Dataset Information

Improved Quantification of Cardiac Amyloid Burden in Systemic Light Chain Amyloidosis: Redefining Early Disease?

ABSTRACT:

Objectives

The purpose of this study was to determine phenotypes characterizing cardiac involvement in AL amyloidosis by using direct (fluorine-18-labeled florbetapir {[¹⁸F]florbetapir} positron emission tomography [PET]/computed tomography) and indirect (echocardiography and cardiac magnetic resonance [CMR]) imaging biomarkers of AL amyloidosis.

Background

Cardiac involvement in systemic light chain amyloidosis (AL) is the main determinant of prognosis and, therefore, guides management. The hypothesis of this study was that myocardial AL deposits and expansion of extracellular volume (ECV) could be identified before increases in N-terminal pro-B-type natriuretic peptide or wall thickness.

Methods

A total of 45 subjects were prospectively enrolled in 3 groups: 25 with active AL amyloidosis with cardiac involvement (active-CA), 10 with active AL amyloidosis without cardiac involvement by conventional criteria (active-non-CA), and 10 with AL amyloidosis with cardiac involvement in remission for at least 1 year (remission-CA). All subjects underwent echocardiography, CMR, and [¹⁸F]florbetapir PET/CT to evaluate cardiac amyloid burden.

Results

The active-CA group demonstrated the largest myocardial AL amyloid burden, quantified by [¹⁸F]florbetapir retention index (RI) 0.110 (interquartile range [IQR]: 0.078 to 0.139) min^-1, and the lowest cardiac function by global longitudinal strain (GLS), median GLS -11% (IQR: -8% to -13%). The remission-CA group had expanded extracellular volume (ECV) and [¹⁸F]florbetapir RI of 0.097 (IQR: 0.070 to 0.124 min^-1), and abnormal GLS despite hematologic remission for >1 year. The active-non-CA cohort had evidence of cardiac amyloid deposition by advanced imaging metrics in 50% of the subjects; cardiac involvement was identified by late gadolinium enhancement in 20%, elevated ECV in 20%, and elevated [¹⁸F]florbetapir RI in 50%.

Conclusions

Evidence of cardiac amyloid infiltration was found based on direct and indirect imaging biomarkers in subjects without CA by conventional criteria. The findings from [¹⁸F]florbetapir PET imaging provided insight into the preclinical disease process and on the basis of interpretation of expanded ECV on CMR and have important implications for future research and clinical management of AL amyloidosis. (Molecular Imaging of Primary Amyloid Cardiomyopathy [MICA]; NCT02641145).

SUBMITTER: Cuddy SAM

PROVIDER: S-EPMC8218539 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundLight chain (AL) amyloidosis is a rare disease characterized by misfolded amyloid protein deposits in tissues and vital organs, and little is known about the burden of AL amyloidosis on health-related quality of life. This study aimed to quantify the burden of AL amyloidosis in terms of health-related quality of life in a diverse, community-based sample of AL amyloidosis patients.ResultsThe SF-36v2® Health Survey (SF-36v2), a widely used generic measure of health-related quality of life (using physical and mental summary scales and subscales assessing eight aspects of functioning and well-being), was administered as an online survey of AL amyloidosis patients with AL amyloidosis (ClinicalTrials.gov, NCT02574676 ; n = 341). Compared with adjusted general population sample norms, health-related quality of life of AL amyloidosis patients was significantly worse across all SF-36v2 scales and summary measures based on analysis of variance (p < 0.05 for all). The largest decrement in AL amyloidosis patients was related to General Health (Δ = 9.7; p < 0.001). With the exception of Bodily Pain and Mental Health, differences were also clinically meaningful based on established clinically minimal important differences. The burden of AL amyloidosis overall and in key subgroups tended to be greater on physical health than on mental health. Stratified analyses indicated additional burden among patients with recently diagnosed disease and those with cardiac involvement than among their respective counterparts.ConclusionUnderstanding the burden of AL amyloidosis highlights the unmet need for treatment, helps physicians identify ancillary treatments and services geared towards improving patients' functioning, well-being, and overall health-related quality of life. These findings also help to support the use of health-related quality of life end points as important outcome measures in current and future treatment studies.Trial registrationClinicalTrials.gov, NCT02574676 . Registered October 5, 2015.