ABC | Volume 114, Nº4, Suplement, April 2020

Case Report Transthyretin Amyloidosis (ATTR) - The Role of Multimodality in the Definitive Diagnosis Tonnison de Oliveira Silva, 1, 2 E duardo Sahade Darze, 1,2 Luiz Eduardo Fonteles Ritt, 1, 2 A ndré Luiz Cerqueira Almeida, 3 Antônio Ximenes 1 Hospital Cardio Pulmonar - Centro de Estudos em Cardiologia, 1 Salvador, BA - Brazil Escola Bahiana de Medicina e Saúde Pública, 2 Salvador, BA - Brazil Santa Casa de Misericórdia de Feira de Santana, 3 Feira de Santana, BA - Brazil Introduction Transthyretin amyloidosis (ATTR) is a rare cause of restrictive cardiomyopathy and/or peripheral polyneuropathy, of a progressive, irreversible and fatal nature, underdiagnosed and with its definitive diagnosis performed late. 1 Early diagnosis, characterization of the type of amyloidosis and subsequent establishment of specific therapy are fundamental for a better prognosis of this disease. 1 We present a case of ATTR where clinical suspicion associated with multimodality diagnosis — nuclear medicine — was able to safely deliver diagnosis, without the need for biopsy. 2 Case Report Male patient, 75 years old, previously diagnosed with stage 1 systemic arterial hypertension (SAH), reporting dyspnea on moderate exertion for 2 months. He was regularly taking Losartan 50 mg a day, with proper blood pressure control. Physical examination with no relevant finding, electrocardiogram (ECG) showing sinus rhythm of 64 bpm and isolated ventricular extrasystoles. Echocardiography revealed mild biatrial dilation, mild left ventricular systolic dysfunction, ejection fraction = 49% (Simpson), grade II diastolic dysfunction and severe concentric hypertrophy of the left ventricle disproportionate to his history of SAH, which led to the suspicion of cardiac amyloidosis. Magnetic resonance imaging of the heart (figure 1-B) showed ventricular hypertrophy with diffuse heterogeneous subendocardial late enhancement. Two-dimensional speckle tracking echocardiography showed reduced global longitudinal strain (GLS = -10%), ejection fraction/GLS ratio = 4.9, with diffuse impairment of the subendocardial strain, but with preserved apex (figure 1-A), which reinforced the initial clinical suspicion. Immunofixation of proteins in blood and urine associatedwith blood search for light chains, all negative, was requested. Still without a conclusive diagnosis and in view of the clinical findings and suggestive imaging findings, a rarer type of amyloidosis, ATTR, was suspected. In this type of amyloidosis, laboratory tests do not help and biopsies may not be conclusive. 1,2 Pyrophosphate scintigraphy was then requested because of its high diagnostic accuracy for this type of amyloidosis. 2,3 The scintigraphy findings were compatible with ATTR (Figure 2). The patient underwent genetic study to differentiate ATTRw (wild) x ATTRm (mutant), through DNA testing using saliva swab, confirming it is ATTRm, with valine to isoleucine mutation (figure 1-C). He had also been diagnosed with bilateral carpal tunnel syndrome with no clear cause. Electroneuromyography was performed and showed distal axonal polyneuropathy (characteristic of amyloid neuropathy). 1,5 Treatment started with Tafamidis, a drug that stabilizes transthyretin, decreasing progression of neurological disease and, more recently, showing an important benefit in hospitalizations and mortality. 1,4 Discussion Amyloidosis is a localized or systemic infiltrative disease, where the degree of cardiac involvement can define its prognosis. It is a recognized cause of restrictive cardiomyopathy, heart failure and polyneuropathy. 1 There are more than twenty types of amyloid protein, most notably two: Light chain (AL) and transthyretin-related (ATTR). 1 In the AL type, which is more prevalent, more common in the elderly and in males, fibrillar proteins are formed by light chains (Kappa and Lambda) produced by plasma cells in the bone marrow. Mutant or hereditary ATTRm is caused by an autosomal dominant mutation, similarly affecting both sexes, with the onset of symptoms above 60 years of age. However, this will depend on the type of mutation found. 1 As for ATTRw, known as a “wild” or senile type, there is no associated mutation and it is more prevalent in men >70 years of age. 1 The two organs most frequently affected by amyloidosis are the heart and the kidney. Severe proteinuria leading to nephrotic syndrome and renal dysfunction are the main manifestations of renal involvement of this clinical disorder. The clinical presentation of amyloid cardiomyopathy involves restrictive cardiomyopathy, right heart failure (HF), with ascites, hepatomegaly and lower limb edema, HF with preserved ejection fraction and, less frequently, a condition that is similar to that of an asymmetric hypertrophic septal cardiomyopathy. 1 Impairment of the autonomic system with orthostatic hypotension, peripheral nervous system with sensory-motor polyneuropathy, conduction system disorders and also carpal tunnel syndrome (CTS), especially if bilateral, Mailing Address: Tonnison Oliveira Silva • Hospital Cardio Pulmonar - Centro de Estudos em Cardiologia - Av. Anita Garibaldi, 2199. Postal Code 40170-130, Ondina, Salvador, BA – Brazil E-mail: tonnisonsilva@hotmail.com Manuscript received July 15, 2018, revised manuscript December 24, 2018, accepted February 13, 2019 Keywords A m y l o i d o s i s / c o m p l i c a t i o n s ; P r e a l b u m i n ; Cardiomyopathy,Restrictive; Endomyocardial Fibrosis; Hypertension; Heart Failure; Diagnostic Imaging. DOI: https://doi.org/10.36660/abc.20180077 8