JACC Advances · Mar 2026

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

By Debonnaire P, Dujardin K, Donal E et al.

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.

doi.org/10.1016/j.jacadv.2026.102631 Open access PubMed 41906617 Biomarkers