Chemotherapy-induced Cardiotoxicity Research Articles

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<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.

Tissue-specific regulation of p53 by PKM2 is redox dependent and provides a therapeutic target for anthracycline-induced cardiotoxicity.

Chemotherapy-induced cardiotoxicity (CIC) is a common clinical problem that compromises effective anticancer therapies. Many chemotherapeutics (including anthracyclines, such as doxorubicin) induce the proapoptotic transcription factor p53 in the tumor and nonspecifically in the heart, promoting heart failure. Although inhibition of p53 shows benefit in preclinical heart failure models, it would not be an attractive adjuvant therapy for CIC, because it would prevent tumor regression. A p53-targeting therapy that would decrease chemotherapy-induced apoptosis in the myocardium and, at the same time, enhance apoptosis in the tumor would be ideal. Here, we propose that differences in oxygen tension between the myocardium and the tumor could provide a platform for redox-dependent tissue-specific therapies. We show by coimmunoprecipitation and mass spectrometry that the redox-regulated pyruvate kinase muscle 2 (PKM2) directly binds with p53 and that the redox status of cysteine-423 of tetrameric (but not monomeric) PKM2 is critical for the differential regulation of p53 transcriptional activity. Tetrameric PKM2 suppresses p53 transcriptional activity and apoptosis in a high oxidation state but enhances them in a low oxidation one. We show that the oxidation state (along with cysteine-423 oxidation) is higher in the heart compared to the tumor of the same animal. Treatment with TEPP-46 (a compound that stabilizes tetrameric PKM2) suppressed doxorubicin-induced cardiomyocyte apoptosis, preventing cardiac dysfunction, but enhanced cancer cell apoptosis and tumor regression in the same animals in lung cancer models. Thus, our work suggests that redox-dependent differences in common proteins expressed in the myocardium and tumor can be exploited therapeutically for tissue selectivity in CIC.

In vivo positron emission tomographic blood pool imaging in an immunodeficient mouse model using 18F-fluorodeoxyglucose labeled human erythrocytes.

99m-Technetium-labeled (99mTc) erythrocyte imaging with planar scintigraphy is widely used for evaluating both patients with occult gastrointestinal bleeding and patients at risk for chemotherapy-induced cardiotoxicity. While a number of alternative radionuclide-based blood pool imaging agents have been proposed, none have yet to achieve widespread clinical use. Here, we present both in vitro and small animal in vivo imaging evidence that the high physiological expression of the glucose transporter GLUT1 on human erythrocytes allows uptake of the widely available radiotracer 2-deoxy-2-(18F)fluoro-D-glucose (FDG), at a rate and magnitude sufficient for clinical blood pool positron emission tomographic (PET) imaging. This imaging technique is likely to be amenable to rapid clinical translation, as it can be achieved using a simple FDG labeling protocol, requires a relatively small volume of phlebotomized blood, and can be completed within a relatively short time period. As modern PET scanners typically have much greater count detection sensitivities than that of commonly used clinical gamma scintigraphic cameras, FDG-labeled human erythrocyte PET imaging may not only have significant advantages over 99mTc-labeled erythrocyte imaging, but may have other novel blood pool imaging applications.

Effect of Rosuvastatin in Preventing Chemotherapy-Induced Cardiotoxicity in Women With Breast Cancer: A Randomized, Single-Blind, Placebo-Controlled Trial.

Chemotherapy-induced cardiotoxicity is a major and leading cause of death in breast cancer survivors. It can present decades after chemotherapy and can manifest in different ways; some chemotherapeutic agents have a powerful dose-dependent relationship with cardiotoxicity. The aim of this study was to investigate the effect of rosuvastatin on preventing chemotherapy-induced cardiotoxicity in patients with breast cancer. Our study was a randomized, single-blind, placebo-controlled trial that involved 89 women with newly diagnosed breast cancer who were scheduled to receive chemotherapy. Patients were randomly assigned to receive rosuvastatin or a placebo in a 1:1 ratio for 6 months. Echocardiography, using 2-dimensional (2D) Doppler, tissue Doppler, and speckle-tracking methods, was used to determine the absolute changes in the left ventricular systolic ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left atrial (LA) diameter, transmitral Doppler early diastolic velocity (E wave), tissue Doppler early diastolic (e') and peak systolic (s') mitral annular velocities, E/e' ratio, and global longitudinal systolic strain. The LVEF was significantly reduced in the placebo group at the end of the study when compared with the baseline value. However, there was no significant difference in the LVEF in the intervention group (intergroup P = .012). Furthermore, compared with the intervention group at the end of the study, there was a significant increase in the 4- and 2-chamber LVESV, LA diameter, and E/e' ratio in the placebo group (intergroup P = .019, P = .024, P < .001, and P = .021, respectively) and a significant decrease in the e' and s' velocities in the placebo group (intergroup P < .001 and P < .006, respectively). The present study showed that the prophylactic use of rosuvastatin may prevent the development of chemotherapy-induced cardiotoxicity.

Rol del strain miocárdico en cardiotoxicidad por quimioterapia

The advances in conventional therapies and the development of new ones against cancer, has led to a better prognosis, and a continuous increase in survivors. However, the morbidity and mortality rates of cardiovascular diseases have increased due to the direct and indirect effects, or both, of the treatment. Thus, the management approach is not now solely directed on overcoming the malignancy, but emphasis is also placed on the early identification and management of any secondary effects. For this reason, echocardiography is essential for the close follow-up of the patients, myocardial strain imaging, in particular, has become a tool for the early identification of patients with chemotherapy-induced cardiotoxicity. In this review, the role of myocardial strain imaging is evaluated as regards its potential use in detecting sub-clinical changes in cardiac function, as well as to evaluate the prognosis due to chemotherapy-induced cardiotoxicity.

Protective role of beta-blockers in chemotherapy-induced cardiotoxicity\u2014a systematic review and meta-analysis of carvedilol

Some randomized controlled trials (RCTs) have tested the efficacy of beta-blockers as prophylactic agents on cancer therapy-induced cardiotoxicity; however, the quality of this evidence remains undetermined. This systematic review and meta-analysis study aims to evaluate the prophylactic effects of beta-blockers, especially carvedilol, on chemotherapy-induced cardiotoxicity. RCTs were identified by searching the MEDLINE (PubMed), Embase (OvidSP), Cochrane CENTRAL (OvidSP), etc., until December 2017. Inclusion criteria were randomized clinical trial and adult cancer patients started beta-blockers before chemotherapy. We evaluated the mean differences (MD) by fixed- or random-effects model and the odds ratio by Peto’s method. Primary outcome was the left ventricular ejection fraction (LVEF) of patients after chemotherapy, and secondary outcomes were all-cause mortality, clinically overt cardiotoxicity, and other echocardiographic measurements. In total, we included six RCTs that used carvedilol as a prophylactic agent in patients receiving chemotherapy. The LVEF was not significantly distinct between those using carvedilol and placebo after chemotherapy (MD, 1.74; 95% confidence interval (CI), − 0.18 to 3.66; P = 0.08). The incidence of clinically overt cardiotoxicity was lower in the carvedilol group compared with the control group (Peto OR, 0.42; 95% CI, 0.20–0.89; P = 0.02). Furthermore, after chemotherapy, the LV end-diastolic diameter did not increase in the carvedilol group compared with the placebo group (MD, − 1.41; 95% CI, − 2.32 to − 0.50; P = 0.002). The prophylactic use of carvedilol exerted no impact on the early asymptomatic LVEF decrease but seemed to attenuate the frequency of clinically overt cardiotoxicity and prevent ventricular remodeling.

The association between early-onset cardiac events caused by neoadjuvant or adjuvant chemotherapy in triple-negative breast cancer patients and some novel autophagy-related polymorphisms in their genomic DNA: a real-world study

BackgroundAn increasing number of cancer patients die of cardiovascular diseases. The cardiotoxicity of chemotherapy is particularly important in triple-negative breast cancer (TNBC) with limited therapeutic options. Cardiac autophagy is an important mechanism of cardiotoxicity. This research was aimed to investigate the cardiotoxicity of chemotherapy in TNBC, screen the susceptible population, and determine the relationship between cardiotoxicity and autophagy-related polymorphisms.MethodsFrom a total of 2450 stage I-III TNBC patients, 147 met the inclusion criteria and finally recruited. Electrocardiography (ECG) was performed before most chemotherapy cycles, and echocardiography (UCG) was performed according to clinical needs. All ECG and UCG records were re-interpreted by cardiologists at the National Center for Cardiovascular Disease, Fuwai Hospital. According to the National Center for Biotechnology Information and the Catalog of Somatic Mutations in Cancer database, we selected 25 single nucleotide polymorphisms (SNPs) related to autophagy and genotyped the 147 TNBC patients. Paired-sample T tests, Chi squared tests, and logistic regression models were employed for the analysis.ResultsOnly 46 (31.3%) patients had normal ECG records after every chemotherapy cycle. Among the 16 patients who underwent UCG, 2 (12.5%) had a reversible decrease of left ventricular ejection fraction. The use of anthracyclines and excessive alcohol consumption were risk factors of ECG abnormalities. With the continuation of chemotherapy, heart rate gradually increased. Anthracyclines were associated with QRS duration abnormalities (P = 0.043). After genotyping for 25 autophagy-related SNPs, we found that the G allele of autophagy-related 13 (ATG13) rs10838611 was significantly associated with ECG abnormalities (odds ratio = 2.258, 95% confidence interval = 1.318–3.869; P = 0.003).ConclusionECG abnormalities caused by chemotherapy are common in the real world. Autophagy-related SNPs are associated with chemotherapy-induced cardiotoxicity, thereby providing new evidence for autophagy as a cause of chemotherapy-induced cardiac damage.

Application of radionuclide imaging in the monitoring of chemotherapy-induced cardiotoxicity

Chemotherapy is commonly used for cancer treatment. With the development of diagnostic techniques, surgical methods and chemotherapy programs, the survival rate of cancer patients has been improved significantly. On the other hand, many chemotherapy drugs have cardiotoxicity and may cause fatal heart damage, such as myocardial infarction and heart failure. Therefore, it is necessary to monitor the occurrence of cardiotoxicity so that preventive measures could be taken timely. Compared with other methods, radionuclide imaging based on the molecular level has its unique advantage. This review briefly evaluates the current monitoring methods of chemotherapy-induced cardiotoxicity and focuses on the application of radionuclide imaging in the monitoring of chemotherapy-induced cardiotoxicity. Key words: Neoplasms; Drug therapy; Cardiotoxicity; Radionuclide imaging; Trends

Indole Alkaloid Derivative B, a Novel Bifunctional Agent That Mitigates 5-Fluorouracil-Induced Cardiotoxicity.

Clinically approved therapeutics that mitigate chemotherapy-induced cardiotoxicity, a serious adverse effect of chemotherapy, are lacking. The aim of this study was to determine the putative protective capacity of a novel indole alkaloid derivative B (IADB) against 5-fluorouracil (5-FU)-induced cardiotoxicity. To assess the free-radical scavenging activities of IADB, the acetylcholine-induced relaxation assay in rat thoracic aorta was used. Further, IADB was tested in normal and cancer cell lines with assays gauging autophagy induction. We further examined whether IADB could attenuate cardiotoxicity in 5-FU-treated male ICR mice. We found that IADB could serve as a novel bifunctional agent (displaying both antioxidant and autophagy-modulating activities). Further, we demonstrated that IADB induced production of cytosolic autophagy-associated structures in both cancer and normal cell lines. We observed that IADB cytotoxicity was much lower in normal versus cancer cell lines, suggesting an enhanced potency toward cancer cells. The cardiotoxicity induced by 5-FU was significantly relieved in animals pretreated with IADB. Taken together, IADB treatment, in combination with chemotherapy, may lead to reduced cardiotoxicity, as well as the reduction of anticancer drug dosages that may further improve chemotherapeutic efficacy with decreased off-target effects. Our data suggest that the use of IADB may be therapeutically beneficial in minimizing cardiotoxicity associated with high-dose chemotherapy. On the basis of the redox status difference between normal and tumor cells, IADB selectively induces autophagic cell death, mediated by reactive oxygen species overproduction, in cancer cells. This novel mechanism could reveal novel therapeutic targets in chemotherapy-induced cardiotoxicity.

Amino acid modified [70] fullerene derivatives with high radical scavenging activity as promising bodyguards for chemotherapy protection

Despite the great efforts for tumor therapy in the last decades, currently chemotherapy induced toxicity remains a formidable problem for cancer patients, and it usually prohibits the cancer therapy from successful completion due to severe side effects. In general, the main side effects of chemotherapeutic agents are from the as-produced reactive oxygen species (ROS) that not only harm the tumor cells but also damage the patients’ organs. Here we report the application of amino acid derivatives of fullerene (AADF) in the chemotherapy which strongly scavenge the excess ROS to protect the tested mice against the chemotherapy-induced hepatotoxicity and cardiotoxicity. Two amino acids, i.e., L-lysine and β-alanine were separately employed to chemically modify C70 fullerene, and L-lysine derivative of fullerene (C70-Lys) exhibits superior radical scavenging activity to β-alanine derivative of C70 (C70-Ala). As expected, C70-Lys show much better protective effect than C70-Ala against the chemotherapy injuries in vivo, which is verified by various histopathological, haematological examinations and antioxidative enzyme studies. Moreover, the L-glutathione level is increased and the cytochrome P-450 2E1 expression is inhibited. They are potentially developed as promising bodyguards for chemotherapy protection.

Prevention of Trastuzumab and Anthracycline-induced Cardiotoxicity Using Angiotensin-converting Enzyme Inhibitors or β-blockers in Older Adults With Breast Cancer.

Although clinical trials have provided some data on the benefit of angiotensin-converting enzyme inhibitors (ACEIs) or β-blockers (BBs) in patients with chemotherapy-induced cardiotoxicity, evidence of ACEIs/BBs on prevention of trastuzumab and/or anthracycline-induced cardiotoxicity outside trials is limited. A cohort study of 142,990 women (66 y and above) newly diagnosed with breast cancer from 2001 to 2009 was conducted using the Surveillance, Epidemiology, and End Results-Medicare-linked database. The ACEI/BB exposure was defined as filled prescription(s) before or after the initiation of trastuzumab/anthracyclines. The nonexposed group was defined as those who had never been prescribed ACEIs/BBs. Cumulative rates of cardiotoxicity and all-cause mortality were estimated and marginal structural Cox models were used to determine factors associated with cardiotoxicity and all-cause mortality adjusting for baseline covariates and use of chemotherapy. All statistical tests were 2 sided. The final sample included 6542 women. Adjusted hazard ratio for cardiotoxicity and all-cause mortality for the ACEI/BB exposed group were 0.77 (95% confidence interval, 0.62-0.95) and 0.79 (95% confidence interval, 0.70-0.90) compared with the nonexposed group, respectively. Starting ACEIs/BBs≤6 months after the initiation of trastuzumab/anthracyclines and having exposed duration≥6 months were also associated with decreased risk of cardiotoxicity and all-cause mortality. Baseline characteristics, including age, non-Hispanic black, advanced cancer, region, comorbidity, preexisting cardiovascular conditions, lower socioeconomic status, and concomitant treatment were significantly associated with an elevated risk of all-cause mortality and/or cardiotoxicity (all P<0.05). ACEIs/BBs show favorable effects on preventing cardiotoxicity and improving survival in female breast cancer patients undergoing trastuzumab/anthracycline treatment.

Renin–Angiotensin System Inhibitors to Mitigate Cancer Treatment–Related Adverse Events

Treatment-related side effects are a major clinical problem in cancer treatment. They lead to reduced compliance to therapy as well as increased morbidity and mortality. Well-known are the sequelae of chemotherapy on the heart, especially in childhood cancer survivors. Therefore, measures to mitigate the adverse events of cancer therapy may improve health and quality of life in patients with cancer, both in the short and long term. The renin-angiotensin system (RAS) affects all hallmarks of cancer, and blockage of the RAS is associated with an improved outcome in several cancer types. There is also increasing evidence that inhibition of the RAS might be able to alleviate or even prevent certain types of cancer treatment-related adverse effects. In this review, we summarize the potential of RAS inhibitors to mitigate cancer treatment-related adverse events, with a special emphasis on chemotherapy-induced cardiotoxicity, radiation injury, and arterial hypertension. Clin Cancer Res; 24(16); 3803-12. ©2018 AACR.

Strategies to increase cardioprotection through cardioprotective chemokines in chemotherapy-induced cardiotoxicity

BackgroundCardiotoxicity is one of the most important side effects of chemotherapy and its management save myocardium from injury and its consequences. AimIn this review we discuss cardioprotective chemokines and cardioprotective mechanisms and pathways that induce cardioprotection through cardioprotective chemokines. MethodWe searched English literature articles in Google scholar and PubMed from “1990 to 2018” through using the terms “Cardioprotection; Cardioprotective Chemokine; Chemotherapy Induced Cardiotoxicity; Cardiomyocytes; Cytokine”. DiscussionThe routine cardioprotective strategies during chemotherapy such as angiotensin-converting enzyme inhibitors and β-blockers have cardioprotective effects. Cardioprotective mechanisms and strategies can offer the oncologist several methods to protect the cardiac system through using efficient cardioprotective agents. Chemokines such as SDF-1a, IL-6,IL-8,IL-12 and G-CSF are cardioprotective chemokines. Accelerating the cardioprotection through inducing cardioprotective chemokines production can be useful in chemotherapy. ConclusionStimulating the production of cardioprotective chemokines through the pathways which induce the production of cardioprotective chemokines can work strongly beside the β-blockers and ACE inhibitors. The ambiguous point in cardioprotective pathways is that JAK2/STAT3 pathway which is linked to IL-6 production pathway, which induce intracellular adhesion molecule-1 in the area of the ischemia in myocardium and this process is not benefit in cardioprotection however IL-6 induce cardiomyocytes regeneration so it enhance our dull vision about IL-6. Finally there are several choices which can increase cardioprotection during the chemotherapy and if we overcome the boundaries in confirming the efficiency of cardioprotective chemokines and the activation of them through using several mechanisms we will break through the difficulties over chemotherapy-induced cardiotoxicity.

Chemotherapy-induced cardiotoxicity: new insights into mechanisms, monitoring, and prevention

: Chemotherapy-induced cardiotoxicity (CTX) remains a determining factor for the quality of life and mortality of patients treated with potentially cardiotoxic drugs. Considerable advances have been made in this field with increase in awareness regarding chemotherapy-induced CTX, which has changed the treatment approach to include cardiovascular risk among the first factors to be evaluated before therapy. Moreover, a better understanding of the pathophysiology of chemotherapy-induced CTX has also facilitated early identification of patients at risk with the help of new imaging technologies. The newly developed imaging tools in cardio-oncology have led to the introduction of novel parameters for evaluation of myocardial function. This, together with a renewed standardization of measurements, has increased the adherence to monitoring protocols. With respect to treatment and prevention, researchers have started focusing attention on the development of new strategies as well as new cardioprotective agents that will play a crucial role in the prevention of CTX in the near future.

Investigating the Cardioprotective role of Metformin during Sunitinib-induced Cardiotoxicity by qRT-PCR profiling of microRNAs associated with myocardial injury

Background: Sunitinib chemotherapy is associated with severe cardiovascular adverse effects. The anti-diabetic drug Metformin has shown to be cardioprotective during chemotherapy-induced cardiotoxicity. This study used an organ culture model to investigate the expression of microRNAs associated with myocardial injury in cardiac tissue treated with Sunitinib and Metformin.

Development of new 18F-labelled small molecules for the detection of oxidative stress using positron emission tomography

Background: Reactive oxygen species are endogenously generated as by-products of the mitochondrial electron transport chain, and play important roles in the regulation of cell growth, neurotransmission, and the immune system. In elevated levels however, ROS ultimately lead to oxidation of DNA, proteins, and cell membranes. The resulting oxidative stress underlies the pathogenesis of numerous disease states, including cardiovascular disease, and chemotherapy-induced cardiotoxicity. Despite their widespread pathological importance, there is currently no means of non-invasively detecting elevated ROS levels in humans.

A Similar Metabolic Profile Between the Failing Myocardium and Tumor Could Provide Alternative Therapeutic Targets in Chemotherapy-Induced Cardiotoxicity.

A Similar Metabolic Profile Between the Failing Myocardium and Tumor Could Provide Alternative Therapeutic Targets in Chemotherapy-Induced Cardiotoxicity.

Pharmacogenetics of Chemotherapy-Induced Cardiotoxicity.

The goal of this review is to summarize current understanding of pharmacogenetics and pharmacogenomics in chemotherapy-induced cardiotoxicity. Most of the studies rely on in vitro cytotoxic assays. There have been several smaller scale candidate gene approaches and a handful of genome-wide studies linking genetic variation to susceptibility to chemotherapy-induced cardiotoxicity. Currently, pharmacogenomic testing of all childhood cancer patients with an indication for doxorubicin or daunorubicin therapy for RARG rs2229774, SLC28A3 rs7853758, and UGT1A6*4 rs17863783 variants is recommended. There is no recommendation regarding testing in adults. There is clear evidence pointing to the role of pharmacogenetics and pharmacogenomics in cardiotoxicity susceptibility to chemotherapeutic agents. Larger scale studies are needed to further identify susceptibility markers and to develop pharmacogenomics-based risk profiling to improve quality of life and life expectancy in cancer survivors.

Cardiotoxicity in Hematological Diseases: Are the Tyrosine Kinase Inhibitors Imatinib and Nilotinib Safe?

Chemotherapy-induced cardiotoxicity is a growing concern. The cardiotoxic impact of new drugs such as tyrosine kinase inhibitors is unknown, especially the ones used for chronic myeloid leukemia. We aim to evaluate nilotinib- and imatinib-induced cardiotoxicity. Single-center prospective study of consecutive patients with chronic myeloid leukemia treated with tyrosine kinase inhibitors was conducted during 2015. Patients underwent an initial clinical, laboratorial and echocardiographic evaluation, repeated after 1year. Eleven patients were included [60.0 (11) years, 63.6% of males; seven patients treated with imatinib and four with nilotinib]. After 1year of follow-up, all patients remained in functional NYHA class I, with a similar Minnesota quality of life score. Also there was no difference in the biomarkers evaluated (cystatin-C and NT-proBNP). Likewise, no modification in systolic or diastolic function evaluated by echocardiography was observed. All patients presented normal values of longitudinal, circumferential and radial strain in the baseline study, without changes during follow-up. In addition, there were no differences between the two tyrosine kinase inhibitors used, considering all the aforementioned variables. No clinical, laboratory or echocardiographic evidence of nilotinib- and imatinib-induced cardiotoxicity was observed. However, these results should be confirmed in multicenter studies given the low incidence of chronic myeloid leukemia.

Breast Cancer and the Heart: Burden on the Chest

Breast cancer survivors after successful treatment face various complications in their life. These problems are related to their psycho-social life and/or related to altered body image or may be because of the side effects of breast cancer therapy. Different types of treatment show various hemodynamic/physiological changes on one or more organ/systems. Cardiovascular is the mainly affected system after breast cancer treatment. Radiation-induced heart diseases (RIHD) involve a broad cardiac pathology comprising myocardial fibrosis and cardiomyopathies, pericardial disease, valvular heart diseases, arrhythmias and coronary artery diseases. Chemotherapy induced cardiotoxicity (CIC) affects the morbidity and mortality in breast cancer survivors. Regardless of cancer prognosis; it impacts the quality of life and overall survival with major limitations in life. Conventional diagnostic procedures and biomarkers can be used to detect RIHD and CIC. Cardio-oncology helps in filling the gap between cardiologist and oncologist to reduce the future cardiac risk in survivors.