Incidence and Clinical Features of Transthyretin Amyloidosis Diagnosed by Histologic Analysis of Tenosynovial Tissue From Patients Undergoing Carpal Tunnel Surgery

Introduction: 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 series have demonstrated that amyloidogenic TTR (ATTR) deposition in tenosynovial sheaths such as that causing carpal tunnel syndrome precedes the onset of HF due to ATTR CA by several years. Methods: We conducted an analysis of 136 patients (pts) who presented for carpel tunnel surgery from whom tenosynovial material was analyzed with Congo Red staining to determine the frequency of samples positive for ATTR deposition and to explore whether this approach might lead to earlier diagnosis and treatment of ATTR CA. Results: Among these 136 pts, 31 were confirmed to have positive Congo Red staining tenosynovial tissue, all of which demonstrated the ATTR subtype determined by liquid chromatography/mass-spectroscopic analysis. ATTR positive pts were significantly older than negative pts (74 + 8 yrs vs. 59 + 13 yrs, p<0.01). 58 % of ATTR positive pts were male and 42% female. At the time of this submission, only 1 of these 31 subjects demonstrated a TTR mutation (valine-isoleucine 122). 19 pts have undergone cardiac screening of which 2 males demonstrated ATTR CA by bone scintigraphic imaging. Conclusions: 23% of pts undergoing carpal tunnel release exhibit ATTR amyloid deposition by histologic analysis, all of whom tested positive for the ATTR subtype with 2 asymptomatic male pts exhibiting cardiac involvement. Among our positive ATTR pts, 42% are female exceeding the 10-20% percent female prevalence among patients with HF due to ATTR CA reported previously. This preliminary observation supports a protective role of female gender in limiting progression to HF due to ATTR amyloidosis. The evaluation of this population is ongoing and will be reported at the annual meeting. Broadly, however, our data support that identifying ATTR amyloid protein within tenosynovial tissue obtained during routine surgery is warranted as this approach, when combined with appropriate cardiac screening, facilitates early diagnosis and treatment of ATTR CA before the onset of overt clinical heart failure.