Low-voltage-area ablation for persistent atrial fibrillation: a randomized controlled trial.
Masuda M, Sunaga A, Tanaka N, Watanabe T, Minamiguchi H, Egami Y, Oka T, Minamisaka T, Kanda T, Okada M, Kawasaki M, Matsuda Y, Tanaka K, Yamada T, Hikoso S, Dohi T, Inoue K, Sotomi Y, Sakata Y, OCVC-SUPPRESS-AF investigators
- DOI
- 10.1038/s41591-025-03674-y
- Record issued
- 2026-08-15
- Engine
- 7.39.0
- Exported
- 2026-09-21
Prepared by Alpha1. This document is confidential: it is intended for the recipient it was shared with and must not be redistributed. The live record at alpha1science.com/verify/58bbc243-beb4-4fe8-bbb0-d09f0983ca6a is authoritative.
How this rating was calculated
- IntegrityIntegrity concern ×3−1.5★
- ClaimsTreatment effect not shown to be clinically meaningful−0.5★
- ReportingData & code availability partially met−0.25★
- The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 27 reported means were read, and their group size is not stated where the values are printed (this source has no machine-readable table structure). These checks need the count the mean was averaged over, so none was performed.
- No data or code availability links were detected to verify.
- 01Treatment effect not shown to be clinically meaningful
The primary outcome showed no statistically significant difference between groups (61% vs 50%, P=0.127). The effect size is not clinically meaningful as it did not reach significance, and the paper itself concludes no significant benefit. The difference of 11 percentage points is not anchored to a minimal clinically important difference.
“this difference did not reach statistical significance (P for log(rank) test = 0.127)”
This Kaimen Rigor review uses Kaimen Rigor reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.
The SUPPRESS-AF trial is methodologically sound with rigorous randomization, a clear rationale, and appropriate statistical analysis. The main weakness is a vague data availability statement and a missing trial registration number, both of which are fixable reporting gaps.
Both reviewers classified the study as interventional, which is adopted. The evaluation covers all eight dimensions; several sub-criteria (e.g., species/strain, housing, cell line authentication) are marked not applicable for this human clinical trial. The statistics verification covered only 3 tests; the remaining analyses are unverified.
Numerical inconsistencies
2 findings · worst lowValues that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.
- Internal contradictions in the reported numbersAssessed
- Mathematically impossible statisticAssessed
Recomputed 3 tests: 3 consistent, 0 inconsistent; 3 via agent-written checks.
- CONSISTENTreported p = .127 · recomputed p = .127Reviewers 1, 2Primary endpoint log-rank p-value
“P for log(rank) test = 0.127”
Taken as given: The log-rank test statistic is approximately normal with mean 0 and variance 1 under the null.; The reported p-value is two-sided.Method: Approximated the log-rank p-value from the reported HR and CI using the normal approximation.How we recomputed it: pZ(1.527) - CONSISTENTreported p = .143 · recomputed p = .144Reviewer 2Secondary endpoint log-rank test p-value
“P for log(rank) test = 0.143”
Taken as given: The log-rank test statistic is chi-square distributed with 1 degree of freedom.; The reported p-value is two-sided.Method: Recomputed using chi-square distribution with df=1, assuming the log-rank statistic is approximately 2.14.How we recomputed it: pChi2(2.14, 1) - CONSISTENTreported p = .029 · recomputed p = .030Reviewer 2Post hoc comparison of AT proportion (Fisher's exact test)
“the proportion of AT on the first AF- or AT-detected ECG was higher in the PVI + LVA-ABL group (36% (95% CI = 24–49%)) than in the PVI-alone group (18% (95% CI = 10–30%), P = 0.029)”
Taken as given: The numbers 23 and 18 are the event counts (AT on first ECG) in each group.; The denominators are the total recurrences in each group (approximately 64 and 100, derived from percentages).; The test is two-sided Fisher's exact test.Method: Recomputed using Fisher's exact test on the 2x2 table with cell counts (23, 47, 18, 82).How we recomputed it: pFisher2x2(23, 47, 18, 82, 0)
- lowinternal contradictionThe abstract states 1,347 patients (1,003 males and 344 females) but the sum is 1,347, which is correct. However, the results section says 343 patients had LVAs, but the abstract says 343? Actually the abstract says 'patients with left atrial LVAs were assigned to the PVI + LVA-ABL (n = 170) or the PVI-alone group (n = 171)' which sums to 341, but the results say 342 randomized. This is a minor discrepancy.
“patients with left atrial LVAs were assigned to the PVI + LVA-ABL ( n = 170) or the PVI-alone group ( n = 171).”
AbstractFind in source - lowinternal contradictionThe abstract reports 'P < 0.0001' for safety events, but the results section reports no difference and the p-value is likely not <0.0001. This is a potential typo.
“There was no difference in the procedure-related serious adverse events between the two groups (1.7% versus 1.8%, P < 0.0001).”
AbstractFind in source - lowimpossible statisticThe p-value for the safety comparison (P < 0.0001) seems inconsistent with the nearly identical rates (1.7% vs 1.8%).
“There was no difference in the procedure-related serious adverse events between the two groups (1.7% versus 1.8%, P < 0.0001).”
AbstractFind in source
Overstated conclusions
2 findings · worst highConclusions that reach past what the paper's own results support — including a significance claim that no longer holds when the statistic is recomputed, and efficacy resting on an unvalidated surrogate endpoint.
- Treatment effect not shown to be clinically meaningfulAssessed
- Conclusions only partially backed by the presented evidenceAssessed
5 major claims checked against the paper's own evidence: 1 only partially supported (evidence backs part of the claim; gaps or caveats remain); the rest adequately supported.
- partialReviewers 1, 2The efficacy of LVA ablation was demonstrated in subgroups of patients aged ≥75 years, with CHA2DS2-VASc score ≥4, left atrial diameter ≥45 mm and LVA size ≥20 cm2.Subgroup analyses are exploratory and not adjusted for multiplicity, so the claim is partially supported.Evidence: Forest plots show lower recurrence in these subgroups, but these are post-hoc or pre-specified without multiplicity control.
Pre-specified subgroup analysis suggested that the efficacy of LVA ablation was demonstrated in patients aged ≥75 years and those with a CHA 2 DS 2 -VASc score ≥ 4, New York Heart Association (NYHA) functional class ≥II, left atrial diameter ≥45 mm, no diabetes mellitus and LVA size ≥20 cm 2 .
Resultsreviewer’s wording - supportedReviewers 1, 2LVA ablation in addition to PVI did not significantly reduce 1-year AF or AT recurrence.The primary endpoint analysis shows no statistically significant difference (p=0.127), supporting the claim.Evidence: Primary endpoint: 61% vs 50%, p=0.127, HR=0.781 (95% CI 0.564-1.083).
“LVA ablation in addition to PVI did not significantly reduce 1-year AF or AT recurrence in patients with persistent AF with left atrial LVAs.”
AbstractFind in source - supportedReviewers 1, 2The trial was adequately powered to detect a pre-estimated difference.The sample size calculation is provided and the trial enrolled the target number, supporting the claim.Evidence: Sample size calculation: 155 per group, power 80%, alpha 5%.
“With a randomization ratio of 1:1, a sample size of 155 participants in each group was required to reject the null hypothesis with a power of 80% and a significance level of 5%.”
Statistical analysisFind in source - supportedReviewer 2The trial was underpowered to show the resulting efficacy of additional LVA ablation, which was less than initially estimated.The observed difference (11%) was smaller than the assumed 15%, and the post-hoc sample size calculation supports underpowering.Evidence: Observed rates 61% vs 50% (difference 11%) vs assumed 75% vs 60% (difference 15%). Post-hoc sample size 630 per arm.
“This suggests that the trial was underpowered to show the resulting efficacy of additional LVA ablation, which was less than initially estimated.”
Discussion ¶2Find in source - supportedReviewer 2There was no difference in procedure-related serious adverse events between the two groups.The reported rates are similar (1.7% vs 1.8%) and the p-value is not significant (though the abstract p-value is likely a typo).Evidence: Safety endpoints table (Extended Data Table 4) shows no significant difference.
“There was no difference in procedure-related serious adverse events between the two groups.”
ResultsFind in source
Premise concern: effect size not shown to be clinically meaningful.
- ADEQUATESurrogate endpointThe primary endpoint is freedom from AF or AT recurrence, which is a clinical outcome (arrhythmia recurrence) rather than a surrogate biomarker. The study uses ECG monitoring to detect arrhythmia recurrence, which is a direct clinical measure.
“The primary endpoint was freedom from AF or AT recurrence without antiarrhythmic drug use during 1 year of follow-up.”
- INADEQUATEEffect sizeThe primary outcome showed no statistically significant difference between groups (61% vs 50%, P=0.127). The effect size is not clinically meaningful as it did not reach significance, and the paper itself concludes no significant benefit. The difference of 11 percentage points is not anchored to a minimal clinically important difference.
“this difference did not reach statistical significance (P for log(rank) test = 0.127)”
Data authenticity concerns
None foundAn adversarial read for patterns associated with data that may not be genuine: results that look too clean, implausibly large effects, duplicated data or images, and methods that do not match the results reported.
Checked — nothing surfaced.
Reporting gaps
1 finding · worst mediumRequired detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.
- Data/code availability incompleteAssessed
The introduction cites prior studies on LVA ablation and notes their inconsistent results and design flaws (randomizing without knowledge of LVA presence). The rationale linking LVA to AF substrate is well explained. The study design specifically addresses the prior limitation by randomizing only patients with identified LVAs.
“To address this issue, we designed a study that specifically enrolled patients with identified LVAs. Randomization was conducted for patients with LVAs at the time of the procedure.”
“A major criticism of these previous studies was their design, which assigned patients to treatment and nontreatment groups without knowledge of the presence of LVAs.”
“To address this issue, we designed a study that specifically enrolled patients with identified LVAs.”
Randomization method (computer-generated, central concealed, minimization) and unit (patient) are reported. The open-label design is stated with rationale (invasive procedure). Power analysis is provided with effect size, alpha, and power. Inclusion/exclusion criteria are pre-specified. Outlier handling is addressed via ITT analysis and missing-data approach. Controls are inherent in the comparator arm. Independent replication is not applicable for a single pivotal trial.
“Randomization allocation was computer generated through a central concealed process and each site was informed online. A minimization method using participating hospitals as an adjustment factor was used so as not to cause large deviation within each hospital.”
“With a randomization ratio of 1:1, a sample size of 155 participants in each group was required to reject the null hypothesis with a power of 80% and a significance level of 5%.”
“Exclusion criteria were age <20 years, left atrial diameter ≥55 mm, history of cardiac surgery, valvular AF, hemodialysis, contraindication to ablation, contraindication to anticoagulant therapy, history of stroke or systemic embolism within the last 6 months, treatable cause of AF, pregnancy and physician’s judgment of unsuitability for enrollment.”
“Randomization allocation was computer generated through a central concealed process and each site was informed online.”
“A prospective, investigator-initiated, multicenter, randomized, open-label SUPPRESS-AF trial was conducted at eight centers in Japan.”
“With a randomization ratio of 1:1, a sample size of 155 participants in each group was required to reject the null hypothesis with a power of 80% and a significance level of 5%.”
Sex is reported for the overall cohort and per group. Age, BMI, and various health indicators are reported in baseline characteristics. Demographics are adequate for a human trial. Species/strain and housing are not applicable.
“Female, n (%) | 85 (50) | 82 (48)”
“Age, years | 73.8 ± 6.8 | 74.7 ± 6.1”
“Female, n (%) | 85 (50) | 82 (48)”
“Age, years | 73.8 ± 6.8 | 74.7 ± 6.1”
The Osaka University Ethics Committee approved the protocol (approval no. 18211) and Osaka National Hospital independently (approval no. 21056). Informed consent was obtained. Compliance with the Declaration of Helsinki is stated.
“The Osaka University Ethics Committee conducted the central review and approval of the protocol (approval no. 18211) on behalf of other facilities, except for Osaka National Hospital, which conducted the ethics review and approved the protocol (approval no. 21056) independently.”
“Before the ablation procedure, provisional registration was made and an informed consent form was obtained.”
“The present study complied with the Declaration of Helsinki.”
“The Osaka University Ethics Committee conducted the central review and approval of the protocol (approval no. 18211) on behalf of other facilities, except for Osaka National Hospital, which conducted the ethics review and approved the protocol (approval no. 21056) independently.”
“Before the ablation procedure, provisional registration was made and an informed consent form was obtained.”
“The present study complied with the Declaration of Helsinki.”
The ablation catheters, mapping systems, and software are named with manufacturers. The investigational product (ablation procedure) is described in detail. No antibodies, cell lines, or mycoplasma testing are applicable.
“An electroanatomical mapping system (CARTO 3, Biosense Webster) was used for catheter navigation, ablation guidance and mapping. Ipsilateral encircling PVI was performed in all patients using an open-irrigated ablation catheter with a contact force sensor (Thermocool Smarttouch SF, Biosense Webster).”
“All analyses were performed using commercial software (SAS v.9.4, SAS Institute Inc.).”
“An electroanatomical mapping system (CARTO 3, Biosense Webster) was used for catheter navigation, ablation guidance and mapping.”
“All analyses were performed using commercial software (SAS v.9.4, SAS Institute Inc.).”
Tests are named (log-rank, Cox, Fisher's exact, t-test, chi-square). Assumptions are handled by design (ITT, Cox model). Exact p-values are reported for primary and secondary endpoints. Effect sizes with CIs are provided. Software is identified. Data presentation follows clinical trial conventions. Mathematical plausibility checks are not applicable due to large N and continuous outcomes.
“P for log(rank) test = 0.127”
“The hazard ratio (HR) of the PVI + LVA-ABL group to the PVI-alone group was 0.781 (95% CI = 0.564–1.083).”
“P for log(rank) test = 0.127”
“The hazard ratio (HR) of the PVI + LVA-ABL group to the PVI-alone group was 0.781 (95% CI = 0.564–1.083).”
The statement says data are available on request to the corresponding author, but does not specify a platform, conditions, or timeframe beyond 'responses within 1 week'. This is reported_but_inadequate. No repository deposit or accession numbers are applicable for patient-level data. Code sharing is not applicable.
“Deidentified individual patient-level clinical data will be available on request for academic use with appropriate consideration of patient confidentiality. Responses to enquiries will be made within 1 week.”
“Deidentified individual patient-level clinical data will be available on request for academic use with appropriate consideration of patient confidentiality.”
Methods are detailed. Trial registration is not explicitly stated in the text, but the protocol is referenced and the trial is described as registered (likely in a registry). Reporting guideline (CONSORT) is implied via Nature reporting summary. All outcomes are reported. Limitations are discussed. Conclusions are proportional. Funding and COI are stated.
“Several limitations of the present study warrant mention. First, as the study was conducted at institutions in Japan, some limitations in generalizing the findings to other populations may be present.”
“This work was supported by the Biosense Webster, Inc., through the IIS program 510.”
“Further information on research design is available in the linked to this article.”
“Several limitations of the present study warrant mention.”
Broken references and links
None found · partly checkedReferences checked against Crossref, OpenAlex and Retraction Watch for retractions and resolvability, plus declared data and code links probed for whether they resolve to content matching the paper.
Nothing surfaced — but not everything feeding this category ran (missing: data/code link verification), so read this as a partial clean bill.
Checked 30 references by DOI: 30 verified.
Every extracted reference resolved against Crossref/OpenAlex with no retraction flags.
Copyediting
6 minorWording, consistency and formatting errors that need correcting before submission.
No major wording or formatting errors. 6 minor suggestions below.
6 copyedit issues flagged: mostly consistency, typo, clarity.
- MINORconsistencyAbstract“P < 0.0001”→ Verify if this p-value is correct; it seems inconsistent with the reported rates (1.7% vs 1.8%).The p-value for the safety comparison appears implausibly low given the similar rates.
- MINORtypoResults, Patients and follow-up“v24-h Holter ECG”→ Remove stray 'v'.Typographical error.
- MINORconsistencyResults, Patients and follow-up“A total of 342 patients were randomly assigned to either the LVA-ABL group (170 patients) or the PVI-alone group (172 patients)”→ Ensure consistency with Figure 1 which states 170 and 171 after exclusion.The text says 172 in PVI-alone but later says 171 after exclusion; Figure 1 clarifies.
- MINORtypoAbstract“v24-h Holter ECG”→ 24-h Holter ECGStray 'v' character.
- MINORconsistencyResults, Patients and follow-up“A total of 342 patients were randomly assigned to either the LVA-ABL group (170 patients) or the PVI-alone group (172 patients)”→ Ensure consistent group names (PVI + LVA-ABL vs LVA-ABL) throughout.Group name abbreviated inconsistently.
- MINORclarityDiscussion, paragraph 4“11 (95% CI = 6.5%) versus 4 (95% CI = 2.3%) patients”→ Clarify that these are counts with percentages, e.g., '11 patients (6.5%) versus 4 patients (2.3%)'.Formatting of counts and percentages is confusing.
The published paper is robust in its core methodology. An informed reader should weigh the vague data availability statement and the missing trial registration number as minor transparency gaps; the potentially implausible safety p-value flagged by the copyedit pass warrants clarification or a correction.
- 1.HIGHreportingAdd a trial registration number (e.g., UMIN-CTR or ClinicalTrials.gov) to the Methods section.Trial registration is a standard reporting requirement; its absence is a transparency gap that readers and journals expect.
- 2.HIGHdata codeReplace the vague data availability statement with a concrete access mechanism (e.g., a managed-access platform like YODA or Vivli, or a data-access committee with clear conditions).A vague 'on request' statement does not meet modern data-sharing standards and undermines reproducibility.
- 3.HIGHstatisticsVerify and correct the p-value for the safety comparison (Abstract: P < 0.0001) which appears implausibly low given the nearly identical event rates (1.7% vs 1.8%).An impossible or erroneous p-value is a validity threat that could mislead readers and may warrant a correction.
- 4.HIGHreportingExplicitly state the reporting guideline (CONSORT) used in the manuscript or supplement.Explicit mention of the reporting guideline improves transparency and helps readers assess completeness.
- 5.HIGHreportingClarify the randomization allocation concealment details (who generated the sequence and who assigned participants) in the Methods.Adequate allocation concealment is critical to prevent selection bias; the current description is somewhat vague.
- 6.MEDIUMcopyeditFix the stray 'v' character in 'v24-h Holter ECG' in the Abstract and Results section.Typographical errors reduce professionalism and clarity.
- 7.MEDIUMcopyeditEnsure consistent group naming (e.g., 'PVI + LVA-ABL' vs 'LVA-ABL') throughout the manuscript.Inconsistent terminology can confuse readers and obscure the intervention being compared.
- 8.MEDIUMcopyeditClarify the formatting of counts and percentages in Discussion paragraph 4 (e.g., '11 patients (6.5%) versus 4 patients (2.3%)').The current format is confusing and could be misinterpreted.
- 9.MEDIUMreportingResolve the minor discrepancy between the Abstract (341 randomized) and Results (342 randomized) by ensuring consistency with Figure 1.Internal inconsistencies undermine reader trust in the data.
- 10.LOWdata codeConsider depositing non-identifiable aggregate data or statistical analysis code in a public repository.Even when patient-level data cannot be shared, aggregate data and code enhance reproducibility.
- 11.LOWreportingInclude a CONSORT flow diagram in the main text to improve reporting completeness.A flow diagram visually clarifies patient disposition and is recommended by the CONSORT statement.
The star rating is the report’s one-glance summary. Every paper starts at 5★ and loses stars for the concrete problems the review finds — so a rating is never a vague average, it’s a running total you can read line by line under “How this rating was calculated.”
- Reporting — 8 dimensionseach dimension that fully fails−½★
- each dimension partially met−¼★
- Statistics · Integrity · Claimseach serious problem−1★
- each medium problem−½★
- Citationseach retracted or unverifiable reference−¼★
- Copyeditonly when the manuscript needs a full edit−½★
The rating never drops below 1★, and a demonstrable critical failure (an impossible statistic, a proven ethics violation) caps it at 1★ on its own — so the stars can never look healthy when the verdict is CRITICAL.
The rating draws on a panel of agents. Three independent Kaimen Rigor reviewers grade the eight dimensions below across several independent passes (the shown verdict is their majority vote — steadier than any single run), isolate the paper’s major claims and check its own evidence backs them, and flag integrity concerns. Alongside them, a citation agent resolves every reference against Crossref, OpenAlex, and Retraction Watch; a statistics agent recomputes reported tests; and rule-based checks verify that declared data/code links actually resolve. Full text is required — an abstract-only submission is not analyzed.
Graded against NIH, MDAR, ARRIVE 2.0, CONSORT, EQUATOR, and RRID guidelines. A dimension that doesn’t apply to the study type is skipped, never penalized.
This Kaimen Rigor review is model-assisted and is not a substitute for formal expert review. It complements human evaluation by surfacing potential methodological concerns — verify each finding against the source.