Targeted Testing for ATTR Among Aortic Stenosis Patients-Pilot

Aortic Valve Stenosis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT04363294
• Other study ID #: STU-2020-0386
• Status: Withdrawn
• Phase: N/A
• Start date: March 2022
• Est. completion date: August 2023

Study information

• Verified date: March 2021
• Source: University of Texas Southwestern Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: August 2023
• Est. primary completion date: September 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 75 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyloidosis
• Aortic Valve Stenosis
• Cardiac Amyloidosis
• Constriction, Pathologic

Intervention

Diagnostic Test:
• PYP scan
99mTc-labeled pyrophosphate

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
University of Texas Southwestern Medical Center	Mid America Heart Institute

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Primary	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
Primary	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	Sensitivity AVi	Sensitivity of AVi <0.5 mm Hg/beats per minute	Within 28 days after TAVR when bone scan completed
Secondary	Specificity AVi	Specificity of AVi =0.5 mm Hg/beats per minute	Within 28 days after TAVR when bone scan completed
Secondary	Positive predictive value AVi	Positive predictive value of AVi <0.5 at predicting ATTR	Within 28 days after TAVR when bone scan completed
Secondary	Negative predictive value AVi	Negative predictive value of AVi =0.5 at ruling out ATTR	Within 28 days after TAVR when bone scan completed