Prevalence and Characteristics of Transthyretin Amyloidosis in Patients With Left Ventricular Hypertrophy of Unknown Etiology: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prevalence and Characteristics of Transthyretin Amyloidosis in Patients With Left Ventricular Hypertrophy of Unknown Etiology (NCT03842163), a registered phase not stated study. The primary outcome is Percentage of Participants With Cardiac Fixation at the Radionuclide Bone Scintigraphy and/or Single Photon Emission Computed Tomography (SPECT): FAS1.

2. Clinical Question

The study focuses on the frequency of a scan finding in a selected clinical population, rather than on whether one treatment changes an outcome relative to another. Its stated purpose is to determine the prevalence of transthyretin amyloid cardiomyopathy among patients admitted with LVH of unknown etiology. The primary outcome is narrower in wording: it counts participants with cardiac fixation on the specified imaging tests. That scan finding is the endpoint being measured; the result itself is not reported in the registry record.

The outcome definition includes cardiac fixation identified by radionuclide bone scintigraphy and/or SPECT, using 99mTc-DPD, 99mTc-PYP, or 999mTc-HMDP as listed in the record. It defines uptake grades from absent cardiac uptake to high uptake greater than bone. The record does not give a primary result broken down by grade, nor does it state how the prevalence objective is linked to any particular grade threshold. Thus, the primary question can be described from the endpoint definition, but its numerical answer and the precise classification threshold used for that answer are not reported in the registry record.

3. Trial Design

The registry record describes a completed diagnostic study with one listed group: patients with LVH of unknown etiology. The study intervention is titled “Diagnosis of TTR amyloidosis cardiomyopathy” and is categorized as a diagnostic test. The stated purpose is to assess the prevalence of ATTR cardiomyopathy among patients admitted with LVH greater than 15 mm of unknown etiology, using a 99mTc-tracer-based scintigraphy protocol.

Enrollment was 812. The study start date is 2018-07-09, and the primary completion date is 2022-06-08. The primary outcome timeframe describes collection and observation during that period, approximately 3.11 years. These dates describe the study period; they do not establish how long each participant was observed or when each participant underwent imaging. Individual timing is not reported in the registry record.

The primary outcome population is FAS1, defined as eligible participants who had radionuclide bone scintigraphy and/or SPECT performed with one of the specified tracers. This is a more specific definition than enrollment alone. The number of enrolled participants who met the FAS1 definition is not reported in the registry record, so enrollment should not be treated as the primary-outcome denominator.

No randomized allocation or separate comparator arm is described. Allocation is not stated, and the listed arms are not a like-for-like control comparison. The record therefore supports describing a single-group diagnostic assessment, not a randomized treatment comparison. Details such as recruitment procedures, site structure, blinding, the timing of tests relative to other assessments, and a prespecified statistical analysis plan 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: Data from eligible participants were retrieved and observed from 09-Jul-2018 to 08-Jun-2022 (approximately 3.11 years).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: FAS1 included all participants who met eligibility criteria and with a radionuclide bone scintigraphy and/or SPECT performed with 99mTc-DPD/99mTc-PYP/99mTc-HMDP.

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: Full Analysis Set 1 (FAS1) included all participants who met eligibility criteria and with a radionuclide bone scintigraphy and/or SPECT performed with 99mTechnetium-3,3-diphosphono-1,2-propanodi-carboxylic acid (99mTc-DPD) or 99mTechnetium-pyrophosphate (99mTc-PYP) or 99mTechnetium-hydroxymethylene diphosphonate (99mTc-HMDP).

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Cardiac Fixation at the Radionuclide Bone Scintigraphy and/or Single Photon Emission Computed Tomography (SPECT): FAS1, measured over During collection and observation duration from 09-Jul-2018 to 08-Jun-2022 (approximately 3.11 years).

The primary endpoint is the percentage of FAS1 participants with cardiac fixation on radionuclide bone scintigraphy and/or SPECT. FAS1 includes participants who met eligibility criteria and received the specified imaging test with 99mTc-DPD, 99mTc-PYP, or 999mTc-HMDP. The endpoint is therefore a proportion in a defined tested population, not a measure of change over time or a comparison between treatment groups.

The registry description defines scintigraphy uptake by grade: Grade 0 is absent cardiac uptake, Grade 1 is mild uptake less than bone, Grade 2 is moderate uptake equal to bone, and Grade 3 is high uptake greater than bone. The record does not state in the primary outcome description which grade or grades count as “cardiac fixation” for the reported percentage. The exact operational threshold is therefore not reported in the registry record.

A percentage is used to express how common the specified scan finding is among the participants in the analysis population. The associated 95% confidence interval is intended to convey statistical uncertainty around that estimate: in general, an interval gives a range of values compatible with the data and the method used to calculate it. Neither the observed percentage nor its confidence interval is reported in the registry record. The endpoint can be identified, but its estimate and precision cannot be evaluated from the posted primary outcome information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The available information identifies a percentage endpoint, a defined analysis population, and a 95% confidence interval. It does not describe the statistical procedures used to estimate the percentage or interval. The explanations below distinguish the general meaning of these methods from what can be established about the study.

What does a percentage endpoint represent?

For a binary outcome, each participant is classified as having or not having the defined event. The percentage is the share of the analysis population classified as having the event. In this study, the event is cardiac fixation on radionuclide bone scintigraphy and/or SPECT, and the analysis population is FAS1. The registry record does not report the number of FAS1 participants or the number with the event, so the observed percentage cannot be recovered from the information available.

The denominator matters because it defines the population to which the percentage refers. Enrollment is 812, whereas FAS1 includes eligible participants who also had the specified imaging test. Those populations need not be identical. The number enrolled who entered FAS1, and the reasons any enrolled participants did not enter that population, are not reported in the registry record.

What does a confidence interval communicate?

In general, a confidence interval expresses the uncertainty associated with an estimate under a particular statistical procedure and its assumptions. For a percentage, its width depends in part on the amount of information in the analysis population and on the observed proportion. The interval does not remove uncertainty about how participants were selected, how the endpoint was classified, or whether missing outcomes could affect the estimate.

The registry identifies a 95% confidence interval as the dispersion measure for the primary outcome. It does not report the interval limits or the calculation method. It is therefore not possible to assess its width, check the calculation, or determine whether the method accounted for design features or other sources of variation. The confidence level alone is not a result.

How does the imaging definition affect interpretation?

The endpoint uses cardiac fixation on radionuclide bone scintigraphy and/or SPECT, with specified tracers. The description gives an uptake grading system, but it does not state which grades count toward the primary percentage. That detail is important for reproducing the endpoint classification and interpreting what the percentage represents. The record also does not report reader training, independent review, adjudication, or blinding procedures. These operational details are not reported in the registry record.

More generally, a diagnostic test result is an observed classification, while a diagnosis may require additional criteria. The registry lists secondary outcomes for ATTR and several ATTR subtypes, as well as a combined outcome involving suspected MGUS or AL. Without reported definitions and results for those outcomes, the primary imaging percentage should not be treated as interchangeable with a percentage of participants who have a particular amyloid diagnosis.

What can be inferred from the design?

The listed population consists of patients with LVH of unknown etiology, and the study has a diagnostic test intervention rather than a described treatment contrast. The record does not identify a separate control group, randomized allocation, or a comparison of diagnostic strategies. A prevalence-oriented percentage in this setting describes the frequency of the defined finding in the studied analysis population; it does not by itself estimate a treatment effect or establish how the result would differ in another population.

Generalizability depends on how participants entered the study and how closely the studied population resembles the population of interest. The record states the clinical context and the LVH criterion in the study summary, but recruitment details and the representativeness of participants are not reported in the registry record. Those omissions limit conclusions about applying any prevalence estimate outside the study population, even if a numerical estimate were available.

What is not established about the analysis?

The registry record does not report the statistical analysis plan, the method for calculating the confidence interval, any covariate adjustment, or handling of incomplete or indeterminate test results. It also does not report a sample-size justification or interim-analysis plan. These details should not be inferred from the outcome label or from the study duration.

The record lists 115 outcome measures, including multiple measures of ATTR and its subtypes. In general, examining multiple outcomes can raise questions about multiplicity: when many statistical claims are assessed, the chance of at least one apparently notable result can increase unless the analysis addresses that issue. The record does not state whether any multiplicity procedure or outcome hierarchy was used. It also lists 0 analyses, so no analysis-specific result or adjustment can be described from the registry information.

Any planning illustrations based on an observed effect are not observed trial results and are not a substitute for the actual estimate and its uncertainty. Sample-size calculations are planning tools, not measures of the probability that a completed study has produced a correct finding. The registry record does not report the primary endpoint estimate required to interpret such an illustration, nor does it provide a trial-specific design justification. The observed outcome and the methods used to estimate it remain unreported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 115 outcome measures. The named secondary outcomes include percentages with ATTR, ATTRv, and ATTRwt, as well as a combined outcome involving ATTR or suspicion of MGUS or AL. The record does not describe a hierarchy for testing these outcomes, a primary-secondary testing sequence, or a method for controlling multiplicity. In general, multiplicity matters when multiple outcomes or subgroup questions are assessed, because interpreting each result separately can overstate the strength of evidence. Whether that issue was addressed in the study analysis is not reported in the registry record.

The record identifies FAS1 for the primary endpoint and gives definitions for several secondary analysis populations, including FAS2 and FAS3. It does not report the numbers of participants in these populations or how participants were allocated among them. Nor does it describe how missing, unreadable, indeterminate, or technically unsuccessful imaging results were handled. The extent and pattern of missing data are not reported in the registry record.

Missingness can affect a percentage when participants without an evaluable result are excluded or classified in a particular way. The direction and size of any effect depend on the data and the handling rules; neither can be inferred. The record also does not state whether sensitivity analyses were used to assess the effect of missing outcomes.

The registry lists 0 analyses, and no statistical analysis plan is described. Therefore, adjustments for multiplicity, handling of missing data, and analysis-population decisions cannot be assessed from the posted record.

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

The study addresses a clinically defined prevalence question: how often cardiac fixation is observed on specified imaging among eligible patients with LVH of unknown etiology who underwent the test. The registry provides a primary endpoint definition and identifies its intended analysis population. It does not report the observed percentage, confidence interval limits, or denominator. The central numerical result is therefore not reported in the registry record.

Even if the percentage were available, its meaning would be tied to the participants included in FAS1 and to the study’s endpoint classification rules. The enrollment figure of 812 does not establish how many people were included in that analysis. The stated scan grading system helps describe uptake, but the record does not specify which grades qualify as cardiac fixation for the primary result. These details are necessary to understand precisely what a reported percentage would count.

The primary endpoint is an imaging finding, whereas the study purpose refers to ATTR cardiomyopathy and the secondary outcomes include amyloid types and related diagnostic categories. These concepts should not be treated as identical without the study’s diagnostic criteria and results. The record does not report those criteria or the subtype findings. The primary endpoint alone cannot establish how many participants had each listed amyloid subtype.

This is not a comparison of treatments. No separate control group or randomized treatment allocation is described, and allocation is not stated. The outcome therefore cannot be interpreted as evidence that a treatment changed the frequency of a finding. Nor can a prevalence result from this selected group automatically be generalized to people with other causes of LVH or to populations recruited in different ways.

In general, an estimate and its confidence interval describe both the observed frequency and uncertainty under the analysis method. Here, the estimate, interval limits, denominator, and interval method are not reported in the registry record. The record supports describing the question and the planned measurement, but not a numerical conclusion about the prevalence or precision of the finding.

12. Why This Trial Matters Statistically

Prevalence questions require careful definition of both the population and the condition being counted. This study’s record specifies a population with LVH of unknown etiology, a diagnostic imaging approach, and a primary outcome based on cardiac fixation. Keeping those elements distinct helps readers see that a prevalence estimate depends on who was tested and how the scan result was classified.

The FAS1 definition makes the tested population central to interpretation: it includes eligible participants who had the specified scintigraphy and/or SPECT. Enrollment was 812, but the record does not report the FAS1 denominator. That distinction is statistically important because the analysis population, rather than enrollment alone, determines the base of the reported percentage. Without its size and the event count, neither the estimate nor its precision can be checked.

The endpoint also illustrates why diagnostic findings and diagnostic labels should not be conflated. The primary measure concerns an imaging finding; separate secondary measures concern ATTR and subtypes. A clear analysis needs operational definitions that connect the observed test result to the condition being counted. The record gives a grading scale but does not state the primary threshold or report the corresponding result.

Finally, the registry lists many outcome measures but does not describe the analysis plan or any approach to multiplicity. This leaves uncertainty about how the primary and secondary questions were prioritized and how the results were intended to be interpreted together. These are important statistical features of a prevalence study, even when it does not compare treatments. The missing numerical results and analysis details prevent assessment of the study’s estimate and its reliability.

13. 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 primary limitation for interpreting the posted information is that the primary outcome result is not reported in the registry record. The percentage, confidence interval limits, and FAS1 denominator are absent, so the prevalence estimate and its statistical precision cannot be evaluated. Although enrollment was 812, that number does not establish the analyzed population size.

The endpoint description leaves a classification detail unresolved: it defines uptake grades but does not identify which grade or grades count as cardiac fixation for the primary percentage. The diagnostic criteria linking imaging findings to ATTR cardiomyopathy are not reported in the registry record. The secondary outcomes name ATTR, ATTRv, ATTRwt, and suspected MGUS or AL categories, but their definitions and numerical findings are not available in the record.

Recruitment methods, participant characteristics, site information, and the representativeness of the enrolled group are not reported in the registry record. Consequently, the extent to which results would apply to other groups with LVH cannot be assessed. The record does not report how many participants lacked evaluable imaging, why they might have lacked it, or how incomplete or indeterminate findings were handled.

Statistical limitations also include the absence of a reported analysis plan, confidence-interval method, sample-size justification, multiplicity approach, and details of any interim analyses. These omissions do not establish that such procedures were absent from the study; they mean they are not reported in the registry record. No separate control group or randomized comparison is described, so the study cannot be interpreted from this record as a comparative treatment trial.

14. Related Tutorials

15. Related Statistical Calculators

16. Sources

• ClinicalTrials.gov: Prevalence and Characteristics of Transthyretin Amyloidosis in Patients With Left Ventricular Hypertrophy of Unknown Etiology — NCT03842163.
• Registry record last updated 2024-02-12; status last verified 2023-05.
• Results first posted 2024-02-12.
• 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.

17. Record Summary

The registry record describes a completed study titled “Prevalence and Characteristics of Transthyretin Amyloidosis in Patients With Left Ventricular Hypertrophy of Unknown Etiology.” Its stated purpose is to assess ATTR cardiomyopathy prevalence among patients admitted with LVH greater than 15 mm of unknown etiology using a 99mTc-tracer-based scintigraphy protocol. Enrollment was 812; the recorded study dates are 2018-07-09 to 2022-06-08.

The primary outcome is the percentage of FAS1 participants with cardiac fixation on radionuclide bone scintigraphy and/or SPECT. FAS1 comprises eligible participants who underwent the specified imaging. The record lists secondary outcome measures concerning ATTR and subtypes, and identifies a 95% confidence interval for the primary endpoint. It lists 115 outcome measures and 0 analyses.

The primary percentage, confidence interval limits, analysis denominator, and statistical methods are not reported in the registry record. The study has no described like-for-like control comparison.