CHANG, IAN C.

Background Prognostic staging systems in transthyretin amyloid (ATTR) cardiomyopathy were developed before the introduction of disease‐modifying treatment. We therefore evaluated contemporary risk stratification according to different staging systems in patients with ATTR cardiomyopathy. Methods All patients with newly diagnosed ATTR cardiomyopathy and baseline biomarker measurements from 2019 to 2023 were included from Mayo Clinic, Rochester, MN. Prognostic outcomes were calculated with Kaplan–Meier analysis for 3e staging systems in the main analysis: the National Amyloidosis Centre (NAC) staging system; a modified Mayo staging system using hsTNT (high‐sensitivity troponin T) cutoff >65 ng/L; the extended NAC model with a fourth stage (NT‐proBNP [N‐terminal pro‐B‐type natriuretic peptide] >10 000 ng/L). Results The study population consisted of 441 patients with a median age of 76 years, 93% were men, 85% were initiated on tafamidis, and 94% had wild‐type ATTR. Median follow‐up was 3.4 years, and 109 deaths occurred during follow‐up. The 3‐year survival for the Mayo stages were 92.3% (88.7–95.9) for stage I, 71.6% (63.0–81.3) for stage II, and 43.5% (32.4–58.5) for stage III. For the NAC system, 3‐year survival were 92.0% (89.0–95.7), 67.5% (59.0–77.3), and 47.0% (34.7–63.5) for stages I, II, and III, respectively. The 3‐year survival by the extended NAC system was 92.0 (69.0–79.2), 69.0% (60.1–79.2), 53.2% (39.9–70.8) and 34.4% (17.4–68.0) for stages I, II, III, and IV, respectively. Conclusions In a contemporary cohort of patients with ATTR cardiomyopathy, the NAC and modified Mayo staging systems remained equally effective in delineating clinically meaningful prognostic groups, whereas the extended NAC system identified a stage IV subgroup with high mortality.

BACKGROUND: Technetium-based cardiac amyloid radionuclide imaging enables noninvasive diagnosis of transthyretin amyloid cardiomyopathy (ATTR-CM), but conventional planar and visual semiquantitative approaches have important limitations. We developed the quantitative 3-dimensional Mayo 3D Score, defined as the ratio of mean left ventricular myocardial radiotracer uptake to right atrial blood-pool uptake using computed tomography (CT)-fused single-photon emission CT (SPECT) volumes of interest, and sought to validate its diagnostic performance against myocardial pathology. METHODS: Consecutive patients who underwent 99m Tc-pyrophosphate SPECT/CT at Mayo Clinic for suspected ATTR-CM between June 2017 and January 2025 with archived myocardial tissue were included. Baseline characteristics, including demographics, echocardiogram, biomarkers, visual semiquantitative, and Mayo 3D Score metrics, were collected. Myocardial specimens underwent histopathologic confirmation of amyloid, with amyloid subtype determination and further semiquantitative grading of amyloid burden and deposition patterns. RESULTS: Among 230 patients (median age, 72 years; 78% male), 107 (47%) had ATTR-CM, of whom 9 had hereditary ATTR-CM. The Mayo 3D Score showed excellent discrimination against pathology (area under the receiver operating characteristic curve, 0.92 [0.88–0.96]), exceeding planar Perugini (0.87 [0.83–0.92]; P =0.006), and heart-to-contralateral lung ratio (0.86 [0.81–0.91]; P =0.004) and comparable to SPECT Perugini (0.90 [0.86–0.94]; P =0.12). A cutoff ≥1.0 yielded 86.0% sensitivity, 92.7% specificity, 91.1% positive predictive value, and 88.4% negative predictive value. Among ATTR-positive cases, the Mayo 3D Score correlated strongly with semiquantitative amyloid burden (Spearman ρ=0.69), was higher in pericellular than nodular deposition patterns ( P <0.001), and was not associated with vascular involvement ( P =0.42). CONCLUSIONS: In patients with suspected ATTR-CM undergoing 99m Tc-pyrophosphate SPECT/CT, the Mayo 3D Score demonstrated superior diagnostic performance compared with planar metrics and comparable to SPECT Perugini, while correlating with myocardial ATTR burden and deposition patterns on pathology. These findings support its integration as a quantitative adjunct within clinical diagnostic ATTR-CM workflows.