Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Each monoclonal antibody light chain associated with AL amyloidosis has a unique sequence. Defining how these sequences drive amyloid deposition could facilitate faster diagnosis and lead to new treatments. ⋯ Rarely-observed light chain variable genes may carry a high risk of AL amyloidosis. New approaches are needed to define sequence-associated risk factors for AL amyloidosis. AL-Base is a foundational resource for such studies.
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The clinical efficacy of transthyretin (TTR) tetramer stabilisers and TTR gene silencers in addition to liver transplantation has been established for hereditary ATTR (ATTRv) amyloidosis. Accordingly, non-central nervous system (CNS) systemic amyloidosis manifestations, such as peripheral neuropathy and cardiomyopathy, are now being overcome. However, emerging disease-modifying therapeutics have limited effects on CNS amyloidosis since they target the blood-circulating TTR produced in the liver, and not the cerebral spinal fluid (CSF) TTR synthesised in the choroid plexus. ⋯ V50M) variant. Treatment-wise, blood-brain barrier-permeable stabilisers, intrathecal injection of silencers, and monoclonal antibodies against misfolded TTR and/or ATTR amyloid may potentially ameliorate CNS ATTR amyloidosis. The development of novel imaging/CSF biomarkers and disease-modifying therapies are the greatest unmet medical need in ATTRv amyloidosis and require further clinical trials.
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Multicenter Study
Prognostic value of CMR-derived extracellular volume in AL amyloidosis: a multicenter study.
This study aimed to assess the prognostic value of cardiac magnetic resonance (CMR) variables and compare them with biological and echocardiographic markers in patients with AL cardiac amyloidosis (CA). ⋯ ECV is a powerful predictor of outcomes in AL CA, providing additional prognostic value on top of Mayo Clinic staging.
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Multicenter Study
International prevalence of transthyretin amyloid cardiomyopathy in high-risk patients with heart failure and preserved or mildly reduced ejection fraction.
Transthyretin amyloid cardiomyopathy (ATTR-CM) is an underdiagnosed cause of heart failure (HF). ⋯ ATTR-CM was diagnosed in 18% (95% CI: 13.7-22.5) of evaluable patients with HF, LVEF >40%, and risk markers for ATTR-CM, but no previous diagnosis of amyloidosis. Recruitment bias may have contributed to regional variability. NCT04424914.