Elsevier

Heart Rhythm

Volume 12, Issue 11, November 2015, Pages 2207-2212
Heart Rhythm

Prospective, multicenter validation of a clinical risk score for left atrial arrhythmogenic substrate based on voltage analysis: DR-FLASH score

https://doi.org/10.1016/j.hrthm.2015.07.003Get rights and content

Background

Left atrial (LA) low-voltage areas (LVAs) are frequently observed in patients with atrial fibrillation (AF) and may predict AF recurrence after catheter ablation.

Objective

The aim of this study was to develop and validate a clinical tool to identify LVAs that are associated with AF recurrence after pulmonary vein isolation (PVI).

Methods

In a cohort of 238 patients, voltage maps were created during LA procedures. LVAs were defined as areas with electrogram amplitudes <0.5 mV. On the basis of regression analysis, predictors of LA substrate were identified. These parameters were used to establish a dedicated risk score (DR-FLASH score, based on diabetes mellitus, renal dysfunction, persistent form of AF, LA diameter >45 mm, age >65 years, female sex, and hypertension). This risk score was then prospectively validated in a multicenter cohort of 180 patients. The association of the score with long-term recurrence of atrial arrhythmias after circumferential PVI was tested in a retrospective cohort of 484 patients.

Results

The DR-FLASH score effectively identified LVA substrate (C statistic = 0.801, P < .001). In the prospective multicenter validation cohort, the predictive value of the DR-FLASH score was confirmed (C statistic = 0.767, P < .001). The probability for the presence of LA substrate increased by a factor of 2.2 (95% confidence interval [CI] 1.6–2.9, P < .001) with each point scored. Furthermore, the risk of AF recurrence after PVI increased by a factor of 1.3 (95% CI 1.1–1.5, P < .001) with every additional point and was almost 2 times higher in patients with a DR-FLASH score >3 (odds ratio 1.7, 95% CI 1.1–2.8, P = .026).

Conclusion

The DR-FLASH score may be useful to identify patients who may require extensive substrate modification instead of PVI alone.

Introduction

Catheter ablation is an established nonpharmacologic therapy option for atrial fibrillation (AF). Over the past several decades, trigger elimination by pulmonary vein isolation (PVI) has become the cornerstone of ablation strategies.1 Although this approach has a potentially curative effect in selected cohorts, further modification of AF-maintaining atrial substrate appears necessary in at least some patients.

Atrial structural remodeling involving atrial fibrosis is a well-recognized factor in AF pathogenesis and can be detected invasively by direct catheter-based left atrial (LA) voltage mapping. Furthermore, the presence of low-voltage areas (LVAs) has been shown to be a powerful predictor of arrhythmia recurrence after catheter ablation.2, 3, 4, 5, 6 Similarly, the detection of atrial fibrosis, which corresponds to LVAs, in late-enhancement magnetic resonance imaging (MRI) was associated with poorer outcomes of ablation procedures.7 Finally, it has been reported recently that tailored substrate modification that targets atrial LVAs can improve ablation outcomes significantly.8

In this context, an easy and reliable a priori method to identify patients with LVAs who might benefit from additional substrate modification is of crucial importance for patient selection, planning of the ablation strategy, and selection of suitable ablation technology. In this study, we aimed to establish and validate a simple clinical risk score for prediction of significant LVAs. Furthermore, we hypothesized that such a score might be associated with long-term outcome after PVI.

Section snippets

Study Design

The present study comprised 3 parts: (1) establishment of the DR-FLASH score (based on diabetes mellitus, renal dysfunction, persistent form of AF, LA diameter >45 mm, age >65 years, female sex, and hypertension) in a prospective, single-center cohort (basic cohort); (2) validation of the score in a prospective multicenter, international cohort (validation cohort); and (3) analysis of the impact of the score on long-term outcomes after PVI without any additional substrate modification in a

Univariate predictors of LVAs in the Basic Cohort and Establishment of the DR-FLASH Score

LVAs were detected in 66 patients (28%) in the basic cohort. In univariate analysis, patients with LVAs were predominantly female (35% vs 20%, P = .020), were older (66 ± 8 vs 59 ± 9 years, P < .001), and more frequently had comorbidities such as diabetes mellitus (29% vs 11%, P = .001), hypertension (91% vs 71%, P = .001), and impaired eGFR (70 ± 18 vs 83 ± 23 mL/min/1.73 m2, P < .001). Furthermore, in patients with LVAs, dilatation of the LA (46 ± 6 mm vs 43 ± 7 mm, P = .005) and a persistent

Main Findings

This multicenter study, based on analysis of more than 900 patients, describes for the first time a simple and validated clinical score that effectively identifies patients with LVAs. Furthermore, the score correlates with the size of the diseased LA area and long-term rhythm outcomes after a PVI procedure.

Clinical Implication

In recent years, catheter-based PVI has evolved to be the therapy of choice for treatment of drug-refractory AF.14 The rapid technological development in this field brought up an entire

Conclusion

The DR-FLASH score represents a reliable clinical tool to identify LVAs, which are associated with higher AF recurrence after catheter PVI. The score may be useful to identify patients who may require extensive substrate modification instead of PVI alone.

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