Cardiotoxicidade subclínica tardia em pacientes com linfoma não hodgkin tratados com antraciclina
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2023-05-26
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Lousada, Ana Paula Mena
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Universidade Estadual Paulista (Unesp)
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Introdução: Sobreviventes de neoplasias que foram tratados com antraciclinas podem apresentar cardiotoxicidade tardia sem, entretanto, apresentar sinais e sintomas de insuficiência cardíaca (IC) ou redução da função sistólica do ventrículo esquerdo (VE). O estudo da função do VE, por meio de métodos diagnósticos mais sensíveis para detecção de disfunção miocárdica precoce, pode contribuir com o diagnóstico e tratamento da cardiotoxicidade em sua forma subclínica. Objetivos: Identificar sinais tardios de cardiotoxicidade subclínica nos pacientes com linfoma não-Hodgkin (LNH) que foram tratados com doxorrubicina há mais de nove anos, por meio de avaliações por ecocardiografia transtorácica com speckle tracking e teste ergométrico convencional. Correlacionar parâmetros ecocardiográficos com a a capacidade funcional estimada pelo teste ergométrico e comparação linear de perda de função ventricular subclínica ao longo do tempo. Metodologia: Estudo caso-controle, 1:2, que inclui sobreviventes de LNH tratados com antraciclina há cerca de 9,8 anos, e que foram estudados quanto a presença de cardiotoxicidade no atual momento (M3), em 2015 (M2) e 2012 (M1), e indivíduos saudáveis (grupo controle) pareados por sexo e idade. Foram avaliados parâmetros clínicos, capacidade funcional pelo teste ergométrico e parâmetros ecocardiográficos convencionais, com cálculo do strain global longitudinal (SGL). Resultados: O grupo antraciclina foi constituído por 18 indivíduos com idade média de 53,614,4 anos, 68% do sexo masculino, com dose total acumulada de 311108 mg/m2 de doxorrubicina, e 32 indivíduos no grupo controle. Os indivíduos do grupo antraciclina foram avaliados 38,55,19 meses (M1), 74,35,04 meses (M2) e 1225,19 meses (M3) após término de doxorrubicina. O ecocardiograma evidenciou menor valor de FEVE (61,57,59 vs 67,35,04; p=0,002) e SGL (-16,44,12 vs -20,53,55; p<0,001) no grupo antraciclina comparado ao controle. Houve correlação entre a variação do SGL com a FEVE no grupo antraciclina (p=0,0031), o que não ocorreu no grupo controle (p=0,142). Entretanto, considerando os valores de referência para cada método, não houve queda abaixo do normal de FEVE, o que ocorreu com o SGL. Em relação a função diastólica, não houve diferença em volume atrial esquerdo indexado (25,55,68 vs 24,57,03; p=0,600), relação E/A [0,84 (0,70-1,27) vs 1,00 (0,78-1,40); p=0,379] e relação E/e’ médio (7,712,21 vs 6,632,11; p=0,092) entre os grupos antraciclina e controle. Quando se comparou os diferentes momentos no grupo antraciclina, a análise da função diastólica do VE mostrou piora da relação E/A [0,78 (0,65-1,15) vs 0,83 (0,78-1,36); p<0,005] nos momentos M2 e M3,comparados com M1. Não houve diferença entre os momentos na FEVE (p=0,150) e SGL (p=0,690). O teste ergométrico revelou menor capacidade de exercício em MET no grupo antraciclina em relação ao controle (7,993,41 vs 12,63,18; p=0,003). Não foi observado correlação entre SGL e VO2 máximo calculado nos grupos antraciclina (p=0,151) e controle (p=0,394). A FEVE e o VO2 máximo calculado também não mostrou correlação significante no grupo antraciclina (p=0,989) e controle (p=0,145). Em relação a função diastólica, houve correlação significativa entre a relação E/e’ e o VO2 máximo calculado para o grupo antraciclina (p=0,0496), o que não ocorreu no grupo controle (p=0,0704). Conclusão: Na avaliação de cardiotoxicidade tardia de pacientes com LNH tratados com doxorrubicina há 9,8 anos, não houve sinais de cardiotoxicidade a longo prazo. Em análise comparativa com o grupo controle, apenas o SGL se mostrou significativamente reduzido. A capacidade funcional foi menor no grupo antraciclina, sem correlação com FEVE e SGL.
Background: Non Hodking’s Lymphoma (NHL) survivors treated with anthracyclines may have late cardiotoxicity without, however, showing signs of heart failure (HF) or reduced left ventricular (LV) systolic function. The study of LV function, through more sensitive methods for detecting early myocardial dysfunction, can contribute to the diagnosis and treatment of cardiotoxicity in its subclinical form. Objectives: Identify late signs of subclinical cardiotoxicity in patients with NHL treated with doxorubicin for more than nine years, through assessments by transthoracic echocardiography with speckle tracking and conventional exercise testing. Correlate echocardiographic parameters with the functional capacity estimated by the exercise test and linear comparison of subclinical ventricular function loss over time. Methods: non-randomized controlled trial, 1:2, which includes NHL survivors treated with anthracycline for 9,8 years, studied for the presence of cardiotoxicity at the present time (M3), in 2012 (M1) and 2015 (M3), and healthy people (control group) matched by sex and age. Clinical parameters, functional capacity by exercise test and conventional echocardiographic parameters with longlitudinal global strain (GLS) were evaluated. Results: Anthracycline group consist of 18 individuals with a mean age of 53.6±14.4 years, 68% male, with 311±108 mg/m2 doxorrubicin accumulated dose, and 32 individuals in the control group. Anthracycline group was evaluated 38.5±5.19 months (M1), 74.3±5.04 months (M2) and 122±5.19 months (M3) after last dose of doxorubicin. The echocardiogram showed a lower LVEF (61.5±7.59 vs 67.3±5.04; p=0.002) and GLS (-16.4±4.12 vs -20.5±3.55; p <0.001) in the anthracycline group compared to the control. There was a correlation between the GLS variation and LVEF in the anthracycline group (p=0.0031), which did not occur in the control group (p=0.142). However, considering the reference values for each method, there was no drop below normal in LVEF, which occurred with GLS. Regarding diastolic function, there was no difference in indexed left atrial volume (25.5±5.68 vs 24.5±7.03; p=0.600), E/A ratio [0.84 (0.70-1 .27) vs 1.00 (0.78-1.40); p=0.379] and E/e' ratio (7.71±2.21 vs 6.63±2.11; p=0.092) between anthracycline and control groups. When comparing the different moments in the anthracycline group, the analysis of the LV diastolic function showed a worsening of the E/A ratio [0.78 (0.65-1.15) vs 0.83 (0.78-1.36) ; p<0.005] at moments M2 and M3, compared with M1. There was no difference between the moments in LVEF (p=0.150) and GLS (p=0.690). The exercise test revealed lower exercise capacity in MET in the anthracycline group compared to the control (7.99±3.41 vs 12.6±3.18; p=0.003). No correlation was observed between GLS and maximum VO2 calculated in the anthracycline (p=0.151) and control (p=0.394) groups. LVEF and calculated VO2 max also didn’t show a significant correlation in the anthracycline (p=0.989) and control (p=0.145) groups. Regarding diastolic function, there was a significant correlation between the E/e' ratio and the maximum VO2 calculated for the anthracycline group (p=0.0496), which did not occur in the control group (p=0.0704). Conclusion: There was no signs of late cardiotoxicity n patients with NHL treated with doxorubicin for 9,8 years. In a comparative analysis with the control group, only the GLS was significantly reduced. Functional capacity was lower in the anthracycline group, with no correlation with LVEF and GLS. Keywords: cardiotoxicity, anthracyclines, chemotherapy, global longitudinal strain, myocardial strain, echocardiography, exercise capacity.
Background: Non Hodking’s Lymphoma (NHL) survivors treated with anthracyclines may have late cardiotoxicity without, however, showing signs of heart failure (HF) or reduced left ventricular (LV) systolic function. The study of LV function, through more sensitive methods for detecting early myocardial dysfunction, can contribute to the diagnosis and treatment of cardiotoxicity in its subclinical form. Objectives: Identify late signs of subclinical cardiotoxicity in patients with NHL treated with doxorubicin for more than nine years, through assessments by transthoracic echocardiography with speckle tracking and conventional exercise testing. Correlate echocardiographic parameters with the functional capacity estimated by the exercise test and linear comparison of subclinical ventricular function loss over time. Methods: non-randomized controlled trial, 1:2, which includes NHL survivors treated with anthracycline for 9,8 years, studied for the presence of cardiotoxicity at the present time (M3), in 2012 (M1) and 2015 (M3), and healthy people (control group) matched by sex and age. Clinical parameters, functional capacity by exercise test and conventional echocardiographic parameters with longlitudinal global strain (GLS) were evaluated. Results: Anthracycline group consist of 18 individuals with a mean age of 53.6±14.4 years, 68% male, with 311±108 mg/m2 doxorrubicin accumulated dose, and 32 individuals in the control group. Anthracycline group was evaluated 38.5±5.19 months (M1), 74.3±5.04 months (M2) and 122±5.19 months (M3) after last dose of doxorubicin. The echocardiogram showed a lower LVEF (61.5±7.59 vs 67.3±5.04; p=0.002) and GLS (-16.4±4.12 vs -20.5±3.55; p <0.001) in the anthracycline group compared to the control. There was a correlation between the GLS variation and LVEF in the anthracycline group (p=0.0031), which did not occur in the control group (p=0.142). However, considering the reference values for each method, there was no drop below normal in LVEF, which occurred with GLS. Regarding diastolic function, there was no difference in indexed left atrial volume (25.5±5.68 vs 24.5±7.03; p=0.600), E/A ratio [0.84 (0.70-1 .27) vs 1.00 (0.78-1.40); p=0.379] and E/e' ratio (7.71±2.21 vs 6.63±2.11; p=0.092) between anthracycline and control groups. When comparing the different moments in the anthracycline group, the analysis of the LV diastolic function showed a worsening of the E/A ratio [0.78 (0.65-1.15) vs 0.83 (0.78-1.36) ; p<0.005] at moments M2 and M3, compared with M1. There was no difference between the moments in LVEF (p=0.150) and GLS (p=0.690). The exercise test revealed lower exercise capacity in MET in the anthracycline group compared to the control (7.99±3.41 vs 12.6±3.18; p=0.003). No correlation was observed between GLS and maximum VO2 calculated in the anthracycline (p=0.151) and control (p=0.394) groups. LVEF and calculated VO2 max also didn’t show a significant correlation in the anthracycline (p=0.989) and control (p=0.145) groups. Regarding diastolic function, there was a significant correlation between the E/e' ratio and the maximum VO2 calculated for the anthracycline group (p=0.0496), which did not occur in the control group (p=0.0704). Conclusion: There was no signs of late cardiotoxicity n patients with NHL treated with doxorubicin for 9,8 years. In a comparative analysis with the control group, only the GLS was significantly reduced. Functional capacity was lower in the anthracycline group, with no correlation with LVEF and GLS. Keywords: cardiotoxicity, anthracyclines, chemotherapy, global longitudinal strain, myocardial strain, echocardiography, exercise capacity.
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Palavras-chave
Cardiotoxicidade, Antraciclina, Strain global longitudinal, Capacidade funcional, Quimioterapia, Ecocardiografia, Anthracyclines, Chemotherapy, Global longitudinal strain, Myocardial strain, Echocardiography, Exercise capacity, Cardiotoxicity