ABC | Volume 113, Nº5, November 2019

Review Article Fernandes et al. Deposit diseases and ventricular hypertrophy Arq Bras Cardiol. 2019; 113(5):979-987 Figure 2 – Evaluation of patients with suspected cardiac amyloidosis. 1 Diagnostic algorithm for amyloid cardiomyopathy ECHO strain, ECG, heart failure, syncope, bradyarrhytmia Serum and urine immunofixation + serum free light chain assy Monoclonal protein present Positive Histological confirmation and typing of amyloid Amyloid deposits Echo/CMR suggesting Cardiac amyloidosis Negative Bone scintigraphy (m Tc-DPD/HMDP/PYP) Grade 0-1 Grade 2 e 3 TTR Endomyocardial biopsy TTR genotyping Wild-type ATTR Variant ATTR – – + + Gb3 deposits are present in all cellular components of the myocardium, such as cardiomyocytes, conduction system, valvular fibroblasts, endothelial cells and vascular smooth muscle cells, but their totality represents only 1% to 2% of all cardiac mass, suggesting activation of other signaling pathways leading to hypertrophy, apoptosis, necrosis and fibrosis. 37 Concentric ventricular hypertrophy is the most typically found in FD, but approximately 5% of cases present as asymmetric septal hypertrophy with dynamic LV outflow tract obstruction. Although LVH has been detected in some children, cardiovascular signs and symptoms are usually present in the third or fourth decade of life in men and one decade later in women. 38,39 The presence of LVH leads to a reduction in life expectancy by approximately 20 years in men and 15 years in women when untreated compared to the general population. 40,41 The magnitude of hypertrophy increases with age and is inversely related to renal function and α -Gal A activity. Right ventricular involvement is common with no functional or clinical consequences. 42 Cardiac manifestations may occur as the only manifestation of the disease called “cardiac variant”. 43 The diagnosis of myocardial hypertrophy is performed by echocardiography with the presence of bright endocardium or binary appearance of the border of the endocardium. This fact represents the compartmentalization of Gb3 and was proposed as a marker of Fabry's disease. 44 However, subsequent studies demonstrated limited sensitivity (15%‑35%) and specificity (73%-80%). 45,46 Diastolic dysfunction occurs early more frequently than systolic dysfunction, and before the development of hypertrophy. 47,48 Delayed gadolinium enhancement is common in patients with FD. 49-51 The enhancement presenting with a non-ischemic pattern, located in the mesocardium and not affecting subendocardium, in basal and middle segments of the anterolateral and inferolateral walls. 52 Among men, myocardial fibrosis occurs only in those with ventricular hypertrophy, differently myocardial fibrosis emerge without LVH in women. 38,53 Other findings are commonly identified in FD patients: mild thickening and mitral and/or aortic valves regurgitation but usually without the need for valve repair. 37,38,54 Coronary artery disease manifested as angina often occurs in men and women. 55,56 Atrial arrhythmias, including atrial fibrillation, are common and appear to be age-related. Non‑sustained ventricular tachycardia usually associated to LV wall thickness. Conduction abnormalities may be caused by glycolipid deposition in the atrioventricular (AV) node, His bundle, and branches. 57,58 The short PR interval, particularly in younger patients, 59,60 and EKG changes compatible with LVH (QRS complex voltages and repolarization change, opposite to other depository diseases with low QRS complex voltages on electrocardiogram. Sinus node dysfunction and atrioventricular blocks result in bradyarrhythmia requiring pacemaker implantation in older patients. 58,60,61 The definitive diagnosis of FD in male patients is generally confirmed by measuring alpha-Gal A activity of leukocytes. 62 However, this assay will identify less than 50% female heterozygotes. In female with suspected Fabry disease (and men with marginal levels of alpha-Gal A activity), genetic testing is recommended. 63,64 982