Temporal evolution of transthyretin cardiac amyloidosis phenotypes on cardiac magnetic resonance

Background: Advances in cardiac imaging and disease awareness have led to earlier and more frequent diagnosis of Transthyretin Cardiac Amyloidosis (ATTR-CA). Cardiac magnetic resonance (CMR) is a key tool for the diagnosis and phenotypic characterization of ATTR-CA. This study aimed to characterize the temporal evolution of ATTR-CA phenotypes on CMR and their potential prognostic implications. Methods: We retrospectively analyzed all consecutive ATTR-CA patients referred to the CMR unit of the University Hospital of Padua. Patients were stratified by the year of their CMR scan (≤2020 vs. >2020). Clinical, biomarker, and CMR data, including LGE patterns (classified as subendocardial, transmural, or atypical), were compared. The primary endpoint was a composite of all-cause death or heart failure (HF) hospitalization. Results: a total of 72 patients were included [67 (93%) male, median age 75 years (IQR 72–80)]. The >2020 cohort presented with a significantly milder disease phenotype versus the ≤2020 cohort, including a higher proportion of NAC stage I (83% vs. 46%, p=0.004), lower NTproBNP (median 1032 vs. 1791 ng/L, p=0.043), and lower indexed LV mass (median 89 vs. 105 gr/m2, p=0.004). The prevalence of atypical LGE was significantly higher in the >2020 group (30% vs. 8%, p=0.026). In the ≤2020 cohort, transmural LGE was the strongest predictor of the composite endpoint (HR 3.98, p=0.029). In the >2020 cohort, the atypical LGE pattern emerged as a strong predictor of favourable outcome (HR 0.16, p=0.049). Conclusion: The interpretation of CMR findings in ATTR-CA has evolved over time. In the modern era of earlier diagnosis, atypical LGE patterns have become increasingly recognized and are associated with a milder phenotype and a significantly better prognosis. Therefore, atypical LGE should not be dismissed as a non-specific finding but rather considered an early indicator of ATTR-CA.