Diagnostic, Therapeutic, and Prognostic Implications of Carpal Tunnel Syndrome and Spinal Stenosis in Wild-type ATTR-Cardiomyopathy

Abstract

Background In wild-type transthyretin cardiac amyloidosis (ATTRwt-CM), the prognostic role of carpal tunnel syndrome (CTS) is unclear and that of lumbar spinal stenosis (SS) remains unexplored. Objectives The aim was to examine the diagnostic, therapeutic, and prognostic relevance of bilateral CTS and SS in ATTRwt-CM, in relation to the tafamidis treatment. Methods Clinical characteristics of 1,449 patients with ATTRwt-CM were evaluated in a multicenter cohort. The primary endpoint was all-cause mortality. Cox multivariable regression was used to assess mortality in patients with and without CTS and SS. Results Preceding an ATTRwt-CM diagnosis, CTS and SS were present in 29% and 22% of patients, respectively, without sex-difference. CTS (P < 0.001), but not SS, was more prevalent among younger patients. Tenosynovial red flags and ATTRwt-CM diagnosis occurred approximately 4 years later in females vs males, with similar preceding time, suggesting later female ATTRwt-CM disease onset. Patients with vs without CTS and SS had lower National Amyloidosis Centre disease stage (P <= 0.001), despite similar symptomatic status. During a mean follow-up of 2.3 +/- 1.8 years, 73% (1,052/1,449) of patients were initiated on tafamidis and 28% (406) died. Tafamidis was initiated more in CTS positive vs negative patients (78% vs 71%; P = 0.008), on average 2.3 years earlier (P < 0.001). More SS positive than negative patients received tafamidis (78% vs 71%; P = 0.018), but at similar age (P = 0.394). CTS (HR: 0.70; 95% CI: 0.52-0.95) and SS (HR: 0.68; 95% CI: 0.48-0.97) predicted lower mortality. Conclusions Both CTS and SS not only enable early ATTRwt-CM diagnosis and treatment initiation, but independently relate to improved survival, potentiating a role for opportunistic screening. (c) 2026 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).