quantitative-imaging in cardiac transthyretin amyloidosis

Conditions: ATTR-CM

Summary: transthyretin amyloid cardiomyopathy (attr-cm), is a heart muscle disease that's stops the heart muscle working properly. with an ageing population, it is increasingly common but untreated, it has a poor prognosis. several novel expensive treatments have become available, although we do not understand exactly how they work and why some patients respond, and others do not. the challenge is to develop better methods for monitoring the effects of these treatments, maximizing their benefits and cost-effectiveness. in i-care we aim to bring a new imaging technique, named 18f-fluoride pet, to the clinic and thereby improve the care of patients with attr-cm. hypotheses: 1. a delayed imaging protocol and state-of-the-art pet motion correction will optimise 18f-fluoride imaging in attr-cm and provide a clear threshold in myocardial tbr values for the diagnosis of attr-cm. 2. optimised 18f-fluoride pet will provide a quantitative marker of the attr-cm burden that will allow disease progression and treatment response to be tracked. 3. myocardial 18f-fluoride tbr values will reduce in patients responding to tafamidis treatment and increase in non-responders and patients not receiving therapy

studies have shown that there is calcium deposition in the heart muscle in attr-cm but exactly how this happens is not completely understood. tafamidis, a new drug treatment, has shown improved outcomes for patients with attrcm by reducing hospitalisations and improving survival but the mechanism of action of tafamidis is also not clearly understood yet. 18f-fluoride pet/ct offers the opportunity to study this phenomenon of calcium deposition in attr-cm in more detail and study and track response to the new drug treatment. this will also provide an opportunity to investigate whether tafamidis therapy reduces calcium deposition in the heart muscle associated with attr-cm. we have designed the study specifically to answer our research questions as best as possible, whilst keeping burdens to the patients at a minimum. to the best of our knowledge this will be the first human study to utilise this imaging technique to assess and track response to the new drug treatment in attr-cm. we hope that it will provide major insights in to complex interactions at play, that could drive forward the development of novel therapeutic strategies for patients with attr-cm.

Eligibility criteria:
inclusion criteria: * completion of informed consent * age \> 40 years for patients with attr or al cardiac amyloidosis and age \>30 years for patients with hcm * attr cardiac amyloid according to expert consensus recommendations * al amyloidosis according to expert consensus recommendations * hypertrophic cardiomyopathy according to european society of cardiology guidelines exclusion criteria: * inability or unwilling to give informed consent * women who are pregnant, breastfeeding or of child-bearing potential (women who have experienced menarche, are pre-menopausal and have not been sterilised) will not be enrolled into the trial. * renal dysfunction (egfr ≤30 ml/min/1.73m2) * nyha class iv heart failure * patients with atrial fibrillation and poor rate control. * contraindications to mr * previous history of contrast allergy of adverse reactions (gadolinium) * contraindications to tafamidis therapy

Keywords: amyloidosis heart failure 18f-fluoride positron emission tomography (pet) cardiovascular magnetic resonance (cmr) tafamidis