Incidence And Demographics Of Transthyretin Amyloidosis-Positive Subjects Identified By Histologic Analysis Of Tenosynovial Tissue Obtained During Carpal Tunnel Surgery

Abstract

<h3>Background</h3> Transthyretin (TTR) cardiac amyloidosis (CA) is an increasingly recognized cause of heart failure (HF) with preserved ejection fraction (HFpEF) that is associated with a poor prognosis. Retrospective analyses reported that amyloidogenic TTR (ATTR) deposition in tenosynovial sheaths such as that causing carpal tunnel syndrome often precedes the onset of HF due to ATTR CA by several years. <h3>Methods</h3> We conducted an analysis of 135 consecutive subjects who presented for carpel tunnel surgery from which tenosynovial sheaths were analyzed for evidence of amyloid deposition to explore the frequency of samples positive for ATTR and whether this approach might lead to earlier diagnosis and treatment of ATTR CA. <h3>Results</h3> From these 135 subjects, 31 were confirmed to have positive Congo Red staining deposits within tenosynovial tissue obtained during carpal tunnel release, all of which demonstrated ATTR subtype determined by liquid chromatography/mass-spectroscopic analysis. ATTR positive patients were significantly older than the negative patients (74 ± 8 yrs vs. 59±13 yrs). 55<i>%</i> of the ATTR positive patients were male and 45% female. At the time of this submission, only 1 of these 31 demonstrated a TTR mutation (valine-isoleucine 122). Seventeen patients have undergone screening for cardiac involvement of which 2 men have been diagnosed with ATTR CA by bone scintigraphic imaging. <h3>Conclusion</h3> 23% of subjects undergoing carpal tunnel release exhibit amyloid deposition by histologic analysis, all of whom tested positive for the ATTR subtype, with 2 male subjects demonstrating cardiac involvement. Within our positive ATTR population, 45% are female which far exceeds the 20% percent female prevalence among patients with HF due to ATTR CA reported previously supporting that female gender may offer protection from the subsequent development of ATTR CA. The evaluation of this population is ongoing and will be reported at the annual meeting. Broadly, our data support that histologic testing for amyloid protein deposition within tenosynovial tissue obtained at the time of surgery is warranted as this approach likely facilitates early diagnosis and treatment of ATTR CA before the onset of overt clinical heart failure.