This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Correlation of Auscultatory Severity of Aortic Stenosis With Trans Thoracic Echocardiography (NCT01605669), a registered phase not stated study. The primary outcome is Aortic Stenosis Acceleration Index Compared to Aortic Stenosis Severity.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01605669 |
| Phase | Phase not stated |
| Condition | Aortic Stenosis |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 50 |
| Arms in the primary outcome | n/a |
| Lead sponsor | United States Naval Medical Center, San Diego |
| Results posted | Yes |
2. Clinical Question
Population
The study enrolled 50 participants with aortic stenosis. The eligibility description specifies patients with varying degrees of disease and excludes those with significant additional valvular disease. The registry record does not report further demographic or clinical characteristics of the enrolled participants.
Intervention
Participants had cardiac auscultation recorded with an electronic stethoscope. The study evaluated the aortic stenosis acceleration index (ASAI), a measure based on the timing of the systolic murmur’s peak intensity relative to the systolic interval.
Comparator
The reference measurements were obtained by transthoracic echocardiography (TTE). The record identifies peak and mean aortic valve gradients and aortic valve area derived from the continuity equation as measures of aortic stenosis severity. This is a within-participant comparison, not a randomized treatment comparison.
Primary question
The central question was whether ASAI measurements corresponded to echocardiographic measures of aortic stenosis severity. The registry description says ASAI was averaged and compared with mean aortic gradient, and that a receiver operating characteristic (ROC) curve was calculated for identifying a mean gradient >30 mmHg. It states that ASAI 34 was selected as the threshold with the optimal combination of sensitivity and specificity. Numerical estimates of the association and diagnostic performance are not reported in the registry record.
3. Trial Design
This was a completed, single-group observational measurement study sponsored by United States Naval Medical Center, San Diego. The registry lists an enrollment of 50 and study dates from 2012-05 to 2013-06. It does not describe a randomized allocation, treatment assignment, or control arm. Participants with varying degrees of aortic stenosis were eligible if they did not have significant additional valvular disease.
Each participant was to have a transthoracic echocardiogram and a recorded cardiac auscultation assessment. The registry describes both measurements as occurring at the same visit, with a single measurement on the day of enrollment and no additional visits or study follow-up. Thus, the intended comparison was between two assessments of disease severity collected at the same time, rather than a comparison of treatment effects or changes over time.
The electronic-stethoscope recording was used to derive the aortic stenosis acceleration index (ASAI). Echocardiographic severity measures were peak and mean aortic valve gradients and aortic valve area derived from the continuity equation. The registry description specifically states that ASAI was averaged and compared with the mean aortic gradient, and that an ROC curve was calculated for ASAI to identify a mean gradient >30 mmHg.
The record labels the primary outcome as a number of participants, although its description focuses on a measured index, echocardiographic severity values, and an ROC analysis. That difference in presentation makes the exact outcome-data structure difficult to establish from the record alone. A detailed protocol, recruitment flow, or fuller account of the analysis population is not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Aortic Stenosis Patients |
|---|---|
| STARTED | 50 |
| COMPLETED | 50 |
| NOT COMPLETED | 0 |
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.
| Characteristic | Unit | Aortic Stenosis Patients |
|---|---|---|
| Participants analysed | 50 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 14 |
| Age, Categorical: >=65 years | Participants | 36 |
| Sex: Female, Male: Female | Participants | 15 |
| Sex: Female, Male: Male | Participants | 35 |
| Region of Enrollment: United States | participants | 50 |
6. Primary Endpoint
The registry lists the primary outcome as Aortic Stenosis Acceleration Index Compared to Aortic Stenosis Severity, measured over There is a single measurement taken on the day of enrollment. The ascultatory recording and echocardiogram will occur at the same visit. There will be no additional visits or study followup..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary outcome is titled “Aortic Stenosis Acceleration Index Compared to Aortic Stenosis Severity.” ASAI describes the timing of the systolic murmur’s peak intensity in relation to the total systolic interval. In the registry’s notation, the interval from the first heart sound to the murmur peak is compared with the interval spanning the first and second heart sounds. The rationale is to evaluate whether a feature of the audible murmur tracks severity assessed by imaging.
The reference severity measures are peak and mean aortic valve gradients and aortic valve area derived from the continuity equation. The outcome description says ASAI was averaged and compared with mean aortic gradient. It also says an ROC curve was calculated to assess ASAI for identifying a mean gradient >30 mmHg, with ASAI 34 selected as the threshold for the optimal combination of sensitivity and specificity.
These measures address related but distinct questions. An association analysis asks whether ASAI varies with the echocardiographic measure. An ROC analysis assesses how well a threshold separates participants on either side of a defined reference condition. The registry record does not report the numerical association, area under the ROC curve, sensitivity, specificity, or uncertainty intervals. It also does not explain how the primary outcome’s stated unit of participants relates to the continuous measurements described.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry describes a study designed to compare an auscultatory measure with echocardiographic assessments of aortic stenosis severity. All participants were to receive both assessments at the same visit. This paired measurement structure is relevant to interpretation: the aim was to examine whether the two types of measurements corresponded, not whether one treatment changed an outcome relative to another treatment.
The outcome description reports that ASAI was averaged and compared with mean aortic gradient. It also states that an ROC curve was calculated for identifying a mean gradient >30 mmHg and that ASAI 34 was selected as the threshold with the optimal combination of sensitivity and specificity. This is the extent of the numerical finding reported in the registry description. The record does not give a correlation coefficient or other association estimate, an area under the ROC curve, sensitivity, specificity, confidence intervals, or p-values. Without those estimates, readers cannot assess the strength or precision of the reported relationship or the operating characteristics of the threshold.
A threshold selected as optimal in the data used to choose it is not, by itself, evidence of how well it will classify participants in a separate group. Threshold performance depends on the study sample and on how the reference condition is defined. The record does not report external validation or another evaluation of the threshold in an independent sample. It also does not report the number of participants on each side of the mean-gradient criterion or how many were correctly classified at ASAI 34.
The registry lists an enrollment of 50, but enrollment alone does not establish how many participants contributed to each analysis. The number with complete ASAI and echocardiographic measurements, the handling of missing measurements, and the analysis population are not reported in the registry record. Nor does the record provide participant characteristics that would help readers judge how broadly the findings might apply.
Accordingly, the posted description supports a cautious account of the study’s purpose and stated threshold, but not a quantitative conclusion about the association’s magnitude, precision, or diagnostic accuracy. The findings should be read as a reported comparison in this enrolled group, not as evidence of a causal effect or a treatment benefit. The record does not establish whether the selected threshold performs consistently beyond the study sample.
9. Statistical Methods Explained
What does an association analysis ask?
In general, an association analysis asks whether two measured variables tend to vary together. In this study, the variables of interest were ASAI and echocardiographic measures of aortic stenosis severity. A positive association would mean that larger values of one measure tend to accompany larger values of the other; a negative association would mean that larger values of one tend to accompany smaller values of the other. The direction and strength need to be expressed with an estimate to be evaluated. The registry says ASAI was averaged and compared with mean aortic gradient, but it does not report the coefficient, the specific correlation method, or an uncertainty interval.
Correlation describes a pattern of co-variation, not cause and effect. Even a strong association would not show that the auscultatory measure causes a change in valve severity or that the measure predicts how disease changes over time. The described assessments were collected at the same visit, and the record states there was no follow-up.
What does the ROC analysis address?
In general, a receiver operating characteristic analysis examines the ability of a measurement to distinguish between participants who do and do not meet a reference definition. Here the registry identifies a mean aortic gradient >30 mmHg as the reference condition for the ROC analysis. The analysis can assess candidate ASAI thresholds across possible cut points. Sensitivity describes the fraction of reference-positive participants identified by a threshold, while specificity describes the fraction of reference-negative participants correctly classified. These quantities are related: changing the threshold can make one improve while the other declines.
The registry states that ASAI 34 was selected for the optimal combination of sensitivity and specificity. It does not report the underlying sensitivity or specificity, the area under the ROC curve, or the method used to define “optimal.” Therefore, the statement identifies a selected threshold but does not allow readers to quantify its classification performance. The number of participants who met the mean-gradient criterion, and the number classified correctly at the selected threshold, are not reported in the registry record.
How should measurement timing be understood?
The record describes one measurement on the day of enrollment, with auscultation and echocardiography at the same visit. This permits a contemporaneous comparison between the murmur timing measure and imaging-based severity measures. It does not provide information about repeatability across separate recordings, measurement variation between assessors, or whether the relationship persists over time. Those details are not reported in the registry record.
The echocardiographic reference measures listed are peak and mean aortic valve gradients and aortic valve area derived from the continuity equation. The outcome description gives more detail about comparison with mean gradient than about analyses involving the other measures. The specific statistical handling of peak gradient and valve area is not reported in the registry record.
What can planning calculations tell readers?
General sample-size planning estimates depend on assumptions about the comparison, the effect to detect, the statistical threshold for evidence, and the desired power. The planning illustration accompanying these results is described as based on the observed effect and as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It varies the effect to detect as a stated fraction of the observed effect. Those are planning assumptions, not characteristics of the observed study design.
The study itself is described as a single-group, paired-measurement investigation, not a randomized comparison between two arms. Consequently, a two-arm planning illustration should not be read as the protocol’s design justification or as proof that the study had a particular probability of finding a result. The registry record does not report its own sample-size justification or power calculation. Planning estimates are not observed power, and they do not replace estimates of the association and its uncertainty.
What remains unspecified?
The registry record does not report the exact correlation test, regression model, confidence-interval method, handling of outliers, or prespecified analysis plan. It also does not report whether the ASAI threshold was prespecified or selected after examination of the study data. These omissions matter because analysis choices can affect estimates and the interpretation of a data-selected threshold. General statistical principles can describe what the analyses are intended to do, but they cannot fill in methods that the record does not state.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists three analyses, but does not describe their individual hypotheses, specify which were primary or secondary, or report analysis-specific estimates. The outcome description names several echocardiographic measures—peak gradient, mean gradient, and aortic valve area—and specifically describes averaging ASAI and comparing it with mean gradient, as well as an ROC analysis for a mean gradient >30 mmHg. It does not give a complete account of all three analyses or identify any adjustment for multiple testing.
Multiplicity arises when several questions or thresholds are examined. In general, testing many associations or selecting a cut point from the same data can increase the chance that an apparently notable result reflects sampling variation. Whether and how that issue was addressed cannot be determined from the record. A multiplicity adjustment or prespecified testing hierarchy is not reported in the registry record.
The record does not state how missing ASAI recordings or echocardiographic measurements were handled, whether any participants were excluded from an analysis, or how many contributed to each result. It also does not describe an intention-to-treat or per-protocol population; those treatment-trial terms may not fit a study in which participants were measured rather than assigned to treatment. The registry record does not report an analysis population definition or missing-data method. These gaps limit assessment of whether the reported comparisons used all enrolled participants and whether the analyzed group differed from the enrolled group.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Aortic Stenosis Patients | 0 | 50 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Aortic Stenosis Patients | 0 of 50 |
The adverse-event record lists 50 participants at risk for serious events and 0 with a serious event. It also lists 50 at risk for other events and 0 with another event. No serious adverse-event terms are listed. The death count is not reported in the registry record.
These are event counts recorded for the study group, not comparisons between randomized treatment arms. The study description concerns auscultation and echocardiography at a single visit, and does not identify an assigned treatment whose safety could be compared with a control. The counts therefore should not be interpreted as a comparative safety estimate.
In general, observing no events in a study group does not establish that the underlying risk is zero. Event counts can be informative about what was recorded during the study, but their interpretation depends on the observation period, event definitions, and completeness of reporting. The registry describes no additional visits or follow-up, but does not provide detailed adverse-event collection procedures or further information about the period covered by safety monitoring. Those details are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The study addresses whether a timing feature of the systolic murmur, summarized as ASAI, corresponds to aortic stenosis severity measured by transthoracic echocardiography. The registry description reports that ASAI was averaged and compared with mean aortic gradient and that an ROC analysis was conducted for identifying a mean gradient >30 mmHg. It also records ASAI 34 as the selected threshold for the optimal combination of sensitivity and specificity.
That description does not provide the numerical results needed to judge the magnitude or precision of the association. No correlation estimate, ROC area, sensitivity, specificity, or confidence interval is reported in the registry record. The selected threshold is therefore not enough to determine how reliably ASAI separates participants according to the stated gradient criterion. It also cannot show whether performance would be similar in a different sample.
The study is not described as a randomized trial of treatment, and it has no treatment-control comparison. Its measurements were collected at a single visit, so it does not establish whether ASAI tracks progression over time. The record does not report follow-up measurements or a longitudinal analysis. Nor does the comparison establish that an auscultatory measure can replace imaging; that question would require evidence about measurement performance and clinical use that is not reported in the registry record.
The enrolled group consisted of participants with varying degrees of aortic stenosis and without significant additional valvular disease, according to the eligibility description. The record does not give further participant characteristics or an external validation sample. Generalizability beyond the studied group therefore cannot be assessed from the registry description alone.
In short, the record documents the comparison that was undertaken and names a threshold selected in the analysis, but leaves key quantitative performance results unavailable. It does not support a conclusion about treatment effects, disease progression, or performance in other populations.
13. Why This Trial Matters Statistically
This study is statistically interesting because it compares two different ways of characterizing aortic stenosis severity: a measure derived from the timing of an audible murmur and measures derived from transthoracic echocardiography. Comparing measurements taken during the same visit can address whether an auscultatory feature corresponds to imaging-based severity at that time. The question is distinct from whether either measure predicts future disease course or whether using one changes patient outcomes.
The registry description also distinguishes two statistical tasks that are often conflated. Comparing ASAI with mean gradient concerns the association between measurements. Selecting an ASAI threshold for a defined mean-gradient criterion concerns classification. A measure can be associated with a reference value without necessarily classifying individuals accurately at a particular cut point. Reporting an association estimate and its uncertainty alongside threshold performance would help readers assess those questions separately; the registry record does not report those numerical estimates.
Threshold selection raises an additional issue: a cut point chosen to optimize performance in the analyzed data may appear more accurate in that sample than it would elsewhere. Independent evaluation helps establish whether performance carries over. The record states that ASAI 34 was selected as optimal, but does not report an external validation or the sensitivity and specificity underlying that choice.
Finally, a record can describe the intended analysis more fully than it reports the resulting estimates. Here, the outcome description identifies the measurement and threshold question, while important details about coefficients, precision, analysis populations, and missing data are not reported in the registry record. This distinction matters for statistical reading: a clear research question and a selected threshold do not substitute for quantitative evidence about the size and reliability of an association.
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 registry outcome is presented as a number of participants, while its description centers on an index, echocardiographic measurements, and an ROC analysis. The relationship between that count-style outcome label and the underlying measurement data is not explained. This makes the reported outcome format difficult to interpret without further documentation.
The registry description gives no numerical association estimate or diagnostic-performance values. It does not report the correlation coefficient, an area under the ROC curve, sensitivity, specificity, confidence intervals, or p-values. Although it states that ASAI 34 was selected as the threshold with the optimal combination of sensitivity and specificity for a mean gradient >30 mmHg, it does not provide the values that support that characterization or define the optimization criterion.
The record does not report participant characteristics beyond the eligibility description, the number of participants with usable paired measurements, or whether any measurements were excluded. Missing-data handling, measurement quality procedures, repeatability, and assessor blinding are not reported in the registry record. These details would help readers assess potential measurement error and the completeness of the analysis.
The study has a single-visit measurement plan and no follow-up, so its design as described cannot address change over time. The record does not report external validation, and the generalizability of the selected threshold cannot be assessed from the enrolled group alone. It also does not provide a full statistical analysis plan, the handling of multiple analyses, or the rationale for the enrollment target. These limitations concern what can be learned from the registry record; they do not establish whether additional information exists outside it.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Correlation of Auscultatory Severity of Aortic Stenosis With Trans Thoracic Echocardiography — NCT01605669.
- Registry record last updated 2016-09-23; status last verified 2016-08.
- Results first posted 2013-11-05.
- 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.
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18. Record Summary
NCT01605669 is a completed study sponsored by United States Naval Medical Center, San Diego, with an enrollment of 50. The registry lists study dates from 2012-05 to 2013-06. Participants with varying degrees of aortic stenosis and without significant additional valvular disease were eligible.
The study planned a single visit with recorded cardiac auscultation using an electronic stethoscope and transthoracic echocardiography. Its stated aim was to compare ASAI with echocardiographic severity measures. The outcome description says ASAI was averaged and compared with mean aortic gradient, and an ROC analysis was conducted for identifying a mean gradient >30 mmHg. ASAI 34 is stated as the selected threshold with the optimal combination of sensitivity and specificity.
The registry record does not report numerical estimates of association or diagnostic performance, confidence intervals, analysis populations, or missing-data handling. It lists 0 serious events and 0 other events among 50 participants at risk in each category; deaths are not reported in the registry record.