A 69-year-old African-American man was referred for evaluation of heart failure (HF). He presented to his primary care provider with 6 months of worsening dyspnea on exertion and lower extremity edema. The patient reported sleeping in a recliner for the week prior. He also noticed that his blood pressure had been lower recently, necessitating reduction of the dose of some of his antihypertensives.
His vital signs today include heart rate 78 bpm and blood pressure 101/68 mm Hg. His body mass index is 23 kg/m2.
Physical examination reveals an irregular heart rhythm without murmur or gallop. He has bibasilar crackles and 3+ pitting edema on the bilateral lower extremities to his upper thigh. Examination of his hands reveals flattening of the thenar eminence and numbness of his thumb, index, and middle finger bilaterally. Electrocardiography shows atrial fibrillation with a rate of 75-80 bpm and left bundle branch block. A transthoracic echocardiogram reveals ejection fraction 60-65% with concentric left ventricular wall thickening (1.7 cm posterior wall, 1.6 cm interventricular septum). There is biatrial enlargement with thickening of the interatrial septum and moderate tricuspid regurgitation.
A pyrophosphate scan shows grade 3 uptake, kappa free light chain 4.02 mg/dL, lambda free light chain 2.01 mg/dL, free light chain ratio 2.0, and an M-spike on serum immunofixation.
Which one of the following is the best next step for the diagnosis of this patient's cardiomyopathy?
Show Answer
The correct answer is: D. Schedule an endomyocardial biopsy and perform liquid chromatography tandem mass spectrometry for further amyloidosis typing.
Answer choice D is the correct choice. In this setting, the patient must undergo tissue biopsy to rule out light chain (AL) amyloidosis. AL cardiac amyloidosis is a rapidly progressive illness that, if left untreated, may have a patient's survival as low as 4-6 months.1 Monoclonal gammopathy of unknown significance (MGUS) is an abnormality of plasma cells and can coexist in up to 40% of patients with wild type cardiac amyloidosis and almost 50% of patients with the V122I variant; however, it must not be assumed that this patient has coexistent MGUS until AL amyloidosis has been ruled out.2 In addition, in the setting of MGUS, referral to hematology should be made due to the risk of conversion to AL amyloidosis or multiple myeloma over time.
Answer choice A is incorrect choice because a negative fat pad biopsy is not sufficient to rule out AL amyloidosis in the setting of a high clinical suspicion. The affected organ should be the target for biopsy.
Answer choice B is an incorrect choice. Cardiac magnetic resonance imaging (MRI) with late gadolinium enhancement (LGE) and spin-lattice relaxation time (T1) mapping can be useful additions in the evaluation of cardiac amyloidosis. MRI provides information regarding the extent of amyloid infiltration with LGE and quantification of the amyloid burden with T1 mapping and extracellular volume.3,4 However, it does not distinguish amyloid types.
Answer choice C is an incorrect choice because this patient has a monoclonal protein on serum immunofixation. The nonbiopsy diagnosis of transthyretin (TTR) can be performed only if all the following are true: 1) The patient should have unexplained HF or be a pathogenic TTR mutation carrier; 2) the patient must have echocardiographic or cardiac MRI findings consistent with or suggestive of amyloidosis; 3) the patient must have grade 2 or 3 cardiac uptake on scintigraphy; and 4) there is an absence of monoclonal protein on serum and urine immunofixation with an unremarkable free light ratio.5 This patient has a monoclonal protein and must undergo additional evaluation to rule out AL amyloidosis.
References
Kumar S, Dispenzieri A, Lacy MQ, et al. Revised prognostic staging system for light chain amyloidosis incorporating cardiac biomarkers and serum free light chain measurements. J Clin Oncol 2012;30:989-95.
Phull P, Sanchorawala V, Connors LH, et al. Monoclonal gammopathy of undetermined significance in systemic transthyretin amyloidosis (ATTR). Amyloid 2018;25:62-7.
Fontana M, Chung R, Hawkins PN, Moon JC. Cardiovascular magnetic resonance for amyloidosis. Heart Fail Rev 2015;20:133-44.
Martinez-Naharro A, Treibel TA, Abdel-Gadir A, et al. Magnetic resonance in transthyretin cardiac amyloidosis. J Am Coll Cardiol 2017;70:466-77.
Gillmore JD, Maurer MS, Falk RH, et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation 2016;133:2404-12.
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