Repetitive Activation Patterns and Focal Impulses Identification and Ablation in Persistent AF: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Repetitive Activation Patterns and Focal Impulses Identification and Ablation in Persistent AF (NCT03064451), a na na study. The primary outcome is Percentage of Participants With Acute Success Post CartoFinder Guided Ablation (CFGA) Only (Before Pulmonary Vein Isolation [PVI] and Without Cardioversion)..

2. Clinical Question

The study’s stated purpose was to assess the effectiveness of CARTOFINDER-guided ablation in terminating persistent atrial fibrillation to normal sinus rhythm or atrial tachycardia, compared with pulmonary vein isolation in treating persistent atrial fibrillation. The registered procedure, however, is a single sequence: CARTOFINDER-guided ablation followed by pulmonary vein isolation. That design does not provide a separate PVI-only group for a like-for-like comparison.

The primary endpoint focuses specifically on the rhythm outcome after the first procedural component. It therefore addresses acute conversion associated with CARTOFINDER-guided ablation before the subsequent PVI step, rather than a comparison of longer-term outcomes between independent treatment groups. Follow-up visits were planned at 7 days, 3, 6 and 12 months after the procedure, while the primary endpoint itself has a timeframe of up to 7 days.

3. Trial Design

This was a completed, single-group procedural study in persistent atrial fibrillation. The registry lists enrollment of 60 and a study period from 2017-02-22 to primary completion on 2019-04-10. The planned procedure was CARTOFINDER-guided ablation followed by pulmonary vein isolation. The brief summary describes an approximate enrollment range of 40-70 subjects and follow-up visits at 7 days, 3, 6 and 12 months postprocedure.

The study is not described as randomized: allocation is listed as NA, and the design model is single group. Masking is listed as none. Consequently, the record does not describe independent arms assigned to different procedures. A sequence in which all participants undergo one procedure followed by another cannot by itself separate the effects of the two components or establish what would have happened under a different procedural strategy.

The registered primary endpoint is acute success after CARTOFINDER-guided ablation only. It is defined as conversion from atrial fibrillation to normal sinus rhythm or atrial tachycardia, before PVI and without cardioversion. The endpoint population includes enrolled participants with catheter insertion and CARTOFINDER-guided ablation performed; this is an evaluable population rather than an unrestricted count of everyone enrolled.

The registry lists 11 outcome measures and 0 analyses. Secondary outcomes include confirmation of entrance block after adenosine/isoproterenol challenge; change in intra-cycle length from baseline to post-CFGA and post-PVI; and counts of serious adverse device effects, serious adverse events, adverse device effects, and procedure-related serious and non-serious adverse events. A detailed statistical analysis plan, including how these outcomes were tested or summarized, is not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The evaluable participant population included all enrolled participants who had the RHYTHMFINDER 192 Catheter inserted and where CARTOFINDER-guided ablation was performed.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Acute Success Post CartoFinder Guided Ablation (CFGA) Only (Before Pulmonary Vein Isolation [PVI] and Without Cardioversion)., measured over Up to 7 days.

The primary endpoint is the percentage of participants with acute success after CARTOFINDER-guided ablation alone. Acute success is defined as conversion of atrial fibrillation to either normal sinus rhythm or atrial tachycardia, assessed before pulmonary vein isolation and without cardioversion. The timeframe is up to 7 days. The evaluable population consists of enrolled participants who had the RHYTHMFINDER-192 catheter inserted and underwent CARTOFINDER-guided ablation.

This endpoint is used to describe an immediate rhythm outcome following the CARTOFINDER-guided component of the procedure. Specifying that assessment occurs before PVI distinguishes it from a rhythm outcome measured after the full procedural sequence. Excluding cardioversion from the definition also makes clear that conversion attributed to this endpoint is not counted when cardioversion is used.

Because the endpoint is a participant-level binary outcome—conversion meeting the definition or not—the percentage is a way to express how often the defined event occurred in the evaluable group. It does not, by itself, describe the duration of a rhythm after conversion, later recurrence, or a comparison with a separate control group. The registry record does not report the observed primary endpoint value, its denominator, or a confidence interval. The endpoint definition and population are available, but the extent and precision of the observed result cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help clarify what the registered endpoint could show and what cannot be inferred from the available record. These are general explanations, not claims about unreported procedures used in this study.

What does a percentage endpoint represent?

A binary endpoint classifies each participant according to whether a defined event occurred. For this study’s primary endpoint, the event is conversion from atrial fibrillation to normal sinus rhythm or atrial tachycardia after CARTOFINDER-guided ablation alone, before PVI and without cardioversion. A percentage expresses the frequency of participants meeting that definition relative to the endpoint population. Its meaning depends on a clear event definition and on knowing who was included in the denominator.

The registry defines the primary endpoint population as enrolled participants who had the RHYTHMFINDER-192 catheter inserted and underwent CARTOFINDER-guided ablation. This matters because that population may not be identical to everyone enrolled. If participants do not meet the evaluability criteria, or if endpoint status is unavailable for some participants, the reported percentage and its interpretation depend on how those cases are handled. Such handling is not reported in the registry record.

Why does precision matter?

A point estimate describes the observed frequency in the study population, but it does not by itself show how much uncertainty surrounds that estimate. A confidence interval is a general statistical tool for expressing uncertainty around an estimate under a specified method and assumptions. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. No confidence interval for the primary endpoint is reported in the registry record, so the precision of that endpoint cannot be assessed.

Precision is not the same as clinical importance, and an interval does not remove limitations in study design. Even a precise estimate from a single group would remain a description of that group under the study procedure. It would not turn a non-randomized, single-group design into a controlled comparison or establish what would have occurred under another procedure.

What can a single-group design estimate?

In general, a single-group study can describe outcomes observed among participants who receive the studied procedure. A separate comparison group is needed to directly compare outcomes across treatment strategies. Here, the registered procedure is CARTOFINDER-guided ablation followed by PVI, and the primary endpoint is assessed between those steps. That sequence can define the timing of an endpoint, but it is not equivalent to having one group receive CARTOFINDER-guided ablation and another group receive PVI alone.

When outcomes are measured in sequence, interpretation also depends on the timing and definition of each measurement. The primary endpoint’s before-PVI timing makes it distinct from outcomes measured after completion of both procedural components. The registry describes additional electrophysiological and safety outcomes, but the methods used to analyze them are not reported in the registry record.

How should planning illustrations be understood?

Sample-size planning is a general design exercise that estimates how many participants per arm might be needed under specified assumptions to detect a chosen effect with a chosen statistical power. A planning illustration based on an observed effect is not an observed-power calculation and does not show that the study was designed prospectively around that effect. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. The stated sample-size illustrations are not the trial’s own design justification.

The registry record does not report the calculated planning values or a sample-size justification for this study. It also does not report a separate randomized two-arm design. Therefore such planning assumptions should not be read as evidence that this single-group study had a two-arm allocation or a specified power for its primary endpoint. Sample-size illustrations are planning quantities, not a measure of observed evidence.

What does the analysis record establish?

The registry lists 0 analyses. This means the registry record does not list statistical analyses; it does not establish whether analyses were conducted outside the record. A prespecified statistical analysis plan, including tests, adjustment methods, missing-data handling, and confidence-interval methods, is not reported in the registry record. Without those details, readers cannot determine how the listed outcomes were intended to be analyzed or whether any analysis choices were prespecified.

For binary outcomes, analysis choices can include how the denominator is defined, how unavailable event status is treated, and whether estimates are accompanied by uncertainty intervals. For comparisons, choices can include the comparison population and how confounding is addressed. These are general considerations. The registry record does not report that a particular method was used for this study, so no specific inferential method should be attributed to it.

Likewise, a count of events and a count of participants with events are not always interchangeable: one participant may experience more than one event. Safety summaries need to be interpreted according to whether they count participants, events, or event terms. The registry labels several safety outcomes as numbers of participants, but the listed serious-event terms and their percentages do not provide enough detail to reconstruct event-level patterns or overlap. The record’s endpoint definitions, analysis populations and missing-data procedures are not reported in sufficient detail to resolve those questions.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Participants With Persistent Atrial Fibrillation (")
n      <- c(48)
events <- c(11)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Participants With Persistent Atrial Fibrillation (  48  11  22.9  12.0  37.3  13.3  36.5  13.3  36.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary acute-success endpoint and secondary electrophysiological and safety outcomes. Considering multiple outcomes can raise a general multiplicity issue: when many statistical tests are performed, the chance of at least one apparently unusual result can increase unless the analysis plan addresses that risk. The registry record does not report a multiplicity strategy, a hierarchy of confirmatory outcomes, or which outcomes were intended for formal testing. It lists 0 analyses, so the record does not establish which tests, if any, were conducted.

Missing data are also important for a percentage endpoint. The registry defines an evaluable population based on catheter insertion and performance of CARTOFINDER-guided ablation, but it does not report how participants with missing endpoint status were handled. It does not describe imputation, exclusion rules beyond the stated evaluability definition, or sensitivity analyses for missing outcomes. These details are not reported in the registry record.

The primary endpoint population is not necessarily interchangeable with the group used for safety summaries. The registry identifies 52 participants at risk in the serious and other adverse-event summaries, while the primary endpoint population is defined procedurally. The registry record does not report whether the populations match or explain any difference in inclusion.

The record also does not report an intention-to-treat analysis population, a per-protocol population, or other prespecified analysis populations. Without these details, readers should not assume that every enrolled participant contributed to every outcome or that missingness was handled in a particular way. The reported endpoint definition and safety counts can be described, but the full analysis-population and missing-data procedures are not reported in the registry record.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac tamponade (1.9%), pericardial effusion (1.9%), pericarditis (1.9%), infection (1.9%), arteriovenous fistula (1.9%).

The registry reports a serious adverse-event summary for participants with persistent atrial fibrillation: 10 participants were affected among 52 at risk. The other adverse-event summary reports 6 affected among 52 at risk. The registry also reports 0 deaths. These are descriptive counts; they do not establish a comparison between treatment strategies, because the registered design is single group.

The serious-event terms listed are cardiac tamponade, pericardial effusion, pericarditis, infection, arteriovenous fistula and haematoma, each with a reported frequency of 1.9%. The registry record does not clarify whether participants could contribute to more than one term or whether those percentages refer to distinct participants or event occurrences. The terms should therefore not be added together or interpreted as mutually exclusive categories.

Safety outcome titles include serious adverse device effects and serious adverse events up to 12 months, as well as adverse device effects and procedure-related serious and non-serious adverse events. Counts alone do not describe severity, duration, relatedness assessment or timing for each event. Those details are not reported in the registry record. The counts are best read as reported descriptive safety information, not as estimates of comparative risk or proof of causation.

13. What the Result Does, and Does Not, Mean

The study addresses a specific procedural question: whether acute conversion to normal sinus rhythm or atrial tachycardia is observed after CARTOFINDER-guided ablation alone, before PVI and without cardioversion. This is a focused endpoint tied to a particular point in the procedural sequence. Its definition helps distinguish an acute rhythm outcome after the CARTOFINDER-guided step from outcomes measured after the full procedure or during later follow-up.

However, the observed primary endpoint value is not reported in the registry record. Without that value and its denominator, the registry record does not show how often the defined acute conversion occurred. Without an uncertainty interval, the precision of the endpoint estimate cannot be assessed either. The endpoint definition alone does not establish the frequency or reliability of an outcome.

The record also does not support a direct comparison of CARTOFINDER-guided ablation with PVI alone. Although the study purpose describes a comparison, the registered design is single group and the procedure is CARTOFINDER-guided ablation followed by PVI. The primary outcome is measured before PVI, but there is no separate control group described. The design therefore does not provide a like-for-like treatment contrast.

Safety counts offer descriptive information about adverse events in the reported group. They do not determine whether an event was caused by one component of the procedure, nor do they quantify a difference in safety compared with another strategy. The serious-event terms and percentages should be interpreted with caution because the record does not explain possible overlap or provide further event-level detail.

More broadly, the absence of a reported statistical analysis plan, primary endpoint result, confidence interval, and missing-data methods limits what can be concluded statistically. This does not mean that the procedure did or did not produce a particular outcome. It means that the registry record does not supply the information needed to quantify the primary result or assess its precision. The study’s design and definitions can be described, but claims about comparative effects or the strength of evidence would go beyond the reported information.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of why endpoint timing and design structure must be read together. The registered procedure includes CARTOFINDER-guided ablation followed by PVI, while the primary endpoint is deliberately defined after the first component and before the second. That distinction identifies the point in the sequence at which acute conversion is to be assessed, but it does not create a separate comparison group.

The registry’s stated aim refers to comparison with PVI, whereas the listed design is single group and allocation is NA. This illustrates an important difference between a research objective and the comparison that a study design can estimate. A comparative question generally requires clearly defined groups or another suitable comparison strategy. A sequential procedure in one group can describe outcomes at different stages, but it cannot by itself estimate the counterfactual outcome under a different treatment pathway.

The primary endpoint also shows why the analysis population matters. The endpoint applies to enrolled participants who had catheter insertion and CARTOFINDER-guided ablation, not automatically to every enrolled participant. A result is interpretable only when its numerator, denominator, endpoint definition and handling of unavailable status are clear. The registry provides the population definition but does not report the primary endpoint result or missing-data handling.

Finally, the record lists many outcome measures but no analyses. This distinction matters: registered outcomes describe what was planned to be measured, while statistical analyses specify how observations are summarized and compared. Without reported results and methods, the record cannot answer how precise the acute endpoint estimate was or whether any secondary outcome differences were assessed. The study therefore underscores the value of transparent reporting of estimates, uncertainty, analysis populations and the limits imposed by design.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The primary limitation for statistical interpretation is that the registry record does not report the observed primary endpoint result. It also does not report a confidence interval or the endpoint denominator, preventing assessment of both the event frequency and its precision. The evaluable population is defined, but the number meeting that definition is not reported in the registry record.

The design is single group, with allocation listed as NA and masking listed as none. There is no separate randomized comparator arm described. The procedure sequence and the endpoint’s before-PVI timing do not allow a direct comparison with PVI alone. The stated comparative purpose should therefore be distinguished from the comparison supported by the registered design.

The registry lists 11 outcome measures and 0 analyses. A statistical analysis plan, including methods for primary and secondary outcomes, multiplicity, missing data, and any adjustment for relevant factors, is not reported in the registry record. The record also does not report how participants with missing endpoint information were handled or whether the evaluable population was defined before outcome data were reviewed.

Safety information is descriptive and does not include a separate control group. The record does not clarify whether the listed adverse-event terms overlap within participants or provide detailed event-level timing and relatedness. The safety counts should not be treated as comparative risk estimates.

Finally, the registry lists a planning illustration framework, but its calculated values and a study-specific sample-size justification are not reported in the registry record. Those illustrations are not the trial’s own design rationale and should not be interpreted as observed power. Collectively, these gaps constrain conclusions about endpoint magnitude, uncertainty, comparative effects and the analysis of secondary outcomes.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Repetitive Activation Patterns and Focal Impulses Identification and Ablation in Persistent AF — NCT03064451.
• Registry record last updated 2020-05-11; status last verified 2020-05.
• Results first posted 2020-04-21.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT03064451 is a completed, single-group study of CARTOFINDER-guided ablation followed by PVI in persistent atrial fibrillation. The registry lists enrollment of 60, no masking, and study dates from 2017-02-22 to primary completion on 2019-04-10. The primary endpoint is acute conversion to normal sinus rhythm or atrial tachycardia after CARTOFINDER-guided ablation alone, before PVI and without cardioversion, with a timeframe of up to 7 days.

The primary endpoint population is defined by catheter insertion and performance of CARTOFINDER-guided ablation. Its observed result is not reported in the registry record. Safety summaries report 10 affected among 52 at risk for serious adverse events, 6 affected among 52 for other adverse events, and 0 deaths. The registry lists 11 outcome measures and 0 analyses. The single-group design does not provide a separate randomized comparison with PVI alone.