Shifting clinical landscape of wild-type transthyretin amyloid cardiomyopathy: earlier detection, milder cardiac involvement, and reduced new-onset of atrial fibrillation in the contemporary era
H Kondo, K Yonezu, S Saito, N TakahashiAbstract
Background
With increasing awareness of transthyretin amyloid cardiomyopathy (ATTR-CM) and advances in diagnostic techniques, early diagnosis and earlier initiation of disease-modifying therapy have become increasingly feasible.
Purpose
We sought to compare the clinical profiles and outcomes of patients with wild-type ATTR-CM (ATTRwt-CM) diagnosed during the early phase of ATTR-CM recognition and those diagnosed during a more mature phase of contemporary clinical practice.
Methods
In this multicenter observational study based on our ATTR-CM cohort, we compared patients diagnosed with ATTRwt-CM between January 2020 and December 2022 (early-phase group) and those diagnosed between January 2023 and December 2025 (mature-phase group). Clinical characteristics at diagnosis were analyzed, and long-term outcomes, including all-cause mortality, cardiovascular death, heart failure hospitalization, and new-onset atrial fibrillation (AF), were evaluated.
Results
A total of 82 patients were included in the early-phase group and 160 in the mature-phase group. Patients diagnosed during the mature phase tended to be older (P = 0.0698) but exhibited higher baseline serum transthyretin levels (P = 0.0350) and better-preserved renal function, as reflected by higher estimated glomerular filtration rate (P = 0.0400). Baseline NT-proBNP and troponin T levels were significantly lower in the mature-phase group (P = 0.0451 and 0.0031). Echocardiographic parameters indicated less advanced cardiac involvement in the mature-phase group, with a trend toward higher left ventricular ejection fraction (LVEF, P = 0.086), less interventricular septal (IVST, P = 0.0002) and posterior wall (PLVWT, P = 0.0012) thickening, preserved global longitudinal strain (GLS, P = 0.0264), and lower E/e′ (P < 0.0001) and left ventricular mass (P = 0.0044). The prevalence of AF at the time of diagnosis did not differ significantly between the two groups (50% vs. 49%). Although no significant differences were observed in all-cause mortality, cardiovascular death, or heart failure hospitalization during follow-up (log-rank, P = 0.0880, P = 0.1491 and P = 0.4301, respectively), the incidence of new-onset AF was significantly lower in the mature-phase group (log-rank, P = 0.0417).
Conclusion
These findings suggest that early diagnosis of ATTR-CM has progressed in recent years, and contemporary patients are being diagnosed and treated at an earlier stage of disease, characterized by less advanced cardiac involvement.Shifting clinical landscape of ATTRwt-CMReduced new-onset of atrial fibrillation