Assessment of Chemotherapy-Induced Cardiac Dysfunction in Breast Cancer Patients: A Prospective Study.

Background Advances in cancer treatment have markedly improved survival rates but have also heightened morbidity due to treatment-related side effects. Despite this, the literature remains scarce on predicting the incidence of acute cardiac toxicity resulting from chemotherapy. We conducted a prospective evaluation to assess the incidence, timing, clinical correlates, global longitudinal strain (GLS), and response to heart failure (HF) therapy in patients experiencing cardiotoxicity. Aims and objectives Our study aimed to assess the cardiovascular complications of cancer therapy in breast cancer patients, with particular emphasis on therapy-related cardiac dysfunction. Materials and methods We conducted a prospective observational study to detect chemotherapy-related cardiac dysfunction (CTRCD) in breast cancer patients attending the outpatient department (OPD) or admitted to Dayanand Medical College and Hospital (DMCH), Ludhiana, Punjab, between March 1, 2020, and October 31, 2021. We assessed left ventricular ejection fraction (LVEF) at baseline, mid-chemotherapy, and post-chemotherapy. Patients who developed left ventricular dysfunction (LVD) had their chemotherapy regimen modified and were initiated on HF therapy. Results Ninety-seven patients (mean age: 50.74±10.30 years) were enrolled and categorized into the LVD group (n=13) and non-LVD group (n=84). CTRCD developed in 13 patients (13.4%). Patients with estrogen receptor (ER) positive, progesterone receptor (PR) positive, and human epidermal growth factor receptor 2 (HER2) positive status, as well as those in cancer stages III and IV, are at higher risk of developing LV dysfunction. Among the 13 patients, 10 (77%) experienced complete recovery, while three (23%) had partial recovery. Markers for partial recovery included cancer stages III-IV, younger age, lower body mass index (BMI), lower radiotherapy dosage, lower mean chemotherapy dosage, and left breast involvement. Conclusion Our findings suggest that acute cardiotoxicity is not linked to the cumulative dose of anthracyclines. Early detection, modification of chemotherapy regimens, and prompt initiation of CTRCD therapy can lead to substantial recovery of cardiac dysfunction.

Early Increases in Blood Pressure and Major Adverse Cardiovascular Events in Patients With Renal Cell Carcinoma and Thyroid Cancer Treated With VEGFR TKIs.

BACKGROUND: Although VEGFR tyrosine kinase inhibitors (TKIs) are a preferred systemic treatment approach for patients with advanced renal cell carcinoma (RCC) and thyroid carcinoma (TC), treatment-related cardiovascular (CV) toxicity is an important contributor to morbidity. However, the clinical risk assessment and impact of CV toxicities, including early significant hypertension, among real-world advanced cancer populations receiving VEGFR TKI therapies remain understudied. METHODS: In a multicenter, retrospective cohort study across 3 large and diverse US health systems, we characterized baseline hypertension and CV comorbidity in patients with RCC and those with TC who are newly initiating VEGFR TKI therapy. We also evaluated baseline patient-, treatment-, and disease-related factors associated with the risk for treatment-related early hypertension (within 6 weeks of TKI initiation) and major adverse CV events (MACE), accounting for the competing risk of death in an advanced cancer population, after VEGFR TKI initiation. RESULTS: Between 2008 and 2020, 987 patients (80.3% with RCC, 19.7% with TC) initiated VEGFR TKI therapy. The baseline prevalence of hypertension was high (61.5% and 53.6% in patients with RCC and TC, respectively). Adverse CV events, including heart failure and cerebrovascular accident, were common (occurring in 14.9% of patients) and frequently occurred early (46.3% occurred within 1 year of VEGFR TKI initiation). Baseline hypertension and Black race were the primary clinical factors associated with increased acute hypertensive risk within 6 weeks of VEGFR TKI initiation. However, early significant "on-treatment" hypertension was not associated with MACE. CONCLUSIONS: These multicenter, real-world findings indicate that hypertensive and CV morbidities are highly prevalent among patients initiating VEGFR TKI therapies, and baseline hypertension and Black race represent the primary clinical factors associated with VEGFR TKI-related early significant hypertension. However, early on-treatment hypertension was not associated with MACE, and cancer-specific CV risk algorithms may be warranted for patients initiating VEGFR TKIs.

Variability of cardiac troponin levels in normal subjects and in patients with cardiovascular diseases: analytical considerations and clinical relevance.

In accordance with all the most recent international guidelines, the variation of circulating levels of cardiac troponins I and T, measured with high-sensitivity methods (hs-cTnI and hs-cTnT), should be used for the detection of acute myocardial injury. Recent experimental and clinical evidences have demonstrated that the evaluation of hs-cTnI and hs-cTnT variations is particularly relevant: a) for the differential diagnosis of Acute Coronary Syndromes (ACS) in patients admitted to the Emergency Department (ED); b) for the evaluation of cardiovascular risk in patients undergoing major cardiac or non-cardiac surgery, and in asymptomatic subjects of the general population aged >55 years and with co-morbidities; c) for the evaluation of cardiotoxicity caused by administration of some chemotherapy drugs in patients with malignant tumors. The aim of this document is to discuss the fundamental statistical and biological considerations on the intraindividual variability of hs-cTnI and hs-cTnT over time in the same individual. Firstly, it will be discussed in detail as the variations of circulating levels strictly depend not only on the analytical error of the method used but also on the intra-individual variability of the biomarker. Afterwards, the pathophysiological interpretation and the clinical relevance of the determination of the variability of the hs-cTnI and hs-cTnT values ​​ in patients with specific clinical conditions are discussed. Finally, the evaluation over time of the variation in circulating levels of hs-cTnI and hs-cTnT is proposed for a more accurate estimation of cardiovascular risk in asymptomatic subjects from the general population.

The predictive value of high sensitivity troponin measurements in patients treated with immune checkpoint inhibitors.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of cancer; however, at the potential cost of serious adverse events including cardiac injury. OBJECTIVE: To assess the baseline and longitudinal changes in high sensitivity-Troponin (hs-Tn) in patients treated with pembrolizumab as a potential predictor for the development of major adverse cardiac events (MACE) and survival. METHODS: We performed a retrospective analysis of cancer patients treated with pembrolizumab at our center. All participants had baseline measurements of hs-TnI prior to initiation of pembrolizumab (T1), with half of the patients performing follow-up measurements at their second encounter for therapy introduction (T2). We first evaluated the prevalence of abnormally elevated serum hs-TnI (> 50 nanogram per liter) at T1 and T2. We then evaluated the predictive value of abnormal levels at T1 or T2 in relation to the development of MACE (composite outcomes of myocarditis, acute coronary syndrome, heart failure, venous thromboembolism, cardiovascular hospitalization and cardiovascular mortality) and all-cause mortality. RESULTS: Among 135 patients, the mean age was 72 years, predominantly male (61%). Abnormally elevated hs-TnI at T1 was observed in 7 (5%) patients and emerged as a significant independent predictor for MACE (HR 8.1, 95% CI 1.67-37.4, p = 0.009) and all-cause mortality (HR 5.37, 95% CI 2.1-13.57, p < 0.001). Abnormally elevated hs-TnI at T2 was observed in 8 (11%) patients and emerged as a significant independent predictor for MACE (HR 10.49, 95% CI 1.68-65.5, p = 0.009), but not for mortality (p = 0.200). CONCLUSIONS: Abnormally elevated baseline and follow-up hs-TnI served as significant independent predictors for MACE, with an increased risk of development being 8-tenfold. Furthermore, elevated baseline hs-TnI showed a predictive value for all-cause mortality. Central illustration: Novel immune checkpoint inhibitor (ICIs) therapy has been found to revolutionize cancer therapy through increased activation of host immune systems to target and reduce tumor burden, but may come at the cost of serious adverse cardiac events. Identification of early biomarkers for the prediction and detection of these events is necessary.

Cardioprotective effect of Hrudroga Chintamani Rasa in isoproterenol induced cardiotoxicity in male Sprague Dawley rats.

Purpose: Ayurvedic system, a traditional medicinal system has mentioned a preparation Bruhat Vata Chintamani Rasa (Suvarnayukta) for management of heart diseases. Hrudroga Chintamani Rasa (HCR) is a formulation containing Bruhat Vata Chintamani Rasa and a few additional ingredients having beneficial effects in heart diseases. The present study was designed to investigate the cardioprotective activity of the Hrudroga Chintamani Rasa in isoproterenol (ISO)-induced myocardial infarction in rats. Methods: Male Sprague Dawley rats were treated with HCR at a dose of 56.16 and 112.32 mg/kg for 30 days. Animals received ISO (85 mg/kg. s.c.) on 28th and 29th day at an interval of 24 h. Result: Disease control animals treated with HCR at a dose of 56.16 mg/kg and 112.32 mg/kg to rats showed a significant reduction in elevated levels of aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and creatine phosphokinase MB (CK-MB), and prevented loss of depleted antioxidant enzymes from the cardiac tissue. ISO-altered electrocardiogram pattern and haemodynamic parameters were also brought about to normal by treatment with HCR. HCR treatment also improved the levels of 5' adenosine monophosphate-activated protein kinase (AMPK) and Silent information regulator 1 (SIRT1) which have potent role in antioxidant defence mechanism. Histopathological findings also showed HCR treatment prevented cardiac tissue from damage. Conclusion: HCR treatment showed a significant cardioprotective effect in ISO-induced cardiotoxicity in rats probably because of the potent antioxidant activity. Supplementary information: The online version contains supplementary material available at 10.1007/s40200-022-01012-4.

Theranostic magnetic nanoparticles enhance DNA damage and mitigate doxorubicin-induced cardio-toxicity for effective multi-modal tumor therapy.

The chemo-therapeutic efficacy of Doxorubicin (Dox), a potent anti-cancer drug used in the treatment of several solid tumors, is severely compromised by its cardio-toxicity. To overcome this shortcoming and exploit the utmost theranostic potential of nano-formulations, magnetic nanoparticles co-encapsulated with Dox and indocyanine green (ICG) in a liposomal carrier and tagged with cyclic RGD peptide were rationally designed and synthesized. These magneto-liposomes (T-LMD) showed αvß3-integrin receptor targeting and higher cyto-toxicity in several cancer cell lines (i.e. lung, breast, skin, brain and liver cancer) in combination with or without gamma radiation or magnetic hyperthermia therapy as compared to clinical liposomal nano-formulation of Dox (Lippod™). Mechanism of chemo-radio-sensitization was found to involve activation of JNK mediated pro-apoptotic signaling axis and delayed repair of DNA double strand breaks. Real time imaging of ICG labeled T-LMD suggested ~6-18 fold higher tumor accumulation of T-LMD as compared to off-target organs (kidney, liver, spleen, intestine, lungs and heart) and resulted in its higher combinatorial (chemo-radio-hyperthermia) tumor therapy efficacy as compared to Lippod™. Moreover, T-LMD showed insignificant toxicity to the heart tissue as suggested by serum levels of CK-MB, histo-pathological analysis, anti-oxidant enzyme activities (Catalase and GST) and markers of cardiac fibrosis, suggesting its potential for targeted multi-modal therapy of cancer.

A Peculiar Case of Fentanyl-Induced Cardiomyopathy.

An alarming rise in prescription and non-prescription misuse of opioids has been observed recently, leading to potentially devastating consequences. Opioid misuse contributes to cardiac risk burden and can cause diseases such as acute coronary syndrome, congestive heart failure, arrhythmias, QTc prolongation, and endocarditis. Here, we describe the case of a 35-year-old male with recreational fentanyl use who was found to have a cardiogenic shock on point-of-care ultrasound (POCUS), likely due to fentanyl-induced cardiomyopathy. Opioid-induced cardiomyopathy without any underlying cardiac disease in an adult appears to be a rare case. Our case highlights the importance of promptly recognizing fentanyl toxicity, screening for possible cardiomyopathy secondary to its use, and emergent resuscitation with the maintenance of ventilation, diuretics, and vasopressor support. The use of the reversal agent, naloxone, is a crucial part of management.

Potential of chitosan nanoparticle/fluoride nanocomposite for reducing the toxicity of fluoride an in-vivo study on the rat heart functions: Hematopoietic and immune systems.

The present work-study the decreasing fluoride ions toxicity on the rat heart via loading them on the chitosan nanoparticles (Cs NPs) surface to form the biologically compatible composite (Cs@NaF). The obtained nanocomposite was characterized by different techniques such as field emission scanning electron microscopy (FEG-SEM), zeta potential, and x-ray diffraction (XRD). The biochemical parameters in the albino rats perform, where twenty-eight male adult Sprague Dawley rats (average body weight of 150 ± 10 g) were obtained from the Faculty of Agriculture, Alexandria University, then acclimatized for two weeks before the experiment and divided into four groups in galvanized wire cages at room temperature (22-25 °C) with a 12-h photoperiod and fed a well-balanced commercial diet. The blood samples were obtained from the vena cava of the rat heart via estimation of the troponin T, Lactate dehydrogenase, and creatine phosphokinase. Also, immunoglobulins (IgA, IgM, and IgG) and hematological measurements have been performed on the rat heart. To express all of the data, the mean and standard error of the mean are utilized by (ANOVA), followed by Tukey's multiple comparison test. The modified chitosan with fluoride decreases the toxicity of fluoride via improving the rat heart function due to the presence of Cs NPs helped to mitigate some of the negative effects of fluoride therapy.

Cabozantinib-Induced Severe Cardiac Dysfunction: A Case Report and a Systematic Review of the Literature.

Cabozantinib is a novel multitargeted receptor tyrosine kinase inhibitor commonly used to treat advanced renal cell carcinoma. Cardiotoxicity is not a previously well-described adverse effect of cabozantinib. We present a rare case of a 74-year-old male with a history of renal cell carcinoma who underwent partial nephrectomy. The patient had been recently started on cabozantinib for advanced metastatic renal cell carcinoma. He developed acute onset of heart failure and subclinical hypothyroidism within nine months of treatment. Our case report postulates a causal relationship between cabozantinib and the development of non-ischemic cardiomyopathy.

The Cardioprotective Effect of Vitamin D in Breast Cancer Patients Receiving Adjuvant Doxorubicin Based Chemotherapy.

PURPOSE: The primary objective of this study was to investigate the potential protective effect of Vitamin D (Vit D) on DOX induced cardio toxicity (DIC) in early breast cancer patients receiving adjuvant DOX based chemotherapy (AC). The secondary objective was to investigate the anti-inflammatory effect of Vit D by measuring serum IL-6 and its correlation with cardio toxicity. METHODS: This study was carried out on 150 newly diagnosed women with breast cancer who were planned to receive four cycles of adjuvant AC chemotherapy regimen (60 mg/m2 DOX and 600 mg/m2 cyclophosphamide) every 21 days. Study patients were randomized 1:1 into a control group treated with AC and a Vit D group treated with AC plus 0.5 µg of Vit D (Bon One 0.5 µg) orally once daily during the whole treatment course. The cardio protective effect of Vit D was assessed by measuring serum levels of Lactate dehydrogenase (LDH), cardiac troponin T (cTnT), and anti-inflammatory Interleukin 6 (IL-6) at baseline, and after 4 cycles of AC in all study patients. RESULTS: Vit D supplementation in Vit D group patients was associated with a significant decrease (P < 0.001) in serum levels of LDH, cTnT, and IL-6 compared to the control group . CONCLUSION: The present work provides a promising clinical evidence to support the cardio protective effects of Vit D against DIC through attenuating the evoked pro-inflammatory cytokines induced by DOX.

Cardiac Function Checkup During Trastuzumab Therapy Among Patients With Breast Cancer.

BACKGROUND: Appropriate cardiac function evaluation before trastuzumab therapy is recommended. However, there are no data that show the current practice of appropriate cardiac evaluation for patients receiving postsurgical adjuvant trastuzumab (adjuvant group) and patients with metastatic disease (metastatic group). MATERIALS AND METHODS: We assessed patients with newly diagnosed breast cancer who received trastuzumab between October 2011 and December 2016 using the national database of the Hospital-Based Cancer Registry. We defined appropriate cardiac function checkup as having ultrasound echocardiogram (UCG) before the start of trastuzumab as well as within 6 months after trastuzumab initiation for the adjuvant group, and having UCG before trastuzumab for the metastatic group. RESULTS: In the adjuvant group (14,501 patients), 34.7% of patients received appropriate UCG checkup. Factors related to appropriate UCG were 65 years or older (OR 1.54, 95% CI 1.41-1.69), advanced stage (stage II OR 1.18, 95% CI 1.07-1.30, stage III OR 1.08, 95% CI 0.96-1.23 compared to stage I), and surgical department (OR 0.57, 95% CI 0.47-0.70). In the metastatic group (1734 patients), appropriate UCG checkup was performed in 72.1% of the patients. Factors associated with appropriate UCG included 65 years or older (OR 1.45, 95% CI 1.10-1.91) and anthracycline use before trastuzumab (OR 0.59, 95% CI 0.44-0.80). UCG checkup rate improved from 2012 to 2015 in both the adjuvant and metastatic groups. CONCLUSION: Although many patients still received suboptimal UCG checkup, it has been improving over time. The level of appropriate UCG checkup was different between physicians with different specialties.

CircRNA-32011 regulates apoptosis induced by arsenic trioxide in cardiac myocytes / 中国药理学通报

Aim To investigate the effect of circRNA- 32011 on myocardial apoptosis induced by arsenic triox- ide (ATO).Methods Primary cardioniyocytes of suckling neonate mouse were treated with ATO ( final concentration 10 (xniol • L_1 ) for 24 h.Then cell via¬bility was measured by M IT assay.The mKNA expres¬sion levels of Bel-2/ Bax and circRNA-3201 I were de¬tected by KT-PCK.Bcl-2/Bax protein expression lev¬els were detected by Western blot.Overexpression and knock down circHNA-32011 respectively by plasmid and siHNA were used to verify its function in ATO-in- duced cardiomyocyte apoptosis.Results Myocardial cell viability decreased, Bel-2 expression significantly decreased while Bax expression increased in ATO group compared with the control group.CircKNA- 32011 was down-regulated in ATO ineuhated cardio¬niyocytes.Ovcrex press ion of circRNA-32011 in ATO- incubated cardioniyocytes increased myocardial cell vi¬ability and Bel-2 expression and decreased the expres¬sion of Bax.Knockdown of circRNA-32011 could fur¬ther reduce cardiomyoevte activity and Bel-2 expression and increase the experssion of Bax induced by ATO.Conclusions CircRNA-32011 protects cardiac myo¬cytes from apoptosis induced by arsenic trioxide, which may provide a new potential therapeutic strategy for ATO-induced myocardial injury.

Immediate evaluation of global longitudinal strain at initiation of trastuzumab treatment in breast cancer patients.

BACKGROUND: Global longitudinal strain (GLS) is recommended to detect subclinical changes preceding reduced left ventricular ejection fraction (LVEF) in trastuzumab related cardiotoxicity. Since the possibility to detect signs of acute myocardial deterioration at treatment initiation is not clarified, the objective of this study was to assess changes in GLS and biomarkers within the first 2 weeks of trastuzumab treatment. METHODS: In a prospective cohort study, 45 patients with non-metastatic breast cancer (age 54, LVEF 62.8%, GLS -19.9%, 40% hypertension) scheduled for trastuzumab treatment were included. Echocardiography and measurement of troponin and NT-proBrain-Natriuretic-Peptide were conducted before initiation of trastuzumab, at days 3, 7, and 14 and after 3, 6, and 9 months. RESULTS: A significant deterioration in LVEF from 62.8% (SD±3.6) to 58.4% (SD±4.1) (p < 0.0001), GLS from -19.9 (SD±2.1) to -18.1 (SD±2.5) (p = 0.004), s' (p < 0.0001), e' septal (p = 0.008), and s' RV (p < 0.0001) occurred at 9 months and was preceded by significant changes in these parameters within the first 14 days. After 14 days, 12 patients (27%) had a ≥10% deterioration in GLS, which was associated with significantly lower LVEF at 55.2% (SD±4.1) at 9 months compared to patients with < 10% early deterioration in GLS (LVEF = 59.5% (SD±3.5) (p = 0.001)). No difference in plasma concentrations of biomarkers was observed between the two groups. CONCLUSION: In this study deteriorations in key echocardiographic parameters within normal limits were detected during the first 2 weeks of trastuzumab treatment, and an early ≥10% deterioration in GLS was associated with a lower LVEF at 9 months.

Cardiogenic Shock Due to Multisystem Inflammatory Syndrome in a Young Adult Female.

Multisystem inflammatory syndrome in adults (MIS-A) was initially described by pediatricians after reporting a temporal association of a mimicker of Kawasaki disease shortly after the resolution of a COVID-19 illness. Since June 2020, there have been an increased amount of reports of adults and adolescents above the age of 18 presenting with the syndrome. We report a case of a 20-year-old female with no medical history who presented with cardiogenic shock and was found to have MIS-A.

Chemotherapy and adverse cardiovascular events in colorectal cancer patients undergoing surgical resection.

BACKGROUND: Colorectal cancer patients undergoing surgical resection are at increased short-term risk of post-operative adverse events. However, specific predictors for long-term major adverse cardiac and cerebrovascular events (MACCE) are unclear. We hypothesised that patients who receive chemotherapy are at higher risk of MACCE than those who did not. METHODS: In this retrospective study, 412 patients who underwent surgical resection for newly diagnosed colorectal cancer from January 2013 to April 2015 were grouped according to chemotherapy status. MACCE was defined as a composite of cardiovascular death, myocardial infarction, stroke, unplanned revascularisation, hospitalisation for heart failure or angina. Predictors of MACCE were identified using competing risks regression, with non-cardiovascular death a competing risk. RESULTS: There were 200 patients in the chemotherapy group and 212 patients in the non-chemotherapy group. The overall prevalence of prior cardiovascular disease was 20.9%. Over a median follow-up duration of 5.1 years from diagnosis, the incidence of MACCE was 13.3%. Diabetes mellitus and prior cardiovascular disease were associated with an increased risk of MACCE (subdistribution hazard ratio, 2.56; 95% CI, 1.48-4.42) and 2.38 (95% CI, 1.36-4.18) respectively. The chemotherapy group was associated with a lower risk of MACCE (subdistribution hazard ratio, 0.37; 95% CI, 0.19-0.75) compared to the non-chemotherapy group. CONCLUSIONS: Amongst colorectal cancer patients undergoing surgical resection, there was a high incidence of MACCE. Diabetes mellitus and prior cardiovascular disease were associated with an increased risk of MACCE. Chemotherapy was associated with a lower risk of MACCE, but further research is required to clarify this association.

Right ventricular involvement in cancer therapy-related cardiotoxicity: the emerging role of strain echocardiography.

The involvement of the right ventricle (RV) in various cardiovascular pathologies is usually explored and demonstrated after thorough research of the left ventricle (LV). This is also true in cardio-oncology, where multimodality imaging with cardiac magnetic resonance and nuclear imaging is essential, but echocardiography plays pivotal role in everyday clinical practice. Chemotherapy and radiotherapy effect on RV has been studied mainly in breast cancer patients and survivors from childhood cancer. Right ventricular geometry and shape limit the ability of classical echocardiographic indices like RV ejection fraction (RVEF), RV fractional area change (FAC), and tricuspid annular plane systolic excursion (TAPSE) to identify reliably subtle changes in RV systolic function in cancer patients. The assessment of diastolic function of the RV in various timepoints during or after chemotherapy leads to conflicting results too. However, longitudinal strain of the RV (RV LS) seems to detect myocardial injury with consistent results. Remarkably, cardiotoxicity of the RV is identified by RV LS almost simultaneously with LV cardiotoxicity and with similar cutoff percent change suggesting the uniform effect of cancer and its treatments on myocardium. The prognostic value of cardiotoxic effects on the RV needs to be investigated by large prospective studies.

High-sensitivity cardiac troponin I and T methods for the early detection of myocardial injury in patients on chemotherapy.

Important advances achieved in pharmacological cancer treatment have led progressively to a reduction in mortality from many forms of cancer, and increasing numbers of previously incurable patients can now hope to become cancer-free. Yet, to achieve these improved outcomes a high price has been paid in terms of untoward side effects associated with treatment, cardio-toxicity in particular. Several recent studies have reported that cardiac troponin assay using high-sensitivity methods (hs-cTn) can enable the early detection of myocardial injury related to chemotherapy or abuse of drugs that are potentially cardiotoxic. Several authors have recently suggested that changes in hs-cTn values enable the early diagnosis of cardiac injury from chemotherapy, thus potentially benefitting cancer patients with increased troponin values by initiating early cardioprotective therapy. However, large randomised clinical trials are needed in order to evaluate the cost/benefit ratio of standardised protocols for the early detection of cardiotoxicity using the hs-cTn assay in patients treated with chemotherapy.

Metabolic Imaging in Cardio-oncology.

Tremendous progress in cancer detection and therapy has improved survival. However, cardiovascular complications are a major source of morbidity in cancer survivors. Cardiotoxicity is currently defined by structural myocardial changes and cardiac injury biomarkers. In many instances, such changes are late and irreversible. Therefore, diagnostic modalities that can identify early alterations in potentially reversible biochemical and molecular signaling processes are of interest. This review is focused on emerging translational metabolic imaging modalities. We present in context relevant mitochondrial biology aspects that ground the development and application of these technologies for detection of cancer therapy-related cardiac dysfunction (CTRCD). The application of these modalities may improve the assessment of cardiovascular risk when anticancer treatments with a defined cardiometabolic toxic mechanism are to be used. Also, they may serve as screening tools for cardiotoxicity when novel lines of cancer therapies are applied.

Ameliorative effect of rosiglitazone, a peroxisome proliferator gamma agonist on adriamycin-induced cardio toxicity via suppressing oxidative stress and apoptosis.

We investigated the rosiglitazone (RSG) effect on adriamycin (ADM)-induced cardio toxicity in experimental animals. Forty adult Wistar male rats were separated into four groups as follows: normal control; RSG (10 mg/kg)-treated; ADM (10 mg/kg)-administered; and ADM (10 mg/kg) + RSG (10 mg/kg)-treated. Serum lipid level, different biochemical biomarkers, histological analysis, and nuclear factor erythroid 2-related factor/heme oxygenase-1 (Nrf2/HO-1), Caspase 3, B-cell lymphoma 2 (Bcl-2), and Bax gene expression were assessed in serum and cardiac tissue samples. Our results show that RSG treatment in ADM-administered animals significantly diminished low-density lipoprotein cholesterol, triglyceride, and total cholesterol, and increases high-density lipoprotein cholesterol (HDL-c) in comparison with the ADM group. RSG treatment reduced the effect of ADM administration on cardiac dysfunction markers such as cardiac troponin T Creatine Kinase-MB, aspartate aminotransferase, and lactate dehydrogenase, showing the amelioration of cardio toxicity in ADM-administered rats. Additionally, RSG treatment significantly decreased the level of malondialdehyde and nitric oxide in cardiovascular tissue. RSG-treated rats in combination with ADM likewise showed a significant increase in reduced glutathione, superoxide dismutase, catalase content, and the activity of glutathione peroxidase (GPx) as compared with ADM group. Moreover, RSG treatment in ADM rats significantly increased an Nrf2 and HO-1 expression in comparison with ADM group. While in apoptosis parameters, RSG treatment in ADM rats significantly diminished a cleaved caspase-3 and Bax expression as well as expanded Bcl-2 expression when contrasted with ADM group of rats. In conclusion, RSG is capable of protecting heart toxicity in ADM-treated animals through defensive effects on oxidative stress and biochemical markers.