Quantitative Analysis of Myocardial Uptake of Bone Radiopharmaceuticals in Patients With Cardiac ATTR Amyloidosis

Official title

Quantitative Analysis of Myocardial Uptake of 99mTclabeled Bone Radiopharmaceuticals Using New Whole-body CZT-based SPECT-CT Cameras, at Baseline and During Medical Treatment With Tafamidis in Patients With Cardiac Transthyretin Amyloidosis

Overview

Introduction: Transthyretin cardiac amyloidosis (ATTR) is an important cause of heart failure. Cardiac planar radionuclide imaging using 99mTc-labeled bone seeking radiopharmaceuticals is used as a noninvasive diagnostic criterion in patients without detectable monoclonal protein. The visual assessment remains the main noninvasive criterion for the diagnosis. Medical therapy using tafamidis meglumine that binds to transthyretin and prevents amyloidogenesis, recently demonstrated a reduction in all-cause mortality and cardiovascular-related hospitalizations. As a consequence, there is a need for quantitative approaches that would be useful for diagnosis and prognosis assessment but also for the evaluation of patient therapeutic response. Materials and methods: The investigators aim to include 35 patients with a suspected diagnosis of cardiac ATTR amyloidosis in whom a cardiac planar radionuclide imaging using 99mTc-labeled bone seeking radiopharmaceuticals is planned as part of routine noninvasive diagnosis work-up. Using a test-retest approach, the aim is to compare a quantitative method vs. conventional semi-quantitative approaches for the assessment of cardiac uptake of bone radiopharmaceuticals using new 3D CZT-based SPECT-CT cameras in patients with suspected cardiac ATTR amyloidosis. The investigators estimated that 20 patients will have a diagnosis of cardiac ATTR amyloidosis. In the latter patients, the aim is to evaluate the impact of 6-month therapy using tafamidis on quantitative and semi-quantitative assessment of cardiac uptake of bone radiopharmaceuticals Perspectives: This new non invasive imaging techniques for the quantitative assessment of the amyloid burden in patients with cardiac ATTR amyloidosis may help identify the responders and the patients who should benefit from dose intensification.

Interventions

• Diagnostic test Whole-body & CZT bone tracer imaging (SPECT)
  Quantitative analysis of myocardial uptake of 99mTc-labeled bone radiopharmaceuticals using new whole-body CZT-based SPECT-CT cameras

Primary outcome measures

• Test-retest reproducibility [Time frame: 10 days]
• Correlations between the quantitative assessment of the myocardial uptake of bone tracers and semi-quantitative approaches [Time frame: 10 days]
• Comparison between the quantitative assessment of the myocardial uptake of bone tracers (COV) between baseline and follow-up imaging of each patient, 6 months after the beginning of the treatment by tafamidis [Time frame: 6 months]

Eligibility criteria

Inclusion criteria

• Medical history of Heart Failure (HF) with at least 1 prior hospitalization for HF or clinical evidence of HF (without hospitalization) manifested by signs or symptoms of volume overload or elevated intracardiac pressures that required/requires treatment with a diuretic for improvement, and an increase of BNP >200 pg/mL and/or NT-proBNP >500 pg/mL
• Suspected cardiac ATTR amyloidosis
• Evidence of cardiac involvement by echocardiography with an end-diastolic interventricular septal wall thickness > 12 mm
• Patient signed consent
• Contraception method

Exclusion criteria

• New York Heart Association (NYHA) functional class IV despite diuretic treatment
• Life expectancy <6 month due to the severity of cardiac amyloidosis and/or comorbidities
• Aortic valve surgical or percutaneous replacement within 30 days or planned within months
• Presence of primary (light chain) amyloidosis
• Contraindication to tafamidis
• Pregnancy and breast feeding ; pregnancy test in women of reproductive age irrespective of contraception method)
• Adults with protective measures

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Diagnostic

Study locations

France · 2 centers

• CHU de Caen — Caen
• Clinique du Bois — Lille

Publications

• Legallois D, Turcan L, Agostini D, Manrique A. Test-retest reproducibility of myocardial 99mTc-HMDP uptake quantification by SPECT-CT in suspected transthyretin cardiac amyloidosis. J Nucl Cardiol. 2025 Sep;51:102273. doi: 10.1016/j.nuclcard.2025.102273. Epub 2025 Jun 13. PMID 40518108

Identifiers

NCT: NCT04535349 · 19-226

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗