ABC | Volume 114, Nº2, February 2020

Update Update of the Brazilian Guideline on Nuclear Cardiology – 2020 Arq Bras Cardiol. 2020; 114(2):325-429 14.6. Cardiac Amyloidosis The CA is a rare form of cardiomyopathy. Frequently subdiagnosed, it is characterized by extracellular deposition of fibrils, composed of varied serum protein subunits, which have low molecular weight. Although more than 30 different amyloid proteins have been described, the 2 that most frequently infiltrate the heart are: light chain immunoglobulin (AL) and transthyretin (TTR). The AL and TTR forms possess different clinical courses, prognoses, and distinct forms of treatment. In the AL form, fibrils are composed of light-chain immunoglobulins and produced by a population of plasma cell clones located in the bone marrow. In the TTR form, deposits are made up of anomalous monomers or dimers of the hepatic tetrameric protein whose origin may be related to genetic mutations of familial origin (mutated TTR or [mTTR]) or the wild type, formerly known as the senile type (sTTR). More than 100 known mutations are related to mTTR and to autosomal dominant inheritance, which may affect individuals in any age group, especially middle-aged men. The most common manifestation of CA is HF with preserved ejection fraction. In its final stage, it is present as restrictive cardiomyopathy, implying very poor prognosis. Definitive diagnosis requires amyloid deposits on endomyocardial biopsy or, in patients with suggestive cardiac findings, amyloid deposits on histological exams of other tissues (e.g., abdominal fat, rectum, or kidneys). 445 Echocardiography is the initial non-invasive exam of choice for diagnosing CA, but its specificity is limited. 446  However, complementary sequence with MR, which has satisfactory sensitivity, may suggest a pattern of cardiomyopathy due to amyloid deposition, except in patients with moderate to severe kidney disease. It has been reported that scintigraphy with intravenous administration of bisphosphonate radiotracers labeled with 99m-technetium (Pyrophosphate- 99m Tc is the most used in Brazil) localizes cardiac amyloid deposition. It is considered sensitive and highly specific for TTR CA, identifying the disease early at onset. 447,448 One hypothesis for the binding of these bone markers to amyloid fibers is related to the higher quantity of calcium present in TTR protein, in relation to AL. In a recent multicenter study which included 1,217 patients with suspected CA, the combination of moderate to accentuated increase in myocardial uptake of the radiotracer and the absence of specific monoclonal protein in blood serum or urine, had specificity and positive predictive value of 100% for the TTR form of CA. However, scintigraphy with bisphosphonate radiotracers does not reliably detect other types of CA, and it cannot be used quantitatively for therapeutic monitoring. 418 The intensity of the concentration of Pyrophosphate- 99m Tc in the cardiac area is correlated to the amyloid subtype. Degree of concentration is compared to bone uptake in the ribcage, considering the following: degree 3, greater uptake than the ribs; degree 2, equal to the intensity of concentration in the ribs; degree 1, lower concentration than in the ribs; and degree zero, no significant cardiac tracer concentration. Severely increased concentration (degrees 2 and 3) (Figure 61) is strongly associated with TTR CA, to the extent that some authors suggest dispensing cardiac biopsy in these situations. Less intense increased concentration (degree 1) and absence of increased concentration suggest the AL form, when there is clinical suspicion. Semiquantitative analysis of radiotracer uptake should also be performed (Figure 62). 449 Figure 60 – Patient with cardiac sarcoidosis. Myocardial perfusion scintigraphy (MPS) with MIBI- 99m Tc (left), showing evidence of accentuated persistent hypoperfusion in the anterior and anterolateral walls of the left ventricle; FDG- 18 F - PET imaging (right) for metabolic study shows that regions with apparent fibrosis were in fact inflammation due to sarcoidosis. Source: INCOR, FMUSP, SP. PERFUSION Glycolytic Metabolism FDG- 18 F 409