124I-Evuzamitide Positron Emission Tomography/Computed Tomography for Diagnosing Cardiac Amyloidosis: The REVEAL Nonrandomized Clinical Trial.

Diagnosing cardiac amyloidosis remains challenging because current imaging approaches are limited to transthyretin amyloidosis. A noninvasive test capable of directly imaging cardiac amyloidosis from various amyloid types and in multiple organs could address an important unmet diagnostic need. To evaluate the sensitivity and specificity of 124I-evuzamitide positron emission tomography (PET)/computed tomography (CT) for diagnosing cardiac amyloidosis. Prospective, multicenter (18 US centers), single-group study evaluating the efficacy of 124I-evuzamitide to diagnose cardiac amyloidosis. This study was conducted from January 14, 2025, to March 12, 2026, including a 60-day follow-up period. Three physicians with cardiac PET/CT experience independently reviewed PET/CT images for visual cardiac 124I-evuzamitide uptake while blinded to clinical data. Three expert clinical amyloidosis physicians, blinded to PET/CT data, independently adjudicated the diagnosis based on the standard-of-care diagnostic algorithm. A total of 195 adults suspected of having cardiac amyloidosis were enrolled when they presented for diagnostic evaluation at participating institutions, excluding patients with an established diagnosis of cardiac or systemic amyloidosis. PET/CT scans were obtained 3 to 5 hours after intravenous administration of 1 mCi of 124I-evuzamitide. Potassium iodide (130 mg) was given orally for 3 days starting at least 30 minutes prior to 124I-evuzamitide injection. Coprimary end points of this study were to assess the sensitivity and specificity of 124I-evuzamitide for the diagnosis of cardiac amyloidosis. Overall, 170 patients were included (median [IQR] age, 72 [64-79] years; 75.3% male, 19.2% Black, 79.0% White). Median N-terminal pro-brain natriuretic peptide was 471 pg/mL and 61.7% had New York Heart Association class II or III heart failure symptoms. The overall sensitivity was 94% (95% CI, 85%-98%; P < .001); specificity, 86% (95% CI, 77%-92%; P < .001); positive predictive value, 85% (95% CI, 75%-92%); and negative predictive value, 94% (95% CI, 87%-98%). 124I-evuzamitide PET/CT is highly sensitive and specific for diagnosing cardiac amyloidosis with an acceptable safety profile. These results support 124I-evuzamitide PET/CT as a diagnostic test to evaluate patients with suspected cardiac amyloidosis. ClinicalTrials.gov Identifier: NCT06788535.