Clinical clues for suspecting wild-type transthyretin cardiac amyloidosis in patients with monoclonal gammopathy of undetermined significance: a case report

Abstract

Background: Myeloproliferative disorders, including monoclonal gammopathy of undetermined significance (MGUS), are often associated with amyloid light-chain (AL)-type cardiac amyloidosis (CA) but occasionally with wild-type transthyretin (ATTR) CA. In recent years, ATTR amyloidosis has attracted necessity for its reliable diagnosis with the addition of new treatments. Usually, both wild-type ATTR CA and AL-type CA present with marked cardiac hypertrophy, but renal dysfunction is milder in wild-type ATTR amyloidosis than in AL-type amyloidosis. Peripheral neurologic and autonomic symptoms such as numbness and dysesthesia are moderately present in AL-type amyloidosis, but less so in wild-type ATTR amyloidosis. Furthermore, the prognosis of ATTR-type amyloidosis is better than that of AL-type amyloidosis.

Case presentation: A 72-year-old man with cardiac hypertrophy presented with New York Heart Association functional class III dyspnea and leg edema. He had no history of carpal tunnel syndrome. An electrocardiogram showed atrial fibrillation and low voltage. The N-terminal pro-B-type natriuretic peptide level was 3310 pg/mL, and troponin T was elevated to 0.073 ng/mL. However, the glomerular filtration rate was only slightly decreased at 69.0 mL/min/1.73 m². The serum free light-chain assay revealed a significant increase in the kappa chain, with positive results in Bence Jones proteins and serum immunoelectrophoresis. Bone marrow examination confirmed the diagnosis of monoclonal gammopathy of undetermined significance (MGUS). AL-type amyloidosis associated with a myeloproliferative disorder was suspected, and the prognosis was initially predicted to be poor, classified as Mayo stage IV. Contrary to this prognosis, the patient showed a slow progression of heart failure. Further imaging modalities and cardiac tissue findings confirmed the diagnosis as transthyretin type amyloidosis, and a favorable prognosis was established with the use of tafamidis.

Conclusions: MGUS occasionally coexists with wild-type ATTR CA. Scant autonomic symptoms, mild renal dysfunction, and slow progression of heart failure might be clues that the CA associated with the myeloproliferative disease is wild-type ATTR amyloidosis.

Keywords: Cardiac amyloidosis; Monoclonal gammopathy of undetermined significance; Transthyretin.

Fig. 1

Diffuse cardiac hypertrophy and apical sparing pattern on transthoracic echocardiography. Symmetric left ventricular hypertrophy and mild systolic dysfunction are observed in the parasternal long axis view (a, b) and four-chamber view (c, d). Two-dimensional speckle-tracking echocardiography shows a reduced longitudinal strain in the basal segments and preserved longitudinal strain in the apical segments of the left ventricular myocardium (apical sparing) (e)

Fig. 2

Increased uptake into the myocardium in ^99mTechnetium pyrophosphate (Tc-PYP) scintigram and histological findings of endomyocardial biopsy samples. Myocardial uptake of ^99mTc-PYP was greater than bone uptake, which was classified as Grade 3 (a). Congo red-positive amyloid deposits in the myocardium (b). Apple-green birefringence under polarized light (c). Myocardial amyloid deposits were immunologically stained with anti-transthyretin (d) but not with anti-kappa (e) and anti-AA (f)