Evaluation of Cardiac Toxicity of Anthracyclines in Children with Acute Leukemia Based on Tei Index / 昆明医科大学学报

Objective To apply ultrasound to monitor cardiac function changes after anthracycline exposure in children with acute leukemia,in order to obtain the indicators of early changes in their cardiac function.Methods Children with acute leukemia from 2018 March to December 2020 in the Children's Hospital of Kunming Medical University were enrolled according to the inclusion and exclusion criteria,their routine cardiac ultrasound and tissue Doppler condition were recorded,and the changes in systolic function were evaluated by Tei index including TeiS,TeiRL,TeiM and TeiT.Results The mean values of LVEF in the normal and the experimental group were both above 60%.FS,SV,and EDV were all in the normal range.While common indicant,the index of TDI or Tei was not statistically significant(P>0.05).The levels of TeiM,TeiRL and TieT in the groups that received a total dose of 200 mg/m2 anthracyclines and 250 mg/m2 were significantly different from that before treatment(P<0.05).Conclusion Tei index can be utilized as a sensitive indicator for early changes in left and right heart function after children with acute leukemia are exposed to anthracyclines.

Role of cerium oxide nanoparticles in doxorubicin-induced cardiotoxicity and its effect on P53 gene expression / 中国现代医生

@#Objective To study the effect of nano-ceria on doxorubicin-induced cardiotoxic injury and its effect on P53 gene expression,and to explore the mechanism of nano-ceria on doxorubicin-induced cardiotoxic injury.Methods H9C2 myocardial cells were cultured and randomly divided into five groups:control group,model group(1μmol/L adriamycin),nano-cerium oxide group(10μg/ml nano-cerium oxide),experimental group(1μmol/L adriamycin +10μg/ml nano-cerium oxide),and positive control group(1μmol/L adriamycin+10μmol/L dexperimine).The adriamycin induced cardiotoxicity model was established,and the viability of myocardial cells was measured by CCK-8 method.The contents of lactate dehydrogenase(LDH)and malondialdehyde(MDA)in myocardial cells were detected by biochemical method.The levels of reactive oxygen(ROS)and the apoptosis rate in myocardial cells were detected by flow cytometry.The expressions of Bax,Bcl-2 and P53 proteins in myocardial cells were detected by Western blot.Results Compared with the control group,the cell viability was decreased in the model group,the cell LDH and MDA contents were increased,the intracellular ROS level and apoptosis rate were increased,the expressions of Bax and P53 proteins were increased,and the expression of Bcl-2 protein was decreased,and the ratio of Bcl-2/Bax was decreased(all P<0.001).Compared with the model group,the experimental group showed increased cell viability,decreased cell LDH and MDA contents,decreased cell ROS content and apoptosis rate,decreased Bax and P53 protein expressions,and increased Bcl-2 protein expression,and the Bcl-2/Bax ratio was increased(all P<0.001).Conclusion Ceria nanoparticles can effectively prevent adriamycin-induced cardiotoxic injury,and its effect may be related to the down-regulation of P53 gene to inhibit cardiomyocyte apoptosis.

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%.

Incidência de Complicações Cardiovasculares em Pacientes Pediátricos Tratados com Antraciclinas em um Centro Oncológico Brasileiro / Incidence of Cardiovascular Complications in Pediatric Patients Treated with Anthracyclines at a Brazilian Cancer Center

Resumo Fundamento: A introdução das antraciclinas no tratamento do câncer infantojuvenil propiciou um aumento significativo na sobrevida, mas também nas taxas de morbimortalidade devido às complicações cardiovasculares (CVs). Objetivos: Conhecer o perfil cardiológico de pacientes pediátricos tratados com antraciclinas em um centro oncológico no Brasil e a incidência das complicações CVs. Métodos: Foram coletados, de prontuários de pacientes de ambos os sexos com idade até 19 anos - frequência e forma de apresentação clínica das complicações CVs Gerais (G1) e relacionadas à Disfunção Ventricular (G2) - e correlacionados com fatores de risco, faixa etária e estado vital, medicações cardiológicas e cardioprotetoras. Um valor de p < 0,05 foi considerado significativo. Resultados: Foram incluídos 326 pacientes, destes, 214 (65,6%) eram menores de 10 anos e 192 (58,89%) do sexo masculino. As complicações do G1 ocorreram em 141 (43,3%) pacientes e a mais frequente foi a hipertensão arterial sistêmica; as complicações do G2 ocorreram em 84 pacientes (25,76%). Uma Dose Cumulativa (DC) das antraciclinas > 250mg/m2 foi usada em 26,7% dos pacientes e a associação de complicações do G2 com essa DC não mostrou significância estatística (p=0,305; RC=1,330 e [95% IC= 0,770- 2,296]). As medicações cardiológicas mais usadas foram os diuréticos em 34,7% dos pacientes. Conclusões: O estudo mostrou, como na literatura, uma alta incidência de complicações CVs no tratamento do câncer infantojuvenil, sendo as do G1 as mais frequentes.

Abstract Background: The introduction of anthracyclines in the treatment of children and adolescents with cancer has promoted a significant increase in survival, but also in morbidity and mortality rates due to cardiovascular (CV) complications. Objectives: To determine the cardiovascular profile of pediatric patients treated with anthracyclines at a cancer center in Brazil and the incidence of CV complications. Methods: The following data were collected from the medical records of patients of both sexes, aged younger than 19 years - frequency and form of clinical presentation of general CV complications (G1) and CV complications related to ventricular dysfunction (G2) - and correlated with risk factors, age range and vital status, cardiovascular and cardioprotective medications. A p<0.05 was considered statistically significant. Results: A total of 326 patients were included, 214 (65.6%) were younger than 10 years and 192 (58.9%) of male sex. G1 complications occurred in 141 (43.3%) patients, and the most frequent was systemic arterial hypertension; G2 complications occurred in 84 patients (25.8%). Cumulative dose (CD) of anthracyclines > 250mg/m2 was used in 26.7% of patients and the association of G2 complications with this CD was not statistically significant (p=0.305; OR=1.330 and [95% CI = 0.770- 2.296]). The most used cardiac medications were diuretics (34.7% of patients). Conclusions: In accordance with literature, the study showed a high incidence of CV complications in the treatment of children and adolescents with cancer, with general CV complications as the most prevalent.

Acute promyelocytic leukemia in childhood and adolescence: treatment results of a modified AIDA protocol at a Brazilian center

ABSTRACT Introduction: Acute promyelocytic leukemia currently presents an excellent chance of cure with protocols based on all-trans-retinoic acid (ATRA) and anthracycline or only differentiation agents. However, high early mortality rates continue to be reported Methods: Between 2000 and 2018, patients were enrolled and retrospectively analyzed by medical records. A modified AIDA protocol, with a 1-year shortening of the treatment duration, reduction in the number of drugs and a strategy to reduce early mortality by the postponement of the initiation of anthracyclines were employed. Overall and event-free survival rates and toxicity were analyzed Results: Thirty-two patients were enrolled, of whom 56% were female, with a median age of 12 years and 34% belonged to the high-risk group. Two patients had the hypogranular variant and three had another cytogenetic alteration, in addition to the t(15;17). The median start of the first anthracycline dose was 7 days. There were two early deaths (6%) due to central nervous system (CNS) bleeding. All patients achieved molecular remission after the consolidation phase. Two children relapsed and were rescued by arsenic trioxide and hematopoietic stem cell transplantation. The presence of disseminated intravascular coagulation (DIC) at diagnosis (p = 0.03) was the only factor with survival impact. The five-year event-free survival (EFS) was 84% and 5-year overall survival (OS) was 90% Conclusion: The survival results were comparable to those found in the AIDA protocol, with a low rate of early mortality in relation to the Brazilian reality.

Dose-dense paclitaxel plus carboplatin in combination with trastuzumab neoadjuvant versus standard adjuvant therapy in human epidermal growth factor receptor-2 positive and hormone receptor negative breast cancer: a prospective cohort study / 中华肿瘤杂志

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.

Dose-dense paclitaxel plus carboplatin in combination with trastuzumab neoadjuvant versus standard adjuvant therapy in human epidermal growth factor receptor-2 positive and hormone receptor negative breast cancer: a prospective cohort study / 中华肿瘤杂志

Objective: To provide survival evidence of anthracycline-free neoadjuvant chemotherapy for patients with stages Ⅱ-Ⅲ human epidermal growth factor receptor-2 (HER-2) positive and hormone receptor (HR) negative breast cancer. Methods: The prospective cohort study was conducted at the Department of Medical Oncology of Cancer Hospital, Chinese Academy of Medical Sciences. Patients with HER-2 positive and HR negative breast cancer in stages Ⅱ-Ⅲ were enrolled to receive neoadjuvant therapy (NAT) of dose-dense paclitaxel (175 mg/m(2)) plus carboplatin (AUC=4.0) biweekly for 6 cycles in combination with trastuzumab (PCbH), and matched patients who received standard adjuvant therapy of physicians' choice were recruited for survival and safety comparison. Results: From July 2013 to November 2019, 166 patients were included (neoadjuvant 51, adjuvant 115). Compared with those who received adjuvant therapy, patients receiving NAT were younger (<35 years: 19.6% vs 5.2%, P=0.014), had larger tumors (T3: 62.7% vs 7.8%, P<0.001) and more advanced diseases (stage ⅡA: 2.0% vs 41.7%, P<0.001). Patients in the neoadjuvant group all received surgery, and 96 (83.5%) in the adjuvant group received anthracycline-and-taxane-containing regimens. A total of 98 patients (49 pairs) were matched, and the covariates between the two groups were acceptably balanced. Within a median follow-up of 46.5 (range, 14-87) months, the 4-year recurrence-free survival (RFS) rate among patients who received NAT was 73.3% (95% CI: 59.0%-87.6%), versus 80.6% (95% CI: 67.9%-93.3%) among those in the adjuvant group without statistical difference (P=0.418). A similar result was observed for the 4-year overall survival (OS) [neoadjuvant versus adjuvant: 91.5% (95% CI: 81.7%-100.0%) vs 97.8% (95% CI: 93.5%-100.0%), P=0.314]. Compared with standard adjuvant therapy, PCbH was related to less neutropenia and better cardiac safety. Conclusions: These results support the consideration of anthracycline-free neoadjuvant chemotherapy combined with anti-HER-2 therapy for patients with stages Ⅱ-Ⅲ HER-2-positive and HR-negative breast cancer. Optimized regimens with both efficacy and safety are needed and to be further investigated.

Valor Diagnóstico de Parâmetros Tridimensionais de Strain de Imagem de Speckle Tracking para Detecção de Disfunção Cardíaca Relacionada à Quimioterapia do Câncer: Uma Metanálise / Diagnostic Value of Three-Dimensional Speckle Tracking Imaging Strain Parameters for Detection of Cancer Chemotherapy-Related Cardiac Dysfunction: A Meta-Analysis

Resumo Fundamento Agentes quimioterápicos (por exemplo, antraciclinas, trastuzumabe) comumente usados para o tratamento de tumores malignos demonstraram ter efeitos cardiotóxicos, que estão associados a um prognóstico ruim. A ecocardiografia tridimensional tem sido usada para prever a disfunção cardíaca induzida pela quimioterapia do câncer. Objetivos Avaliação do desempenho diagnóstico de parâmetros de strain, área global de strain (AGS), strain longitudinal (SLG), strain circunferencial (SCG) e strain radial (SRG) por metanálise. Métodos Estudos relevantes foram pesquisados nas bases de dados Embase, PubMed e Web of Science. A análise estatística foi realizada usando Stata 12. O resumo da curva característica operacional do receptor, sensibilidade, especificidade, razão de verossimilhança positiva (RVP), razão de verossimilhança negativa (RVN), e o correspondente intervalo de confiança de 95% para os quatro parâmetros de strain foram combinados. P<0,05 foi considerado estatisticamente significativo. Resultados Nove estudos envolvendo 650 participantes foram incluídos. AGS e SLG mostraram vantagens diagnósticas significativas sobre SCG e SRG. Para AGS, a sensibilidade foi de 0,85 (0,70, 0,93) e a especificidade foi de 0,82 (0,78, 0,86) com RVP de 4,76 (3,55, 6,39) e RVN de 0,18 (0,09, 0,39) e uma área sob a curva (AUC) de 0,85 (0,82, 0,88). Para SLG, a sensibilidade foi de 0,81 (0,74, 0,86) e a especificidade foi de 0,81 (0,68, 0,90) com RVP de 4,35 (2,42, 7,80) e RVN de 0,23 (0,17, 0,33) e uma AUC de 0,85 (0,82, 0,88).OGCS mostrou uma sensibilidade de 0,63 e uma especificidade de 0,79 com uma AUC de 0,77.O SRG mostrou uma sensibilidade de 0,74e uma especificidade de 0,66 com umAUC de 0,73. Conclusão Parâmetros 3D-STI de strain AGS e SLG mostraram bom desempenho na detecção precoce de disfunção cardíaca em pacientes com tumores recebendo quimioterapia.

Abstract Background Chemotherapeutic agents (e.g., anthracyclines, trastuzumab) commonly used for treating malignant tumors have been demonstrated to have cardiotoxic effects, which is associated with poor prognosis. Three-dimensional echocardiography has been used to predict cancer chemotherapy-induced cardiac dysfunction. Objectives Evaluation of the diagnostic performance of strain parameters, global area strain (GAS), longitudinal strain (GLS), circumferential strain (GCS), and radial strain (GRS) by meta-analysis. Methods Relevant studies were searched from the Embase, PubMed, and Web of Science databases. Statistical analysis was performed using Stata 12. The summary receiver operating characteristic curve, sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), and corresponding 95% confidence interval for the four strain parameters were pooled. P<0.05 was considered statistically significant. Results Nine studies involving 650 participants were included. GAS and GLS showed significant diagnostic advantages over GCS and GRS. For GAS, the sensitivity was 0.85 (0.70, 0.93) and specificity was 0.82(0.78, 0.86) with PLR of 4.76 (3.55, 6.39) and NLR of 0.18 (0.09, 0.39) and an area under the curve (AUC) of 0.85 (0.82, 0.88). For GLS, the sensitivity was 0.81 (0.74, 0.86) and specificity was 0.81(0.68, 0.90) with PLR of 4.35(2.42, 7.80) and NLR of 0.23 (0.17, 0.33) and an AUC of 0.85 (0.82, 0.88). The GCS showed a sensitivity of 0.63 and a specificity of 0.79 with an AUC of 0.77. The GRS showed a sensitivity of 0.74 and a specificity of 0.66 with an AUC of 0.73. Conclusion 3D-STI strain parameters GAS and GLS showed good performance in detecting early cardiac dysfunction in patients with tumors receiving chemotherapy.

Antagonistas do Sistema Renina-Angiotensina e Betabloqueadores na Prevenção da Cardiotoxicidade por Antraciclinas: Revisão Sistemática e Metanálise / Renin-angiotensin System Antagonists and Beta-blockers in Prevention of Anthracycline Cardiotoxicity: a Systematic Review and Meta-analysis

Resumo Fundamento As evidências que embasam o uso de inibidores do sistema-renina-angiotensina aldosterona (SRAA) e betabloqueadores para prevenção de cardiomiopatia induzida por antraciclinas são controversas. Objetivo Realizamos uma metanálise para avaliar a eficácia desses medicamentos na prevenção da cardiotoxicidade. Métodos A metanálise incluiu estudos prospectivos e randomizados com adultos submetidos à quimioterapia com antraciclina e comparou o uso de terapias SRAA ou betabloqueadores versus placebo com seguimento de 6 a 18 meses. O desfecho primário foi alteração da fração de ejeção do ventrículo esquerdo (FEVE) durante a quimioterapia. Os desfechos secundários foram: a incidência de insuficiência cardíaca, mortalidade por todas as causas e alterações na medida do diâmetro diastólico final. A avaliação da heterogeneidade foi realizada por estratificação e meta-regressão. O nível de significância adotado foi p < 0,05. Resultados A busca resultou em 17 estudos, totalizando 1.530 pacientes. A variação (delta) da FEVE foi avaliada em 14 estudos. A terapia neuro-hormonal foi associada a um menor delta na FEVE pré-terapia versus pós-terapia (diferença média ponderada 4,42 [intervalo de confiança de 95% 2,3 a 6,6]) e maior FEVE final (p < 0,001). O tratamento resultou em menor incidência de insuficiência cardíaca (risk ratio 0,45 [intervalo de confiança de 95% 0,3 a 0,7]). Não houve efeito na mortalidade (p = 0,3). Para a análise da FEVE, foi documentada heterogeneidade substancial, não explicada pelas variáveis exploradas no estudo. Conclusão O uso de inibidores do SRAA e betabloqueadores para prevenção da cardiotoxicidade induzida por antraciclinas foi associado a redução menos pronunciada da FEVE, maior FEVE final e menor incidência de insuficiência cardíaca. Não foram observadas alterações na mortalidade. (CRD PROSPERO 42019133615)

Abstract Background The evidence supporting the use of renin-angiotensin-aldosterone system (RAAS) inhibitors and beta-blockers for the prevention of anthracycline-induced cardiomyopathy is controversial. Objective We performed a meta-analysis to assess the effectiveness of these drugs in preventing cardiotoxicity. Methods The meta-analysis included prospective, randomized studies in adults receiving anthracycline chemotherapy and compared the use of RAAS inhibitors or beta-blockers versus placebo with a follow-up of 6 to 18 months. The primary outcome was change in left ventricular ejection fraction (LVEF) during chemotherapy. Secondary outcomes were the incidence of heart failure, all-cause mortality, and changes in end-diastolic measurement. Heterogeneity was assessed by stratification and meta-regression. A significance level of p < 0.05 was adopted. Results The search resulted in 17 studies, totaling 1,530 patients. The variation (delta) in LVEF was evaluated in 14 studies. Neurohormonal therapy was associated with a lower delta in pre- versus post-therapy LVEF (weighted mean difference 4.42 [95% confidence interval 2.3 to 6.6]) and higher final LVEF (p < 0.001). Treatment resulted in a lower incidence of heart failure (risk ratio 0.45 [95% confidence interval 0.3 to 0.7]). There was no effect on mortality (p = 0.3). For analysis of LVEF, substantial heterogeneity was documented, which was not explained by the variables explored in the study. Conclusion The use of RAAS inhibitors and beta-blockers to prevent anthracycline-induced cardiotoxicity was associated with less pronounced reduction in LVEF, higher final LVEF, and lower incidence of heart failure. No changes in mortality were observed. (CRD PROSPERO 42019133615)

Physical Training Improves Cardiac Structure and Function of Rats After Doxorubicin-Induced Cardiomyopathy

Abstract Background: The use of doxorubicin in chemotherapy has been associated with cardiotoxicity and heart failure. Physical exercise produces favorable morphofunctional adaptations in the cardiovascular system and may reverse cardiac dysfunction in patients undergoing chemotherapy. Objective: To assess the effects of physical training on myocardial structure, cardiac function, and exercise tolerance in Wistar rats initiated after the onset of cardiotoxicity-induced cardiotoxicity. Methods: This study investigated 30 adult male Wistar rats randomly divided into four groups: control (C), exercise (EX), doxorubicin (DX), and doxorubicin and exercise (DXEX). The DX and DXEX groups received six doses of doxorubincin from 1.25 mg/kg body weight up to a cumulative dose of 7.5 mg/kg. Injections were administered intraperitoneally three times a week for two weeks; after this stage, the EX and DXEX groups started physical training (swimming) sessions three times a week with a load of 5% of their body weight. Echocardiography and exercise tolerance tests were performed. Generalized linear models were used in statistical analysis, and a p<0.05 was set as statistically significant. Results: Left ventricular shortening fraction and ejection fraction were reduced in the DX group compared to C, EX, and DXEX. The DXEX group showed greater tolerance to effort when compared to the DX and C groups. Conclusion: Physical training, initiated after the onset of doxorubicin-induced cardiotoxicity, improved cardiac function and exercise tolerance in rats.

Treinamento muscular inspiratório na qualidade de vida e capacidade funcional na cardiotoxicidade: relato de caso / Entrenamiento muscular inspiratorio en la calidad de vida y capacidad funcional en la cardiotoxicidad: reporte de un caso / Inspiratory muscle training in quality of life and functional capacity in cardiotoxicity: case report

RESUMO Pacientes oncológicos desenvolvem problemas cardíacos frequentes devido à toxidade dos quimioterápicos, com consequente impacto na capacidade funcional (CF) e na qualidade de vida (QV). O treinamento muscular inspiratório (TMI) pode ser um recurso terapêutico viável, já que estudos de causa-efeito demonstraram melhora da CF e da QV em outras populações. Contudo, seu efeito ainda não foi avaliado em pacientes cardio-oncológicos. Assim, o objetivo deste estudo foi descrever o efeito de um programa de TMI sobre a CF e a QV de uma paciente com cardiotoxicidade: LDM, com 41 anos, mulher e sedentária, que desenvolveu insuficiência cardíaca após tratamento quimioterápico. A QV foi avaliada pelo teste de Minnesota. Foram avaliados também a força muscular inspiratória dinâmica (S-Index) e o limiar glicêmico (LG) dos músculos inspiratórios. O LG foi determinado pela glicemia capilar por meio do glicosímetro digital (Accu-Chek - Roche) no menor valor da glicemia da carga correspondente ao teste muscular inspiratório incremental (TMII). A progressão da carga foi realizada a cada duas semanas. Ao final de dois meses, todos os testes foram reaplicados. No teste de Minnesota, os valores relacionados à CF, antes e após o TMI, foram de 36 vs. 8 (melhora de 78%); aos aspectos clínicos e psicológicos foram de 32 vs. 7 (melhora de 78%), a S-Index foram de 41 vs. 51cmH2O (melhora de 24%). O TMI melhorou a CF e a QV de uma paciente cardio-oncológica, configurando-se como um recurso terapêutico viável para essa população.

RESUMEN Los pacientes con cáncer desarrollan problemas cardíacos frecuentes debido a la cardiotoxicidad de la quimioterapia, con el consiguiente impacto en la capacidad funcional (FC) y la calidad de vida (CV). El entrenamiento muscular inspiratorio (IMT) puede ser un recurso terapéutico viable, ya que los estudios de causa-efecto han demostrado una mejora en la FC y la CV en otras poblaciones. Sin embargo, su efecto aún no se ha evaluado en pacientes cardio-oncológicos. Por lo tanto, el objetivo de este estudio fue describir el efecto de un programa de IMT sobre la FC y la CV de un paciente con cardiotoxicidad: LDM, 41 años, mujer y sedentaria, que desarrolló insuficiencia cardíaca después del tratamiento de quimioterapia. La CV se evaluó mediante la prueba de Minnesota. También se evaluaron la fuerza muscular inspiratoria dinámica (índice S) y el umbral glucémico (LG) de los músculos inspiratorios. El LG se determinó por glucemia capilar mediante el glucómetro digital (Accu-Chek - Roche) al valor más bajo de la carga glucélica correspondiente a la prueba muscular inspiratoria incremental (IMI). La progresión de la carga se realizó cada dos semanas. Después de dos meses, todas las pruebas se volvieron a aplicar. En la prueba de Minnesota, los valores relacionados con la FC, antes y después de THE, fueron 36 vs. 8 (78% de mejora); los aspectos clínicos y psicológicos fueron 32 vs. 7 (mejora del 78%), el índice S fue de 41 vs. 51cmH2O (mejora del 24%). El IMT mejoró la FC y la CV de un paciente cardio-oncológico, constituyendo un recurso terapéutico viable para esta población.

ABSTRACT Cancer patients develop frequent cardiac problems due to chemotherapy toxicity, which impacts functional capacity (FC) and quality of life (QoL). Inspiratory Muscle Training (IMT) may be a viable therapeutic resource since cause-effect studies have shown improvement in FC and QoL in other populations. However, its effect was not evaluated in cardio-oncology patients. The study aimed to describe the effect of an IMT program on the FC and QoL of a patient with cardiotoxicity, LDM, aged 41 years, female and, sedentary that developed heart failure after chemotherapy. The QoL was evaluated by the Minnesota test. Dynamic Inspiratory Muscle Strength (S-Index) and Glycemic Threshold (GT) of the inspiratory muscles were also evaluated. The GT was determined by capillary glycemia with a digital glucometer (Accu-Chek - Roche), at the lowest value of glycemia of the load corresponding to the Incremental Inspiratory Muscle Test (IIMT). The load progression was performed every two weeks. After two months, all tests were reapplied. In the Minnesota test, the values related to FC, pre and post IMT, were 36 v. 8 (78% improvement); the clinical and psychological aspects 32 v. 7 (78% improvement); S-Index was 41 v. 51cmH2O (24% improvement). IMT improved the FC and QoL of a cardio-oncology patient, configuring itself as a possible and viable therapeutic resource for this population.

Shengmai San for Treatment of Cardiotoxicity from Anthracyclines: A Systematic Review and Meta-Analysis / 中国结合医学杂志

OBJECTIVE@#To systematically evaluate the efficacy of Shengmai San in patients with cardiotoxicity of anthracyclines.@*METHODS@#Randomized controlled trials (RCTs) were identified by searching China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), PubMed, Cochrane Library, and Embase Databases from the inceptions until December 2020. The Cochrane Handbook was used to evaluate the risk of bias in the included studies. Data analysis was conducted using RevMan 5.3 software.@*RESULTS@#Totally 19 RCTs with 2,331 participants were included in this review. Results showed that in improving arrhythmia (13 RCTs, n=1,877, RR=0.37, 95%CI 0.25 to 0.52, P<0.00001), the treatment group was superior to the control group. In terms of reducing left ventricular end-diastolic diameter (LVEDD, 2 RCTs, n=128, MD=-0.79, 95%CI -0.93 to -0.65, P<0.00001) and left ventricular end systolic diameter (LVESD, 2 RCTs, n=128, MD=-0.58, 95%CI -0.82 to -0.35, P<0.00001), the treatment group was also better than the control group. In reducing myocardial enzymes such as creatine kinase (CK) [(3 RCTs, n=256, SMD=-0.80, 95%CI -1.16 to -0.44, P<0.0001), (2 RCTs, n=126, SMD=-0.62, 95%CI -0.98 to -0.26, P=0.0007)], the treatment group was superior to the control group.@*CONCLUSION@#Shengmai San has a positive effect on the treatment of cardiotoxicity from anthracyclines. However, in the future, it is still necessary to conduct high-quality RCTs to verify its efficacy.

Effect of changes in body mass index on left heart function in early breast cancer patients undergoing anthracycline chemotherapy / 肿瘤研究与临床

Objective:To explore the effect of changes in BMI (ΔBMI) on left ventricular function in early breast cancer patients undergoing anthracycline chemotherapy.Methods:The clinical data of 170 breast cancer patients treated in the Lianyungang Oriental Hospital from January 2018 to October 2021 were retrospectively analyzed. The clinicopathological data and cardiac color doppler ultrasound examination results of the patients were collected. Single-factor and multiple-factor were used to analyze the risk factors of cardiotoxicity in patients after chemotherapy. ΔBMI was calculated and the receiver operating characteristic (ROC) curve was drawn; the cut-off value of the ΔBMI was measured to obtain the diagnostic accuracy.Results:Compared with before chemotherapy, the mean values of BMI, left ventricular end-diastolic volume (EDV), left ventricular end-systolic volume (ESV), left ventricular end-diastolic diameter (LVD), and left ventricular end-systolic diameter (LVS) were increased after chemotherapy, while left ventricular ejection fraction (LVEF) value was decreased. Before and after chemotherapy, the differences between BMI [(22.30±1.88) kg/m 2 vs. (23.59±2.32) kg/m 2] and LVEF [(63.69±4.69)% vs. (59.08±4.28)%] were statistically significant ( t = 3.40 and 4.98, all P < 0.05). The range of ΔBMI was 0-41.3%, and the range of the change of LVEF (ΔLVEF) was 0-15.9%. There was a significant correlation between ΔLVEF and ΔBMI ( r = 0.709, P < 0.001). The incidence of cardiotoxicity was 21.2% (36/170). Logistic regression analysis showed that BMI( OR = 1.639, 95% CI 1.263-2.127, P = 0.000) and ΔBMI ( OR = 1.147, 95% CI 1.071-1.228, P = 0.000) were independent risk factors for cardiotoxicity in early breast cancer patients undergoing anthracycline chemotherapy. According to the cardiotoxicity, the area under the ROC curve of ΔBMI and BMI was 0.757 and 0.687, respectively. When the ΔBMI value was 4.28%, the maximum Youden index was 0.399, the sensitivity was 0.750, and the specificity was 0.649. Conclusion:For breast cancer patients treated with anthracycline chemotherapy, ΔBMI can be used as an effective indicator for predicting cardiotoxicity; when ΔBMI exceeds 4.28%, the risk of cardiotoxicity is high.

The protective effect of Dexrazoxane on onco-Cardiology induced by anticancer agents other than anthracyclines / 中国药理学通报

Aim To evaluate the protective effect of Dexrazoxane(Dex)on onco-Cardiology caused by chemotherapeutic drugs other than anthracycline antitumor drugs using zebrafish embryos, including:cisplatin, paclitaxel, vincristine sulfate, 5-fluorouracil and cyclophosphamide. Methods Zebrafish embryos at 24 hpf(hours post-fertilization)were exposed to different concentrations of drugs. The survival rate and the overall animal morphology at 48 hpf, 72 hpf and 96 hpf were observed with a microscope. Heart rate, ventricular contraction fraction, ventricular volume, and cardiac output were measured and calculated by video recordings made with a VCD system. The protective effect of Dex was evaluated using the established model of onco-Cardiology induced by anti-tumor drugs other than anthracyclines. Results In terms of acute toxicity, cisplatin, vincristine sulfate, 5-fluorouracil and cyclophosphamide all significantly reduced the survival rate of zebrafish embryos. The LC50 value was 437.655, 25.538, 65.606 and 19.021 mmol·L-1, respectively. In addition to paclitaxel, the other four anti-tumor drugs all showed significant changes in overall animal morphology and cardiac function indicators. In the study of the protective effect of Dex on four kinds of tumor heart diseases except anthracyclines, only cisplatin had a significant protective effect, which could improve the cardiotoxicity caused by cisplatin. The optimal concentration of Dex was 80 μmol·L-1. Conclusions Zebrafish models of drug toxicity caused by cisplatin, vincristine sulfate, 5-fluorouracil, and cyclophosphamide is established, which proves that Dex only has a protective effect on the toxicity caused by cisplatin.

Early-onset Cardiotoxicity assessment related to anthracycline in children with leukemia. A Prospective Study / Evaluación de la cardiotoxicidad temprana asociada al tratamiento con antraciclinas en niños con Leucemia. Estudio prospectivo

Abstract Background: Acute leukemias are the most frequent malignancies in children. Advances in treatment have improved the overall survival to 80%. Almost 10% of children with cancer develop clinical cardiac toxicity. Total anthracycline cumulative dose is a risk factor for early-onset cardiotoxicity. Objective: To describe the incidence of early-onset cardiotoxicity in children with acute leukemia treated with chemotherapy. Methods: A prospective descriptive study of patients >1 y and <18 years diagnosed with acute leukemia. Assessed with electrocardiograma, echocardiography, and blood biomarkers at diagnosis and during the follow-up. Results: 94 patients with acute lymphoblastic leukemia and 18 with acute myeloid leukemia were included. 20 patients (17.9%) developed early-onset cardiotoxicity. Statistically significant data was seen after anthracycline dose >150 mg/m2, between the first echocardiographic evaluation and posterior analyses in the left ventricular fraction ejection with Teicholz p 0.05, Simpson p 0.018 and GLS p 0.004. In this study, there was no relation between blood biomarkers and cardiotoxicity. Conclusions: Cancer therapeutic-related cardiac dysfunction is related to anthracycline cumulative dose. In this study, echocardiographic follow-up was useful to predict risk factors for early cardiac dysfunction.

Resumen Antecedentes: Las leucemias son la principal causa de cáncer infantil. Los avances en el tratamiento han llevado a los pacientes a una supervivencia global hasta del 80%. Cerca del 10% de los niños con cáncer tienen toxicidad cardiovascular sintomática, la dosis acumulada de antraciclinas es un factor de riesgo para afección cardíaca. Objetivo: Describir la frecuencia de afectación cardíaca temprana en niños con leucemias agudas que recibieron tratamiento antineoplásico. Métodos: Estudio prospectivo observacional, de pacientes <18 años con diagnóstico confirmado de leucemia aguda. Fueron evaluados con electrocardiograma, ecocardiograma bidimensional y biomarcadores séricos en diferentes momentos durante el tratamiento. Resultados: Se evaluaron 94 pacientes con leucemia linfoide aguda y 18 con leucemia mieloide aguda. 20 pacientes (17.9%) tuvieron disfunción cardiaca de inicio temprano. Se observaron diferencias estadísticamente significativas, después de recibir 150 mg/m2 de antraciclinas, entre la evaluación del ecocardiograma basal y evaluaciones posteriores de la fracción de eyección ventricular izquierda por Teicholz p 0.05, fracción de eyección ventricular izquierda por Simpson p 0.018 y la deformación longitudinal global p 0.004. No se encontraron alteraciones en los niveles séricos de las troponinas y péptido natriurético cerebral. Conclusiones: La disfunción cardíaca relacionada con quimioterapia estuvo directamente relacionada con las dosis acumuladas de antraciclinas. En este estudio el uso del ecocardiograma como método de seguimiento permitió identificar factores predictores de riesgo para disfunción cardiaca temprana.

Cardiotoxicidad en una Cohorte de pacientes con Diagnóstico de Cáncer de Mama que Recibieron Quimioterapia con Antraciclinas. Seguimiento a 12 años / Cardiotoxicity in a Cohort of Patients Diagnosed with Breast Cancer Who Received Anthracycline Chemotherapy. 12-year follow-up

Introducción: Los esquemas de quimioterapia en el tratamiento de cáncer de mama incluyen Antraciclinas con una efectividad de respuesta alta, sin embargo en algunos casos el potencial efecto terapéutico se ve limitado por la Cardiomiopatía Inducida por Antraciclinas (CIPA).El objetivo del estudio fue establecer la prevalencia longitudinal de esta entidad. Métodos:Este estudiolongitudinalfue realizado en el Instituto Oncológico Nacional "Dr.Juan Tanca Marengo" -SOLCA-Guayaquil. El período de exposición fue abril a diciembredel 2008,laobservación terminó enjunio 2020.Seincluyó mujeres con cáncer de mama, en tratamiento con antraciclinas, clasificadas por riesgo Cardiovascular de Framingham Bajo (A), moderado (B) y alto (C).Se midió lasalteraciones electrocardiográficas (AEKG) basales, a las 6 y 24 horas.Desarrollo de CIPA en seguimiento a 12 años.La muestra fue no probabilística tipo censo. Se utiliza estadística descriptivacon Intervalo de confianza para proporciones. Resultados: Ingresaron al estudio 50 casos son AEKG. El desarrollo de AEKG a 6 horas en 18/50 casos (36% IC95% 34.1-37.9%), estas AEKG persistieron hasta las 24 horas. Las AEKG se presentaron en un 18.5% en mujeres con Riesgo A, 52.4% enRiesgo B y 100%en Riesgo C. El desarrollo de CIPA a12 años fue de 3.6% (2.3-4.9%) en CIPA-Subaguda y de 7.1% (5.3-9.0%)en CIPA crónica. CIPA Subaguda+ crónica 10.7% (8.6-12.9%). Conclusiones: los eventos de cardiotoxicidad aguda fueron detectados por AEKG,en el seguimiento a largo plazo laCIPAsedesarrollóen un porcentaje un poco mayor a la literatura reportada.

Introduction:Chemotherapy regimens in the treatment of breast cancer include Anthracyclines with a high response effectiveness, however in some cases the potential therapeutic effect is limited by Anthracycline Induced Cardiomyopathy (CIPA). The objective of the study was to establish the longitudinal prevalence of this entity. Methods: This longitudinal, observational study was conducted at the National Oncological Institute "Dr. Juan Tanca Marengo "-SOLCA-Guayaquil. The exposure period was April to December 2008. The observation period ended on June 30, 2020. It included women> 18 years with breast cancer, treated with anthracyclines, classified by Framingham Cardiovascular Risk as Low Risk (A) , moderate risk (B) and high risk (C). Electrocardiographic abnormalities (AEKG) were measured at baseline, at 6 hours and at 24 hours and development of CIPA at 12-yearfollow-up. The sample was non-probabilistic, census type. Descriptive statistics with confidence interval for proportions are used. Results: Fifty cases entered the study are AEKG. The development of AEKG at 6 hours in 18/50 cases (36% 95% CI 34.1-37.9%),these AEKG persisted until 24 hours. AEKG were presented in 18.52% in women with Risk A, 52.38% in Risk B and 100% in Risk C. The development of CIPA at 12 years was 3.57% (2.27-4.87%) in CIPA-Subacute and 7.14 % (5.34-8.95% in chronic CIPA. Subacute + chronic CIPA 10.71% (8.55-12.88%). Conclusions: In this study it is concluded that acute cardiotoxicity events were detected by electrocardiographic changes and that in the long-term follow-up they were evident in a slightly higher percentage than that reported in the international literature.

Factores predictivos de cardiotoxicidad inducida por antraciclinas en una cohorte retroprolectiva de niños supervivientes de cáncer / Predictors of anthracycline-induced cardiotoxicity in a retro-prolective cohort of children surviving cancer

Resumen Introducción: La cardiotoxicidad es una reacción adversa asociada al uso de antraciclinas. Objetivo: Estimar los factores asociados al desarrollo de cardiotoxicidad por antraciclinas en pacientes pediátricos supervivientes de cáncer. Método: Cohorte retroprolectiva de niños con diagnóstico de cáncer tratados con antraciclinas. Se realizó determinación ecocardiográfica basal de la fracción de expulsión (FEVi0) antes del inicio del tratamiento y a los 12 meses (FEVi1). Del expediente se obtuvieron las características demográficas y el tratamiento. Se realizó un modelo de regresión logística múltiple (RLM); la FEVi1 < 50 % fue la variable dependiente, que se ajustó por las principales variables confusoras. Resultados: Se incluyeron 65 pacientes, 36.9 % fue del sexo femenino y 56.8 % presentó un tumor sólido. La FEVi0 fue de 74.79 ± 7.3 % y la FEVi1, de 67.96 ± 6.7 % (p = 0.001); 60 % desarrolló cardiotoxicidad. En la RLM solo la dosis acumulada > 430 mg se asoció a cardiotoxicidad (p = 0.001). Conclusiones: En los niños mexicanos se debe evitar una dosis acumulada > 430 mg de antraciclinas para evitar la cardiotoxicidad.

Abstract Introduction Cardiotoxicity is an adverse reaction associated with the use of anthracyclines. Objective: To estimate the factors associated with the development of anthracycline cardiotoxicity in pediatric patients surviving cancer. Method: Retro-prolective cohort of children diagnosed with cancer and treated with anthracyclines. Baseline echocardiographic determination of ejection fraction (LVEF0) was carried out before the start of treatment and again at 12 months (LVEF1). Demographic characteristics and treatment were obtained from the medical record. A multiple logistic regression (MLR) model was constructed; LVEF1 < 50 % was the dependent variable, which was adjusted for the main confounding variables. Results: Sixty-five patients were included, out of which 36.9 % were females and 56.8 % had a solid tumor. LVEF0 was 74.79 ± 7.3 % and LVEF1, 67.96 ± 6.7 % (p = 0.001); 60 % developed cardiotoxicity. In the MLR, only a cumulative dose > 430 mg was associated with cardiotoxicity (p = 0.001). Conclusions: In Mexican children, an anthracycline cumulative dose > 430 mg should be avoided in order to prevent cardiotoxicity.