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Níveis circulantes de péptido natriurético de tipo B (NT-PROBNP) e de galectina-3 em doentes com miocardiopatia hipertrófica sarcomérica e a sua relação com parâmetros clínicos e ecocardiográficos
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Introdução e objetivos: Uma das características da miocardiopatia hipertrófica sarcomérica é a presença de fibrose cardíaca, a qual constitui substrato para arritmias ventriculares, disfunção ventricular esquerda, remodelagem e insuficiência cardíaca. Os níveis de NT-ProBNP estão elevados na doença e são um marcador de um pior prognóstico. A galectina-3, marcador de fibrose, poderá também ser útil como marcador da gravidade do fenótipo na miocardiopatia hipertrófica e associar-se à ocorrência de efeitos adversos. Neste trabalho, investigámos a associação entre os níveis circulantes de galectina-3 e de NT-proBNP e a expressão fenotípica (morfológica e funcional) de doentes com miocardiopatia hipertrófica sarcomérica.
Métodos: De uma vasta população de doentes com miocardiopatia hipertrófica sarcomérica regularmente seguida em consulta dedicada a miocardiopatias, foram selecionados 60 doentes com miocardiopatia hipertrófica sarcomérica (critério ecocardiográfico major e presença de mutação patogénica associada à doença). Nesta seleção foram incluídos apenas os indivíduos que, após realização de história clínica, observação e painel laboratorial completo, não tivessem qualquer doença ou condição suscetível de interferir com os níveis circulantes de galectina-3. Os doentes foram submetidos a realização de electrocardiograma, ecocardiograma (incluindo estudo por Doppler tecidular) e colheita de sangue para determinação dos níveis circulantes de NT-proBNP e galectina-3. Avaliou-se possíveis associações entre os níveis circulantes de ambos os biomarcadores e entre estes e índices e parâmetros ecocardiográficos estruturais e funcionais, bem como com a presença de sintomas, arritmias ventriculares significativas e hospitalizações de causa cardiovascular.
Resultados: Não se verificou qualquer correlação entre os níveis circulantes de galectina-3 e as variáveis ecocardiográficas estudadas. Porém, o Log NT-proBNP correlacionou-se com o score de hipertrofia ventricular esquerda (r=0.592; p<0.001), espessura parietal máxima (r=0.580; p<0.001), dimensão da aurícula esquerda (r=0.387; p<0.026), E/E’ septal (r=0.489; p<0.004) e E/E’ lateral (r=0.590; p<0.001), E’ septal (r= -0.535; p=0.001), A’ septal (r= -0.698; p<0.001), S’ septal (r= -0.577; p<0.001) e E’ lateral (r= -0.581; p<0.001), independentemente da idade e do índice de massa corporal. Níveis circulantes mais elevados de NT-proBNP foram relacionados com a presença de sintomatologia (2038.24±2354.34 vs 557.30±733.04; p=0.001) e de hospitalizações (2345.33±2478.99 vs 698.38±1054.72; p=0.001), contrariamente aos níveis periféricos de galectina-3.
Conclusões: Nesta população com miocardiopatia hipertrófica sarcomérica, os níveis plasmáticos de NT-proBNP associaram-se a índices ecocardiográficos de hipertrofia ventricular esquerda e de função ventricular, à pressão tele-diastólica do ventrículo esquerdo e à dimensão da aurícula esquerda. Correlacionaram-se também com a presença de sintomas e hospitalizações pela doença, o que indica que o NT-proBNP parece ser um biomarcador com utilidade clínica nesta patologia. A utilidade da galectina-3 na avaliação diagnóstica e prognóstica dos doentes com miocardiopatia hipertrófica sarcomérica permanece incerta.
Background and aims: Cardiac fibrosis is a hallmark of sarcomeric hypertrophic cardiomyopathy and presents a substrate for ventricular arrhythmias, left ventricular dysfunction, remodeling and heart failure. Increased levels of galectin-3, a marker of cardiac fibrosis, has been described in patients with sarcomeric hypertrophic cardiomyopathy, as well as increased NT-proBNP plasma levels. In this study, we evaluated the association between galectin-3 and NT-proBNP circulating levels with the phenotypic expression in patients with sarcomeric hypertrophic cardiomyopathy. Methods: 60 patients with sarcomeric hypertrofic cardiomyopaty were enrolled (on the basis of echocardiographic major criteria and a positive genotype) after exclusion by medical history, clinical examination and a complete laboratorial evaluation of any factor that might act as a confounder regarding galectine-3 levels. Patients were submitted to an electrocardiogram, echocardiogram (including Doppler study tissue) and blood samples for determining circulating levels of NT-proBNP and galectin-3. Associations between circulating galectine-3 and NT-proBNP levels, and between both biomarkers and imaging data (structural and functional evaluation by echo-Doppler/tissue Doppler imaging), presence of symptoms, hospitalization due to cardiovascular cause or presence of significant ventricular arrhythmias on Holter, were looked for. Results: There was no correlation between circulating levels of galectin-3 and echocardiographic variables. However, Log NT-proBNP correlated with left ventricular hypertrophy score (r=0.592, p <0.001), maximum wall thickness (r=0.580, p<0.001), left atrium dimension (r = 0.387; p <0.026), septal E/E' (r = 0.489, p <0.004), lateral E/E' (r=0,590, p<0.001), septal E' (r= -0,535; p=0.001), septal A' (r= -0,698, p<0.001), septal S' (r= -0,577, p<0.001) and lateral E' (r= -0,581, p<0.001), regardless of age and BMI. Higher circulating levels of NT-proBNP were associated with the presence of symptoms (2038.24 ± 2354.34 vs 557.30 ± 733.04; p=0.001) and hospitalizations (2345.33 ± 2478.99 vs 698.38 ± 1054.72; p=0.001). Galectine-3 levels did not associate with the presence of symptoms or cardiovascular hospitalizations. None biomarker was associated with the presence of significant arrhythmias on 24-h-Holter monitoring. Conclusions: In this series, NT-proBNP plasma levels correlated with echocardiographic indices of left ventricular hypertrophy and function, left ventricular diastolic pressure and left atrial dimension. Additionally, NT-proBNP also correlated with presence of symptoms and cardiovascular hospitalization, findings suggesting that NT-proBNP appears to be a clinically useful biomarker in patients with sarcomeric hypertrophic cardiomyopathy. However, the usefulness of galectin-3 remains uncertain in this disease.
Background and aims: Cardiac fibrosis is a hallmark of sarcomeric hypertrophic cardiomyopathy and presents a substrate for ventricular arrhythmias, left ventricular dysfunction, remodeling and heart failure. Increased levels of galectin-3, a marker of cardiac fibrosis, has been described in patients with sarcomeric hypertrophic cardiomyopathy, as well as increased NT-proBNP plasma levels. In this study, we evaluated the association between galectin-3 and NT-proBNP circulating levels with the phenotypic expression in patients with sarcomeric hypertrophic cardiomyopathy. Methods: 60 patients with sarcomeric hypertrofic cardiomyopaty were enrolled (on the basis of echocardiographic major criteria and a positive genotype) after exclusion by medical history, clinical examination and a complete laboratorial evaluation of any factor that might act as a confounder regarding galectine-3 levels. Patients were submitted to an electrocardiogram, echocardiogram (including Doppler study tissue) and blood samples for determining circulating levels of NT-proBNP and galectin-3. Associations between circulating galectine-3 and NT-proBNP levels, and between both biomarkers and imaging data (structural and functional evaluation by echo-Doppler/tissue Doppler imaging), presence of symptoms, hospitalization due to cardiovascular cause or presence of significant ventricular arrhythmias on Holter, were looked for. Results: There was no correlation between circulating levels of galectin-3 and echocardiographic variables. However, Log NT-proBNP correlated with left ventricular hypertrophy score (r=0.592, p <0.001), maximum wall thickness (r=0.580, p<0.001), left atrium dimension (r = 0.387; p <0.026), septal E/E' (r = 0.489, p <0.004), lateral E/E' (r=0,590, p<0.001), septal E' (r= -0,535; p=0.001), septal A' (r= -0,698, p<0.001), septal S' (r= -0,577, p<0.001) and lateral E' (r= -0,581, p<0.001), regardless of age and BMI. Higher circulating levels of NT-proBNP were associated with the presence of symptoms (2038.24 ± 2354.34 vs 557.30 ± 733.04; p=0.001) and hospitalizations (2345.33 ± 2478.99 vs 698.38 ± 1054.72; p=0.001). Galectine-3 levels did not associate with the presence of symptoms or cardiovascular hospitalizations. None biomarker was associated with the presence of significant arrhythmias on 24-h-Holter monitoring. Conclusions: In this series, NT-proBNP plasma levels correlated with echocardiographic indices of left ventricular hypertrophy and function, left ventricular diastolic pressure and left atrial dimension. Additionally, NT-proBNP also correlated with presence of symptoms and cardiovascular hospitalization, findings suggesting that NT-proBNP appears to be a clinically useful biomarker in patients with sarcomeric hypertrophic cardiomyopathy. However, the usefulness of galectin-3 remains uncertain in this disease.
Descrição
Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2016
Palavras-chave
Miocardiopatia hipertrófica Fibrose Galectina-3 NT-proBNP cardiologia