Seeing the Light: Transthyretin Cardiac Amyloid Misdiagnosed as Light Chain Amyloid

Amyloidosis News - December 2020

Cardiac amyloidosis is caused by insoluble protein deposition into the myocardium. Distinction between the different subtypes has significant management implications, thus emphasizing the importance of establishing an accurate diagnosis.

A 75-year-old man presented with anemia at the University of California, Los Angeles. Work up revealed IgA-lambda fraction and bone marrow biopsy with 10% plasmacytosis and excess lambda light chain. Echocardiography demonstrated left ventricular hypertrophy and apical sparing strain pattern on imaging. At an outside center, myocardial biopsy confirmed amyloid deposition by Congo red staining. The patient was diagnosed with light chain amyloidosis and initiated chemotherapy. Shortly thereafter patient was hospitalized for decompensated heart failure.

A presumptive diagnosis of light chain amyloid was made based on the presence of myocardial amyloid by Congo red staining, in the context of a monoclonal gammopathy. However, neither adequate amyloid subtyping nor 99mTechnetium-pyrophosphate (99mTc-PYP) scintigraphy were performed. Subsequent 99mTc-PYP scan was consistent with transthyretin cardiac amyloid (ATTR-CA), grade 3. Repeat myocardial biopsy with mass spectrometry revealed wild type ATTR-CA devoid of light chains. Genotype confirmed wild-type ATTR-CA. light chain chemotherapy was discontinued which improved symptoms. Determined to have monoclonal gammopathy (MGUS) with wild-type ATTR-CA. Patient was initiated on diflunisal (later transitioned to TTR stabilizer therapy, further improving symptoms.

Current amyloid diagnostic guidelines recommend first obtaining serum free light chains, serum and urine immunofixation.1,2 If one or more abnormal, proceeding to biopsy of affected organ with subtyping precursor protein is recommended. In this case, immunofluorescence was inadequate and misleading. Mass spectrometry analysis of tissue has greater specificity for amyloid protein subtype.

There is a high prevalence (40%) of coexistent monoclonal gammopathy of undetermined significance with TTR-CA.3 It is reasonable to perform 99mTc-PYP scintigraphy in suspected cardiac amyloidosis and perform mass spectrometry on cardiac tissue where ATTR-CA and monoclonal gammopathy coexist.

Monoclonal gammopathy of undetermined significance is common among patients with TTR-CA. Joseph B. Negusei, MD, Cardiologist, Hackensack Meridian Health Jersey Shore University Medical Center, Neptune, NJ, and colleagues advised, ā€œ99mTc-PYP scintigraphy should be considered prior to cardiac biopsy to identify individuals with ATTR-CA and gammopathy. Amyloid subtype delineation by cardiac biopsy with mass spectrometry significantly impacts patient management.ā€

References

  1. Maurer MS, Bokhari S, Damy T, et al. Expert consensus recommendations for the suspicion and diagnosis of transthyretin cardiac amyloidosis. Circ Heart Fail. 2019;12:e00675.
  2. Ruberg FL, Grogan M, Hanna M, et al. Transthyretin amyloid cardiomyopathy: JACC state-of-the-art review. J Am Coll Cardiol .2019;73:2872-2891.
  3. Phull P, Sanchorawala V, Connor LH, et al. Monoclonal gammopathy of undetermined significance in systemic transthyretin amyloidosis (ATTR). Amyloid. 2018;25:62-67.

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