Targeted Testing for ATTR Among Aortic Stenosis Patients-Pilot

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Aortic Valve Stenosis; Cardiac Amyloidosis
• Intervention / Treatment: Diagnostic test: PYP scan

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 Type: Interventional
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 75 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Screening
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Participants; Patients who had TAVR and underwent evaluation for ATTR with PYP scan	Diagnostic test: PYP scan; 99mTc-labeled pyrophosphate; Other Names: Bone scan

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence ATTR with s'<6 plus AVi <0.5	Prevalence of ATTR among participants with both s'<6 and AVi <0.5 mm Hg/beats per minute	Within 28 days after TAVR when bone scan completed
Prevalence ATTR with s'≥6 plus AVi <0.5	Prevalence of ATTR among participants with both s'≥6 and AVi <0.5 mm Hg/beats per minute	Within 28 days after TAVR when bone scan completed
KCCQ-12	Kansas City Cardiomyopathy Questionnaire(KCCQ) - a shortened 12 question version of the 23-item, self-administered instrument that quantifies physical function, symptoms (frequency, severity and recent change), social function, self-efficacy and knowledge, and quality of life. Scores are transformed to a range of 0-100, in which higher scores reflect better health status.	1 year after TAVR
Favorable outcome	Proportion of subjects who are alive with reasonable quality of life. Reasonable quality of life is defined as KCCQ-12 ≥60 without any meaningful worsening (decrease in KCCQ-12 summary score ≥10).	1 year after TAVR

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: Mid America Heart Institute
• Investigators: Principal Investigator: Anthony A Bavry, MD MPH, UT Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): September 1, 2022
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: April 23, 2020
• First Submitted That Met QC Criteria: April 23, 2020
• First Posted (Actual): April 27, 2020

Study Record Updates

• Last Update Posted (Actual): March 23, 2021
• Last Update Submitted That Met QC Criteria: March 18, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: aortic stenosis; ATTR; TAVR; transcatheter aortic valve replacement; transthyretin cardiac amyloid; AortoVentricular index; AVi; invasive cardiac hemodynamics
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Metabolic Diseases; Pathological Conditions, Anatomical; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Proteostasis Deficiencies; Aortic Valve Stenosis; Amyloidosis; Constriction, Pathologic
• Other Study ID Numbers: STU-2020-0386

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The primary investigator will upload de-identified individual data after study results have been published
• IPD Sharing Time Frame: Data will become available after study results have been published
• IPD Sharing Access Criteria: The primary investigator will upload study protocol, statistical analysis plan, informed consent form, and clinical study report after study results have been published
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No