Multimodality Imaging Characterization of Perugini Scintigraphic Grades in Transthyretin Amyloid Cardiomyopathy: a single center experience

Background Transthyretin amyloid cardiomyopathy (ATTR-CM) has undergone a shift towards non-invasive diagnostics using bone tracer scintigraphy with Perugini grading. While both grades 2 and 3 are considered diagnostic, potential phenotypic differences between these groups remain uncertain. We aimed to evaluate the diagnostic yield of technetium-99m pyrophosphate (99mTc-PYP) scintigraphy and to compare clinical and multimodality imaging characteristics across scintigraphic grades in a single-center cohort. Methods We retrospectively reviewed all patients who underwent 99mTc-PYP scintigraphy for suspected cardiac amyloidosis between 2018 and 2025. Patients with confirmed ATTR-CM were stratified by Perugini grade (grade 2 vs. grade 3). Clinical features, biomarkers, electrocardiography, echocardiography, and cardiac magnetic resonance (CMR) parameters were compared. Correlations between scintigraphic grade, imaging markers, and biomarkers were assessed. Results Among 302 scans, 101 (33.4%) demonstrated myocardial uptake. Fifty-three patients were diagnosed with ATTR-CM, including 8 (15.1%) with grade 2 and 45 (84.9%) with grade 3 uptake. Grade 3 patients exhibited worse functional status, shorter 6-minute walk distance, and higher troponin I levels. Echocardiography showed greater maximal wall thickness, lower left ventricular ejection fraction, and worse global longitudinal strain. In the subset with CMR (N = 38), grade 3 patients (N = 30) had significantly higher left ventricular mass index, extracellular volume fraction, right ventricular free wall thickness, and more frequent right ventricular involvement. Perugini grade correlated strongly with left ventricular mass index (r = 0.61, p < 0.01) and extracellular volume (r = 0.53, p < 0.01), and moderately with troponin I (r = 0.55) and B-type natriuretic peptide (r = 0.36, p < 0.05). Grade 1 uptake was not associated with subsequent ATTR-CM diagnosis. Conclusions Non-invasive scintigraphy provides effective detection of ATTR-CM in a referral population. Although grades 2 and 3 both meet diagnostic criteria, grade 3 uptake is associated with greater myocardial amyloid burden, more advanced structural remodeling, and worse functional impairment. In our cohort, Perugini grade appears to reflect disease severity rather than serving solely as a binary diagnostic marker.