Early Detection Of Chemotherapy-induced Cardiotoxicity Research Articles

Early detection of chemotherapy-induced cardiotoxicity in breast cancer patients: a comprehensive analysis using speckle tracking echocardiography.

Chemotherapy-induced cardiotoxicity poses a significant challenge in the treatment of breast cancer, potentially compromising both the efficacy of cancer therapy and cardiac health of patients. This study aimed to enhance the early detection of cardiotoxic effects by integrating advanced imaging modalities and biomarker analysis, thereby facilitating timely interventions to mitigate cardiac risk. A prospective cohort design was employed, enrolling breast cancer patients scheduled for potentially cardiotoxic chemotherapy regimens. The study utilized a comprehensive diagnostic toolkit, including echocardiography with strain imaging, cardiac MRI, and serial measurements of cardiac biomarkers such as high-sensitivity troponins and natriuretic peptides. The analysis revealed that subtle changes in myocardial strain parameters and early biomarker elevations were predictive of subsequent declines in left ventricular function, preceding conventional echocardiographic evidence of cardiotoxicity. Logistic regression analysis highlighted the additive predictive value of integrating biomarker data with advanced imaging findings to identify patients with the highest risk of significant cardiotoxicity. The study concluded that an integrated diagnostic approach, combining detailed imaging assessments with sensitive biomarker analysis, offers a superior strategy for the early detection of chemotherapy-induced cardiotoxicity in breast cancer patients. This proactive diagnostic strategy empowers clinicians to tailor cancer therapy more precisely, balancing oncologic efficacy with cardiovascular safety and underscores the importance of a multidisciplinary approach in the management of patients undergoing potentially cardiotoxic chemotherapy.

Global Longitudinal Strain for the Early Detection of Chemotherapy-Induced Cardiotoxicity: A Systematic Review and Meta-analysis

AimsLeft ventricular ejection fraction is used to monitor patients undergoing cardiotoxic chemotherapy. A decrease in left ventricular ejection fraction represents a relatively late stage of systolic involvement. Global longitudinal strain has been studied to detect early changes in left ventricular myocardial contractile function. The aim of the present study was to evaluate the global longitudinal strain measurement in the early detection of cardiotoxicity induced by cardiotoxic chemotherapeutic agents. Materials and methodsA study search strategy based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was carried out to report systematic reviews. A search on PubMed, EMBASE, Web of Science and SCOPUS was carried out using the following keywords: ‘echocardiography’ and ‘cardiotoxicity’ and their variations, without language or date restrictions (until March 2021). ResultsIn total, 4873 articles were identified for title and abstract analysis. The systematic review included 10 studies comprising 661 patients with cancer, including mainly breast cancer and haematological malignancies, mainly treated with anthracyclines. The meta-analysis included four studies: patients with cardiotoxicity showed a reduction in strain, compared with baseline, 14.13% greater than patients without cardiotoxicity (95% confidence interval 5.07–23.19; P < 0.01). No heterogeneity was observed between studies (I2 = 0). ConclusionThe meta-analysis showed that strain is a tool with proper predictive capacity for the detection of cardiotoxicity.

The integrated role of NT-pro BNP and STE-GLS for the early detection of chemotherapy-induced cardiotoxicity

Abstract Background Chemotherapeutic agents, used for the treatment of breast cancer, have many side effects, among them is cardiomyopathy. Ejection fraction (EF) is fails to detect the subtle alterations of left ventricular (LV) function. There comes the need for a more sensitive tool for the detection of preclinical chemotherapy-induced cardiomyopathy. Aim Detection of subclinical LV systolic dysfunction in breast cancer patients after 6 weeks of the initiation of their chemotherapeutic treatment, using N-terminal pro brain natriuretic peptide (NT-proBNP) plasma level as well as Speckle tracking echo-global longitudinal strain (STE-GLS). Methods Seventy-four asymptomatic, non-metastasizing breast cancer female patients were included. They were assessed before taking their first chemotherapeutic session and 6 weeks thereafter. Assessment included baseline clinical characteristics, conventional two-dimensional (2D) as well as three-dimensional (3D) echocardiography. Loops of different apical views were recorded for later offline STE-GLS analysis. Blood samples for NT-BNP plasma level were collected before and 6 weeks after the initiation of chemotherapy. Samples were later analyzed using a Sandwich ELISA technique. Results The median NT-proBNP almost doubled after 6 weeks of chemotherapy (73.50 vs 34.4 pg/L, p value &amp;lt;0.001). One patient died before her scheduled follow up visit, and the cause of death is unknown. Fifty patients showed NT-proBNP elevation at their follow up, compared to the baseline visit, 22 (44%) of them had worse (less negative) LV-GLS in their follow up visit. Five patients had an abnormally elevated NT-proBNP plasma level, all of them had a worse follow up LV-GLS. Only two patients showed significant reduction of LVEF &amp;gt;10% to less &amp;lt;53% (chemotherapy-induced cardiotoxicity) but their NT-proBNP did not exceed the cutoff limit. Conclusion The integration of LV-GLS and NT-proBNP is useful in the diagnosis of subclinical, subtle chemotherapy-induced cardiotoxicity. Early detection will prompt early cardioprotective measures and thus helps improving the clinical outcomes. Funding Acknowledgement Type of funding source: None

Cumulative incidence of chemotherapy-induced cardiotoxicity during a 2-year follow-up period in breast cancer patients.

Cardiotoxicities are adverse effects often reported in chemotherapy-treated breast cancer patients. This study evaluated the potential risk factors and cumulative incidence of doxorubicin-induced cardiotoxicity in Korean breast cancer patients. We retrospectively analyzed the data of 613 breast cancer patients who underwent a multigated acquisition (MUGA) scan or echocardiography prior to chemotherapy and at least one post-chemotherapy follow-up MUGA scan/echocardiography between 2007 and 2016 at National Cancer Center, Korea. The Cox proportional hazards models were used to evaluate cardiotoxicity risks. Competing risks analyses were performed to estimate cumulative incidence of cardiotoxicity. Risk factors associated with cardiotoxicity within 2years of doxorubicin administration included age [adjusted hazard ratio (aHR) = 1.02, 95% confidence interval (CI) 1.00-1.04; p = 0.05], metastasis (aHR = 2.66; 95% CI 1.36-5.20; p < 0.01), and concomitant trastuzumab (aHR = 4.08; 95% CI 2.31-7.21; p < 0.01). The cumulative incidence of patients with cardiotoxicity was 6.1% at 2years (without substantial change from about 9months)and 20.2% at 2years (without substantial change from about 15months) after initiation of doxorubicin-containing therapy without and with trastuzumab, respectively. Susceptibility to chemotherapy-induced cardiotoxicity within 2years of doxorubicin initiation in breast cancer patients was elevated with old age, metastasis, and concomitant trastuzumab. Regular imaging monitoring at least up to 9months after doxorubicin initiation in patients treated without concomitant trastuzumab, and 15months in patients treated with concomitant trastuzumab, is needed for early detection of chemotherapy-induced cardiotoxicity.

Research progress of biomarkers in early detection of chemotherapy-induced cardiotoxicity.

With the advances of drug therapy, the prognosis of cancer patients has seen remarkable improvements, and cancer-related mortality has decreased significantly. However, the followed drug-related cardiotoxicity becomes a serious threat to patients' living quality and survival rate. Cardiovascular toxicity associated with some chemotherapy drugs is reversible and dose-dependent. If early identification is possible, early cardiovascular protection measures or adjustment of chemotherapy regimens can be taken to improve the prognosis of patients. Therefore, early prevention and monitoring of chemotherapy-related cardiotoxicity are critical for cancer patients and survivors. Among them, biomarkers are an important method for the early identification of myocardial injury.

Abstract P1-12-08: Association of CBR3 polymorphisms with an early change in cardiac function as assessed by left ventricular global longitudinal strain in breast cancer patients treated with doxorubicin

Abstract Progress made in early cancer diagnosis and therapy has translated into increased longevity for patients with breast cancer. As survival has increased, the potential cardiotoxicity of cancer chemotherapy regimens has become an important issue for survivorship. Doxorubicin-induced cardiotoxicity has been demonstrated at a cumulative dose of ≤ 300mg/m2, with histopathological changes seen in endomyocardial biopsy tissue from patients receiving as little as 240mg/m2 of doxorubicin. Individual risk stratification and early detection of chemotherapy-induced cardiotoxicity are crucial to prevent irreversible cardiac dysfunction. There is accumulating evidence for the utility of echocardiographic indices such as left ventricular global longitudinal strain (GLS) in the detection of early chemotherapy induced cardiac injury. We have previously highlighted a predictive role of genetic polymorphisms in the carbonyl reductase 3 gene CBR3 in anthracycline-related cardiomyopathy following childhood cancer. Consistent with our prior work, we hypothesized that breast cancer patients homozygous for the CBR3 V244M G allele would exhibit worsening GLS following DOX treatment when compared with patients homozygous for the A allele. We recruited 138 patients with breast cancer receiving treatment with DOX (total cumulative dose: 240mg/m2). 72 patients received an echocardiogram analyzing global longitudinal strain by speckle tracking at baseline (t0 month) and at 6 months (t6 months) of follow up after DOX treatment. Patients were genotyped for variants associated with anthracycline-related toxicity. In agreement with our previous findings and hypothesis, our interim analysis suggested that patients homozygous for the CBR3 V244M G allele (CBR V244) exhibited GL changes at 6 months after DOX therapy suggestive of cardiotoxicity in comparison to individuals homozygous for the A allele (CBR3 M244) (-1.2 ±3.5 vs 1±1.6; mean±SEM, p=0.8 by Mann-Whitney test). Although the differences between CBR3 genotype groups are not significant at p&amp;lt;0.05, the direction and magnitude of changes in ventricular GL are well in line with various reports describing early detection of cardiotoxicity in similarly treated breast cancer patients. This study outlines a potential role for screening CBR3 polymorphisms in patients prior to DOX therapy and highlights a need for further investigation into the pharmacogenomics of chemotherapy-induced cardiotoxicity. Citation Format: Lang JK, Quinones AL, Hageman Blair R, Early AP, Levine EG, Opyrchal M, Blanco JG, O'Connor T. Association of CBR3 polymorphisms with an early change in cardiac function as assessed by left ventricular global longitudinal strain in breast cancer patients treated with doxorubicin [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-08.

Abstract P3-14-07: Early detection of chemotherapy-induced cardiotoxicity in breast cancer patients

Abstract BACKGROUND The incidence of cardiotoxicity in patients receiving treatment for breast cancer is unknown. There is not enough evidence about early detection and appropriate management of cardiotoxicity. The aim of this study is to identify early markers of risk of cardiac toxicity. MATERIAL AND METHOD Prospective study was conducted between 2014 and 2017 based on a cohort of 97 patients diagnosed with breast cancer treated with chemotherapy. Analytical biomarkers (natriuretic peptide, ultra-sensitive T troponin), echocardiogram parameters (left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS)) and electrocardiogram were performed. Analytical biomarkers were measured each chemotherapy cycle and cardiology test were performed before starting chemotherapy, 3 months afterwards, and then every six months during 5 years. Cardiotoxicity was defined as a reduction in basal LVEF &amp;gt;10% with LVEF&amp;lt;55% in asymptomatic patients or &amp;gt;5% with LVEF&amp;lt;55% in symptomatic patients. RESULTS Patients characteristics are shown in table 1 Patients characteristicsVariablesNo cardiotoxicity (n=88)Cardiotoxicity (n=12)Gender (women/men)88/012/0Median age (range)53 years (29-79)47 years (37-70)Smoker (former smoker)13 (3)2 (2)Arterial hypertension202Dyslipemia160Diabetes62Previous chemotherapy11Prior mediastinal radiation therapy01 . All patients had the basal LVEF in normal range. Median follow-up was 26.5 months (13,5-39,6 months). A total of 10.3% had cardiotoxicity with reduction in basal LVEF &amp;gt;10% with LVEF&amp;lt;55% being asymptomatic and 2.1% were symptomatic. Five of these patients were treated with heart failure therapy: 5 with ACE (angiotensin converting enzyme) inhibitors and 3 with beta- blockers. Two of those (40%) who received specific treatment recovered basal LVEF-levels, 2 maintained LVEF dysfunction, and 1 died during follow-up due to tumor-related causes. In 83.3% of patients, cardiotoxicity occurred within the first year of follow-up. In 50 patients SLG was calculated, in 30% it was lower than -12% in some measurement phase. In 5 cases the LVEF fell below 55% and the LRP decreased by 12% coincided. The others patients, although they did not develop cardiotoxicity according to the established criteria, a decrease of the LVEF is observed during the treatment and in the first control, between 3-7%, which subsequently tends to recover spontaneously. miRNA 21-5p, miRNA-133b, miRNA 210-3p, miRNA 423-5p, and miRNA-663b were analyzed. A model has been evaluated where a correlation between the levels of miRNA-133b, miRNA-21-5p and miRNA-210-3p and the decrease of LVEF in relation to treatment was observed. CONCLUSIONS Control by echocardiography and serum markers allowed us to detect early cardiotoxicity events and provide us an opportunity to start heart failure therapy on time with the aim of improving the control and evolution of it.Levels of miR-133b, miR-21-5p and miR-210 may alert for a risk of cardiotoxicity and can help to make decisions about treatments. Acknowledgements: Project funded by European Comission (Hecatos FP7-HEALTH-2013-INNOVATION-1. Reference: CP-IP 602156-1) and RETICS program (RD12/0019/0025) cofunded by FEDER "una manera de hacer Europa”. Citation Format: Salvador-Coloma C, Hernándiz A, Tejedor S, Miró V, Palomar L, Salvador A, Sepúlveda P, Santaballa A. Early detection of chemotherapy-induced cardiotoxicity in breast cancer patients [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-14-07.

Cardiovascular imaging in the diagnosis and monitoring of cardiotoxicity: cardiovascular magnetic resonance and nuclear cardiology.

Chemotherapy-induced cardiotoxicity (CTX) is a determining factor for the quality of life and mortality of patients administered potentially cardiotoxic drugs and in long-term cancer survivors. Therefore, prevention and early detection of CTX are highly desirable, as is the exploration of alternative therapeutic strategies and/or the proposal of potentially cardioprotective treatments. In recent years, cardiovascular imaging has acquired a pivotal role in this setting. Although echocardiography remains the diagnostic method most used to monitor cancer patients, the need for more reliable, reproducible and accurate detection of early chemotherapy-induced CTX has encouraged the introduction of second-line advanced imaging modalities, such as cardiac magnetic resonance (CMR) and nuclear techniques, into the clinical setting. This review of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology aims to afford an overview of the most important findings from the literature about the role of CMR and nuclear techniques in the management of chemotherapy-treated patients, describe conventional and new parameters for detecting CTX from both diagnostic and prognostic perspectives and provide integrated insight into the role of CMR and nuclear techniques compared with other imaging tools and versus the positions of the most important international societies.

Chemotherapy-induced cardiomyopathy in breast cancer patients.

Dear Editor The globally increasing incidence of cancer and its associated mortality has become a main challenge for humankind. This problem is more serious in developing countries, like Iran. Among different malignancies affecting people, breast cancer continues to be a main and worldwide cause of morbidity and mortality (1). Parallel to the increasing cancer burden in the modern world, there have been notable progresses in the management and therapy (either medical or nonmedical) of malignancies including breast cancer, leading to a significant increase in the number of survived patients. This necessitates a close follow-up of such patients after their initial management (2). Patients with cancer face daily problems, some of which are difficult to overcome. Among these are possible complications associated with their chemotherapeutic regimens, particularly cardiovascular issues (3). Cardiotoxic nature of drugs used for the management of patients with cancer puts them at risk of numerous life-threatening cardiovascular events, like pericarditis, cardiomyopathy, cardiac arrhythmias, myocardial ischemia, and some others. Factors including cumulative drug doses, mediastinal radiation, rate of drug administration, younger age, advanced age, female gender, hypertension, and preexisting heart diseases are the recognized risk factors for developing early (within one year, but not acute) and late chemotherapy-induced cardiotoxicity (Table 1) (4). Table 1. Cardiac Review and Evaluation Committee Diagnostic Criteria for Drug-Associated Cardiotoxicity (3) a A wide variety of chemotherapeutic drugs can cause cardiotoxicity, among which anthracyclines, a main drug class used for patients with breast cancer, are one of the most common etiologies (5). Doxorubicin, a main member of this group, can lead to dose-dependent, irreversible and recurrent cardiotoxicity. It can cause myocardial damage through disorganization of myofibrillar morphology, necrosis and interstitial fibrosis (6). The other instance is Trastuzumab, a monoclonal antibody which inhibits growth of tumor cells that overexpress human epidermal growth factor 2 protein. This medication can cause reversible cardiac side effects regardless of the administration dosage, and with low possibility of recurrence (7). Some points were suggested to be beneficial in reducing the risk of cardiotoxicity following chemotherapy. Among these are decreasing the cumulative doses of anthracyclines, administration of anthracyclines as infusion (rather than bolus), and the liposomal encapsulation of doxorubicin. Using β receptor blockers (like carvedilol or metoprolol), angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and using nutritional supplements (antioxidants like vitamin E) are the other recommendations (4, 8). Access to cancer medicine is of great importance for patients, also their follow-up for early detection of chemotherapy-induced cardiotoxicity is important. At present, different methods including measurement of left ventricular ejection fraction as the most common screening technique, measurement of serum biochemical cardiac markers, targeted cardiac imaging and some others have been used to reach this purpose. However, each of these methods has its own advantages and disadvantages. In fact, lack of a comprehensive guideline for approaching chemotherapy-induced cardiotoxicity necessitate the need for further investigations in this area of research (9). The incidence of breast cancer in Iran has increased over the recent years (10). As a point of criticism, a review of the current medical literature reveals no available strong survey for the assessment of forthcoming problems, in particular cardiovascular diseases, facing Iranian patients with breast cancer after their initial treatment. Undeniably, after the diagnosis of such patients, every effort is made to provide them an appropriate care and therapy; however, there is a strong need for a close collaboration between oncologists and cardiologists for a systematic and planned follow-up of patients with breast cancer following receiving their medical therapies. This would be a valuable help in decreasing morbidity in this group of patients from cardiovascular problems and improving their quality of life after the initiation of therapy.