Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trial.

AIMS: Clinical concerns exist about the potential proarrhythmic effects of the sodium channel blockers (SCBs) flecainide and propafenone in patients with cardiovascular disease. Sodium channel blockers were used to deliver early rhythm control (ERC) therapy in EAST-AFNET 4. METHODS AND RESULTS: 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 (HF) or acute coronary syndrome) during SCB intake for patients with ERC (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. Flecainide or propafenone was given to 689 patients [age 69 (8) years; CHA2DS2-VASc 3.2 (1); 177 with HF; 41 with prior myocardial infarction, coronary artery bypass graft, or percutaneous coronary intervention; 26 with left ventricular hypertrophy >15 mm; median therapy duration 1153 [237, 1828] days]. The primary efficacy outcome occurred less often in patients treated with SCB [3/100 (99/3316) patient-years] than in patients who never received SCB [SCBnever 4.9/100 (150/3083) patient-years, P < 0.001]. There were numerically fewer primary safety outcomes in patients receiving SCB [2.9/100 (96/3359) patient-years] than in SCBnever patients [4.2/100 (135/3220) 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 HF. Clinical Trial Registration ISRCTN04708680, NCT01288352, EudraCT2010-021258-20, www.easttrial.org.

Left Atrial Reservoir Strain and Recurrence of Atrial Fibrillation Following De-Novo Pulmonary Vein Isolation　- Results of the ASTRA-AF Pilot Study.

BACKGROUND: Achieving early rhythm control and maintaining sinus rhythm are associated with improved outcomes in patients with atrial fibrillation (AF). Pulmonary vein isolation (PVI) is a validated alternative to medical rhythm control. This study determined associations between left atrial strain reservoir (LASR) and AF recurrence after PVI.Methods and Results: In all, 132 patients (88 with paroxysmal AF [PAF], 44 with persisting AF [PersAF]) who presented in sinus rhythm for de novo PVI of AF between December 2017 and January 2019 were included in the study. All patients underwent preprocedural echocardiography. After 12 months, all patients underwent 24-h Holter electrocardiogram monitoring to screen for AF recurrence. Kaplan-Meier curve analysis revealed an association between decreasing LASRand increased AF recurrence, with a cut-off at 31.4%. In univariable Cox regression analysis, LASRdemonstrated an association with AF recurrence, with hazard ratios (HR) of 0.83 (95% confidence interval [CI] 073-0.93; P=0.001) per 5% increase in univariable models and 0.83 (95% CI 073-0.95; P=0.005) in multivariable analysis. When clinical variables with age, sex and type of AF (PAF/PersAF) were included in the multivariable analysis, LASRremained relevant in a model with age (HR 0.86; 95% CI 073-1.00; P=0.046). CONCLUSIONS: In patients undergoing de novo PVI for AF, LASRcould be of use in risk stratification regarding AF recurrence.

Use of class IC antiarrhythmic drugs in patients with structural heart disease and implantable cardioverter defibrillator.

BACKGROUND: Due to suspected pro-arrhythmic effects and increased mortality associated with class-IC antiarrhythmic drugs (AADs) in previous trials, AAD therapy in structural heart disease (SHD) is mainly restricted to amiodarone. In the presence of diagnostic and therapeutic advancements in cardiovascular medicine, it remains unclear if previous studies adequately reflect contemporary patients. In clinical practice, class-IC-AADs are occasionally used in individual cases, particularly in patients with an implantable cardioverter defibrillator (ICD). METHODS: This study retrospectively investigated outcome in ICD-carriers with SHD in whom class-IC-AADs were used as an individualized therapy due to failure, side effects, or unacceptable risk of alternative therapeutic options. RESULTS: Fifty patients from four tertiary centers were included (median age 48.5 years; 52% female). The most common underlying SHD were dilated (42%) or ischemic cardiomyopathy (26%) (median LVEF = 45%). Indications for AAD were sustained ventricular arrhythmias (VA) (58%), symptomatic premature ventricular contractions (26%), or atrial arrhythmias (16%). Median follow-up was 27.8 months. Freedom from sustained VA was 72%, and freedom from ICD therapy was 80%. In 19 patients (38%), AAD therapy was terminated. The most common reason was insufficient efficacy (n = 8). Pro-arrhythmia was suspected in three patients. Five patients died during follow-up (10.0%), two of cardiovascular cause (4.0%). CONCLUSION: In a multicenter cohort of ICD-carriers with SHD, class-IC-AADs were associated with a low rate of pro-arrhythmic effects or cardiovascular mortality. The majority of patients remained free from sustained VA during a follow-up of > 2 years. Further efforts should be made to evaluate the safety of class-IC-AADs in SHD patients receiving contemporary cardiovascular therapy.

Pulmonary Vein Isolation or Pace & Ablate in Elderly Patients with Persistent Atrial Fibrillation (ABLATE versus PACE) - Rationale, Methods and Design.

Age is a major risk-factor for atrial fibrillation (AF) and associated hospitalizations. With increasing emphasis on rhythm-control, pulmonary-vein isolation (PVI) is often suggested, even to elderly patients (≥75 years). Efficacy of PVI aiming at rhythm-control is limited in persistent AF. Pacemaker implantation with atrioventricular-node ablation may represent a reasonable alternative, with the aim of controlling symptoms and improving quality-of-life in elderly patients. In this investigator-initiated, randomized, multicenter trial, we test the hypothesis that pacemaker-implantation and atrioventricular-node (AVN) ablation provides superior symptom-control over PVI in elderly patients with symptomatic persistent AF, without any increase in adverse-event profile. In the "ABLATE versus PACE" (NCT04906668) prospective, open-label superiority trial 196 elderly patients with normal ejection fraction and symptomatic persistent AF despite guideline-indicated medical therapy, will be randomized to either cryoballoon-PVI (ABLATE) or dual-chamber pacemaker implantation with subsequent AVN ablation (PACE), and followed for a minimum of 12 months. The primary efficacy outcome is a composite endpoint of rehospitalization for atrial arrhythmia or cardiac decompensation/ heart failure, (outpatient) electrical cardioversion or upgrade to cardiac resynchronization therapy due to worsening of left-ventricular ejection fraction ≤35%. Secondary endpoints include death from any cause, stroke, quality of life or procedure-related complications. Sample-size is designed to achieve 80% power for the primary endpoint (two-tailed alpha of 5%). "ABLATE versus PACE" will determine whether pacemaker implantation and AVN ablation can improve symptom-control in elderly patients with persistent AF over PVI without increasing safety endpoints.

Association of atrial mechanical dispersion with atrial fibrillation recurrence following catheter ablation: results of the ASTRA-AF pilot study.

AIMS: For patients with symptomatic drug-refractory atrial fibrillation (AF), catheter ablation to achieve rhythm control is an important therapeutic option. The atrial mechanical dispersion measured as standard deviation of the time to peak strain (SD-TPS) is associated with the risk of AF recurrence following catheter ablation. METHODS: The study cohort prospectively enrolled n = 132 consecutive patients with paroxysmal (n = 88) or persistent AF (n = 44) presenting for de novo pulmonary vein isolation (PVI) and followed for 1 year. We related left atrial (LA) volume, LA ejection fraction, SD-TPS, and global longitudinal strain of the left ventricle and clinical variables (sex, age, and type of AF) to AF recurrence. RESULTS: Kaplan-Meier curves showed higher AF recurrence rate with an increase of SD-TPS with the calculated cut-off of 38.6 ms. Uni- and multivariable Cox regression analysis could show that SD-TPS had the highest relevance regarding AF recurrence with a HR of 1.05 (95% CI, 1.01; 1.09, p = 0.01) and HR of 1.05 (95% CI, 1.01; 1.09, p = 0.02) per 10 ms increase. In the additional analyses for the model including the clinical variables age, sex, and type of AF with paroxysmal or persisting AF, SD-TPS did only show a trend and after adjusting for covariates, SD-TPS showed a HR of 1.04 (95% CI, 0.99; 1.09, p = 0.09) per 10 ms increase. CONCLUSION: Atrial mechanical dispersion was associated with recurrent AF.

Catheter-based ablation to improve outcomes in patients with atrial fibrillation and heart failure with preserved ejection fraction: Rationale and design of the CABA-HFPEF-DZHK27 trial.

AIMS: Atrial fibrillation (AF) is common in heart failure (HF) and negatively impacts outcomes. The role of ablation-based rhythm control in patients with AF and HF with preserved (HFpEF) or mildly reduced ejection fraction (HFmrEF) is not known. The CABA-HFPEF-DZHK27 (CAtheter-Based Ablation of atrial fibrillation compared to conventional treatment in patients with Heart Failure with Preserved Ejection Fraction) trial will determine whether early catheter ablation for AF can prevent adverse cardiovascular outcomes in patients with HFpEF or HFmrEF. METHODS: CABA-HFPEF-DZHK27 (NCT05508256) is an investigator-initiated, prospective, randomized, open, interventional multicentre strategy trial with blinded outcome assessment. Approximately 1548 patients with paroxysmal or persistent AF diagnosed within 24 months prior to enrolment and HFpEF or HFmrEF will be randomized to early catheter ablation within 4 weeks after randomization or to usual care. All patients receive anticoagulation, rate control, and HF management according to current guideline recommendations. Usual care can include rhythm control in symptomatic patients. Patients will be followed until the end of the trial for the primary outcome, a composite of cardiovascular death, stroke, and total unplanned hospitalizations for HF or acute coronary syndrome. The safety outcome comprises complications of catheter ablation and death. The trial is powered for a rate ratio of 0.75 (two-sided alpha = 0.05, 1-beta = 0.8). CONCLUSION: CABA-HFPEF-DZHK27 will define the role of systematic and early catheter ablation in patients with AF and HFpEF or HFmrEF.

A Randomized Trial of Electrographic Flow-Guided Redo Ablation for Nonparoxysmal Atrial Fibrillation (FLOW-AF).

BACKGROUND: Electrographic flow (EGF) mapping enables full spatiotemporal reconstruction of organized wavefront propagation to identify extrapulmonary vein sources of atrial fibrillation (AF). OBJECTIVES: FLOW-AF (A Randomized Controlled Study to Evaluate the Reliability of the Ablacon Electrographic FLOW [EGF] Algorithm Technology [Ablamap Software] to Identify AF Sources and Guide Ablation Therapy in Patients With Persistent Atrial Fibrillation) was multicenter, randomized controlled study of EGF mapping to: 1) stratify a nonparoxysmal AF population undergoing redo ablation; 2) guide ablation of these extrapulmonary vein AF sources; and 3) improve AF recurrence outcomes. METHODS: FLOW-AF enrolled persistent atrial fibrillation (PerAF)/long-standing PerAF patients undergoing redo ablation at 4 centers. One-minute EGF maps were recorded from standardized biatrial basket positions. Patients with source activity ≥26.5% were randomized 1:1 to PVI + EGF-guided ablation vs PVI only; patients without sources ≥26.5% threshold were not randomized. Follow-up and electrocardiographic monitoring occurred at 3, 6, and 12 months. RESULTS: We enrolled 85 patients (age 65.6 ± 9.3 years, 37% female, 24% long-standing PerAF). Thirty-four (40%) patients had no sources greater than threshold; at least 1 source greater than threshold was present in 46 (60%) (EGF-guided ablation, n = 22; control group, n = 26). Patients with sources were older (68.2 vs 62.6 years; P = 0.005) with higher CHA2DS2-VASc scores (2.8 vs 1.9; P = 0.001). The freedom from safety events was 97.2%, and 95% of EGF-identified sources were successfully ablated. In randomized patients, AF-free survival at 12 months was 68% for EGF-guided ablation vs 17% for the control group (P = 0.042); freedom from AF/atrial tachycardia/atrial flutter at 12 months was 51% vs 14% (P = 0.103), respectively. CONCLUSIONS: In nonparoxysmal AF patients undergoing redo ablation, EGF mapping identified AF sources in 60% of patients, and could be successfully ablated in 95%. Compared with PVI alone, PVI + source ablation improved AF-free survival by 51% on an absolute basis. (FLOW-AF: A Study to Evaluate the Ablacon Electrographic FLOW EGF Technology [A Randomized Controlled Study to Evaluate the Reliability of the Ablacon Electrographic FLOW (EGF) Algorithm Technology (Ablamap Software) to Identify AF Sources and Guide Ablation Therapy in Patients With Persistent Atrial Fibrillation]; NCT04473963).

[Lead placement in cardiac implantable electronic devices]. / Elektrodenplatzierung in der kardialen Devicetherapie.

The implantation of electrodes for cardiac implantable electronic devices (CIED) requires profound technical understanding and precise execution. The positioning of electrodes in the right ventricle and atrium has significant implications for patient safety and the effectiveness of CIED therapy. Particular focus is given to the distinction between apical and septal stimulation in ventricular positioning. Based on current data, this article provides a practice-oriented guide that leads implanters through the individual steps of electrode positioning. The implantation of electrodes for physiological stimulation (cardiac resynchronization therapy, CRT, and conduction system pacing, CSP) is not addressed in this article.

[Perioperative management for cardiovascular implantable electronic devices]. / Perioperatives Management bei der Versorgung mit aktiven Rhythmusimplantaten.

Cardiovascular implantable electronic devices (CIED) are an important part of modern cardiology and careful perioperative planning of these procedures is necessary. All information relevant to the indication, the procedure, and the education of the patient must be available prior to surgery. This provides the basis for appropriate device selection. Preoperative antibiotic prophylaxis and perioperative anticoagulation management are essential to prevent infection. After surgery, postoperative monitoring, telemetric control, and device-based diagnostics are required before discharge. These processes need to be adapted to the increasing trend towards outpatient care. This review summarises perioperative management based on practical considerations.