Impact of the IWT score in timely diagnosis and disease profile of cardiac amyloidosis patients

Abstract Background Timely diagnosis of cardiac amyloidosis (CA) remains a clinical challenge due to nonspecific symptoms and overlapping phenotypes. The Increased Wall Thickness (IWT) echocardiographic score has been proposed as a tool to facilitate the identification the of patients. However, its role in detecting earlier and less severe disease has not been confirmed. Purpose To assess the impact of implementing the IWT score on the time from symptom onset to diagnosis and disease features in patients with confirmed CA. Methods We conducted an ambispective multicenter study across 12 cardiac imaging units. The study included two cohorts: a retrospective CA group diagnosed before routine implementation of the IWT score; and a prospective group of unselected patients with unexplained left ventricular hypertrophy (LVH) screened using the IWT score and diagnosed with CA between November 2023 and November 2024. Time from symptom onset to diagnosis was compared between cohorts. Clinical, laboratory, ECG, and echocardiographic data—including IWT score components—were systematically recorded and analyzed. Results The prospective cohort included 581 patients (mean age 71 ± 13 years, 63% male) screened using the IWT score, of whom 22 (3.8%) were diagnosed with CA (median age 78.5 years, 90.1% male). Among these confirmed patients, 20 had wild-type transthyretin amyloidosis (ATTRwt), 1 had hereditary transthyretin amyloidosis (ATTRv), and 1 had light-chain amyloidosis (AL). The retrospective cohort comprised 84 patients with cardiac amyloidosis (median age 75 years, 86% male), including 51 with ATTRwt, 27 with ATTRv and 6 with AL. Main characteristics of both cohorts are summarized in Table 1. A statistically significant reduction in diagnostic delay was observed in the prospective cohort (median 2.5 vs. 17 months, p < 0.001). No significant differences were found between cohorts regarding comorbidities, symptom profile, or prior diagnoses. Atrial fibrillation was more prevalent in the prospective group (53.3% vs. 21.9%, p = 0.028). Patients diagnosed using the IWT score had a higher relative wall thickness (RWT 0.77 vs. 0.66 mm, p < 0.001), posterior wall thickness (15.41 vs 13.89 mm, p=0.042) and left atrium volume (100 vs 73.5 ml, p=0.01), worse diastolic function (p=0.039) and global longitudinal strain (−10.43% vs. −13%, p = 0.047), and more frequent right ventricular dysfunction (TAPSE 15.5 vs. 19 mm, p < 0.001). Conclusions Implementing the IWT echocardiographic score in a real-world, multicenter setting of unselected LVH patients significantly shortened the time to diagnosis of CA. Despite similar clinical profiles, patients identified via the IWT-based screening showed more advanced structural and functional cardiac involvement. Further studies with larger cohorts are warranted to confirm its role in detecting early disease.