Biomarkers and prediction of anthracyclic cardiotoxicity in breast cancer.

BACKGROUND: Chemotherapy with doxorubicin may lead to left ventricular dysfunction. There is a controversial recommendation that biomarkers can predict ventricular dysfunction, which is one of the most feared manifestations of anthracycline cardiotoxicity. OBJECTIVE: The aim of this study was to evaluate the behavior of biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin in predicting cardiotoxicity in a cohort of women with breast cancer undergoing chemotherapy with anthracycline. METHODS: This is an observational, prospective, longitudinal, unicentric study, which included 40 women with breast cancer, whose therapeutic proposal included treatment with doxorubicin. The protocol had a clinical follow-up of 12 months. Biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin were measured pre-chemotherapy and after the first, third, fourth, and sixth cycles of chemotherapy. RESULTS: There was a progressive increase in type B natriuretic peptide and myoglobin values in all chemotherapy cycles. Although creatine phosphokinase fraction MB showed a sustained increase, this increase was not statistically significant. Troponin, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB were the cardiotoxicity markers with the earliest changes, with a significant increase after the first chemotherapy session. However, they were not able to predict cardiotoxicity. CONCLUSION: Troponin I, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB are elevated during chemotherapy with doxorubicin, but they were not able to predict cardiotoxicity according to established clinical and echocardiographic criteria. The incidence of subclinical cardiotoxicity resulting from the administration of doxorubicin was 12.5%.

Biomarkers and prediction of anthracyclic cardiotoxicity in breast cancer

SUMMARY BACKGROUND: Chemotherapy with doxorubicin may lead to left ventricular dysfunction. There is a controversial recommendation that biomarkers can predict ventricular dysfunction, which is one of the most feared manifestations of anthracycline cardiotoxicity. OBJECTIVE: The aim of this study was to evaluate the behavior of biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin in predicting cardiotoxicity in a cohort of women with breast cancer undergoing chemotherapy with anthracycline. METHODS: This is an observational, prospective, longitudinal, unicentric study, which included 40 women with breast cancer, whose therapeutic proposal included treatment with doxorubicin. The protocol had a clinical follow-up of 12 months. Biomarkers such as Troponin I, type B natriuretic peptide, creatine phosphokinase fraction MB, and myoglobin were measured pre-chemotherapy and after the first, third, fourth, and sixth cycles of chemotherapy. RESULTS: There was a progressive increase in type B natriuretic peptide and myoglobin values in all chemotherapy cycles. Although creatine phosphokinase fraction MB showed a sustained increase, this increase was not statistically significant. Troponin, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB were the cardiotoxicity markers with the earliest changes, with a significant increase after the first chemotherapy session. However, they were not able to predict cardiotoxicity. CONCLUSION: Troponin I, type B natriuretic peptide, myoglobin, and creatine phosphokinase fraction MB are elevated during chemotherapy with doxorubicin, but they were not able to predict cardiotoxicity according to established clinical and echocardiographic criteria. The incidence of subclinical cardiotoxicity resulting from the administration of doxorubicin was 12.5%.

Cardiovascular adverse effects associated with the use of anti-HER2 in breast cancer treatment.

Background: Cancer represents an important public health problem with increasing incidence, prevalence, and mortality, affecting the entire Western population, especially in developed and developing countries. The use of monoclonal antibodies has revolutionized the treatment of cancer, but this treatment can cause adverse cardiovascular effects (AE). Objective: The objective of this paper is to identify and classify AE in breast cancer patients in the use of Trastuzumab in two health institutions. Methods: Retrospective study of medical records of patients with breast cancer Her 2+ submitted the therapy with trastuzumab in early and advanced stage of the disease. Review conducted in a university hospital and a private clinic, both located in Rio de Janeiro State, Brazil. Results: Cardiovascular events were late for trastuzumab, with predominance of moderate reactions. There was a predominance of dyspnea, increased blood pressure, fatigue and reduced left ventricular ejection. Conclusion: The results resemble similarities in the pattern of the institutions' reactions. Identify possible AE and know the toxicity profile of trastuzumab can contribute to a safer therapy.

Análise de efeito idade-período-coorte na mortalidade por doenças cerebrovasculares em Maceió e Florianópolis / Analysis of age-period-cohort effect on mortality due to cerebrovascular diseases in Maceió and Florianópolis, Brazil

Resumo Introdução A doença cerebrovascular (DCBV) é a segunda principal causa de morte no mundo e no Brasil. Objetivo Avaliar as tendências da mortalidade por DCBV em duas cidades brasileiras (Maceió e Florianópolis) com diferenças socioeconômicas extremas, entre 1981 e 2015, estimando os efeitos idade, período e coorte. Método Estudo de séries temporais da mortalidade por DCBV em indivíduos com ≥ 40 anos, empregando a ferramenta Web tool. Resultados A mortalidade por DCBV diminuiu com o tempo, aumentou com a idade e foi menor para gerações mais novas. O efeito foi igual para ambos os sexos. Houve diminuição da mortalidade nas duas cidades, mas a diferença foi grande e a mortalidade continua alta em Maceió. Com base na amplitude dos efeitos estimados, foi possível verificar que o efeito de coorte foi o termo mais significativo para explicar a variabilidade temporal das taxas de mortalidade por DCBV no período. Conclusão A comparação da tendência temporal nas duas cidades mostrou a importância da melhora das condições de vida, do acesso a serviços de saúde para prevenção e controle dos fatores de risco, assim como assistência hospitalar aos casos para diminuirmos a mortalidade por DCBV em todo o território nacional.

Abstract Background Cerebrovascular disease (CBVD) is the second leading cause of death in the world and Brazil. Objective To evaluate trends in mortality from CBVD in two Brazilian cities (Maceió and Florianópolis) with extreme socioeconomic differences, between 1981 and 2016, estimating the age, cohort effect. Method Study of CBVD mortality time series in individuals aged ≥40 years, using the Age, Period, Cohort (APC) analysis and the Web tool. Results CBVD mortality decreased with time, increased with age and was lower for younger generations. The effect was the same for both sexes. There was a decrease in mortality in both cities, but the difference was large, and mortality remains high in Maceió. Based on the amplitude of the estimated effects, it was possible to verify that the cohort effect was the most significant term to explain the temporal variability of mortality rates due to CVD in the period. Conclusion The comparison of the time trend in the two cities showed the importance of improving living conditions, access to health services for the prevention and control of risk factors, as well as hospital care for cases to reduce mortality from CVD nationwide.

Familial breast cancer, pregnancy and cardiotoxicity associated with the use of doxorubicin and reaction with trastuzumab.

INTRODUCTION: Breast Cancer (BC) is a neoplasm with the highest prevalence in women in Brazil and worldwide. Pregnancy-associated with BC is defined as that which occurs during pregnancy or within 1 to 2 years postpartum. The objective is to present a clinical case of a young patient with a history of familial BC who had cancer during pregnancy. The patient had cardiotoxicity after using doxorubicin and trastuzumab. CASE REPORT: She was a young patient within infiltrating ductal carcinoma in the right breast She was diagnosed within nine weeks of gestation and submitted to neoadjuvant chemotherapy with AC protocol (doxorubicina and cyclophosphamide) and mastectomy. Developed left atrial overload after treatment and still responding to hypersensitivity to trastuzumab. MANAGEMENT AND OUTCOME: The patient presented an alteration in the electrocardiogram (ECG) after the use of doxorubicin. The exam was repeated and the ECG was normal. Trastuzumab was started after delivery and the patient had a hypersensitivity reaction. Administration of trastuzumab was stopped and hydrocortisone was administered. The patient showed improvement in symptoms with cessation of trastuzumab. DISCUSSION: Although anthracycline-induced cardiotoxicity and hypersensitivity reactions to trastuzumab are common reactions, there are few studies on the effects of these drugs in patients with Gestational breast cancer (GBC). Monitoring cardiotoxicity in breast cancer treatment in pregnant patients is essential to avoid two complications: for the pregnant woman and the fetus.

Myocardial Injury after Non-cardiac Surgery - State of the Art. / Lesão Miocárdica após Cirurgia Não Cardíaca ­ Estado da Arte.

Approximately 300 million non-cardiac surgeries are performed annually worldwide and adverse cardiovascular events are the main cause of morbidity and mortality in the peri- and postoperative period. Myocardial injury after non-cardiac surgery (MINS) is a new clinical entity associated with adverse cardiovascular outcomes. MINS is defined as myocardial injury that can result in necrosis due to ischemia, marked by increase in biomarker levels. It has prognostic relevance and occurs within up to 30 days after non-cardiac surgery. The diagnostic criteria for MINS are an elevated postoperative measure of troponin judged as secondary to myocardial ischemia, i.e., with no evidence of a non-ischemic etiology, during or within 30 days after non-cardiac surgery, and without the requirement of an ischemic symptom or electrocardiographic finding of ischemia. Recently, patients at higher risk for MINS have been recognized using clinical variables and biomarkers and established protocols for greater surveillance in relation to electrocardiographic monitoring and cardiac troponin dosage. Elderly patients with previous atherosclerotic disease need to measure troponin daily in the postoperative period. The aim of the present work is to describe this new public health problem, its clinical impact and contemporary therapeutic approach.

Aproximadamente 300 milhões de cirurgias não cardíacas são realizadas anualmente no mundo, e eventos cardiovasculares adversos são as principais causas de morbimortalidade no período perioperatório e pós-operatório. A lesão miocárdica após cirurgia não cardíaca (MINS, do inglês myocardial injury after non-cardiac surgery) é uma nova entidade clínica associada com desfechos cardiovasculares adversos. MINS é definida como uma lesão miocárdica que pode resultar em necrose secundária à isquemia, com elevação dos biomarcadores. A lesão tem importância prognóstica e ocorre em até 30 dias após a cirurgia não cardíaca. Os critérios diagnósticos para MINS são: níveis elevados de troponina durante ou em até 30 dias após a cirurgia não cardíaca, sem evidência de etiologia não isquêmica, sem que haja necessariamente sintomas isquêmicos ou achados eletrocardiográficos de isquemia. Recentemente, pacientes com maior risco para MINS têm sido identificados por variáveis clínicas e biomarcadores, bem como por protocolos de vigilância quanto ao monitoramento eletrocardiográfico e dosagem de troponina cardíaca. Pacientes idosos com doença aterosclerótica prévia necessitam medir troponina diariamente no período pós-operatório. O objetivo deste trabalho é descrever este novo problema de saúde pública, seu impacto clínico e a abordagem terapêutica contemporânea.

Characteristics and Temporal Trends in the Mortality of Different Heart Failure Phenotypes in Primary Care. / Características e Tendências na Mortalidade em Diferentes Fenótipos de Insuficiência Cardíaca na Atenção Primária.

BACKGROUND: The classification of heart failure (HF) by phenotypes has a great relevance in clinical practice. OBJECTIVE: The study aimed to analyze the prevalence, clinical characteristics, and outcomes between HF phenotypes in the primary care setting. METHODS: This is an analysis of a cohort study including 560 individuals, aged ≥ 45 years, who were randomly selected in a primary care program. All participants underwent clinical evaluations, b-type natriuretic peptide (BNP) measurements, electrocardiogram, and echocardiography in a single day. HF with left ventricular ejection fraction (LVEF) < 40% was classified as HF with reduced ejection fraction (HFrEF), LVEF 40% to 49% as HF with mid-range ejection fraction (HFmrEF) and LVEF ≥ 50% as HF with preserved ejection fraction (HFpEF). After 5 years, the patients were reassessed as to the occurrence of the composite outcome of death from any cause or hospitalization for cardiovascular disease. RESULTS: Of the 560 patients included, 51 patients had HF (9.1%), 11 of whom had HFrEF (21.6%), 10 had HFmrEF (19.6%) and 30 had HFpEF (58.8%). HFmrEF was similar to HFpEF in BNP levels (p < 0.001), left ventricular mass index (p = 0.037), and left atrial volume index (p < 0.001). The HFmrEF phenotype was similar to HFrEF regarding coronary artery disease (p = 0.009). After 5 years, patients with HFmrEF had a better prognosis when compared to patients with HFpEF and HFrEF (p < 0.001). CONCLUSION: The prevalence of ICFEI was similar to that observed in previous studies. ICFEI presented characteristics similar to ICFEP in this study. Our data show that ICFEi had a better prognosis compared to the other two phenotypes.

FUNDAMENTO: A classificação da insuficiência cardíaca (IC) por fenótipos possui grande relevância na prática clínica. OBJETIVO: O estudo visou analisar a prevalência, as características clínicas e os desfechos entre os fenótipos de IC no contexto da atenção primária. MÉTODOS: Trata-se de uma análise de um estudo de coorte que incluiu 560 indivíduos, com idade ≥ 45 anos, que foram selecionados aleatoriamente em um programa de atenção primária. Todos os participantes foram submetidos a avaliações clínicas, dosagem do peptídeo natriurético tipo B (BNP), eletrocardiograma e ecocardiografia em um único dia. A IC com fração de ejeção do ventrículo esquerdo (FEVE) < 40% foi classificado como IC com fração de ejeção reduzida (ICFEr), FEVE de 40% a 49% como IC com fração de ejeção intermediária (ICFEi) e FEVE ≥ 50% como IC com fração de ejeção preservada (ICFEp). Após 5 anos, os pacientes foram reavaliados quanto à ocorrência do desfecho composto de óbito por qualquer causa ou internação por doença cardiovascular. RESULTADOS: Dos 560 pacientes incluídos, 51 pacientes tinham IC (9,1%), 11 dos quais tinham ICFEr (21,6%), 10 tinham ICFEi (19,6%) e 30 tinham ICFEp (58,8%). A ICFEi foi semelhante à ICFEp nos níveis de BNP (p < 0,001), índice de massa do ventrículo esquerdo (p = 0,037) e índice de volume do átrio esquerdo (p < 0,001). O fenótipo de ICFEi foi semelhante ao de ICFEr em relação à doença arterial coronariana (p = 0,009). Após 5 anos, os pacientes com ICFEi apresentaram melhor prognóstico quando comparados aos pacientes com ICFEp e ICFEr (p < 0,001). CONCLUSÃO: A prevalência de ICFEI foi semelhante ao observado em estudos anteriores. A ICFEI apresentou características semelhantes a ICFEP neste estudo. Nossos dados mostram que a ICFEi teve melhor prognóstico em comparação com os outros dois fenótipos.

Lesão Miocárdica após Cirurgia Não Cardíaca - Estado da Arte / Myocardial Injury after Non-cardiac Surgery - State of the Art

Resumo Aproximadamente 300 milhões de cirurgias não cardíacas são realizadas anualmente no mundo, e eventos cardiovasculares adversos são as principais causas de morbimortalidade no período perioperatório e pós-operatório. A lesão miocárdica após cirurgia não cardíaca (MINS, do inglês myocardial injury after non-cardiac surgery) é uma nova entidade clínica associada com desfechos cardiovasculares adversos. MINS é definida como uma lesão miocárdica que pode resultar em necrose secundária à isquemia, com elevação dos biomarcadores. A lesão tem importância prognóstica e ocorre em até 30 dias após a cirurgia não cardíaca. Os critérios diagnósticos para MINS são: níveis elevados de troponina durante ou em até 30 dias após a cirurgia não cardíaca, sem evidência de etiologia não isquêmica, sem que haja necessariamente sintomas isquêmicos ou achados eletrocardiográficos de isquemia. Recentemente, pacientes com maior risco para MINS têm sido identificados por variáveis clínicas e biomarcadores, bem como por protocolos de vigilância quanto ao monitoramento eletrocardiográfico e dosagem de troponina cardíaca. Pacientes idosos com doença aterosclerótica prévia necessitam medir troponina diariamente no período pós-operatório. O objetivo deste trabalho é descrever este novo problema de saúde pública, seu impacto clínico e a abordagem terapêutica contemporânea.

Abstract Approximately 300 million non-cardiac surgeries are performed annually worldwide and adverse cardiovascular events are the main cause of morbidity and mortality in the peri- and postoperative period. Myocardial injury after non-cardiac surgery (MINS) is a new clinical entity associated with adverse cardiovascular outcomes. MINS is defined as myocardial injury that can result in necrosis due to ischemia, marked by increase in biomarker levels. It has prognostic relevance and occurs within up to 30 days after non-cardiac surgery. The diagnostic criteria for MINS are an elevated postoperative measure of troponin judged as secondary to myocardial ischemia, i.e., with no evidence of a non-ischemic etiology, during or within 30 days after non-cardiac surgery, and without the requirement of an ischemic symptom or electrocardiographic finding of ischemia. Recently, patients at higher risk for MINS have been recognized using clinical variables and biomarkers and established protocols for greater surveillance in relation to electrocardiographic monitoring and cardiac troponin dosage. Elderly patients with previous atherosclerotic disease need to measure troponin daily in the postoperative period. The aim of the present work is to describe this new public health problem, its clinical impact and contemporary therapeutic approach.

Is lipid accumulation product a better cardiovascular risk predictor in elderly individuals than anthropometric measures?

INTRODUCTION: Population aging is associated with increased prevalence of cardiovascular diseases that have a significant impact on overall morbidity and mortality. Insulin resistance (IR) and visceral obesity are risk factors for vascular damage and cardiometabolic diseases. AIMS: Estimating the correlation between lipid accumulation product (LAP) and IR in elderly individuals and comparing them to traditional anthropometric indices. METHODS: Cross-sectional study comprising 411 individuals >60 years, who were treated in a primary care service. Body mass index (BMI), neck circumference (NC), waist circumference (WC), hip circumference (HC), arm circumference (AC), sagittal abdominal diameter (SAD) and waist-hip ratio (WHR) were recorded. IR was estimated based on HOMA-IR (homeostasis model assessment IR index). LAPa index was calculated as [WC-65]×[triglyceride (TG)] in men, and as [WC-58]×[TG] in women, whereas LAPb was calculated by using the minimum WC values recorded for the current sample, i.e., 61.5 cm for women and 71.5 cm for men. RESULTS: There was correlation among LAPa (0.506), LAPb (0.515) and HOMA-IR. LAP was better correlated to HOMA-IR and showed higher area under the curve than BMI, NC, WHR and SAD. Based on the receiver operating characteristic curve analysis, LAPb≥47.40 and LAPa≥52.5 were the best cut-off values used to identify individuals with IR presenting 68.8% and 68.2% sensitivity, and 68.6% and 68.6% specificity, respectively. CONCLUSION: LAP may be a useful and simple clinical marker to assess cardiometabolic risk factors in the elderly population treated at a primary care service.

Características e tendências na mortalidade em diferentes fenótipos de insuficiência cardíaca na atenção primária / Characteristics and temporal trends in the mortality of different heart failure phenotypes in primary care

Resumo Fundamento: A classificação da insuficiência cardíaca (IC) por fenótipos possui grande relevância na prática clínica. Objetivo: O estudo visou analisar a prevalência, as características clínicas e os desfechos entre os fenótipos de IC no contexto da atenção primária. Métodos: Trata-se de uma análise de um estudo de coorte que incluiu 560 indivíduos, com idade ≥ 45 anos, que foram selecionados aleatoriamente em um programa de atenção primária. Todos os participantes foram submetidos a avaliações clínicas, dosagem do peptídeo natriurético tipo B (BNP), eletrocardiograma e ecocardiografia em um único dia. A IC com fração de ejeção do ventrículo esquerdo (FEVE) < 40% foi classificado como IC com fração de ejeção reduzida (ICFEr), FEVE de 40% a 49% como IC com fração de ejeção intermediária (ICFEi) e FEVE ≥ 50% como IC com fração de ejeção preservada (ICFEp). Após 5 anos, os pacientes foram reavaliados quanto à ocorrência do desfecho composto de óbito por qualquer causa ou internação por doença cardiovascular. Resultados: Dos 560 pacientes incluídos, 51 pacientes tinham IC (9,1%), 11 dos quais tinham ICFEr (21,6%), 10 tinham ICFEi (19,6%) e 30 tinham ICFEp (58,8%). A ICFEi foi semelhante à ICFEp nos níveis de BNP (p < 0,001), índice de massa do ventrículo esquerdo (p = 0,037) e índice de volume do átrio esquerdo (p < 0,001). O fenótipo de ICFEi foi semelhante ao de ICFEr em relação à doença arterial coronariana (p = 0,009). Após 5 anos, os pacientes com ICFEi apresentaram melhor prognóstico quando comparados aos pacientes com ICFEp e ICFEr (p < 0,001). Conclusão: A prevalência de ICFEI foi semelhante ao observado em estudos anteriores. A ICFEI apresentou características semelhantes a ICFEP neste estudo. Nossos dados mostram que a ICFEi teve melhor prognóstico em comparação com os outros dois fenótipos.

Abstract Background: The classification of heart failure (HF) by phenotypes has a great relevance in clinical practice. Objective: The study aimed to analyze the prevalence, clinical characteristics, and outcomes between HF phenotypes in the primary care setting. Methods: This is an analysis of a cohort study including 560 individuals, aged ≥ 45 years, who were randomly selected in a primary care program. All participants underwent clinical evaluations, b-type natriuretic peptide (BNP) measurements, electrocardiogram, and echocardiography in a single day. HF with left ventricular ejection fraction (LVEF) < 40% was classified as HF with reduced ejection fraction (HFrEF), LVEF 40% to 49% as HF with mid-range ejection fraction (HFmrEF) and LVEF ≥ 50% as HF with preserved ejection fraction (HFpEF). After 5 years, the patients were reassessed as to the occurrence of the composite outcome of death from any cause or hospitalization for cardiovascular disease. Results: Of the 560 patients included, 51 patients had HF (9.1%), 11 of whom had HFrEF (21.6%), 10 had HFmrEF (19.6%) and 30 had HFpEF (58.8%). HFmrEF was similar to HFpEF in BNP levels (p < 0.001), left ventricular mass index (p = 0.037), and left atrial volume index (p < 0.001). The HFmrEF phenotype was similar to HFrEF regarding coronary artery disease (p = 0.009). After 5 years, patients with HFmrEF had a better prognosis when compared to patients with HFpEF and HFrEF (p < 0.001). Conclusion: The prevalence of ICFEI was similar to that observed in previous studies. ICFEI presented characteristics similar to ICFEP in this study. Our data show that ICFEi had a better prognosis compared to the other two phenotypes.