IPM Take
Cardiac amyloidosis is becoming increasingly treatable. That makes diagnostic uncertainty increasingly expensive.
Current pathways often combine echocardiography or cardiac MRI with monoclonal-protein testing and bone-tracer scintigraphy. When AL amyloidosis has been excluded, technetium-based scintigraphy can establish ATTR cardiac amyloidosis non-invasively in selected patients. But ambiguous results, the presence of monoclonal proteins, or concern about AL disease can still push patients toward additional imaging or tissue biopsy. American College of Cardiology
Iodine-124 evuzamitide offers a different proposition. Rather than detecting a signal associated mainly with ATTR, the synthetic peptide is designed to bind directly to amyloid fibrils and has been studied across both ATTR and light-chain amyloidosis. In the Phase III REVEAL study, the PET/CT approach achieved high sensitivity and a high negative predictive value. JAMA Network
The key question is therefore not simply whether the tracer works.
It is where it belongs in a diagnostic pathway that already contains several tests.
Executive Summary
The prospective REVEAL study enrolled 195 adults undergoing evaluation for suspected cardiac amyloidosis at 18 US centres. The primary analysis included 170 patients, with a median age of 72 years; approximately three quarters were men. Three PET/CT readers interpreted the iodine-124 evuzamitide scans while blinded to clinical information, while three amyloidosis specialists independently adjudicated the diagnosis using standard-of-care clinical data. JAMA Network
The tracer achieved 94% sensitivity and 86% specificity for cardiac amyloidosis. Its positive predictive value was 85% and negative predictive value 94%. The study included patients with both ATTR and AL cardiac amyloidosis. JAMA Network
The test is not yet approved. Bayer, which acquired evuzamitide from Attralus in early 2026, says the agent has FDA Breakthrough Therapy Designation for PET imaging in suspected or known cardiac amyloidosis and Orphan Drug status in the US and EU. Bayer has said it plans to discuss regulatory submissions with the FDA and other authorities. Bayer Global
Why it matters
- HTA bodies: If approved, the central value question will not be sensitivity alone. Assessment will need to establish whether evuzamitide reduces invasive biopsies, shortens diagnostic pathways, changes subtype classification or enables treatment to start earlier.
- Payers: A new PET tracer adds acquisition, radiopharmacy and scanning costs. Its economic case will depend on where it replaces, rather than simply adds to, existing tests.
- Industry / innovation partners: Evuzamitide illustrates how molecular imaging is moving deeper into precision cardiology. Diagnostic value increasingly lies not just in visualising anatomy, but in directly identifying disease biology.
Cardiac amyloidosis is one of the diseases where therapeutic progress has made diagnostic precision more urgent.
The condition results from amyloid fibrils depositing in the myocardium, producing ventricular thickening, heart failure, conduction abnormalities and arrhythmias. The two major systemic forms affecting the heart, transthyretin amyloidosis and immunoglobulin light-chain amyloidosis, have very different underlying biology and treatment pathways. News Center
That makes simply recognising “amyloid” insufficient.
Current diagnostic practice is therefore deliberately layered. In patients with suspected disease, clinicians first assess for a circulating monoclonal protein using serum free light chains and serum and urine immunofixation. When AL amyloidosis has been excluded, technetium-labelled bone scintigraphy can establish ATTR cardiac amyloidosis in the appropriate clinical setting. Cardiac MRI, echocardiography, genetic testing and biopsy may also be required depending on the result. American College of Cardiology
The pathway works, but it can leave difficult cases.
A patient may have a suggestive cardiac MRI without definitive scintigraphy. A monoclonal gammopathy may complicate interpretation. Or clinicians may remain highly suspicious despite non-diagnostic testing.
The Phase III REVEAL trial tested whether iodine-124 evuzamitide could fill part of that gap.
Unlike conventional ATTR scintigraphy, evuzamitide is a radiolabelled synthetic peptide designed to bind directly to amyloid fibrils. In REVEAL, PET/CT imaging was performed three to five hours after intravenous administration of the tracer. Patients also received potassium iodide to reduce thyroid uptake of radioactive iodine. JAMA Network
The primary results were encouraging.
Among the 170 patients included in the efficacy analysis, the test correctly identified cardiac amyloidosis with 94% sensitivity and excluded it with 86% specificity. The negative predictive value was also 94%, suggesting potential value when clinicians need greater confidence in ruling disease out. JAMA Network
But those numbers need context.
The trial did not compare the PET result against biopsy in every patient. Instead, three independent amyloidosis experts, blinded to the PET result, adjudicated the diagnosis using the existing standard-of-care diagnostic algorithm. That is clinically relevant, but it means the test was benchmarked against the real-world diagnostic framework rather than universal histological confirmation. JAMA Network
The study population also skewed older and male, with a median age of 72 and 75% male representation, so additional evidence will help establish performance across broader populations. JAMA Network
Most importantly, a specificity of 86% means the tracer is not a standalone answer to every diagnostic problem. False-positive results remain possible, and laboratory testing for monoclonal proteins would still be essential because identifying the amyloid subtype determines treatment.
That is why the likely clinical position may be more targeted.
Northwestern cardiologist Richard Weinberg, a REVEAL investigator, suggested the tracer could be particularly useful when existing testing remains equivocal rather than automatically replacing a diagnostic pathway that has already produced a clear answer. News Center
That may ultimately be where its value is greatest.
Precision medicine often focuses on finding the right treatment for the right patient. Cardiac amyloidosis is a reminder that precision starts one step earlier: being certain what disease the patient actually has.
