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

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.

• No cardiac ATTR amyloidosis

  Cardiac echocardiography at baseline and whole-body & CZT bone tracer imaging (SPECT).

  day 3 - day 10 : second whole-body & CZT bone tracer imaging (SPECT), test-retest Bone tracer imaging Perugini 0 : no cardiac TTR amyloidosis No further follow-up.

  Intervention: Diagnostic Test: Whole-body & CZT bone tracer imaging (SPECT)
• Cardiac ATTR amyloidosis, no treatment with tafamidis planned

  Cardiac echocardiography at baseline and whole-body & CZT bone tracer imaging (SPECT).

  day 3 - day 10 : second whole-body & CZT bone tracer imaging (SPECT), test-retest Bone tracer imaging demonstrating cardiac ATTR amyloidosis but no treament with tafamidis planned.

  Cardiac echocardiography at 3 months and whole-body & CZT bone tracer SPECT and cardiac echocardiography at 6 months

  Intervention: Diagnostic Test: Whole-body & CZT bone tracer imaging (SPECT)
• Cardiac ATTR amyloidosis, treatment with tafamidis planned

  Cardiac echocardiography at baseline and whole-body & CZT bone tracer imaging (SPECT).

  day 3 - day 10 : second whole-body & CZT bone tracer imaging (SPECT), test-retest Bone tracer imaging demonstrating cardiac ATTR amyloidosis. Start of the treament with tafamidis.

  Cardiac echocardiography at 3 months and whole-body & CZT bone tracer SPECT and cardiac echocardiography at 6 months

  Intervention: Diagnostic Test: Whole-body & CZT bone tracer imaging (SPECT)

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