Prospective Elimination Of Distal Coronary Sinus-Left Atrial Connections for Atrial Fibrillation Ablation Trial: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prospective Elimination Of Distal Coronary Sinus-Left Atrial Connections for Atrial Fibrillation Ablation Trial (NCT03646643), a randomized na study. The primary outcome is Recurrence Rate of Atrial Arrhythmias.

2. Clinical Question

The trial addresses whether targeting a possible arrhythmia trigger alongside standard ablation is associated with recurrence during follow-up. The registry’s background states that distal connections between coronary sinus musculature and left atrial musculature may provide a substrate for reentry beats that can trigger atrial fibrillation. This is the rationale stated in the record, not evidence that the connection is responsible for recurrence in every participant.

The comparison is between two procedural strategies, not between ablation and no ablation. Both arms include pulmonary vein isolation and non-pulmonary-vein trigger ablation; one arm adds elimination of the coronary sinus–left atrial connection. The registry describes distal coronary sinus pacing to localize the earliest connection in that arm, aside from septal connections. Further procedural details are not reported in the registry record.

The intended outcome is a recurrence after the 90-day post-ablation blanking period, with follow-up to 180±45 days post-ablation. The registry record does not report the number of recurrences, the estimated difference between arms, or uncertainty around an effect estimate. Therefore, the clinical question is clear, but the posted record does not provide results that answer it.

3. Trial Design

The trial is recorded as randomized, double-masked, and parallel-group, with an enrollment of 35. Its status is completed. The record lists the study start as 2018-08-18 and primary completion as 2019-11-20. The phase is recorded as NA. The sponsor is the University of Pennsylvania.

Participants were assigned to one of two procedural strategies. The comparator arm received atrial fibrillation ablation with conventional pulmonary vein isolation and non-pulmonary-vein trigger ablation. The intervention arm received those procedures plus elimination of a coronary sinus–left atrial connection. The registry describes distal coronary sinus pacing to localize the earliest connection, aside from septal connections. The remaining details of the procedure are not reported in the registry record.

Random allocation is intended to create groups that are comparable on average, including with respect to factors that might affect recurrence. In a small trial, however, randomization does not guarantee that the groups will be similar in every characteristic. The record does not report the allocation sequence method, concealment procedures, or which people were masked. It identifies the trial as double-masked but does not specify the masked roles or how masking was maintained during a procedural comparison.

The registry reports an enrollment of 35, while the safety summaries use 15 participants at risk in each arm. The record does not explain how those safety denominators relate to enrollment, such as whether they refer to a particular analysis population or follow-up set. It also does not report the number randomized to each arm for the primary endpoint or the number included in its analysis.

The study is described as examining suppression of recurrent atrial arrhythmias after ablation. The registry specifies survival statistical models for the primary endpoint, but does not report model details or primary endpoint results. A sample-size justification, planned interim analyses, and other statistical-plan details are 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:

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.

Population: The study is a single-center, randomized, controlled trial, enrolling drug-refractory symptomatic patients who presented for first-time AF ablation at the Hospital of the University of Pennsylvania between August 2018 and August 2019.

6. Primary Endpoint

The registry lists the primary outcome as Recurrence Rate of Atrial Arrhythmias, measured over Time to atrial arrhythmia recurrence will be recorded as time to the first ECG or monitor that shows atrial arrhythmia recurrence between the end of the blanking period (90 days post ablation) and the end of the study (180±45 days post ablation)..

The primary endpoint is the recurrence rate of atrial arrhythmias, assessed as time to the first qualifying recurrence after the 90-day post-ablation blanking period. A qualifying event is a non-self-terminating episode of atrial fibrillation, atrial flutter, or atrial tachycardia lasting more than 30 seconds. Recurrence is identified by an ECG or monitor. If no atrial fibrillation occurs during the study period, the record says censoring occurs at 180±45 days post-ablation.

Time to event is useful when the timing of recurrence matters and participants may have different lengths of observation. In general, survival methods use both whether an event occurred and how long a participant remained under observation before recurrence or censoring. Censoring means that the exact event time is not observed during the defined follow-up; it is not itself evidence that recurrence could never occur.

The blanking period separates early post-procedure events from the period used for the primary outcome. The registry sets this period at 90 days and defines the end of follow-up as 180±45 days after ablation. The record does not report how recurrence was adjudicated, how monitoring was scheduled, or how episodes detected outside scheduled monitoring were handled. Although the endpoint definition is stated, its arm-level results and survival estimates are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Why use a time-to-event outcome?

The endpoint is defined by time from ablation to the first qualifying atrial arrhythmia recurrence after the 90-day blanking period. In general, time-to-event methods are appropriate when both event occurrence and timing are relevant, and when participants may have unequal observation time. The analysis can use information from participants whose event has not been observed by the end of follow-up, rather than treating every such participant as though the event time were known.

The registry says that survival statistical models will measure time to failure between the two arms. Failure is defined as a non-self-terminating episode of atrial fibrillation, atrial flutter, or atrial tachycardia lasting more than 30 seconds after the blanking period. If no AF occurs during the study period, censoring is stated to occur at 180±45 days post-ablation. The specific model, its assumptions, and its parameterization are not reported in the registry record.

What does censoring mean?

In general, censoring occurs when a participant’s event time is not observed within the analysis window. The participant contributes follow-up information up to the last time they are known not to have experienced the event, but the exact later event time is unknown. Proper interpretation depends on how censoring arises and on the assumptions used by the analysis. The registry gives a censoring time for participants with no AF during the study period, but does not describe other possible reasons for censoring or how they would be handled.

Censoring is not equivalent to proof that an event will never occur. It marks the limit of the observation used in the analysis. For this trial, the stated follow-up endpoint is 180±45 days post-ablation. The record does not explain how variation within that follow-up window affects analysis time or whether all participants had the same monitoring schedule.

How should an effect estimate be read?

In general, a time-to-event analysis may report a comparison of event rates over time or a relative measure of time to event, depending on the selected model. The meaning of an estimate depends on the model and on its assumptions. For example, some models rely on a proportional-hazards assumption: the relative event rate is treated as stable over the observed follow-up. The registry does not name the model or state whether this assumption was assessed, so no model-specific interpretation can be made.

Confidence intervals communicate uncertainty around an estimate. In general, they show the range of values compatible with the observed data under the analysis method and its assumptions. They are not a guarantee that the true effect lies within the interval, and they do not describe the probability that a particular treatment effect is true. The registry record does not report a primary effect estimate or confidence interval, so neither the estimated effect nor its precision can be evaluated.

A p-value, if reported, would address compatibility between the observed data and a specified statistical null model. In general, it does not measure clinical importance, the probability that the null hypothesis is true, or the size of an effect. The registry does not report a primary endpoint p-value. Without an effect estimate and uncertainty interval, a significance test alone would not convey the magnitude or precision of a comparison in any case.

What is over-dispersion, and is it relevant?

In general, over-dispersion occurs when count outcomes vary more than expected under a statistical model’s assumptions. It can make standard errors too small if the extra variability is ignored. The registered primary endpoint is a time-to-first-recurrence outcome, not a count of repeated events, so the registry’s stated primary analysis is survival-based. The record does not describe a repeated-event count analysis or report a model that would allow assessment of over-dispersion. This general concept should not be taken as a claim that over-dispersion affected this trial.

What do planning illustrations mean?

In general, sample-size calculations are planning tools that depend on assumptions about the effect to detect, variability or event frequency, significance level, allocation, and analysis method. The assumptions described for the planning illustration use a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is specified as a fraction of the observed effect. Time-to-event illustrations use a total number of events, while other illustrations use participants per arm. These are planning illustrations, not the trial’s own design justification and not observed power.

Observed power is not a substitute for reporting the estimated effect and its uncertainty. A completed study’s results are more informatively described by the event data, effect estimate, and confidence interval. The registry record does not report a sample-size justification, the planning values, or the primary endpoint estimates needed to evaluate the study’s precision. No sample-size calculation can fill in the missing outcome results.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome measure, but the outcome description includes several arrhythmia types: atrial fibrillation, atrial flutter, and atrial tachycardia. It also defines a time window after the 90-day blanking period and follow-up through 180±45 days post-ablation. The record does not report whether additional outcome measures, subgroup analyses, or multiple model specifications were part of the prespecified analysis plan, nor whether any adjustment for multiple testing was planned.

In general, multiplicity arises when several hypotheses or comparisons are tested. The more analyses considered, the greater the opportunity for a nominally unusual result to occur by chance if each is interpreted independently. Whether an adjustment is appropriate depends on the analysis plan and the inferential purpose. Since the registry does not report the full statistical analysis plan or primary endpoint results, it is not possible to assess how multiplicity was addressed.

The record does not describe missing-data procedures for the primary endpoint, the handling of incomplete monitoring, or the treatment of withdrawal and loss to follow-up. It states that censoring occurs at 180±45 days post-ablation if no AF occurs during the study period, but does not provide additional censoring rules or report the extent of missing endpoint information. In general, missing outcome data and censoring can affect a time-to-event comparison if the reasons they occur are related to the likelihood of recurrence.

The registry does not identify the primary analysis population, such as whether analysis followed randomized assignment or included only participants who received the assigned procedure. It also does not report how many participants were analyzed for the primary outcome. These omissions limit assessment of the analysis population, departures from the randomized groups, and the potential effect of missing observations.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: pericarditis (6.7%).

The registry’s safety summary lists 15 participants at risk in each arm. In the arm receiving pulmonary vein isolation and non-pulmonary-vein trigger ablation plus coronary sinus–left atrial connection elimination, one serious adverse event is listed. In the comparator arm, none is listed. The summary reports zero other adverse events in both arms and zero deaths in both arms.

These figures are counts within the stated risk groups. They are descriptive and do not, by themselves, establish that the intervention caused or prevented an event. With small event counts, estimates of comparative safety would be imprecise; the registry does not report a comparative effect estimate or confidence interval for adverse events. The total enrollment is 35, while the safety denominators are 15 per arm; how these denominators relate to the enrolled population is not reported in the registry record.

Pericarditis is listed among the top serious adverse event terms at 6.7%. The registry does not identify the arm associated with that term or provide further event-level details. The listed safety summary does not establish the timing, duration, severity beyond the serious classification, or relationship of the event to the procedure. No deaths are listed, but this limited summary should not be interpreted as evidence that no other safety concerns occurred outside the reported categories or observation period.

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

The trial asks a focused procedural question: whether adding elimination of a coronary sinus–left atrial connection to atrial fibrillation ablation is associated with a different time to recurrent atrial arrhythmia. The randomized, double-masked, parallel design is intended to support a comparison between the two strategies. The registered endpoint and event definition make clear what recurrence was meant to capture.

However, the registry record does not report the primary endpoint results. It gives no arm-specific recurrence counts, time-to-event estimates, effect size, confidence interval, or p-value. As a result, the posted information does not show whether recurrence was more or less frequent in either group, when events occurred, or how precisely a difference could be estimated. The absence of reported results is not evidence of no difference.

Even when trial results are available, an estimated average effect does not imply that every participant has the same outcome. In general, a group comparison describes outcomes under the study conditions and depends on the population, procedures, follow-up, endpoint definition, and analysis. The registry does not provide detailed eligibility criteria, monitoring procedures, the full statistical analysis plan, or primary outcome data. Those omissions restrict interpretation of how broadly any eventual estimate might apply.

The safety figures offer limited descriptive information: one serious adverse event is listed in the additional-procedure arm and none in the comparator arm, with no deaths listed. The small risk denominators and lack of a comparative uncertainty estimate mean that these counts cannot establish a precise difference in safety. The registry also does not report the arm associated with the listed pericarditis term.

Accordingly, the record supports understanding the study question, design, and intended outcome, but not an efficacy or safety conclusion. The intervention’s effect on recurrence and the precision of any comparison are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because it compares two procedural strategies that share core components and differ by an added connection-elimination procedure. That structure makes the intended contrast specific: the additional procedure is evaluated alongside conventional pulmonary vein isolation and non-pulmonary-vein trigger ablation, rather than against no ablation.

The primary outcome is time to first recurrence after a defined blanking period, not simply the presence of any rhythm event during the entire post-ablation period. The use of a time-to-event framework recognizes that both the occurrence and timing of recurrence matter, and that follow-up may end without an observed recurrence. Understanding the event definition, blanking period, and censoring time is therefore central to interpreting the intended analysis.

Randomization and masking are important design features, but a design label is not a substitute for reported methods and results. The record does not identify the masking roles, allocation procedures, primary analysis population, or model specification. It also does not report endpoint estimates or their uncertainty. These gaps illustrate why readers need both a clear protocol-level question and transparent outcome reporting to evaluate a trial’s evidence.

The enrollment of 35 and the safety denominators of 15 per arm also underscore the importance of knowing exactly who contributed to each analysis. Small studies can produce estimates with substantial uncertainty, particularly when outcomes are relatively uncommon. Without the primary event counts and estimates, however, the precision of this trial’s comparison cannot be quantified.

Finally, the posted safety counts are useful as descriptive observations but do not provide a definitive comparative safety analysis. The record supplies a limited count of serious events and deaths, but not a detailed account of event attribution or uncertainty. The study matters statistically as an example of how the design and endpoint can be described clearly while the available registry record remains insufficient to judge the primary result.

14. 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 for interpretation is that primary outcome results are not reported in the registry record. The record does not give recurrence counts by arm, a time-to-event estimate, a confidence interval, or a p-value. Without these, neither the direction nor magnitude of the primary comparison can be assessed.

Several details needed to evaluate the analysis are also not reported: the survival model, model assumptions, analysis population, handling of missing endpoint information, censoring beyond the stated rule, and any multiplicity strategy. The registry says the primary endpoint will be assessed with survival statistical models, but does not identify the particular model or provide its results.

The registry describes the study as double-masked but does not identify which parties were masked or explain how masking was maintained in a procedural trial. It also does not provide detailed eligibility criteria, monitoring frequency, adjudication procedures, or full procedural details. These gaps limit evaluation of outcome ascertainment and the applicability of any potential findings.

The total enrollment is 35, whereas the adverse-event summary lists 15 participants at risk in each arm. The registry does not explain the relationship between those numbers or report the primary endpoint analysis denominators. The safety summary is limited to counts, does not provide comparative uncertainty, and does not assign the pericarditis term to an arm. Finally, a sample-size justification and interim-analysis plan are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Prospective Elimination Of Distal Coronary Sinus-Left Atrial Connections for Atrial Fibrillation Ablation Trial — NCT03646643.
• Registry record last updated 2024-11-29; status last verified 2024-10.
• Results first posted 2024-11-29.
• 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.

18. Record Summary

NCT03646643 is a completed randomized, double-masked, parallel-group trial sponsored by the University of Pennsylvania, with an enrollment of 35. The study compared atrial fibrillation ablation with conventional pulmonary vein isolation and non-pulmonary-vein trigger ablation against the same approach with additional coronary sinus–left atrial connection elimination.

The primary outcome was time to first qualifying atrial arrhythmia recurrence after the 90-day post-ablation blanking period, with follow-up through 180±45 days post-ablation. The registry defines recurrence as a non-self-terminating episode of atrial fibrillation, atrial flutter, or atrial tachycardia lasting more than 30 seconds.

The registry record does not report primary outcome results or key details of the statistical analysis. Its safety summary lists one serious adverse event among 15 participants at risk in the additional-procedure arm and none among 15 at risk in the comparator arm; no deaths are listed. The relationship between the safety denominators and total enrollment is not reported.