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Advisor(s)
Abstract(s)
Sob o ponto de vista histórico, tanto as miocardiopatias com origem no ventrículo esquerdo como a doença arterial coronária têm sido reconhecidas, ao longo do tempo, como as principais causas de arritmia ventricular e morte súbita. Todavia, nas últimas duas décadas, arritmias com origem no ventrículo direito têm atraído cada vez mais atenção científica face a um elevado número de razões. As arritmias geradas no ventrículo direito normalmente afetam indivíduos mais jovens e podem culminar em episódios de morte súbita cardíaca. Os mecanismos fisiopatológicos implícitos ainda não se encontram totalmente compreendidos, o que motiva diferentes interpretações acerca dos mesmos.
A miocardiopatia arritmogénica corresponde a uma doença hereditária do músculo cardíaco, onde ocorre substituição do miocárdio por tecido fibroadiposo e que se caracteriza clinicamente por arritmias ventriculares potencialmente letais, principalmente em indivíduos jovens e atletas. Apesar de acometer o ventrículo direito com maior frequência, o envolvimento biventricular ou de predomínio esquerdo também já foi descrito. Sendo considerada a “doença dos desmossomas”, várias mutações foram reportadas em genes codificadores de proteínas desmossómicas, conduzindo a alterações intracelulares na transdução de sinal e, por conseguinte, à transformação dos miócitos cardíacos.
O diagnóstico clínico tem por base um sistema que conjuga fatores genéticos e familiares, variações eletrocardiográficas, eventos arrítmicos, achados histopatológicos e ainda, variantes funcionais ou estruturais do ventrículo direito, pertinentes no reconhecimento das características inespecíficas desta entidade. Indivíduos afetados, apresentam-se na sua maioria durante a segunda ou terceira décadas de vida com sintomas como palpitações, síncope ou paragem cardiorrespiratória tendo, contudo, a presença de portadores assintomáticos sido igualmente relatada, em prol do sequenciamento genético tendencial. O objetivo primordial do tratamento consiste na prevenção de eventos de morte súbita.
Dado a sua crescente relevância clínica e impacto científico significativo, esta dissertação considera a revisão alargada relativa à patogénese, diagnóstico e terapêutica atual, relacionados com esta forma rara de miocardiopatia.
Historically, left ventricular cardiomyopathy and coronary heart disease have been regarded as the main causes of ventricular arrhythmia and sudden cardiac death. However, within the last two decades, arrhythmias originating from the right ventricular have begun to attract the attention of the scientific world for many reasons. Ventricular arrhythmias originating from the right ventricular usually affect younger patients and can lead to sudden cardiac death. The pathophysiologic mechanism of these arrhythmias is not fully understood, which can lead to a range of different interpretations. Arrhythmogenic cardiomyopathy corresponds to a hereditary disease of the cardiac muscle, where the myocardium is replaced by fibro-fatty tissue and is characterized clinically by potentially lethal ventricular arrhythmias, especially in young individuals and athletes. Although the right ventricle is affected more frequently, biventricular or left dominant involvement has also been described. Considering the "disease of the desmosomes", several mutations have been reported in genes coding for desmosomal proteins, leading to intracellular changes in signal transduction and, consequently, myocyte transformation. The clinical diagnosis is based on a system that combines genetic and familial factors, electrocardiographic variations, ventricular arrhythmias, histopathological findings and functional or structural variants of the right ventricle, pertinent in the recognition of the nonspecific characteristics of this entity. Affected individuals present mostly during the second or third decades of life with symptoms such as palpitations, syncope or cardiorespiratory arrest. However, the presence of asymptomatic carriers has also been reported in favor of trend genetic sequencing. The primary goal of treatment is to prevent sudden death events. Given its increasing clinical relevance and significant scientific impact, this dissertation considers the broad review of the pathogenesis, diagnosis and current therapy related to this rare form of cardiomyopathy.
Historically, left ventricular cardiomyopathy and coronary heart disease have been regarded as the main causes of ventricular arrhythmia and sudden cardiac death. However, within the last two decades, arrhythmias originating from the right ventricular have begun to attract the attention of the scientific world for many reasons. Ventricular arrhythmias originating from the right ventricular usually affect younger patients and can lead to sudden cardiac death. The pathophysiologic mechanism of these arrhythmias is not fully understood, which can lead to a range of different interpretations. Arrhythmogenic cardiomyopathy corresponds to a hereditary disease of the cardiac muscle, where the myocardium is replaced by fibro-fatty tissue and is characterized clinically by potentially lethal ventricular arrhythmias, especially in young individuals and athletes. Although the right ventricle is affected more frequently, biventricular or left dominant involvement has also been described. Considering the "disease of the desmosomes", several mutations have been reported in genes coding for desmosomal proteins, leading to intracellular changes in signal transduction and, consequently, myocyte transformation. The clinical diagnosis is based on a system that combines genetic and familial factors, electrocardiographic variations, ventricular arrhythmias, histopathological findings and functional or structural variants of the right ventricle, pertinent in the recognition of the nonspecific characteristics of this entity. Affected individuals present mostly during the second or third decades of life with symptoms such as palpitations, syncope or cardiorespiratory arrest. However, the presence of asymptomatic carriers has also been reported in favor of trend genetic sequencing. The primary goal of treatment is to prevent sudden death events. Given its increasing clinical relevance and significant scientific impact, this dissertation considers the broad review of the pathogenesis, diagnosis and current therapy related to this rare form of cardiomyopathy.
Description
Keywords
Displasia Arritmogénica do Ventrículo Direito Estratificação do Risco Etiologia Morte Súbita Tratamento