Outcomes

The primary outcome was CA diagnosis by biopsy or ^99mTc-PYP scintigraphy. Histological CA diagnosis was defined by positive Congo red staining with typical apple green birefringence in each specimen. In most histologically diagnosed CA patients, distinction between AL and TTR-associated amyloidosis (AL-CA and TTR-CA) was performed based on genotyping and/or immunohistochemistry. Patients with CA who showed amyloid infiltration by extra-cardiac biopsy had the diagnosis confirmed by ruling out other causes of LVH using clinical data, echocardiography, CMR, or ^99mTc-PYP scintigraphy. Additionally, ^99mTc-PYP scintigraphy is relatively specific for TTR-CA imaging [10]. Accordingly, ^99mTc-PYP scintigraphy was scored using the following grading system: grade 0, no cardiac uptake; grade 1, mild uptake less than bone; grade 2, moderate uptake equal to bone; and grade 3, high uptake greater than bone [11]. Essentially, the non-invasive diagnosis of TTR-CA using 99mTc-PYP scintigraphy also requires a monoclonal protein assay [10], but since it was not available to all patients in this retrospective study, we expediently defined TTR-CA as cases measuring ≥2 on this score using 99mTc-PYP scintigraphy.

The secondary outcomes were all-cause death and admission for unexpected heart failure after the index echocardiographic examination. Medical records were used to conduct follow-up assessments. Patients were censored at the time of the outcome or at the end of follow-up (December 31, 2019).