natriuretic-peptide--brain and Cardiotoxicity

Targeted prevention of heart failure (HF) remains a critical need given the high prevalence of HF morbidity and mortality. Similar to risk-based prevention of atherosclerotic cardiovascular disease, optimal HF prevention strategies should include quantification of risk in the individual patient. In this review, we discuss incorporation of a quantitative risk-based approach into the existing HF staging landscape and the clinical opportunity that exists to translate available data on risk estimation to help guide personalized decision making. We first summarize the recent development of key HF risk prediction tools that can be applied broadly at a population level to estimate risk of incident HF. Next, we provide an in-depth description of the clinical utility of biomarkers to personalize risk estimation in select patients at the highest risk of developing HF. We also discuss integration of genomics-enhanced approaches (eg,

Topics: Antineoplastic Agents; Autoimmune Diseases; Biomarkers; Cardiac Imaging Techniques; Cardiotoxicity; Carrier Proteins; Comorbidity; Connectin; Female; Genomics; Heart Failure; HIV Infections; Humans; Liver Diseases; Natriuretic Peptide, Brain; Peptide Fragments; Pre-Eclampsia; Prealbumin; Precision Medicine; Pregnancy; Premature Birth; Radiotherapy; Renal Insufficiency, Chronic; Risk Assessment; Risk Factors; Troponin T

In recent years, the cancer survival of patients has improved thanks to advances in the pharmacological field. In many guidelines, cardiotoxicity induced by anticancer drugs was defined as a reduction from baseline in the left ventricular ejection fraction (LVEF) assessed by echocardiography. It is known that LVEF is not a sensible parameter in the detection of cardiotoxicity. Therefore, a decrease from baseline in the global longitudinal strain (GLS) or troponins elevation is used to detect subclinical cardiotoxicity. LVEF and GLS as well as the increase in some biomarkers are influenced by loading conditions that are frequent during chemotherapy. Other parameters not influenced by loading conditions should be used in the early diagnosis of cardiotoxicity. The aim of this review is to delineate the role of current strategies used in the early diagnosis of cardiotoxicity and to identify new strategies that could have greater application in the future in cardioncology.

Topics: Antineoplastic Agents; Biomarkers; Cardiotoxicity; Early Diagnosis; Echocardiography; Humans; Magnetic Resonance Imaging; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Troponin; Ventricular Dysfunction, Left; Ventricular Function, Left

Improvements in cancer survival have led to the emergence of cardiovascular disease as an important determinant of adverse outcome in survivors. Cancer therapeutics-related cardiac dysfunction is the most well-known form of cardiotoxicity. However, newer cancer therapies bring a broader range of cardiotoxicities. The optimal method to identify patients at risk of these complications is unclear, but circulating biomarkers comprise one possible approach. Troponins and natriuretic peptides have garnered the broadest evidence base for cardiotoxicity risk prediction, but other markers are being investigated. In this review, we explore evidence for circulating biomarkers in cardiotoxicity prediction associated with cancer therapies.

Topics: Antineoplastic Agents; Biomarkers; Cardiotoxicity; Humans; Immune Checkpoint Inhibitors; Immunotherapy, Adoptive; Natriuretic Peptide, Brain; Peptide Fragments; Receptors, Chimeric Antigen; Troponin; Vascular Endothelial Growth Factor A

Cardiac biomarkers are a mainstay in diagnosis of cardiovascular disease but their role in cardio-oncology has not yet been systematically evaluated. This meta-analysis aims to determine whether cardiac troponins and (N-terminal pro) brain natriuretic peptide (BNP/NT-proBNP) predict cancer therapy-related left ventricular (LV) dysfunction.. Scientific databases were searched for studies that assessed troponins or BNP/NT-proBNP in adult patients undergoing cancer therapy. Data from 61 trials with 5691 patients were included. Cancer therapy was associated with an increase in troponin levels [odds ratio (OR) 14.3, 95% confidence interval (CI) 6.0-34.1; n = 3049]. Patients with elevated troponins receiving chemotherapy or human epidermal growth factor receptor 2 inhibitor therapy were at higher risk for LV dysfunction (OR 11.9, 95% CI 4.4-32.1; n = 2163). Troponin had a negative predictive value of 93%. Mean BNP/NT-proBNP levels were increased in patients post-treatment (standardized mean difference 0.6, 95% CI 0.3-0.9; n = 912), but the available evidence did not consistently indicate prediction of LV dysfunction (OR 1.7, 95% CI 0.7-4.2; n = 197). β-blocker and angiotensin-converting enzyme inhibitor therapy to mitigate cardiotoxicity during cancer therapy was associated with a decline in serum troponins (OR 4.1, 95% CI 1.7-9.8; n = 466).. Elevated troponin levels predict LV dysfunction in patients receiving cancer therapy. Assessment of troponin levels may qualify as a screening test to identify patients who require referral to cardio-oncology units and benefit from preventive strategies. Further evidence is required for both biomarkers.

Topics: Adult; Biomarkers; Cardiotoxicity; Humans; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Troponin

Childhood cancer therapy is associated with a significant risk of therapy-related cardiotoxicity. This meta-analysis aims to evaluate cardiac biomarkers for the detection of cancer therapy-related left ventricular (LV) dysfunction in childhood cancer patients.. PubMed, Cochrane Library, Wiley Library, and Web of Science were screened for studies investigating brain natriuretic peptide (BNP)/N-terminal proBNP (NT-proBNP) or cardiac troponin in childhood cancer patients. The odds ratios (OR) for elevation of cardiac biomarkers and association with LV dysfunction were calculated using a random-effects model. Data from 27 studies with 1651 subjects were included. BNP/NT-proBNP levels were higher post-treatment compared with controls or pre-treatment values [standardized mean difference = 1.0; 95% confidence interval (CI) = 0.6-1.4; n = 320; P < 0.001]. LV dysfunction was present in 11.76% of included patients, and risk for LV dysfunction was increased in patients with elevated BNP/NT-proBNP (OR = 7.1; 95% CI = 2.0-25.5; n = 350; P = 0.003). The sensitivity of BNP/NT-proBNP for the detection of LV dysfunction was 33.3%, and the specificity was 91.5%. Sensitivity increased when selecting for studies that assessed patients < 5 years after anthracycline exposure and for studies including high cumulative anthracycline doses. Anthracycline chemotherapy was associated with an increased frequency of elevated troponin (OR = 3.7; 95% CI = 2.1-6.5; n = 348; P < 0.001). The available evidence on the association between elevated troponin and LV dysfunction was insufficient for an adequate analysis. In five included studies, the frequency of LV dysfunction was not increased in patients with elevated troponin (OR = 2.5; 95% CI = 0.5-13.2; n = 179; P = 0.53).. BNP/NT-proBNP is associated with cardiotoxicity in paediatric cancer patients receiving anthracycline therapy, but owing to low sensitivity, BNP/NT-proBNP has to be evaluated in the context of further parameters including clinical assessment and echocardiography. Future studies are needed to determine whether troponin serves as a marker for cardiotoxicity in children. Standardized recommendations for the application of cardiac biomarkers in children undergoing cardiotoxic cancer therapy may benefit management and clinical outcome.

Topics: Anthracyclines; Biomarkers; Cardiotoxicity; Child; Humans; Natriuretic Peptide, Brain; Neoplasms; Ventricular Dysfunction, Left

Anthracyclines are effectively used in many therapeutic regimens for breast cancer (BC). However, the dose-dependent cardiotoxic effect causes certain limitations on their use. Laboratory tests for risk prediction and early diagnosis of anthracycline-induced cardiotoxicity (ACIC) based on measuring the activity and concentration of topoisomerase 2β, the levels of troponins T and I (TnT и TnI), N-terminal fragment of brain natriuretic peptide progenitor, remain relevant, but complicate the risk stratification with low specificity. Recently, the number of works devoted to the study of new biomarkers ACIC has been growing: galectin-3, soluble ST-2 (sST-2), and myeloperoxidase (MPO). In this review we analyzed current understanding of the classical markers ACIC and the results of recent studies dedicated to new predictors.

Topics: Anthracyclines; Biomarkers; Breast Neoplasms; Cardiotoxicity; DNA Topoisomerases, Type II; Early Detection of Cancer; Female; Galectin 3; Humans; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Peroxidase; Troponin I; Troponin T

Trastuzumab prolongs progression-free and overall survival in patients with human epidermal growth factor receptor 2 (HER2) positive breast cancer. However, trastuzumab treatment is hampered by cardiotoxicity, defined as a left ventricular ejection fraction (LVEF) decline with a reported incidence ranging from 3 to 27% depending on variable factors. Early identification of patients at increased risk of trastuzumab-induced myocardial damage is of great importance to prevent deterioration to irreversible cardiotoxicity. Although current cardiac monitoring with multi gated acquisition (MUGA) scanning and/or conventional 2D-echocardiography (2DE) have a high availability, their reproducibility are modest, and more sensitive and reliable techniques are needed such as 3D-echocardiography (3DE) and speckle tracking echocardiography (STE). But which other diagnostic imaging modalities are available for patients before and during trastuzumab treatment? In addition, what is the optimal frequency and duration of cardiac monitoring? At last, which biomarker monitoring strategies are currently available for the identification of cardiotoxicity in patients treated with trastuzumab?

Topics: Antineoplastic Agents, Immunological; Biomarkers; Breast Neoplasms; C-Reactive Protein; Cardiotoxicity; Echocardiography; Echocardiography, Three-Dimensional; Female; Humans; Immunoglobulin E; Incidence; Interleukin-1 Receptor-Like 1 Protein; Natriuretic Peptide, Brain; Peptide Fragments; Peroxidase; Receptor, ErbB-2; Trastuzumab; Troponin; Ventricular Dysfunction, Left

As the number of cancer survivors increases due to early screening and modern (antineoplastic) treatments, cancer treatment associated cardiotoxicity (CTAC) is becoming an increasing health burden that affects survival and quality of life among cancer survivors. Thus, clinicians need to identify adverse events early, in an effort to take suitable measures before the occurrence of permanent or irreversible cardiac dysfunction.. Cardiac troponin (cTn) and B-type natriuretic peptide (BNP) have been proven to detect subclinical cardiotoxicity during antineoplastic treatment. As such, these cardio-specific biomarkers could predict which patients are at risk of developing CTAC even before the start of therapy. Nevertheless, there are inconsistent data from published studies, and the recommendations regarding the use of these biomarkers and their validity are mostly based on expert consensus opinion. In this review, we summarize available literature that evaluates biomarkers of CTAC, and we encourage strategies that integrate circulating biomarkers and cardiac imaging in identifying cancer patients that are at high risk.

Topics: Antineoplastic Agents; Biomarkers; Cardiotoxicity; Humans; Natriuretic Peptide, Brain; Neoplasms; Troponin

To analyze whether BNP could be a potential biomarker for cardiac damage of breast cancer after radiotherapy.. PubMed, Web of Science, ProQuest and Medline were searched using the key words "breast cancer" ("breast tumor", "breast neoplasm", or "breast carcinoma"), "brain natriuretic peptide" (or BNP) and "radiotherapy" (or "radiation therapy"). Four articles were selected and analyzed using the STATA 12.0 software package. The standard mean difference (SMD) and its standard error for BNP were calculated to assess the relationship between BNP and radiotherapy for breast cancer patients.. In total, 172 patients with breast cancer were identified. The pooled SMD was -0.233 (95% CI -1.113, -0.057). The pooled estimated SMD for all studies showed obvious significant difference (z = 3.99, P = .000). There was no publication bias.. This meta-analysis suggested that BNP could be a biomarker of cardiac damage at high heart absorbed doses according to radiotherapy, especially for left breast cancer patients.

Topics: Biomarkers; Breast Neoplasms; Cardiotoxicity; Chemotherapy, Adjuvant; Female; Humans; Mastectomy; Natriuretic Peptide, Brain; Radiotherapy, Adjuvant

Cardiac biomarkers have been extensively investigated as early detectors of cardiac toxicity from cancer therapies. Whereas the role of biomarkers in monitoring anthracycline toxicity is generally well understood, substantial uncertainty remains regarding their role in monitoring newer targeted cancer therapies.. This review article examines all major published studies using cardiac troponins and/or N-terminal pro-B-type natriuretic peptide (NT-proBNP) in monitoring for cardiac toxicity with trastuzumab, tyrosine kinase inhibitors, and mammalian target of rapamycin (mTOR) inhibitors. There is substantial variability among studies regarding biomarker assays used, sensitivity of the assays, and definitions of abnormal results. In general, troponin I predicts early but not late cardiac events when trastuzumab is administered after anthracyclines, but troponin increases likely reflect anthracycline injury rather than trastuzumab injury. NT-proBNP detects cardiac toxicity with tyrosine kinase inhibitors and mTOR inhibitors, but not independently from echocardiography.. Troponin I can serve as a marker for susceptibility to cardiac toxicity during early trastuzumab treatment in patients who have received recent anthracyclines. NT-proBNP can serve as a useful marker of cardiac toxicity in patients treated with tyrosine kinase inhibitors or mTOR inhibitors if echocardiographic screening is not being used.

Topics: Antineoplastic Agents; Biomarkers; Cardiomyopathies; Cardiotoxicity; Humans; Natriuretic Peptide, Brain; Neoplasms; Troponin I

Modern treatment strategies have led to improvements in cancer survival, however, these gains might be offset by the potential negative effect of cancer therapy on cardiovascular health. Cardiotoxicity is now recognized as a leading cause of long-term morbidity and mortality among cancer survivors. This guideline, authored by a pan-Canadian expert group of health care providers and commissioned by the Canadian Cardiovascular Society, is intended to guide the care of cancer patients with established cardiovascular disease or those at risk of experiencing toxicities related to cancer treatment. It includes recommendations and important management considerations with a focus on 4 main areas: identification of the high-risk population for cardiotoxicity, detection and prevention of cardiotoxicity, treatment of cardiotoxicity, and a multidisciplinary approach to cardio-oncology. All recommendations align with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Key recommendations for which the panel provides a strong level of evidence include: (1) that routine evaluation of traditional cardiovascular risk factors and optimal treatment of preexisting cardiovascular disease be performed in all patients before, during, and after receiving cancer therapy; (2) that initiation, maintenance, and/or augmentation of antihypertensive therapy be instituted per the Canadian Hypertension Educational Program guidelines for patients with preexisting hypertension or for those who experience hypertension related to cancer therapy; and (3) that investigation and management follow current Canadian Cardiovascular Society heart failure guidelines for cancer patients who develop clinical heart failure or an asymptomatic decline in left ventricular ejection fraction during or after cancer treatment. This guideline provides guidance to clinicians on contemporary best practices for the cardiovascular care of cancer patients.

Topics: Antineoplastic Agents; Arrhythmias, Cardiac; Biomarkers; C-Reactive Protein; Cardiotonic Agents; Cardiotoxicity; Cardiotoxins; Coronary Thrombosis; Early Diagnosis; Echocardiography, Three-Dimensional; Humans; Hypertension; Magnetic Resonance Imaging, Cine; Myocardial Ischemia; Natriuretic Peptide, Brain; Neoplasms; Primary Prevention; Radiotherapy; Risk Factors; Troponin T; Ventricular Dysfunction, Left

Early detection of anticancer drug-induced cardiotoxicity (CTX) has been evaluated by most international scientific cardiology and oncology societies. High expectations have been placed on the use of specific biomarkers. In recent years, conventional biomarkers and molecules of more recent interest have been tested and compared in the context of anticancer drug-related CTX. Encouraging results were obtained from studies on molecules of myocardial damage, such as troponin and markers of myocardial wall stress, including circulating natriuretic peptides, as well as from the assessment of the products of inflammation or circulating levels of free radicals. However, clear guidelines on their sensitivity, specificity, and accuracy are not yet available, and many challenges, such as the optimal time of assessing, optimal schedule for evaluation, optimal cut-off point for positivity with the highest level of specificity, and optimal comparability of different assays for the measurements, remain unresolved. Given the importance of having a reliable and accurate tool for monitoring anticancer drug-induced CTX, this review will focus on the available data on the most effective and widely used biomarkers and the studies that are currently underway that aim to identify the effectiveness of new approaches in this therapeutic setting.

Topics: Antineoplastic Agents; Biomarkers; Cardiotoxicity; Early Diagnosis; Humans; Natriuretic Peptide, Brain; Neoplasms; Sensitivity and Specificity; Troponin

To review the evidence for the use of various biomarkers in the detection of chemotherapy associated cardiac damage.. Pubmed.gov was queried using the search words chemotherapy and cardiac biomarkers with the filters of past 10years, humans, and English language. An emphasis was placed on obtaining primary research articles looking at the utility of biomarkers for the detection of chemotherapy-mediated cardiac injury.. Biomarkers may help identify patients undergoing treatment who are at high risk for cardiotoxicity and may assist in identification of a low risk cohort that does not necessitate continued intensive screening. cTn assays are the best studied biomarkers in this context and may represent a promising and potentially valuable modality for detecting cardiac toxicity in patients undergoing chemotherapy. Monitoring cTnI levels may provide information regarding the development of cardiac toxicity before left ventricular dysfunction becomes apparent on echocardiography or via clinical symptoms. A host of other biomarkers have been evaluated for their utility in the field of chemotherapy related cardiac toxicity with intermittent success; further trials are necessary to determine what role they may end up playing for prediction and prognostication in this setting.. Biomarkers represent an exciting potential complement or replacement for echocardiographic monitoring of chemotherapy related cardiac toxicity which may allow for earlier realization of the degree of cardiac damage occurring during treatment, creating the opportunity for more timely modulation of therapy.

Topics: Animals; Antineoplastic Agents; Biomarkers; Cardiotoxicity; Heart Diseases; Humans; Natriuretic Peptide, Brain; Troponin I; Troponin T

An ever-increasing array of chemotherapeutic agents is being used in the treatment of solid organ or hematologic malignancies. The success of many of these agents has led to an increasing survival of patients with cancer. However, many of these agents, particularly anthracyclines and trastuzumab, are associated with the development of cardiotoxicity. The current standard for the evaluation of chemotherapy-associated cardiotoxicity typically involves the use of serial measurements of left ventricular (LV) function by echocardiogram (Echo) and radionuclide ventriculogram (MUGA). Unfortunately, this time-honored method offers low sensitivity to the early prediction or detection of cardiac events. Frequently, by the time cardiotoxicity is detected, significant LV dysfunction has occurred and ultimately this may not respond to standard cardioprotective treatment. Cardiac biomarkers, troponin I and B-type natriuretic peptide, may allow a more accurate and timely monitoring strategy. The current data and a summarized understanding of how to utilize cardiac biomarkers for the prevention and early detection of cardiac dysfunction during chemotherapy are presented.

Topics: Anthracyclines; Antineoplastic Agents; Biomarkers; Cardiotoxicity; Echocardiography; Humans; Natriuretic Peptide, Brain; Neoplasms; Stroke Volume; Trastuzumab; Troponin C; Troponin I; Ventricular Dysfunction, Left

Doxorubicin (DOX) causes deleterious cardiotoxicity. We aimed to investigate the protective roles of metformin and donepezil against DOX-induced cardiotoxicity. In this randomized-controlled trial, 143 female breast cancer patients were enrolled. Metformin (n = 43), donepezil (n = 52), or placebo (n = 48) were prescribed during DOX treatment. The primary endpoint was a proportion of patients with high sensitivity troponin-I (hsTnI) more than the 99th percentile value (> 15.6 ng/L) after DOX treatment. The secondary outcomes were the changes in the hsTnI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), global longitudinal strain (GLS) and peripheral blood mononuclear cells analysis for mitochondrial respiration. Baseline characteristics were similar between the groups. The primary endpoint occurred in 58.54% of metformin group, 76.92% in donepezil group, and 69.77% in placebo group (p = 0.215). The level of hsTnI increased after receiving DOX with subsequent decline in LVEF and GLS. Metformin and donepezil did not attenuate hsTnI elevation, LVEF or GLS reduction. There was no significant change in NT-proBNP level. Mitochondrial respiratory dysfunction was observed in the placebo and donepezil groups. However, metformin preserved mitochondrial respiration during DOX therapy. In conclusion, co-treatment with metformin or donepezil did not prevent myocardial injury. Metformin had a favorable mitochondrial outcome and warranted future studies.

Topics: Breast Neoplasms; Cardiotoxicity; Donepezil; Doxorubicin; Female; Humans; Leukocytes, Mononuclear; Metformin; Natriuretic Peptide, Brain; Peptide Fragments; Stroke Volume; Ventricular Function, Left

An improved understanding of the pathophysiology of trastuzumab-mediated cardiotoxicity is required to improve outcomes of patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We aimed to characterize the cardiac and cardiometabolic phenotype of trastuzumab-mediated toxicity and potential interactions with cardiac pharmacotherapy.. This study was an analysis of serial magnetic resonance imaging (MRI) and circulating biomarker data acquired from patients with HER2-positive early-stage breast cancer participating in a randomized-controlled clinical trial for the pharmaco-prevention of trastuzumab-associated cardiotoxicity. Circulating biomarkers (B-type natriuretic peptide, troponin I, MMP-2 and -9, GDF-15, neuregulin-1, and IGF-1) and MRI of cardiac structure and function and abdominal fat distribution were acquired prior to trastuzumab, post-cycle 4 and post-cycle 17. Ninety-four participants (51 ± 8 years) completed the study with 30 on placebo, 33 on perindopril, and 31 on bisoprolol. Post-cycle 4, global longitudinal strain deteriorated from baseline in both placebo (+2.0 ± 2.7%, P = 0.002) and perindopril (+0.9 ± 2.5%, P = 0.04), but not with bisoprolol (-0.2 ± 2.1%, P = 0.55). In all groups combined, extracellular volume fraction and GDF-15 increased post-cycle 4 (+1.3 ± 4.4%, P = 0.004; +130 ± 150%, P ≤ 0.001, respectively). However, no significant change in troponin I was detected throughout trastuzumab. In all groups combined, visceral and intermuscular fat volume increased post-cycle 4 (+7 ± 17%, P = 0.02, +8 ± 23%, P = 0.02, respectively), while muscle volume and IGF-1 decreased from post-cycle 4 to 17 (-2 ± 10%, P = 0.008, -18 ± 28%, P < 0.001, respectively).. Trastuzumab results in impaired cardiac function and early myocardial inflammation. Trastuzumab is also associated with deleterious changes to the cardiometabolic phenotype which may contribute to the increased cardiovascular risk in this population.

Topics: Breast Neoplasms; Cardiotoxicity; Female; Humans; Natriuretic Peptide, Brain; Trastuzumab; Troponin I

Topics: Adult; Antineoplastic Agents; Biomarkers; Breast Neoplasms; Cardiotoxicity; Cohort Studies; Echocardiography; Female; Germany; Humans; Logistic Models; Middle Aged; Natriuretic Peptide, Brain; Odds Ratio; Peptide Fragments; Prevalence; Risk Factors; Stroke Volume; Troponin T

Breast cancer treatment is associated with the occurrence of various cardiac adverse events. One of the mechanisms associated with cardiotoxicity is oxidative stress, against which cells are protected by antioxidative enzymes. Genetic variability of antioxidative enzymes can affect enzyme activity or expression, which modifies the ability of cells to defend themselves against oxidative stress and could consequently contribute to the occurrence of treatment-related cardiotoxicity. Our aim was to evaluate the association of common polymorphisms in antioxidative genes with cardiotoxicity after adjuvant radiotherapy (RT) in HER2-positive breast cancer patients.. Our retrospective study included 101 HER2-positive early breast cancer patients who received trastuzumab and adjuvant RT. We isolated DNA from buccal swabs and used competitive allele-specific PCR for genotyping of. Carriers of at least one polymorphic. In our study, polymorphisms

Topics: Adult; Antineoplastic Agents; Aryldialkylphosphatase; Breast Neoplasms; Cardiotoxicity; Catalase; Female; Glutathione S-Transferase pi; Heart Diseases; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Middle Aged; Natriuretic Peptide, Brain; Polymorphism, Single Nucleotide; Radiotherapy, Adjuvant; Receptor, ErbB-2; Superoxide Dismutase; Trastuzumab

Anthracycline chemotherapy (AC) is associated with acute reductions in cardiopulmonary fitness (V˙O2peak). We sought to determine whether changes in V˙O2peak and cardiac function persisted at 12 months post-AC completion, and whether changes in cardiac function explain the heightened long-term heart failure risk.. Women with breast cancer scheduled for AC (n = 28) who participated in a nonrandomized trial of exercise training (ET; n = 14) or usual care (UC; n = 14) during AC completed a follow-up evaluation 12 months post-AC completion (16 months from baseline). At baseline, 4 months, and 16 months, participants underwent a resting echocardiogram (left ventricular ejection fraction; global longitudinal strain), a blood sample (troponin; B-type natriuretic peptide), a cardiopulmonary exercise test, and cardiac MRI measures of stroke volume (SV), heart rate, and cardiac output (Qc) at rest and during intense exercise.. Seventeen women (UC, n = 8; ET, n = 9) completed evaluation at baseline, 4 months, and 16 months. At 4 months, AC was associated with 18% and 6% reductions in V˙O2peak in the UC and ET groups, respectively, which persisted at 16 months (UC, -16%; ET, -7%) and was not attenuated by ET (interaction, P = 0.10). Exercise Qc was lower at 16 months compared with baseline and 4 months (P < 0.001), which was due to a blunted augmentation of SV during exercise (P = 0.032; a 14% reduction in peak SV), with no changes in heart rate response. There was a small reduction in resting left ventricular ejection fraction (baseline to 4 months) and global longitudinal strain (between 4 and 16 months) and an increase in troponin (baseline to 4 months), but only exercise Qc was associated with V˙O2peak (R = 0.47, P < 0.01).. Marked reductions in V˙O2peak persisted 12 months after anthracycline-based chemotherapy, which was associated with impaired exercise cardiac function.. ACTRN12616001602415.

Topics: Aged; Anthracyclines; Antineoplastic Agents; Breast Neoplasms; Cardiac Output; Cardiorespiratory Fitness; Cardiotoxicity; Echocardiography; Exercise Therapy; Exercise Tolerance; Female; Heart Rate; Hemoglobins; Humans; Magnetic Resonance Imaging; Middle Aged; Natriuretic Peptide, Brain; Oxygen Consumption; Risk Factors; Stroke Volume; Troponin I

Anthracyclines are chemotherapeutic agents frequently used in breast cancer (BC) treatment. Although it improves disease-free and overall survival, the use of anthracyclines is associated with a cumulative risk of cardiac toxicity. Preventive strategies to optimize cardiac health are needed and exercise is proposed as a potential non-pharmacological approach for counteracting anthracycline-related cardiotoxicity (ARC). Most of the data on the effects of exercise to reduce ACT are from animal studies, with only a few studies in a limited number of patients indicating beneficial effects. To better understand the effectiveness of exercise in the mitigation of ARC, clinical, real-world trials claim require a larger sample size and more accurate and valuable clinical biomarkers. In this study, we intend to include a large sample and investigate cardiac function through serial measures of biomarkers and imaging techniques.. This protocol describes a two-arm, prospective, randomized controlled trial that will explore the cardioprotective effect of a structured exercise program in women with BC undergoing anthracycline-containing chemotherapy (ACT). Ninety adult women with early BC and recommended to receive ACT will be randomly assigned (1:1) to an intervention group or a control group. Patients allocated to the intervention group will perform a supervised exercise program three times per week, consisting of a combination of aerobic and resistance training with progressive intensity and volume, during the time period they receive ACT. The control group will receive standard BC care. Primary outcomes related to cardiac (dys)function will be circulating N-terminal pro-brain natriuretic peptide (NT-proBNP) levels, resting left ventricular (LV) longitudinal strain, and resting LV ejection fraction. Secondary outcomes will include the assessment of resting blood pressure, resting heart rate (HR), resting HR variability (HRV), recovery HR, physical function outcomes, self-reported physical activity level, health-related quality of life, and fatigue. Data will be obtained at baseline (t. The implementation of the present study design, using novel clinical biomarkers, will determine the effect of structured exercise interventions at mitigating ARC, with the overall aim of finding means to further improve BC care.. ISRCTN, ISRCTN32617901 . Registered on 24 October 2018. Last updated on 11 January 2019.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Breast Neoplasms; Cardiotoxicity; Female; Health Status; Heart Diseases; Hemodynamics; Humans; Natriuretic Peptide, Brain; Peptide Fragments; Portugal; Prospective Studies; Randomized Controlled Trials as Topic; Resistance Training; Risk Factors; Time Factors; Treatment Outcome; Ventricular Function, Left

Biomarkers of cardiac damages, such as troponin T (TnT) and the amino-terminal fragment of brain natriuretic peptide (NT-proBNP), may be useful as early predictors of cardiac dysfunction. The role of these biomarkers in patients receiving lapatinib and/or trastuzumab before anthracyclines is unknown. This study explores TnT and NT-proBNP as predictors of early cardiac toxicity in neoadjuvant breast cancer patients.. This sub-study of the NEOALTTO trial tested if changes in the levels of TnT and NT-proBNP occurred after 2 weeks of anti-HER2 therapy (lapatinib, trastuzumab or their combination) alone and/or after 18 weeks of anti-HER2 therapy plus weekly paclitaxel.. 173 and 172 were tested at all three timepoints for NT-proBNP and TnT, respectively. The incidence of biomarker elevation was overall low at all timepoints for all the three treatment arms. A total of 13 CEs in 11 patients occurred. Biomarker elevations in patients with CEs were very rare; only one patient with subsequent CE had a NT-proBNP elevation at baseline and at week 2.. These results suggest that TnT and proBNP may not be useful as early predictors of cardiac toxicity in anthracycline-naïve patients receiving trastuzumab and/or lapatinib.

Topics: Aged; Biomarkers; Breast Neoplasms; Cardiotoxicity; Cardiovascular Abnormalities; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Lapatinib; Middle Aged; Natriuretic Peptide, Brain; Neoplasm Staging; Paclitaxel; Receptor, ErbB-2; Trastuzumab; Troponin T

Anthracyclines are associated with cardiotoxic effects. Cardiovascular biomarkers may reflect myocardial injury, dysfunction, inflammation, and fibrosis and may precede and predict the development of left ventricular impairment. The aim of this study was to assess: (1) longitudinal change in circulating cardiovascular biomarkers, (2) the effect of metoprolol succinate and candesartan cilexetil on the biomarker response, and (3) the associations between on-treatment changes in biomarker concentrations and subsequent left ventricular dysfunction in patients with early breast cancer receiving anthracyclines.. This report encompasses 121 women included in the 2×2 factorial, placebo-controlled, double-blind PRADA (Prevention of Cardiac Dysfunction During Adjuvant Breast Cancer Therapy) trial with metoprolol and candesartan given concomitantly with anticancer therapy containing the anthracycline, epirubicin (total cumulative dose, 240-400 mg/m. Treatment with contemporary anthracycline doses for early breast cancer is associated with increase in circulating cardiovascular biomarkers. This increase is, however, not associated with early decline in ventricular function. Beta-blockade may attenuate early myocardial injury, but whether this attenuation translates into reduced risk of developing ventricular dysfunction in the long term remains unclear.. URL: http://www.clinicaltrial.gov. Unique identifier: NCT01434134.

Topics: Adrenergic beta-1 Receptor Antagonists; Adult; Angiotensin II Type 1 Receptor Blockers; Antibiotics, Antineoplastic; Benzimidazoles; Biomarkers; Biphenyl Compounds; Breast Neoplasms; Cardiotoxicity; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Epirubicin; Female; Humans; Metoprolol; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Protein Precursors; Tetrazoles; Treatment Outcome; Troponin I; Troponin T; Ventricular Dysfunction, Left

Myocardial strain imaging and blood biomarkers have been proposed as adjuncts to left ventricular ejection fraction (LVEF) monitoring for the early detection of cardiotoxicity during cancer therapy. We report the results of a preplanned cardiac safety analysis of global longitudinal strain (GLS), and troponin-I (TnI) and brain natriuretic peptide (BNP) levels in the phase II study of paclitaxel, trastuzumab, and pertuzumab (THP) for metastatic HER2-positive breast cancer.. Patients with 0-1 lines of prior therapy were treated with weekly paclitaxel (80 mg/m(2)) plus trastuzumab (8 mg/kg loading dose followed by 6 mg/kg) and pertuzumab (840 mg loading dose followed by 420 mg) every 3 weeks. Exploratory endpoints were GLS measured with speckle-tracking echocardiography every 3 months and TnI and BNP levels measured every 6 weeks (immediately pre- and postchemotherapy infusion) at 6 time points.. Sixty-seven of 69 enrolled patients were treated with THP: 19 (28%) had hypertension, 8 (12%) had diabetes, 11 (16%) had hyperlipidemia, and 26 (38%) had smoking history. After a median follow-up of 21 months (range: 3-38 months), no patients developed symptomatic heart failure. Two patients (3.0%) experienced asymptomatic LVEF decline (grade 2). The mean GLS (±SD) was 19% ± 2% (baseline), 19% ± 2% (month 6), and 19% ± 3% (month 12). Detectable TnI (>0.06 ng/mL) and elevated BNP (>100 pg/mL) levels were observed in 3 (4.3%) and 2 (3.0%) patients, respectively, but were not associated with LVEF decline.. The absence of any significant changes in GLS and cardiac biomarkers (TnI and BNP) further support the cardiac safety of THP in patients with metastatic HER2-positive breast cancer.. Dual anti-HER2 therapy with trastuzumab and pertuzumab in combination with taxane-based chemotherapy improves overall survival in patients with metastatic HER2-positive breast cancer. There is a critical need to investigate the potential cardiotoxicity of dual anti-HER2 blockade, given the importance of HER2 signaling in cardiac homeostasis and stress response. Global longitudinal strain and cardiac biomarkers have been proposed as adjuncts to left ventricular ejection fraction for the early detection of cardiotoxicity. In this phase II study of combination trastuzumab and pertuzumab with paclitaxel, no clinically significant change was observed in global longitudinal strain or cardiac biomarkers. These results further support the cardiac safety of dual anti-HER2 blockade previously reported in the CLEOPATRA study. The findings in the current study also call into question the role of intensive cardiac monitoring among patients treated with anti-HER2 therapy in the absence of anthracyclines. Less frequent cardiac assessments could lead to a reduction in unnecessary treatment interruption and is an important consideration given the rise in medical expenditures, but this requires further investigation.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal, Humanized; Breast Neoplasms; Cardiotoxicity; Female; Humans; Middle Aged; Natriuretic Peptide, Brain; Neoplasm Metastasis; Paclitaxel; Receptor, ErbB-2; Trastuzumab; Troponin I; Ventricular Function, Left

This is the first randomized placebo-controlled evaluation of a medical intervention for the prevention of trastuzumab-related cardiotoxic effects.. To determine as the primary end point whether angiotensin II antagonist treatment with candesartan can prevent or ameliorate trastuzumab-related cardiotoxic effects, defined as a decline in left ventricular ejection fraction (LVEF) of more than 15% or a decrease below the absolute value 45%.. This randomized, placebo-controlled clinical study was conducted between October 2007 and October 2011 in 19 hospitals in the Netherlands, enrolling 210 women with early breast cancer testing positive for human epidermal growth factor receptor 2 (HER2) who were being considered for adjuvant systemic treatment with anthracycline-containing chemotherapy followed by trastuzumab.. A total of 78 weeks of candesartan (32 mg/d) or placebo treatment; study treatment started at the same day as the first trastuzumab administration and continued until 26 weeks after completion of trastuzumab treatment.. The primary outcome was LVEF. Secondary end points included whether the N-terminal of the prohormone brain natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hs-TnT) can be used as surrogate markers and whether genetic variability in germline ERBB2 (formerly HER2 or HER2/neu) correlates with trastuzumab-related cardiotoxic effects.. A total of 206 participants were evaluable (mean age, 49 years; age range, 25-69 years) 103 in the candesartan group (mean age, 50 years; age range, 25-69 years) and 103 in the placebo group (mean age, 50 years; age range, 30-67 years). Of these, 36 manifested at least 1 of the 2 primary cardiac end points. There were 3.8% more cardiac events in the candesartan group than in the placebo group (95% CI, -7% to 15%; P = .58): 20 events (19%) and 16 events (16%), respectively. The 2-year cumulative incidence of cardiac events was 0.28 (95% CI, 0.13-0.40) in the candesartan group and 0.16 (95% CI, 0.08-0.22) in the placebo group (P = .56). Candesartan did not affect changes in NT-proBNP and hs-TnT values, and these biomarkers were not associated with significant changes in LVEF. The Ala1170Pro homozygous ERBB2 genotype was associated with a lower likelihood of the occurrence of a cardiac event compared with Pro/Pro + Ala/Pro genotypes in multivariate analysis (odds ratio, 0.09; 95% CI, 0.02-0.45; P = .003).. The findings do not support the hypothesis that concomitant use of candesartan protects against a decrease in left ventricular ejection fraction during or shortly after trastuzumab treatment in early breast cancer. The ERBB2 germline Ala1170Pro single nucleotide polymorphism may be used to identify patients who are at increased risk of trastuzumab-related cardiotoxic effects.. clinicaltrials.gov Identifier: NCT00459771.

Topics: Adult; Aged; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Antineoplastic Agents; Benzimidazoles; Biphenyl Compounds; Breast Neoplasms; Cardiotoxicity; Chemotherapy, Adjuvant; Double-Blind Method; Echocardiography; Female; Genetic Variation; Genotype; Humans; Middle Aged; Multivariate Analysis; Natriuretic Peptide, Brain; Neoplasm Staging; Netherlands; Odds Ratio; Peptide Fragments; Polymorphism, Single Nucleotide; Receptor, ErbB-2; Stroke Volume; Tetrazoles; Trastuzumab; Troponin T; Ventricular Function, Left

Anthracycline-induced cardiotoxicity is (partly) mediated by free radical overload. A randomized study was performed in breast cancer patients to investigate whether free radical scavenger super oxide dismutase (SOD) protects against anthracycline-induced cardiotoxicity as measured by changes in echo, electrocardiography and an array of biomarkers.. Eighty female, chemotherapy-naïve breast cancer patients (median age 49, range 24-67 years) scheduled for four or five courses of adjuvant 3 weekly doxorubicin plus cyclophosphamide (AC) chemotherapy, were randomly assigned to receive 80 mg PC-SOD (human recombinant SOD bound to lecithin) or placebo, administered intravenously (i.v.) immediately prior to each AC course. The primary end point was protection against cardiac damage evaluated using echocardiography, QT assessments and a set of biochemical markers for myocardial function, oxidative stress and inflammation. Assessments were performed before and during each course of chemotherapy, and at 1, 4 and 9 months after completion of the chemotherapy regimen. In all patients cardiac effects such as increases in NT-proBNP concentration and prolongation of the QTc interval were noticed. There were no differences between the PC-SOD and placebo-treated patients in systolic or diastolic cardiac function or for any other of the biomarkers used to assess the cardiac effects of anthracyclines.. PC-SOD at a dose of 80 mg i.v. is not cardioprotective in patients with breast carcinoma treated with anthracyclines.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Breast Neoplasms; Cardiotonic Agents; Cardiotoxicity; Cyclophosphamide; Doxorubicin; Drug Administration Schedule; Echocardiography; Electrocardiography; Female; Free Radical Scavengers; Humans; Injections, Intravenous; Middle Aged; Natriuretic Peptide, Brain; Netherlands; Peptide Fragments; Phosphatidylcholines; Superoxide Dismutase; Young Adult

Cardiotoxicity represents a major limitation for the use of anthracyclines or trastuzumab in breast cancer patients. Data on longitudinal studies about early and late onset cardiotoxicity in this group of patients is scarce. The objective of the present study was to assess predictors of early and late onset cardiotoxicity in patients with breast cancer treated with A.. 100 consecutive patients receiving anthracycline-based chemotherapy (CHT) to treat breast cancer were included in this prospective study. All patients underwent evaluation at baseline, at the end of CHT, 3 months after the end of CHT and 1 and 4 years after the beginning of CHT. Clinical data, systolic and diastolic echo parameters and cardiac biomarkers including high sensitivity Troponin T (TnT), N-terminal pro-brain natriuretic peptide (NT-proBNP) and Heart-type fatty acid binding protein (H-FABP) were assessed.. Mean doxorubicin dose was 243 mg/m2. Mean follow-up was 51.8 ± 8.2 months. At one-year incidence of anthracycline related-cardiotoxicity (AR-CT) was 4% and at the end of follow-up was 18% (15 patients asymptomatic left ventricular systolic dysfunction, 1 patients heart failure and 2 patients a sudden cardiac death). Forty-nine patients developed diastolic dysfunction (DD) during first year. In the univariate analysis DD during first year was the only parameter associated with AR-CT (Table 1). In the logistic regression model DD was independently related with the development of AR-CT, with an odds ratio value of 7.5 (95% CI 1.59-35.3).. Incidence of late-onset cardiotoxicity is high but mostly subclinical. Diastolic dysfunction early after chemotherapy is a strong predictor of anthracycline cardiotoxicity.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Breast Neoplasms; Cardiomyopathies; Cardiotoxicity; Female; Humans; Incidence; Natriuretic Peptide, Brain; Prospective Studies

Topics: Anthracyclines; Breast Neoplasms; Cardiotoxicity; Chemotherapy, Adjuvant; Female; Humans; Natriuretic Peptide, Brain; Stroke Volume

The indications for immune checkpoint inhibitors (ICIs) are expanding in cancer drug therapy, and while cardiac events associated with ICIs are often fatal, there are few reports regarding cardiac complications associated with long-term ICI therapy. We aimed to study cardiac complications in patients undergoing long-term ICI therapy. From the database of our local cardio-oncology unit, we enrolled patients with cancer undergoing ICI therapy for more than 6 months and for whom cardiologists continuously performed routine follow-ups. We defined the primary endpoint as discontinuation of ICI due to cardiac events. We also analyzed changes in cardiac biomarkers and echocardiographic parameters. We retrospectively analyzed 55 consecutive patients (43 males, mean age: 65 ± 11 years) treated with ICI therapy in our hospital between January 2017 and June 2021. None of the patients discontinued ICI therapy due to cardiac events more than 6 months after treatment was initiated. Among the participants, we observed four patients with elevated serum troponin I levels, seven patients with decreased global longitudinal strain values, and two patients with elevated plasma brain natriuretic peptide levels. No patient required drug intervention for these cardiac events; furthermore, there were no cases of clinically diagnosed myocarditis. In the present study, there were no cardiac events causing ICI discontinuation in patients undergo ICI therapy for more than 6 months.

Topics: Aged; Antineoplastic Agents, Immunological; Biomarkers; Cardiotoxicity; Female; Humans; Immune Checkpoint Inhibitors; Male; Middle Aged; Myocarditis; Natriuretic Peptide, Brain; Retrospective Studies; Troponin I

Myocardial toxicity is a common side effect of doxorubicin (DOXO) therapy in breast cancer patients. We hypothesized that DOXO-induced cardiotoxicity may be related to the release of inflammatory cytokines in response to the treatment. This study aimed to assess changes in plasma levels of interleukin (IL)-1β, IL-6, IL-10 and tumor necrosis factor (TNF) after chemotherapy and to correlate these levels with cardiac biomarkers and clinical data.. Sixty-four patients with breast cancer treated with DOXO were included. Twenty-two subjects (cases) developed cardiotoxicity until one year after the end of DOXO treatment. Cytokines and cardiac markers were evaluated before starting chemotherapy (T0), up to 7 days after the last infusion (T1) and 12 months after the last infusion (T2).. Higher IL-10 levels were observed in the case group compared to controls at T1 (. Our study demonstrated that DOXO induced an increase in plasma IL-10 levels in patients who presented cardiotoxicity after treatment, which correlated with NT-proBNP levels.

Topics: Biomarkers; Breast Neoplasms; Cardiotoxicity; Doxorubicin; Female; Follow-Up Studies; Humans; Interleukin-10; Natriuretic Peptide, Brain; Peptide Fragments

Today, cancer ranks as one of the leading causes of death. Despite the large number of novel available therapies, radiotherapy (RT) remains as the most effective non-surgical method to cure cancer patients. In fact, approximately 50% of all cancer patients receive some type of RT and among these 60% receive RT-treatment with a curative intent. However, as occurs with any other oncological therapy, RT treated patients may experience toxicity side effects that range from moderate to severe. Among these, cardiotoxicity represents a significant threat for premature death. Current methods evaluate cardiotoxic damage based on volumetric changes in the Left Ventricle Ejected Fraction (LVEF). Indeed, a 10% drop in LVEF is commonly used as indicator of cardiotoxicity. More recently, a number of novel techniques have been developed that significantly improve specificity and sensitivity of heart's volumetric changes and early detection of cardiotoxicity even in asymptomatic patients. Among these, the Strain by Speckle Tracking (SST) is a technique based on echocardiographic analysis that accurately evaluates myocardial deformation during the cardiac cycle (ventricular and atrial function). Studies also suggest that Magnetic Resonance Imaging (MRI) is a high-resolution technique that enables a better visualization of acute cardiac damage.. This protocol will evaluate changes in SST and MRI in cancer patients that received thoracic RT. Concomitantly, we will assess changes in serum biomarkers of cardiac damage in these patients, including: high-sensitivity cardiac Troponin-T (hscTnT), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) and Circulating Endothelial Cells (CECs), a marker of endothelial dysfunction and vascular damage.. The presented protocol is to our knowledge the first to prospectively and with a multimodal approach, study serological and image biomarkers off early cardiac damage due to radiotherapy. With a practical clinical approach we will seek early changes that could potentially be in the future be linked to clinical mayor events with consequences for cancer survivors.

Topics: Breast Neoplasms; Cardiotoxicity; Clinical Protocols; Echocardiography; Endothelial Cells; Esophageal Neoplasms; Female; Humans; Lung Neoplasms; Magnetic Resonance Imaging; Male; Myocardial Contraction; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Radiation Dosage; Radiation Injuries; Stroke Volume; Troponin T; Ventricular Dysfunction, Left

Rapid development of anticancer treatments in recent years has greatly improved prognosis of cancer patients. However, with extension of survival time of cancer patients, various short-term and long-term side effects brought about by anticancer treatments, especially cardiotoxicity, have become increasingly prominent. Nonetheless, at present, there is few diagnostic methods with extremely high sensitivity and specificity to detect and accurately predict whether patients with anticancer treatment will experience cardiovascular complications. Inflammation, fibrosis and oxidative stress are considered to be important mechanisms involved in cardiotoxicity anticancer treatments. The cardiovascular biomarkers having the ability to predict and detect cardiovascular dysfunction earlier than clinical symptoms as well as left ventricular ejection fraction monitored by echocardiography, are of great value to timely treatment adjustment and prognosis evaluation. Cardiac troponin T/I and brain natriuretic peptide/N-terminal prohormone of brain natriuretic peptide have been routinely used in clinical practice to monitor cardiotoxicity, and some new biomarkers such as soluble suppression of tumorigenecity-2, myeloperoxidase, growth differentiation factor-15, galectin-3, endothelin-1, have potential in this area. In the future, larger-scale experimental studies are needed to provide sufficient evidences, and how to detect them quickly and at low cost is also a problem to be dealed with.

Topics: Biomarkers; Cardiotoxicity; Humans; Natriuretic Peptide, Brain; Stroke Volume; Ventricular Function, Left

To assess acute cardiac toxicity caused by intraoperative radiotherapy (IORT) with low-energy x‑rays for early breast cancer.. We prospectively analyzed pre- and postoperative troponin I and NT-proBNP in 94 women who underwent breast-conserving surgery between 2013 and 2017 at the Department of Gynecology and Obstetrics of the University Medical Center Mannheim, Germany. Thirty-nine women received IORT using low-energy x‑rays during breast-conserving surgery while 55 patients without IORT formed the control group. Demographic and surgical parameters as well as cardiac markers were evaluated.. There were no significant differences concerning age and side of breast cancer between the groups. Furthermore, no significant difference between the troponin I assays of the IORT and control groups could be found (preoperatively: 0.017 ± 0.006 ng/ml vs. 0.018 ± 0.008 ng/ml; p = 0.5105; postoperatively: 0.019 ± 0.012 ng/ml vs. 0.018 ± 0.010 ng/ml; p = 0.6225). N‑terminal fragment of B‑type natriuretic peptide (NT-proBNP) was significantly higher in the control group 24 h after surgery (preoperatively: 158.154 ± 169.427 pg/ml vs. 162.109 ± 147.343 pg/ml; p = 0.56; postoperatively: 168.846 ± 160.227 pg/ml vs. 232.527 ± 188.957 pg/ml; p = 0.0279).. Troponin I levels as a marker of acute cardiac toxicity did not show any significant differences in patients who received IORT during breast-conserving surgery compared to those who did not.

Topics: Aged; Biomarkers; Breast Neoplasms; Cardiomyopathies; Cardiotoxicity; Female; Humans; Intraoperative Care; Mastectomy, Segmental; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Radiotherapy, Adjuvant; Troponin I

Accidental bromine spills are common and its large industrial stores risk potential terrorist attacks. The mechanisms of bromine toxicity and effective therapeutic strategies are unknown. Our studies demonstrate that inhaled bromine causes deleterious cardiac manifestations. In this manuscript we describe mechanisms of delayed cardiac effects in the survivors of a single bromine exposure. Rats were exposed to bromine (600 ppm for 45 min) and the survivors were sacrificed at 14 or 28 days. Echocardiography, hemodynamic analysis, histology, transmission electron microscopy (TEM) and biochemical analysis of cardiac tissue were performed to assess functional, structural and molecular effects. Increases in right ventricular (RV) and left ventricular (LV) end-diastolic pressure and LV end-diastolic wall stress with increased LV fibrosis were observed. TEM images demonstrated myofibrillar loss, cytoskeletal breakdown and mitochondrial damage at both time points. Increases in cardiac troponin I (cTnI) and N-terminal pro brain natriuretic peptide (NT-proBNP) reflected myofibrillar damage and increased LV wall stress. LV shortening decreased as a function of increasing LV end-systolic wall stress and was accompanied by increased sarcoendoplasmic reticulum calcium ATPase (SERCA) inactivation and a striking dephosphorylation of phospholamban. NADPH oxidase 2 and protein phosphatase 1 were also increased. Increased circulating eosinophils and myocardial 4-hydroxynonenal content suggested increased oxidative stress as a key contributing factor to these effects. Thus, a continuous oxidative stress-induced chronic myocardial damage along with phospholamban dephosphorylation are critical for bromine-induced chronic cardiac dysfunction. These findings in our preclinical model will educate clinicians and public health personnel and provide important endpoints to evaluate therapies.

Topics: Animals; Bromine; Calcium-Binding Proteins; Cardiomegaly; Cardiotoxicity; Diastole; Disease Models, Animal; Fibrosis; Male; Mitochondria, Heart; Myocardium; NADPH Oxidase 2; Natriuretic Peptide, Brain; Oxidative Stress; Peptide Fragments; Phosphorylation; Protein Phosphatase 1; Rats, Sprague-Dawley; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Systole; Time Factors; Troponin I; Ventricular Dysfunction, Left; Ventricular Dysfunction, Right; Ventricular Function, Left; Ventricular Function, Right; Ventricular Remodeling

To evaluate, in a series of early breast cancer (BC) patients treated with hypofractionated adjuvant radiotherapy (RT), whether N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I assay measurements can predict acute clinical or preclinical cardiotoxicity.. The study comprised 44 consecutive patients, who underwent conservative surgery with or without (neo)adjuvant chemotherapy and hypofractionated adjuvant RT. The RT schedule consisted in a total dose of 42.4 Gy in 16 fractions administered 5 days per week. Twenty-one patients received a subsequent boost to the tumor bed consisting of a total dose of 10 Gy in 4 fractions delivered via a direct electron field. All patients underwent 12-lead electrocardiogram, echocardiogram, and cardiac clinical examinations before RT to assess cardiovascular risk factors; these examinations were repeated yearly for 5 consecutive years. High-sensitivity cardiac troponin I and NT-proBNP were analyzed from serum samples at baseline, after delivery of the fourth and 16th RT fractions, and 12 months after treatment completion.. No increase in cardiac troponin I and B-type natriuretic peptide levels related to left breast irradiation was observed. No statistical difference in NT-proBNP and high-sensitivity troponin I levels between left- and right-sided BC was found. An increase was observed of B-type natriuretic peptide levels at baseline, during treatment, and until 12 months after RT related to hypertension, with the P value near to the .05 threshold for age and chemotherapy.. Conformational hypofractionated RT in left-sided BC may not cause acute myocardial damage. Early cardiac screening may be used to identify patients with cardiologic risk factors, patients who are older than 60 years, and patients who received chemotherapy that could result in clinically relevant cardiac pathologies.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Cardiotoxicity; Chemotherapy, Adjuvant; Female; Heart; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Radiation Dose Hypofractionation; Unilateral Breast Neoplasms

This prospective study was conducted to evaluate the clinical reliability of N-terminal fragment of proB-type natriuretic peptide (NT-proBNP) in identifying patients with cardiotoxicity in the early hours following scorpion sting.. This study involved 483 children aging between 2-17 years who were admitted to Minia University Poisoning Control Center from 1st January 2010 to 31st December 2019 with a history of scorpion sting, and on clinical evaluation symptoms were manifested. All subjects were clinically examined, investigated for NT-proBNP and CPK-MB on admission, 6 h and 24 h post-envenomation; and subjected to 24 h cardiac monitoring with periodic ECG every 6 h.. Assessment of CPK-MB levels showed a significant increase in all moderate to severe cases 6 h post-envenomation. Assessment of NT-proBNP levels showed a significant increase in all moderate to severe cases on admission and 6 h post-envenomation. Moreover, there was a significant decrease in the NT-proBNP level after 24 h compared with that measured on admission. The sensitivity of NT-proBNP for the diagnosis of myocardial injury at hospital admission was significantly higher than that of CPK-MB.. NT-proBNP may be a valuable and sensitive laboratory biomarker to predict cardiotoxicity of scorpion sting in the early hours.

Topics: Adolescent; Age Factors; Biomarkers; Cardiotoxicity; Child; Child, Preschool; Egypt; Female; Humans; Male; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Scorpion Stings; Scorpion Venoms; Symptom Assessment

Survivors of childhood cancer exposed to cardiotoxic therapies are at significant cardiovascular risk. The utility of cardiac biomarkers for identifying the risk of future cardiomyopathy and mortality is unknown.. N-terminal pro-B-type natriuretic peptide (NT-proBNP) and cardiac troponin T (cTnT) were assessed in 1213 adults 10 or more years from a childhood cancer diagnosis; 786 were exposed to anthracycline chemotherapy and/or chest-directed radiation therapy (RT). NT-proBNP values above age- and sex-specific 97.5th percentiles were considered abnormal. Generalized linear models estimated cross-sectional associations between abnormal NT-proBNP and anthracycline or chest RT doses as risk ratios with 95% confidence intervals (CIs). A Poisson distribution estimated rates and a Cox proportional hazards model estimated hazard ratios (HRs) for future cardiac events and death.. At a median age of 35.5 years (interquartile range, 29.8-42.5 years), NT-proBNP and cTnT were abnormal in 22.5% and 0.4%, respectively. Exposure to chest RT and exposure to anthracycline chemotherapy were each associated with a dose-dependent increased risk for abnormal NT-proBNP (P for trend <.0001). Among exposed survivors with no history of Common Terminology Criteria for Adverse Events-graded cardiomyopathy and with normal systolic function, survivors with abnormal NT-proBNP had higher rates per 1000 person-years of cardiac mortality (2.93 vs 0.96; P < .0001) and future cardiomyopathy (32.10 vs 15.98; P < .0001) and an increased risk of future cardiomyopathy (HR, 2.28; 95% CI, 1.28-4.08) according to a multivariable assessment.. Abnormal NT-proBNP values were prevalent and, among survivors who were exposed to cardiotoxic therapy but did not have a history of cardiomyopathy or current systolic dysfunction, identified those at increased risk for future cardiomyopathy. Further longitudinal studies are needed to confirm this novel finding.

Topics: Adult; Biomarkers; Cancer Survivors; Cardiomyopathies; Cardiotoxicity; Child; Cohort Studies; Female; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Troponin T; Young Adult

Our goal was to evaluate the ability of cardiovascular magnetic resonance for detecting and predicting cardiac dysfunction in patients receiving cancer therapy. Left ventricular ejection fraction, global and regional strain utilizing fast-strain-encoded, T1 and T2 mapping, and cardiac biomarkers (troponin and BNP [brain natriuretic peptide]) were analyzed.. Sixty-one patients (47 with breast cancer, 11 with non-Hodgkin lymphoma, and 3 with Hodgkin lymphoma) underwent cardiovascular magnetic resonance scans at baseline and at regular intervals during 2 years of follow-up. The percentage of all left ventricular myocardial segments with strain ≤-17% (normal myocardium [%]) was analyzed. Clinical cardiotoxicity (CTX) and sub-CTX were defined according to standard measures.. Nine (15%) patients developed CTX, 26 (43%) had sub-CTX. Of the 35 patients with CTX or sub-CTX, 24 (69%) were treated with cardioprotective medications and showed recovery of cardiac function. The amount of normal myocardium (%) exhibited markedly higher accuracy for the detection of CTX and sub-CTX compared with left ventricular ejection fraction, T1, and T2 mapping as well as troponin I (Δareas under the curve=0.20, 0.24, and 0.46 for normal myocardium (%) versus left ventricular ejection fraction, troponin I, and T1 mapping,. Normal myocardium (%) derived by fast-strain-encoded cardiovascular magnetic resonance, is an accurate and sensitive tool that can establish cardiac safety in patients with cancer undergoing cardiotoxic chemotherapy not only for the early detection but also for the prediction of those at risk of developing CTX. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03543228.

Topics: Aged; Antineoplastic Agents; Biomarkers; Breast Neoplasms; Cardiotoxicity; Early Diagnosis; Female; Follow-Up Studies; Heart Diseases; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Myocardial Contraction; Natriuretic Peptide, Brain; Predictive Value of Tests; Prospective Studies; Time Factors; Troponin I; Ventricular Function, Left

Arbutin is a glycoside reported for its anti-oxidant, anti-inflammatory and anti-tumor properties. However, the cardioprotective effect of Arbutin is not well established. The study aims to understand the effect of arbutin on isoproterenol (ISO)-induced cardiac hypertrophy in mice. The animals were pretreated with Arbutin for a week and ISO was administered for 10 days and then sacrificed. Cardiac injury markers such as creatinine kinase and lactate dehydrogenase concentrations were measured in the serum. The mRNA expression of cardiac hypertrophy markers namely atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were measured using qRT-PCR. The levels of pro-inflammatory cytokines TNF-α and IL-6 were quantified by ELISA in isolated tissues and serum. Other tissue anti-oxidant parameters such as GST, GSH, SOD and TBARS were also measured. TUNEL assay was performed to detect apoptosis. Histology studies were performed using H & E and Masson trichome staining. Immunoblot analysis was used to quantify the protein expression of TLR-4 and NF-κB. ISO-alone-treated group showed significant increase in CK-MB, LDH along with increase in hypertrophic markers ANP and BNP, TNF-α and IL-6 levels in serum and tissues and increased cardiomyocyte apoptosis. Anti-oxidant parameters were significantly decreased and TLR-4 and NF-κB protein expression was found to be upregulated in comparison to the control group. Pretreatment with Arbutin-exhibited significant inhibition of TLR-4/NF-κB pathway with decreased levels of pro-inflammatory cytokines and enhanced myocardial anti-oxidant status. Our study demonstrated that pretreatment with Arbutin exhibits marked protective effects on ISO-induced cardiac hypertrophy in mice. Thus, Arbutin may be used as potential pharmacological interventions in the management of cardiac hypertrophy.

Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Arbutin; Atrial Natriuretic Factor; Cardiomegaly; Cardiotoxicity; Disease Models, Animal; Interleukin-6; Isoproterenol; Male; Mice, Inbred C57BL; Myocytes, Cardiac; Natriuretic Peptide, Brain; NF-kappa B; Oxidative Stress; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha; Ventricular Remodeling

Pregabalin (PRG) possesses great therapeutic benefits in the treatment of epilepsy, neuropathic pain, and fibromyalgia. However, clinical data have reported incidence or exacerbation of heart failure following PRG administration. Experimental data exploring cardiac alterations and its underlying mechanisms are quite scarce. The aim of the present work was to investigate the effect of PRG on morphometric, echocardiographic, neurohumoral, and histopathological parameters in rats. It was hypothesized that alterations in cardiac renin angiotensin system (RAS) might be involved in PRG-induced cardiotoxicity. To further emphasize the role of RAS in the mechanism of PRG-induced cardiotoxicity, the protective potential of diminazene aceturate (DIZE), an ACE2 activator, was investigated. Results showed 44% decrease in ejection fraction and sevenfold increase in plasma N-terminal pro-brain natriuretic peptide. Histopathological examination also showed prominent vacuolar changes and edema in cardiomyocytes. In addition, PRG significantly increased angiotensin II (Ang II), angiotensin converting enzyme (ACE) and angiotensin II type 1 receptor (AT1R) levels, while decreased angiotensin 1-7 (Ang 1-7), angiotensin converting enzyme 2 (ACE2), and Mas receptor (MasR) cardiac levels. DIZE co-administration showed prominent protection against PRG-induced echocardiographic, neurohumoral, and histopathological alterations in rats. In addition, downregulation of ACE/Ang II/AT1R and upregulation of ACE2/Ang 1-7/MasR axes were noted in DIZE co-treated rats. These findings showed, for the first time, the detailed cardiac deleterious effects of PRG in rats. The underlying pathophysiological mechanism is probably mediated via altered balance between the RAS axes in favor to the ACE/Ang II/AT1R pathway. Accordingly, ACE2 activators might represent promising therapeutic agents for PRG-induced cardiotoxicity.

Topics: Angiotensin I; Angiotensin II; Angiotensin-Converting Enzyme 2; Animals; Biomarkers; Cardiotoxicity; Cyclic AMP-Dependent Protein Kinases; Heart Diseases; Male; Myocytes, Cardiac; Natriuretic Peptide, Brain; Peptide Fragments; Peptidyl-Dipeptidase A; Phosphatidylinositol 3-Kinase; Pregabalin; Proto-Oncogene Mas; Proto-Oncogene Proteins; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Receptors, G-Protein-Coupled; Renin-Angiotensin System; Signal Transduction; Stroke Volume; Ventricular Function, Left

The purpose of this study was to investigate the effect of the temporal and observer variability of cardiac magnetic resonance (CMR)-measured native T. Biomarkers and serial quantitative CMR tissue characterization may help identify early myocardial changes of CTRCD, but these parameters require both accuracy and reliability.. A total of 50 participants (age 48.9 ± 12.1 years) underwent 3 CMR studies (1.5-T) and biomarker measurements (high-sensitivity troponin-I and B-type natriuretic peptide) at 3-month intervals: 20 with HER2-positive breast cancer (10 with and 10 without CTRCD), and 30 prospectively recruited healthy participants. T. The temporal changes in both biomarkers and tissue characterization measures in individual patients overlap with the temporal variability in healthy participants and approach the minimal detectable temporal differences. While the accuracy of the parameters awaits further study, the temporal variability of these methods may pose challenges to routine clinical application in individual patients receiving cancer therapy.

Topics: Adult; Anthracyclines; Antineoplastic Agents; Biomarkers; Breast Neoplasms; Cardiotoxicity; Case-Control Studies; Female; Heart Diseases; Humans; Magnetic Resonance Imaging, Cine; Male; Middle Aged; Natriuretic Peptide, Brain; Observer Variation; Predictive Value of Tests; Prospective Studies; Reproducibility of Results; Time Factors; Trastuzumab; Troponin I

Background We examined the longitudinal associations between changes in cardiovascular biomarkers and cancer therapy-related cardiac dysfunction (CTRCD) in patients with breast cancer treated with cardotoxic cancer therapy. Methods and Results Repeated measures of high-sensitivity cardiac troponin T (hs-cTnT), NT-proBNP (N-terminal pro-B-type natriuretic peptide), myeloperoxidase, placental growth factor, and growth differentiation factor 15 were assessed longitudinally in a prospective cohort of 323 patients treated with anthracyclines and/or trastuzumab followed over a maximum of 3.7 years with serial echocardiograms. CTRCD was defined as a ≥10% decline in left ventricular ejection fraction to a value <50%. Associations between changes in biomarkers and left ventricular ejection fraction were evaluated in repeated-measures linear regression models. Cox regression models assessed the associations between biomarkers and CTRCD. Early increases in all biomarkers occurred with anthracycline-based regimens. hs-cTnT levels >14 ng/L at anthracycline completion were associated with a 2-fold increased CTRCD risk (hazard ratio, 2.01; 95% CI, 1.00-4.06). There was a modest association between changes in NT-proBNP and left ventricular ejection fraction in the overall cohort; this was most pronounced with sequential anthracycline and trastuzumab (1.1% left ventricular ejection fraction decline [95% CI, -1.8 to -0.4] with each NT-proBNP doubling). Increases in NT-proBNP were also associated with CTRCD (hazard ratio per doubling, 1.56; 95% CI, 1.32-1.84). Increases in myeloperoxidase were associated with CTRCD in patients who received sequential anthracycline and trastuzumab (hazard ratio per doubling, 1.28; 95% CI, 1.04-1.58). Conclusions Cardiovascular biomarkers may play an important role in CTRCD risk prediction in patients with breast cancer who receive cardiotoxic cancer therapy, particularly in those treated with sequential anthracycline and trastuzumab therapy. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT01173341.

Topics: Adult; Anthracyclines; Antibiotics, Antineoplastic; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Breast Neoplasms; Cardiotoxicity; Female; Growth Differentiation Factor 15; Heart Disease Risk Factors; Heart Diseases; Humans; Longitudinal Studies; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Peroxidase; Placenta Growth Factor; Predictive Value of Tests; Prospective Studies; Risk Assessment; Time Factors; Trastuzumab; Troponin T

Doxorubicin is a widely used anticancer drug that causes dose-related cardiotoxicity. The exact mechanisms of doxorubicin toxicity are still unclear, partly because most in vitro studies have evaluated the effects of short-term high-dose doxorubicin treatments. Here, we developed an in vitro model of long-term low-dose administration of doxorubicin utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Moreover, given that current strategies for prevention and management of doxorubicin-induced cardiotoxicity fail to prevent cancer patients developing heart failure, we also investigated whether the GATA4-targeted compound 3i-1000 has cardioprotective potential against doxorubicin toxicity both in vitro and in vivo. The final doxorubicin concentration used in the chronic toxicity model in vitro was chosen based on cell viability data evaluation. Exposure to doxorubicin at the concentrations of 1-3 µM markedly reduced (60%) hiPSC-CM viability already within 48 h, while a 14-day treatment with 100 nM doxorubicin concentration induced only a modest 26% reduction in hiPCS-CM viability. Doxorubicin treatment also decreased DNA content in hiPSC-CMs. Interestingly, the compound 3i-1000 attenuated doxorubicin-induced increase in pro-B-type natriuretic peptide (proBNP) expression and caspase-3/7 activation in hiPSC-CMs. Moreover, treatment with 3i-1000 for 2 weeks (30 mg/kg/day, i.p.) inhibited doxorubicin cardiotoxicity by restoring left ventricular ejection fraction and fractional shortening in chronic in vivo rat model. In conclusion, the results demonstrate that long-term exposure of hiPSC-CMs can be utilized as an in vitro model of delayed doxorubicin-induced toxicity and provide in vitro and in vivo evidence that targeting GATA4 may be an effective strategy to counteract doxorubicin-induced cardiotoxicity.

Topics: Animals; Antibiotics, Antineoplastic; Cardiotoxicity; Caspases, Effector; Cell Line; Cell Survival; Disease Models, Animal; Doxorubicin; GATA4 Transcription Factor; Heart Diseases; Humans; Induced Pluripotent Stem Cells; Male; Myocytes, Cardiac; Natriuretic Peptide, Brain; Protective Agents; Protein Precursors; Rats, Sprague-Dawley; Rats, Wistar; Signal Transduction; Stroke Volume; Time Factors; Ventricular Function, Left

Topics: Biomarkers; Brain; Cardiotoxicity; Heart Failure; Humans; Natriuretic Peptide, Brain; Neoplasms; Troponin

Anthracycline is used to treat various types of cancer; however, cardiotoxicity negatively affects patient prognosis.. The aim of the present study was to investigate serial changes in levels of cardiac troponin I (TnI) and B-type natriuretic peptide (BNP) in patients treated with anthracycline-containing therapy.. 91 consecutive cancer patients planned for anthracycline treatment were enrolled and followed up for 12 months. All patients underwent echocardiography and blood sampling at baseline, 3, 6, and 12 months.. The patients were divided into two groups based on their TnI level during the follow-up period: the elevated TnI group (TnI ≥0.03 ng/mL; n = 37) and the normal TnI group (n = 54). In the elevated TnI group, the TnI levels increased at 3 and 6 months, but they returned to within normal range at 12 months after anthracycline administration. Unlike TnI, the BNP levels began to increase after 6 months, and remained increased at 12 months. The occurrence of cancer therapeutics-related cardiac dysfunction was higher in the elevated TnI group than in the normal TnI group. When we set the cut-off value of TnI at 0.029 ng/mL, sensitivity and specificity to predict an elevated BNP level of more than 100 pg/mL were 90 and 63%, respectively. Multivariate logistic regression analysis revealed that elevated TnI was an independent predictor of elevated BNP levels.. Elevated TnI was an independent predictor for the development of BNP increase. The different characteristics of TnI and BNP should be considered when managing patients treated with anthracycline-containing therapy.

Topics: Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Cardiotoxicity; Echocardiography; Female; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Predictive Value of Tests; Troponin I

To demonstrate the usefulness of N-Terminal Pro-B-Type natriuretic peptide (NT-proBNP) as an early biomarker of carbon monoxide-induced myocardial injury in children. It also aimed to identify the correlation between NT-proBNP and left ventricular systolic dysfunction findings shown by echocardiography.. Prospective, observational study conducted at a paediatric emergency department between October 2017 and April 2019 which involved children aged 0-17 years. The patients were divided into three groups based on severity; mild, moderate and severe groups. The patient characteristics, carboxyhaemoglobin, CK-MB Mass (CKMB-M), troponin-T, and NT-proBNP levels were measured, and echocardiography was performed and left ventricular ejection fraction was measured.. Sixty-nine patients and 60 healthy controls were included. Male gender, younger age, higher carboxyhaemoglobin levels, and altered mental status were found as independent predictors of carbon monoxide-induced myocardial injury. If the cut-off value for NT-proBNP level is >480 pg/ml, the sensitivity-specificity for decreased left ventricular ejection fraction, which is the strongest carbon monoxide-induced myocardial injury sign, were 100-96%, respectively. A high negative correlation was found between NT-proBNP levels and left ventricular ejection fraction (r = -0.769, p < 0.01) in the carbon monoxide poisoning group, and there was a positive correlation between the carboxyhaemoglobin and NT-proBNP levels (r = 0.583, p < 0.01).. Echocardiography is an ideal tool and very sensitive, but its routine use is limited due to its non-availability. An increased level of NT-proBNP (>480pg/ml) may be useful as an ideal biomarker for early detection of carbon monoxide-induced myocardial injury sign and reduced left ventricular ejection fraction which is the most crucial point in making a decision on hyperbaric oxygen therapy.

Topics: Biomarkers; Carbon Monoxide Poisoning; Cardiotoxicity; Child; Echocardiography; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Stroke Volume; Ventricular Dysfunction, Left; Ventricular Function, Left

Due to growing long-term survival rate of oncologic patients, there is increased interest in cardiotoxicity of oncologic treatment among medical professionals. It is concerning both paediatric and adult patients. When prescribing oncologic treatment, there should be focus on the efficacy and safety of the used drugs. Nowadays, the main problem is early dia-gnosis of cardiotoxicity.. In our work we wanted to investigate whether the increase in bio-markers after the cytostatic therapy with anthracyclines can predict further increase in the left ventricular volume and decrease of the left ventricular ejection fraction.. We were monitoring 36 patients with the dia-gnosis of non-Hodgkins lymphoma who received therapy with anthracyclines. After the therapy we were measuring the cardiac bio-markers NT-proBNP and high-sensitivity troponin I and performed echocardiography.. In our group of patients there is a statistically significant correlation between increased levels of troponin I, NT-proBNP and increment of the left ventricular volume measured before the treatment and 3 months after the treatment. There is also a significant inverse correlation between the left ventricular volume and left ventricular ejection fraction. There was no relationship between higher cumulative doses of anthracyclines and the increment of the left ventricular volume. There is a significant correlation between higher cumulative doses of anthracyclines and higher levels of troponin I.. The measurement of bio-markers troponin I and NT-proBNP should be considered for an early dia-gnosis of cardiotoxicity in oncologic patients. Echocardiography is also beneficial for the dia-gnosis in these patients. All efforts after the dia-gnosis should be focused on the therapy with cardioprotective drugs, which can prevent the development of severe heart failure.

Topics: Anthracyclines; Antineoplastic Agents; Cardiotoxicity; Cytostatic Agents; Heart; Humans; Lymphoma, Non-Hodgkin; Natriuretic Peptide, Brain; Peptide Fragments; Troponin I

Trastuzumab is a drug used in HER2-positive breast cancer that increases patient survival. Due to cardiotoxicity is the most important side effect of trastuzumab treatment, cardiac monitoring should be a priority. The purpose of this study is to evaluate plasma NT-proBNP level and major cardiovascular risk factors as possible early predictors of trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients.. We conducted a retrospective observational study involving 66 patients with HER2-positive breast cancer treated with trastuzumab. Left ventricle ejection fraction (LVEF), NT-proBNP values, and the history of cardiovascular risk factors were collected. Cardiotoxicity was diagnosed considering a decrease of the LVEF from baseline or clinical manifestation of congestive heart failure. NT-proBNP cut-off points were considered to establish normal or abnormal values according to patient age.. 27.3% of the patients suffered cardiotoxicity during trastuzumab treatment. Most cases were diagnosed due to the appearance of cardiac symptomatology (66.7%). Logistic regression analysis showed a significant association of diabetes mellitus (OR 5.9, 95% CI 1.2-28.5, p = 0.028) and high NT-proBNP levels (OR 22.0, 95% CI 5.7-85.4, p < 0.0001) with the development of trastuzumab-induced cardiotoxicity.. NT-proBNP levels above the upper limit of the normal range adjusted to age or diabetes mellitus seem to be associated with a higher risk of developing cardiotoxicity. However, some limitations of the present study make necessary further studies aimed to clarify whether NT-proBNP and diabetes-associated markers determinations can be useful in the monitoring of cardiotoxicity risk in breast cancer patients undergoing trastuzumab therapy.

Topics: Adult; Aged; Antineoplastic Agents; Biomarkers, Pharmacological; Breast Neoplasms; Cardiotoxicity; Diabetes Mellitus; Drug Monitoring; Female; Heart Disease Risk Factors; Heart Failure; Humans; Logistic Models; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Receptor, ErbB-2; Retrospective Studies; Stroke Volume; Trastuzumab; Ventricular Function, Left

The aim of CATS (Cardiotoxicity of Adjuvant Trastuzumab Study) was to prospectively assess clinical, biochemical, and genomic predictors of trastuzumab-related cardiotoxicity (TRC).. Cardiac dysfunction is a common adverse effect of trastuzumab. Studies to identify predictive biomarkers for TRC have enrolled heterogeneous populations and yielded mixed results.. A total of 222 patients with early-stage human epidermal growth factor receptor 2-positive breast cancer scheduled to receive adjuvant anthracyclines followed by 12 months of trastuzumab were prospectively recruited from 17 centers. Left ventricular ejection fraction (LVEF), troponin T, and N-terminal prohormone of brain natriuretic peptide were measured at baseline, post-anthracycline, and every 3 months during trastuzumab. Germline single-nucleotide polymorphisms in ERBB2, FCGR2A, and FCGR3A were analyzed. TRC was defined as symptomatic heart failure; cardiac death, arrhythmia, or infarction; a decrease in LVEF of >15% from baseline; or a decrease in LVEF of >10% to <50%.. TRC occurred in 18 of 217 subjects (8.3%). Lower pre-anthracycline LVEF and greater interval decline in LVEF from pre- to post-anthracycline were each associated with TRC on multivariate analyses (odds ratio: 3.9 [p = 0.0001] and 7.9 [p < 0.0001] for a 5% absolute change in LVEF). Higher post-anthracycline N-terminal prohormone of brain natriuretic peptide level was associated with TRC on univariate but not multivariate analyses. There were no associations between troponin T or ERBB2/FGCR polymorphisms and TRC. Baseline LVEF and LVEF change post-anthracycline were used to generate a "low-risk TRC score" to identify patients with low TRC incidence.. Low baseline LVEF and greater LVEF decline post-anthracycline were both independent predictors of TRC. The other biomarkers did not further improve the ability to predict TRC. (Cardiotoxicity of Adjuvant Trastuzumab [CATS]; NCT00858039).

Topics: Adult; Anthracyclines; Antineoplastic Agents, Immunological; Biomarkers; Breast Neoplasms; Cardiotoxicity; Cohort Studies; Female; Heart Failure; Humans; Natriuretic Peptide, Brain; Predictive Value of Tests; Receptor, ErbB-2; Stroke Volume; Trastuzumab; Troponin T

Tyrosine kinase inhibitors (TKIs) have revolutionized the treatment of chronic myelogenous leukaemia (CML). However, cardiotoxicity of these agents remains a serious concern. The underlying mechanism of these adverse cardiac effects is largely unknown. Delineation of the underlying mechanisms of TKIs associated cardiac dysfunction could guide potential prevention strategies, rescue approaches, and future drug design. This study aimed to determine the cardiotoxic potential of approved CML TKIs, define the associated signalling mechanism and identify potential alternatives.. In this study, we employed a zebrafish transgenic BNP reporter line that expresses luciferase under control of the nppb promoter (nppb:F-Luciferase) to assess the cardiotoxicity of all approved CML TKIs. Our in vivo screen identified ponatinib as the most cardiotoxic agent among the approved CML TKIs. Then using a combination of zebrafish and isolated neonatal rat cardiomyocytes, we delineated the signalling mechanism of ponatinib-induced cardiotoxicity by demonstrating that ponatinib inhibits cardiac prosurvival signalling pathways AKT and extra-cellular-signal-regulated kinase (ERK), and induces cardiomyocyte apoptosis. As a proof of concept, we augmented AKT and ERK signalling by administration of Neuregulin-1β (NRG-1β), and this prevented ponatinib-induced cardiomyocyte apoptosis. We also demonstrate that ponatinib-induced cardiotoxicity is not mediated by inhibition of fibroblast growth factor signalling, a well-known target of ponatinib. Finally, our comparative profiling for the cardiotoxic potential of CML approved TKIs, identified asciminib (ABL001) as a potentially much less cardiotoxic treatment option for CML patients with the T315I mutation.. Herein, we used a combination of in vivo and in vitro methods to systematically screen CML TKIs for cardiotoxicity, identify novel molecular mechanisms for TKI cardiotoxicity, and identify less cardiotoxic alternatives.

Topics: Animals; Animals, Genetically Modified; Antineoplastic Agents; Apoptosis; Cardiotoxicity; Cells, Cultured; Extracellular Signal-Regulated MAP Kinases; Heart Diseases; Imidazoles; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Myocytes, Cardiac; Natriuretic Peptide, Brain; Niacinamide; Proof of Concept Study; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-akt; Pyrazoles; Pyridazines; Rats; Signal Transduction; Zebrafish

Data regarding the cardiac toxicity of cabozantinib lacks. The aim of our study was to assess the risk of cabozantinib-related cardiotoxicity in mRCC patients.. We performed a multicentre prospective study on mRCC patients treated with cabozantinib between October 2016 and November 2017. Transthoracic echocardiogram and plasma biomarkers assay were assessed at baseline, 3 and 6 months after cabozantinib initiation.. The study population included 22 mRCC patients. At baseline, 9.1% had a reduced left ventricular ejection fraction (LVEF), but none had a left ventricular systolic dysfunction. Patients with baseline reduced LVEF did not show further significant LVEF modification after 3 months. After 6 months, only 1 had an LVEF decline >10% compared to baseline, resulting in LV systolic dysfunction. At baseline, 64.7% and 27.3% of patients had elevated precursor brain natriuretic peptide (proBNP) and high-sensitivity troponin I (hsTnI), respectively. Among patients with basal normal proBNP and hsTnI, none had elevated values at 3 and 6 months. No correlation was found between basal elevated proBNP and basal reduced LVEF (P = .29), and between elevated proBNP and reduced LVEF after 6 months (P = .37). Similarly, we found no correlations between elevated hsTnI and reduced LVEF or elevated proBNP at baseline (P = .47; P = .38), at 3 (P = .059; P = .45) and after 6 months (P = .72; P = 1.0).. This prospective study revealed a modest risk of developing left ventricular systolic dysfunction related to cabozantinib. A lack of correlation between elevated cardiac biomarkers and reduced LVEF at different time-points was detected. Assessments of the cardiac function should be reserved at the occurrence of clinical symptoms.

Topics: Aged; Anilides; Antineoplastic Agents; Biomarkers; Carcinoma, Renal Cell; Cardiotoxicity; Female; Humans; Incidence; Italy; Kidney Neoplasms; Male; Natriuretic Peptide, Brain; Prospective Studies; Protein Kinase Inhibitors; Pyridines; Risk Assessment; Risk Factors; Stroke Volume; Time Factors; Troponin I; Ventricular Dysfunction, Left; Ventricular Function

Topics: Antineoplastic Agents; Cardiotoxicity; Heart Failure; Humans; Natriuretic Peptide, Brain; Risk Assessment

To evaluate the role of N-terminal pro-brain-type natriuretic peptide (NT-proBNP) and a cardiovascular (CV) risk score named FRESCO for predicting anthracycline-induced cardiotoxicity (AIC) in diffuse large B-cell lymphoma (DLBCL).. A total of 130 consecutive DLBCL patients treated in first-line with anthracycline-containing immunochemotherapy. Competitive risk between NT-proBNP, FRESCO, and time to AIC was considered.. Cumulative incidence of AIC was 12.2% and 17.5% at 1 and 5 years, respectively. Median time to development cardiotoxicity was 6.4 months, with half of the cases showing heart failure and the other half silent AIC. Both NT-proBNP levels and FRESCO score were independently associated with higher risk of AIC (P = 0.001 and P = 0.03, respectively). Patients with NT-proBNP ≥600 pg/mL or those with FRESCO ≥4.5% had 3.97 or 2.54 times higher risk of AIC than those with lower values (P = 0.001 and P = 0.048, respectively). According to the previous cutoffs, three groups of patients with a significantly different risk of AIC could be identified (P < 0.0001).. Doxorubicin-containing chemotherapy is associated with increased risk of silent and overt AIC. Baseline NT-proBNP levels and FRESCO CV risk score are accurate predictors of AIC and can identify groups of patients at different risk, in which personalized cardiologic evaluation should be offered.

Topics: Aged; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Cardiotoxicity; Female; Heart Diseases; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Spain

Doxorubicin-induced (DXR) cardiomyopathy is a serious health issue in oncology patients. Effective treatment of this clinical situation still remains to be discovered. In this experimental animal study, we aimed to define therapeutic effects of liraglutide, oxytocin and granulocyte colony-stimulating factor in DXR-induced cardiomyopathy model. 40 male Sprague-Dawley rats were included to study. 32 rats were given doxorubicin (DXR) for cardiomyopathy model. DXR was administered intraperitonally (i.p.) at every other day of 2.5 mg/kg/day at six times. Eight rats were taken as normal group and no treatment was performed. 32 rats given doxorubicin were divided into 4 groups. Group 1 rats were assigned to a placebo group and was given with a 0.9% NaCl saline solution at a dose of 1 ml/kg/day i.p. (DXR + saline), Group 2 rats were given with 1.8 mg/kg/day of Liraglutide i.p. (DXR + LIR), Group 3 rats were given with 160 μg/kg/day oxytocin i.p. (DXR + OX), Group 4 rats were given with 100 μg/kg/day filgrastim i.p. (DXR + G-CSF). All medications were given for 15 days. On day 16, under anesthesia, ECG was recorded from derivation I. After that, blood samples were taken by tail vein puncture for biochemical analysis. Finally, the animals were euthanized and the heart removed and prepared for immunohistochemical examination. All three treatments were shown to ameliorate the toxic effect of doxorubicin in cardiac tissue with the best results in DXR + OX group. DXR + OX group had the most preserved tissue integrity examined by light microscopy, least immune expression level of CASPASE-3 (5.3 ± 0.9) (p < 0.001) the highest ECG QRS wave voltage amplitude (0.21 ± 0.008 mV) (p < 0.00001) least plasma MDA (115.3 ± 19.8 nm) (p < 0.001), TNF-alpha (26.6 ± 3.05 pg/ml) (p < 0.001), pentraxin-3 (2.7 ± 0.9 ng/ml) (p < 0.001), Troponin T (1.4 ± 0.08 pg/ml) (p < 0.001), pro-BNP (11.1 ± 3.6 pg/ml) (p < 0.001) levels among all three treatment groups. Consistent with previous literature, we found that OX treatment decreased oxidative, apoptotic and inflammatory activity in DXR-induced cardiomyopathy rat model as well as provided better tissue integrity and better results in clinically relevant measures of ECG assessment, plasma Troponin T and pro-BNP levels. LIR and G-CSF treatment caused similar results with less powerful effects. Our findings suggest that with the best results in OX treatment group, all three agents including LIR and G-CSF attenuates DXR-induced cardiomyopathy in

Topics: Animals; Apoptosis; C-Reactive Protein; Cardiomyopathies; Cardiotoxicity; Caspase 3; Disease Models, Animal; Doxorubicin; Granulocyte Colony-Stimulating Factor; Heart Rate; Humans; Inflammation Mediators; Lipid Peroxidation; Liraglutide; Malondialdehyde; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxidative Stress; Oxytocin; Rats, Sprague-Dawley; Serum Amyloid P-Component; Signal Transduction; Troponin T; Tumor Necrosis Factor-alpha

Little is known about the comparison of multiple-gated acquisition (MUGA) scanning with cardiovascular magnetic resonance (CMR) for serial monitoring of HER2+ breast cancer patients receiving trastuzumab. The association of cardiac biomarkers with CMR left ventricular (LV) function and volume is also not well studied. Our objectives were to compare CMR and MUGA for left ventricular ejection fraction (LVEF) assessment, and to examine the association between changes in brain natriuretic peptide (NT-BNP) and troponin-I and changes in CMR LV function and volume. This prospective longitudinal two-centre cohort study recruited HER2+ breast cancer patients between January 2010 and December 2013. MUGA, CMR, NT-BNP and troponin-I were performed at baseline, 6, 12, and 18 months after trastuzumab initiation. In total, 41 patients (age 51.7 ± 10.8 years) were enrolled. LVEF comparison between MUGA and CMR demonstrated weak agreement (Lin's correlation coefficient r = 0.46, baseline; r = 0.29, 6 months; r = 0.42, 12 months; r = 0.39, 18 months; all p < 0.05). Bland-Altman plots demonstrated wide LVEF agreement limits (pooled agreement limits 3.0 ± 6.2). Both modalities demonstrated significant LVEF decline at 6 and 12 months from baseline, concomitant with increased LV volumes on CMR. Changes in NT-BNP correlated with changes in LV diastolic volume at 12 and 18 months (p < 0.05), and LV systolic volume at 18 months (p < 0.05). Changes in troponin-I did not correlate with changes in LV function or volume at any timepoint. In conclusion, CMR and MUGA LVEF are not interchangeable, warranting selection and utility of one modality for serial monitoring. CMR is useful due to less radiation exposure and accuracy of LV volume measurements. Changes in NT-BNP correlated with changes in LV volumes.

Topics: Adult; Antineoplastic Agents, Immunological; Biomarkers; Breast Neoplasms; Cardiac-Gated Imaging Techniques; Cardiotoxicity; Female; Humans; Magnetic Resonance Imaging; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Radiopharmaceuticals; Reproducibility of Results; Risk Factors; Sodium Pertechnetate Tc 99m; Stroke Volume; Time Factors; Tomography, Emission-Computed; Trastuzumab; Treatment Outcome; Troponin I; Ventricular Dysfunction, Left; Ventricular Function, Left

Pirarubicin (THP) is an anthracycline antibiotic, frequently used for the treatment of various human cancers. Unfortunately, the clinical effectiveness of THP is limited by its dose-related cardiotoxicity.

Topics: Animals; Antioxidants; Apocynum; Apoptosis; Cardiotoxicity; Creatine Kinase; Doxorubicin; Drugs, Chinese Herbal; Humans; Male; Malondialdehyde; Natriuretic Peptide, Brain; Plant Leaves; Rats; Rats, Wistar; Superoxide Dismutase; Troponin

To compare methamphetamine users who develop heart failure to those who do not and determine predictors.. Patients presenting over a two-year period testing positive for methamphetamine on their toxicology screen were included. Demographics, vital signs, echocardiography and labs were compared between patients with normal versus abnormal B-type natriuretic peptide (BNP).. 4407 were positive for methamphetamine, 714 were screened for heart failure, and 450 (63%) had abnormal BNP. The prevalence of abnormal BNP in methamphetamine-positive patients was 10.2% versus 6.7% for those who were negative or not tested. For methamphetamine-positive patients, there was a tendency for higher age and male gender with abnormal BNP. A higher proportion of Whites and former smokers had abnormal BNP and higher heart and respiratory rates. Echocardiography revealed disparate proportions for normal left ventricular ejection fraction (LVEF) and severe dysfunction (LVEF <30%), LV diastolic function, biventricular dimensions, and pulmonary arterial pressures between subgroups. For methamphetamine-positive patients with abnormal BNP, creatinine was significantly higher, but not Troponin I. Logistic regression analysis revealed predictors of abnormal BNP and LVEF <30% in methamphetamine-positive patients, which included age, race, smoking history, elevated creatinine, and respiratory rate.. Methamphetamine-positive patients have a significantly higher prevalence of heart failure than the general emergency department population who are methamphetamine-negative or not tested. The methamphetamine-positive subgroup who develop heart failure tend to be male, older, White, former smokers, and have higher creatinine, heart and respiratory rates. This subgroup also has greater biventricular dysfunction, dimensions, and higher pulmonary arterial pressures.

Topics: Adult; Biomarkers; California; Cardiotoxicity; Echocardiography; Female; Heart Failure; Humans; Logistic Models; Male; Methamphetamine; Middle Aged; Natriuretic Peptide, Brain; Prevalence; Retrospective Studies; Risk Factors; Stroke Volume; Trauma Centers; Troponin I; Ventricular Function, Left

Trastuzumab is associated with cardiotoxicity, manifesting as a decrease of the left-ventricular ejection fraction (LVEF). Administration of anthracyclines prior to trastuzumab increases risk of cardiotoxicity. High-sensitive troponin T and N-terminal-pro-brain natriuretic peptide (NT-proBNP) are molecular markers that may allow earlier detection of drug-induced cardiotoxicity. In this analysis we aimed to quantify the kinetics and exposure-response relationships of LVEF, troponin T and NT-proBNP measurements, in patients receiving anthracycline and trastuzumab. Repeated measurements of LVEF, troponin T and NT-proBNP and dosing records of anthracyclines and trastuzumab were available from a previously published clinical trial. This trial included 206 evaluable patients with early breast cancer. Exposure to anthracycline and trastuzumab was simulated based on available dosing records and by using a kinetic-pharmacodynamic (K-PD) and a fixed pharmacokinetic (PK) model from literature, respectively. The change from baseline troponin T was described with a direct effect model, affected by simulated anthracycline concentrations, representing myocyte damage. The relationship between trastuzumab and LVEF was described by an indirect effect compartment model. The EC

Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents, Immunological; Biomarkers, Tumor; Breast Neoplasms; Cardiotoxicity; Female; Heart Ventricles; Humans; Middle Aged; Muscle Cells; Natriuretic Peptide, Brain; Peptide Fragments; Trastuzumab; Troponin T

Dasatinib is a new selective tyrosine kinase inhibitor that targets certain kinases involved in cellular growth and development. This drug belongs to a novel anticancer therapy aiming to increase the survival in patients with imatinib-resistant mutations. However, the dasatinib toxicity was reported as a side effect leading to arrhythmias and/or heart failure. Here, we investigated the possibility of dasatinib-induced toxicity in rat cardiomyocyte H9c2 cells. Our objectives were to investigate the ability of dasatinib to induce expression of cytochrome P450 (CYP1A1, CYP1B1) and cardiac hypertrophy markers (BNP, β-MHC) genes in H9c2 cells. To test this hypothesis, H9c2 cells were incubated with dasatinib at two concentrations (20 and 40 μM). Thereafter, CYP1A1, CYP1B1, BNP, and β-MHC were determined at gene expression level. Our findings showed that dasatinib induces the CYP1A1, CYP1B1, BNP, and β-MHC mRNA. The involvement of AhR/CYP1A1 pathway in dasatinib toxicity was tested by resveratrol (RES), an AhR antagonist. Interestingly, the increase in mRNA of different genes by dasatinib was not affected by RES, which confirms that these effects are not mediated through AhR. In addition, this was accompanied by a significant inhibition of constitutive expression of these genes by RES. The current work provides the first evidence for the ability of dasatinib to induce hypertrophic markers in H9c2 cells through AhR-independent pathway.

Topics: Animals; Antineoplastic Agents; Biomarkers; Cardiomegaly; Cardiotoxicity; Cell Culture Techniques; Cell Line; Cell Survival; Cytochrome P-450 CYP1A1; Cytochrome P-450 CYP1B1; Dasatinib; Gene Expression; Myocytes, Cardiac; Myosin Heavy Chains; Natriuretic Peptide, Brain; Rats

The current study was to evaluate soluble ST-2 level and left ventricular ejection fraction (LVEF) in patients with breast cancer receiving doxorubicin or trastuzumab treatment for 6 months and determine whether soluble ST-2 level can be used to predictive left ventricular function impairment.Patients who were diagnosed as having breast cancer receiving doxorubicin or trastuzumab or combined therapy were enrolled. Demographic data, prior medical history and related medical therapy, and site and stage of breast cancer information were collected from electronic health record. Fasting blood was used to detect soluble ST-2 and brain natriuretic peptide (BNP) levels before and after 6 months doxorubicin or trastuzumab therapy. Echocardiography was performed before and after 6 months of doxorubicin or trastuzumab therapy.Participants were divided into 3 groups based on tertiary soluble ST-2 level. Compared with 1st tertiary group, patients in the 3rd tertiary group had higher proportion receiving combined therapy (14.3% vs 4.7%, P < .05). Baseline soluble ST-2 level was similar across groups. After 6 months' therapy, soluble ST-2 level was significantly higher in the 3rd tertiary group. Pearson correlation analysis showed that soluble ST-2 level was positively correlated with left ventricular volume and E/e' ratio while negatively correlated with LVEF. Doxorubicin, trastuzumab, combined therapy, soluble ST-2 level, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker treatment were all independently associated with LVEF change.In breast cancer patients receiving doxorubicin or trastuzumab therapy, soluble ST-2 level can be used to predict cardiac function and structure changes.

Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiotoxicity; Doxorubicin; Echocardiography; Female; Heart Ventricles; Humans; Middle Aged; Natriuretic Peptide, Brain; Predictive Value of Tests; Stroke Volume; Trastuzumab; Ventricular Dysfunction, Left; Ventricular Function, Left

To describe the high-risk profile group, susceptible to develop anthracycline-induced cardiomyopathy in children with acute leukemia.. The study involved 35 pediatric patients diagnosed with acute lymphoblastic (ALL) or acute myeloblastic leukemia (AML), from March 2014 to December 2016. Serologic markers used for the analysis of cardiac dysfunction were troponin T, NT-proBNP and PCRhs. Also, the patients have had echocardiographic evaluation at the beginning of treatment to determine LVEF, SF and A, E, E' Doppler waves.. Positive linear correlation was shown between NT-proBNP and leukocyte values, NT-proBNP and blast cells value, and NT-proBNP and LDH. Significant linear negative correlations between LVEF with leukocyte values, blast cells values, LDH, SF and leukocyte values, LVEF and NT-proBNP values and LVEF and troponin T values were also identified. A weak negative correlation between E/E' ratio and blast cells values has been observed. All of these correlations were statistically significant (p<0.05).. Leukocyte value, as well as the other serological markers assessed (NT-proBNP, Troponin T), are useful tools to evaluate the risk of anthracycline-induced cardiotoxicity. The variation of the biological markers at the beginning of the cytotoxic treatment confirms the presence of an early myocardial dysfunction, emphasizing the importance of systematic evaluation of this particular group of patients.

Topics: Adolescent; Anthracyclines; Antibiotics, Antineoplastic; Biomarkers; Cardiotoxicity; Child; Child, Preschool; Echocardiography; Female; Follow-Up Studies; Humans; Infant; Leukemia, Myeloid, Acute; Male; Natriuretic Peptide, Brain; Peptide Fragments; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Risk Assessment; Survival Rate; Troponin T

Trastuzumab following anthracycline causes cardiotoxicity in up to 28% of patients. Although the cardiotoxicity is often irreversible once cardiac dysfunction is detected, the early predictor has not been established yet.. We prospectively observed breast cancer patients treated with anthracycline or trastuzumab at Tonan Hospital. All patients underwent echocardiography and blood sampling at baseline, and every three months during chemotherapy. Cardiotoxicity was defined as a decline in left ventricular ejection fraction >10% points.. Of 40 patients, 34 patients (85%) were treated with anthracycline (epirubicin), 18 (45%) with trastuzumab, and 12 (30%) with both agents. Cardiotoxicity was observed in four patients (10%), who were all treated with both agents. The absolute levels of high-sensitive troponin T (hs-TnT) were increased in all four patients with cardiotoxicity, and all the highest points were observed before or at the time of detection of cardiotoxicity. The highest level of hs-TnT was not significantly different in patients with and without cardiotoxicity. "Hs-TnT increment from baseline to the highest value" and "hs-TnT integration value above baseline" were significantly greater in patients with cardiotoxicity (0.039 vs. 0.007 ng/mL, P = 0.046, 0.113 vs. 0.022 ng months/mL, P = 0.013, respectively). The integration value had 100% sensitivity and specificity with a cutoff level at 0.070 ng months/mL.. Hs-TnT assay may be able to predict anthracycline- and trastuzumab-induced cardiotoxicity in breast cancer patients, and the hs-TnT increment or hs-TnT integration value above baseline was more reliable than the absolute value.

Topics: Anthracyclines; Antibiotics, Antineoplastic; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiotoxicity; Echocardiography; Epirubicin; Female; Humans; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Sensitivity and Specificity; Trastuzumab; Troponin T

There is inconclusive evidence about the role of sex as a risk factor for doxorubicin (DOX)-induced cardiotoxicity. Recent experimental studies have shown that adult female rats are protected against DOX-induced cardiotoxicity. However, the mechanisms of this sexual dimorphism are not fully elucidated. We have previously demonstrated that DOX alters the expression of several cytochrome P450 (CYP) enzymes in the hearts of male rats. Nevertheless, the sex-dependent effect of DOX on the expression of CYP enzymes is still not known. Therefore, in the present study, we determined the effect of acute DOX exposure on the expression of CYP genes in the hearts of both male and female C57Bl/6 mice.. Acute DOX cardiotoxicity was induced by a single intraperitoneal injection of 20 mg/kg DOX in male and female adult C57Bl/6 mice. Cardiac function was assessed 5 days after DOX exposure by trans-thoracic echocardiography. Mice were euthanized 1 day or 6 days after DOX or saline injection. Thereafter, the hearts were harvested and weighed. Heart sections were evaluated for pathological lesions. Total RNA was extracted and expression of natriuretic peptides, inflammatory and apoptotic markers, and CYP genes was measured by real-time PCR.. Adult female C57Bl/6 mice were protected from acute DOX-induced cardiotoxicity as they show milder pathological lesions, less inflammation, and faster recovery from DOX-induced apoptosis and DOX-mediated inhibition of beta-type natriuretic peptide. Acute DOX exposure altered the gene expression of multiple CYP genes in a sex-dependent manner. In 24 h, DOX exposure caused male-specific induction of Cyp1b1 and female-specific induction of Cyp2c29 and Cyp2e1.. Acute DOX exposure causes sex-dependent alteration of cardiac CYP gene expression. Since cardiac CYP enzymes metabolize several endogenous compounds to biologically active metabolites, sex-dependent alteration of CYP genes may play a role in the sexual dimorphism of acute DOX-induced cardiotoxicity.

Topics: Animals; Antibiotics, Antineoplastic; Atrial Natriuretic Factor; Cardiotoxicity; Cyclooxygenase 2; Cytochrome P-450 Enzyme System; Doxorubicin; Female; Gene Expression Regulation, Enzymologic; Heart; Male; Mice, Inbred C57BL; Myocardium; Natriuretic Peptide, Brain; Proto-Oncogene Proteins c-bcl-2; Sex Characteristics

Purpose Women receiving trastuzumab with chemotherapy are at risk for trastuzumab-related cardiac dysfunction (TRCD). We explored the prognostic value of cardiac markers (troponins I and T, N-terminal prohormone of brain natriuretic peptide [NT-proBNP]) to predict baseline susceptibility to develop TRCD. We examined whether development of cardiac end points or significant left ventricular ejection fraction (LVEF) drop was associated with markers' increases. Patients and Methods Cardiac marker assessments were coupled with LVEF measurements at different time points for 533 patients from the Herceptin Adjuvant (HERA) study who agreed to participate in this study. Patients with missing marker assessments were excluded, resulting in 452 evaluable patients. A primary cardiac end point was defined as symptomatic congestive heart failure of New York Heart Association class III or IV, confirmed by a cardiologist, and a significant LVEF drop, or death of definite or probable cardiac causes. A secondary cardiac end point was defined as a confirmed significant asymptomatic or mildly symptomatic LVEF drop. Results Elevated baseline troponin I (> 40 ng/L) and T (> 14 ng/L), occurring in 56 of 412 (13.6%) and 101 of 407 (24.8%) patients, respectively, were associated with an increased significant LVEF drop risk (univariate analysis: hazard ratio, 4.52; P < .001 and hazard ratio, 3.57; P < .001, respectively). Few patients had their first elevated troponin value recorded during the study (six patients for troponin I and 25 patients for troponin T). Two patients developed a primary and 31 patients a secondary cardiac end point (recovery rate of 74%, 23 of 31). For NT-proBNP, higher increases from baseline were seen in patients with significant LVEF drop. Conclusion Elevated troponin I or T before trastuzumab is associated with increased risk for TRCD. A similar conclusion for NT-proBNP could not be drawn because of the lack of a well-established elevation threshold; however, higher increases from baseline were seen in patients with TRCD compared with patients without.

Topics: Adult; Antineoplastic Agents; Biomarkers; Breast Neoplasms; Cardiotoxicity; Female; Humans; Middle Aged; Natriuretic Peptide, Brain; Neoplasm Staging; Peptide Fragments; Proportional Hazards Models; Randomized Controlled Trials as Topic; Receptor, ErbB-2; Stroke Volume; Trastuzumab; Troponin I; Troponin T

Topics: Biomarkers; Breast Neoplasms; Cardiotoxicity; Female; Humans; Immunoglobulin E; Natriuretic Peptide, Brain; Peptide Fragments; Trastuzumab; Troponin I; Troponin T

Our study evaluated brain natriuretic peptide (BNP) changes over time after adjuvant radiotherapy (RT) in women with left-sided breast cancer investigating its correlation with heart dosimetric parameters.. Forty-three patients underwent clinical cardiac examination, electrocardiogram (ECG), echocardiography and BNP measurement before RT (T0) and 1 (T1), 6 (T6) and 12 months (T12) after. After T12 cardiac assessment was performed annually in each patient. Mean values and standard deviation (SD) of BNP, left ventricular ejection fraction (LVEF), V20, V25, V30, V45 and mean dose were calculated. Normalized BNP (BNPn) was calculated as follows: BNPnT1 = BNPT1/BNPT0, BNPnT6 = BNPT6/BNPT0, BNPnT12 = BNPT12/BNPT0. Absolute BNP and BNPn values were used for data analysis.. Median follow-up from the end of RT to the last check-up was 87 months (range 37-120 months). Minimum follow-up was 74 months except for two patients, who died at respectively 37 and 47 months after RT. In all patients LVEF did not change significantly (p = 0.22) after RT. BNP increased significantly (p < 0.001), particularly 1 and 6 months after RT. It slightly decreased after 12 months. BNP did not correlate with V20, V25, V30, V45, mean dose and MHD. All BNPn correlated significantly (p < 0.05) with V20, V25, V30, V45, mean dose and MHD. Four patients had a cardiac event; in the only subject who developed myocardial infarction, V20, V25, V30 and V45 were the highest and BNP increased from T1 and persisted high even at T12.. Our results confirm that BNP could be a useful minimally invasive marker of early RT related cardiac impairment.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers; Cardiotoxicity; Electrocardiography; Female; Follow-Up Studies; Heart; Humans; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Radiotherapy, Adjuvant; Stroke Volume; Unilateral Breast Neoplasms; Ventricular Function, Left

Carfilzomib (Cfz) has been associated with an ~5% incidence of unexplained and unpredictable cardiovascular toxicity in clinical trials. We therefore implemented a detailed, prospective, clinical cardiac and renal evaluation of 62 Cfz-treated myeloma patients, including serial blood pressure (BP), creatinine, troponin, NT-proBNP and pre- and post-treatment echocardiograms, including ejection fraction (EF), average global longitudinal strain and compliance. Pre-treatment elevations in NT-proBNP and BP, as well as abnormal cardiac strain were common. A rise in NT-proBNP occurred frequently post-treatment often without corresponding cardiopulmonary symptoms. A rise in creatinine was common, lessened with hydration and often reversible. All patients had a normal EF pre-treatment. Five patients experienced a significant cardiac event (four decline in EF and one myocardial infarction), of which 2 (3.2%) were considered probably attributable to Cfz. None were rechallenged with Cfz. The ideal strategy for identifying patients at risk for cardiac events, and parameters by which to monitor for early toxicity have not been established; however, it appears baseline echocardiographic testing is not consistently predictive of toxicity. The toxicities observed suggest an endothelial mechanism and further clinical trials are needed to determine whether or not this represents a class effect or is Cfz specific.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Biomarkers; Cardiotoxicity; Female; Heart Diseases; Humans; Kidney Diseases; Male; Middle Aged; Multiple Myeloma; Natriuretic Peptide, Brain; Oligopeptides; Peptide Fragments; Proteasome Inhibitors; Stroke Volume

Sheng-Mai Yin (SMY), a modern Chinese formula based on Traditional Chinese Medicine theory, has been used to treat cardiovascular diseases in Eastern Asia. Our study focuses on the cardioprotection of SMY against doxorubicin (DOX)-induced cardiac toxicity in vivo.. Rats were injected with DOX (2.5 mg/kg) in six injections over a 2-week period. SMY was administrated intragastrically at the dose of 8.35, 16.7 and 33.4 g/kg, or 16.7 g/kg only twice a day concurrently with DOX for the 2-weeks. A series of assays were performed to detect the effects of SMY on: (i) heart weight index (HWI) and left ventricular mass index (LVMI); (ii) cardiac function; (iii) heart tissue morphology; (iv) the contents of carboxy terminal propeptide of procollagen typeI (PICP), amino terminal propeptide of procollagen type III (PШNP), transforming growth factor-β1 (TGF-β1), B-type natriuretic peptide (BNP), monocyte chemoattractant protein-1 (MCP-1), interferon gamma (INF-γ) and interleukin 6 (IL-6) by ELISA; (v) the mRNA levels of TGF-β1 and toll-like receptor-2 (TLR2); and (vi) protein level of TGF-β1.. Rats treated with SMY displayed the reductions of BNP and CK-MB increased by DOX in a dose-dependent manner. Moderate dose of SMY exhibited the correction for the increased HWI, LVMI, and the injured cardiac function, as well as the collagen accumulation. In addition, cardioprotection of SMY against DOX-induced cardiac toxicity was demonstrated by the reduction of myocardial fibrosis, characterized by the suppression of PICP, PШNP and TGF-β1, as well as the anti-inflammation and the regulation for cardiac immune microenvironment, characterized by the inhibition of TLR2, MCP-1, INF-γ and IL-6.. SMY may protect heart function through the restriction of myocardial fibrosis induced by DOX, which suggests the potentially therapeutic effect of SMY on DOX-induced cardiomyopathy.

Topics: Animals; Cardiomyopathies; Cardiotonic Agents; Cardiotoxicity; Creatine Kinase, MB Form; Disease Models, Animal; Doxorubicin; Drug Combinations; Drugs, Chinese Herbal; Heart; Inflammation Mediators; Male; Natriuretic Peptide, Brain; Organ Size; Rats; Rats, Wistar

The purpose of this pilot study was to evaluate the usefulness of selected echocardiographic parameters, NT-proBNP and cardiac troponin I (cTnI) in the detection of cardiotoxicity in dogs treated with doxorubicin for various malignancies. Echocardiographic studies and biomarker measurements were performed before each administration of doxorubicin, then 1 and 3 months after completion of therapy. Thirteen dogs were included, with a total cumulative dose of doxorubicin ranging from 30 to 150 mg/m(2). E/A ratio significantly decreased during doxorubicin administration (p=0.047). cTnI level was also significantly affected by treatment (p=0.046), increasing above normal at least at one time point in 11 of 13 dogs. The results of this pilot study suggest that monitoring of left ventricular diastolic function and cTnI level measurement might be useful in the early detection of cardiotoxic signs of doxorubicin therapy in dogs.

Topics: Animals; Antibiotics, Antineoplastic; Biomarkers; Cardiotoxicity; Diastole; Dogs; Doxorubicin; Echocardiography, Doppler; Female; Male; Natriuretic Peptide, Brain; Neoplasms; Peptide Fragments; Pilot Projects; Prospective Studies; Troponin I; Ventricular Function, Left

Anthracycline chemotherapy is associated with an increased risk of developing heart failure (HF). The current standard for detecting HF or cardiotoxicity during chemotherapy involves episodic cardiac imaging typically at prescribed intervals and there are limited studies examining techniques beyond measuring left ventricular (LV) function. This study explores whether cardiac biomarkers troponin I (TnI) and B-type natriuretic peptide (BNP) could be part of a screening strategy for early detection of the development of cardiotoxicity in patients undergoing anthracycline chemotherapy.. Patients were enrolled from a single medical center. Cardiac biomarkers (TnI, BNP) were measured before and within 24 hours after completion of anthracycline administration for each cycle of therapy. Cardiac imaging was obtained at baseline and at completion of chemotherapy (commonly at 6 or 12 months) or based on clinical suspicion of a cardiac event. Of the enrolled 109 patients, 11 (10.1%) experienced cardiac events; all of these patients had at least 1 BNP value >100 pg/mL before the cardiac event. Significant reduction in LV ejection fraction as defined for cardiotoxicity occurred in only 3 of 10 patients (30%) with a cardiac event.. The use of cardiac biomarkers, particularly BNP, may allow early detection of cardiotoxicity related to anthracycline chemotherapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anthracyclines; Biomarkers; Cardiotoxicity; Feasibility Studies; Female; Heart Diseases; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Neoplasms; Point-of-Care Systems; Troponin I; Young Adult

Cardiotoxicity is an important side effect of trastuzumab therapy and cardiac surveillance is recommended.. The aim of our study was to prospectively assess baseline patients' characteristics, level of N-terminal pro-brain natriuretic peptide (NT-proBNP) and echocardiographic parameters as possible predictors of trastuzumab-related cardiac dysfunction.. In a prospective cohort study, clinical, echocardiographic and neurohumoral assessment was performed at baseline, after 4, 8 and 12 months in breast cancer patients undergoing post-anthracycline (3-4 cycles) adjuvant therapy with trastuzumab. Trastuzumab-related cardiac dysfunction was defined as a decline of ≥ 10% in left ventricular ejection fraction (LVEF).. 92 patients (mean age, 53.6 ± 9.0 years) were included. Patients who developed trastuzumab-related LVEF decline ≥ 10% (20.6%) during treatment had significantly higher baseline LVEF (70.7 ± 4.4%) than those without (64.8 ± 5.5%) (p = 0.0035). All other measured baseline parameters (age, body mass index, arterial hypertension, level of NT-proBNP and other echocardiographic parameters) were not identified as significant.. Our findings suggest that baseline patient' characteristics, level of NT-proBNP and echocardiographic parameters, as long as they are within normal range, are not a reliable tool to predict early trastuzumab-related cardiac dysfunction in patients undergoing post-low dose anthracycline adjuvant trastuzumab therapy. A LVEF decline in patients with high-normal baseline level although statistically significant is not clinically relevant.

Topics: Adult; Aged; Animals; Anthracyclines; Antineoplastic Agents; Blood Pressure; Body Mass Index; Breast Neoplasms; Cardiotoxicity; Chemotherapy, Adjuvant; Echocardiography, Doppler; Female; Heart Failure; Humans; Logistic Models; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Receptor, ErbB-2; Reference Values; Risk Factors; Stroke Volume; Time Factors; Trastuzumab; Treatment Outcome

An increasing awareness of chemotherapy and radiotherapy as preventable causes of cardiac failure among large numbers of patients surviving cancer has contributed to the development of cardio-oncology as a subspecialty. Perhaps the most important driver has been that the aging of the population undergoing cancer therapy has provided an increasing number of patients at risk for the development of heart failure. Cardio-oncology has many unresolved questions. In this article the 6 most important unresolved issues requiring additional research are discussed: (1) the frequency of overt heart failure as a manifestation of cardiotoxicity; (2) the optimal diagnostic approach to cardiotoxicity in the context of large numbers of patients requiring repeated testing; (3) the need for better risk prediction; (4) alternatives to the use of ejection fraction as the cornerstone of evaluation; (5) definition of the best strategy for protection; and (6) the need for evidence-based algorithms to guide late follow-up. When this evidence base is mature, we will have a better understanding of the magnitude of the problem of cardiotoxicity, who best to screen (and how), who justifies the use of cardioprotective therapy, and how all at-risk patients should be followed over the decades following cancer therapy.

Topics: Antineoplastic Agents; Biomarkers; Cardiotonic Agents; Cardiotoxicity; Cardiotoxins; Heart Failure; Humans; Magnetic Resonance Imaging, Cine; Natriuretic Peptide, Brain; Neoplasms; Troponin; Ventricular Dysfunction, Left

The long-term prognosis of patients after haematopoietic stem cell transplantation (HSCT) has greatly improved. Cardiac complications represent unresolved and potentially life-threatening conditions in these patients. We prospectively examined 37 consecutive patients with a median age of 28 years who underwent allogeneic HSCT. Biomarkers of cardiac injury were measured serially before the conditioning regimen, the first day after HSCT and then 14, 30, 90 and 180 days after HSCT. Echocardiography was performed before and 1 month after HSCT. Eleven patients (30%) had persistently increased NT-proBNP values, 14 patients (38%) had only transient elevations and 12 (32%) had no changes in NT-proBNP concentrations for a period exceeding 14 days after HSCT. Elevated NT-proBNP values at day 14 after HSCT remained an independent predictor of cardiotoxicity during the first 6 months after HSCT (P < 0.01). Patients with persistent elevations in NT-proBNP also had significant elevations in hs-cTnT concentrations (P < 0.01). Only patients with persistently increased NT-proBNP had a significant worsening in systolic and some diastolic echocardiographic parameters, and we observed in this group the highest values of both cardiomarkers during the 6-month period. Forty-five percent of these patients developed clinical manifestation of cardiotoxicity. Elevations in NT-proBNP concentrations at day 14 after HSCT can predict patients at risk of developing cardiac events during the first 6 months after HSCT. Simultaneous elevations of both cardiomarkers (NT-proBNP and hs-cTnT) persisting 14 days after HSCT had a sensitivity of 83% and a specificity of 80.69%.

Topics: Adult; Biomarkers; Cardiotoxicity; Female; Follow-Up Studies; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Predictive Value of Tests; Prospective Studies; Troponin T; Young Adult

The anticancer efficacy of anthracyclines is limited by cumulative dose-dependent early and delayed cardiotoxicity resulting in congestive heart failure. Mechanisms responsible for anthracycline-induced heart damage are controversially discussed and effective preventive measures are preferable. Here, we analyzed the influence of the lipid lowering drug lovastatin on anthracycline-induced late cardiotoxicity three month after treatment of C57BL/6 mice with five low doses of doxorubicin (5×3mg/kg BW; i.p.). Doxorubicin increased the cardiac mRNA levels of BNP, IL-6 and CTGF, while the expression of ANP remained unchanged. Lovastatin counteracted these persisting cardiac stress responses evoked by the anthracycline. Doxorubicin-induced fibrotic alterations were neither detected by histochemical collagen staining of heart sections nor by analysis of the mRNA expression of collagens. Extensive qRT-PCR-array based analyses revealed a large increase in the mRNA level of heat shock protein Hspa1b in doxorubicin-treated mice, which was mitigated by lovastatin co-treatment. Electron microscopy together with qPCR-based analysis of mitochondrial DNA content indicate that lovastatin attenuates doxorubicin-stimulated hyperproliferation of mitochondria. This was not paralleled by increased expression of oxidative stress responsive genes or senescence-associated proteins. Echocardiographic analyses disclosed that lovastatin protects from the doxorubicin-induced decrease in the left ventricular posterior wall diameter (LVPWD), while constrictions in fractional shortening (FS) and ejection fraction (EF) evoked by doxorubicin were not amended by the statin. Taken together, the data suggest beneficial effects of lovastatin against doxorubicin-induced delayed cardiotoxicity. Clinical studies are preferable to scrutinize the usefulness of statins for the prevention of anthracycline-induced late cardiotoxicity.

Topics: Animals; Antibiotics, Antineoplastic; Cardiotonic Agents; Cardiotoxicity; Connective Tissue Growth Factor; DNA Damage; DNA, Mitochondrial; Doxorubicin; Female; Fibrosis; Gene Expression Profiling; HSP70 Heat-Shock Proteins; Interleukin-6; Lovastatin; Mice, Inbred C57BL; Myocardium; Natriuretic Peptide, Brain

Trastuzumab induced cardiotoxicity (TIC) was defined as the most serious side effect. Long term cardiac effects of trastuzumab are still not known, thus we aimed to compare the long term cardiac effects of adjuvant trastuzumab therapies of HER2-positive breast cancer according to the treatment duration.. Patients who completed adjuvant trastuzumab treatment at least 6 months before for the adjuvant setting in HER2-positive breast cancer were included in the study. A total of 164 patients were included in this study: 108 and 56 patients were treated with 9 weeks and 52 weeks of trastuzumab, respectively. The main limitation of our study is that due to the cross-sectional evaluation of cardiac biomarkers we cannot predict the status of baseline cardiac biomarkers of this population.. The median follow-up of the study was 32 (10-95) months. The accompanying chronic diseases were similar in both groups. Baseline left ventricular ejection fraction (LVEF) was 65.5 ± 3.4% vs 67.1 ± 4.5% in the 9 weeks and 52 weeks trastuzumab treatment groups, respectively (p = 0.13). Symptomatic heart failure was not observed during trastuzumab treatment in either group. Trastuzumab induced cardiotoxicity (TIC) was observed in 2 (1.9%) and 17 (30.3%) patients in the 9 and 52 weeks trastuzumab treatment groups, respectively (p < 0.001). After a median 24 months of follow-up from the last dose of trastuzumab, mean LVEF values were similar between the two treatment arms (p = 0.29). In the subgroup analyses, mean LVEF values were significantly lower in patients who developed TIC compared to those who did not develop TIC (61.9 ± 3.6% vs 64.4 ± 2.6%, p = 0.04). Average mean LVEF loss from baseline was significantly higher in patients who developed TIC compared to those who did not develop TIC (10.0 ± 6.0% vs 1.5 ± 6.2%, p < 0.001). Cardiac biomarkers were similar in both treatment groups. In the subgroup analyses serum High-sensitivity C-reactive protein (hs-CRP) and prohormone brain natriuretic peptide (pro-BNP) levels were significantly higher in patients who developed TIC compared to those who did not develop TIC.. TIC was observed to be significantly higher in the 52 weeks trastuzumab group. At the end of 32 months of follow-up mean LVEF values and cardiac biomarkers were similar between the two treatment groups. In the subgroup analyses, significant LVEF loss and higher cardiac biomarkers which show cardiac damage in patients who developed TIC can be permanent in some of the patients and long term cardiac damage may be underestimated.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Breast Neoplasms; C-Reactive Protein; Cardiotoxicity; Cross-Sectional Studies; Early Detection of Cancer; Early Medical Intervention; Female; Heart; Heart Diseases; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Receptor, ErbB-2; Stroke Volume; Time; Trastuzumab

Doxorubicin (DOX) is known to induce serious cardiotoxicity, which is believed to be mediated by oxidative stress and complex interactions with iron. However, the relationship between iron and DOX-induced cardiotoxicity remains controversial and the role of iron chelation therapy to prevent cardiotoxicity is called into question. Firstly, we evaluated in vitro the effects of DOX in combination with dextran-iron on cell viability in cultured H9c2 cardiomyocytes and EMT-6 cancer cells. Secondly, we used an in vivo murine model of iron overloading (IO) in which male C57BL/6 mice received a daily intra-peritoneal injection of dextran-iron (15mg/kg) for 3weeks (D0-D20) and then (D21) a single sub-lethal intra-peritoneal injection of 6mg/kg of DOX. While DOX significantly decreased cell viability in EMT-6 and H9c2, pretreatment with dextran-iron (125-1000μg/mL) in combination with DOX, paradoxically limited cytotoxicity in H9c2 and increased it in EMT-6. In mice, IO alone resulted in cardiac hypertrophy (+22%) and up-regulation of brain natriuretic peptide and β-myosin heavy-chain (β-MHC) expression, as well as an increase in cardiac nitro-oxidative stress revealed by electron spin resonance spectroscopy. In DOX-treated mice, there was a significant decrease in left-ventricular ejection fraction (LVEF) and an up-regulation of cardiac β-MHC and atrial natriuretic peptide (ANP) expression. However, prior IO did not exacerbate the DOX-induced fall in LVEF and there was no increase in ANP expression. IO did not impair the capacity of DOX to decrease cancer cell viability and could even prevent some aspects of DOX cardiotoxicity in cardiomyocytes and in mice.

Topics: Animals; Cardiomegaly; Cardiotoxicity; Cell Line; Cell Line, Tumor; Cell Survival; Dextrans; Doxorubicin; Heart Ventricles; Iron; Iron Overload; Male; Mice; Mice, Inbred C57BL; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxidative Stress; Up-Regulation; Ventricular Myosins

Adjuvant trastuzumab with chemotherapy is the treatment of choice for patients with human epidermal growth factor receptor positive (HER2+) breast cancer and improves the outcome of patients with early breast cancer. However, it is potentially cardiotoxic and there are no validated methods of early detection of cardiotoxicity from trastuzumab following anthracycline-based chemotherapy. Currently, changes in left ventricular ejection fraction (LVEF) are assessed but this approach has limited sensitivity and specificity. Early identification of patients at risk for cardiotoxic effects is a primary goal for both cardiologists and oncologists. Plasma markers such as b-type natriuretic peptide (BNP - an index of elevated filling pressure) and troponin I (TnI - an index of cardiomyocyte damage) may be used to identify the risk of developing cardiac dysfunction during treatment. In this review, we discuss if TnI and/or BNP could be used to help the prevention or treatment of cardiac dysfunction at the earliest possible time.

Topics: Adjuvants, Immunologic; Anthracyclines; Antineoplastic Agents; Biomarkers; Breast Neoplasms; Cardiotoxicity; Early Detection of Cancer; Female; Humans; Natriuretic Peptide, Brain; Risk Assessment; Trastuzumab; Troponin I

Identification of patient with increased risk of cardiotoxicity would allow not only prevention and early diagnosis of chemotherapy related cardiotoxicity but also administration of optimal dose and duration of chemotherapy.. Fifty-two women with HER2(+) breast cancer treated with trastuzumab were included in this study. Patients were prospectively followed with routine cardiac evaluation. Before and after administration of trastuzumab blood samples for NT-proBNP were also taken.. The median age was 48.5 year (range: 26-74). Hypertension and obesity were two most common co-morbidities. The median duration application of trastuzumab was 52 weeks. During median 14.5 (3-33) months follow-up cardiac adverse events occurred in 5 (9.6%) patients and 2 out of 5 was grade III-IV heart failure. Both patients had preserved left ventricular ejection fraction and no symptom of heart failure before trastuzumab but older than 65 years old and had diabetes mellitus and obesity. High level of NT-proBNP (> 300 ng/ml) was observed in both patients and heart failure recovery was not observed. There was statistically significant difference regarding body mass index (p = 0.004) and diabetes mellitus (p = 0.002) between patients with and without cardiotoxicity.. Although, cardiac biomarkers still cannot replace routine cardiac monitoring, natriuretic peptides may provide additional tool for detection of patients with high risk of cardiotoxicity and early detection of cardiotoxicity.

Topics: Adult; Aged; Antibodies, Monoclonal, Humanized; Antineoplastic Agents; Biomarkers; Breast; Breast Neoplasms; Cardiotoxicity; Female; Follow-Up Studies; Heart; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Trastuzumab

Phycotoxins are marine toxins produced by phytoplankton that can get accumulated in filter feeding shellfish. Human intoxication episodes occur due to contaminated seafood consumption. Okadaic acid (OA) and dynophysistoxins (DTXs) are phycotoxins responsible for a severe gastrointestinal syndrome called diarrheic shellfish poisoning (DSP). Yessotoxins (YTXs) are marine toxins initially included in the DSP class but currently classified as a separated group. Food safety authorities from several countries have regulated the content of DSPs and YTXs in shellfish to protect human health. In mice, OA and YTX have been associated with ultrastructural heart damage in vivo. Therefore, this study explored the potential of OA, DTX-1 and YTX to cause acute heart toxicity. Cardiotoxicity was evaluated in vitro by measuring hERG (human èter-a-go-go gene) channel activity and in vivo using electrocardiogram (ECG) recordings and cardiac damage biomarkers. The results demonstrated that these toxins do not exert acute effects on hERG channel activity. Additionally, in vivo experiments showed that these compounds do not alter cardiac biomarkers and ECG in rats acutely. Despite the ultrastructural damage to the heart reported for these toxins, no acute alterations of heart function have been detected in vivo, suggesting a functional compensation in the short term.

Topics: Animals; Cardiotoxicity; CHO Cells; Cricetinae; Cricetulus; Electrocardiography; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels; Female; Mollusk Venoms; Natriuretic Peptide, Brain; Okadaic Acid; Oxocins; Pyrans; Rats; Rats, Sprague-Dawley; Troponin I; Troponin T

Childhood cancer survivors treated with anthracyclines and mediastinal irradiation are at risk for late onset cardiotoxicity.. To assess the role of N-terminal pro-brain natriuretic peptide (NT-proBNP) and tissue Doppler imaging (TDI) as early predictors of late onset cardiotoxicity in asymptomatic survivors of childhood cancer treated with doxorubicin with or without mediastinal irradiation.. A cross-sectional study on 58 asymptomatic survivors of childhood cancer who received doxorubicin in their treatment protocols and 32 asymptomatic Hodgkin's lymphoma survivors who received anthracycline and mediastinal irradiation. Levels of NT-proBNP, TDI, and conventional echocardiography were determined.. Thirty percent of survivors had abnormal NT-proBNP levels. It was significantly related to age at diagnosis, duration of follow-up, and cumulative dose of doxorubicin. TDI detected myocardial affection in 20% more than conventional echocardiography. Furthermore, abnormalities in TDI and NT-pro-BNP levels were more common in Hodgkin lymphoma survivors receiving both chemotherapy and radiotherapy.. TDI could detect early cardiac dysfunction even in those with normal conventional echocardiography. Measurement of NT-proBNP represents an interesting strategy for detecting subclinical cardiotoxicity. We recommend prospective and multicenter studies to validate the role of NT-proBNP as an early marker for late onset doxorubicin-induced cardiotoxicity.

Topics: Antineoplastic Agents; Biomarkers; Cardiotoxicity; Child; Child, Preschool; Doxorubicin; Female; Heart Diseases; Hodgkin Disease; Humans; Male; Natriuretic Peptide, Brain; Peptide Fragments; Radiotherapy; Survivors

Assessing a diverse biomarker panel (NT-proBNP, TNF-α, galectin-3, IL-6, Troponin I, ST2 and sFlt-1) to detect subclinical cardiotoxicity after treatment with anthracyclines.. Of 55 breast cancer patients biomarkers were assessed and echocardiography was performed one year after treatment with anthracyclines.. 29.1% of patients showed abnormal biomarker levels: NT-proBNP in 18.2%, TNF-α and Galectin-3 in 7.3%. IL-6, troponin I, ST2 and sFlt-1 were normal in all patients. A correlation between left ventricular ejection fraction (LVEF) and NT-proBNP was observed (r = -0.564, p ≤ 0.01).. The evaluated biomarkers do not contribute to early detection. Future research should focus on NT-proBNP.

Topics: Adolescent; Adult; Aged; Antineoplastic Agents; Biomarkers; Breast Neoplasms; Cardiotoxicity; Cardiovascular Diseases; Cyclophosphamide; Docetaxel; Doxorubicin; Echocardiography; Electroencephalography; Enzyme-Linked Immunosorbent Assay; Female; Galectin 3; Heart; Humans; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Sensitivity and Specificity; Taxoids; Tumor Necrosis Factor-alpha; Young Adult

Biomarkers may play an important role in identifying patients at risk for cancer therapy cardiotoxicity. Our objectives were to define the patterns of change in biomarkers with cancer therapy and their associations with cardiotoxicity.. In a multicenter cohort of 78 breast cancer patients undergoing doxorubicin and trastuzumab therapy, 8 biomarkers were evaluated at baseline and every 3 months over a maximum follow-up of 15 months. These biomarkers, hypothesized to be mechanistically relevant to cardiotoxicity, included high-sensitivity cardiac troponin I (hs-cTnI), high-sensitivity C-reactive protein (hsCRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), myeloperoxidase (MPO), placental growth factor (PlGF), soluble fms-like tyrosine kinase receptor-1 (sFlt-1), and galectin 3 (gal-3). We determined if biomarker increases were associated with cardiotoxicity at the same visit and the subsequent visit over the entire course of therapy. Cardiotoxicity was defined by the Cardiac Review and Evaluation Criteria; alternative definitions were also considered.. Across the entire cohort, all biomarkers except NT-proBNP and gal-3 demonstrated increases by 3 months; these increases persisted for GDF-15, PlGF, and hs-cTnI at 15 months. Increases in MPO, PlGF, and GDF-15 were associated with cardiotoxicity at the same visit [MPO hazard ratio 1.38 (95% CI 1.10-1.71), P = 0.02; PlGF 3.78 (1.30-11.0), P = 0.047; GDF-15 1.71 (1.15-2.55), P = 0.01] and the subsequent visit. MPO was robust to alternative outcome definitions.. Increases in MPO are associated with cardiotoxicity over the entire course of doxorubicin and trastuzumab therapy. Assessment with PlGF and GDF-15 may also be of value. These findings motivate validation studies in additional cohorts.

Topics: Adult; Antineoplastic Agents; Biomarkers; Breast; Breast Neoplasms; C-Reactive Protein; Cardiotoxicity; Cardiotoxins; Doxorubicin; Female; Galectin 3; Growth Differentiation Factor 15; Heart; Humans; Longitudinal Studies; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Prognosis; Trastuzumab; Troponin I; Vascular Endothelial Growth Factor Receptor-1

This study was undertaken to prospectively evaluate and compare the acute effect of high-dose (HD), cyclophosphamide (CY) and HD etoposide (ET) on cardiac function assessed by plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) in patients undergoing stem-cell mobilization. NT-proBNP was measured at baseline and 6h after completion of mobilization chemotherapy (MC) in 58 patients. Of 58 patients, 33 received HD CY, and 25 received HD ET. The mean baseline NT-proBNP values were similar between the CY and ET group (119.5 vs 149, respectively, p>0.05). NT-proBNP levels were increased in almost all patients, except 2 from CY group. A significant difference between NT-proBNP concentrations at baseline and 6h after completion of MC was observed in both groups (p<0.001). The value of changes in NT-proBNP was more significant in the ET group. The changes in NT-proBNP according to the MC regimens were analyzed and a cut-off value of 422pg/ml was determined. Based on this cut-off value, only the type of MC was significantly correlated with the chances in NT-proBNP concentrations. Receiving HD ET as a MC was found to be 5.25 times more cardiotoxic compared to the HD CY. Congestive heart failure was seen in 3 (5.2%) patients. Our results suggest that stem cell mobilization with HD CY and HD ET cause acute cardiac toxicity mediated by neurohumoral activation, which was detected by the increases in cardiac biomarker NT-proBNP, and as a matter of fact cardiotoxicity of HD ET seems to be more potent than those exhibited by HD CY.

Topics: Adult; Aged; Antineoplastic Agents; Cardiotoxicity; Cyclophosphamide; Etoposide; Female; Heart; Hematologic Neoplasms; Hematopoietic Stem Cell Mobilization; Humans; Male; Middle Aged; Myocardium; Natriuretic Peptide, Brain; Peptide Fragments; Prospective Studies; Risk; ROC Curve; Time Factors; Treatment Outcome; Young Adult

Doxorubicin is widely used against cancer; however, it can produce heart failure (HF). Among other hallmarks, oxidative stress is a major contributor to HF pathophysiology. The late INa inhibitor ranolazine has proven effective in treating experimental HF. Since elevated [Na+]i is present in failing myocytes, and has been recently linked with reactive oxygen species (ROS) production, our aim was to assess whether ranolazine prevents doxorubicin-induced cardiotoxicity, and whether blunted oxidative stress is a mechanism accounting for such protection.. In C57BL6 mice, doxorubicin treatment for 7 days produced LV dilation and decreased echo-measured fractional shortening (FS). Ranolazine (305 mg/kg/day) prevented LV dilation and dysfunction when co-administered with doxorubicin. Doxorubicin-induced cardiotoxicity was accompanied instead by elevations in atrial natriuretic peptide (ANP), BNP, connective tissue growth factor (CTGF), and matrix metalloproteinase 2 (MMP2) mRNAs, which were not elevated on co-treatment with ranolazine. Alterations in extracellular matrix remodelling were confirmed by an increase in interstitial collagen, which did not rise in ranolazine-co-treated hearts. Levels of poly(ADP-ribose) polymerase (PARP) and pro-caspase-3 measured by western blotting were lowered with doxorubicin, with increased cleavage of caspase-3, indicating activation of the proapoptotic machinery. Again, ranolazine prevented this activation. Furthermore, in HL-1 cardiomyocytes transfected with HyPer to monitor H2O2 emission, besides reducing the extent of cell death, ranolazine prevented the occurrence of oxidative stress caused by doxorubicin. Interestingly, similar protective results were obtained with the Na+/Ca2+ exchanger (NCX) inhibitor KB-R7943.. Ranolazine protects against experimental doxorubicin cardiotoxicity. Such protection is accompanied by a reduction in oxidative stress, suggesting that INa modulates cardiac redox balance, resulting in functional and morphological derangements.

Topics: Acetanilides; Animals; Antibiotics, Antineoplastic; Atrial Natriuretic Factor; Blotting, Western; Cardiotoxicity; Connective Tissue Growth Factor; Doxorubicin; Enzyme Inhibitors; Matrix Metalloproteinase 2; Mice; Mice, Inbred C57BL; Myocytes, Cardiac; Natriuretic Peptide, Brain; Oxidative Stress; Piperazines; Poly(ADP-ribose) Polymerases; Ranolazine; Reactive Oxygen Species; Real-Time Polymerase Chain Reaction; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Sodium; Ultrasonography; Ventricular Dysfunction, Left