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Atrial fibrillation (AF) is a common arrhythmic complication in cancer patients and can be exacerbated by traditional cytotoxic and targeted anticancer therapies. Increased incidence of AF in cancer patients is independent of confounding factors, including preexisting myocardial arrhythmogenic substrates, type of cancer, or cancer stage. Mechanistically, AF is characterized by fast unsynchronized atrial contractions with rapid ventricular response, which impairs ventricular filling and results in various symptoms such as fatigue, chest pain, and shortness of breath. Due to increased blood stasis, a consequence of both cancer and AF, concern for stroke increases in this patient population. To compound matters, cardiotoxic anticancer therapies themselves promote AF; thereby exacerbating AF morbidity and mortality in cancer patients. In this review, we examine the relationship between AF, cancer, and cardiotoxic anticancer therapies with a focus on the shared molecular and electrophysiological mechanisms linking these disease processes. We also explore the potential role of sodium-glucose co-transporter 2 inhibitors (SGLT2i) in the management of anticancer-therapy-induced AF.
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Antineoplásicos , Fibrilação Atrial , Neoplasias , Humanos , Fibrilação Atrial/etiologia , Fibrilação Atrial/tratamento farmacológico , Neoplasias/tratamento farmacológico , Neoplasias/complicações , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Animais , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversosRESUMO
BACKGROUND: Prediabetes, which is a precedent of overt diabetes, is a known risk factor for adverse cardiovascular outcomes. Its impact on adverse cardiovascular outcomes in patients with cancer who are prescribed anthracycline-containing chemotherapy (ACT) is uncertain. The objective of this study was to evaluate the association of prediabetes with cardiovascular events in patients with cancer who are prescribed ACT. METHODS: The authors identified patients with cancer who received ACT from 2000 to 2019 from Clinical Data Analysis Reporting System of Hong Kong. Patients were divided into diabetes, prediabetes, and normoglycemia groups based on their baseline glycemic profile. The Primary outcome, a major adverse cardiovascular event (MACE), was the composite event of hospitalization for heart failure and cardiovascular death. RESULTS: Among 12,649 patients at baseline, 3997 had prediabetes, and 5622 had diabetes. Over median follow-up of 8.7 years, the incidence of MACE was 211 (7.0%) in the normoglycemia group, 358 (9.0%) in the prediabetes group, and 728 (12.9%) in the diabetes group. Compared with normoglycemia, prediabetes (adjusted hazard ratio [HR], 1.20; 95% confidence interval [CI], 1.01-1.43) and diabetes (adjusted HR, 1.46; 95% CI, 1.24-1.70) were associated with an increased risk of MACE. In the prediabetes group, 475 patients (18%) progressed to overt diabetes and exhibited a greater risk of MACE (adjusted HR, 1.76; 95% CI, 1.31-2.36) compared with patients who remained prediabetic. CONCLUSIONS: In patients with cancer who received ACT, those who had prediabetes at baseline and those who progressed to diabetes at follow-up had an increased risk of MACE. The optimization of cardiovascular risk factor management, including prediabetes, should be considered in patients with cancer who are treated before and during ACT to reduce cardiovascular risk. PLAIN LANGUAGE SUMMARY: Patients with cancer who have preexisting diabetes have a higher risk of cardiovascular events, and prediabetes is often overlooked. In this study of 12,649 patients with cancer identified in the Clinical Data Analysis Reporting System of Hong Kong who were receiving treatment with anthracycline drugs, prediabetes was correlated with increased deaths from cardiovascular disease and/or hospitalizations for heart failure. Patients who progressed from prediabetes to diabetes within 2 years had an increased risk of combined hospitalization for heart failure and death from cardiovascular disease. These findings indicate the importance of paying greater attention to cardiovascular risk factors, including how prediabetes is managed, in patients who have cancer and are receiving chemotherapy with anthracyclines, emphasizing the need for surveillance, follow-up strategies, and consideration of prediabetes management in cancer care.
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Antraciclinas , Neoplasias , Estado Pré-Diabético , Humanos , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/induzido quimicamente , Estado Pré-Diabético/complicações , Antraciclinas/efeitos adversos , Antraciclinas/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Neoplasias/epidemiologia , Idoso , Hong Kong/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/induzido quimicamente , Adulto , Fatores de Risco , Diabetes Mellitus/epidemiologia , IncidênciaRESUMO
BACKGROUND: The risk of incident atrial fibrillation (AF) among breast cancer survivors, especially for younger women, and cancer treatment effects on the association remain unclear. This study aimed to investigate the risk of AF among breast cancer survivors and evaluate the association by age group, length of follow-up, and cancer treatment. METHODS: Using data from the Korean Health Insurance Service database (2010-2017), 113,232 women newly diagnosed with breast cancer (aged ≥ 18 years) without prior AF history who underwent breast cancer surgery were individually matched 1:5 by birth year to a sample female population without cancer (n = 566,160) (mean[SD] follow-up, 5.1[2.1] years). Sub-distribution hazard ratios (sHRs) and 95% confidence intervals (CIs) considering death as a competing risk were estimated, adjusting for sociodemographic factors and cardiovascular/non-cardiovascular comorbidities. RESULTS: BCS had a slightly increased AF risk compared to their cancer-free counterparts (sHR 1.06; 95% CI 1.00-1.13), but the association disappeared over time. Younger BCS (age < 40 years) had more than a 2-fold increase in AF risk (sHR 2.79; 95% CI 1.98-3.94), with the association remaining similar over 5 years of follow-up. The increased risk was not observed among older BCS, especially those aged > 65 years. Use of anthracyclines was associated with increased AF risk among BCS (sHR 1.57; 95% CI 1.28-1.92), which was more robust in younger BCS (sHR 1.94; 95% CI 1.40-2.69 in those aged ≤ 50 years). CONCLUSIONS: Our findings suggest that younger BCS had an elevated risk of incident AF, regardless of the length of follow-up. Use of anthracyclines may be associated with increased mid-to-long-term AF risk among BCS.
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Fibrilação Atrial , Neoplasias da Mama , Sobreviventes de Câncer , Humanos , Feminino , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/diagnóstico , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/cirurgia , Sobreviventes , Antraciclinas , Fatores de Risco , IncidênciaRESUMO
Anthracyclines are highly potent anti-cancer drugs, but their clinical use is limited by severe cardiotoxic side effects. The impact of anthracycline-induced cardiotoxicity (AIC) on left ventricular (LV) microarchitecture and diffusion properties remains unknown. This study sought to characterize AIC by cardiovascular magnetic resonance diffusion tensor imaging (DTI). Mice were treated with Doxorubicin (DOX; n = 16) for induction of AIC or saline as corresponding control (n = 15). Cardiac function was assessed via echocardiography at the end of the study period. Whole hearts (n = 8 per group) were scanned ex vivo by high-resolution DTI at 7 T. Results were correlated with histopathology and mass spectrometry imaging. Mice with AIC demonstrated systolic dysfunction (LVEF 52 ± 3% vs. 43 ± 6%, P < 0.001), impaired global longitudinal strain (-19.6 ± 2.0% vs. -16.6 ± 3.0%, P < 0.01), and cardiac atrophy (LV mass index [mg/mm], 4.3 ± 0.1 vs. 3.6 ± 0.2, P < 0.01). Regional sheetlet angles were significantly lower in AIC, whereas helix angle and relative helicity remained unchanged. In AIC, fractional anisotropy was increased (0.12 ± 0.01 vs. 0.14 ± 0.02, P < 0.05). DOX-treated mice displayed higher planar and less spherical anisotropy (CPlanar 0.07 ± 0.01 vs. 0.09 ± 0.01, P < 0.01; CSpherical 0.89 ± 0.01 vs. 0.87 ± 0.02, P < 0.05). CPlanar and CSpherical yielded good discriminatory power to distinguish between mice with and without AIC (c-index 0.91 and 0.84, respectively, P for both < 0.05). AIC is associated with regional changes in sheetlet angle but no major abnormalities of global LV microarchitecture. The geometric shape of the diffusion tensor is altered in AIC. DTI may provide a new tool for myocardial characterization in patients with AIC, which warrants future clinical studies to evaluate its diagnostic utility.
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INTRODUCTION: Breast cancer is the most common cancer in women with a 5-year survival over 90%. However, anthracycline-based chemotherapy causes significant cardiotoxicity often requiring discontinuation of chemotherapeutic regimen among breast cancer survivors. We conducted a systematic review and meta-analysis to evaluate the efficacy of exercise training in mitigating anthracycline-related cardiotoxicity among women with breast cancer. METHODS: We searched PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases. The outcomes of interest were left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), early to atrial filling velocity (E/A) ratio, maximal oxygen consumption (VO2 max), and cardiac output (CO). We used the Cochrane risk-of-bias tool for randomized trials (RoB 2) to assess the risk of bias in individual studies. RESULTS: We identified a total of 596 articles with 5 trials included in the final analysis. Exercise training was associated with an increase in VO2 max compared with no exercise training (mean difference, 3.95 [95% CI, 0.63-7.26]; I2 = 99.68%). Other cardiovascular outcomes such as LVEF (mean difference, 1.76 [95% CI, -1.95 to 5.46]; I2 = 99.44%), GLS (mean difference, 0.30 [95% CI, -0.49 to 1.10]; I2 = 96.63%), E/A ratio (mean difference, 0.05 [95% CI, -0.05 to 0.15]; I2 = 94.16%), and CO (mean difference, 0.38 [95% CI, -0.91 to 1.66]; I2 = 99.73%) are similar between patients who underwent exercise training and those who did not. CONCLUSIONS: Exercise was associated with an improvement in maximal oxygen uptake among women with breast cancer receiving anthracycline-based chemotherapy.
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Antraciclinas , Neoplasias da Mama , Cardiotoxicidade , Humanos , Neoplasias da Mama/tratamento farmacológico , Feminino , Cardiotoxicidade/etiologia , Cardiotoxicidade/prevenção & controle , Antraciclinas/efeitos adversos , Exercício Físico , Consumo de Oxigênio/efeitos dos fármacos , Volume Sistólico/efeitos dos fármacos , Terapia por Exercício/métodosRESUMO
The clinical use of the DNA damaging anticancer drug doxorubicin (DOX) is limited by irreversible cardiotoxicity, which depends on the cumulative dose. The RAS-homologous (RHO) small GTPase RAC1 contributes to DOX-induced DNA damage formation and cardiotoxicity. However, the pathophysiological relevance of other RHO GTPases than RAC1 and different cardiac cell types (i.e., cardiomyocytes, non-cardiomyocytes) for DOX-triggered cardiac damage is unclear. Employing diverse in vitro and in vivo models, we comparatively investigated the level of DOX-induced DNA damage in cardiomyocytes versus non-cardiomyocytes (endothelial cells and fibroblasts), in the presence or absence of selected RHO GTPase inhibitors. Non-cardiomyocytes exhibited the highest number of DOX-induced DNA double-strand breaks (DSB), which were efficiently repaired in vitro. By contrast, rather low levels of DSB were formed in cardiomyocytes, which however remained largely unrepaired. Moreover, DOX-induced apoptosis was detected only in non-cardiomyocytes but not in cardiomyocytes. Pharmacological inhibitors of RAC1 and CDC42 most efficiently attenuated DOX-induced DNA damage in all cell types examined in vitro. Consistently, immunohistochemical analyses revealed that the RAC1 inhibitor NSC23766 and the pan-RHO GTPase inhibitor lovastatin reduced the level of DOX-induced residual DNA damage in both cardiomyocytes and non-cardiomyocytes in vivo. Overall, we conclude that endothelial cells, fibroblasts and cardiomyocytes contribute to the pathophysiology of DOX-induced cardiotoxicity, with RAC1- and CDC42-regulated signaling pathways being especially relevant for DOX-stimulated DSB formation and DNA damage response (DDR) activation. Hence, we suggest dual targeting of RAC1/CDC42-dependent mechanisms in multiple cardiac cell types to mitigate DNA damage-dependent cardiac injury evoked by DOX-based anticancer therapy.
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Aminoquinolinas , Doxorrubicina , Células Endoteliais , Fibroblastos , Miócitos Cardíacos , Pirimidinas , Proteína cdc42 de Ligação ao GTP , Proteínas rac1 de Ligação ao GTP , Proteínas rac1 de Ligação ao GTP/metabolismo , Proteínas rac1 de Ligação ao GTP/antagonistas & inibidores , Proteínas rac1 de Ligação ao GTP/genética , Animais , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Miócitos Cardíacos/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Fibroblastos/patologia , Proteína cdc42 de Ligação ao GTP/metabolismo , Doxorrubicina/toxicidade , Doxorrubicina/efeitos adversos , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/patologia , Células Endoteliais/metabolismo , Cardiotoxicidade , Antibióticos Antineoplásicos/toxicidade , Camundongos , Apoptose/efeitos dos fármacos , Masculino , Humanos , Camundongos Endogâmicos C57BL , Quebras de DNA de Cadeia Dupla/efeitos dos fármacos , Neuropeptídeos/metabolismo , Dano ao DNA/efeitos dos fármacos , Células CultivadasRESUMO
BACKGROUND: In the present study, we aimed to investigate whether early cardiac biomarker alterations and echocardiographic parameters, including left atrial (LA) strain, can predict anthracycline-induced cardiotoxicity (AIC) and thus develop a predictive risk score. METHODSâANDâRESULTS: The AIC registry is a prospective, observational cohort study designed to gather serial echocardiographic and biomarker data before and after anthracycline chemotherapy. Cardiotoxicity was defined as a reduction in left ventricular ejection fraction (LVEF) ≥10 percentage points from baseline and <55%. In total, 383 patients (93% women; median age, 57 [46-66] years) completed the 2-year follow-up; 42 (11.0%) patients developed cardiotoxicity (median time to onset, 292 [175-440] days). Increases in cardiac troponin T (TnT) and B-type natriuretic peptide (BNP) and relative reductions in the left ventricular global longitudinal strain (LV GLS) and LA reservoir strain [LASr] at 3 months after anthracycline administration were independently associated with subsequent cardiotoxicity. A risk score containing 2 clinical variables (smoking and prior cardiovascular disease), 2 cardiac biomarkers at 3 months (TnT ≥0.019 ng/mL and BNP ≥31.1 pg/mL), 2 echocardiographic variables at 3 months (relative declines in LV GLS [≥6.5%], and LASr [≥7.5%]) was generated. CONCLUSIONS: Early decline in LASr was independently associated with subsequent cardiotoxicity. The AIC risk score may provide useful prognostication in patients receiving anthracyclines.
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Antraciclinas , Cardiotoxicidade , Peptídeo Natriurético Encefálico , Humanos , Antraciclinas/efeitos adversos , Pessoa de Meia-Idade , Feminino , Masculino , Estudos Prospectivos , Idoso , Peptídeo Natriurético Encefálico/sangue , Biomarcadores/sangue , Troponina T/sangue , Ecocardiografia , Sistema de Registros , Diagnóstico PrecoceRESUMO
PURPOSE OF REVIEW: The aim of this review is two-fold: (1) To examine the mechanisms by which statins may protect from anthracycline-induced cardiotoxicity and (2) To provide a comprehensive overview of the existing clinical literature investigating the role of statins for the primary prevention of anthracycline-induced cardiotoxicity. RECENT FINDINGS: The underlying cardioprotective mechanisms associated with statins have not been fully elucidated. Key mechanisms related to the inhibition of Ras homologous (Rho) GTPases have been proposed. Data from observational studies has supported the beneficial role of statins for the primary prevention of anthracycline-induced cardiotoxicity. Recently, several randomized controlled trials investigating the role of statins for the primary prevention of anthracycline-induced cardiotoxicity have produced contrasting results. Statins have been associated with a lower risk of cardiac dysfunction in cancer patients receiving anthracyclines. Further investigation with larger randomized control trials and longer follow-up periods are needed to better evaluate the long-term role of statin therapy and identify the subgroups who benefit most from statin therapy.
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BACKGROUND: The treatment of choice for Extra-osseous Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET), a rare neoplasm, is the VAC/IE regimen. This regimen includes Doxorubicin, Vincristine, Cyclophosphamide, Ifosfamide, and Etoposide, all of which have cardiotoxic effects. Myocarditis, a potentially threatening side effect following cancer therapy, can be accurately managed and diagnosed. CASE PRESENTATION: In the current study, we report the case of a 19-year-old female with a mass on the abdominal wall, diagnosed with ES/PNET. She was treated with the VAC/IE regimen. A month after the last session of chemotherapy, she experienced dyspnea. Upon evaluation, a high level of troponin and a low left ventricular ejection fraction (LVEF) were detected via transthoracic echocardiography. She was treated with anti-heart failure drugs, but the response was unsatisfactory. The possibility of Cancer therapy-related myocarditis was suspected, and cardiac magnetic resonance imaging (CMR) confirmed acute myocarditis. This patient exhibited a significant response to intravenous immunoglobulin (IVIG), with her LVEF improving from 30-35% to 50% within three months. CONCLUSION: In this case, based on negative tests and the absence of viral signs and symptoms, Cancer therapy-related myocarditis is highly suspected as the cause of myocarditis. This case underscores the importance of accurately utilizing CMR as a non-invasive method for diagnosing myocarditis. It effectively highlights the identification of reversible myocarditis with appropriate treatment and the notable response to IVIG, suggesting its potential as a favorable treatment for myocarditis in younger patients.
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Protocolos de Quimioterapia Combinada Antineoplásica , Miocardite , Função Ventricular Esquerda , Humanos , Feminino , Miocardite/induzido quimicamente , Miocardite/diagnóstico , Miocardite/terapia , Miocardite/diagnóstico por imagem , Adulto Jovem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do Tratamento , Função Ventricular Esquerda/efeitos dos fármacos , Sarcoma de Ewing/tratamento farmacológico , Sarcoma de Ewing/terapia , Sarcoma de Ewing/diagnóstico , Imunoglobulinas Intravenosas/administração & dosagem , Cardiotoxicidade , Volume Sistólico , Recuperação de Função Fisiológica , Valor Preditivo dos TestesRESUMO
BACKGROUND: Antineoplastic medications, including doxorubicin, idarubicin, and epirubicin, have been found to adversely affect the heart due to oxidative stress - mitochondrial dysfunction - ferroptosis (ORMFs), which act as contributing attributes to anthracycline-induced cardiotoxicity. To better understand this phenomenon, the time-resolved measurements of ORMFS genes were analyzed in this study. METHODS: The effect of three anthracycline drugs on ORMFs genes was studied using a human 3D cardiac microtissue cell model. Transcriptome data was collected over 14 days at two doses (therapeutic and toxic). WGCNA identified key module-related genes, and functional enrichment analysis investigated the biological processes quantified by ssGSEA, such as immune cell infiltration and angiogenesis. Biopsies were collected from heart failure patients and control subjects. GSE59672 and GSE2965 were collected for validation. Molecular docking was used to identify anthracyclines's interaction with key genes. RESULTS: The ORMFs genes were screened in vivo or in vitro. Using WGCNA, six co-expressed gene modules were grouped, with MEblue emerging as the most significant module. Eight key genes intersecting the blue module with the dynamic response genes were obtained: CD36, CDH5, CHI3L1, HBA2, HSD11B1, OGN, RPL8, and VWF. Compared with control samples, all key genes except RPL8 were down-regulated in vitro ANT treatment settings, and their expression levels varied over time. According to functional analyses, the key module-related genes were engaged in angiogenesis and the immune system pathways. In all ANT-treated settings, ssGSEA demonstrated a significant down-regulation of angiogenesis score and immune cell activity, including Activated CD4 T cell, Immature B cell, Memory B cell, Natural killer cell, Type 1 T helper cell, and Type 2 T helper cell. Molecular docking revealed that RPL8 and CHI3L1 show significant binding affinity for anthracyclines. CONCLUSION: This study focuses on the dynamic characteristics of ORMFs genes in both human cardiac microtissues and cardiac biopsies from ANT-treated patients. It has been highlighted that ORMFs genes may contribute to immune infiltration and angiogenesis in cases of anthracycline-induced cardiotoxicity. A thorough understanding of these genes could potentially lead to improved diagnosis and treatment of the disease.
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Cardiotoxicidade , Ferroptose , Simulação de Acoplamento Molecular , Estresse Oxidativo , Humanos , Estresse Oxidativo/efeitos dos fármacos , Ferroptose/efeitos dos fármacos , Ferroptose/genética , Mitocôndrias Cardíacas/efeitos dos fármacos , Mitocôndrias Cardíacas/metabolismo , Mitocôndrias Cardíacas/patologia , Mitocôndrias Cardíacas/genética , Redes Reguladoras de Genes , Fatores de Tempo , Transcriptoma , Epirubicina/efeitos adversos , Doxorrubicina , Antibióticos Antineoplásicos/efeitos adversos , Estudos de Casos e Controles , Idarubicina , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/genética , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Perfilação da Expressão Gênica , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Estudos Longitudinais , Antraciclinas/efeitos adversos , Regulação da Expressão Gênica , Transdução de SinaisRESUMO
Cardiovascular diseases and cancer have a complex relationship and show a reciprocal linkage and influence. Mutual risk factors, demographic changes and increasing multimorbidity result in an increase in the incidence of both diseases. Advances in oncological and cardiological treatment lead to a further increase in patients with cured or chronic diseases as a relevant comorbidity. The induction of cardiovascular side effects by cancer therapies leads to increased cardiovascular morbidity and mortality in cancer patients. Recent data also show that cardiovascular disease, through various factors, can also promote the development and progression of cancer. An understanding of the interrelationship between cardiovascular diseases and cancer can be seen as a major medical challenge for the future. To this end, scientific, structural, clinical and educational interfaces between cardiology and oncology are essential. This article outlines the complex relationships between cardiovascular diseases and cancer and defines current and future challenges for the best possible care of affected patients.
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Doenças Cardiovasculares , Neoplasias , Humanos , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Cardio-Oncologia , Cardiotoxicidade , Neoplasias/epidemiologia , Neoplasias/terapia , Neoplasias/complicações , OncologiaRESUMO
Recent advancements in personalized treatments, such as anthracycline chemotherapy, coupled with timely diagnoses, have contributed to a decrease in cancer-specific mortality rates and an improvement in cancer prognosis. Anthracyclines, a potent class of antibiotics, are extensively used as anticancer medications to treat a broad spectrum of tumors. Despite these advancements, a considerable number of cancer survivors face increased risks of treatment complications, particularly the cardiotoxic effects of chemotherapeutic drugs like anthracyclines. These effects can range from subclinical manifestations to severe consequences such as irreversible heart failure and death, highlighting the need for effective management of chemotherapy side effects for improved cancer care outcomes. Given the lack of specific treatments, early detection of subclinical cardiac events post-anthracycline therapy and the implementation of preventive strategies are vital. An interdisciplinary approach involving cardiovascular teams is crucial for the prevention and efficient management of anthracycline-induced cardiotoxicity. Various factors, such as age, gender, duration of treatment, and comorbidities, should be considered significant risk factors for developing chemotherapy-related cardiotoxicity. Tools such as electrocardiography, echocardiography, nuclear imaging, magnetic resonance imaging, histopathologic evaluations, and serum biomarkers should be appropriately used for the early detection of anthracycline-related cardiotoxicity. Furthermore, understanding the underlying biological mechanisms is key to developing preventive measures and personalized treatment strategies to mitigate anthracycline-induced cardiotoxicity. Exploring specific cardiotoxic mechanisms and identifying genetic variations can offer fresh perspectives on innovative, personalized treatments. This chapter aims to discuss cardiomyopathy following anthracycline therapy, with a focus on molecular mechanisms, preventive strategies, and emerging treatments.
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Anthracycline chemotherapy is associated with the left ventricular (LV) dysfunction, but the conventional echocardiographic parameter is insensitive in detecting subclinical cardiac dysfunction, and the role of echocardiography in children cancer survivors (CCSs) has not been well established. Here, the myocardial work (MW) was employed to evaluate the early effect of the anthracyclines on LV function in children lymphoma survivors, as well as to explore the clinical application value of this modality. 51 children lymphoma survivors treated with anthracyclines were included. During the treatments, the echocardiography was performed at baseline (T0 phase), the 3rd (T1 phase) and 6th (T2 phase) chemotherapeutic cycle, respectively. After that, the conventional echocardiographic parameters, LV global longitudinal strain (GLS), and global myocardial work (GMW) parameters were obtained. Finally, these echocardiographic parameters were compared to distinguish the differences among three groups, and correlation analysis was used to identify relationship between GMW parameters and LV GLS. Compared with the baseline, we found that there are no significant differences for LVEF and other conventional echocardiographic parameters after chemotherapy, but the value of LV lateral E/E' increased at T1 and T2 group. The GLS, global work index, global constructed work, and global work efficiency were decreased, while the global wasted work was increased after chemotherapy (all P < 0.05). The correlation analysis showed that the GLS has significant correlation with GMW parameters (all P < 0.001). The MW, as a new noninvasive echocardiography modality, could be used to quantitatively evaluate the LV MW in children lymphoma survivors treated with anthracyclines, which providing a sensitive method to early detect the children's LV dysfunction after the chemotherapy.
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Chemotherapies have changed the prognosis of patients affected by cancer over the last 20 years, with a significant increase in survival rates. However, they can cause serious adverse effects that may limit their use. In particular, anthracyclines, widely used to treat both hematologic cancers and solid cancers, may cause cardiac toxicity, leading to the development of heart failure in some cases. This review aims to explore current evidence with regards to anthracyclines' cardiotoxicity, with particular focus on the classifications and underlying molecular mechanisms, in order to provide an overview on the current methods of its diagnosis, treatment, and prevention. An attentive approach and a prompt management of patients undergoing treatment with anthracyclines is imperative to avoid preventable antineoplastic drug discontinuation and is conducive to improving both short-term and long-term cardiovascular morbidity and mortality.
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AIM: To evaluate the effect of Sacubitril/Valsartan (S/V) on the functional status, systolic and diastolic function of the left ventricle (LV), tolerability of therapy and to determine predictors of its effectiveness in patients with cancer therapy-related heart failure (СTRHF). MATERIALS AND METHODS: Forty patients 58 [46; 65.5] years of age with HF associated with anthracycline-containing cancer therapy were enrolled. Clinical examination, echocardiography, and assessment of potassium and creatinine levels were performed at baseline and after 6 months of S/V therapy. RESULTS: NYHA functional class (FC) improvement was observed in 22 (64.7%) patients. Radiation therapy (RT) decreased (OR 0.091; 95% CI 0.01-0.83; p=0.03) while baseline low LV EF increased (OR 9.0; 95% CI 1.78-45.33; p=0.008) the odds of FC improvement. LV EF increased from 37.3 [30; 42.5] % to 45 [38; 48] % (p<0.0001) and exceeded 50% in 7 (20.6%) patients. The odds of LV EF recovery increased when S/V therapy was initiated ≤1 year after anthracycline therapy (OR 10.67; 95% CI 1.57-72.67; p=0.0016) and decreased in patients with the history of RT (OR 0.14; 95% CI 0.02-0.89; p=0.0037) and in patients over 58 years (OR 0.07; 95% CI 0.01-0.68; p=0.022). LV diastolic function improvement included E/e' descent from 13.6 [10; 18.3] to 8.9 [6.9; 13.7] (p=0.0005), and decrease in diastolic dysfunction grade in 18 (45%) patients (p=0.0001). No significant change in serum potassium (4.45 [4.2; 4.8] versus 4.5 [4.3; 4.8]; p=0.5) and creatinine (75.4 [67.6; 85.1] versus 75.5 [68.2; 98.3]; p=0.08) levels were observed. CONCLUSION: S/V therapy is associated with improvement of EF, systolic and diastolic LV function, demonstrates a favorable tolerability profile in patients with СTRHF. Lack of RT and low baseline LV EF increased the odds of LV EF improvement; lack of RT, early (≤1 year) start of treatment after discontinuation of anthracycline therapy, and age <58 years increased the odds of LV EF recovery.
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Insuficiência Cardíaca , Neoplasias , Humanos , Pessoa de Meia-Idade , Creatinina , Tetrazóis/efeitos adversos , Valsartana/farmacologia , Valsartana/uso terapêutico , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Função Ventricular Esquerda , Combinação de Medicamentos , Antraciclinas/farmacologia , Antraciclinas/uso terapêutico , Potássio/farmacologia , Potássio/uso terapêutico , Volume Sistólico , Neoplasias/tratamento farmacológicoRESUMO
Aims: This study aimed to evaluate the global research trend in the prevention and treatment of cardiotoxicity caused by anthracyclines from 2000 to 2023, and to explore international cooperation, research hotspots, and frontier trends. Methods: The articles on the prevention and treatment of anthracycline-induced cardiotoxicity published from 2000 to 2023 were searched by Web of Science. The bibliometrics software CiteSpace was used for visual analysis of countries, institutions, journals, authors, cited authors, cited references, and keywords. Results: This study analyzed the current status of global research on the prevention and treatment of cardiotoxicity caused by anthracyclines. A total of 3,669 papers were searched and 851 studies were included. The number of publications increased gradually throughout the years. Cardiovascular Toxicology (15) is the journal with the most publications. Circulation (547) ranked first among cited journals. In this field, the country with the most publications is the United States (229), and the institution with the most publications is Charles Univ Prague (18). In the analysis of the authors, Tomas S (10) ranked first. Cardinale D (262) ranked first among cited authors. In the ranking of cited literature frequency, the article ranked first is "Early detection of anthracycline cardiotoxicity and improvement with heart failure therapy" (121). The keywords "heart failure" (215) and "oxidative stress" (212) were the most frequent. "Enalapril", "inflammation", "cell death", "NF-κB" and "Nrf2" were the advanced research contents in 2019-2023. Conclusions: This study provided valuable information for cardio-oncology researchers to identify potential collaborators and institutions, discover hot topics, and explore new research directions. The prevention and treatment of anthracycline-induced cardiotoxicity focuses on early detection and timely treatment. The results of the current clinical studies on the treatment of anthracycline-induced cardiotoxicity are contradictory, and more studies are needed to provide more reliable clinical evidence in the future.
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BACKGROUND: Cancer-therapy-related cardiac dysfunction (CTRCD) is a growing concern for public health, with a growing incidence due to improved survival rates of patients with hematological malignancies due to diagnostic and therapeutic advances. The identification of patients at risk for CTRCD is vital to developing preventive strategies. METHODS: A single-center retrospective cohort study was conducted between 1 January 2017 and 15 February 2023. Medical records of patients with lymphoma treated with first-line anthracyclines were reviewed. Demographic data, cardiovascular risk factors, biomarkers of myocardial damage, and echocardiographic information were collected. RESULTS: A total of 200 patients were included. The incidence of CTRCD was 17.4% (35/200). Patients with CTRCD were older than those without CTRCD, with a mean age of 65.17 years vs. 56.77 (p = 0.008). Dyslipidemia (DL) (31.4% vs. 13.4% p = 0.017) and previous cardiovascular disease (40% vs. 13.3%; p < 0.001) were more frequent in the group who developed an event. Mean baseline NT-proBNP levels in the subgroup with cardiovascular events were 388.73 kg/L ± 101.02, and they were 251.518 kg/L ± 26.22 in those who did not (p = 0.004). Differences in Troponin I levels were identified during and after treatment without exceeding the laboratory's upper reference limit. Patients were followed for a median of 51.83 months (0.76-73.49). The presence of a CTCRD event had a negative impact on overall mortality from any cause (HR = 2.23 (95% CI: 1.08-2.93); p = 0.031). CONCLUSIONS: Early identification of risk factors is crucial to manage patients at risk for CTRCD.
Assuntos
Antraciclinas , Doenças Cardiovasculares , Linfoma , Humanos , Antraciclinas/efeitos adversos , Antraciclinas/uso terapêutico , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Doenças Cardiovasculares/induzido quimicamente , Linfoma/tratamento farmacológico , Fatores de Risco , Cardiotoxicidade , IncidênciaRESUMO
The global incidence of breast cancer is on the rise, a trend also observed in South Korea. However, thanks to the rapid advancements in anticancer therapies, survival rates are improving. Consequently, post-treatment health and quality of life for breast cancer survivors are emerging as significant concerns, particularly regarding treatment-related cardiotoxicity. In this review, we delve into the cardiovascular complications associated with breast cancer treatment, explore surveillance protocols for early detection and diagnosis of late complications, and discuss protective strategies against cardiotoxicity in breast cancer patients undergoing anticancer therapy, drawing from multiple guidelines.
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BACKGROUND: This meta-analysis and systematic review aim to consolidate evidence on cardiotoxicity prevention and treatment strategies in patients receiving anthracyclines or HER2 receptor inhibitors, vital treatments for breast cancer and hematologic malignancies. By synthesizing existing research, the goal is to provide impactful insights that enhance patient care and outcomes. METHODS: Comprehensive research across PubMed, Scopus, EMBASE, and the Cochrane Central Register for Controlled Trials was conducted, selecting clinical trials focusing on cardioprotection in anthracyclines or HER2 inhibitor-treated individuals. Effect sizes were computed using OpenMeta (Analyst), with leave-out meta-analysis to assess potential small study effects. Meta-regression explored treatment duration and sample size effects. Evidence quality for primary outcomes was evaluated using ROB, Robins 2, and Newcastle-Ottawa tools. RESULTS: Twenty -three studies involving a total of 14,652 patients (13,221 adults and 1431 kids) were included in the current systematic review and meta-analysis. The risk of bias and methodological quality of the included studies suggested good and moderate quality. Patients prescribed ß-blockers demonstrated a 74% lower likelihood of exhibiting cardiotoxicity symptoms (OR 1.736). Similarly, the use of dexrazoxane was linked to a threefold decrease in cardiac abnormalities risk (OR 2.989), and ACE inhibitor administration showed half the risk compared with the control group (OR 1.956). CONCLUSIONS: Through this systematic review and meta-analysis, it was shown that there is a reduction in cardiotoxicity from either anthracyclines or HER2 inhibitors in patients receiving pharmacoprophylaxis.
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The introduction of chemotherapy agents has significantly transformed cancer treatment, with anthracyclines being one of the most commonly used drugs. While these agents have proven to be highly effective against various types of cancers, they come with complications, including neurotoxicity, nephrotoxicity, and cardiotoxicity. Among these side effects, cardiotoxicity is the leading cause of morbidity and mortality, with anthracyclines being the primary culprit. Chemotherapy medications have various mechanisms that can lead to cardiac injury. Hence, numerous studies have been conducted to decrease the cardiotoxicity of these treatments. Combination therapy with beta-blockers, Angiotensin-converting enzyme inhibitors, and angiotensin receptor blockers have effectively reduced such outcomes. However, a definitive preventive strategy is yet to be established. Meanwhile, sodium-glucose co-transporter-2 (SGLT-2) inhibitors lower blood glucose levels in type 2 diabetes by reducing its re-absorption in the kidneys. They are thus considered potent drugs for glycemic control and reduction of cardiovascular risks. Recent studies have shown that SGLT-2 inhibitors are crucial in preventing chemotherapy-induced cardiotoxicity. They enhance heart cell viability, prevent degenerative changes, stimulate autophagy, and reduce cell death. This drug class also reduces inflammation by inhibiting reactive oxygen species and inflammatory cytokine production. Moreover, it can not only reverse the harmful effects of anticancer agents on the heart structure but also enhance the effectiveness of chemotherapy by minimizing potential consequences on the heart. In conclusion, SGLT-2 inhibitors hold promise as a therapeutic strategy for protecting cancer patients from chemotherapy-induced heart damage and improving cardiovascular outcomes.