Abstract 4362348: A Case of Concomitant Wild-Type Transthyretin and Systemic Light Chain Amyloidosis Involving Separate Organs

Abstract

Description of Case: A 72-year-old man with atrial fibrillation and spontaneous bicep rupture presents as a referral to clinic for a 2-year history of progressively worsening dyspnea. A prior cardiac magnetic resonance showed subendocardial LGE throughout the left ventricle, with elevated T1 values and LVEF 25%. Prior coronary angiography with no coronary disease. Subsequently, a 99m Tc HDP scan showed II/III in myocardial radiotracer uptake concerning for transthyretin cardiac amyloidosis (ATTR-CA) (Fig.1). Physical examination was notable for a BP of 93/59mmHg. JVP 16cmH 2 0 with HJR. Heart had an irregularly irregular rate and rhythm, no murmurs. 1+ edema to the mid shins bilaterally. ECG low voltage and atrial fibrillation. Labs notable for Cr 1.17g/dL, NT-proBNP 4,872pg/mL. Serum free light chain assay with κ light chain 11.03mg/L and λ light chain 2080.7mg/L, for a κ/λ ratio of 0.01. The 24-hour urine sample with a free λ light chain excretion rate of 356.50 mg/24 hours. Bone marrow biopsy demonstrated 10% λ restricted plasma cell neoplasm with free λ/κ ratio of 188, meeting criteria for multiple myeloma. An endomyocardial biopsy with Congo red showed apple green birefringence and typing by mass spectrometry consistent with ATTR-CA (Fig. 2). Gene sequencing revealed his TTR gene was wild-type. Biopsy of the kidney with Congo red stain was focally positive for λ amyloid consistent with systemic AL amyloidosis (Fig. 3). He completed 6 cycles of cyclophosphamide, bortezomib, dexamethasone and daratumumb with a very good hematologic partial response. For his ATTR-CA, he was initiated on acoramidis, spironolactone, and empagliflozin with improvement in his symptoms and cardiac biomarkers over the following months. Discussion: This is a case of concurrent ATTRwt-CA with systemic AL amyloidosis and kidney involvement. Although our case is unique in that these amyloid subtypes were identified in separate organs which is exceedingly rare, the key message of this case is the importance of a rigorous, thorough approach to diagnosing the etiology of suspected CA – which must include an evaluation for the evidence of AL, whether ATTR is suspected. A radionuclide scan for suspected cardiac amyloidosis should never be ordered in isolation. In the present case, had light chains not been ordered concurrently, the positive radionuclide scan may have led to a premature diagnosis of isolated ATTR-CA, but missed a crucial diagnosis of plasma cell dyscrasia.