August 19, 2023

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

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