Left Atrial Distensibility to Predict Left Ventricular Filling Pressure and Prognosis in Patients With Severe Mitral Regurgitation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Left Atrial Distensibility to Predict Left Ventricular Filling Pressure and Prognosis in Patients With Severe Mitral Regurgitation (NCT01172184), a registered phase not stated study. The primary outcome is Left Ventricular Filling Pressure More Than 15 mmHg Measured by Left Ventricular Catheterization.

2. Clinical Question

The central clinical measurement question is whether a left atrial property can help characterize filling pressure when severe mitral regurgitation affects the accuracy of estimates based on tissue Doppler imaging. The study description presents left atrial volume as a longer-term marker related to diastolic dysfunction, while distensibility is considered in relation to atrial pressure and wall stretch. These are the rationale and questions recorded for the study, not reported findings.

The prognosis aims are broader than the registered primary endpoint. The description names operation mortality, post-operation atrial fibrillation and late heart failure events; the secondary outcome list specifically names post-operation atrial fibrillation and heart failure requiring rehospitalization during follow-up. Numerical results for those outcomes are not reported in the registry record, apart from the serious-event information discussed separately.

3. Trial Design

The registry record describes a completed clinical study sponsored by Kaohsiung Veterans General Hospital. The recorded study start is 2010-07 and primary completion is 2011-01. Enrollment is listed as 111. Its stated focus is the relationship between left atrial distensibility and left ventricular filling pressure among patients with severe mitral regurgitation, with additional interest in prognosis after operation.

The listed procedure is cardiac catheterization. The arm description says that patients with severe mitral regurgitation were admitted for pre-operation cardiac catheterization and were willing to participate. The record does not describe a randomized allocation, and allocation is stated as not stated. It also explicitly cautions that the arms are not a like-for-like control comparison. Therefore, any arm-based comparison should not be treated as a randomized estimate of a treatment effect.

The primary outcome is named as left ventricular filling pressure above 15 mmHg measured by left ventricular catheterization, with a one-year timeframe. Its registered measure type is a mean of a continuous measure, with mmHg as the unit and standard deviation as the dispersion. The description also says that the study assessed correlation between filling pressure and left atrial distensibility and used an ROC curve to estimate a distensibility cut-off for identifying pressure above the stated threshold.

The record lists post-operation atrial fibrillation and heart failure requiring rehospitalization during follow-up as secondary outcomes. It does not report a detailed visit schedule, the method for determining follow-up completion, eligibility criteria beyond the brief arm description, or the statistical analysis plan. Those details are not reported in the registry record. The study is therefore best understood from its stated measurement aims and available outcome entries, without assuming unlisted design features.

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: Severe mitral regurgitation affects the accuracy of left ventricular filling pressure estimated by tissue Doppler imaging. Therefore, we conducted this study using left atrial parameters to assess left ventricular filling pressure in patients with severe mitral regurgitation.

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 Left Ventricular Filling Pressure More Than 15 mmHg Measured by Left Ventricular Catheterization, measured over 1 year.

The primary endpoint concerns left ventricular filling pressure measured by left ventricular catheterization. The title identifies pressure above 15 mmHg as the outcome of interest, and the description explains that this threshold was selected because prior reports had treated such pressure as an indicator of poor ventricular compliance and more cardiovascular events. This is the rationale recorded by the study, not evidence that the same relationship was demonstrated in this study.

The endpoint entry also specifies a mean continuous measure in mmHg, with standard deviation as the dispersion measure and a one-year timeframe. Alongside the threshold question, the description states that the study assessed the correlation between filling pressure and left atrial distensibility. It further describes using an ROC curve to estimate a distensibility cut-off for predicting pressure above 15 mmHg. These related analyses address different statistical questions: a continuous pressure value, its relationship with another measure, and the classification of pressure around a specified threshold.

The registry record does not report the observed mean, standard deviation, correlation, ROC results, selected cut-off or counts of participants above the threshold. It therefore permits description of what the endpoint was intended to measure and why, but not an estimate of the observed pressure or the accuracy of distensibility as a predictor.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry description names several statistical questions: association between two measurements, discrimination around a pressure threshold, and prognosis. These approaches answer different questions. The record does not report the numerical analyses, so the explanations below are general descriptions of what the named methods assess, not claims about results from this study.

What does a correlation assess?

In general, correlation describes how two measured quantities vary together. Here, the stated pair is left ventricular filling pressure and left atrial distensibility. A correlation can describe the direction and strength of an association in the analyzed observations, but by itself it does not show that one quantity causes a change in the other. It also does not establish that a measure can accurately classify individual patients or predict future events. A numerical correlation estimate, its uncertainty and the exact analysis population are not reported in the registry record.

For continuous measurements, the form of the relationship matters. A single correlation summary may not capture a curved relationship or patterns that differ across the measurement range. General statistical practice is to inspect the data and assess whether the chosen summary is suitable. The registry record does not report diagnostic plots, transformation choices, adjustment variables or model specifications, so no such choices can be attributed to this study.

What does an ROC curve address?

In general, a receiver operating characteristic curve evaluates how a continuous marker distinguishes observations classified into two outcome categories across possible cut-offs. In this study description, the categories are defined around left ventricular filling pressure above 15 mmHg, and the marker is left atrial distensibility. Different cut-offs trade off the ability to identify observations above the threshold against the ability to identify those not above it. An ROC analysis can describe discrimination across cut-offs, but it does not by itself show that a marker improves clinical decisions or predicts outcomes in a new population.

The description says that an ROC curve was used to estimate a best cut-off, but the criterion for “best” is not reported in the registry record. The selected value, ROC area, uncertainty, sensitivity, specificity and any validation procedure are also not reported. A cut-off selected and assessed in the same data can appear more informative than it would in new observations; general statistical evaluation often distinguishes development from validation for this reason. The record does not say whether validation was performed.

Why distinguish a continuous measure from a threshold?

The endpoint entry identifies a mean continuous measure in mmHg, while its title and description emphasize pressure above 15 mmHg. These perspectives are complementary but not interchangeable. A continuous analysis retains information about the observed pressure values, whereas a threshold analysis groups measurements according to whether they cross a defined boundary. Turning a continuous measure into categories can make a particular clinical threshold easier to discuss, but it discards variation within each category. The record does not report the observed distribution or how the continuous and threshold analyses were connected in the final analysis.

What does a mean and standard deviation convey?

In general, the mean describes the central level of a continuous measurement, while the standard deviation describes variation among the observed measurements. The standard deviation is not the same as the uncertainty in the estimated mean. A confidence interval for a mean, when reported, expresses a range of values compatible with the data and analysis under its assumptions. No mean, standard deviation or confidence interval for the primary endpoint is reported in the registry record, so none can be interpreted for this study.

Measurement context is important as well. The record states that severe mitral regurgitation affects the accuracy of filling-pressure estimates from tissue Doppler imaging and identifies catheterization as the measurement approach for the primary outcome. It does not provide details on measurement procedures, reader blinding, repeatability or quality control. Those matters are relevant to how precisely a measured association reflects the underlying physiology, but the record does not report them.

How should planning calculations be read?

In general, a sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability, allocation and statistical method. The record describes a planning illustration based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation and a normal approximation. It states that the illustration is not the trial’s own design. Any resulting sample sizes are planning illustrations, not observed power and not evidence about whether the study found an effect. The registry record does not report the trial’s own sample-size justification.

Such an illustration is conditional on its assumptions. If the observed effect used as a reference is imprecise or not representative, calculations based on it inherit that limitation. General interpretation should therefore focus on the assumptions and intended future design question, rather than treating a planning number as an outcome. No planning values need to be interpreted as observed study findings.

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("Patients With Either Chronic or Acute Mitral Regur")
n   <- c(111)
m   <- c(25.5)
sp  <- c(5.7)
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  Patients With Either Chronic or Acute Mitral Regur  111  25.500  5.700  24.428  26.572

11. Multiplicity, Missing Data and Analysis Populations

The study description names multiple aims: the relationship between left atrial distensibility and filling pressure, prediction of pressure above 15 mmHg, and prognosis including operation mortality, post-operation atrial fibrillation and late heart failure events. The registry also lists secondary outcomes for post-operation atrial fibrillation and heart failure requiring rehospitalization during follow-up. Considering multiple outcomes or analyses raises a general multiplicity issue: the more questions assessed, the greater the chance that some findings may appear noteworthy by chance when each is considered separately.

The registry record does not report a multiplicity adjustment, hierarchy of confirmatory outcomes, prespecified analysis sequence or interim analyses. These items are not reported in the registry record, so it is not possible to determine how the study planned to control or interpret multiple statistical tests. The record lists no analyses, and it does not provide outcome-specific estimates or uncertainty measures.

Missing-data handling and analysis populations are also not reported in the registry record. There is no description of exclusions from analysis, incomplete measurements, follow-up losses, imputation, or whether analyses used all enrolled participants or a defined subset. Without this information, the degree to which the analyzed observations represent those enrolled cannot be evaluated.

These absences do not establish that a particular method was or was not used; they mean that it is not reported in the registry record. In general, transparent reporting of prespecified outcomes, analysis populations and missing-data methods helps readers judge whether results are robust and whether analyses may have been influenced by incomplete follow-up or selective reporting.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: heart failure requiring rehospitalizaion (8.1%).

The registry’s serious-event entry lists a group described as patients with either chronic or acute mitral regurgitation. For the serious-event count, it reports 111 at risk and 9 affected; for the other-event count, it reports 111 at risk and 2 affected. The registry also lists “Heart failure requiring rehospitalizaion” as the top serious term, with 8.1%. These entries are reported as registry event information and should not automatically be treated as results of a randomized safety comparison.

The record does not clarify the relationship between the serious-event and other-event counts, or whether the counts refer to mutually exclusive categories. They should not be added together or interpreted as a total. The event-term percentage is presented separately; the registry does not provide enough detail to establish its denominator or how it relates to the counts.

No death count is reported in the registry record. The listed serious-event information also does not replace the specified secondary outcome results: numerical results for post-operation atrial fibrillation and heart failure requiring rehospitalization as study outcomes are not reported in the registry record. Event definitions, ascertainment details and follow-up completeness are not reported, so the figures support only a limited description of what was entered.

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

The record establishes that the study asked whether left atrial distensibility is related to catheter-measured left ventricular filling pressure in severe mitral regurgitation. It also records an intended predictive analysis around pressure above 15 mmHg and broader prognostic aims. The registry record does not report the numerical primary results needed to determine the observed association, its precision, or the performance of distensibility as a predictor.

Accordingly, the record does not establish that distensibility accurately predicts filling pressure, that a particular cut-off is useful, or that it predicts post-operative events. Those conclusions would require reported estimates and sufficient information about their uncertainty, outcome definitions, analysis populations and validation. The listed serious-event figures do not resolve these questions and should not be interpreted as a causal comparison.

In general, a statistically detectable association and a clinically useful prediction are distinct. Association describes how measurements vary together; prediction concerns how well information classifies or forecasts outcomes, ideally in observations separate from those used to develop a rule. A prediction result also needs context about the outcome’s frequency and the consequences of errors. The registry record does not report the necessary performance measures or validation details.

The design description is also not a basis for comparing treatments. Allocation is not stated, and the record explicitly says the arms are not a like-for-like control comparison. Thus, the information supports a description of the study’s objectives, measures and limited event entries, rather than a causal claim about an intervention or an individual clinical recommendation.

The principal contribution visible in the record is the question it sought to address: whether a left atrial measure could inform assessment of filling pressure in a setting where tissue Doppler estimates may be inaccurate. Whether the collected data answered that question cannot be judged from the numerical primary results, which are not reported in the registry record.

14. Why This Trial Matters Statistically

This study matters statistically because it brings together measurement, association and prediction questions that can easily be conflated. A continuous catheter-measured pressure, its relationship with left atrial distensibility, classification around a threshold and prediction of future events each require distinct estimands and interpretations. The registry description identifies these aims, making clear why the endpoint’s form and analysis details matter.

The record also highlights a general challenge in clinical measurement: a marker may reflect a longer-term physiological state while a pressure measurement is made under particular examination conditions. The study rationale proposes left atrial measures as relevant to filling pressure in severe mitral regurgitation. Whether the measures actually provide useful information is an empirical question; the registry’s missing numerical results prevent evaluation of its answer.

Threshold-based prediction is another important statistical issue. A chosen threshold can make a continuous clinical measure easier to classify, but ROC-based cut-off selection should be interpreted with its uncertainty and validation context. The stated use of an ROC curve is not itself evidence of predictive accuracy. Reporting the selected cut-off and its performance would be necessary to judge the claim.

Finally, the record demonstrates why study design and outcome reporting shape inference. Without a stated allocation method, a like-for-like comparator or reported analysis details, group entries cannot be treated as causal effects. Clear reporting of estimates, uncertainty, missing-data handling and analysis populations would be needed for a fuller assessment of the study’s statistical contribution.

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 for interpreting the registry record is that numerical results for the primary endpoint are not reported. The mean, standard deviation, correlation, ROC performance and estimated distensibility cut-off are absent. This prevents assessment of the size, direction and precision of the primary findings, as well as the stated predictive objective.

The record describes several prognostic aims, but numerical results for operation mortality, post-operation atrial fibrillation and late heart failure events are not reported in the registry record. Although serious-event entries are present, their relationship to the named secondary outcomes is not fully explained. The death count is not reported in the registry record.

Design and analysis details are limited. Allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison. Eligibility information beyond the brief arm description, measurement procedures, outcome definitions, follow-up completeness and analysis populations are not reported in the registry record. Missing-data methods, covariate adjustment, multiplicity handling and validation of any selected cut-off are also not reported.

The endpoint is described both as a mean continuous measure in mmHg and in terms of pressure above 15 mmHg, with correlation and ROC analyses also mentioned. The registry record does not provide results that would clarify how these analyses were implemented or how they relate to each other. These limitations restrict interpretation to the study’s stated aims and the limited event entries, rather than conclusions about the strength or usefulness of the proposed marker.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Left Atrial Distensibility to Predict Left Ventricular Filling Pressure and Prognosis in Patients With Severe Mitral Regurgitation — NCT01172184.
• Registry record last updated 2011-06-07; status last verified 2010-06.
• Results first posted 2011-06-07.
• 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

This completed study, sponsored by Kaohsiung Veterans General Hospital, enrolled 111 and focused on left atrial distensibility and left ventricular filling pressure in severe mitral regurgitation. Its listed procedure was cardiac catheterization. The primary outcome concerns catheter-measured filling pressure, with the description emphasizing pressure above 15 mmHg, correlation with distensibility and an ROC-based cut-off. The stated timeframe is one year.

The registry also lists post-operation atrial fibrillation and heart failure requiring rehospitalization as secondary outcomes. Serious-event entries include 9 affected in the serious-event count and 2 affected in the other-event count, each with 111 at risk; the top serious term is reported as 8.1%. These entries do not supply the missing primary analysis.

Numerical results for the primary association and prediction questions, detailed analysis methods, missing-data handling and analysis populations are not reported in the registry record. Allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison.