Characterising the Stable and Dynamic Left Atrial Substrate in Atrial Fibrillation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Characterising the Stable and Dynamic Left Atrial Substrate in Atrial Fibrillation (NCT04229472), a non-randomized na study. The primary outcome is To Define the Normal Range of Voltage Amplitude.

2. Clinical Question

The broader scientific question concerns how stable structural features and dynamic conduction patterns in the left atrium relate to atrial fibrillation. The study description identifies voltage amplitude as a mapping measure that may reflect tissue properties, while noting that recorded signals can depend on mapping technology and pacing rate. It also describes assessment of electrogram morphology and conduction velocity at different pacing cycle lengths, and comparisons with cardiac magnetic resonance findings.

This is a characterization question rather than a randomized test of a treatment. The registry record does not report numerical primary outcome results, so it does not establish the measured normal range or quantify how the mapping measures relate to each other.

3. Trial Design

The registry record describes a completed, nonrandomized, parallel-group study sponsored by Oxford University Hospitals NHS Trust. Enrollment is listed as 31. The recorded start date is 2020-12-07, and primary completion is recorded as 2023-11-02. The phase is listed as NA. Masking is listed as none.

Three groups are described: a normal subject control group, an atrial fibrillation group, and an AcQMap atrial fibrillation group. The normal subject control group is described as undergoing high density mapping of left atrial voltages in patients with supraventricular tachycardia. The atrial fibrillation group is described as undergoing high density mapping of left atrial voltages. The AcQMap group is described as undergoing high density mapping of left atrial voltages and AcQMap propagation-pattern assessment alongside cardiac MRI.

Because allocation was nonrandomized, group membership should not be treated as assigned by chance. The groups also differ in their described procedures and populations, so a simple contrast between them would not isolate the effect of a single intervention. The registry record does not report the method used to assign participants to groups or further details about eligibility and recruitment.

The study description says mapping was to assess the effect of pacing rate on conduction properties, using signal morphology and conduction velocity. The primary outcome concerns the mean and distribution of left atrial voltage amplitude across the chamber and by segments. Secondary outcome descriptions include comparisons of mapping technologies, electrogram morphology and velocity, and MRI late gadolinium enhancement. The registry record does not report numerical outcome results or analysis records.

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

Analysis population for the primary outcome, as defined in the registry: It was not possible to maintain sinus rhythm during recordings at long pacing cycle lengths in all patients.

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: Due to recruitment challenges during the COVID-19 pandemic, we were unable to enroll normal subjects as initially planned.

6. Primary Endpoint

The registry lists the primary outcome as To Define the Normal Range of Voltage Amplitude, measured over During ablation procedure.

The primary outcome is titled “To Define the Normal Range of Voltage Amplitude.” It is a continuous measure expressed in mV, summarized as a mean with standard deviation, with a timeframe of during the ablation procedure. The description specifies voltage amplitude across the whole left atrium and by segments. It defines the lower limit of normal using the upper 95% value within the segment with the lowest mean amplitude at long pacing cycle length.

In general, a continuous measure preserves information about the magnitude of a recorded signal rather than reducing it to a category. A mean describes the central value of a set of measurements, while a standard deviation describes their spread around that mean. Reporting both can help readers distinguish the average signal level from variability across measurements. The registry record does not report the actual means, standard deviations, segment-level values, or the resulting lower limit of normal.

The endpoint is relevant to the study’s stated aim of characterizing left atrial electrical signals. The record describes voltage amplitude as a surrogate measure of tissue properties, and the study aims to examine how mapping and pacing conditions relate to those signals. A numerical result would be needed to assess the range observed in the study. The endpoint description alone is not a result and does not establish a clinical threshold or diagnostic performance.

The record also notes that it was not possible to maintain sinus rhythm during recordings at long pacing cycle lengths in all patients. This is important context for interpreting the planned endpoint because the stated definition refers to long-cycle-length recordings. The number of affected participants, the handling of unavailable measurements, and the resulting impact on the endpoint are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a continuous endpoint represent?

Left atrial voltage amplitude is recorded as a continuous quantity in mV. In general, continuous measurements can take a range of values, and summaries such as a mean and standard deviation describe different features of that range. The mean describes the central level of the observed measurements. The standard deviation describes how dispersed measurements are around that central level. A mean alone would not show whether values cluster tightly or vary substantially.

The primary outcome description specifies summaries across the whole chamber and by segments. Segment-level summaries can make spatial variation visible, while a whole-chamber summary gives an overall description. Those summaries answer related but different questions: a chamber-wide average can conceal local variation, whereas segment summaries focus attention on differences by location. The registry record does not report the measured values or the number and definition of the segments.

How should the stated normal-range definition be understood?

The record defines a lower limit of normal using the upper 95% value within the segment with the lowest mean amplitude at long pacing cycle length. This is part of the endpoint description, not a reported numerical finding. It should not be mistaken for a confidence interval around the primary outcome or for a threshold that has been validated in other populations. The registry record does not report the value of this limit, its uncertainty, or a validation assessment.

In general, a reference range or threshold depends on how the population and measurement conditions are defined. Here, the stated definition is tied to a particular segment-selection rule and pacing condition. Interpretation therefore depends on the measurements available under that condition. The registry record notes that sinus rhythm could not be maintained at long pacing cycle lengths in all patients, but does not describe how this affected the calculation.

Why do pacing conditions matter?

The study description says that mapping was to be conducted while pacing at long and short cycle lengths to assess effects on conduction properties, including signal morphology and conduction velocity. As a general measurement principle, conditions under which a signal is recorded can affect the observed values. Comparing measurements under different pacing conditions can therefore help characterize whether a measure is stable or changes with the condition. The registry record does not report the actual paired or group-level comparisons, estimates, or statistical tests.

The inability to maintain sinus rhythm for some long-cycle-length recordings is relevant because measurements may not be available in the same way for every participant. If the availability of a measurement is related to participant features or observed electrical characteristics, analyses limited to available recordings may not represent everyone enrolled. This is a general concern, not a finding about the study; the record does not provide enough information to determine whether such a pattern occurred.

What can a confidence interval add?

In general, a confidence interval expresses uncertainty around an estimate under a specified statistical model and sampling process. It can help readers distinguish a relatively precise estimate from one with substantial uncertainty. A point estimate without an interval gives less information about precision. No confidence intervals for the primary or secondary outcomes are reported in the registry record, and no significance tests or model estimates are listed.

Standard deviation and confidence interval are not interchangeable. Standard deviation describes variability among measurements; a confidence interval describes uncertainty in an estimated quantity. The primary outcome description names mean and standard deviation, but does not state a confidence-interval method. It is therefore not possible to infer the uncertainty around the proposed normal limit from the endpoint description.

How do the group descriptions affect interpretation?

The design is listed as nonrandomized and parallel. In general, random allocation can help balance measured and unmeasured participant characteristics across groups, while nonrandomized group membership can leave differences that influence observed comparisons. This does not make descriptive comparisons unusable, but it limits causal interpretation. The registry record explicitly cautions that the arms are not a like-for-like control comparison.

The groups also have different descriptions: one involves patients with supraventricular tachycardia, one involves atrial fibrillation, and one involves atrial fibrillation with AcQMap propagation-pattern assessment alongside cardiac MRI. Differences in population and measurement procedures make it especially important to distinguish a descriptive comparison from an estimate of an intervention effect. The registry record does not report a statistical adjustment strategy.

What can be inferred from the analysis record?

The registry record lists ten outcome measures and no analysis records. This means that the posted record does not provide a documented set of outcome-specific estimates or statistical tests to interpret. It does not establish which modeling approach was used, whether outcomes were adjusted for covariates, how repeated or segment-level measurements were handled, or whether sensitivity analyses were performed. Those details are not reported in the registry record.

In general, repeated measurements from the same participant are not independent observations. A suitable analysis may need to account for within-participant correlation, especially when measurements are taken across locations or pacing conditions. This is a general statistical consideration, not a claim about the method used in this study. The registry record does not report the analysis approach for such measurements.

Likewise, mapping measures and MRI findings may be compared using methods suited to their scales and distributions. The record lists objectives involving electrogram amplitude, morphology, conduction velocity, and late gadolinium enhancement, but does not report how any such association was quantified. No effect estimates, uncertainty measures, or model specifications are available in the registry record. Statistical interpretation must therefore remain focused on the stated objectives and design rather than undocumented analyses.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Atrial Fibrillation Group", "AcQMap Atrial Fibrillation Group")
n   <- c(9, 8)
m   <- c(2, 1.92)
sp  <- c(2.39, 2.37)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Atrial Fibrillation Group  9  2.000  2.390  0.163  3.837
CARM  AcQMap Atrial Fibrillation Group  8  1.920  2.370  -0.061  3.901

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists ten outcome measures, including the primary voltage-amplitude objective and secondary objectives concerning pacing cycle length, electrogram morphology, conduction velocity, comparisons between mapping approaches, and MRI late gadolinium enhancement. When a study examines multiple outcomes or multiple comparisons, the chance of finding at least one apparently notable result can increase. In general, multiplicity procedures can control that risk, but no multiplicity adjustment or testing hierarchy is reported in the registry record.

The record lists no analysis records. It does not report which outcomes were analyzed, the order in which they were considered, whether analyses were exploratory or confirmatory, or how any multiplicity was handled. No conclusions about statistical significance or selective reporting can be drawn from those omissions alone.

The primary outcome description states that it was not possible to maintain sinus rhythm during recordings at long pacing cycle lengths in all patients. This identifies a potential source of unavailable measurements for an important condition in the endpoint definition. The number affected, reasons for unavailable recordings, and handling of missing values are not reported in the registry record. There is also no reported description of an analysis population for each endpoint, or of sensitivity analyses for missing measurements.

In general, missing-data interpretation depends on how much information is absent and whether its absence is related to participant characteristics or measurements. Without those details, readers cannot assess whether analyses based only on available recordings might differ from analyses that included all enrolled participants. Enrollment is listed as 31, but the number contributing to each outcome is 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 0% reporting threshold.

The registry record lists serious adverse events, other adverse events, and deaths for the named groups. For the normal subject control group, the recorded at-risk counts are 0 for serious events and 0 for other events, with 0 deaths. For the atrial fibrillation group, 18 are listed at risk for serious events and 18 for other events; the recorded affected counts are 0 and deaths are 0. For the AcQMap atrial fibrillation group, 10 are listed at risk for serious events and 10 for other events; the recorded affected counts are 0 and deaths are 0.

These are registry safety counts, not a comparative safety analysis. The control group has 0 listed at risk in these safety fields, so its zero affected count should not be read as evidence that participants in that group were observed without events. The record does not report the safety observation window, event ascertainment procedures, or additional detail about the groups’ safety populations.

A recorded zero means no affected events are entered for the specified group and category in the registry record. It does not prove that an event is impossible or that the study can rule out uncommon harms. The registry record lists no top serious-event terms. These safety entries should be interpreted descriptively and separately from the study’s mapping outcomes.

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

The registry record establishes that the study was designed to characterize left atrial voltage amplitude and related electrical mapping features in the context of atrial fibrillation. It describes a primary objective to define a normal range, along with secondary questions involving pacing conditions, mapping approaches, and cardiac MRI. It also records that long-cycle-length sinus-rhythm recordings could not be maintained in all patients.

What the record does not establish is the observed normal range, the measured voltage values, or the magnitude and precision of any differences or associations. Numerical outcome results are not reported in the registry record. The stated endpoint definition is not itself an empirical result, and the study objectives do not show that a particular mapping measure corresponds to a specific tissue state or predicts a clinical outcome.

The nonrandomized design also limits what can be concluded from comparisons between groups. The groups differ in their descriptions, and the record cautions that they are not a like-for-like control comparison. In general, such differences can complicate attribution: an observed contrast may reflect participant or procedural differences rather than the mapping method alone. The registry record does not report an adjustment strategy that would address this concern.

The study is therefore best understood as a measurement and characterization project. Its stated questions may help describe how left atrial signals vary by location, pacing condition, and mapping approach, but the registry information does not provide the results needed to judge those patterns. It also does not report evidence about treatment benefit, clinical outcomes, or the diagnostic performance of any proposed threshold. No medical decision should be inferred from the endpoint description or safety counts alone.

14. Why This Trial Matters Statistically

This study raises an important statistical issue in cardiac mapping: a recorded signal is a measurement made under particular technical and physiological conditions. The registry description specifically identifies pacing cycle length and signal morphology as relevant to left atrial conduction assessment. Considering these conditions together can help distinguish a stable measurement feature from one that varies with the recording context. The registry record states this motivation but does not report the results needed to quantify such variation.

The primary objective also emphasizes spatial structure by describing voltage amplitude across the whole chamber and by segments. Statistically, a single overall average may not capture local heterogeneity. Segment-level summaries can offer a more detailed picture, but they also create analytical questions about how locations are defined, how many measurements contribute, and how dependence among measurements is handled. These methods are not reported in the registry record.

The study also brings together distinct measurement approaches: high density contact mapping, AcQMap propagation patterns, and cardiac MRI findings. Comparing these sources may help characterize how electrical measurements relate to other features, but interpretation depends on measurement quality and analysis choices. The record lists relevant objectives without reporting numerical associations or uncertainty.

Finally, the nonrandomized design is central to statistical interpretation. The study can address descriptive questions about observed measurements, but comparisons across groups do not have the protection against confounding that random allocation can provide. Recognizing that boundary matters: precise measurement and careful description can be valuable without supporting causal claims. Because results and analysis details are not reported in the registry record, the contribution that can be assessed from this record is its measurement framework and stated research questions, rather than its empirical findings.

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 registry record provides limited information for evaluating the study’s statistical execution. It lists enrollment as 31 and describes the groups and objectives, but does not report group enrollment totals for the primary outcome or the number contributing usable measurements. The safety at-risk counts do not establish the analysis population for the mapping endpoints.

The record notes that sinus rhythm could not be maintained during long pacing cycle length recordings in all patients. It does not report how many participants were affected, whether recordings were unavailable for other reasons, or how missing measurements were handled. Because the primary endpoint’s stated definition relies on long pacing cycle length, this limitation is directly relevant to interpretation.

Allocation was nonrandomized, masking was none, and the groups are not described as a like-for-like control comparison. The registry record does not report how participants entered each group or whether analyses accounted for differences among them. These design features limit causal interpretation of between-group contrasts.

Although ten outcome measures are listed, no analysis records or numerical outcome results are reported. Statistical models, uncertainty estimates, adjustment for multiple outcomes, and analysis populations are not reported in the registry record. The record also does not provide detail about the number and definition of left atrial segments or the handling of repeated measurements. These omissions prevent assessment of the precision, robustness, and reproducibility of the stated outcome analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Characterising the Stable and Dynamic Left Atrial Substrate in Atrial Fibrillation — NCT04229472.
• Registry record last updated 2025-08-19; status last verified 2025-07.
• Results first posted 2025-08-19.
• 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

NCT04229472 is a completed, nonrandomized, parallel-group study sponsored by Oxford University Hospitals NHS Trust, with enrollment listed as 31. The recorded start date is 2020-12-07 and primary completion date is 2023-11-02. The phase is listed as NA, and masking is listed as none.

The study concerns high density mapping of left atrial voltage amplitude in atrial fibrillation, with a normal subject control group and an AcQMap atrial fibrillation group also described. Its primary objective is to define a normal range of voltage amplitude across the chamber and by segments. Secondary objectives include assessment of pacing cycle length, morphology, conduction velocity, mapping approaches, and cardiac MRI findings.

Numerical primary and secondary outcome results, analysis details, missing-data handling, and multiplicity methods are not reported in the registry record. The record notes that sinus rhythm was not maintainable for long-cycle-length recordings in all patients, which is relevant to the primary endpoint definition.