Targeted Testing for ATTR Among Aortic Stenosis Patients-Pilot

Not Applicable

Withdrawn

• Conditions: Cardiac Amyloidosis; Aortic Valve Stenosis
• Interventions: Diagnostic Test: PYP scan

• Registration Number: NCT04363294
• Lead Sponsor: University of Texas Southwestern Medical Center

Brief Summary

Our ultimate goal is to design a multi-center randomized trial to test the hypothesis that targeted testing for transthyretin cardiac amyloid (ATTR) will improve survival and health status among aortic stenosis patients who undergo transcatheter aortic valve replacement (TAVR). The hypothesis of this pilot study is to evaluate if invasive cardiac hemodynamics obtained after TAVR, by using the AortoVentricular index (AVi), can be used as a novel test to help identify participants with ATTR.

Aim 1. To determine if an abnormal AVi value can identify ATTR among aortic stenosis patients undergoing TAVR.

Aim 2. To determine if s' from echocardiography plus AVi can enhance the prediction of ATTR among aortic stenosis patients undergoing TAVR.

Aim 3. To design a pilot trial to improve patient outcomes after TAVR by targeted testing for ATTR.

Detailed Description

Aim 1. To determine if an abnormal AVi value can identify ATTR among aortic stenosis patients undergoing TAVR. Patients undergoing TAVR for symptomatic severe aortic stenosis, with pre-TAVR echocardiography and post-implantation invasive hemodynamic assessment are eligible for study participation. The AVi will be recorded from post-implantation invasive hemodynamic assessment. Participants will undergo bone scintigraphy (99mTc-pyrophosphate Planar/SPECT imaging) within 28 days after TAVR. Participants with abnormal bone scintigraphy require evaluation for a monoclonal protein with blood/urine laboratory testing, and possible tissue biopsy/Hematology consultation to exclude light-chain amyloidosis. Participants who are ATTR positive will receive comprehensive heart failure management and possible genetic testing to evaluate for mutated ATTR. The prevalence of ATTR will be reported among participants with AVi \<0.5 versus ≥0.5 mm Hg/beats per minute. Test performance of AVi to predict ATTR will be reported.

Aim 2. To determine if s' obtained from echocardiography tissue Doppler imaging plus AVi can enhance the prediction of ATTR among aortic stenosis patients undergoing TAVR. The s' will be recorded from pre-TAVR tissue Doppler imaging of the mitral annulus. The prevalence of ATTR will be reported among participants with both s' ≤6 cm/second and AVi \<0.5 mm Hg/beats per minute versus s' \>6 cm/second and AVi \<0.5 mm Hg/beats per minute.

Aim 3. To design a pilot trial to improve patient outcomes after TAVR by targeted testing for ATTR. The change in Kansas City Cardiomyopathy Questionnaire-12 from baseline to 12-months and survival with reasonable quality of life at 12-months will be reported among participants who are ATTR positive vs. ATTR negative.

Study Timeline

• Study First Submitted: 2020-04-23
• Study First Submitted QC: 2020-04-23
• Study First Posted: 2020-04-27
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-18
• Last Update Posted: 2021-03-23
• Study Start: 2022-03
• Primary Completion: 2022-09
• Study Completion: 2023-08

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

• Successful implantation of a transcatheter heart valve with a commercially available valve (i.e. Sapien 3, Sapien Ultra, Evolut R, Evolut Pro, Evolut Pro+, or Lotus Edge) for native or bioprosthetic aortic stenosis
• Pre-implantation echocardiography with tissue Doppler imaging, if feasible
• Post-implantation invasive cardiac hemodynamics

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Exclusion Criteria

• Age <75 years
• Moderate to severe paravalvular aortic regurgitation on post-operative echocardiography

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Participants	PYP scan	Patients who had TAVR and underwent evaluation for ATTR with PYP scan

Primary Outcome Measures

Name	Time	Method
Prevalence ATTR with AVi <0.5	Within 28 days after TAVR when bone scan completed	Prevalence of ATTR among participants with AVi \<0.5 mm Hg/beats per minute
Prevalence ATTR with AVi ≥0.5	Within 28 days after TAVR when bone scan completed	Prevalence of ATTR among participants with AVi ≥0.5 mm Hg/beats per minute

Secondary Outcome Measures

Name	Time	Method
Sensitivity AVi	Within 28 days after TAVR when bone scan completed	Sensitivity of AVi \<0.5 mm Hg/beats per minute
Specificity AVi	Within 28 days after TAVR when bone scan completed	Specificity of AVi ≥0.5 mm Hg/beats per minute
Positive predictive value AVi	Within 28 days after TAVR when bone scan completed	Positive predictive value of AVi \<0.5 at predicting ATTR
Negative predictive value AVi	Within 28 days after TAVR when bone scan completed	Negative predictive value of AVi ≥0.5 at ruling out ATTR