Ethanol Infusion of the Vein of Marshall-Based Strategies for Persistent Atrial Fibrillation: A Systematic Review and Meta-Analysis of Randomized Trials

Figures

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  Figure 1. PRISMA flowchart.

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  Figure 2. Risk of bias assessment of included randomized clinical trials. Assessment was performed using the Cochrane Risk of Bias 2 (RoB-2) tool. (A) Weighted summary plot illustrating the proportion of studies with low risk, some concerns, or high risk of bias for each domain. (B) Study-level ‘traffic light’ plot detailing judgments for each domain across the 5 included trials. Abbreviations: D1 = Randomization process; D2 = Deviations from intended interventions; D3 = Missing outcome data; D4 = Measurement of the outcome; D5 = Selection of the reported result.

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  Figure 3. Forest plot of freedom from any atrial arrhythmia at 12 months. Pooled analysis of 5 randomized controlled trials demonstrating a statistically significant benefit of EIVOM-based strategies compared with control. Abbreviations: CI = confidence interval; EIVOM = ethanol infusion in the vein of Marshall; PVI = pulmonary vein isolation; RR = relative risk.

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  Figure 4. Forest plot of freedom from atrial fibrillation at 12 months. Pooled analysis indicating a statistically significant improvement in freedom from atrial fibrillation with EIVOM-based strategies compared with control. Abbreviations: CI = confidence interval; EIVOM = ethanol infusion in the vein of Marshall; PVI = pulmonary vein isolation; RR = relative risk.

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  Figure 5. Forest plot of freedom from atrial tachycardia and atrial flutter at 12 months. Pooled analysis demonstrating comparable rates of freedom from organized atrial tachyarrhythmias (atrial tachycardia or atrial flutter) between EIVOM-based strategies and control groups. Abbreviations: CI = confidence interval; EIVOM = ethanol infusion in the vein of Marshall; PVI = pulmonary vein isolation; RR = relative risk.

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  Figure 6. Forest plot of the time-to-event meta-analysis for any atrial arrhythmia. Pooled time-to-event analysis demonstrating a significant reduction in the hazard of any atrial arrhythmia recurrence at 12 months with EIVOM-based ablation strategies compared with PVI alone. Abbreviations: CI = confidence interval; EIVOM = ethanol infusion in the vein of Marshall; HR = hazard ratio; PVI = pulmonary vein isolation.

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  Figure 7. Trial sequential analysis of arrhythmia recurrence. Trial sequential analysis for (A) any arrhythmia recurrence, (B) atrial fibrillation recurrence, and (C) atrial tachycardia/flutter recurrence. The blue numbered line indicates cumulative Z-scores; curved lines indicate monitoring boundaries; and red wedges indicate futility boundaries. The vertical blue line represents the required information size. Numbered data points represent the cumulative addition of studies in chronological order: 1, Valderrábano et al; 2, Zuo et al; 3, Sang et al; 4, Derval et al; and 5, Zhu et al. Parameters: Two-sided α = 5%, Power = 80%, Relative Risk Reduction = 20%. Abbreviations: EIVOM = ethanol infusion of the vein of Marshall.

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  Figure 8. Forest plot of procedural efficiency metrics. Forest plots illustrating pooled mean differences for (A) total procedure time, (B) fluoroscopy time, and (C) total radiofrequency ablation time. Abbreviations: CI = confidence interval; EIVOM = ethanol infusion in the vein of Marshall; MD = mean difference; PVI = pulmonary vein isolation.

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  Figure 9. Acute mitral isthmus block achievement in the EIVOM arm. Forest plot illustrating the pooled proportion of successful bidirectional mitral isthmus block verified in patients treated with the EIVOM strategy. Abbreviations: CI = confidence interval; EIVOM = ethanol infusion in the vein of Marshall.

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  Figure 10. Forest plot of repeat ablation. This forest plot illustrates the relative risk of requiring a repeat ablation procedure. Abbreviations: CI = confidence interval; EIVOM = ethanol infusion in the vein of Marshall; PVI = pulmonary vein isolation; RR = relative risk.

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  Figure 11. Safety endpoints. Forest plots illustrating pooled relative risks for (A) the overall complication profile, (B) pericardial effusion or pericarditis, and (C) major adverse events. Abbreviations: CI = confidence interval; EIVOM = ethanol infusion in the vein of Marshall; PVI = pulmonary vein isolation; RR = relative risk.