Targeted Testing for ATTR Among Aortic Stenosis Patients-Pilot

Study Overview
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Brief Summary
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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
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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.

Official Title
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Targeted Testing for Transthyretin Cardiac Amyloid Among Aortic Stenosis Patients-Pilot

Conditions
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Aortic Valve Stenosis, Cardiac Amyloidosis

Intervention / Treatment
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* Diagnostic Test: PYP scan


Participation Criteria
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Eligibility Criteria
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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 Exclusion Criteria: Age <75 years Moderate to severe paravalvular aortic regurgitation on post-operative echocardiography

Ages Eligible for Study
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Minimum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Intervention Model: Single Group Assignment
Interventional Model Description: Participants 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Participants<br>Patients who had TAVR and underwent evaluation for ATTR with PYP scan | Diagnostic Test: PYP scan<br>* 99mTc-labeled pyrophosphate<br>* Other names: Bone scan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Prevalence ATTR with AVi <0.5 | Prevalence of ATTR among participants with AVi <0.5 mm Hg/beats per minute | Within 28 days after TAVR when bone scan completed | 
| Prevalence ATTR with AVi ≥0.5 | Prevalence of ATTR among participants with AVi ≥0.5 mm Hg/beats per minute | Within 28 days after TAVR when bone scan completed | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity AVi | Sensitivity of AVi <0.5 mm Hg/beats per minute | Within 28 days after TAVR when bone scan completed | 
| Specificity AVi | Specificity of AVi ≥0.5 mm Hg/beats per minute | Within 28 days after TAVR when bone scan completed | 
| Positive predictive value AVi | Positive predictive value of AVi <0.5 at predicting ATTR | Within 28 days after TAVR when bone scan completed | 
| Negative predictive value AVi | Negative predictive value of AVi ≥0.5 at ruling out ATTR | Within 28 days after TAVR when bone scan completed | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aortic stenosis, transthyretin cardiac amyloid, transcatheter aortic valve replacement, AortoVentricular index, ATTR, TAVR, AVi, invasive cardiac hemodynamics