Influência da espironolactona na redução da fibrose miocárdica em portadores de Cardiomiopatia Hipertrófica

• Ano de defesa: 2020
• Autor(a) principal: Sales, Ana Luiza Ferreira
• Orientador(a): Rocha, Ricardo Mourilhe
• Banca de defesa: Brandão, Andréa Araujo , Bomfim, Alfredo de Souza , Garcia, Marcelo Iorio , Martins, Wolney de Andrade
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade do Estado do Rio de Janeiro
• Programa de Pós-Graduação: Programa de Pós-Graduação em Ciências Médicas
• Departamento: Centro Biomédico::Faculdade de Ciências Médicas
• País: BR
• Palavras-chave em Português: Cardiomiopatia hipertrófica; Fibrose; Ressonância magnética e micro RNA; Miocárdio Doenças; Espironolactona; Imagem por ressonância magnética
• Palavras-chave em Inglês: Hypertrophic cardiomyopathy; Fibrosis; Magnetic resonance imaging and micro RNA
• Área do conhecimento CNPq: CNPQ::CIENCIAS DA SAUDE::MEDICINA::CLINICA MEDICA::CARDIOLOGIA
• Link de acesso: http://www.bdtd.uerj.br/handle/1/8548

Hypertrophic cardiomyopathy (HCM) is the most common genetic disease in the heart. The pathophysiological features are the presence of different degrees of myocardial hypertrophy, fibrosis and cardiomyocyte deformation. Myocardial fibrosis is associated with a worse prognosis in this disease.The trigger for fibrosis has not been elucidated. Magnetic resonance imaging (MRI) can identify areas of myocardial fibrosis with high definition. Some micro RNA (miRNA) are related to myocardial fibrosis, but its role in HCM has not been established. Aldosterone inhibitors seem to block the signals that promote myocardial fibrosis. To assess whether the use of aldosterone antagonist (Spironolactone) may decrease the areas of myocardial fibrosis in MRI in patients with HCM. To describe clinical and genetic characteristics. To evaluate the influence of spironolactone on systolic function. To analyze the pathogenic mutations found, as well as the polymorphism of Aldosterone synthase and its influence on the prognosis, especially regarding the evolution of the percentage of myocardial fibrosis and left ventricular systolic function. Finally, to describe the variations of the miRNA 21 and 29a, to correlate its variation with the prognosis and as a form of evaluation of the therapeutic response to Spironolactone. A single-center, prospective, randomized, double-blind, placebo-controlled study. Excluded were patients with contraindications to the use of spironolactone, who were already using this drug and those with contraindication to MRI. The minimum follow-up was 21 months. In the first three months, transthoracic echocardiography, MRI and electrocardiogram were performed. In addition, blood samples were taken for biochemical analysis and genetic study. At the end of 18 months, the patients repeated MR and miRNA. 53 patients were included between september 2014 and april 2016. During 18 months, patients were given Spironolactone (N = 27) or placebo (N = 26). The mean age was 48 years, 49% were men. There was a death during the follow-up period and the drug was suspended in two cases. In 43% of the patients, it was possible to describe the pathogenic mutation. MYH7 was the major mutated sarcomeric protein. The identification of the mutations did not correlate with a worse prognosis. Comparing the evolution of groups, there was a symptomatic improvement in both groups as in the percentage of fibrosis in those who used Spironolactone. However, there was no statistically significant difference for fibrosis variation (p = 0,371), systolic dysfunction (p = zero, 5) as well as in miRNA 21 (p = 0, 5) and 29a (p = 0, 08). Elevation of miRNA 21 was associated with the presence of severe fibrosis (p = 0,043). The most common Aldosterone synthase´s polymorphism was T/C. The C allele was more frequent among patients with systolic dysfunction or severe fibrosis, but there was no relation between polymorphism and myocardial fibrosis (p = 0, 29) or systolic dysfunction (p = 0, 62). Spironolactone showed no benefit in the systolic function or in the percentage of myocardial replacement due to fibrosis. The identification of pathogenic mutations had no prognostic impact. Aldosterone synthase´s polymorphism did not have its prognostic role established in this disease. MiRNA 21 signals the presence of severe myocardial fibrosis. MiRNA 21 and 29a should not be used as a means of monitoring spironolactone therapy.