strategies, while treatment with continuous positive airway pressure lowers the rate of AF recurrence. Currently, the number of apneas and hypopneas per hour (apnea-hypopnea-index, AHI) determined during a single overnight sleep study is clinically used to assess the severity of SDB. However, recent studies suggest that SDB-severity in an individual patient is not stable over time but exhibits a considerable night-to-night variability which cannot be detected by only one overnight sleep assessment. Nightly SDB-severity assessment rather than the single-night diagnosis by one overnight sleep study may better reflect the exposure to SDB-related factors and yield a superior metric to determine SDB-severity in the management of AF. In this review we discuss mechanisms of night-to-night SDB variability, arrhythmogenic consequences of night-to-night SDB variability, strategies for longitudinal assessment of nightly SDB-severity and clinical implications for screening and management of SDB in AF patients

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

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)

Anticoagulation, therapy of concomitant conditions, and early rhythm control therapy: a detailed analysis of treatment patterns in the EAST - AFNET 4 trial.

AIMS: Treatment patterns were compared between randomized groups in EAST-AFNET 4 to assess whether differences in anticoagulation, therapy of concomitant diseases, or intensity of care can explain the clinical benefit achieved with early rhythm control in EAST-AFNET 4. METHODS AND RESULTS: Cardiovascular treatment patterns and number of visits were compared between randomized groups in EAST-AFNET 4. Oral anticoagulation was used in >90% of patients during follow-up without differences between randomized groups. There were no differences in treatment of concomitant conditions between groups. The type of rhythm control varied by country and centre. Over time, antiarrhythmic drugs were given to 1171/1395 (84%) patients in early therapy, and to 202/1394 (14%) in usual care. Atrial fibrillation (AF) ablation was performed in 340/1395 (24%) patients randomized to early therapy, and in 168/1394 (12%) patients randomized to usual care. 97% of rhythm control therapies were within class I and class III recommendations of AF guidelines. Patients randomized to early therapy transmitted 297 166 telemetric electrocardiograms (ECGs) to a core lab. In total, 97 978 abnormal ECGs were sent to study sites. The resulting difference between study visits was low (0.06 visits/patient/year), with slightly more visits in early therapy (usual care 0.39 visits/patient/year; early rhythm control 0.45 visits/patient/year, P < 0.001), mainly due to visits for symptomatic AF recurrences or recurrent AF on telemetric ECGs. CONCLUSION: The clinical benefit of early, systematic rhythm control therapy was achieved using variable treatment patterns of antiarrhythmic drugs and AF ablation, applied within guideline recommendations

Acute success and short-term follow-up of catheter ablation of isthmus-dependent atrial flutter; a comparison of 8 mm tip radiofrequency and cryothermy catheters

Objectives: To compare the acute success and short-term follow-up of ablation of atrial flutter using 8 mm tip radiofrequency (RF) and cryocatheters. Methods: Sixty-two patients with atrial flutter were randomized to RF or cryocatheter (cryo) ablation. Right atrial angiography was performed to assess the isthmus. End point was bidirectional isthmus block on multiple criteria. A pain score was used and the analgesics were recorded. Patients were followed for at least 3 months. Results: The acute success rate for RF was 83% vs 69% for cryo (NS). Procedure times were similar (mean 144±48 min for RF, vs 158±49 min for cryo). More applications were given with RF than with cryo (26±17 vs. 18±10, p<0.05). Fluoroscopy time was longer with RF (29±15 vs. 19±12 min, p<0.02). Peak CK, CK-MB and CK-MB mass were higher, also after 24 h in the cryo group. Troponin T did not differ. Repeated transient block during application (usually with cryoablation) seemed to predict failure. Cryothermy required significantly less analgesia (p<0.01), and no use of long sheaths (p<0.005). The isthmus tended to be longer in the failed procedures (p=0.117). This was similar for both groups, as was the distribution of anatomic variations. Recurrences and complaints in the successful patients were similar for both groups, with a very low recurrence of atrial flutter after initial success. Concl

Impact of renal impairment on atrial fibrillation: ESC-EHRA EORP-AF Long-Term General Registry

Background: Atrial fibrillation (AF) and renal impairment share a bidirectional relationship with important pathophysiological interactions. We evaluated the impact of renal impairment in a contemporary cohort of patients with AF. Methods: We utilised the ESC-EHRA EORP-AF Long-Term General Registry. Outcomes were analysed according to renal function by CKD-EPI equation. The primary endpoint was a composite of thromboembolism, major bleeding, acute coronary syndrome and all-cause death. Secondary endpoints were each of these separately including ischaemic stroke, haemorrhagic event, intracranial haemorrhage, cardiovascular death and hospital admission. Results: A total of 9306 patients were included. The distribution of patients with no, mild, moderate and severe renal impairment at baseline were 16.9%, 49.3%, 30% and 3.8%, respectively. AF patients with impaired renal function were older, more likely to be females, had worse cardiac imaging parameters and multiple comorbidities. Among patients with an indication for anticoagulation, prescription of these agents was reduced in those with severe renal impairment, p&nbsp;&lt;.001. Over 24&nbsp;months, impaired renal function was associated with significantly greater incidence of the primary composite outcome and all secondary outcomes. Multivariable Cox regression analysis demonstrated an inverse relationship between eGFR and the primary outcome (HR 1.07 [95% CI, 1.01–1.14] per 10&nbsp;ml/min/1.73&nbsp;m2 decrease), that was most notable in patients with eGFR &lt;30&nbsp;ml/min/1.73&nbsp;m2 (HR 2.21 [95% CI, 1.23–3.99] compared to eGFR ≥90&nbsp;ml/min/1.73&nbsp;m2). Conclusion: A significant proportion of patients with AF suffer from concomitant renal impairment which impacts their overall management. Furthermore, renal impairment is an independent predictor of major adverse events including thromboembolism, major bleeding, acute coronary syndrome and all-cause death in patients with AF

Clinical complexity and impact of the ABC (Atrial fibrillation Better Care) pathway in patients with atrial fibrillation: a report from the ESC-EHRA EURObservational Research Programme in AF General Long-Term Registry

Background: Clinical complexity is increasingly prevalent among patients with atrial fibrillation (AF). The ‘Atrial fibrillation Better Care’ (ABC) pathway approach has been proposed to streamline a more holistic and integrated approach to AF care; however, there are limited data on its usefulness among clinically complex patients. We aim to determine the impact of ABC pathway in a contemporary cohort of clinically complex AF patients. Methods: From the ESC-EHRA EORP-AF General Long-Term Registry, we analysed clinically complex AF patients, defined as the presence of frailty, multimorbidity and/or polypharmacy. A K-medoids cluster analysis was performed to identify different groups of clinical complexity. The impact of an ABC-adherent approach on major outcomes was analysed through Cox-regression analyses and delay of event (DoE) analyses. Results: Among 9966 AF patients included, 8289 (83.1%) were clinically complex. Adherence to the ABC pathway in the clinically complex group reduced the risk of all-cause death (adjusted HR [aHR]: 0.72, 95%CI 0.58–0.91), major adverse cardiovascular events (MACEs; aHR: 0.68, 95%CI 0.52–0.87) and composite outcome (aHR: 0.70, 95%CI: 0.58–0.85). Adherence to the ABC pathway was associated with a significant reduction in the risk of death (aHR: 0.74, 95%CI 0.56–0.98) and composite outcome (aHR: 0.76, 95%CI 0.60–0.96) also in the high-complexity cluster; similar trends were observed for MACEs. In DoE analyses, an ABC-adherent approach resulted in significant gains in event-free survival for all the outcomes investigated in clinically complex patients. Based on absolute risk reduction at 1 year of follow-up, the number needed to treat for ABC pathway adherence was 24 for all-cause death, 31 for MACEs and 20 for the composite outcome. Conclusions: An ABC-adherent approach reduces the risk of major outcomes in clinically complex AF patients. Ensuring adherence to the ABC pathway is essential to improve clinical outcomes among clinically complex AF patients