Diagnostic, therapeutic and prognostic implications of carpal tunnel syndrome and spinal stenosis in wild-type transthyretin cardiac amyloidosis

Background and aims Bilateral carpal tunnel syndrome (CTS) and lumbar spinal stenosis (SS) represent common tenosynovial red flags, preceding wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) by many years. The prognostic and therapeutic relevance of CTS and SS in ATTRwt-CM, in relation to tafamidis treatment, are unexplored and were studied. Methods An international, multicentric cohort of 1449 ATTRwt-CM patients was evaluated, including for all-cause mortality endpoint. Results Preceding CTS and SS were present in 29% (414) and 22% (316), respectively, without sex-difference (p=NS). CTS (p<0.001), but not SS (p=0.354), was more prevalent amongst progressively younger patients. Identification of both tenosynovial red flags and ATTRwt-CM diagnosis occurred approximately 4 years later in females versus males, with similar preceding time, suggesting later female ATTRwt-CM disease onset. Patients with versus without CTS and SS had lower National Amyloidosis Centre disease stage (p≤0.001), despite similar symptomatic status (p=NS). During a mean follow-up of 2.3±1.8 years, 73% (1052/1449) of patients were initiated on tafamidis and 28% (406) died. Tafamidis was initiated more in CTS positive versus negative patients (78% versus 71%, p=0.008), on average 2.3 years earlier (p<0.001). More SS positive than negative patients received Tafamidis (78% versus 71%, p=0.018), but at similar age (p=0.394). CTS (HR 0.69, 95%CI 0.51-0.93, p=0.016) and SS (HR 0.69, 95%CI 0.48-0.97, p=0.035) predicted lower mortality, independent of age, gender, disease stage components and tafamidis treatment. Conclusion 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.Graphical abstract Cumulative survival.