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 noninvasive 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-99 m 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, 103 (34.1%) had reported cardiac uptake on planar imaging. 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-min 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 showed strong rank-based correlations with left ventricular mass index (ρ = 0.61, P < 0.01) and extracellular volume (ρ = 0.53, p < 0.01), and a moderate correlation with troponin I (ρ = 0.55, P < 0.01). A modest correlation with brain natriuretic peptide (BNP) was also observed (ρ = 0.36, P < 0.05), although BNP levels did not differ significantly between grade groups. Grade 1 uptake was not associated with subsequent ATTR-CM diagnosis on available follow-up. CONCLUSIONS: Noninvasive scintigraphy provides effective detection of ATTR-CM in a referral population. Although grades 2 and 3 both meet diagnostic criteria, in this retrospective cohort, grade 3 uptake was associated with markers of more advanced structural remodeling, higher extracellular volume, greater right ventricular involvement, and worse functional impairment.