Chronotropic Incompetence (CI) Diagnostic Algorithm in Heart Failure Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Chronotropic Incompetence (CI) Diagnostic Algorithm in Heart Failure Patients (NCT02358603), a randomized na study. The primary outcome is Chronotropic Incompetence Index of Patients With Heart Failure Disease.

2. Clinical Question

3. Trial Design

The registry describes a randomized, parallel-group study with no masking. It lists heart failure as the condition and the chronotropic incompetence diagnostic algorithm as the diagnostic-test intervention. The record lists enrollment of 48 and identifies the study status as terminated. The reason for termination is not reported in the registry record. The listed study start is 2014-06 and primary completion is 2015-06. The case group is described as completing an echocardiogram and a related BNP laboratory test at the beginning of the study. During the study, participants were to complete a six-minute walk test and 24-hour ambulatory monitoring while wearing an ActiGraph device on the wrist and a Holter device. The control group is described as completing the same tests and examination. The primary outcome description characterizes the comparison as algorithm-based assessment versus standard-of-care diagnostics, but the registry does not explain the diagnostic workflow or specify how the algorithm influenced care or outcome measurement. The reported group summaries are for 40 participants in the case group and 8 in the control group. The registry reports a mean chronotropic index of 0.61 with standard deviation 0.11 for the case group, and a mean of 0.72 with standard deviation 0.01 for the control group. These are descriptive summaries. The record lists no analyses, and the registered outcome does not have a posted inferential comparison. The phase is listed as NA. Further details about allocation procedures, concealment, the planned analysis, and the reason for the unequal group sizes are not reported in the registry record. Randomization is recorded, but its method and implementation cannot be assessed from the listed information.

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: Compare the case group for chronotropic incompetence using the interventional algorithm versus those in the control group.

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 Chronotropic Incompetence Index of Patients With Heart Failure Disease, measured over Implant through 6 months.

The primary endpoint is the chronotropic incompetence index in patients with heart failure, reported as a continuous measure with a mean and standard deviation. The registry gives the timeframe as implant through 6 months. It describes the chronotropic index as the heart-rate reserve divided by metabolic reserve, and also expresses it as achieved maximal heart rate minus resting heart rate, divided by age-predicted maximal heart rate minus resting heart rate. The registry characterizes normal chronotropic index as approximately 1 and considers an index below 0.8 low. The index is intended to represent the heart-rate response in relation to an expected or available reserve. In general, a continuous physiological measure can retain more detail than a classification that divides participants into categories. The endpoint description does not report a separate threshold-based primary outcome; it specifies comparison of group index values. The registry does not explain how the endpoint was calculated for individual participants, how measurements were selected or processed, or whether any measurements were excluded. Those operational details are not reported in the registry record. The posted summaries are mean 0.61 and standard deviation 0.11 in the case group, and mean 0.72 and standard deviation 0.01 in the control group. A mean describes the group’s average observed value, while a standard deviation describes the spread of observations around that average. Neither measure alone supplies the uncertainty in the difference between groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure summarized by a mean and standard deviation. In general, a mean gives the arithmetic average of observed measurements, and a standard deviation describes how dispersed individual measurements are around that average. The chronotropic index values posted for the case group are mean 0.61 and standard deviation 0.11; for the control group they are mean 0.72 and standard deviation 0.01. These summaries provide a compact description of each group, but not a direct estimate of the uncertainty in the difference between group means. A comparative analysis would ordinarily report a between-group estimate and a measure of its uncertainty. A confidence interval is a range generated by a statistical procedure to express the precision of an estimated quantity under its assumptions. If a confidence interval for a group contrast were reported, its location and width would help readers assess both the direction and precision of the estimate. No such interval is reported in the registry record. A p-value, if reported, would address compatibility of the data with a specified null hypothesis under a model; it would not measure the probability that the null hypothesis is true or establish clinical importance. The record reports no p-value or statistical test for this endpoint. The registry lists zero analyses. It also indicates that a two-arm comparison for this continuous outcome could not be estimated from the posted summary statistics. As a result, no recalculated comparative estimate is available. A recalculated result, when available, would be an unadjusted calculation based on group summaries and should be distinguished from a sponsor’s prespecified or adjusted analysis. In this record, no sponsor analysis is posted for the primary outcome, and the record does not provide enough information to produce a comparative calculation. The arm sizes are unequal: 40 participants are listed for the case group and 8 for the control group. In general, unequal allocation can affect the precision of a group comparison, particularly when the smaller group contributes less information to the estimate. The posted standard deviations also differ, so methods that assume equal variability across groups would require scrutiny. The registry does not report which model, variance assumption, covariate adjustment, or inferential procedure was planned or used. Those methods are not reported in the registry record. The record contains a sample-size planning assumption describing a two-sided significance level of 0.05, equal allocation, a normal approximation, and detection of a stated fraction of the observed effect. This is a planning framework, not an analysis of observed power. The registry does not provide a usable estimated between-group effect for this endpoint, and its notes indicate that values were missing or not estimable for the continuous comparison. No participant-per-arm planning estimates can therefore be interpreted from the registry record. In general, sample-size planning illustrations describe hypothetical future study requirements under stated assumptions; they do not show the probability that the completed study detected an effect. The outcome is a mean-based continuous measure. In general, this kind of summary is most informative when the measurement is sufficiently comparable across participants and the distribution is suitable for the chosen analysis. The record does not report distributional checks, transformations, robust methods, or an approach to unusual values. It also does not report whether the endpoint’s calculation or interpretation differed by participant characteristics or measurement conditions. These omissions limit assessment of whether a particular statistical model would be appropriate. The registry describes the design as randomized and parallel, but gives no allocation sequence or concealment details. In general, randomization is intended to reduce systematic baseline differences between groups, while concealment concerns whether upcoming assignments could be anticipated during enrollment. The registry label alone does not establish how these protections were implemented. Masking is listed as none, so the design was not masked according to the record. Whether lack of masking could influence measurement, conduct, or interpretation depends on the study procedures, which are not described in sufficient detail in the registry record. Finally, a descriptive group comparison and a diagnostic-performance evaluation answer different questions. Means and standard deviations describe the index distribution at group level. They do not quantify how well the algorithm identifies individual cases or distinguish patients with and without chronotropic incompetence. Diagnostic accuracy measures and a reference-standard procedure are not reported in the registry record. The posted endpoint summaries should therefore be read as group descriptions rather than evidence of diagnostic performance.

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("Case Group", "Control Group")
n   <- c(40, 8)
m   <- c(0.61, 0.72)
sp  <- c(0.11, 0.01)
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  Case Group  40  0.610  0.110  0.575  0.645
CARM  Control Group  8  0.720  0.010  0.712  0.728

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and zero analyses. It does not list secondary outcomes. With no set of posted hypothesis tests, there is no reported multiplicity adjustment to assess. In general, multiplicity arises when several statistical hypotheses are tested; repeated testing can increase the chance of at least one apparently notable result. Whether the study protocol specified other outcomes or analyses is not reported in the registry record, so the listed outcome count should not be taken to establish the full analysis plan. The record does not report how missing endpoint measurements were handled, whether participants with incomplete data were excluded, or whether any imputation method was used. It also does not report the number of participants with evaluable endpoint data separately from the arm enrollment figures. The listed group sizes accompany the reported summaries, but the analysis population and participant flow are not described. Missing-data assumptions and their consequences for the comparison cannot be evaluated from the registry record. The record does not specify whether the analysis followed an intention-to-treat, per-protocol, or other population definition. It does not report protocol deviations, withdrawals, or endpoint completion. In general, the analysis population matters because excluding participants or measurements after randomization can affect comparability and the meaning of an estimate. Without a stated population and a flow of participants through measurement and analysis, the reader cannot determine whether the group summaries represent all randomized participants or a subset. The study is listed as terminated, but the reason and its implications for missingness or analysis are not reported in the registry record. These gaps do not prove that data were missing or that an analysis was selectively omitted; they mean those aspects cannot be assessed from the posted information.

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 0% reporting threshold.

For the case group, the registry reports zero participants affected by serious adverse events among 40 at risk and zero affected by other adverse events among 40 at risk. For the control group, it reports zero participants affected by serious adverse events among 8 at risk and zero affected by other adverse events among 8 at risk. No serious adverse event terms are listed. The death figures are not reported in the registry record. These entries describe what the registry reports; they should not be interpreted as proof that no adverse events occurred outside the recorded categories or reporting period. The record does not provide event definitions, surveillance procedures, event-level details, severity categories beyond serious versus other, or timing. It also does not explain whether the zero counts reflect active monitoring with no events, incomplete reporting, or another circumstance. The at-risk counts are the registry’s stated denominators for these safety summaries and should not be conflated with a separate analysis population. The available entries do not support a detailed comparison of safety between groups.

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

The posted result establishes that the registry contains descriptive chronotropic index summaries for the case and control groups. It reports mean 0.61 with standard deviation 0.11 for the case group and mean 0.72 with standard deviation 0.01 for the control group. The registry record does not report a formal estimate of the difference, a confidence interval, or a statistical test. Thus, the summaries do not quantify the precision of a comparative effect. The result does not establish that the diagnostic algorithm caused a change in chronotropic index. Although the study is recorded as randomized, the registry does not provide enough information about assignment procedures, endpoint analysis, missing observations, or adjustment to evaluate a causal estimate. Nor do group averages demonstrate how individual participants were classified. The low-index criterion in the record is below 0.8, but the number of individuals meeting that criterion is not reported in the registry record. The outcome summaries also do not establish diagnostic accuracy. No sensitivity, specificity, predictive value, agreement statistic, or comparison against a stated reference standard is reported. The study’s stated purpose was to collect activity and ECG data to aid development of a diagnostic algorithm, but details of the algorithm and its performance are not provided. The safety entries report zero participants affected by serious and other adverse events in each group, while deaths are not reported in the registry record. These counts are limited to the registry entries and do not provide a comprehensive account of how safety was monitored. Overall, the available information supports a descriptive reading of the reported group means, standard deviations, enrollment, and registry status. It does not support a conclusion about efficacy, diagnostic validity, or the magnitude and certainty of a between-group effect. The reason for termination and the relationship between termination and the posted outcome are not reported in the registry record.

14. Why This Trial Matters Statistically

This study raises a useful statistical distinction between describing a physiological measure and validating a diagnostic algorithm. The registry posts group-level means and standard deviations for the chronotropic index. Those summaries can describe observed index values, but a diagnostic question generally concerns how well a procedure classifies individuals against an appropriate reference. Such performance information is not reported in the registry record. The record also illustrates why a randomized label does not by itself provide a complete comparative result. Readers need an estimate of the contrast, its uncertainty, and a description of the analysis population and methods to interpret a comparative question. Here, the registry reports no analysis and no inferential comparison for the continuous endpoint. It notes that the two-arm comparison could not be estimated from the posted summary statistics. The means therefore remain descriptive rather than a quantified randomized effect. The unequal group sizes and differing reported standard deviations are relevant to precision and model choice. In general, comparisons may be sensitive to how variability and allocation are handled. Since the planned or executed analysis is not reported, readers cannot assess those decisions. Likewise, no explanation for termination is recorded, limiting interpretation of how study conduct affected the available outcome information. These features matter for future study reporting: endpoint calculation, diagnostic reference standards, participant flow, missing-data handling, analysis populations, and uncertainty estimates are needed to connect collected measurements to a robust comparative or diagnostic conclusion. The posted record is informative about the study’s stated aim and descriptive summaries, while leaving those statistical links unresolved.

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.

Several trial-specific details needed to interpret the endpoint are not reported in the registry record. The calculation is described using heart-rate reserve and metabolic reserve, but the record does not specify the operational measurement procedures, data processing rules, or handling of incomplete or unusable measurements. It also does not explain how the diagnostic algorithm was implemented or how the control group’s standard-of-care diagnostics were defined. The record reports a terminated status but does not give the reason. It does not report participant flow, withdrawals, endpoint completion, or the analysis population. Although randomization is listed, allocation generation and concealment are not described. Masking is listed as none, and the record does not describe safeguards against measurement or assessment bias. These omissions make it difficult to assess the conduct of the comparison. For the primary endpoint, group means and standard deviations are posted, but there is no inferential estimate, confidence interval, or p-value. The record lists no analyses and indicates that a two-arm comparison could not be estimated from the posted summary statistics. No diagnostic performance measures or individual-level threshold counts are reported, despite the endpoint description’s low-index criterion. The reason for the substantially unequal group sizes is not reported in the registry record. Safety information is also limited to the recorded counts of affected participants; event definitions, timing, and monitoring methods are not described. Deaths are not reported in the registry record. These limitations constrain interpretation of both the comparative outcome and safety summaries, without establishing why particular information is absent.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Chronotropic Incompetence (CI) Diagnostic Algorithm in Heart Failure Patients — NCT02358603.
• Registry record last updated 2020-02-05; status last verified 2020-01.
• Results first posted 2020-02-05.
• 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.

19. Record Summary

The registry record describes a randomized, unmasked, parallel-group study of a chronotropic incompetence diagnostic algorithm in people with heart failure. Enrollment is listed as 48, and status is terminated. The listed start is 2014-06 and primary completion is 2015-06. The sponsor is Medtronic Cardiac Rhythm and Heart Failure. The primary outcome is mean chronotropic index, with the timeframe described as implant through 6 months. The case group summary is mean 0.61, standard deviation 0.11, with 40 participants; the control group summary is mean 0.72, standard deviation 0.01, with 8 participants. No formal comparison is reported, and the registry lists zero analyses. The record describes zero serious and zero other adverse events affecting participants in each group; deaths are not reported in the registry record. The reason for termination, analysis plan, missing-data handling, and diagnostic performance results are not reported in the registry record.