A rare case of mutant transthyretin cardiac amyloidosis

Abstract A 65–year–old man with a history of multiple hospitalizations in the past 12 months for heart failure with preserved left ventricular ejection fraction (HFpEF) attended the emergency department for exertional dyspnea, peripheral edema, abdominal bloating, and weight gain. An ECG showed sinus bradycardia with first degree AV block, RBBB, and inferior pseudo–q. Blood tests showed NT–proBNP 8985 pg/ml, troponin hs–cTnI 106 ng/L. An echocardiogram demonstrated severe left ventricular hypertrophy, EF 50%, GLS –11% with apical sparing, and restrictive transmitral pattern, raising suspicion of infiltrative disease (Figure 1). A cardiac MRI corroborated the suspicion, showing altered gadolinium kinetics, diffuse subendocardial LGE, and increased native T1 and extracellular volume (Figure 2). A search for monoclonal components on serum and urine was negative. A bone tracer scintigraphy showed cardiac uptake (Perugini grade 2). A genetic test showed the presence of p.Ile88Leu (Ile68Leu) mutation in heterozygosity, so a non–biopsy diagnosis of mutant transthyretin cardiac amyloidosis (ATTRv) was posed. A thorough neurological evaluation did not document signs of amyloid neuropathy. The patient was then started on tafamidis therapy. Transthyretin cardiac amyloidosis (ATTR) is still an underdiagnosed but increasingly recognized condition, causing up to 13% of HFpEF cases. ATTR is caused by extracellular accumulation of amyloid substance resulting from transthyretin misfolding. In Italy ATTRv is rare and Ile68Leu is among the most frequent mutations, especially in the Tuscan–Emilian Apennines. Ile68Leu is usually associated with an almost exclusively cardiac phenotype, clinically indistinguishable from ATTR wild type, except for an earlier age of onset. Because effective treatments are available for ATTRv with cardiac and/or neurological involvement, it is important to suspect the diagnosis of ATTR in patients with HFpEF and to proceed with genetic testing to identify individuals with ATTRv.