Prospective Evaluation of CT Guided Ablation of Cardiac Ganglionated Plexi: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prospective Evaluation of CT Guided Ablation of Cardiac Ganglionated Plexi (NCT04642976), a registered phase not stated study. The primary outcome is Correlation Between HFS (High Frequency Stimulation) Response and CT Identified Epicardial Adipose Tissue..

2. Clinical Question

The study's stated aim is to evaluate the feasibility and efficacy of CT- and HFS-guided GP mapping and ablation, and to clarify the innervation network between GP. The defined primary measure addresses spatial correspondence between a stimulation response and CT-identified tissue. It does not, by itself, establish whether the mapping approach changes a patient's clinical course. The registry record does not report a primary result or a comparison of clinical outcomes between the different ablation approaches.

3. Trial Design

The registry describes a prospective, observational, single-center study of patients with atrial fibrillation undergoing catheter ablation with pulmonary vein isolation. It lists an enrollment of 30 and identifies the sponsor as the University of Pennsylvania. The record gives a study start date of 2021-01-20, a primary completion date of 2024-01-01, and a status of COMPLETED.

All patients in the described study group were to undergo pre-procedural CT and HFS mapping and ablation of GP. The intervention is listed as GP mapping and ablation using a Natus Cortical Stimulator and standard ablation catheters. The brief description says participants were allocated among 8 different GP ablation approaches in a non-randomized fashion. Further details about how those approaches were assigned, their specific procedures, or the number of participants in each approach are not reported in the registry record.

Because the study is observational and the approaches were not randomized, any comparison among them would need to be interpreted in light of how participants came to receive each approach. The registry does not report a control arm that did not receive the mapping and ablation procedure, nor does it describe a randomized allocation process. The arm description instead refers to patients undergoing atrial fibrillation ablation with pre-procedural CT and HFS mapping and GP ablation.

The registry lists a primary outcome concerning HFS response near CT-identified epicardial adipose tissue. It also lists secondary outcomes concerning elimination of HFS and global vagal responses, and changes in signal amplitude, duration and fractionation at ablation sites. Outcome time points and operational details beyond those explicitly listed are not reported in the registry record. Results for these outcomes are also not reported in the registry record, so the completed status should not be taken as evidence that results are available in the 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

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 Correlation Between HFS (High Frequency Stimulation) Response and CT Identified Epicardial Adipose Tissue., measured over During Procedure.

The primary endpoint is defined as the number of patients with an HFS response identified within 3 pixels of a location where CT identified epicardial adipose tissue. The stated distance conversion is 0.625x3=1.875mm, and the assessment time is during the procedure. The endpoint therefore counts patients meeting a spatial criterion; it is not defined as a correlation coefficient or as a measure of later clinical outcome.

The rationale for this measure follows the study's aim to evaluate CT-guided localization of GP and HFS-guided mapping. In general, assessing whether two mapping signals or anatomical features occur near one another can help characterize their spatial correspondence. A count based on a prespecified proximity rule can describe how often that criterion was met in the assessed group. However, the count alone does not show the accuracy of CT localization unless a reference standard and suitable comparison are defined and reported.

The endpoint title uses the term “correlation,” while its definition specifies a count of patients meeting the proximity criterion. The statistical interpretation should follow the operational definition: a patient count. The registry record does not report the observed count, the denominator used for the endpoint, or a statistical estimate of association. It also does not report how missing or unevaluable mapping observations were handled. Thus, the endpoint's intended measurement is clear at a descriptive level, while its actual result and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is the primary measure?

The primary endpoint is a count: the number of patients whose HFS response was identified within a stated distance of a CT-identified epicardial adipose tissue location. Counts are useful when the outcome is whether a defined event or criterion occurred for each assessed participant. A count is not the same as a rate or proportion. To interpret a proportion, the count would need to be considered alongside the relevant denominator. The registry defines the unit as the number of patients with an HFS response, but the result and denominator are not reported in the registry record.

The endpoint title refers to a correlation. In general, correlation describes the degree to which two measured quantities vary together, under a specified statistical definition. The operational definition recorded for this endpoint is instead a patient count tied to a spatial proximity rule. A correlation coefficient, its uncertainty, or a formal test of association is not reported in the registry record. Readers should therefore distinguish the title's wording from the outcome's stated measurement.

What does the spatial rule contribute?

The definition identifies a response as meeting the endpoint when it falls within 3 pixels of a location where CT identified epicardial adipose tissue. The registry states the conversion as 0.625x3=1.875mm. In general, a prespecified proximity threshold turns a spatial assessment into a reproducible classification rule: observations meeting the threshold can be counted according to that rule. Interpretation still depends on how locations were identified, how images and stimulation responses were matched, and how ambiguous observations were handled. These implementation details are not reported in the registry record.

Spatial proximity alone does not establish that one feature causes another or that a mapped location is a definitive anatomical reference. In general, evaluating accuracy or agreement requires a clearly defined reference and a method for assessing mismatches as well as matches. The registry record does not describe such an accuracy analysis. The primary endpoint should be understood as the stated count of patients meeting the proximity criterion, not as proof of localization accuracy.

How would uncertainty be assessed?

In general, a point estimate gives a single summary of an observed sample, while a confidence interval conveys statistical uncertainty around that estimate under a specified model. For a count or proportion, the denominator and assumptions used to construct an interval matter. A narrow interval generally indicates greater statistical precision than a wide interval, but precision is not the same as freedom from bias or clinical importance. No primary endpoint estimate, confidence interval, or model is reported in the registry record, so the precision of the finding cannot be evaluated.

The registry entry does not report an inferential test, a p-value, an adjusted estimate, or a prespecified statistical analysis for the primary endpoint. The number of analyses listed is 0. This does not establish what analyses were performed outside the registry; it means that analyses are not detailed in the registry record. In general, a p-value addresses compatibility of data with a statistical null model under assumptions. It does not give the probability that a hypothesis is true, and it cannot replace an estimate of effect and its uncertainty. No p-value is available for interpretation in this record.

Why does the observational allocation matter?

The study is described as observational, with allocation among 8 GP ablation approaches in a non-randomized fashion. In general, randomization can help balance measured and unmeasured participant characteristics across comparison groups, while non-randomized allocation may leave groups different at baseline. If outcomes are compared across approaches, differences may reflect those group characteristics, the procedure, or other factors. This is why a causal interpretation requires caution. The registry does not report the allocation mechanism, group-level characteristics, a like-for-like control comparison, or an adjusted comparison of approaches.

The record does not describe a sample-size justification for the study's own design. Planning illustrations use a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect specified as a fraction of the observed effect. They are described as planning illustrations rather than the trial's design basis. In general, a planning calculation asks what sample size might be needed under assumptions about the effect and analysis; it is not observed power and does not establish what the study could reliably detect. The observed effect used for those illustrations is not reported in the registry record. The illustrations should not be read as evidence that the trial was designed around a particular clinically meaningful effect.

What does over-dispersion mean in general?

For count outcomes, a statistical model may assume a particular relationship between the average count and its variability. Over-dispersion means that observed variability is greater than the model assumes. If it is ignored, standard errors can be too small and uncertainty may be understated. This general issue is most relevant when analyzing variable counts across participants or groups. The primary measure in this study is defined as a number of patients meeting a criterion, and the registry record does not report a count model or an over-dispersion assessment. This concept should not be taken to imply that over-dispersion occurred in this study.

What can be concluded from the recorded methods?

The design and endpoint describe a procedural mapping question, but the registry record does not report the statistical analysis needed to assess the endpoint's observed value and precision. In general, a complete analysis would make clear the analysis population, denominator, handling of missing or unevaluable observations, endpoint calculation, and uncertainty method. These details are not reported in the registry record. Without them, the endpoint cannot be independently interpreted as an estimate of spatial correspondence or compared across approaches.

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("Atrial Fibrillation Ablation")
n      <- c(19)
events <- c(3)
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  Atrial Fibrillation Ablation  19  3  15.8  3.4  39.6  5.5  37.6  5.7  37.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and secondary outcomes covering elimination of HFS responses, elimination of global vagal responses, and changes in signal amplitude, duration and fractionation at ablation sites. Considering several outcomes can raise a multiplicity issue: in general, the more statistical tests performed, the greater the chance of at least one apparently unusual result under a set of null hypotheses. Methods such as prespecifying a primary outcome or adjusting for multiple testing can address particular multiplicity concerns, but the appropriate strategy depends on the study aims and analysis plan.

A multiplicity strategy, including whether secondary outcomes were treated as exploratory or whether any adjustment was used, is not reported in the registry record. The record lists 0 analyses, so it does not provide test results or a documented testing hierarchy from which to assess multiplicity in practice. No multiplicity adjustment should be assumed.

Missing-data handling and the analysis populations are also not reported in the registry record. The record does not state how many participants contributed data to the primary endpoint, whether any procedure-level observations were unevaluable, or how missing outcome information was treated. In general, missingness can affect both the number included in an analysis and the interpretation of the result, particularly if the reason data are unavailable is related to the outcome. No such pattern can be assessed from the registry entry.

The enrollment entry alone does not identify the endpoint denominator or establish that all enrolled participants contributed to every outcome. The record also does not describe an intention-to-treat or per-protocol population, and no imputation or sensitivity analysis is reported. As a result, readers cannot assess whether analyses used a consistent population across outcomes or whether missing data could have affected the estimates.

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.

For the listed Atrial Fibrillation Ablation group, the registry reports 19 participants at risk for the serious adverse event measure and 0 affected. It reports 19 at risk for other adverse events and 0 affected, with 0 deaths. These are the safety figures recorded for this group; the registry does not list serious adverse event terms.

The enrollment entry is 30, while the safety denominators are 19. The reason for the difference, the safety follow-up period, and the method used to collect or classify events are not reported in the registry record. The figures should therefore be read with their stated denominators, rather than treated as a complete account of safety for every enrolled participant. In general, a zero count in a recorded group means that no events were entered for that measure and denominator; it does not establish that an event is impossible or that all potential events were captured.

The record does not provide details about event severity beyond the serious and other categories, timing, relatedness to the procedure, or completeness of follow-up. These figures are descriptive registry entries. They do not establish a comparative safety profile because the study is not presented as a randomized comparison with a control group, and no comparative safety analysis is reported in the registry record.

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

The registry record establishes that a prospective, single-center observational study of CT- and HFS-guided GP mapping and ablation was completed. It specifies a primary procedural measure: a count of patients with an HFS response within the stated distance of a CT-identified epicardial adipose tissue location. These details describe what the study set out to assess, not what it found.

The primary result is not reported in the registry record. There is no reported count meeting the criterion, endpoint denominator, estimate of uncertainty, or statistical test. The record therefore does not show how frequently the criterion was met or how precisely that frequency was estimated. It also does not report results for the listed secondary outcomes. The study's completed status should not be interpreted as a result in itself.

The primary endpoint is procedural and spatial. Even if a result were available, a count of responses meeting a proximity definition would not by itself establish that the mapping approach improves patient outcomes. The registry record does not report a clinical endpoint such as subsequent atrial fibrillation recurrence. Nor does it report a randomized control comparison that could support a causal estimate of the effect of GP ablation versus an alternative.

The description of non-randomized allocation among 8 GP ablation approaches also limits what could be concluded from comparisons between those approaches. In general, differences between non-randomized groups can reflect selection or other group differences as well as the intervention. The registry record does not provide approach-specific results or details needed to assess those comparisons.

The sound conclusion is narrow: the registry documents a procedural mapping study and defines a spatially based primary count, but its outcome results and analysis details are not reported in the registry record. No conclusion about clinical efficacy, comparative effectiveness, or the precision of the primary finding can be drawn from the recorded information.

14. Why This Trial Matters Statistically

This study raises a statistical question about how to evaluate a mapping strategy when the target is defined through the spatial relationship between imaging and a procedural stimulation response. The endpoint makes that question concrete by defining a proximity criterion and counting patients whose responses meet it. Such operational definitions matter because a broad phrase such as “correlation” can suggest a statistical association, while the recorded measure is a count based on a threshold.

For biostatisticians and clinical researchers, this distinction illustrates why an endpoint's title, unit, and calculation should be read together. Counts, proportions, association measures and accuracy measures answer different questions. A patient count alone does not quantify the strength of association or establish agreement with a reference standard. Clear reporting of the numerator, denominator, spatial matching procedure and uncertainty would help readers understand what the measure represents.

The design also highlights the interpretation challenges of non-randomized procedural comparisons. The registry describes allocation among 8 ablation approaches without randomization, but does not report allocation details or comparison results. In general, a credible comparison must distinguish the effect of an approach from potential differences in who received it and how procedures were carried out. That challenge is especially relevant when study aims include choosing an optimal strategy.

Finally, registry completeness is part of statistical interpretation. The outcome definitions and completed status are recorded, but primary and secondary results, missing-data methods and analysis details are not reported in the registry record. A design entry can identify what was intended to be measured; without results and analysis information, it cannot convey the observed evidence or its precision. This separation between trial registration and transparent results reporting is important when judging how much a clinical study can support.

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 main limitation of the available record is that it does not report results for the primary or secondary outcomes. The primary endpoint's observed count, denominator and uncertainty are not reported in the registry record. Consequently, readers cannot assess the magnitude or precision of the endpoint, or determine how many participants contributed data.

The study is described as observational and single-center. Its allocation among 8 approaches is described as non-randomized, but the allocation mechanism and approach-specific group sizes are not reported in the registry record. The record does not describe a like-for-like control group or provide baseline characteristics that would help evaluate comparability. Any comparison across approaches would therefore require caution, and no such result is reported.

The outcome itself is a procedural spatial measure. The registry supplies a distance threshold, but does not report details of image interpretation, mapping adjudication, repeatability, or how ambiguous locations were classified. It also does not describe a reference standard or a formal accuracy analysis. These omissions limit assessment of how reliably the endpoint represents spatial correspondence.

The analysis population, missing-data handling, statistical methods and multiplicity strategy are not reported in the registry record. The safety denominator is 19, while the enrollment entry is 30; the reason for that difference is not reported. Safety follow-up and event ascertainment details are also absent. The listed enrollment and completed status do not resolve these uncertainties.

Finally, the registered primary outcome is not a clinical outcome. The record does not report subsequent atrial fibrillation outcomes or a comparative clinical effectiveness analysis. Thus, even a positive spatial mapping result would not by itself establish a change in clinical outcomes. Since no endpoint results are reported, the record cannot support such an inference in any case.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Prospective Evaluation of CT Guided Ablation of Cardiac Ganglionated Plexi — NCT04642976.
• Registry record last updated 2024-10-15; status last verified 2024-10.
• Results first posted 2024-10-15.
• 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

NCT04642976 is a completed, prospective, observational, single-center study sponsored by the University of Pennsylvania. The registry lists an enrollment of 30 and dates of 2021-01-20 for study start and 2024-01-01 for primary completion. It concerns patients with atrial fibrillation undergoing catheter ablation with pulmonary vein isolation, using pre-procedural CT and HFS-guided GP mapping and ablation.

The primary outcome is a count of patients with an HFS response within 3 pixels, stated as 0.625x3=1.875mm, of a CT-identified epicardial adipose tissue location during the procedure. The record describes non-randomized allocation among 8 GP ablation approaches. It lists secondary measures concerning response elimination and signal changes.

Primary and secondary outcome results, analysis methods, missing-data handling and multiplicity procedures are not reported in the registry record. The listed safety group has 19 at risk for each adverse event measure, with 0 affected for serious events, 0 for other events and 0 deaths.