Beyond conduction disease: a prospective screening study of transthyretin cardiac amyloidosis in older patients referred for device therapy after syncope

Background Syncope in older adults is frequently attributed to bradyarrhythmias or conduction disease leading to cardiac implantable electronic device (CIED) implantation. However, transthyretin cardiac amyloidosis (ATTR-CM), an infiltrative cardiomyopathy associated with left ventricular hypertrophy (LVH), atrial fibrillation, heart failure, and progressive conduction system disease, may remain unrecognized in this setting. Data on ATTR-CM prevalence among older patients referred for CIED after syncope are limited. Objective To determine the prevalence of ATTR-CM in older patients referred for pacemaker or implantable cardioverter-defibrillator implantation after syncope and to evaluate the diagnostic yield of a pragmatic echocardiography-based screening strategy. Methods We conducted a prospective observational study including consecutive patients referred for CIED implantation following syncope over a 12-month period (01-12/2025). Device indication followed guideline-directed syncope and rhythm evaluation. Older age was defined as ≥70 years. Screening for ATTR-CM was triggered by LVH (interventricular septum and/or posterior wall thickness ≥12 mm). In patients with LVH, the presence of ≥1 additional red flag (history suggestive of systemic amyloidosis and/or electrocardiographic low voltage or pseudo-infarct pattern) prompted further evaluation with bone-tracer scintigraphy and monoclonal protein assessment. ATTR-CM was diagnosed according to established criteria [1]. Genetic testing was performed after confirmation. Frailty was assessed using the Clinical Frailty Scale (CFS). Prevalence estimates are reported with 95% confidence intervals (CI). Results Among 457 patients evaluated for syncope, 85 were referred for CIED implantation (median age 78 [73–82] years; 61% male). Of these, 68/85 (80%) were aged ≥70 years. LVH was present in 32/68 (47.1%) older patients. Among those with LVH, 14/32 (43.8%) had ≥1 additional red flag and underwent confirmatory testing. ATTR-CM was diagnosed in 4/14 patients (28.6%; 95% CI 8.4–58.1%). All cases were wild-type ATTR-CM (Figure). Overall, prevalence of ATTR-CM among older individuals aged ≥70 years was 12.5% (95% CI 3.5–29.0). In ATTR-CM patients, device indication was mainly driven by atrial fibrillation–related bradyarrhythmia (3/4, 75%), while high-grade atrioventricular block accounted for 1/4 (25%). All ATTR-CM patients were frail (CFS ≥4). Conclusions Among older patients referred for CIED implantation after syncope, ATTR-CM was present in approximately 1 in 8 individuals with LVH. A simple echocardiography-driven screening strategy combining LVH with at least one additional red flag identified ATTR-CM in nearly one-third of tested patients. These findings suggest that syncope and device referral pathways represent an important opportunity for early identification of ATTR-CM rather than solely a therapeutic endpoint for conduction disease.