Increased occupational exposure to physical stress in wild-type transthyretin amyloid cardiomyopathy – a potential disease promoting mechanism?

Abstract Background The cause of wild-type transthyretin amyloidosis cardiomyopathy (ATTRwt) remains unknown, with mechanical stress being hypothesized as a potential mechanism. No study has investigated the potential impact of occupational physical exposure on ATTRwt development. Methods We enrolled 100 participants, including 50 ATTRwt patients with prior carpal tunnel syndrome surgery (CTS), 25 ATTRwt patients without CTS, and 25 age- and gender-matched stable heart failure patients with reduced ejection fraction (HFrEF) as controls. We evaluated self-reported physical work exposure, Danish occupation classification (DISCO-88), history of orthopedic joint-related disorders beyond CTS surgery, hand volumes, and physical status using the Kansas City Cardiomyopathy Questionnaire. Results ATTRwt patients had significantly higher physical work exposure than the HFrEF control group (p<0.001), with a higher prevalence of blue-collar work. Knee or hip joint replacement was more frequent in ATTRwt patients (31; 41%) compared to HFrEF patients (2; 8%). ATTRwt patients exhibited larger hand volumes than the HFrEF control group (dominant hand [DH]: 518±80 mL vs. 421±64 mL, p<0.001). Conclusion These findings support the hypothesis that long-standing mechanical stress might play an important role in the development of ATTRwt cardiomyopathy and associated ligament disorders. Trial registration The study was approved by the Committee of Scientific Ethics of the Central Denmark Region (project ID: 1-10-72-380-21). Date of registration: 17/03/2022. The study was registered with clinicaltrials.org (ID: NCT05896904). Date: 09/06/2023.