Impact of Diabetes on the Efficacy of Low‐Voltage Area Ablation for Persistent Atrial Fibrillation: A Subanalysis of the SUPPRESS‐AF Trial

Q: What are the key findings of this study?

In persistent AF patients without diabetes, adding low-voltage area ablation to pulmonary vein isolation reduced arrhythmia recurrence (HR 0.642), a benefit absent in diabetics (P for interaction=0.041).

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Persistent atrial fibrillation (n=341). Intervention: Pulmonary vein isolation plus low-voltage area ablation vs. Pulmonary vein isolation alone. Primary outcome: AF/AT recurrence (nondiabetic subgroup) (HR 0.642, 95% CI 0.44-0.94, p=0.021).

Q: What does this research mean for the field?

Low-voltage area ablation added to pulmonary vein isolation reduces atrial fibrillation recurrence in nondiabetic patients with persistent atrial fibrillation but provides no benefit in patients with diabetes. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Tatsuhisa Ozaki; Koichi Inoue; Tsuyoshi Mishima; Takuya Ohashi; Satoshi Osaki; Yasunori Ueda; Masaharu Masuda; Akihiro Sunaga; Nobuaki Tanaka; Tetsuya Watanabe; Hitoshi Minamiguchi; Yasuyuki Egami; Takafumi Oka; Tomoko Minamisaka; Takashi Kanda; Masato Okada; M Kawasaki; Yasuhiro Matsuda; Koji Tanaka; Nobuhiko Makino; Hirota Kida; Shungo Hikoso; Tomoharu Dohi; Yohei Sotomi; Yasushi Sakata; Masaharu Masuda; Yasuhiro Matsuda; H Uematsu; T Tsujimura; Hirotaka Ooka; Satoshi Kudo; Takashi Sumigawa; Akihiro Sunaga; Yuki Matsuoka; Daisaku Nakatani; Katsuki Okada; Hirota Kida; Daisuke Sakamoto; Tetsuhisa Kitamura; Takafumi Oka; Tomoaki Nakano; Takayuki Sekihara; Tomoharu Dohi; Tomomi Yamada; Shungo Hikoso; Yohei Sotomi; K Nishio; Yasushi Sakata; Nobuaki Tanaka; Yuko Hirao; Koji Tanaka; Masato Okada; K Iwasa; Yusuke Ikada; Tomoko Minamisaka; Tetsuya Watanabe; Nobutaka Masunaga; Yukinori Shinoda; Norioki Inui; Ryohei Amiya; Masato Fujiwara; A Murakami; Hitoshi Minamiguchi; Yoshiharu Higuchi; Yasuhiro Ichibori; Naoki Mori; Takashi Kanda; Yuma Hamanaka; Yumi Tsutsui; Mikiko Matsumura; Takashige Sakio; Satoshi Nakawatase; Yuki Shibuya; Shinya Minami; Koichi Ochi; Ken Koda; Naoya Kurata; Hiroshi Kobayashi; Yasuyuki Egami; Masamichi Yano; 松永泰治; Koji Yasumoto; Kohei Ukita; Mizuki Osuga; Noriyuki Kobayashi; Ayako Sugino; Atsushi Shiono; M Kawasaki; Mitsutoshi Asai; Atsushi Kikuchi; Takumi Kondo; Tsutomu Kawai; M Seo; Atsushi Nakamura; Takeshi Fujita; Takuya Omoto; Yuki Kokubu; Yuto Fukuda; Hirota Kida; Yoshitaka Kikuchi

doi:10.1161/jaha.125.047450

June 15, 2026Journal of the American Heart AssociationOpen Access

Impact of Diabetes on the Efficacy of Low‐Voltage Area Ablation for Persistent Atrial Fibrillation: A Subanalysis of the SUPPRESS‐AF Trial

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Key result

Adding low-voltage area ablation to PVI cuts arrhythmia recurrence ~36% only in nondiabetic persistent AF.

HR 0.642
95% CI 0.44-0.94
P=0.021
n=341

Figures

Graphical abstract published by Journal of the American Heart Association — Graphical abstract · Published by Journal of the American Heart Association · CC BY-NC-ND

Why the study?

The determinants of the efficacy of low-voltage area ablation for persistent AF remain unclear.

Does pulmonary vein isolation plus low-voltage area ablation reduce AF/AT recurrence compared to pulmonary vein isolation alone in patients with persistent atrial fibrillation stratified by diabetes status?

Key Points

To assess how diabetes mellitus impacts the efficacy of low-voltage area (LVA) ablation in patients undergoing initial catheter ablation for persistent atrial fibrillation.
This post hoc subanalysis of the multicenter randomized controlled SUPPRESS-AF trial included 343 patients with persistent atrial fibrillation and left atrial LVAs out of 1347 undergoing initial ablation between June 2019 and August 2022.
The primary end point was freedom from atrial fibrillation (AF) or atrial tachycardia (AT) recurrence over follow-up (overall completeness 94.7%).
Overall arrhythmia recurrence rates were 44% in the diabetic group versus 42% in the nondiabetic group (HR, 1.065 [95% CI, 0.73–1.56]; log-rank P=0.658).
In nondiabetic patients, PVI plus LVA ablation significantly lowered recurrence rates compared with PVI alone (35% versus 49%; HR, 0.642 [95% CI, 0.44–0.94]; log-rank P=0.018).
In diabetic patients, recurrence rates did not significantly differ between PVI plus LVA ablation and PVI alone (48% versus 40%; HR, 1.42 [95% CI, 0.72–2.82]; log-rank P=0.290), showing a significant interaction between diabetes and ablation strategy (P for interaction=0.041).

Study Design

Type

RCT (n=341)

Blinding

Open-label

Randomization

1:1 ratio

Multicenter

Yes

Structured PICO

Does pulmonary vein isolation plus low-voltage area ablation reduce AF/AT recurrence compared to pulmonary vein isolation alone in patients with persistent atrial fibrillation stratified by diabetes status?

P

Population

341 adults with persistent atrial fibrillation and left atrial low-voltage areas, stratified by diabetes status, followed for 12 months after their first ablation procedure.

I

Intervention

Pulmonary vein isolation (PVI) plus low-voltage area (LVA) ablation (homogenization ablation covering all LVAs with a bipolar peak-to-peak voltage <0.5 mV)

C

Comparator

Pulmonary vein isolation (PVI) alone

O

Outcome

Composite of atrial fibrillation (AF) or atrial tachycardia (AT) recurrence (documented by scheduled/symptom-triggered ECG or ≥30 seconds on Holter monitoring) at 12 months follow-up, excluding a 3-month blanking period.composite

Main Result

Hazard Ratio: 0.642 (95% CI 0.44–0.94)

Absolute Event Rate: 35% vs 49%

p-value: p=0.021

Additional low-voltage area ablation beyond pulmonary vein isolation reduced arrhythmia recurrence in persistent AF patients without diabetes, but yielded no benefit in those with diabetes.

Limitations

Lack of data on glycemic control, diabetes duration, and therapeutic regimens
East Asian population only, limiting generalizability to other ethnic groups
Post hoc subgroup analysis may be affected by chance imbalances in prognostic factors
No systematic evaluation of intraprocedural electrophysiological endpoints
Absence of continuous monitoring with implantable loop recorders may have led to underestimated asymptomatic recurrences
Exploratory post hoc analysis
Limited sample size in the diabetic subgroup resulting in wide 95% CIs

Implication

Supports adding LVA ablation in nondiabetic persistent AF; challenges uniform use and extends selection criteria from prior trials.

Abstract

Background The potential value of low‐voltage area (LVA) ablation for persistent atrial fibrillation (AF) has been suggested. However, its efficacy determinants remain unclear. We investigated the impact of diabetes on the outcomes of LVA ablation in patients with persistent AF. Methods This post hoc subanalysis of the multicenter randomized controlled trial SUPPRESS‐AF (Efficacy and Safety of Low‐Voltage‐Guided Ablation for Recurrence Prevention Compared With Pulmonary Vein Isolation Alone in Patients With Persistent Atrial Fibrillation) included patients with persistent AF undergoing initial ablation. Following pulmonary vein isolation (PVI), patients with LVAs were randomized to PVI+LVA‐ablation or PVI alone. We compared recurrence‐free survival between patients with and without diabetes. The primary end point was freedom from AF/atrial tachycardia recurrence. Results Of 1347 patients with persistent AF, 343 (25.5%) had left atrial LVAs. The nondiabetic group comprised 264 patients (136 and 128 in the PVI‐alone and PVI+LVA‐ablation arms, respectively), and the diabetic group comprised 77 patients (35 and 42 in each arm, respectively). No significant difference was observed in LVA extent between the groups. Overall recurrence rates were also similar (44% versus 42%; P =0.658). In the nondiabetic group, the PVI+LVA‐ablation arm showed significantly lower recurrence rates compared with the PVI‐alone arm (35% versus 49%; P =0.018). Conversely, patients with diabetes exhibited higher recurrence rates in the PVI+LVA‐ablation arm compared with those in the PVI‐alone arm (48% versus 40%; P =0.290). A significant interaction was observed between diabetes status and LVA ablation efficacy ( P for interaction=0.041). Conclusions In this exploratory post hoc analysis, LVA ablation may benefit patients without diabetes, whereas no clear benefit, and a possible signal of futility, was observed in patients with diabetes.

Discussion

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Cite This Study

Ozaki et al. (2026) conducted an RCT in Persistent atrial fibrillation (n=341). Pulmonary vein isolation plus low-voltage area ablation vs. Pulmonary vein isolation alone was evaluated on AF/AT recurrence (nondiabetic subgroup) (HR 0.642, 95% CI 0.44-0.94, p=0.021). In persistent AF patients without diabetes, adding low-voltage area ablation to pulmonary vein isolation reduced arrhythmia recurrence (HR 0.642), a benefit absent in diabetics (P for interaction=0.041).

synapsesocial.com/papers/6a31570faf7cf7f8256b3d5c https://doi.org/10.1161/jaha.125.047450

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Impact of Diabetes on the Efficacy of Low‐Voltage Area Ablation for Persistent Atrial Fibrillation: A Subanalysis of the SUPPRESS‐AF Trial

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Impact of Diabetes on the Efficacy of Low‐Voltage Area Ablation for Persistent Atrial Fibrillation: A Subanalysis of the SUPPRESS‐AF Trial

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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