Hip and knee arthroplasty are common among patients with transthyretin cardiac amyloidosis, occurring years before cardiac amyloid diagnosis: can we identify affected patients earlier?

Abstract

Transthyretin cardiac amyloidosis (ATTR-CA) causes a restrictive cardiomyopathy in older adults, often diagnosed at advanced stages when emerging therapies in late phase clinical trials may not have clinical benefit. This investigation aimed to detect clinical entities that may provide more advanced warning of ATTR-CA. Since ATTR preferentially deposits in ligaments, tendons, and articular cartilage, we hypothesized that ATTR-CA patients have a greater prevalence of total hip (THA) and knee (TKA) arthroplasties compared with the general population, and that arthroplasty occurs significantly before ATTR-CA diagnosis. Three-hundred and thirteen patients with cardiac amyloidosis (172 with ATTR-CA, 141 with light-chain) from our institutional database were analyzed and compared to published data in over 300 million patients. Overall, 23.3% of patients with ATTR-CA and 9.2% of patients with light-chain cardiac amyloidosis (AL-CA) underwent lower extremity arthroplasty. Compared to the general population, both THA and TKA were significantly more common among patients with ATTR-CA (THA: RR 5.61, 95% CI 2.25–4.64; TKA: RR 3.32, 95% CI 2.25–4.64) but not those with AL-CA (THA: RR 1.87, 95% CI 0.85–4.08; TKA: RR 1.42, 95% CI 0.73–2.84). On an average, arthroplasty occurred 7.2 years before ATTR-CA diagnosis.

Keywords:

• Cardiac amyloidosis
• transthyretin
• light-chain
• arthroplasty

Acknowledgements

Dr. Maurer acknowledges the continued generosity of David and Landon Storrs towards the work of the Clinical Cardiovascular Research Laboratory for the Elderly on Transthyretin Amyloidosis.

Disclosure statement

M. S. Maurer or his institution receives funding for research and serving on advisory boards and DSMBs from Pfizer Inc., Alnylam Pharmaceuticals Inc., GSK Inc., ISIS Pharmaceuticals and Prothena Inc.

Funding

M. S. Maurer receives funding from an NIH K24 AG036778 Midcareer Mentoring Award in Geriatric Cardiology.