Cardiac screening of amyloid TTR pathogenic variant carriers: complementary value of echocardiographic global longitudinal strain imaging and bone scintigraphy

Background Cardiac involvement is the major determinant of mortality in variant TTR amyloidosis (ATTRv). Treatment options have recently become available, which make early diagnosis important. Several imaging modalities for screening are proposed including bone scintigraphy, conventional, and strain echocardiography but data on their relative value is limited in this population. Objectives To investigate the value of left ventricular global longitudinal strain (LV-GLS) for screening for cardiac involvement in a population of transthyretin (TTR) pathogenic variant carriers. Methods Fifty-three TTR pathogenic variant carriers from two Dutch academic hospitals underwent transthoracic echocardiography (TTE) and bone scintigraphy as part of routine out-patient care to assess cardiac involvement. LV-GLS was measured by two blinded reviewers. Abnormalities in LV-GLS (cut-off − 21.5%) and other TTE parameters were evaluated in bone scintigraphy positive (≥ grade 1) and negative cases. Results Carriers with a positive bone scintigraphy ( n = 20/53) were 16 years older than those with a negative scan ( n = 33/53). In 17 out of 20 (85%) of patients with a positive bone scintigraphy, LV-GLS was abnormal. When bone scintigraphy was negative, LV-GLS was abnormal in 11 cases (38%). Although most of these patients had no obvious alternative explanation for the reduced LV-GLS, the clinical significance of this finding remains uncertain. LV-GLS as a single echo parameter was equally sensitive to detect an abnormal bone scintigraphy versus all other TTE parameters together. Conclusions LV-GLS and bone scintigraphy provided complementary information in TTR pathogenic variant carriers. Discordant findings between both modalities warrant further evaluation, as abnormal LV-GLS may reflect early ATTRv-related changes but is not disease-specific. These findings are exploratory and hypothesis-generating and warrant confirmation in prospective studies incorporating additional reference standards.LV-GLS was the most sensitive single echo parameter, making it useful for repeated assessment in this population.