ABC | Volume 114, Nº4, Suplement, April 2020

Case Report Silva et al. Transthyretin Amyloidosis - without the need for biopsy Arq Bras Cardiol 2020; 114(4Suppl.1):8-12 are some of the possible manifestations of systemic infiltration by amyloid material. 1,5 Regarding CTS, a recent study by Sperry BW et al. showed that some of the patients with surgical indication actually had amyloidosis as the underlying disease and, of these, 20% also had cardiac involvement. 5 Transthyretin is a protein synthesized mainly in the liver and carries vitamin A and thyroxine. There are more than one hundred mutations of the genes that encode this protein, ultimately leading to the formation of proteins with incorrect folding and extra-cellular deposition of these amyloid fibrils in the peripheral and autonomic nerves and in organs, such as the heart and kidneys. 1 AL and ATTR present differences in prognosis and have completely different therapeutic strategies. 3,5 Thus, early diagnosis and characterization of their type are crucial for the proper management of these patients. 2,3 On clinical reasoning, the presence of LVH on the echocardiogram (especially if septal thickness >12 mm) and low voltage (LV) ECG, the diagnostic hypothesis of cardiac amyloidosis should always be considered. However, this classical finding of ECG X ECHO dissociation is very little sensitive (present in 50% of AL cases and only 25% in ATTR cases). 1,6 The echocardiogram in this clinical entity classically presents increased ventricular thickness, diastolic dysfunction and, in more advanced stages, systolic dysfunction, but these are non-specific findings. In order to deliver a diagnosis with a high probability of certainty, a more advanced workup is necessary. 2,3,7,8 Magnetic resonance imaging (MRI) of the heart and two-dimensional speckle tracking echocardiogram have good accuracy, playing an important role in the early diagnosis of this pathology. 6-8 According to a study by Austin et al., 9 MRI with late enhancement presents 88% sensitivity (S) 95% specificity (E) 93% positive predictive value (PPV) and 90% negative predictive value (NPV). 9 Impairment is subendocardial, and may be diffuse, heterogeneous or transmural, with the latter presenting the worst prognosis. 8 Cardiac strain can be used for the differential diagnosis of causes of increased ventricular thickness, with diagnostic accuracy provided by the finding of quite satisfactory apex preservation (S = 96 %, E = 88%, in patients without coronary artery disease). 6,7 It is noteworthy that the presence of apical sparing is not exclusive to amyloid disease, and can be found in SAH, aortic stenosis and hypertrophic cardiomyopathy, for example. 7 However, the finding of apex preservation, with RRSR (relative regional strain rate, which represents the sum of apical/basal + medium strain) >1, associated with EF/GLS ratio >4.1 (as seen in this case), are highly suggestive of amyloidosis. 6,7 Both MRI and strain echocardiogram can adequately suggest the diagnosis of cardiac amyloidosis. 2,6-8 The definition of whether it is AL or ATTR, which is essential for managing these patients, can be done accurately using nuclear medicine. 3,10 Scintigraphy with pyrophosphate-labeled technetium can differentiate, in most cases, these types. 3,10 Uptake of Perugini grade 2 or 3 radiotracer (visual evaluation) have sensitivity and specificity around 88%, with an area under the ROC curve of 0.945 (95% CI, 0.901–0.977). 10 Quantitative evaluation, done through the heart/contralateral chest area ratio, is best in terms of accuracy, since a value >1.5 presents S and E around 92%, with an area under the ROC curve of 0.960 Figure 1 – 1-A) Strain echocardiography showing classic apical sparing. 1-B) MRI with diffuse heterogeneous left ventricular late enhancement (arrows on the left) and diffuse increase in LV thickness (arrow on the right). 1-C) Result of genetic study showing valine to isoleucine mutation (VAL142IIe). Systolic peak strain Systolic peak strain Figure 1 - A Figure 1 - B Figure 1 - C Test: Familiar Amyloidosis Panel Result Diagnosis:amyloidosis associatedwithgeneTTR (OMIM#105210) Gene Position Variation Consequence Copies Heterozygosity (1 copy) Definitely pathogenic Genesanalyzed: TTR 9