Early diagnosis of Wild-type Transthyretin Amyloidosis Cardiomyopathy by optimized screening of patients undergoing Carpal Tunnel Syndrome Surgery (CACTuS II)

Background Wild-type transthyretin cardiac amyloidosis (ATTRwt-CM) is an underdiagnosed progressive cardiomyopathy that leads to heart failure and poor prognosis in elderly patients.[1] ATTRwt-CM arises from misfolding of transthyretin (TTR), making TTR aggregate, and forming amyloid fibrils that deposit in the myocardium.[2] ATTRwt-CM is associated with carpal tunnel syndrome (CTS).[3] Purpose Our primary aim is to assess the prevalence of amyloid deposition in carpal tunnel biopsies and the prevalence of ATTRwt-CM among patients with amyloid-positive biopsies. Futhermore, to compare disease stages between clinically-diagnosed symptomatic ATTRwt-CM patients and screening-detected ATTRwt-CM patients. Methods We are conducting a prospective multicenter cohort study including an estimated 150 consecutive patients (men ≥ 65 years and women ≥ 75 years) undergoing surgery for idiopathic CTS. Patients with confirmed amyloid deposition in tenosynovial biopsies from the carpal tunnel undergo a cardiac evaluation for ATTRwt-CM. A control cohort of 50 age- and gender-matched clinically-diagnosed symptomatic ATTRwt-CM patients is included. Results Preliminary results include 83 patients (50 men and 33 women) undergoing surgery for idiopathic CTS. Biopsies confirmed amyloid deposition in 41 (49.4%; 95% CI 38.4-60.6) patients. 33 patients underwent further evaluation, revealing 8 patients (24.2%; 95% CI 11.1-42.3) with ATTRwt-CM. Conclusion In an aged and predominantly male population undergoing idiopathic CTS surgery, 49.4% (95% CI 38.4-60.6) had amyloid deposition in biopsies from the carpal tunnel, and 24.2% (95% CI 11.1-42.3) of those evaluated further were diagnosed with ATTRwt-CM. All patients diagnosed with ATTRwt-CM were in National Amyloidosis Centre (NAC) stage 1, indicating early-stage diagnosis. Perspectives: These findings suggest that idiopathic CTS may serve as an early marker for ATTRwt-CM. With additional investigation in this study, we expect to show that screening-diagnosed ATTRwt-CM patients are in an early clinical disease stage compared to patients diagnosed clinically. We hope to contribute to methods for diagnosing ATTRwt-CM in a significantly earlier disease stage, making it possible to enable targeted treatment while there is still a great potential to avoid severe disabilities and improve prognosis.Karpaltunnel syndrom precede ATTR-CM Study flowchart