- Design
- prospective, multicentre, single-group diagnostic accuracy study, 18 US centres, blinded readers and blinded adjudication (REVEAL)
- Population
- 170 analysed adults presenting with suspected cardiac amyloidosis and no established diagnosis; median age 72 years, 75.3% male
- Primary outcome
- sensitivity and specificity of 124I-evuzamitide PET/CT against adjudicated standard-of-care diagnosis
- Effect
- sensitivity 94% (95% CI 85-98), specificity 86% (95% CI 77-92); PPV 85%, NPV 94%
REVEAL enrolled 195 adults presenting for evaluation of suspected cardiac amyloidosis at 18 US centres, of whom 170 were analysed. Each had PET/CT three to five hours after 1 mCi of intravenous 124I-evuzamitide, with potassium iodide given to block thyroid uptake. Three readers scored cardiac uptake blinded to clinical data; three amyloidosis specialists adjudicated the diagnosis blinded to the scan, using the standard diagnostic algorithm.
Sensitivity was 94% (95% CI 85 to 98) and specificity 86% (95% CI 77 to 92), with positive predictive value 85% and negative predictive value 94%. The median age was 72, and 61.7% had NYHA class II or III symptoms.
The reason to care is what current imaging cannot do. Bone-avid tracer scintigraphy is effectively a transthyretin test; light-chain cardiac amyloidosis still needs biopsy, and a negative bone scan does not exclude it. A tracer that binds amyloid itself is agnostic to type and can show extracardiac deposits in the same acquisition.
This is a single-group accuracy study, not a comparison against existing imaging, and it was done in patients referred because amyloidosis was already suspected. In that high-prevalence setting a positive scan is worth more than it would be in unselected heart failure, and the 85% positive predictive value would fall in a lower-prevalence population. Treat it as a diagnostic advance awaiting availability rather than a test to start requesting: 124I is a cyclotron product with limited distribution, and there is no Indian regulatory position on this agent to report.
- A negative bone-tracer scan does not exclude cardiac amyloidosis; it argues against the transthyretin type only
- Always send serum free light chains and serum and urine immunofixation alongside any amyloid imaging
- Keep light-chain amyloidosis in mind when heart failure comes with raised troponin, low voltage on ECG and a thick ventricle
- Note that 14% of patients without amyloidosis had a positive scan, so a single positive result does not replace the diagnostic algorithm
- Do not change local practice yet: this agent is not generally available and its regulatory status in India is unknown
The statistics, in plain English
Sensitivity of 94% means the scan missed about 1 in 17 people who genuinely had cardiac amyloidosis; specificity of 86% means about 1 in 7 people without it still scanned positive. Predictive values depend on how common the disease is in the group being tested, and here it was common because everyone had been referred with suspicion, so the 85% positive predictive value is an optimistic figure that would drop in general heart-failure clinics. With no comparator arm, this study says the test performs well against expert adjudication; it does not say it performs better than what is already used.
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