Clinical trial NCT04363294: Targeted Testing for ATTR Among Aortic Stenosis Patients-Pilot
Official title: Targeted Testing for Transthyretin Cardiac Amyloid Among Aortic Stenosis Patients-Pilot
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Aortic Valve Stenosis
Cardiac Amyloidosis
Keywords: aortic stenosis
transthyretin cardiac amyloid
transcatheter aortic valve replacement
AortoVentricular index
ATTR
TAVR
AVi
invasive cardiac hemodynamics
Lead sponsor: University of Texas Southwestern Medical Center
Sponsor class: OTHER
Collaborators: name: Mid America Heart Institute
First posted: 2020-04-27
Enrollment: 0
Sex: ALL
Minimum age (years): 75
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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.
Primary purpose: SCREENING

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.

Eligibility criteria: 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

Primary outcomes:
measure: Prevalence ATTR with AVi <0.5
timeFrame: Within 28 days after TAVR when bone scan completed
measure: Prevalence ATTR with AVi ≥0.5
timeFrame: Within 28 days after TAVR when bone scan completed
Secondary outcomes:
measure: Sensitivity AVi
timeFrame: Within 28 days after TAVR when bone scan completed
measure: Specificity AVi
timeFrame: Within 28 days after TAVR when bone scan completed
measure: Positive predictive value AVi
timeFrame: Within 28 days after TAVR when bone scan completed
measure: Negative predictive value AVi
timeFrame: Within 28 days after TAVR when bone scan completed
Other outcomes:
measure: Prevalence ATTR with s'<6 plus AVi <0.5
timeFrame: Within 28 days after TAVR when bone scan completed
measure: Prevalence ATTR with s'≥6 plus AVi <0.5
timeFrame: Within 28 days after TAVR when bone scan completed
measure: KCCQ-12
timeFrame: 1 year after TAVR
measure: Favorable outcome
timeFrame: 1 year after TAVR
Locations:
Study officials:
affiliation: UT Southwestern Medical Center
name: Anthony A Bavry, MD MPH
role: PRINCIPAL_INVESTIGATOR
References: