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Effectiveness of sacubitril-valsartan in cancer patients with heart failure.
Effectiveness of sacubitril-valsartan in cancer patients with heart failure.
ESC Heart Fail. 2020 Feb 05;:
Authors: Martín-Garcia A, López-Fernández T, Mitroi C, Chaparro-Muñoz M, Moliner P, Martin-Garcia AC, Martinez-Monzonis A, Castro A, Lopez-Sendon JL, Sanchez PL
Abstract
AIMS: Current guidelines recommend sacubitril/valsartan for patients with heart failure and reduced left ventricular ejection fraction (LVEF), but there is lack of evidence of its efficacy and safety in cancer therapy-related cardiac dysfunction (CTRCD). Our aim was to analyse the potential benefit of sacubitril/valsartan in patients with CTRCD.
METHODS AND RESULTS: We performed a retrospective multicentre registry (HF-COH) in six Spanish hospitals with cardio-oncology clinics including all patients treated with sacubitril/valsartan. Demographic and clinical characteristics and laboratory and echocardiographic data were collected. Median follow-up was 4.6 [1; 11] months. Sixty-seven patients were included (median age was 63 ± 14 years; 64% were female, 87% had at least one cardiovascular risk factor). Median time from anti-cancer therapy to CTRD was 41 [10; 141] months. Breast cancer (45%) and lymphoma (39%) were the most frequent neoplasm, 31% had metastatic disease, and all patients were treated with combination antitumor therapy (70% with anthracyclines). Thirty-nine per cent of patients had received thoracic radiotherapy. Baseline median LVEF was 33 [27; 37], and 21% had atrial fibrillation. Eighty-five per cent were on beta-blocker therapy and 76% on mineralocorticoid receptor antagonists; 90% of the patients were symptomatic NYHA functional class ≥II. Maximal sacubitril/valsartan titration dose was achieved in 8% of patients (50 mg b.i.d.: 60%; 100 mg b.i.d.: 32%). Sacubitril/valsartan was discontinued in four patients (6%). Baseline N-terminal pro-B-type natriuretic peptide levels (1552 pg/mL [692; 3624] vs. 776 [339; 1458]), functional class (2.2 ± 0.6 vs. 1.6 ± 0.6), and LVEF (33% [27; 37] vs. 42 [35; 50]) improved at the end of follow-up (all P values ≤0.01). No significant statistical differences were found in creatinine (0.9 mg/dL [0.7; 1.1] vs. 0.9 [0.7; 1.1]; P = 0.055) or potassium serum levels (4.5 mg/dL [4.1; 4.8] vs. 4.5 [4.2; 4.8]; P = 0.5). Clinical, echocardiographic, and biochemical improvements were found regardless of the achieved sacubitril-valsartan dose (low or medium/high doses).
CONCLUSIONS: Our experience suggests that sacubitril/valsartan is well tolerated and improves echocardiographic functional and structural parameters, N-terminal pro-B-type natriuretic peptide levels, and symptomatic status in patients with CTRCD.
PMID: 32022485 [PubMed - as supplied by publisher]
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Cardiotoxicity of breast cancer radiotherapy - overview of current results.
Cardiotoxicity of breast cancer radiotherapy - overview of current results.
Rep Pract Oncol Radiother. 2020 Mar-Apr;25(2):182-186
Authors: Soumarová R, Rušinová L
Abstract
Adjuvant radiotherapy after breast cancer surgery is an important part of breast cancer treatment improving local control and overall survival. However, a higher risk of cardiac mortality was observed when conventional radiotherapy techniques were used. Cardiac morbidity and mortality after radiation therapy have been studied in many meta-analyses. In those focused on modern radiotherapy techniques, cardiac morbidity and mortality were no longer presented. However, an extremely long follow-up period is required. Importantly, the cardiac morbidity rates vary depending not only on the dose delivered to the heart, but also on the systemic therapies administrated and the pre-existing cardiac disease. Systematic heart dose monitoring is of great importance, as are efforts to constantly decrease doses, using advanced radiotherapy techniques. Nowadays, it is essential to individualize treatment according to tumor characteristics and anatomical predispositions, and to consider the cost and benefits.
PMID: 32021574 [PubMed]
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Prevention of doxorubicin-induced Cardiotoxicity by pharmacological non-hypoxic myocardial preconditioning based on Docosahexaenoic Acid (DHA) and carvedilol direct antioxidant effects: study protocol for a pilot, randomized, double-blind, controlled trial (CarDHA trial).
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Prevention of doxorubicin-induced Cardiotoxicity by pharmacological non-hypoxic myocardial preconditioning based on Docosahexaenoic Acid (DHA) and carvedilol direct antioxidant effects: study protocol for a pilot, randomized, double-blind, controlled trial (CarDHA trial).
Trials. 2020 Feb 04;21(1):137
Authors: Carrasco R, Ramirez MC, Nes K, Schuster A, Aguayo R, Morales M, Ramos C, Hasson D, Sotomayor CG, Henriquez P, Cortés I, Erazo M, Salas C, Gormaz JG
Abstract
BACKGROUND: Anthracycline-induced cardiotoxicity (AIC), a condition associated with multiple mechanisms of damage, including oxidative stress, has been associated with poor clinical outcomes. Carvedilol, a β-blocker with unique antioxidant properties, emerged as a strategy to prevent AIC, but recent trials question its effectiveness. Some evidence suggests that the antioxidant, not the β-blocker effect, could prevent related cardiotoxicity. However, carvedilol's antioxidant effects are probably not enough to prevent cardiotoxicity manifestations in certain cases. We hypothesize that breast cancer patients taking carvedilol as well as a non-hypoxic myocardial preconditioning based on docosahexaenoic acid (DHA), an enhancer of cardiac endogenous antioxidant capacity, will develop less subclinical cardiotoxicity manifestations than patients randomized to double placebo.
METHODS/DESIGN: We designed a pilot, randomized controlled, two-arm clinical trial with 32 patients to evaluate the effects of non-hypoxic cardiac preconditioning (DHA) plus carvedilol on subclinical cardiotoxicity in breast cancer patients undergoing anthracycline treatment. The trial includes four co-primary endpoints: changes in left ventricular ejection fraction (LVEF) determined by cardiac magnetic resonance (CMR); changes in global longitudinal strain (GLS) determined by two-dimensional echocardiography (ECHO); elevation in serum biomarkers (hs-cTnT and NT-ProBNP); and one electrocardiographic variable (QTc interval). Secondary endpoints include other imaging, biomarkers and the occurrence of major adverse cardiac events during follow-up. The enrollment and follow-up for clinical outcomes is ongoing.
DISCUSSION: We expect a group of anthracycline-treated breast cancer patients exposed to carvedilol and non-hypoxic myocardial preconditioning with DHA to show less subclinical cardiotoxicity manifestations than a comparable group exposed to placebo.
TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN69560410. Registered on 8 June 2016.
PMID: 32019575 [PubMed - in process]
7 February 2020
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Cardiovascular diseases in survivors of childhood cancer.
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Cardiovascular diseases in survivors of childhood cancer.
Cancer Metastasis Rev. 2020 Feb 06;:
Authors: Bansal N, Blanco JG, Sharma UC, Pokharel S, Shisler S, Lipshultz SE
Abstract
Over the past few decades, the diagnosis and management of children with various malignancies have improved tremendously. As a result, there are an increasing number of children who are long-term cancer survivors. With improved survival, however, has come an increased risk of treatment-related cardiovascular complications that can appear decades after treatment. These problems are serious enough that all caregivers of childhood cancer survivors, including oncologists, cardiologists, and other health care personnel, must pay close attention to the short- and long-term effects of chemotherapy and radiotherapy on these children. This review discusses the effects of treatment-related cardiovascular complications from anthracyclines and radiotherapy and the methods for preventing, screening, and treating these complications.
PMID: 32026204 [PubMed - as supplied by publisher]
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An Incorrect Impression of Dose Versus the Ischemic Cardiac Toxicity Risk Profile for Breast and Chest Wall Radiation Therapy.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-PubMedLink.gif Related Articles
An Incorrect Impression of Dose Versus the Ischemic Cardiac Toxicity Risk Profile for Breast and Chest Wall Radiation Therapy.
Int J Radiat Oncol Biol Phys. 2020 02 01;106(2):451-452
Authors: Sarkar B
PMID: 31928645 [PubMed - indexed for MEDLINE]
8 February 2020
15:13
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Downregulation of BIS sensitizes A549 cells for digoxin-mediated inhibition of invasion and migration by the STAT3-dependent pathway.
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Downregulation of BIS sensitizes A549 cells for digoxin-mediated inhibition of invasion and migration by the STAT3-dependent pathway.
Biochem Biophys Res Commun. 2020 Feb 04;:
Authors: Yun HH, Kim S, Kuh HJ, Lee JH
Abstract
Digoxin, a compound of the cardiac glycoside family, was originally prescribed for heart failure but has recently been rediscovered for its potent antitumor activity. However, it has a narrow therapeutic margin due to its cardiotoxicity, limiting its safe use as an antitumor agent in clinical practice. To widen its therapeutic margin, we investigated whether the antitumor effect of digoxin is potentiated by the depletion of BCL-2-interacting cell death suppressor (BIS) in A549 lung cancer cells. BIS is a multifunctional protein that is frequently overexpressed in most human cancers including lung cancer. Our results demonstrated that the inhibitory potential of digoxin on the migratory behavior of A549 cells is significantly enhanced by BIS depletion as assessed by transwell assay and collagen-incorporated 3D spheroid culture. Western blotting revealed that combination treatment significantly reduces p-STAT3 expression. In addition, a STAT3 inhibitor substantially suppressed the aggressive phenotypes of A549 cells. Thus, our results suggest that loss of STAT3 activity is a possible molecular mechanism for the synergistic effect of digoxin and BIS depletion. Our findings suggest the sensitizing role of BIS silencing to reduce the dose of digoxin for treatment of lung cancer with a high metastatic potential.
PMID: 32029272 [PubMed - as supplied by publisher]
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Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis.
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Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis.
J Am Coll Cardiol. 2020 Feb 11;75(5):467-478
Authors: Awadalla M, Mahmood SS, Groarke JD, Hassan MZO, Nohria A, Rokicki A, Murphy SP, Mercaldo ND, Zhang L, Zlotoff DA, Reynolds KL, Alvi RM, Banerji D, Liu S, Heinzerling LM, Jones-O'Connor M, Bakar RB, Cohen JV, Kirchberger MC, Sullivan RJ, Gupta D, Mulligan CP, Shah SP, Ganatra S, Rizvi MA, Sahni G, Tocchetti CG, Lawrence DP, Mahmoudi M, Devereux RB, Forrestal BJ, Mandawat A, Lyon AR, Chen CL, Barac A, Hung J, Thavendiranathan P, Picard MH, Thuny F, Ederhy S, Fradley MG, Neilan TG
Abstract
BACKGROUND: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis.
OBJECTIVES: This study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis.
METHODS: This study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not develop myocarditis (control subjects, n = 92). Where available, GLS was also measured pre-ICI in both groups. Major adverse cardiac events (MACE) were defined as a composite of cardiogenic shock, arrest, complete heart block, and cardiac death.
RESULTS: Cases and control subjects were similar in age, sex, and cancer type. At presentation with myocarditis, 61 cases (60%) had a normal ejection fraction (EF). Pre-ICI, GLS was similar between cases and control subjects (20.3 ± 2.6% vs. 20.6 ± 2.0%; p = 0.60). There was no change in GLS among control subjects on an ICI without myocarditis (pre-ICI vs. on ICI, 20.6 ± 2.0% vs. 20.5 ± 1.9%; p = 0.41); in contrast, among cases, GLS decreased to 14.1 ± 2.8% (p < 0.001).< 0.001).
CONCLUSIONS: GLS decreases with ICI myocarditis and, compared with control subjects, was lower among cases presenting with either a preserved or reduced EF. Lower GLS was strongly associated with MACE in ICI myocarditis presenting with either a preserved or reduced EF.
PMID: 32029128 [PubMed - in process]
9 February 2020
15:43
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The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity.
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The Role of AMPK Activation for Cardioprotection in Doxorubicin-Induced Cardiotoxicity.
Cardiovasc Drugs Ther. 2020 Feb 08;:
Authors: Timm KN, Tyler DJ
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