ABC | Volume 113, Nº5, November 2019

Review Article Fernandes et al. Deposit diseases and ventricular hypertrophy Arq Bras Cardiol. 2019; 113(5):979-987 should be considered as a differential diagnosis in patients with hypertrophic heart disease. 17 In our group, four patients initially diagnosed with HCM had the diagnose of ATTRm form with V142I mutation. Amyloidosis should be suspected in patients with bilateral carpal tunnel syndrome, unexplained neuropathic pain, orthostatic hypotension, and hypertrophic cardiomyopathy diagnosed after the 6th decade of life. 6 Complementary methods (ECHO and CMR) contribute to the recognition of cardiac amyloid infiltration, degree of ventricular hypertrophy and systolic and diastolic dysfunction. 18,19 However, thesemorphological and functional changes represent an advanced picture of disease and correlate it with the amount of amyloid in the whole body. 20 This stage of the disease is also related to worsening clinical signs and symptoms. 21 Typical echocardiographic findings are: Left ventricular thickness with right ventricular (RV) involvement, decreased biventricular longitudinal axis function with normal or near normal ejection fraction (EF) and increased valve thickness. 22 and blood flow assessment by Doppler allows also the identification of cardiac hemodynamics present in the restrictive form. 23,24 Patients with ATTRwt had a higher left ventricular thickness and lower ejection fraction and the longitudinal strain is lower in ATTRwt and AL forms when compared to ATTRm. 2 (Figure 3, 4 and 5) More advanced ECO techniques such as strain and strain rate derived from speckle tracking may assist in the assessment of cardiac torsion movements and facilitate the differentiation between cardiac amyloidosis and hypertrophic cardiomyopathy. In patients with amyloidosis there is a regional variation from the base to the apex to the longitudinal strain, where the apical portion is preserved, and this accurate and reproductive pattern in the differentiation between cardiac amyloidosis and other forms of left ventricular hypertrophy. 18 LV strain analysis at rest is an independent predictor of mortality from both cardiac and other causes. 25 Cardiac magnetic resonance imaging (CMR) provides information on cardiac function and morphology in patients with amyloidosis. 19 However, CMR is better for assessing and quantifying abnormalities in ventricular diastolic function. The images from CMR allow 3-dimensional evaluation of cardiac volumes, cardiac wall thickening and mass. In addition, new techniques used by CMRI such as gadolinium late enhancement are fundamental in identifying cardiac amyloid infiltrates and enable the differentiation between a patient with amyloidosis and patients with ventricular hypertrophy, such as patients with hypertension and hypertrophic cardiomyopathy. However, the clinician should consider the high degree of clinical suspicion combined with complementary imaging methods, as often the anatomical features of hypertrophy can simulate both diseases. 26 The asymmetric pattern of myocardial hypertrophy in patients with ATTR amyloidosis differs from AL patients, usually symmetrical. In a study of 263 patients with TTR amyloidosis confirmed by grade 2 myocardial scintigraphy and compared with 50 patients with AL form, it was observed: in the TTR form there was asymmetric hypertrophy in 79% of cases, symmetrical in 18% and 3% without LVH. The late enhancement pattern was 29% subendocardial and 71% transmural. 26 We can identify three stages of disease by resonance with different prognosis: phase 1 - no evidence of late enhancement, but with increased extracellular volume and T1 map with 92% survival at 24 months; phase 2 - increased extracellular volume and T1 map and appearance of late subendocardial enhancement with 81% survival; and phase 3 - increased extracellular volume and T1 map and progression to late transmural enhancement with 61% survival. In multivariate analysis, the presence of transmural late enhancement increased mortality 4-fold and extravascular space correlated with amyloid loading and was an independent prognostic marker of survival. 19 Technetium bone scintigraphy may be useful for differentiating the AL form from TTR. TTR amyloidosis often has a higher number of microcalcifications, which would justify its higher uptake of these radiopharmaceuticals. Using a visual score (0: absence of uptake, 1: uptake less than bone, 2: uptake equal to bone and 3: uptake upwards - more intense than bone uptake) to assess cardiac technetium uptake, it is possible to differentiate the shape TTR of other types of cardiac amyloidosis in conjunction with absence of light chain immunoglobulins in blood and urine. Thus, the diagnosis of TTR amyloidosis can be performed without the need for biopsy. 6 Figure 2 flowchart for evaluation of patients with suspected cardiac amyloidosis. Amyloidosis is a heart disease with heterogeneous phenotype and in many cases there are symptoms preceding in years the onset of cardiac manifestations. Thus, clinicians should have a high degree of suspicion to be able to direct the exams and do a correct diagnosis Fabry Disease Fabry's disease FD is a genetic, lysosomal storage disorder caused by total or partial alpha-galactosidase ( α -Gal A) deficiency of the enzyme that degrades glycolipid globotriaosylceramide (Gb3) in lysosomes. 27 Therefore Gb3 deposits accumulate in the endothelial cells and heart, resulting in organic dysfunction. 28 The gene that causes FD is located in the long arm of the X chromosome ( locus Xq22) and currently hundreds of pathogenic mutations have been described. 29 Thus, male homozygous patients develop the classic disease, while female heterozygous patients present variable clinical manifestations from conditions without apparent clinical disease to the complete expression of the disease. 29-31 In clinical practice, early diagnosis is important because actually there are specific treatment with enzyme replacement therapy (ERT) that may change the natural history, reducing and/or stabilizing the progression of the disease. 32,33 The FD cardiac phenotype is left ventricular hypertrophy (LVH) and FD should be considered as a differential diagnosis of hypertrophic cardiomyopathy Some studies have shown that up to 5% of these patients would have the diagnosis of FD. 34-36 We have observed in our outpatient clinic patients with FD and onset of hypertrophy in adulthood, a progressive character, with electrocardiographic alterations and echocardiographic findings similar to those of HCM, including LV outflow tract obstruction. Just like amyloidosis, there are also systemic manifestations that may infer the diagnosis of FD. 34-36 981