topics

8/19/23

Abstract

Introduction: Cardiotoxicity is an adverse reaction associated with the use of anthracyclines.

Objective: To estimate the factors associated with the development of anthracycline cardiotoxicity in pediatric patients surviving cancer.

Method: Retro-prolective cohort of children diagnosed with cancer and treated with anthracyclines. Baseline echocardiographic determination of ejection fraction (LVEF0) was carried out before the start of treatment and again at 12 months (LVEF1). Demographic characteristics and treatment were obtained from the medical record. A multiple logistic regression (MLR) model was constructed; LVEF1 < 50 % was the dependent variable, which was adjusted for the main confounding variables.

Results: Sixty-five patients were included, out of which 36.9 % were females and 56.8 % had a solid tumor. LVEF0 was 74.79 ± 7.3 % and LVEF1, 67.96 ± 6.7 % (p = 0.001); 60 % developed cardiotoxicity. In the MLR, only a cumulative dose > 430 mg was associated with cardiotoxicity (p = 0.001).

Conclusions: In Mexican children, an anthracycline cumulative dose > 430 mg should be avoided in order to prevent cardiotoxicity.

PMID: 32539021 [PubMed - in process]

13:30

pubmed: tutte cardiotoxicity...

Metformin and/or low dose radiation reduces cardiotoxicity and apoptosis induced by cyclophosphamide through SIRT-1/SOD and BAX/Bcl-2 pathways in rats.

Mol Biol Rep. 2020 Jun 14;:

Authors: El Kiki SM, Omran MM, Mansour HH, Hasan HF

Abstract

Cyclophosphamide (CP) is a nitrogen mustard alkylating agent with effective antineoplastic, immunomodulatory and immunosuppressive properties. Despite its vast therapeutic uses, it is known to trigger strict cardiac toxicity. The objective of the current study was to examine the protective role of metformin (MET) and/or low dose radiation (LDR) on cardiotoxicity and apoptosis induced by CP in rats. CP (200 mg/kg i.p) induces cardiotoxicity and apoptosis as indicated by elevation of troponin, cardiac caspase-3 and Endothelin-I (ET-1). While, treatment with MET (150 mg/kg, orally for 14 days) and/or LDR (0.5 Gy) before CP hindered CP-induced toxicity. By estimating the apoptotic index (BAX/Bcl-2 ratio) CP showed significantly the highest BAX/Bcl-2 ratio. Administration of MET and/or LDR showed a significant improvement in oxidative stress indices and reverse the inhibitory effect of CP on SIRT-1. Also, Histological examination of cardiac tissues showed a sign of necrosis of myocardium after CP treatment. Conclusions: The results revealed that MET and/or LDR attenuate CP-induced cardiotoxicity by inhibiting oxidative stress and preserving the activity of antioxidant enzymes through SIRT-1/SOD and BAX/Bcl-2 pathways.

PMID: 32537703 [PubMed - as supplied by publisher]

13:30

Video file

Not included, change data exporting settings to download.

00:00, 4.2 KB

13:30

In reply to this message

pubmed: tutte cardiotoxicity...

Protective Role of Enalapril in Anthracycline-Induced Cardiotoxicity: A Systematic Review.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.png Related Articles

Protective Role of Enalapril in Anthracycline-Induced Cardiotoxicity: A Systematic Review.

Front Pharmacol. 2020;11:788

Authors: Zhang Y, Liu J, Li Y, Tan N, Du K, Zhao H, Wang J, Zhang J, Wang W, Wang Y

Abstract

Background: Evidence of the preventive and therapeutic effects of enalapril on cardiotoxicity caused by chemotherapy needs to be further confirmed and updated.

Methods: We performed a systematic review of studies from electronic databases that were searched from inception to January 29, 2019, and included relevant studies analyzing enalapril as a cardioprotective agent before or during the use of anthracyclines by oncology patients. Homogeneous results from different studies were pooled using RevMan 5.3 software. The Cochrane risk-of-bias tool was used to determine the quality of the studies.

Results: We examined and screened 626 studies according to specific criteria and ultimately included seven studies that were relevant to the indicated topic. Among them, three studies reported the incidence of death during 6- and 12-month follow-up periods. Six of the seven included studies showed possible positive results, suggesting that enalapril plays a cardioprotective role, while five of these studies showed that there was a significant difference in the left ventricular ejection fraction (LVEF) between an enalapril group and a control group (weighted mean difference (WMD) = 7.18, 95% CI: 2.49-11.87, I2 = 96%, P < .001). Moreover, enalapril was beneficial in reducing troponin I (TnI), creatine kinase myocardial band (CK-MB) and N-terminal pro-b-type natriuretic peptide (NT-proBNP) levels in cancer patients treated with anthracycline.

Conclusions: Although a protective effect of enalapril on myocardial toxicity was observed in terms of the LVEF values and TnI, CK-MB and NT-proBNP levels, its use in the prevention and treatment of cardiotoxicity caused by anthracycline needs to be investigated by more scientific research.

PMID: 32536868 [PubMed]

13:30

pubmed: tutte cardiotoxicity...

Underuse of ECG monitoring in oncology patients receiving QT-interval prolonging drugs.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--highwire.stanford.edu-icons-externalservices-pubmed-custom-bmjjournals_final.gif Related Articles

Underuse of ECG monitoring in oncology patients receiving QT-interval prolonging drugs.

Heart. 2019 11;105(21):1649-1655

Authors: Pezo RC, Yan AT, Earle C, Chan KK

Abstract

OBJECTIVE: We examined use of ECG monitoring in oncology patients prescribed QT-prolonging drugs.

METHODS: Patients ≥66 years diagnosed with cancer between 2005 and 2011 were identified through the Ontario Cancer Registry and linked to multiple population-based administrative databases to ascertain demographics, comorbidities, prescription drug use, systemic therapy and ECG. QT-prolonging drugs were identified as per drug lists developed by the Arizona Center for Education and Research on Therapeutics. Univariable and multivariable analyses were used to examine factors associated with ECG use in patients on first-line systemic therapy.

RESULTS: A total of 48 236 patients (median age 74; 49% women) received one or more drugs associated with a risk of QT-interval prolongation but only 27% of patients had an ECG performed. Factors associated with more ECG use on multivariable analysis included recent cancer diagnosis (p for trend <0.001

CONCLUSIONS: Our study highlights common use of QT-prolonging drugs and underuse of ECG in oncology patients. Since ECG is an inexpensive, non-invasive and widely available test, it may be readily incorporated in the monitoring of patients for toxicities in routine clinical practice.

PMID: 31129611 [PubMed - indexed for MEDLINE]

18 June 2020

14:48

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

The Diagnostic and Prognostic Value of Echocardiographic Strain.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--jamanetwork.com-images-JAMA_cardio_linkout.gif Related Articles

The Diagnostic and Prognostic Value of Echocardiographic Strain.

JAMA Cardiol. 2019 06 01;4(6):580-588

Authors: Singh A, Voss WB, Lentz RW, Thomas JD, Akhter N

Abstract

Importance: Myocardial deformation or strain by speckle-tracking echocardiography (STE) has become an established echocardiographic modality for the diagnostic and prognostic evaluation of cardiac dysfunction. Current literature supports the incremental value of strain in diagnosis, risk stratification, and prognostication of a multitude of cardiac disease states.

Observations: Strain has been studied across the clinical spectrum from common to obscure pathologic conditions. This review presents the current literature evaluating characteristic strain patterns across this clinical spectrum, discusses prognostic implications, and provides a case series of classic strain polar maps, which are also known as bull's-eye plots.

Conclusions and Relevance: Characteristic bull's-eye patterns can be used to guide patient evaluation and management.

PMID: 31042262 [PubMed - indexed for MEDLINE]

20 June 2020

12:25

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

Uncoupling DNA damage from chromatin damage to detoxify doxorubicin.

Proc Natl Acad Sci U S A. 2020 Jun 17;:

Authors: Qiao X, van der Zanden SY, Wander DPA, Borràs DM, Song JY, Li X, van Duikeren S, van Gils N, Rutten A, van Herwaarden T, van Tellingen O, Giacomelli E, Bellin M, Orlova V, Tertoolen LGJ, Gerhardt S, Akkermans JJ, Bakker JM, Zuur CL, Pang B, Smits AM, Mummery CL, Smit L, Arens R, Li J, Overkleeft HS, Neefjes J

Abstract

The anthracycline doxorubicin (Doxo) and its analogs daunorubicin (Daun), epirubicin (Epi), and idarubicin (Ida) have been cornerstones of anticancer therapy for nearly five decades. However, their clinical application is limited by severe side effects, especially dose-dependent irreversible cardiotoxicity. Other detrimental side effects of anthracyclines include therapy-related malignancies and infertility. It is unclear whether these side effects are coupled to the chemotherapeutic efficacy. Doxo, Daun, Epi, and Ida execute two cellular activities: DNA damage, causing double-strand breaks (DSBs) following poisoning of topoisomerase II (Topo II), and chromatin damage, mediated through histone eviction at selected sites in the genome. Here we report that anthracycline-induced cardiotoxicity requires the combination of both cellular activities. Topo II poisons with either one of the activities fail to induce cardiotoxicity in mice and human cardiac microtissues, as observed for aclarubicin (Acla) and etoposide (Etop). Further, we show that Doxo can be detoxified by chemically separating these two activities. Anthracycline variants that induce chromatin damage without causing DSBs maintain similar anticancer potency in cell lines, mice, and human acute myeloid leukemia patients, implying that chromatin damage constitutes a major cytotoxic mechanism of anthracyclines. With these anthracyclines abstained from cardiotoxicity and therapy-related tumors, we thus uncoupled the side effects from anticancer efficacy. These results suggest that anthracycline variants acting primarily via chromatin damage may allow prolonged treatment of cancer patients and will improve the quality of life of cancer survivors.

PMID: 32554494 [PubMed - as supplied by publisher]

12:25

pubmed: tutte cardiotoxicity...

Successful Heart Transplant in a Childhood Cancer Survivor With Chemoradiotherapy-Induced Cardiomyopathy.

Exp Clin Transplant. 2020 Jun 16;:

Authors: Sipahi NF, Akhyari P, Aubin H, Mehdiani A, Erbel S, Westenfeld R, Scheiber D, Dalyanoglu H, Lichtenberg A, Boeken U

Abstract

Cancer therapy-related cardiotoxicity has been presenting a major problem in cancer survivors, who constitute a growing population caused by a significant improvement in cancer therapy during the past decades. Although some listing criteria have been defined for these patients, it is still a compelling decision to list patients with a complex cancer anamnesis. We describe herein a childhood cancer survivor after a cancer anamnesis with 2 different malignancies and an end-stage heart failure following chemoradiotherapy who was successfully treated with orthotopic heart transplant.

PMID: 32552629 [PubMed - as supplied by publisher]

12:26

pubmed: tutte cardiotoxicity...

A novel FTY720 analogue targets SET-PP2A interaction and inhibits growth of acute myeloid leukemia cells without inducing cardiac toxicity.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles

A novel FTY720 analogue targets SET-PP2A interaction and inhibits growth of acute myeloid leukemia cells without inducing cardiac toxicity.

Cancer Lett. 2020 01 01;468:1-13

Authors: Vicente C, Arriazu E, Martínez-Balsalobre E, Peris I, Marcotegui N, García-Ramírez P, Pippa R, Rabal O, Oyarzábal J, Guruceaga E, Prósper F, Mateos MC, Cayuela ML, Odero MD

Abstract

Acute myeloid leukemia (AML) is an aggressive disease associated with very poor prognosis. Most patients are older than 60 years, and in this group only 5-15% of cases survive over 5 years. Therefore, it is urgent to develop more effective targeted therapies. Inactivation of protein phosphatase 2 A (PP2A) is a recurrent event in AML, and overexpression of its endogenous inhibitor SET is detected in ~30% of patients. The PP2A activating drug FTY720 has potent anti-leukemic effects; nevertheless, FTY720 induces cardiotoxicity at the anti-neoplastic dose. Here, we have developed a series of non-phosphorylable FTY720 analogues as a new therapeutic strategy for AML. Our results show that the lead compound CM-1231 re-activates PP2A by targeting SET-PP2A interaction, inhibiting cell proliferation and promoting apoptosis in AML cell lines and primary patient samples. Notably, CM-1231 did not induce cardiac toxicity, unlike FTY720, in zebrafish models, and reduced the invasion and aggressiveness of AML cells more than FTY720 in zebrafish xenograft models. In conclusion, CM-1231 is safer and more effective than FTY720; therefore, this compound could represent a novel and promising approach for treating AML patients with SET overexpression.

PMID: 31593801 [PubMed - indexed for MEDLINE]

21 June 2020

12:55

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

Pluripotent Stem Cell Modeling of Anticancer Therapy-Induced Cardiotoxicity.

Curr Cardiol Rep. 2020 Jun 19;22(8):56

Authors: Lyra-Leite DM, Burridge PW

Abstract

This study aimed to investigate the potential role of co-treatment with doxorubicin (DOX) and verapamil (VRP) nanoparticles in experimentally induced hepatocellular carcinoma in mice and to investigate the possible mechanisms behind the potential favorable effect of the co-treatment. DOX and VRP were loaded into chitosan nanoparticles (CHNPs), and cytotoxicity of loaded and unloaded drugs against HepG2 cells was evaluated. Male albino mice were divided into eight groups (n = 15): (1) normal control, (2) diethylnitrosamine, (3) CHNPs, (4) free DOX, (5) CHNPs DOX, (6) free VRP, (7) CHNPs VRP, and (8) CHNPs DOX + CHNPs VRP. Either VRP or DOX loaded into CHNPs showed stronger growth inhibition of HepG2 cells than their free forms. DOX or VRP nanoparticles displayed pronounced anticancer activity in vivo through the decline of vascular endothelial growth factor and B cell lymphoma-2 contents in liver tissues, upregulation of antioxidant enzymes, and downregulation of multidrug resistance 1. Moreover, reduced cardiotoxicity was evident from decreased level of tumor necrosis factor-α and malondialdehyde in heart tissues coupled with decreased serum activity of creatine kinase-myocardial band and lactate dehydrogenase. Co-treatment with CHNPs DOX and CHNPs VRP showed superior results versus other treatments. Liver sections from the co-treatment group revealed the absence of necrosis, enhanced apoptosis, and nearly normal hepatic lobule architecture. Co-treatment with CHNPs DOX and CHNPs VRP revealed enhanced anticancer activity and decreased cardiotoxicity versus the corresponding free forms.

PMID: 32519553 [PubMed - as supplied by publisher]

13:54

pubmed: tutte cardiotoxicity...

Speckle-Tracking Echocardiography for Cardioncological Evaluation in Bevacizumab-Treated Colorectal Cancer Patients.

Cardiovasc Toxicol. 2020 Jun 09;:

Authors: Sonaglioni A, Albini A, Fossile E, Pessi MA, Nicolosi GL, Lombardo M, Anzà C, Ambrosio G

Abstract

Angiogenesis inhibitor Bevacizumab (BVZ) may lead to the development of adverse effects, including hypertension and cardiac ischemia. Whether assessment of changes in myocardial strain by two-dimensional speckle-tracking echocardiography (2D-STE) can be of value in detecting BVZ-mediated cardiotoxicity at an earlier stage is not known. We investigated whether 2D-STE can non-invasively detect early evidence of cardiotoxicity in metastatic colorectal cancer (mCRC) patients treated with BVZ. Between January and June 2019, 25 consecutive patients (71.8 ± 7.5 year/old, 17 males) with mCRC were prospectively enrolled. Patients underwent physical examination, blood tests, and conventional 2D-transthoracic echocardiography implemented with 2D-STE analysis, at baseline and at 3 and 6 months following treatment with BVZ (15 mg/kg every 15 days) + 5-fluorouracil/folinic acid plus oxaliplatin (FOLFOX i.v.). At 6-month follow-up, we assessed occurrence of global longitudinal strain (GLS) impairment (> 15% decrease in GLS compared with baseline) as primary end-point and a new-onset systemic hypertension (secondary end-point). On average, GLS showed a progressive significant impairment after BVZ, from - 17.4 ± 3.2% at baseline to - 16 ± 2.9% (p = 0.003) at 6-month follow-up; > 15% decrease in GLS (primary end-point) was detected in 9 patients (36%). All other strain parameters remained unchanged. New-onset systemic hypertension (secondary end-point) was diagnosed in five patients (20%). No significant changes were observed in serial high-sensitivity cardiac troponin I measurements. No patient developed significant changes in LV size or LV ejection fraction; no case of clinically symptomatic HF was observed during BVZ-treatment. Measurement of GLS by 2D-STE analysis can effectively detect BVZ-mediated cardiotoxicity at an early stage.

PMID: 32519318 [PubMed - as supplied by publisher]

13 June 2020

11:28

Cardiotoxicity News

Video file

Not included, change data exporting settings to download.

00:00, 2.7 KB

11:28

In reply to this message

pubmed: tutte cardiotoxicity...

The Evolving Design of NIH-Funded Cardio-Oncology Studies to Address Cancer Treatment-Related Cardiovascular Toxicity.

JACC CardioOncol. 2019 Sep;1(1):105-113

Authors: Minasian L, Dimond E, Davis M, Adhikari B, Fagerstrom R, Fabian C, Floyd J, Unger JM, Douglas PS, Mustian KM, Chow EJ, Lipshultz S, Hundley WG, Armenian S, Ky B

Abstract

Cardiovascular (CV) toxicity from cancer therapy is a significant and growing concern. Conventional oncology clinical trial designs focused singularly on cancer treatment efficacy have not provided sufficient information on both CV risk factors and outcomes. Similarly, traditional CV trials evaluating standard interventions typically exclude cancer patients, particularly those actively receiving cancer therapy. Neither trial type simultaneously evaluates the balance between CV toxicity and cancer outcomes. However, there is increasing collaboration among oncologists and cardiologists to design new cardio-oncology trials that address this important need. In this review, we detail five ongoing, oncology-based trials with integrated CV endpoints. Key design features include: 1) a careful assessment of baseline risk factors for CV disease; 2) an introduction of cardioprotective interventions at various timepoints in cancer therapy; 3) a balance of the risk of subclinical CV injury with the need for ongoing cancer treatment; and 4) an understanding of the time profile for development of clinically apparent CV toxicity. Additional critical priorities in cardio-oncology clinical research include harmonization of data collection and definitions for all physician- and patient-reported exposures and outcomes.

PMID: 32529192 [PubMed]

14 June 2020

11:55

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

Emerging role of immune checkpoint inhibitors and their relevance for the cardiovascular system.

Herz. 2020 Jun 12;:

Authors: Michel L, Totzeck M, Lehmann L, Finke D

Abstract

Immune checkpoint inhibitor (ICI) therapy induces an immune response against cancer cells. Immune checkpoint inhibitor therapy has tremendously improved the prognosis for a large number of cancers, but is associated with considerable immune-related adverse events (irAEs). Cardiovascular complications from ICI therapy occur in a modest proportion of patients, but show the highest lethality rates of all ICI-related complications. While ICI-related myocarditis is the most dangerous complication, its clinical manifestation varies, e.g., asymptomatic reduction of left ventricular function, isolated increase in cardiac troponins, and arrhythmias. This review delineates current data on cardiovascular complications of ICI therapy. The effects of ICI therapy on the cardiovascular system are classified in the context of preclinical data on the biochemical and immunological function of the immune checkpoint signaling pathways in the heart and the vascular system. Incidence, suspected pathomechanisms, typical symptoms, as well as recommended diagnostics are summarized. Current therapy recommendations for ICI-related cardiotoxicity are outlined and innovative new approaches with high potential for improving outcome in ICI-related myocarditis are delineated. A better understanding of cardiovascular complications is essential for the best possible oncocardiology care of the growing number of patients undergoing ICI therapy.

PMID: 32533218 [PubMed - as supplied by publisher]

15 June 2020

12:29

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

Therapeutic implications of the PP2A/MET signalling axis in doxorubicin-induced cardiotoxicity and antitumour properties.

Br J Pharmacol. 2020 Jun 14;:

Authors: Cristóbal I, Rubio J, Santos A, Luque M, Sanz-Alvarez M, Rojo F, García-Foncillas J

PMID: 32535881 [PubMed - as supplied by publisher]

12:29

pubmed: tutte cardiotoxicity...

Effect of anthracycline therapy on myocardial function and markers of fibrotic remodelling in childhood cancer survivors.

Eur Heart J Cardiovasc Imaging. 2020 Jun 14;:

Authors: Mawad W, Mertens L, Pagano JJ, Riesenkampff E, Reichert MJE, Mital S, Kantor PF, Greenberg M, Liu P, Nathan PC, Grosse-Wortmann L

Abstract

AIMS: Anthracyclines are a cornerstone of paediatric cancer treatment. We aimed to quantify myocardial cardiac magnetic resonance (CMR) native T1 (NT1) and extracellular volume fraction (ECV) as markers of fibrosis in a cohort of childhood cancer survivors (CCS).

METHODS AND RESULTS: A cohort of CCS in remission underwent CMR T1 mapping. Diastolic function was assessed by echocardiography. Results were compared to a cohort of normal controls of similar age and gender. Fifty-five CCS and 46 controls were included. Both groups had similar mean left ventricular (LV) NT1 values (999 ± 36 vs. 1007 ± 32 ms, P = 0.27); ECV was higher (25.6 ± 6.9 vs. 20.7 ± 2.4%, P = 0.003) and intracellular mass was lower (37.5 ± 8.4 vs. 43.3 ± 9.9g/m2, P = 0.02) in CCS. The CCS group had lower LV ejection fraction (EF) and LV mass index with otherwise normal diastolic function in all but one patient. The proportion of subjects with elevated ECV compared to controls did not differ between subgroups with normal or reduced LV EF (22% vs. 28%; P = 0.13) and no correlations were found between LVEF and ECV. While average values remained within normal range, mitral E/E' (6.6 ± 1.6 vs. 5.9 ± 0.9, P = 0.02) was higher in CCS. Neither NT1 nor ECV correlated with diastolic function indices or cumulative anthracycline dose.

CONCLUSIONS: There is evidence for mild diffuse extracellular volume expansion in some asymptomatic CCS; myocyte loss could be part of the mechanism, accompanied by subtle changes in systolic and diastolic function. These findings suggest mild myocardial damage and remodelling after anthracycline treatment in some CCS which requires continued monitoring.

PMID: 32535624 [PubMed - as supplied by publisher]

12:29

pubmed: tutte cardiotoxicity...

Cardiovascular risks and toxicity - The Achilles heel of androgen deprivation therapy in prostate cancer patients.

Biochim Biophys Acta Rev Cancer. 2020 Jun 11;:188383

Authors: Muniyan S, Xi L, Datta K, Das A, Teply BA, Batra SK, Kukreja RC

Abstract

Androgen deprivation therapy (ADT) is the primary systemic therapy for treating locally advanced or metastatic prostate cancer (PCa). Despite its positive effect on PCa patient survival, ADT causes various adverse effects, including increased cardiovascular risk factors and cardiotoxicity. Lifespans extension, early use of ADT, and second-line treatment with next-generation androgen receptor pathway inhibitors would further extend the duration of ADT and possibly increase the risk of ADT-induced cardiotoxicity. Meanwhile, information on the molecular mechanisms underlying ADT-induced cardiotoxicity and measures to prevent it is limited, mainly due to the lack of specifically designed preclinical studies and clinical trials. This review article compiles up-to-date evidence obtained from observational studies and clinical trials, in order to gain new insights for deciphering the association between ADT use and cardiotoxicity. In addition, potential cardioprotective strategies involving GnRH receptors and second messenger cGMP are discussed.

PMID: 32535158 [PubMed - as supplied by publisher]

17 June 2020

13:30

Cardiotoxicity News

Video file

Not included, change data exporting settings to download.

00:00, 6.5 KB

13:30

In reply to this message

pubmed: tutte cardiotoxicity...

A Case of Acute Heart Failure Following Immunotherapy for Metastatic Lung Cancer.

Cureus. 2020 May 13;12(5):e8093

Authors: Al-Obaidi A, Parker NA, Choucair K, Alderson J, Deutsch JM

Abstract

Inhibitors of cytotoxic T-lymphocyte-associated antigen-4, programmed cell death protein-1, and programmed death-ligand 1 have been shown to produce significant antitumor activity in multiple malignancies, and have become essential oncology standard-of-care therapies. Despite their success, the checkpoint inhibitors' ability to amplify the immune system response against tumor cells has been associated with a unique panel of side effects known as immune-related adverse events. The involvement of the myocardium has been reported previously, but it's remarkably uncommon. Even more noteworthy is that secondary autoimmune myocarditis and heart failure due to these medications are typically fatal.

PMID: 32542148 [PubMed]

13:30

pubmed: tutte cardiotoxicity...

Analysing the risk factors of doxorubicin-associated heart failure by a retrospective study of integrated, nation-wide databases

Orv Hetil. 2020 06;161(26):1094-1102

Authors: Fogarassy G, Fogarassyné Vathy Á, Kováts T, Hornyák L, Kenessey I, Veress G, Polgár C, Forster T

Abstract

INTRODUCTION: The incidence of dilated cardiomyopathy after anthracycline chemotherapy is mainly influenced by anthracycline cumulative dose. Previous researches showed doxorubicin treatment under cumulative dose of 450 mg/m2 associated with a low incidence of heart failure. Nowadays, doxorubicin is administered with a lower dose, the development of heart failure is largely determined by other factors.

AIM: Our purpose was to identify the risk factors for heart failure due to doxorubicin therapy.

METHOD: With the use of the Hungarian financial healthcare databases merged with the National Cancer Registry, we performed a retrospective study. All the patients having confirmation for breast carcinoma between 2004 and 2015 were enrolled. The subjects with a preceding period characterized by any chemotherapy or diagnoses suggesting heart failure were excluded. Heart failure outcome event was defined by the assignment of I50 diagnosis code at hospital discharge or in autopsy reports.

STATISTICAL ANALYSIS: We used multivariate binary logistic regression to calculate odds ratios for heart failure. Besides the baseline characteristics, oncological state and cumulative doses of the chemotherapies were also taken into account.

RESULTS: Among the analysed 3288, doxorubicin-treated patients, heart failure cumulative incidence was 6.2%. Doxorubicin cumulative dose over 400 mg/m2 increased the risk. The heart failure incidence was essentially influenced by age, even over 50 years the risk rose. Diabetes mellitus and the treatments with pyrimidine-analogues, carboplatin or bevacizumab were also associated with higher risk.

CONCLUSION: By the integration of national financial and clinical databases, we could identify the risk factors for doxorubicin-associated heart failure. Orv Hetil. 2020; 161(26): 1094-1102.

PMID: 32541088 [PubMed - in process]

13:30

pubmed: tutte cardiotoxicity...

Combined chemotherapy with cyclooxygenase-2 (COX-2) inhibitors in treating human cancers: Recent advancement.

Biomed Pharmacother. 2020 Jun 12;129:110389

Authors: Li S, Jiang M, Wang L, Yu S

Abstract

Chemotherapy with a single chemotherapeutic agent or a combined chemotherapeutic regimen is the clinically standardized treatment for almost all human cancers. Upregulated expression of cyclooxygenase (COX)-2, also known as prostaglandin-endoperoxide synthase (PTGS), is associated with human carcinogenesis and cancer progression and COX-2 inhibitors show antitumor activity in different human cancers. Thus, a combination of chemotherapeutic agents with COX-2 inhibitors has been shown to improve therapeutic effects on human cancers. This review discusses and summarizes recent advances in cancer control and treatment using various antineoplastic drugs combined with COX-2 inhibitors. These combinations showed synergistic antitumor effects. At the gene level, COX-2 inhibitors can reduce inflammatory factors thereby regulating macrophage recruitment for activating the antitumor immune microenvironment; downregulating vascular endothelial growth factor (VEGF) to inhibit tumor angiogenesis; and inhibiting the PI3K/Akt signaling pathway to induce tumor cell apoptosis. In addition, such a combination can reduce toxicity and chemoresistance and enhance radiosensitivity, although COX-2 inhibitors-related cardiotoxicity may potentially affect its use. Further in-depth investigation of these drug combinations is needed to maximize antitumor efficacy and minimize the side effects.

PMID: 32540642 [PubMed - as supplied by publisher]

13:30

pubmed: tutte cardiotoxicity...

Major Adverse Cardiovascular Events and the Timing and Dose of Corticosteroids in Immune Checkpoint Inhibitor-Associated Myocarditis.

Circulation. 2020 Jun 16;141(24):2031-2034

Authors: Zhang L, Zlotoff DA, Awadalla M, Mahmood SS, Nohria A, Hassan MZO, Thuny F, Zubiri L, Chen CL, Sullivan RJ, Alvi RM, Rokicki A, Murphy SP, Jones-O'Connor M, Heinzerling LM, Barac A, Forrestal BJ, Yang EH, Gupta D, Kirchberger MC, Shah SP, Rizvi MA, Sahni G, Mandawat A, Mahmoudi M, Ganatra S, Ederhy S, Zatarain-Nicolas E, Groarke JD, Tocchetti CG, Lyon AR, Thavendiranathan P, Cohen JV, Reynolds KL, Fradley MG, Neilan TG

PMID: 32539614 [PubMed - in process]

13:30

pubmed: tutte cardiotoxicity...

Predictors of anthracycline-induced cardiotoxicity in a retro-prolective cohort of children surviving cancer.

Gac Med Mex. 2020;156(3):217-223

Authors: Rivas-Ruiz R, Ureña-Wong K, Castelán-Martínez OD, Betanzos-Cabrera Y, Lazo-Cárdenas C, Ramírez-Portillo C, López-Aguilar E

Abstract

BACKGROUND: Observation indexes used to evaluate the effect of dexrazoxane-anthracycline combinations in breast cancer often only take into account the clinical symptoms, or left ventricular ejection fraction (LVEF), biomarkers [such as creatine kinase MB (CK-MB), brain natriuretic peptide (BNP) and cardiac troponin T (cTnT)], or tumor recurrence rate, improvement of autonomic nerve function or economic benefits. This study aimed to evaluate the effect of dexrazoxane on the changes of mechanical properties of right ventricular myocardium in patients who underwent pirarubicin chemotherapy with three-dimensional speckle-tracking imaging (3D-STI).

METHODS: A total of 64 breast cancer post-operation patients who received pirarubicin chemotherapy were randomly divided into two groups: the experimental group (with dexrazoxane added) and the control group (without dexrazoxane). The mechanical properties of the right ventricular myocardium were monitored by 3D-STI before and after chemotherapy. The levels of serum hypersensitive troponin I (hs-cTnI) and N-terminal B-type pro-natriuretic peptide (NT-proBNP) as well as conventional echocardiographic parameters were also measured.

RESULTS: After chemotherapy, right ventricular global longitudinal strain (RVGLS) and right ventricular global area strain (RVGAS) were significantly reduced in both groups (P<0.05).

CONCLUSIONS: Dexrazoxane can alleviate the toxicity of pirarubicin in the right ventricular myocardium. 3D-STI is a potential new method for early and accurate evaluation of the mechanical properties and functional changes of the right ventricular myocardium.

PMID: 32498534 [PubMed - in process]

14:16

pubmed: tutte cardiotoxicity...

Genetic Factors Involved in Cardiomyopathies and in Cancer.

J Clin Med. 2020 Jun 02;9(6):

Authors: Sabater-Molina M, Navarro-Peñalver M, Muñoz-Esparza C, Esteban-Gil Á, Santos-Mateo JJ, Gimeno JR

Abstract

Cancer therapy-induced cardiomyopathy (CCM) manifests as left ventricular (LV) dysfunction and heart failure (HF). It is associated withparticular pharmacological agents and it is typically dose dependent, but significant individual variability has been observed. History of prior cardiac disease, abuse of toxics, cardiac overload conditions, age, and genetic predisposing factors modulate the degree of the cardiac reserve and the response to the injury. Genetic/familial cardiomyopathies (CMY) are increasingly recognized in general populations with an estimated prevalence of 1:250. Association between cardiac and oncologic diseases regarding genetics involves not only the toxicity process, but pathogenicity. Genetic variants in germinal cells that cause CMY (LMNA, RAS/MAPK) can increase susceptibility for certain types of cancer. The study of mutations found in cancer cells (somatic) has revealed the implication of genes commonly associated with the development of CMY. In particular, desmosomal mutations have been related to increased undifferentiation and invasiveness of cancer. In this article, the authors review the knowledge on the relevance of environmental and genetic background in CCM and give insights into the shared genetic role in the pathogenicity of the cancer process and development of CMY.

PMID: 32498335 [PubMed]

14:16

pubmed: tutte cardiotoxicity...

Interventions to improve adherence to surveillance guidelines in survivors of childhood cancer: a systematic review.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif Related Articles

Interventions to improve adherence to surveillance guidelines in survivors of childhood cancer: a systematic review.

J Cancer Surviv. 2019 Oct;13(5):713-729

Authors: Zabih V, Kahane A, O'Neill NE, Ivers N, Nathan PC

Abstract

PURPOSE: Many survivors of childhood cancer are at high risk of late effects of their cancer therapy, including cardiac toxicity and subsequent malignant neoplasms (SMN). Current North American guidelines recommend periodic surveillance for these late effects. We conducted a systematic review of the literature to estimate rates of adherence to recommended surveillance and summarize studies evaluating interventions intended to increase adherence.

METHODS: We searched MEDLINE, Embase, Web of Science, and the Cumulative Index of Nursing and Allied Health Literature (CINAHL) for articles published between January 2000 and September 2018 that reported adherence to surveillance for cardiac toxicity and SMN (breast and colorectal cancer) and interventions implemented to improve completion of recommended testing. Risk of bias was assessed using relevant Cochrane checklists. Due to heterogeneity and overlapping study populations, we used narrative synthesis to summarize the findings. This review was registered in PROSPERO: CRD42018098878.

RESULTS: Thirteen studies met our inclusion criteria for assessing adherence to surveillance, while five assessed interventions to improve rates of surveillance. No studies met criteria for low risk of bias. Completion of recommended surveillance was lowest for colorectal cancer screening (11.5-30.0%) followed by cardiomyopathy (22.3-48.1%) and breast cancer (37.0-56.5%). Factors such as patient-provider communication, engagement with the health care system, and receipt of information were consistently reported to be associated with higher rates of surveillance. Of five randomized controlled trials aimed at improving surveillance, only two significantly increase completion of recommended testing-one for echocardiography and one for mammography. Both involved telephone outreach to encourage and facilitate these tests.

CONCLUSION: The majority of childhood cancer survivors at high risk of cardiac toxicity or SMN do not receive evidence-based surveillance. There is paucity of rigorous studies evaluating interventions to increase surveillance in this population.

IMPLICATIONS FOR CANCER SURVIVORS: Robust trials are needed to assess whether tailored interventions, designed based on unique characteristics and needs of each survivor population, could improve adherence.

PMID: 31338733 [PubMed - indexed for MEDLINE]

7 June 2020

14:45

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

Nanoformulated Ajwa (Phoenix Dactylifera) Bioactive Compounds Improve the Safety of Doxorubicin without Compromising its Anticancer Efficacy in Breast Cancer.

Molecules. 2020 Jun 03;25(11):

Authors: Godugu K, El-Far AH, Al Jaouni S, Mousa SA

Abstract

One of the major causes of women's death in the world is breast cancer. Consequently, numerous regimens for the control of this severe disease have been created. The chemotherapeutic agent doxorubicin (DOX) is frequently used to treat breast cancer, but DOX can also cause cardiotoxic effects that lead to heart failure. Therefore, many research studies have been done to find a natural product that effectively potentiates or does not interfere with DOX's anticancer effect and protects against its cardiotoxicity. We studied the impact of combined nanoformulated Ajwa (Phoenix dactylifera) selected bioactive compounds (BAC) rutin (R) and quercetin (Q) in nude mice breast cancer xenografts on DOX-mediated anticancer efficacy. We also studied if this Ajwa BAC could safeguard against DOX-mediated cardiomyopathies by evaluating plasma cardiac troponin-I (cTn-I) levels and cardiac histopathology. Nanoformulated Ajwa BAC effectively alleviated weight loss induced by DOX in mice and significantly decreased the elevated cTn-I. Furthermore, 5 mg RQ-NPs/kg of nude mice that subcutaneously daily injected for 11 days, attenuated the histopathological alterations induced in cardiac muscles due to DOX without any interference with the anticancer effects of DOX against breast cancer.

PMID: 32503143 [PubMed - as supplied by publisher]

9 June 2020

12:13

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

The Cardioprotective Role of Flaxseed in the Prevention of Doxorubicin- and Trastuzumab-Mediated Cardiotoxicity in C57BL/6 Mice.

J Nutr. 2020 Jun 08;:

Authors: Asselin CY, Lam A, Cheung DYC, Eekhoudt CR, Zhu A, Mittal I, Mayba A, Solati Z, Edel A, Austria JA, Aukema HM, Ravandi A, Thliveris J, Singal PK, Pierce GN, Niraula S, Jassal DS

Abstract

BACKGROUND: Although the combination of doxorubicin (DOX) and trastuzumab (TRZ) reduces the progression and recurrence of breast cancer, these anticancer drugs are associated with significant cardiotoxic side effects.

OBJECTIVE: We investigated whether prophylactic administration of flaxseed (FLX) and its bioactive components, α-linolenic acid (ALA) and secoisolariciresinol diglucoside (SDG), would be cardioprotective against DOX + TRZ-mediated cardiotoxicity in a chronic in vivo female murine model.

METHODS: Wild-type C57BL/6 female mice (10-12 wk old) received daily prophylactic treatment with one of the following diets: 1) regular control (RC) semi-purified diet; 2) 10% FLX diet; 3) 4.4% ALA diet; or 4) 0.44% SDG diet for a total of 6 wks. Within each arm, mice received 3 weekly injections of 0.9% saline or a combination of DOX [8 mg/(kg.wk)] and TRZ [3 mg/(kg.wk)] starting at the end of week 3. The main outcome was to evaluate the effects of FLX, ALA, and SDG on cardiovascular remodeling and markers of apoptosis, inflammation, and mitochondrial dysfunction. Significance between measurements was determined using a 4 (diet) × 2 (chemotherapy) × 2 (time) mixed factorial design with repeated measures.

RESULTS: In the RC + DOX + TRZ-treated mice at week 6 of the study, the left ventricular ejection fraction (LVEF) decreased by 50% compared with the baseline LVEF (P < 0.05).< 0.05).

CONCLUSION: In a chronic in vivo female C57BL/6 mouse model of DOX + TRZ-mediated cardiotoxicity, FLX, ALA, and SDG were partially cardioprotective.

PMID: 32510147 [PubMed - as supplied by publisher]

12:13

Video file

Not included, change data exporting settings to download.

00:00, 2.9 KB

12:13

In reply to this message

pubmed: tutte cardiotoxicity...

Bibliometric Analysis of the Results of Cardio-Oncology Research.

Evid Based Complement Alternat Med. 2020;2020:5357917

Authors: Wei K, Liao J, Chang J, Zhang X, Chen M, Du J

Abstract

Objective: To analyze the development of cardio-oncology, summarize the research achievements, and provide proposals for its future research.

Methods: The web of science database was used to search for "cardio-oncology" and "oncocardiology" related articles from the beginning of the database (1970) to April 5, 2019. Excel 2016 and Cytoscape were used to analyze the trend of cardio-oncology research.

Results: A total of 356 articles were obtained. The number of articles has grown rapidly in recent years. Cardiac injury caused by tumor therapy was a research hotspot (n = 107). Researchers paid more attention to the prevention and treatment of cardiotoxicity (n = 54). Experimental researches were a small part of all studies (n = 72), mainly focusing on the study of cancer drugs' cardiac injury, test indicators of cardiotoxicity, and preventive drugs. The United States (n = 156.25), Italy (n = 48.5), and Canada (n = 23.5) published the most articles, making a great contribution to the development of cardio-oncology.

Conclusions: Cardio-oncology has been developing rapidly and receiving a large amount of research efforts in recent years. Most articles on cardio-oncology were published by the authors from the United States (44%) and Italy (17%), while other countries need to pay more attention to cardio-oncology. As an independent discipline, cardio-oncology is certainly in need of significant progress, but it has formed a basic framework, which has obtained many leading theories and meaningful achievements in diagnostic criteria, diagnostic methods, prevention and treatment, mechanism research, and influencing factor. Cardiac injury of tumor drugs has always been a research hotspot in this discipline, and there is still a lot of research space. The research about detection methods of cardiotoxicity and preventive drugs is gradually increasing. Basic research lags behind, and many mechanisms are still unclear.

PMID: 32508950 [PubMed]

12:13

pubmed: tutte cardiotoxicity...

Cardio-oncology: management of cardiovascular toxicity.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--cdn.f1000.com.s3.amazonaws.com-images-badges-pm_research_logo.gif //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.png Related Articles

Cardio-oncology: management of cardiovascular toxicity.

F1000Res. 2019;8:

Authors: Markman TM, Markman M

Abstract

Traditional chemotherapeutic agents and newer targeted therapies for cancer have the potential to cause cardiovascular toxicities. These toxicities can result in arrhythmias, heart failure, vascular toxicity, and even death. It is important for oncologists and cardiologists to understand the basic diagnostic and management strategies to employ when these toxicities occur. While anti-neoplastic therapy occasionally must be discontinued in this setting, it can often be maintained with caution and careful monitoring. In the second of this two-part review series, we focus on the management of cardiovascular toxicity from anthracyclines, HER2/ErbB2 inhibitors, immune checkpoint inhibitors, and vascular endothelial growth factor inhibitors.

PMID: 30755794 [PubMed - indexed for MEDLINE]

12:13

Video file

Not included, change data exporting settings to download.

00:00, 3.5 KB

12:13

In reply to this message

pubmed: tutte cardiotoxicity...

Troponins and Natriuretic Peptides in Cardio-Oncology Patients-Data From the ECoR Registry.

Front Pharmacol. 2020;11:740

Authors: Hinrichs L, Mrotzek SM, Mincu RI, Pohl J, Röll A, Michel L, Mahabadi AA, Al-Rashid F, Totzeck M, Rassaf T

Abstract

Background: The long-term survival of cancer patients has significantly improved over the past years. Despite their therapeutic efficacy, various cancer therapies are associated with cardiotoxicity. Therefore, timely detection of cardiotoxic adverse events is crucial. However, the clinical assessment of myocardial damage caused by cancer therapy remains difficult.

Methods: This retrospective study was performed to evaluate the diagnostic value of cardiac troponin I (cTnI) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) for monitoring cancer therapy-induced cardiomyopathy. A total of 485 cancer patients referred to our cardio-oncology unit between July 2018 and January 2020 were selected from our Essen Cardio-oncology Registry (ECoR). We included patients with all types of cancer. Plasma concentrations of cTnI and NT-proBNP were measured by radioimmunoassay, and two-dimensional left ventricular ejection fraction (2D-LVEF), diastolic function, and global longitudinal strain (GLS) were measured by transthoracic echocardiography. In 116 patients, assessment was conducted before the induction of cancer therapy and during a short-term follow-up period; n = 42 of these were treated for malignant melanoma, and n = 42 with serial measurements were under treatment for breast cancer.

Results: In cross-sectional data, elevated NT-proBNP was associated with reduced LVEF and pathological GLS in the total cohort. A total of 116 patients had serial LVEF and biomarker measurements, and changes in NT-proBNP and troponin correlated with changes in LVEF during follow-up investigations. Similar to the total cohort, a subgroup of patients treated for malignant melanoma showed a correlation between the change in cTnI and the change in LVEF. In a subgroup analysis of patients undergoing breast cancer therapy, a correlation between the change in NT-proBNP and the change in LVEF could be detected. Thirty patients presented with chemotherapy-induced cardiomyopathy, defined as a significant LVEF decrease (> 10%) to a value below 50%. The number of patients with increased cTnI and NT-proBNP was significantly higher in patients with chemotherapy-induced cardiomyopathy than in patients without cardiotoxicity. Patients with positive cTnI and NT-proBNP were more likely to have a history of coronary heart disease, atrial fibrillation, and arterial hypertension.

Conclusion: Our data suggest that cardiac biomarkers play an important role in the detection of cancer therapy-induced cardiotoxicity. Larger systematic assessment in prospective cohorts is mandatory.

PMID: 32508657 [PubMed]

10 June 2020

13:12

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

Cardiac Biomarkers in Patients with Cancer: Considerations, Clinical Implications, and Future Avenues.

Curr Oncol Rep. 2020 Jun 09;22(7):67

Authors: Bracun V, Aboumsallem JP, van der Meer P, de Boer RA

Abstract

PURPOSE OF THE REVIEW: 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.

RECENT FINDINGS: 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.

PMID: 32514994 [PubMed - in process]

13:12

pubmed: tutte cardiotoxicity...

New Insights into Mechanisms of Immune Checkpoint Inhibitor-Induced Cardiovascular Toxicity.

Curr Oncol Rep. 2020 Jun 08;22(7):65

Authors: Khunger A, Battel L, Wadhawan A, More A, Kapoor A, Agrawal N

Abstract

PURPOSE OF REVIEW: The review aims to summarize the present knowledge about cardiovascular toxicities associated with immune checkpoint inhibitors (ICI) and dissect underlying mechanism associated with individual cardiovascular toxicity.

RECENT FINDINGS: Widespread use of ICI therapy has allowed for increasing recognition of a wide spectrum of immune-related adverse events that leave all organ systems vulnerable. Immune-mediated cardiovascular toxicities, initially thought to be rare, are more often being reported and present considerable challenges due to their non-specific clinical presentation, potential to have a fulminant progression, and overlap with other cardiovascular and general medical illnesses. Myocarditis is the most common manifestation of ICI-associated cardiovascular toxicity. Pericardial diseases, vasculitis, Takotsubo syndrome, conduction abnormalities, and destabilization of atherosclerotic lesions constitute other significant adverse events. At this stage, mechanisms underlying fundamental biology of cardiac toxicity have not been studied comprehensively and there remain gaps of knowledge in the current literature concerning the underlying pathomechanisms. It is hypothesized that immune-mediated myocarditis is a result of an exaggerated adaptive immune response against shared epitopes in the myocardium and tumor cells. Further, underlying mechanism of other cardiovascular toxicities is still unclear, further compounded by sparsity of epidemiological data. It is paramount to understand the mechanisms behind ICI-induced cardiovascular toxicities to develop appropriate treatment and prevention strategies and minimize the morbidity and mortality of cancer patients undergoing ICI therapy.

PMID: 32514647 [PubMed - in process]

13:13

pubmed: tutte cardiotoxicity...

Oncocardiology: new challenges, new opportunities.

Herz. 2020 Jun 08;:

Authors: Michel L, Schadendorf D, Rassaf T

Abstract

Patients with cancer are at a higher risk of cardiovascular disease, which contributes to significant morbidity and mortality. The rapid progress in the field of oncological treatments has led to a steady increase in long-term cancer survivors. Care for cardiovascular complications is therefore becoming increasingly important. In addition, the establishment of new oncological therapies has resulted in the identification of previously unknown cardiovascular side effects. Oncocardiology aims to detect and treat cardiovascular diseases associated with cancer and cancer therapy. Continuous scientific, clinical, and structural developments are necessary as the basis for the best care of the growing number of affected patients. This review summarizes current developments in the field of oncocardiology with regard to advances in cancer therapy and challenges in clinical oncocardiology work. Cardiovascular side effects by targeted cancer therapies are characterized and recent advances in the field of cardiovascular diagnostics are outlined. Developments to better integrate oncocardiology into the medical care system and perspectives for modern, patient-oriented care are shown. In light of the coronavirus disease 2019 (COVID-19) pandemic, current challenges and opportunities are highlighted. The relevance of profitable further advances in oncocardiology including standardized guidelines and educational programs is delineated as a mandatory requirement for the successful development of oncocardiology.

PMID: 32514587 [PubMed - as supplied by publisher]

11 June 2020

13:54

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

Effect of co-treatment with doxorubicin and verapamil loaded into chitosan nanoparticles on diethylnitrosamine-induced hepatocellular carcinoma in mice.

Hum Exp Toxicol. 2020 Jun 10;:960327120930266

Authors: Abo Mansour HE, El-Batsh MM, Badawy NS, Mehanna ET, Mesbah NM, Abo-Elmatty DM

Abstract

Human type II topoisomerases, molecular motors that alter the DNA topology, are a major target of modern chemotherapy. Groups of catalytic inhibitors represent a new approach to overcome the known limitations of topoisomerase II poisons such as cardiotoxicity and induction of secondary tumors. Here we present a class of substituted 4,5'-bithiazoles as catalytic inhibitors targeting the human DNA topoisomerase IIα. Based on a structural comparison of the ATPase domains of human and bacterial type II topoisomerase, a focused chemical library of 4,5'-bithiazoles was assembled and screened to identify compounds that better fit the topology of the human topo IIα ATP binding site. Selected compounds showed inhibition of human topo IIα comparable or superior to that of the etoposide topo II drug, revealing a new class of inhibitors targeting this molecular motor. Further investigations showed that compounds act as catalytic inhibitors via competitive ATP inhibition. We also confirmed binding to the truncated ATPase domain of topo IIα and modeled the inhibitor molecular recognition with molecular simulations and dynophore models. The compounds also displayed promising cytotoxicity against HepG2 and MCF-7 cell lines comparable to that of etoposide. In a more detailed study with the HepG2 cell line, there was no induction of DNA double-strand breaks (DBS), and the compounds were able to reduce cell proliferation and stop the cell cycle mainly in the G1 phase. This confirms the mechanism of action of these compounds, which differs from topo II poisons also at the cellular level. Substituted 4,5'-bithiazoles appear to be a promising class for further development towards efficient and potentially safer cancer therapies exploiting the alternative topo II inhibition paradigm.

PMID: 32484690 [PubMed - as supplied by publisher]

12:25

pubmed: tutte cardiotoxicity...

Anthracycline-Induced Cardiotoxicity: Causes, Mechanisms, and Prevention.

Adv Exp Med Biol. 2020;1257:181-192

Authors: Bhagat A, Kleinerman ES

Abstract

Doxorubicin is an anthracycline and one of the more effective chemotherapy agents used in the treatment of children, adolescents, and adults with osteosarcoma. Despite its effectiveness, cardiotoxicity is a major late effect that compromises the survival and quality of life of survivors of this and other cancers. Cardiotoxicity is the inability of the heart to pump blood through the body effectively. Doxorubicin-induced cardiotoxicity is dose dependent. Additionally, the age of the patients plays a role in susceptibility with younger patients having a greater risk for cardiotoxicity and heart failure years after treatment is complete. The exact mechanism(s) responsible for doxorubicin-induced cardiotoxicity is poorly understood, and further research needs to be done to elucidate the mechanisms. This chapter summarizes the identified mechanisms that may play a role in anthracycline-induced cardiotoxicity. We will also summarize the types of cardiomyopathies that have been described in survivors treated with doxorubicin and the current recommendations for monitoring survivor for the development of cardiomyopathies. Included will be the important search for defining early biomarkers to identify patients and survivors at risk. Finally, we will summarize some of the interventions proposed for decreasing anthracycline-induced cardiotoxicity.

PMID: 32483740 [PubMed - in process]

12:25

pubmed: tutte cardiotoxicity...

Cardiotoxicity with trabectedin in the treatment of advanced soft tissue sarcoma.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--tools.ovid.com-images-wklogo.jpg Related Articles

Cardiotoxicity with trabectedin in the treatment of advanced soft tissue sarcoma.

Anticancer Drugs. 2019 01;30(1):110-115

Authors: Doherty GJ, Davidson D, Wong HH, Hatcher HM

Abstract

Trabectedin is used routinely in the palliative management of patients with advanced soft tissue sarcoma. It is not generally considered to be cardiotoxic, and there is no specific caution for its use in patients with a history of cardiac disease or risk factors. Here, we report six cases from a single academic centre where life-threatening cardiotoxicity occurred acutely during treatment with trabectedin. These patients had a median age of 72.5 years (range: 68-81) at presentation with cardiotoxicity, significantly higher than the median ages of patients treated with trabectedin in clinical trials. Cardiotoxicity occurred between cycle 1, day 10, and cycle 5, day 5 of treatment (with three events occurring during cycle 2, and one during cycle 3). Two patients had a previous cardiac history and three patients had other relevant cardiac risk factors. Five patients had been treated previously with anthracyclines. Two patients developed acute pulmonary oedema, two developed fast atrial fibrillation, one developed an ST-elevation myocardial infarction and one suffered a fatal cardiac arrest. Two had unequivocal evidence of myocardial ischaemia, and two events were acutely fatal. Trabectedin was immediately discontinued in all cases and, for the four nonfatal events, there were no recurrences of the cardiac events. As no other definitive precipitants were identified, we consider these events to be related to trabectedin toxicity. We therefore urge caution with the use of trabectedin in elderly patients, and those with a previous cardiac history, abnormal cardiac function or significant cardiac risk factors including pericardiac lesions (present in two cases reported here).

PMID: 30540596 [PubMed - indexed for MEDLINE]

4 June 2020

13:00

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

Assessment of myocardial extracellular volume on body computed tomography in breast cancer patients treated with anthracyclines.

Quant Imaging Med Surg. 2020 May;10(5):934-944

Authors: Monti CB, Zanardo M, Bosetti T, Alì M, De Benedictis E, Luporini A, Secchi F, Sardanelli F

Abstract

Background: Cancer treatment with anthracyclines may lead to an increased incidence of cardiac disease due to cardiotoxicity, as they may cause irreversible myocardial fibrosis. So far, the proposed methods for screening patients for cardiotoxicity have led to only limited success, while the analysis of myocardial extracellular volume (mECV) at cardiac magnetic resonance (CMR) has shown promising results, albeit requiring a dedicated exam. Recent studies have found strong correlations between mECV values obtained through computed tomography (CT), and those derived from CMR. Thus, our purpose was to evaluate the feasibility of estimating mECV on thoracic contrast-enhanced CT performed for staging or follow-up in breast cancer patients treated with anthracyclines, and, if feasible, to assess if a rise in mECV is associated with chemotherapy, and persistent over time.

Methods: After ethics committee approval, female patients with breast cancer who had undergone at least 2 staging or follow-up CT examinations at our institution, one before and one shortly after the end of chemotherapy including anthracyclines were retrospectively evaluated. Patients without available haematocrit, with artefacts in CT images, or who had undergone radiation therapy of the left breast were excluded. Follow-up CT examinations at longer time intervals were also analysed, when available. mECV was calculated on scans obtained at 1, and 7 min after contrast injection.

Results: Thirty-two female patients (aged 57±13 years) with pre-treatment haematocrit 38%±4%, and ejection fraction 64%±6% were analysed. Pre-treatment mECV was 27.0%±2.9% at 1 min, and 26.4%±3.8% at 7 min, similar to values reported for normal subjects in the literature. Post-treatment mECV (median interval: 89 days after treatment) was 31.1%±4.9%, and 30.0%±5.1%, respectively, values significantly higher than pre-treatment values at all times (P<0.005).0.548) when compared to post-treatment values.

Conclusions: mECV values from contrast-enhanced CT scans could play a role in the assessment of myocardial condition in breast cancer patients undergoing anthracycline-based chemotherapy. CT-derived ECV could be an imaging biomarker for the monitoring of therapy-related cardiotoxicity, allowing for potential secondary prevention of cardiac damage, using data derived from an examination that could be already part of patients' clinical workflow.

PMID: 32489918 [PubMed]

5 June 2020

13:41

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

Cardiotoxicity of cancer therapy and current research efforts.

Br J Community Nurs. 2020 Jun 02;25(6):308

Authors: Mendes A

PMID: 32496853 [PubMed - as supplied by publisher]

13:41

pubmed: tutte cardiotoxicity...

[Cardiotoxicity of immune checkpoint inhibitors used in cancer treatment].

Rev Med Suisse. 2020 Jun 03;16(696):1165-1168

Authors: Arangalage D, Pavon AG, Hugelshofer S, Desgraz B, Tzimas G, Delyon J, Muller O, Obeid M, Ribi C, Michielin O, Özdemir BC, Monney P

Abstract

Immune checkpoint inhibitors (ICI) have revolutionized the field of oncology, by reshaping the prognosis of many cancers and are progressively becoming the standard of care. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), of which cardiovascular irAEs are particularly feared. ICI-induced myocarditis is often a diagnostic challenge because of the vast heterogeneity of clinical presentations, and it is associated with a high mortality rate of around 50%. The present article summarizes the cardiac manifestations, the diagnostic strategy and the therapeutic management of patients with ICI-induced myocarditis used in the treatment of cancer.

PMID: 32496706 [PubMed - as supplied by publisher]

13:41

pubmed: tutte cardiotoxicity...

Electrocardiographic Changes Associated With Ibrutinib Exposure.

Cancer Control. 2020 Jan-Dec;27(1):1073274820931808

Authors: Fradley MG, Welter-Frost A, Gliksman M, Emole J, Viganego F, Lee DH, Shah B, Chavez JC, Pinilla-Ibarz J, Schabath MB

Abstract

Although ibrutinib-associated atrial and ventricular arrhythmias have been well described, there is little information about ibrutinib's effects on other electrocardiographic parameters, particularly the QT interval. Using our database of 137 patients treated with ibrutinib, we retrospectively identified 21 patients in whom an electrocardiogram (ECG) was obtained both prior to and after ibrutinib exposure. All traditional ECG parameters as well as QT dispersion were manually measured by an electrophysiologist. Compared to baseline ECGs, post ibrutinib ECGs demonstrated QT interval shortening from 386 ms to 356 ms (P = .007), corrected QT interval shortening using Bazett's formula from 446 ms to 437 ms (P = .04), and corrected QT interval shortening using Fridericia's formula from 425 ms to 407 ms (P = .003). QT dispersion also increased post ibrutinib exposure compared to baseline (39.8 ms vs 57.3 ms, P = .002). There was no significant change in other ECG parameters. In conclusion, both the absolute and corrected QT intervals significantly shortened after ibrutinib exposure, while there was a significant increase in QT dispersion. These findings may point to a common underlying electrophysiologic mechanism of ibrutinib-associated arrhythmias.

PMID: 32496158 [PubMed - as supplied by publisher]

13:41

pubmed: tutte cardiotoxicity...

A Case of Reversible Cancer Therapeutics-related Cardiac Dysfunction Complicating Intra-cardiac Thrombi.

Intern Med. 2020 Jun 02;:

Authors: Tsujinaga S, Iwano H, Oshino T, Kadosaka T, Mizuguchi Y, Motoi K, Chiba Y, Koya T, Temma T, Kamiya K, Fukushima A, Koizumi T, Sato T, Takenaka S, Tada A, Ishizaka S, Sarashina M, Omote K, Kamada R, Konishi T, Sato T, Nagai T, Yamashita H, Anzai T

Abstract

Epirubicin-based chemotherapy carries a risk of inducing heart failure, although the frequency is rare. Bevacizumab, an anti-vascular endothelial growth factor monoclonal antibody, has recently been widely used in patients with recurrent breast cancer as a first-line chemotherapeutic agent. Heart failure or arterial thromboembolism has been reported as a rare cardiovascular complication of bevacizumab. We herein report a breast cancer patient with reversible cancer therapeutics-related cardiac dysfunction associated with bevacizumab and epirubicin complicating intracardiac thrombi in the left atrium and left ventricle. This case underscores the importance of tailored medical planning according to the individual status in patients receiving anti-cancer therapies.

PMID: 32493855 [PubMed - as supplied by publisher]

13:41

pubmed: tutte cardiotoxicity...

Cardiotoxicity evaluation using magnetic resonance imaging in breast Cancer patients (CareBest): study protocol for a prospective trial.

BMC Cardiovasc Disord. 2020 Jun 03;20(1):264

Authors: Hong YJ, Kim GM, Han K, Kim PK, Lee SA, An E, Lee JY, Lee HJ, Hur J, Kim YJ, Kim MJ, Choi BW

Abstract

BACKGROUND: Cardiovascular disease is second only to cancer recurrence as a determinant of lifespan in cancer survivors, and cancer therapy-related cardiac dysfunction is a clinically important risk factor. We aim to investigate the use of cardiac magnetic resonance imaging (MRI) to evaluate early tissue changes and perform functional assessment of chemo- and radiation-induced cardiotoxicity and to identify MRI prognostic indicators of cardiotoxicity in breast cancer patients.

METHODS: A 3-min cardiac imaging protocol will be added to the breast MRI examination to diagnose cardiotoxicity in breast cancer patients. Standardized MRI-based evaluation of breast cancer and the left ventricular myocardium will be performed at baseline and at 3, 6, and 12 months and 2 years or more after cancer treatment. We will analyze both ventricular volume and ejection fraction (EF), strain of left ventricle (LV), native T1, extracellular volume fraction (ECV), and T2 values acquired in the mid LV.

DISCUSSION: The primary result of this study will be the comparison of the prognostic value of MRI parameters (native T1, ECV, both ventricular systolic function and LV strain) for cardiotoxicity. The endpoint is defined as the occurrence of a major adverse cardiac event (MACE). The secondary outcome will be an assessment of the temporal relationships between contractile dysfunction and microstructural injury over 4 years using MRI. This study will assess the usefulness of quantitative MRI to diagnose cardiotoxicity and will clarify the temporal relationships between contractile dysfunction and microstructural injury of the LV myocardium using MRI during breast cancer treatment.

TRIAL REGISTRATION: The protocol was registered at clinicaltrials.gov (Clinical trial no. NCT03301389) on October 4, 2017.

PMID: 32493217 [PubMed - in process]

13:41

pubmed: tutte cardiotoxicity...

The COVID-19 Pandemic and its Impact on the Cardio-Oncology Population.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--production.springer.de-OnlineResources-Logos-springerlink.gif //www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--www.ncbi.nlm.nih.gov-corehtml-pmc-pmcgifs-pubmed-pmc.png Related Articles

The COVID-19 Pandemic and its Impact on the Cardio-Oncology Population.

Curr Oncol Rep. 2020 05 28;22(6):60

Authors: Asokan I, Rabadia SV, Yang EH

Abstract

PURPOSE OF REVIEW: The novel Coronavirus (2019-nCoV, COVID-19) is historically one of the most severe acute respiratory syndromes and pandemics to affect the globe in the twenty-first century. Originating in Wuhan, the virus rapidly spread and impacted subsets of populations with initial unclear risk factors contributing to worsening morbidity and mortality. Patients with diagnosis of cancer and undergoing treatment further represent a population at risk for worsening cardiopulmonary outcomes. This review explores specific risk factors, diagnoses, and treatment options that impact cardio-oncologic patients with COVID-19.

RECENT FINDINGS: Multiple studies globally, including Italy, China, and the USA, have documented severe outcomes. Cancer patients are at increased risk of cardiac injury which itself is a risk factor for mortality. Additionally, elderly cancer patients undergoing recent anti-cancer treatment may be at greater risk for sustaining worse outcomes, although data remains suboptimal in this population. Major gaps remain regarding risk associated with type of cancer and type of anti-cancer treatment, as well as the layered risk of cardiovascular disease and cancer. Immunomodulatory therapies used to treat cytokine release syndrome secondary to anti-cancer therapies, as well as other agents being traditionally used to treat cardiovascular and cancer disease states, are being investigated for treatment of COVID-19. Hypertension, cardiovascular disease, diabetes, and cancer have been associated with more severe COVID-19 infection and worse outcomes. Patients undergoing anti-cancer therapy or those who have suffered from coronavirus infection may develop long-standing changes, not limited to pulmonary fibrosis, hyperlipidemia, and worsening atherosclerosis. Those undergoing anti-cancer therapy are at theoretically increased susceptibility for infection, with type of cancer not necessarily dictating outcome. A review of the literature of patients with cardiovascular and/or cancer disease is presented, as well as proposed strategies to attenuate risk regarding treatment, management, and surveillance in this vulnerable population.

PMID: 32462289 [PubMed - indexed for MEDLINE]

13:41

pubmed: tutte cardiotoxicity...

Cardiotoxicity evaluation in pediatric patients with acute lymphoblastic leukemia - results of prospective study.

Med Ultrason. 2019 Nov 24;21(4):449-455

Authors: Radu LE, Ghiorghiu I, Oprescu A, Dorobantu D, Arion C, Colita A

Abstract

AIM: The chemotherapy protocol for acute lymphoblastic leukemia (ALL) uses low doses of anthracyclines (AC), generally associated with subclinical cardiotoxicity. The aim of our study was to evaluate the serum biomarkers and echocardiography parameters in children with ALL treated with AC in order to determine the most useful element for early detection of cardiotoxicity.

MATERIAL AND METHODS: In this prospective study, troponin I (TnI) and heart-type fatty acid binding protein (HFABP) were assessed five times during the first year after the onset of ALL. Serial Tissue Doppler Imaging and conventional cardiac echography were performed by two pediatric cardiologists (intraclass correlation coefficient over 0.85 for all measurements) in three periods during the study protocol.

RESULTS: We evaluated 48 children with ALL. TnI increased during therapy, without returning to baseline values one year after diagnosis. HFABP did not show significant changes during the study protocol. Left ventricle outflow tract time-velocity integral and peak systolic septal mitral annulus velocity decreased during chemotherapy and returned to baseline levels at one year after diagnosis, while peak systolic tricuspid annulus velocity and excursion, maintained a descending tendency. Early filling transmitral flow velocity and E/A ratio were also transiently influenced by chemotherapy.

CONCLUSIONS: The study showed signs of transient cardiotoxicity in the left ventricle and diastolic parameters after chemotherapy, compared to right ventricle parameters which maintained low values even one year after diagnosis. TnI proved to be directly proportional to chemotherapy doses but HFABP was not useful in this setting.

PMID: 31765454 [PubMed - indexed for MEDLINE]

6 June 2020

14:16

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

3D-STI evaluation of the effect of dexrazoxane on the mechanical properties of right ventricular myocardium in breast cancer patients treated with pirarubicin.

Ann Palliat Med. 2020 May;9(3):1187-1197

Authors: Wang Y, Lu C, Li H, Liu K, Yu M, Zhang P

Abstract

Metabolic diseases, such as obesity and type 2 diabetes, is known risk factor for cardiovascular (CV) diseases. Thus, patients with those comorbidities could be at increased risk of experiencing cardiotoxicity related to treatment with Anthracyclines and the other new generation targeted anticancer drugs. However, investigations addressing the mechanisms underlying the development of CV complications and poor outcome in such cohort of patients are still few and controversial. Given the importance of a personalized approach against chemotherapy-induced cardiomyopathy, this review summarizes our current knowledge on the pathophysiology of chemotherapy-induced cardiomyopathy and its association with obesity and type 2 diabetes. Along with clinical evidences, future perspectives of preclinical research around this field and its role in addressing important open questions, including the development of more proactive strategies for prevention, and treatment of cardiotoxicity during and after chemotherapy in the presence of metabolic diseases, is also presented.

PMID: 32464123 [PubMed - as supplied by publisher]

13:53

pubmed: tutte cardiotoxicity...

Baseline cardiovascular risk assessment in cancer patients scheduled to receive cardiotoxic cancer therapies: a Position Statement and new risk assessment tools from the Cardio-Oncology Study Group of the Heart Failure Association of the European Society of Cardiology in collaboration with the International Cardio-Oncology Society.

Eur J Heart Fail. 2020 May 28;:

Authors: Lyon AR, Dent S, Stanway S, Earl H, Brezden-Masley C, Cohen-Solal A, Tocchetti CG, Moslehi J, Groarke JD, Bergler-Klein J, Khoo V, Tan LL, Anker MS, von Haehling S, Maack C, Pudil R, Barac A, Thavendirnathan P, Ky B, Neilan TG, Belenkov Y, Rosen SD, Iakobishvili Z, Sverdlov AL, Hajjar LA, Macedo AVS, Manisty C, Ciardiello F, Farmakis D, De Boer RA, Skouri H, Suter TM, Cardinale D, Witteles RM, Fradley MG, Herrmann J, Cornell RF, Wechelaker A, Mauro MJ, Milojkovic D, de Lavallade H, Ruschitzka F, Coats AJS, Seferovic PM, Chioncel O, Thum T, Bauersachs J, Andres MS, Wright DJ, López-Fernández T, Plummer C, Lenihan D

Abstract

This position statement from the Heart Failure Association of the European Society of Cardiology Cardio-Oncology Study Group in collaboration with the International Cardio-Oncology Society presents practical, easy-to-use and evidence-based risk stratification tools for oncologists, haemato-oncologists and cardiologists to use in their clinical practice to risk stratify oncology patients prior to receiving cancer therapies known to cause heart failure or other serious cardiovascular toxicities. Baseline risk stratification proformas are presented for oncology patients prior to receiving the following cancer therapies: anthracycline chemotherapy, HER2-targeted therapies such as trastuzumab, vascular endothelial growth factor inhibitors, second and third generation multi-targeted kinase inhibitors for CML targeting BCR-ABL, multiple myeloma therapies (proteasome inhibitors and immunomodulatory drugs), RAF and MEK inhibitors or androgen deprivation therapies. Applying these risk stratification proformas will allow clinicians to stratify cancer patients into low, medium, high and very high risk of cardiovascular complications prior to starting treatment, with the aim of improving personalised approaches to minimise the risk of cardiovascular toxicity from cancer therapies. This article is protected by copyright. All rights reserved.

PMID: 32463967 [PubMed - as supplied by publisher]

13:53

pubmed: tutte cardiotoxicity...

Exercise Training for Cancer Survivors.

Curr Treat Options Oncol. 2020 May 27;21(7):53

Authors: Tong CKW, Lau B, Davis MK

Abstract

OPINION STATEMENT: Cardiovascular diseases are a common cause of morbidity and mortality in cancer survivors. Furthermore, some cancer therapies are now being increasingly recognized to have negative cardiovascular effects, or cardiotoxicity. Exercise therapy has been found to improve cardiorespiratory fitness in patients with cancer as well as attenuate the cardiotoxic effects of cancer therapy. It is the centerpiece for cardiac and pulmonary rehabilitation programs. It is also an important component in cardio-oncology rehabilitation. Exercise is generally safe, and its benefit is observed when started as soon as the diagnosis of cancer and throughout cancer survivorship.

PMID: 32462229 [PubMed - in process]

30 May 2020

14:20

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

Cardiotoxicity of the BCR-ABL1 tyrosine kinase inhibitors: Emphasis on ponatinib.

Int J Cardiol. 2020 May 26;:

Authors: Singh AP, Umbarkar P, Tousif S, Lal H

Abstract

The advent of tyrosine kinase inhibitors (TKIs) targeted therapy revolutionized the treatment of chronic myeloid leukemia (CML) patients. However, cardiotoxicity associated with these targeted therapies puts the cancer survivors at higher risk. Ponatinib is a third-generation TKI for the treatment of CML patients having gatekeeper mutation T315I, which is resistant to the first and second generation of TKIs, namely, imatinib, nilotinib, dasatinib, and bosutinib. Multiple unbiased screening from our lab and others have identified ponatinib as most cardiotoxic FDA approved TKI among the entire FDA approved TKI family (total 50+). Indeed, ponatinib is the only treatment option for CML patients with T315I mutation. This review focusses on the cardiovascular risks and mechanism/s associated with CML TKIs with a particular focus on ponatinib cardiotoxicity. We have summarized our recent findings with transgenic zebrafish line harboring BNP luciferase activity to demonstrate the cardiotoxic potential of ponatinib. Additionally, we will review the recent discoveries reported by our and other laboratories that ponatinib primarily exerts its cardiotoxicity via an off-target effect on cardiomyocyte prosurvival signaling pathways, AKT and ERK. Finally, we will shed light on future directions for minimizing the adverse sequelae associated with CML-TKIs.

PMID: 32470534 [PubMed - as supplied by publisher]

14:20

pubmed: tutte cardiotoxicity...

Photo-Electro Active Nanocomposite Silk Hydrogel for Spatiotemporal Controlled Release of Chemotherapeutics: An In Vivo Approach Towards Suppressing Solid Tumor Growth.

ACS Appl Mater Interfaces. 2020 May 29;:

Authors: Gangrade A, Gawali B, Jadi PK, Naidu VG, Mandal BB

Abstract

Conventional systemic chemotherapeutic regimens suffer from challenges such as non-specificity, shorter half-life, clearance of drugs and dose-limiting toxicity. Localized delivery of chemotherapeutic drugs through non-invasive spatiotemporally controllable stimuli-responsive drug delivery systems could overcome these drawbacks while utilizing drugs approved for cancer treatment. In this regard, we developed photo-electro active nanocomposite silk-based drug delivery systems (DDS) exhibiting, on-demand drug release in vivo. A functionally modified single-walled carbon nanotube loaded with doxorubicin was embedded within cross-linker free silk hydrogel. The resultant nanocomposite silk hydrogel showed electrical field responsiveness and near-infrared (NIR) laser-induced hyperthermal effect. The remote application of these stimuli in tandem or independent manner led to the increased thermal and electrical conductivity of nanocomposite hydrogel, which effectively triggered the intermittent on-demand drug release. In a proof-of-concept in vivo tumor regression study, the nanocomposite hydrogel was administered in a minimally invasive way at the periphery of the tumor by covering most of it. During the 21-day study, drastic tumor regression was recorded upon regular stimulation of nanocomposite hydrogel with simultaneous or individual external application of an electric field and NIR laser. Tumor cell death marker expression analysis uncovered the induction of apoptosis in tumor cells leading to its shrinkage. Heart ultrasound and histology revealed no cardiotoxicity associated with localized DOX treatment. To our knowledge, this is also the first report to show the simultaneous application of electric field and NIR laser in vivo for localized tumor therapy, and our results suggested that such strategy might have high clinical translational potential.

PMID: 32469499 [PubMed - as supplied by publisher]

14:20

pubmed: tutte cardiotoxicity...

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

Breast Cancer Res Treat. 2020 May 28;:

Authors: Cho H, Lee S, Sim SH, Park IH, Lee KS, Kwak MH, Kim HJ

Abstract

PURPOSE: 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.

METHODS: 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.

RESULTS: Risk factors associated with cardiotoxicity within 2 years 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),< 0.01).

CONCLUSIONS: Susceptibility to chemotherapy-induced cardiotoxicity within 2 years of doxorubicin initiation in breast cancer patients was elevated with old age, metastasis, and concomitant trastuzumab. Regular imaging monitoring at least up to 9 months after doxorubicin initiation in patients treated without concomitant trastuzumab, and 15 months in patients treated with concomitant trastuzumab, is needed for early detection of chemotherapy-induced cardiotoxicity.

PMID: 32468335 [PubMed - as supplied by publisher]

14:20

pubmed: tutte cardiotoxicity...

Can we optimise doxorubicin treatment regimens for children with cancer? Pharmacokinetic simulations and a Delphi consensus procedure.

BMC Pharmacol Toxicol. 2020 May 28;21(1):37

Authors: Siebel C, Würthwein G, Lanvers-Kaminsky C, André N, Berthold F, Castelli I, Chastagner P, Doz F, English M, Escherich G, Frühwald MC, Graf N, Groll AH, Ruggiero A, Hempel G, Boos J

Abstract

BACKGROUND: Despite its cardiotoxicity doxorubicin is widely used for the treatment of paediatric malignancies. Current treatment regimens appear to be suboptimal as treatment strategies vary and do not follow a clear pharmacological rationale. Standardisation of dosing strategies in particular for infants and younger children is required but is hampered by scarcely defined exposure-response relationships. The aim is to provide a rational dosing concept allowing for a reduction of variability in systemic therapy intensity and subsequently unforeseen side effects.

METHODS: Doxorubicin plasma concentrations in paediatric cancer patients were simulated for different treatment schedules using a population pharmacokinetic model which considers age-dependent differences in doxorubicin clearance. Overall drug exposure and peak concentrations were assessed. Simulation results were used to support a three round Delphi consensus procedure with the aim to clarify the pharmacological goals of doxorubicin dosing in young children. A group of 28 experts representing paediatric trial groups and clinical centres were invited to participate in this process.

RESULTS: Pharmacokinetic simulations illustrated the substantial differences in therapy intensity associated with current dosing strategies. Consensus among the panel members was obtained on a standardised a priori dose adaptation that individualises doxorubicin doses based on age and body surface area targeting uniform drug exposure across children treated with the same protocol. Further, a reduction of peak concentrations in very young children by prolonged infusion was recommended.

CONCLUSIONS: An approach to standardise current dose modification schemes in young children is proposed. The consented concept takes individual pharmacokinetic characteristics into account and involves adaptation of both the dose and the infusion duration potentially improving the safety of doxorubicin administration.

PMID: 32466789 [PubMed - in process]

31 May 2020

14:45

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

Anthracycline-induced cardiotoxicity and renin-angiotensin-aldosterone system-from molecular mechanisms to therapeutic applications.

Heart Fail Rev. 2020 May 30;:

Authors: Sobczuk P, Czerwińska M, Kleibert M, Cudnoch-Jędrzejewska A

Abstract

Few millions of new cancer cases are diagnosed worldwide every year. Due to significant progress in understanding cancer biology and developing new therapies, the mortality rates are decreasing with many of patients that can be completely cured. However, vast majority of them require chemotherapy which comes with high medical costs in terms of adverse events, of which cardiotoxicity is one of the most serious and challenging. Anthracyclines (doxorubicin, epirubicin) are a class of cytotoxic agents used in treatment of breast cancer, sarcomas, or hematological malignancies that are associated with high risk of cardiotoxicity that is observed in even up to 30% of patients and can be diagnosed years after the therapy. The mechanism, in which anthracyclines cause cardiotoxicity are not well known, but it is proposed that dysregulation of renin-angiotensin-aldosterone system (RAAS), one of main humoral regulators of cardiovascular system, may play a significant role. There is increasing evidence that drugs targeting this system can be effective in the prevention and treatment of anthracycline-induced cardiotoxicity what has recently found reflection in the recommendation of some scientific societies. In this review, we comprehensively describe possible mechanisms how anthracyclines affect RAAS and lead to cardiotoxicity. Moreover, we critically review available preclinical and clinical data on use of RAAS inhibitors in the primary and secondary prevention and treatment of cardiac adverse events associated with anthracycline-based chemotherapy.

PMID: 32472524 [PubMed - as supplied by publisher]

14:45

pubmed: tutte cardiotoxicity...

Clinical and Research Tools for the Study of Cardiovascular Effects of Cancer Therapy.

J Cardiovasc Transl Res. 2020 May 29;:

Authors: Feroze RA, Leya J, Herron T, Hayek SS

Abstract

The expansion of cancer therapeutics has paved the way for improved cancer-related outcomes. Cardiotoxicity from cancer therapy occurs in a small but significant subset of patients, is often poorly understood, and contributes to adverse outcomes at all stages of cancer treatment. Given the often-idiopathic occurrence of cardiotoxicity, novel strategies are needed for risk-stratification and early identification of cancer patients experiencing cardiotoxicity. Clinical and research tools extending from imaging to blood-based biomarkers and pluripotent stem cells are being explored as methods to study the cardiovascular impact of various cancer treatments. Here we provide an overview of tools currently available for evaluation of cardiotoxicity and highlight novel techniques in development aimed at understanding underlying pathophysiologic mechanisms.

PMID: 32472498 [PubMed - as supplied by publisher]

2 June 2020

11:49

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

Early Cardiac Remodeling Promotes Tumor Growth and Metastasis.

Circulation. 2020 Jun 01;:

Authors: Avraham S, Abu-Sharki S, Shofti R, Haas T, Korin B, Kalfon R, Friedman T, Shiran A, Saliba W, Shaked Y, Aronheim A

Abstract

Background: Recent evidence suggests that cancer and cardiovascular diseases are associated. Chemotherapy drugs are known to result in cardiotoxicity, and studies have shown that heart failure (HF) and stress correlate with poor cancer prognosis. Yet, whether cardiac remodeling in the absence of HF is sufficient to promote cancer is unknown. Methods: To investigate the effect of early cardiac remodeling on tumor growth and metastasis colonization, we used transverse aortic constriction (TAC), a model for pressure overload-induced cardiac hypertrophy, and followed it by cancer cell implantation. Results: TAC-operated mice developed larger primary tumors with higher proliferation rate and displayed more metastatic lesions compared with controls. Serum derived from TAC-operated mice potentiated cancer cell proliferation in vitro, suggesting the existence of secreted tumor-promoting factors. Using RNA-seq data, we identified elevated mRNA levels of Periostin in the hearts of TAC-operated mice. Periostin levels were also found high in the serum following TAC. Interestingly, depletion of Periostin from the serum abrogated the proliferation of cancer cells, conversely, the addition of Periostin enhanced cancer cell proliferation in vitro. Collectively, this is the first study to show that early cardiac remodeling nurtures tumor growth and metastasis, and therefore promotes cancer progression. Conclusions: Our study highlights the importance of early diagnosis and treatment of cardiac remodeling as it may attenuate cancer progression and improve cancer outcome.

PMID: 32475164 [PubMed - as supplied by publisher]

11:49

pubmed: tutte cardiotoxicity...

The early alteration of left ventricular strain and dys-synchrony index in breast cancer patients undergoing anthracycline therapy using layer-specific strain analysis.

//www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-7388-69-wiley-full-text.png Related Articles

The early alteration of left ventricular strain and dys-synchrony index in breast cancer patients undergoing anthracycline therapy using layer-specific strain analysis.

Echocardiography. 2019 09;36(9):1675-1681

Authors: Li H, Liu C, Zhang G, Wang C, Sun P, Du G, Tian J

Abstract

PURPOSE: The primary aim of this study was to evaluate early changes in cardiac function after anthracycline therapy with layer-specific speckle-tracking echocardiography (STE) and mechanical dys-synchrony.

METHODS: A total of 78 breast cancer patients (ranging 31~72 years) exposed to anthracycline treatment were recruited in this study. All patients received both conventional two-dimensional speckle-tracking echocardiographs at baseline, as well as after the completion of 2 and 4 cycles of the regimen. Layer-specific longitudinal strain (LS) and circumferential strain (CS) of the 3 myocardial layers (endocardium, mid-myocardium, and epicardium) were automatically measured. Peak systolic dispersion (PSD) was defined as the standard deviation of the time to peak strain of the 18 segments, divided by the RR interval.

RESULTS: There were no significant differences in conventional echocardiographic parameters during treatment (all P > .05). Peak endocardium CS at basal level decreased significantly after 2 and 4 cycles compared with baseline (both P = .001), while PSD significantly increased in that same period versus baseline (both P = .000). Endocardium and mid-myocardium LS, peak mid-myocardium and epicardium CS at the basal level, peak CS of all three layers at the papillary level, and peak endocardium and mid-myocardium CS at the apical level all significantly decreased after 4 cycles, compared with baseline and 2 cycles (all P = .000).

CONCLUSION: This study showed that myocardial deformation impairment occurred as early as 2 cycles after anthracycline chemotherapy. Endocardium CS at the basal level and left ventricular dys-synchrony index PSD were the initial cardiac abnormalities in anthracycline-treated breast cancer patients.

PMID: 31454106 [PubMed - indexed for MEDLINE]

11:49

pubmed: tutte cardiotoxicity...

Cardiac tamponade in a patient with stage IV lung adenocarcinoma treated with pembrolizumab.

Immunotherapy. 2019 12;11(18):1533-1540

Authors: Khan AM, Munir A, Thalody V, Munshi MK, Mehdi S

Abstract

Immunotherapy drugs are associated with a multitude of immune-related adverse events. We describe a case of cardiac tamponade in a patient with stage IV lung adenocarcinoma, with almost 100% expression of PDL-1, treated with pembrolizumab. The patient is a 62-year-old male who developed worsening shortness of breath after five cycles of pembrolizumab. He was diagnosed with large pericardial effusion on computed tomography chest. Echocardiogram confirmed tamponade physiology. He was treated with discontinuation of pembrolizumab and urgent pericardial window followed by high dose prednisone with tapering. The patient responded very well to the treatment. We have comprehensively reviewed cases of pericardial effusion secondary to either immune mediated mechanisms or pseudoprogression.

PMID: 31815569 [PubMed - indexed for MEDLINE]

3 June 2020

12:25

Cardiotoxicity News

pubmed: tutte cardiotoxicity...

Substituted 4,5'-Bithiazoles as Catalytic Inhibitors of Human DNA Topoisomerase IIα.

J Chem Inf Model. 2020 Jun 02;:

Authors: Bergant Loboda K, Janezic M, Štampar M, Žegura B, Filipic M, Perdih A

topics

8/19/23

Translate

Search This Blog

Featured Post

Translate

Pages

Popular Posts

البحث

Popular Posts

Popular Posts

Blog Archive

Labels

Popular Posts

Blog Archive