Among patients with orthopedic TTR deposition, 5% had ATTRwt CA at baseline and 20% showed new cardiac involvement over two years, with one progressing to tafamidis therapy.
Does TTR deposition in orthopedic tissues predict the development of ATTRwt CA over two years?
TTR deposition in orthopedic tissues may serve as an early biomarker for ATTRwt CA, with 5% showing baseline cardiac involvement and additional cases emerging over two years.
Absolute Event Rate: 0% vs 0%
Abstract Background Wild-type transthyretin cardiac amyloidosis (ATTRwt CA) is now treatable with tafamidis, highlighting the need for early diagnosis to optimize outcomes(1). Transthyretin amyloid (TTR) deposition in joint and ligament tissues is increasingly recognized in orthopedic conditions like carpal tunnel syndrome (CTS) and rotator cuff tears, which may precede ATTRwt CA by years(2). However, the progression from TTR deposition in orthopedic tissues to cardiac involvement remains unclear. This study evaluated ATTRwt CA prevalence in patients undergoing upper extremity surgery with histopathologically confirmed TTR deposition and assessed their cardiac status over two years. Methods Patients undergoing CTS or rotator cuff tear surgery between June 2021 and July 2024 were prospectively enrolled. Surgical specimens were analyzed for TTR deposition using Congo red staining and immunohistochemistry. Patients with confirmed TTR deposition underwent electrocardiography, echocardiography, and technetium-99m pyrophosphate (99mTc-PYP) scintigraphy to assess cardiac involvement. Those with positive scintigraphy underwent further evaluation, including cardiac MRI, serum biomarkers (NT-proBNP and troponin T), and, when indicated, endomyocardial biopsy and genetic screening. Results Among 162 patients (72 CTS, 90 shoulder cases; mean age 63 years, 36% male), TTR deposition was identified in 39 (24%). At baseline, 5% (n=2) had positive 99mTc-PYP scintigraphy (both Grade 2), but echocardiographic septal wall thickness remained below 12 mm, precluding tafamidis initiation. At the two-year follow-up, 20 patients completed repeated cardiac evaluations. Three additional patients exhibited newly positive 99mTc-PYP scintigraphy (one Grade 3, two Grade 2), and one developed progressive left ventricular septal thickening (12 mm). This patient underwent cardiac biopsy and genetic testing, confirming ATTRwt CA, and subsequently initiated tafamidis therapy. Conclusion Among patients with TTR deposition in orthopedic specimens, 5% had evidence of ATTRwt CA at baseline, with additional cases emerging over two years. One patient progressed to significant myocardial involvement, reinforcing the hypothesis that TTR deposition in joint and ligament tissues may serve as an early biomarker for ATTRwt CA. Given the increasing prevalence of ATTRwt CA and available treatments, clinicians should maintain a high index of suspicion for cardiac involvement in patients with confirmed TTR deposition in orthopedic tissues. Longitudinal surveillance is essential, and current diagnostic criteria for initiating treatment may need reconsideration to enable earlier therapeutic intervention.
Umemoto et al. (Sat,) reported a other. Among patients with orthopedic TTR deposition, 5% had ATTRwt CA at baseline and 20% showed new cardiac involvement over two years, with one progressing to tafamidis therapy.