Contrasting Echocardiographic Trajectories with and Without Tafamidis in Wild-Type Transthyretin Amyloid Cardiomyopathy: A Real-World Observational Study with Two-Dimensional Speckle-Tracking Analysis

Introduction and Objectives: Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive infiltrative disease with high morbidity and mortality in the absence of disease-specific therapy. We aimed to determine the impact of tafamidis on serial echocardiographic parameters—including two-dimensional speckle-tracking echocardiography (2D-STE) of the left ventricle (LV), right ventricle (RV) and left atrium (LA)—in patients with wild-type ATTR-CM followed in a real-world clinical setting, compared with a historical untreated cohort reflecting the natural disease course. Patients and Methods: Single-centre retrospective observational study comparing a historical, treatment-naïve cohort (n = 37) with a tafamidis-treated cohort (n = 22), for a total of 59 patients with confirmed ATTRwt-CM. Serial echocardiograms were performed at baseline and after a median follow-up of 22.4 months (untreated) and 18.2 months (treated). Results: Mean age was 87.0 (SD 4.8) years; 84.7% were male. Untreated patients were older (89.3 vs. 83.0 years; p < 0.001), had more advanced NAC staging (p = 0.016), and higher NT-proBNP (4291 vs. 1675 pg/mL; p = 0.011) and troponin I (p = 0.007). The untreated cohort showed significant worsening of posterior wall thickness (14.3 to 15.7 mm; p = 0.006), LV end-diastolic diameter (44.2 to 41.6 mm; p = 0.005), TAPSE (17.4 to 15.0 mm; p = 0.010), mitral E velocity (93.9 to 83.7 cm/s; p = 0.019), and LA contractile strain (8.5 to 6.4%; p = 0.014, Wilcoxon). All-cause mortality (70.3% vs. 9.1%; p < 0.001) and HF hospitalisation or IV diuretic requirement (78.4% vs. 4.5%; p < 0.001) were markedly higher in the untreated cohort. These parameters remained numerically stable in the tafamidis group (all p > 0.3). On direct between-group comparison of the magnitude of change, only LA contractile strain (Δp = 0.045) and RV longitudinal strain (Δp = 0.031) differed significantly between cohorts; LVEDD and LVEF approached significance (Δp = 0.059 and 0.054), while the remaining parameters did not (Δp > 0.18). Conclusions: Structural and functional echocardiographic parameters deteriorated significantly in the untreated cohort, while remaining numerically stable in tafamidis-treated patients. Serial 2D-STE incorporating RV and LA strain assessment provides a valuable tool for longitudinal monitoring in ATTRwt-CM.