Prognostic implications of Perugini Grading in a contemporary centre referral cohort undergoing evaluation for suspected cardiac amyloidosis

Background Non-invasive diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM) relies on bone scintigraphy using the Perugini grading system. The prognostic value of stratification within the non-diagnostic (grade 0–1) and ATTR-CM (grade 2–3) groups in a contemporary centre referral cohort remains uncertain. Purpose To assess whether Perugini grade stratification is associated with differences in clinical outcomes. Methods In this retrospective cohort study, patients referred for bone scintigraphy due to suspected cardiac amyloidosis in the Capital Region of Denmark (2018–2024) were included. Patients with amyloid light-chain amyloidosis were excluded. Patients were categorised by Perugini grade (0–3). Outcomes were all-cause mortality and heart failure hospitalisation. Baseline was defined as the date of scintigraphy, and follow-up continued until 1 February 2025, death, or 3 years, whichever occurred first. Mortality was analysed using Kaplan–Meier and log-rank testing, and hospitalisation using cumulative incidence functions with Gray’s test. Cox regression adjusted for age and sex was performed. Results We included a total of 483 patients: 375 with grade 0 uptake (median age 75 years; 60% male), 18 with grade 1 (median age 79 years; 67% male), 21 with grade 2 (median age 79 years; 100% male), and 69 with grade 3 (median age 83 years; 84% male). At 3 years after inclusion, overall survival was 81.7% (grade 0), 72.2% (grade 1), 48.1% (grade 2), and 52.0% (grade 3), as illustrated in Figure 1. The 3-year cumulative incidence of heart failure hospitalisation was 17.6% (grade 0), 30.4% (grade 1), 40.0% (grade 2), and 35.5% (grade 3), as shown in Figure 2. Comparing grade 0 and 1 no significant differences were observed in all-cause mortality (subgroup log-rank p=0.35) or cumulative incidence of hospitalisation (Gray’s test p=0.095). Similarly, when comparing grade 2 and 3 no significant differences were observed in all-cause mortality (subgroup log-rank p=0.72) or cumulative incidence of hospitalisation (Gray’s test p=0.38). Comparing grade 0-1 with grade 2-3 a significant higher mortality (subgroup log rank p<0.0001) and hospitalisation (Gray’s test p=0.001) were found. After adjustment for age and sex, mortality differed significantly between grade 0-1 and 2-3 (HR 1.81, 95% CI 1.12-2.92, p=0.015), whereas no differences were observed in the remaining comparisons. Conclusion Perugini grade 2–3 was associated with higher mortality compared with grade 0–1. However, no significant differences in heart failure hospitalisation or all-cause mortality were observed within grade 0 and 1, nor between grade 2 and 3. These findings suggest that the Perugini grading system may not provide additional prognostic value within patients without ATTR-CM (grade 0–1) or among those with ATTR-CM (grade 2–3). The small number of patients with grade 1 and 2 should be considered when interpreting these findings.