ABC | Volume 113, Nº5, November 2019

Review Article Deposit Diseases as Differential Diagnosis of Left Ventricular Hypertrophy in Patients with Heart Failure and Preserved Systolic Function Fábio Fernandes, 1 Murillo Oliveira Antunes, 1 Viviane Tiemi Hotta, 1, 2 C arlos Eduardo Rochitte, 1 Charles Mady 1 Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, 1 São Paulo, SP – Brazil Fleury Medicina e Saúde, 2 São Paulo, SP – Brazil Keywords Heart Failure; Hipertrophy, Ventricular; Cardiomyopaty, Restrictive; Amyloidosis; Fabry Disease. Mailing Address: Fábio Fernandes • Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - Av. Dr. Eneas C. Aguiar, 44. Postal Code 05403-000, São Paulo, SP – Brazil E-mail: fabio.fernandes@incor.usp.br Manuscript received November 22, 2018, revised manuscript April 10, 2019, accepted May 15, 2019 Invited editor for this paper: Dra. Gláucia Maria Moraes de Oliveira DOI: https://doi.org/10.36660/abc.20180370 Heart failure with preserved systolic function is the main clinical manifestations of patients with ventricular hypertrophy. Conventional treatment is based on the improvement of diastolic dysfunction and congestion. However, no drug has been shown to be effective in the survival of these patients. Thus, it is important to look for the etiology of ventricular hypertrophy with the aim of a treatment directed to the underlying disease. Among patients with heart failure with preserved systolic function and increased ventricular wall thickness, the clinician should consider as possible differential diagnoses: hypertensive heart disease, deposit disease and hypertrophic cardiomyopathy (Figure 1). 1 Restrictive cardiomyopathies are the least common forms of heart muscle disease. They can be characterized as infiltrative and non-infiltrative, deposit disease or endomyocardial disorders. Possible restrictive cardiomyopathies that may mimic and even be diagnosed as hypertrophic cardiomyopathy are: Amyloidosis, Fabry disease (FD) and Glycogen deposit disease. 1 We have observed in our group that many patients with deposit disease have been followed for years with a diagnosis of left ventricular hypertrophy (LVH) or hypertrophic cardiomyopathy. A non-systematic literature review was performed to address the principal papers that suggest deposit diseases such as ventricular hypertrophy etiology and the “red flags” for a possible diagnosis. The database consulted was PubMed (www.ncbi.nlm.nih.gov/pubmed ). Original articles and review performed in humans, written in Portuguese and English, were selected and the keywords MeSH hypertrophic cardiomyopathy, amyloidosis, Fabry's disease and glycogen deposit disease were used as keywords. In the present literature review, we will first address amyloidosis and later FD and finally glycogen deposit disease. Amyloidosis is a disease caused by the deposition of amyloid fibrils in various organs, 2 including the heart, where amyloid proteins infiltrate the ventricular wall, with consequent thickening causing systolic and diastolic dysfunction, heart failure (HF) and conduction disorders, with high mortality. 2-4 More than 30 proteins can form amyloidosis, and among these, five can affect the heart. However, the most common types of amyloidosis that infiltrate the heart are: 1) light chain immunoglobulin, also called primary amyloidosis or AL amyloidosis; 5 2) Transthyretin called amyloidosis-ATTR, which may be of genetic origin also called familial form ATTRm and form ATTRwt, also called wild type. Detection and differentiation between these two forms are fundamental because they have different treatment and clinical evolution. Some patients with ATTRm and ATTRwt may have increased serum immunoglobulins, which may confuse the clinician regarding the correct type of amyloidosis. The importance of the proper diagnosis of amyloidosis is based on that the treatment is different from other forms of heart failure and hypertrophic cardiomyopathy. In patients with amyloidosis, digitalis, calcium blockers and high doses of beta-blockers should be avoided, in addition, there are currently new therapeutic possibilities related to the underlying disease. 6 The goal of amyloidosis treatment is to stop protein production by reducing the burden of circulating amyloid proteins. 6-8 In AL amyloidosis there is a direct toxic effect of circulating immunoglobulin that may contribute to myocardial dysfunction and lead to early diastolic dysfunction. This may explain the discrepant findings between the severity of symptoms and changes in diastolic function in patients with little or no thickening evaluated by echocardiography. Patients have seen five clinicians with an average of two years before the correct diagnosis of AL amyloidosis and when this is often made the prognosis is reserved. Therefore, it is important for clinicians to consider AL amyloidosis as a differential diagnosis of hypertrophy or heart failure with preserved systolic function. 1,8 More than 150 mutations are described in genetic form related to the ATTR protein gene. The most common allele in the US is Val122Ile, found in 4%of African American individuals. In our country, the change of valine by methionine to position 30 is the most common mutation (Val30Met). In countries like Japan, there is a bimodal pattern of presentation in this mutation (Val30Met): an early form that occurs around 20 to 40 years, characterized by loss of thermal and sensory sensitivity, family history, high penetrance, autonomic dysfunction and conduction disorders. In the late form, which begins around 50 years of age, patients have sensory-motor symptoms in the lower distal extremities, low penetrance, mild dysautonomia and greater myocardial impairment. The presence of neurological or systemic symptoms should suggest to clinicians as red flags to the possibility of ATTRm amyloidosis. 3,4,7 979