Natural History of Cardiac Transthyretin Amyloidosis - Mechanistic Insights by Multimodality Imaging
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 50
- Locations
- 2
- Primary Endpoint
- Change in FAPI uptake
Study Overview
Brief Summary
The goal of this clinical trial is to investigate whether new imaging techniques can help us to better understand the cardiac amyloidosis. The disease can be slowed down with various medications (e.g., tafamidis, acoramidis, or vutrisiran). However, treatment is not effective in all patients-in about one-third of cases, the disease continues to progress. So far, we know little about the exact causes of this and what biological changes occur in the heart muscle.
The main question it aims to answer is:
Will new imaging techniques help us understand the course of the cardiac amyloidosis?
Participants will have additional examinations:
- At the beginning of the study: one additional heart ultrasound examination, one cardiac MRI and one cardiac PET, blood examination during the regular examination, questionnaires.
- After a year: one additional heart ultrasound examination, one cardiac MRI and one cardiac PET, blood examination during the regular examination.
Time required:
- Heart ultrasound examination: 5-10 Minutes
- Cardiac MRI: 2 hours
- Cardiac PET: 2 hours
- Questionnaires: 5-10 Minutes.
Detailed Description
Experimental Design The study design is an open label prospective longitudinal study with serial imaging at baseline and after 12-month follow-up. The entire study population will include 50 participants with cardiac ATTR amyloidosis, as recently defined by multi-societal criteria.
Conventional markers of disease progression
These markers are collected during routine clinical follow-up of patients in our Outpatient Clinic. The markers are divided into three domains and include the following outcomes:
- Clinical and functional: any heart failure hospitalization, NYHA class, Kansas City Cardiomyopathy Questionnaire, 6-minute walk test;
- Laboratory biomarkers: NT-proBNP, troponin, creatinine;
- Imaging and ECG: LV wall thickness, diastolic dysfunction, LVEF, stroke volume, global longitudinal strain, conduction disturbance.
Data Analysis Plan Power calculation for sample size is challenging as no previous study has evaluated the response of our endpoints in myocardial FAPI uptake or serum BMP4 concentration to tafamidis. We therefore focused sample size calculation of echocardiographic myocardial stiffness. Based on our own preliminary data, we estimate median baseline values for myocardial stiffness of 2.6 m/s [IQR, 1.7-3.8] in cardiac amyloidosis. Disease progression is expected in about 30% of participants. While myocardial stiffness is expected to remain unchanged in cardiac amyloidosis without disease progression a 20% relative increase (i.e. 0.5 ± 0.5 m/s) is considered in cardiac amyloidosis with disease progression. A sample size of 40 participants (i.e. 30 participants without and 10 participants with disease progression) has a statistical power of 80% to predict a difference in response of myocardial stiffness to tafamidis.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Eligibility Criteria
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Participants with cardiac ATTR amyloidosis, as recently defined by multi-societal criteria, who are about to start tafamidis at the University Hospital Zurich
Exclusion Criteria
- •Any other disease-modifying therapy (e.g. patisiran)
- •Ongoing supraventricular arrhythmia
- •Ventricular pacing
- •Prior septal myocardial infarction
Arms & Interventions
18F-FAPI PET/CT
Additional imaging including 18F-FAPI PET/CT is performed
Intervention: FAPI tracer (Diagnostic Test)
Outcomes
Primary Outcomes
Change in FAPI uptake
Time Frame: Baseline and 1 year
F-FAPI-74 PET/CT is performed at baseline and 12-month follow-up. Images are acquired on a PET/CT scanner 60 minutes after intravenous injection of F-FAPI-74. The emission scan is obtained from the apex of the lung to the base of the lung. One bed position is acquired (20 minutes, 3-dimensional mode), and the heart is set at the center of the view. Myocardial F-FAPI-74 uptake is quantified by the mean standardized uptakte value of the LV volume of interest (VOI). The epicardial LV contour is drawn on the CT scan and, to correct for blood pool activity, the endocardial border is defined automatically by thresholding for 2 times the mean SUV of the blood pool.
Secondary Outcomes
- Change in BMP4 expression and serum concentration(Baseline and 1 year)
- Change in echocardiographic myocardial stiffness(Baseline and 1 year)
- Change in extracellular volume (ECV)(Baseline and 1 year)
Investigators
Dominik Benz
PD Dr. med. Dominik C. Benz
University of Zurich