ATTR Cardiomyopathy Meets Multiple Myeloma
Authors: Anthony J. Kanelidis, Patrick Miller, Nicole Prabhu, Mark Joshua Dela Cruz, Francis J. Alenghat, Phillip McMullen, Nitasha Sarswat, Benjamin A. Derman, Tamar S. Polonsky, Jeanne M. DeCara
Journal: JACC CardioOncology (2021)

A 74-year-old man with a past medical history of IgG Kappa multiple myeloma (MM) and persistent atrial fibrillation presented for consideration of autologous stem cell transplantation (ASCT).He was diagnosed with MM after he was found to have anemia, renal failure, and hypercalcemia.His laboratory studies revealed an IgG Kappa monoclonal protein on serum protein electrophoresis and immunofixation with kappa/lambda ratio 96.Bone marrow biopsy revealed 40% monotypic plasmacytosis.He began chemotherapy (bortezomib, lenalidomide, dexamethasone, and later carfilzomib) for his MM and achieved a very good partial response by the end of induction therapy: K/L ratio 5.6 and repeat bone marrow biopsy with 5%-8% residual plasmacytosis.Before proceeding with ASCT, he developed signs and symptoms of heart failure (HF), including lower extremity edema, jugular vein distension, and dyspnea on exertion with New York Heart Association functional class II.He was seen in clinic by a cardio-oncologist who noted that the electrocardiogram demonstrated atrial fibrillation and low voltage.In addition, the transthoracic echocardiogram demonstrated normal left ventricular systolic function, concentric left ventricular hypertrophy with an increased wall thickness of 16 mm, and severe biatrial enlargement.The global longitudinal strain was À8.1% with an apical sparing pattern.These findings were suspicious for cardiac amyloidosis and prompted further diagnostic testing.Both high sensitivity troponin T (122 ng/L) and N-terminal pro-B-type natriuretic peptide (5,821 pg/mL) were elevated.A cardiac magnetic resonance imaging was then performed that showed normal biventricular ejection fraction but severe biatrial enlargement, and extensive diffuse subendocardial and transmural circumferential late gadolinium enhancement.The native T1 relaxation time was elevated at 1,100 ms, T2 weighted value was 225 ms, and there was no evidence of pericardial effusion.These findings were highly suggestive of an infiltrative process, with amyloidosis highest on the differential.Given the patient's initially elevated kappa free light chain level, there was concern that the patient may have had concurrent MM and amyloid light chain (AL) amyloidosis with cardiac involvement (AL-CA).AL-CA is known to lead to poor outcomes, and knowledge of the presence of AL amyloidosis might change post-ASCT and subsequent therapies.Additional diagnostic tests were obtained to ascertain whether there was AL amyloidosis; however, both fat pad and bone marrow biopsies were negative for amyloid by Congo Red staining.Given the high index of suspicion for cardiac amyloidosis (CA), he underwent a right heart catheterization with biopsy; this demonstrated elevated biventricular filling pressures with preserved cardiac output.An endomyocardial biopsy was performed for definitive diagnosis of CA.Ultimately, CA was confirmed because the biopsy demonstrated amyloid deposits on Congo Red stain and fluorescence microscopy (Figure 1),