Cardiac amyloidosis is responsible for significant morbidity associated with heart failure, and carries a poor prognosis. Currently there are very limited treatment options for this condition. Radiotherapy has been used successfully to treat amyloidosis elsewhere in the body, however has not been tried in cardiac amyloidosis. Therefore this study aims to assess the effect of radiotherapy on cardiac amyloidosis, to evaluate whether it can successfully reduce the burden of amyloid deposits in the myocardium as assessed by 18F-Amyloid PET.

The intervention will involve administration of external beam radiotherapy (5 fractions of 2Gy) focused to the heart.

Measurements of effect will be assessed at 12 weeks by:

Amyloid PET Cardiac MRI with administration of gadolinium and ultrasound A blood venous sample (cardiac biomarkers) Quality of life assessments

Inclusion Criteria:

• Age >65 y.o.
• Dyspnoea on exertion (NYHA II or more).
• Stable elevated cardiac enzymes (ultra sensitive Troponin T > 14 ng/L on consecutive sampling or BNP > 100pg/mL)
• A positive 99mTc-DPD cardiac scintigraphy (Grade 2 and 3) suggesting an ATTR or wt amyloidosis.
• Additional imaging also compatible with cardiac amyloidosis (cardiac ultrasound showing basal to apical longitudinal strain gradient and magnetic resonance imaging with elevated T1 value or extracellular volume).
• Compliance with the informed consent as attested by its signature.
• Positive baseline 18F-Florbetapir imaging, as assessed visually and quantitatively by a Tissue to Background Ratio > 1.45

Exclusion Criteria:

• Positive serum protein immunoelectrophoresis with monoclonal gammapathy.
• Previous external beam radiotherapy including the chest.
• Claustrophobia
• Presence of internal non-MR compatible devices
• Creatinine glomerular filtration rate < 30 ml/min
• Oncologic disease (excluding skin cancer) active or in remission from less than 5 years