Light-Chain Pericardial Amyloidosis Emerging Alongside Variant Transthyretin Cardiac Amyloidosis

ardiac amyloidosis (CA) is caused by extracellular deposition of amyloid fibrils composed of misfolded proteins within cardiac tissues, leading to restrictive cardiomyopathy. The majority of CA cases are caused by amyloid proteins derived from transthyretin (leading to transthyretin cardiac amyloidos is [ATTR-CA]), which is predominantly synthesized by hepatocytes, or from immunoglobul in light-chain amyloidosis (AL-CA) typically produced by clonal plasma cells.1 Transthyretin amyloidos is (ATTR) can be further classified as secondary to inherited structurally destabilizing variants in the transthyretin gene (variant transthyretin amyloidos is [ATTRv]) or the acquired unstable wild-type transthyretin protein (wild-type transthyret in amyloidosis [ATTRwt]). Historically, diagnosis included histologic confirmation of amyloid in the affected organ(s) using Congo red staining, with fibril typing suggested by immunohistochemistry and confirmed with proteomic analysis by laser microdissect ion with liquid chromatography-tandem mass spectrometry (LC-MS/MS).1 Radioisotope myocardial uptake on bone scintigraphy now permits nontis sue diagnosis of ATTR-CA in patients without monoclonal gammopathies. Diagnostic pathways for AL-CA and ATTR-CA algorithmically diverge but are not mutually exclusive, with comprehensive assessment critical for timely initiation of treatment appropriate to subtype.1 The presence of multiple precursor proteins for CA in an individual patient is exceedingly rare and limited to case reports/series of co-occurring distinct amyloid subtypes detected at either single or separate anatomic site(s). To our knowledge, a total of 8 cases of CA with distinct subtypes diagnosed concurrently at the initial work-up (n = 6) or autopsy (n = 2) have been reported, all with lambda light-chain amyloidos is (ALl) and ATTRwt.2-7 Separately, in AL-CA patients, the presence of transthyretin variants8 and extracardiac ATTRv deposition3 without variant transthyretin cardiac amyloidosis (ATTRv-CA) have been reported. Here, we present the first case (to our knowledge) of CA with endomyocardial biopsy evidence of ATTRv and, subsequently, after clinical deterioration despite ATTR-CA disease-modifying therapy, evidence of kappa light-chain amyloidosis (ALk) co-occurring with ATTRv in the same pericardial microdissection.