Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve (NCT03249272), a randomized phase 4 study. The primary outcome is Prevalence of Microvascular Dysfunction (MVD) by a CMR Measurement of Whole-heart (Global) Perfusion Reserve Ratio in Patients With Hypertrophic Cardiomyopathy, Non-ischemic Cardiomyopathy, and Controls..

2. Clinical Question

3. Trial Design

The registry describes a Phase 4, randomized, single-masked, parallel study sponsored by Duke University. It lists hypertrophic cardiomyopathy, non-ischemic dilated cardiomyopathy, and controls as the clinical groups. Adenosine and regadenoson are listed as drug interventions. The clinical groups are not presented as randomized treatment arms; randomization and masking details beyond the registry labels are not reported in the registry record.

The study aimed to assess microvascular function using cardiovascular magnetic resonance (CMR) measurement of whole-heart, or global, perfusion reserve. Its stated goal was to determine the prevalence of microvascular dysfunction in hypertrophic cardiomyopathy and idiopathic dilated cardiomyopathy. The study also proposed to examine whether an optimized technique could detect dysfunction and whether a multifaceted assessment could provide insight into the role of myocardial scarring. These aims describe the rationale, not additional results.

The registry records a study start of 2017-09-05 and primary completion of 2019-03-31. Its status is terminated. The registry explains that funding was withdrawn because recruitment proceeded slowly. It reports that 31 participants were recruited against an expected enrollment of 75. The registry states that adenosine and regadenoson groups were combined for analysis as pre-specified because the interventions were considered interchangeable.

The posted primary outcome is a group-level prevalence measure. The reported denominators are 19 for hypertrophic cardiomyopathy, 6 for non-ischemic dilated cardiomyopathy, and 5 for controls. Details of the recruitment process, allocation sequence, masking procedures, and handling of participants who did not contribute to the posted outcome are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: Due to the slow pace of recruitment, the sponsor withdrew funding for the study. Of the expected 75 participants, 31 were recruited. As was pre-specified, the regadenoson and adenosine groups were combined for analysis as these interventions are interchangeable.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Due to the slow pace of recruitment, the sponsor withdrew funding for the study. Of the expected 75 participants, 31 were recruited. As was pre-specified, the regadenoson and adenosine groups were combined for analysis as these interventions are interchangeable.

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: As was pre-specified, the regadenoson and adenosine groups were combined for analysis as these interventions are interchangeable.

6. Primary Endpoint

The registry lists the primary outcome as Prevalence of Microvascular Dysfunction (MVD) by a CMR Measurement of Whole-heart (Global) Perfusion Reserve Ratio in Patients With Hypertrophic Cardiomyopathy, Non-ischemic Cardiomyopathy, and Controls., measured over The prevalence of MVD will be determined based on the findings at the time of the scan on Day 1 of the study..

The primary endpoint is the prevalence of microvascular dysfunction measured by CMR-based global perfusion reserve ratio and regional stress perfusion assessment. The registry defines dysfunction as present if the global perfusion reserve ratio is <2.0 or if regional stress perfusion abnormalities are present. The endpoint is reported as the percentage of each clinical group with dysfunction.

To obtain the ratio, coronary sinus flow was measured before adenosine or regadenoson administration and again during administration. The global perfusion reserve ratio is defined as flow during administration divided by baseline flow. Regional perfusion abnormalities were assessed during administration. The endpoint timeframe is the findings at the scan on Day 1.

As a general statistical concept, a prevalence endpoint describes the proportion of a defined group meeting a condition at an assessment time. It can summarize how common the registry-defined finding was in the participants assessed, but it does not by itself establish why the finding occurred or whether groups differ beyond chance. The endpoint combines two routes to classification: a ratio threshold and regional imaging abnormalities. The registry does not report how many participants met each route separately, so the contributions of the two criteria cannot be distinguished from the posted overall percentages.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help clarify what the posted outcome can and cannot show. The registry reports a prevalence endpoint rather than a treatment-effect estimate. It classifies each assessed participant as having or not having microvascular dysfunction according to the stated CMR criteria, then reports the percentage classified as affected within each clinical group. The percentages are 79.0% for hypertrophic cardiomyopathy, 33.3% for non-ischemic dilated cardiomyopathy, and 20.0% for controls.

What does the prevalence estimate represent?

In general, a prevalence estimate is a proportion observed in a defined group at a specified assessment. Here, the assessment is the scan on Day 1, and the registry gives a group denominator alongside each percentage. The estimate is descriptive: it characterizes participants with posted outcome data. It does not automatically generalize to people outside the study, particularly when recruitment is limited or the enrolled participants may not represent the broader clinical population.

The classification rule uses a global measure and regional imaging findings. Global perfusion reserve is the ratio of coronary sinus flow during adenosine or regadenoson administration to baseline flow measured before administration. The registry regards a ratio <2.0 or regional stress perfusion abnormalities as sufficient for classifying microvascular dysfunction. This “or” rule means that either criterion can qualify a participant. Because the registry does not give counts for each criterion separately, the overall prevalence cannot reveal which criterion was responsible for classification in each group.

Why does uncertainty matter?

Any prevalence estimate based on a sample has uncertainty. General statistical explanation: a confidence interval gives a range of values compatible with the observed data under a specified method and assumptions. Wider intervals generally indicate less precision. The registry does not report confidence intervals or another uncertainty measure for these percentages. The denominators are 19, 6, and 5, so the estimates—especially those for the smaller groups—should be interpreted as limited descriptive evidence rather than precise population values.

A difference between two reported percentages is not, by itself, evidence of a statistically reliable difference. A formal comparison would require an analysis method and an estimate of uncertainty for the contrast. The registry posts no analyses for the primary outcome and no p-values or group-comparison intervals. No comparison should be inferred solely from the ordering or visual spacing of the percentages.

What does combining the drug groups mean?

The registry states that adenosine and regadenoson were combined for analysis as pre-specified because they were considered interchangeable. This means the posted prevalence results do not distinguish the two drugs. The record identifies the trial as randomized, single-masked, and parallel, but further details of randomization and masking are not reported in the registry record. The disease-group prevalence estimates should not be interpreted as randomized comparisons of cardiomyopathy against control status.

General statistical explanation: combining categories can make a pooled summary easier to interpret when a protocol treats the categories as exchangeable, but it removes the ability to inspect drug-specific outcome patterns in that summary. The posted data do not establish whether the observed prevalence was similar across the two drug groups.

Why can small groups and incomplete recruitment affect interpretation?

Small denominators make a proportion more sensitive to the outcome classification of individual participants. Slow recruitment also led to termination after 31 participants were recruited against an expected 75. The record does not report a sample-size justification or a target precision for estimating prevalence. It is therefore not possible to determine from the registry whether the observed groups were intended to support precise prevalence estimates, formal group comparisons, or both.

General statistical explanation: over-dispersion arises when observed variability exceeds what a chosen statistical model assumes. It can make standard errors too small if a model fails to account for that extra variability. The registry does not report a model-based analysis of these prevalence results, so over-dispersion is not an identified feature of the posted analysis; it is a general consideration when choosing methods for clustered or heterogeneous data.

No adjusted analysis is posted. The registry does not report covariate definitions, a statistical model, or a method for handling potential confounding. The posted percentages should thus be read as unadjusted descriptive summaries, not as estimates that isolate the association between clinical group and dysfunction from other characteristics.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and two secondary outcomes: CMR measurement of global perfusion reserve ratio, and the association between global perfusion reserve and regional myocardial scarring. It does not report analysis results for the secondary outcomes. A plan for controlling multiplicity across outcomes or analyses is not reported in the registry record. Because no primary-outcome analysis estimates or p-values are posted, there is no reported family of inferential tests from which to assess multiplicity adjustments.

The registry describes the adenosine and regadenoson groups as combined for analysis, as pre-specified, because the interventions were considered interchangeable. Further statistical-plan details, including how the primary outcome was to be analyzed, are not reported in the registry record. The record does not report interim analyses, stopping rules for statistical evidence, or a sample-size justification. Termination is attributed to slow recruitment and withdrawal of funding.

Missing-data handling and analysis populations are not reported in the registry record. The record does not state whether every recruited participant completed the scan, how unavailable or uninterpretable measurements were handled, or whether the posted denominators include all randomized participants. The enrollment figure is 31, while the primary outcome lists group denominators of 19, 6, and 5; the registry does not explain the relationship between the enrollment total and those outcome denominators. It also does not report an intention-to-treat, per-protocol, or other named analysis population. These omissions limit assessment of potential selection bias and the completeness of the outcome results.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry lists serious adverse events, other adverse events, and deaths separately for the adenosine and regadenoson groups within each clinical category. It reports zero serious adverse events and zero other adverse events in every listed group, and zero deaths in every listed group. The numbers at risk are reported for each group, with the hypertrophic cardiomyopathy groups, non-ischemic dilated cardiomyopathy groups, and control groups shown separately by intervention.

These entries describe what the registry reports for the participants at risk in those groups; they are not evidence that no adverse event could occur outside the recorded observation or reporting process. The registry does not provide further detail about event definitions, observation duration, ascertainment procedures, or whether adverse-event reporting was complete for all recruited participants. The reported safety counts should therefore be interpreted as registry-reported counts, not as a standalone comparison of the safety of adenosine and regadenoson.

The intervention groups were combined for analysis of the primary outcome, but the adverse-event entries remain separated by drug and clinical group. The record does not post a statistical comparison of adverse events between interventions or clinical groups.

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

The posted results describe how often the registry-defined CMR finding of microvascular dysfunction was reported in the assessed clinical groups. The prevalence was 79.0% in hypertrophic cardiomyopathy, 33.3% in non-ischemic dilated cardiomyopathy, and 20.0% in controls. The endpoint combines a global perfusion reserve threshold with regional stress perfusion abnormalities, so these values represent the combined classification rule rather than either component alone.

The results do not establish a statistically significant difference between groups. No formal comparison, p-value, confidence interval, or adjusted estimate is reported for the primary endpoint. The smaller denominators, particularly for non-ischemic dilated cardiomyopathy and controls, also constrain the precision and generalizability of the percentages. The registry does not report how missing or unassessable outcomes were handled.

The findings do not show that cardiomyopathy caused the imaging findings, or that adenosine or regadenoson produced a change in microvascular function. The registry states that the drug groups were combined as pre-specified, and the primary results do not report drug-specific estimates. Nor do the primary results establish the relationship between myocardial scarring and global perfusion reserve; that relationship appears among the secondary outcomes, but its results are not posted.

The study’s recruitment shortfall and termination are important context. The registry reports 31 recruited participants against an expectation of 75, with funding withdrawn because recruitment was slow. The results are consequently best treated as descriptive findings from the participants included in the posted outcome. They may motivate further study, but the registry record does not provide the inferential analysis or precision estimates needed to judge how reliably these group percentages characterize broader populations.

13. Why This Trial Matters Statistically

This trial is statistically informative because it illustrates the distinction between a prevalence summary and a comparative analysis. Reporting the proportion meeting a CMR-based definition can describe the observed sample, while a claim that groups differ requires an estimate of the contrast and its uncertainty. The registry posts the former but not the latter. Readers should not treat a ranking of group percentages as a substitute for a formal comparison.

The endpoint also combines a threshold-based global measure with regional perfusion abnormalities. Such a composite classification can capture more than one imaging feature, but a single prevalence does not show how often each feature contributed. Separate component counts would be needed to understand that composition, and they are not reported in the registry record.

Recruitment shortfall affects what can be learned. The registry reports 31 recruited participants against an expected 75 and notes that funding was withdrawn because recruitment was slow. The outcome denominators are limited, especially in the non-ischemic dilated cardiomyopathy and control groups. Without uncertainty estimates, the precision of the reported prevalences cannot be directly assessed. The record also does not explain the relationship between all recruited participants and the outcome denominators.

Finally, the stated combination of the two drug groups is relevant to interpretation. A pooled outcome is consistent with the registry’s pre-specified treatment of the interventions as interchangeable, but it does not reveal whether the separate drug groups had similar results. The study therefore highlights the value of reporting outcome definitions, group denominators, uncertainty, missing-data handling, and analysis plans alongside descriptive estimates.

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.

Several trial-specific limitations restrict interpretation. Recruitment was slow, the sponsor withdrew funding, and the study was terminated after 31 participants were recruited against an expected 75. This curtailed the available evidence and left small denominators for some clinical groups. The registry does not report a precision target or sample-size justification, so the intended statistical capability of the planned enrollment is not available.

The primary outcome is reported as percentages without confidence intervals or other uncertainty measures. No inferential comparison among clinical groups is posted, and no adjusted analysis is reported. The registry does not provide counts showing how many participants met the global ratio criterion, how many met the regional perfusion criterion, or how many met both. This prevents assessment of the separate components of the combined endpoint.

The posted denominators are 19, 6, and 5, while the registry reports total enrollment of 31. The record does not reconcile these figures or describe the outcome status of participants not represented in the group denominators. Missing-data procedures and the analysis population are not reported in the registry record. These details are needed to assess whether the reported results could be affected by incomplete outcome ascertainment.

Although the registry identifies the study as randomized, single-masked, and parallel, it does not report further details of allocation, masking, or how these design features related to the clinical groups. Adenosine and regadenoson were combined for primary analysis, so the posted outcome cannot be used to compare them. Results for the listed secondary outcomes are not provided, including the association between global perfusion reserve and regional myocardial scarring.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Microvascular Dysfunction in Nonischemic Cardiomyopathy: Insights From CMR Assessment of Coronary Flow Reserve — NCT03249272.
• Registry record last updated 2020-09-16; status last verified 2020-08.
• Results first posted 2020-09-16.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry describes a Phase 4, randomized, single-masked, parallel study of CMR-assessed microvascular dysfunction in hypertrophic cardiomyopathy, non-ischemic dilated cardiomyopathy, and controls. The primary endpoint is the percentage in each group meeting the registry definition, based on a global perfusion reserve ratio <2.0 or regional stress perfusion abnormalities at the scan on Day 1.

Posted prevalences are 79.0% among 19 participants with hypertrophic cardiomyopathy, 33.3% among 6 with non-ischemic dilated cardiomyopathy, and 20.0% among 5 controls. Adenosine and regadenoson were combined for analysis as pre-specified. The registry reports 31 recruited participants against an expected 75 and states that the study was terminated after funding was withdrawn because of slow recruitment.

No inferential primary-outcome analyses, uncertainty intervals, or secondary-outcome results are posted. The registry does not report missing-data procedures, the analysis population, or a detailed statistical plan.