Authors: Keramida K, Farmakis D
Abstract
The involvement of the right ventricle (RV) in various cardiovascular pathologies is usually explored and demonstrated after thorough research of the left ventricle (LV). This is also true in cardio-oncology, where multimodality imaging with cardiac magnetic resonance and nuclear imaging is essential, but echocardiography plays pivotal role in everyday clinical practice. Chemotherapy and radiotherapy effect on RV has been studied mainly in breast cancer patients and survivors from childhood cancer. Right ventricular geometry and shape limit the ability of classical echocardiographic indices like RV ejection fraction (RVEF), RV fractional area change (FAC), and tricuspid annular plane systolic excursion (TAPSE) to identify reliably subtle changes in RV systolic function in cancer patients. The assessment of diastolic function of the RV in various timepoints during or after chemotherapy leads to conflicting results too. However, longitudinal strain of the RV (RV LS) seems to detect myocardial injury with consistent results. Remarkably, cardiotoxicity of the RV is identified by RV LS almost simultaneously with LV cardiotoxicity and with similar cutoff percent change suggesting the uniform effect of cancer and its treatments on myocardium. The prognostic value of cardiotoxic effects on the RV needs to be investigated by large prospective studies.
PMID: 32128669 [PubMed - as supplied by publisher]
12:02
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PARP inhibitor-induced torsades de pointes in long QT syndrome: a case report.
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PARP inhibitor-induced torsades de pointes in long QT syndrome: a case report.
Eur Heart J Case Rep. 2020 Feb;4(1):1-5
Authors: Segan L, Beekman A, Parfrey S, Perrin M
Abstract
Background: Poly ADP-ribose polymerase (PARP) inhibitors target pathogenic BRCA mutations in chemotherapy-resistant malignancies. PARP inhibitors cause modest dose-dependent QT prolongation in the setting of a normal baseline QT interval.
Case summary: We describe a case of PARP inhibitor-induced torsades de pointes (TdP) in an 86-year-old gentleman prescribed rucaparib due to chemotherapy-resistant, metastatic prostate cancer with pre-existing long QT, with an apparent dose-dependent increase in QT interval. The patient presented with syncope and recurrent TdP requiring direct cardioversion reversion (200 J biphasic) and an isoprenaline infusion (2 μg/min). There were no other QT prolonging agents and no electrolyte or metabolic disturbance to account for this arrhythmia. Improvement in QT interval was observed within 72 h of rucaparib cessation.
Discussion: PARP inhibitors cause a modest, dose-dependent increase in QT interval in patients with a normal baseline. The safety of PARP inhibitors in patients with pre-existing long QT has not been evaluated. This is the first reported case of rucaparib-associated TdP in a patient with pre-existing long QT, highlighting the amplified effect of this agent in individuals with pre-existing QT prolongation and the risk of fatal arrhythmias.
PMID: 32128485 [PubMed]
6 March 2020
21:46
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HERG channel and cancer: A mechanistic review of carcinogenic processes and therapeutic potential.
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HERG channel and cancer: A mechanistic review of carcinogenic processes and therapeutic potential.
Biochim Biophys Acta Rev Cancer. 2020 Mar 02;:188355
Authors: He S, Moutaoufik MT, Islam S, Persad A, Wu A, Aly KA, Fonge H, Babu M, Cayabyab FS
Abstract
The human ether-à-go-go related gene (HERG) encodes the alpha subunit of Kv11.1, which is a voltage-gated K+ channel protein mainly expressed in heart and brain tissue. HERG plays critical role in cardiac repolarization, and mutations in HERG can cause long QT syndrome. More recently, evidence has emerged that HERG channels are aberrantly expressed in many kinds of cancer cells and play important roles in cancer progression. HERG could therefore be a potential biomarker for cancer and a possible molecular target for anticancer drug design. HERG affects a number of cellular processes, including cell proliferation, apoptosis, angiogenesis and migration, any of which could be affected by dysregulation of HERG. This review provides an overview of available information on HERG channel as it relates to cancer, with focus on the mechanism by which HERG influences cancer progression. Molecular docking attempts suggest two possible protein-protein interactions of HERG with the ß1-integrin receptor and the transcription factor STAT-1 as novel HERG-directed therapeutic targeting which avoids possible cardiotoxicity. The role of epigenetics in regulating HERG channel expression and activity in cancer will also be discussed. Finally, given its inherent extracellular accessibility as an ion channel, we discuss regulatory roles of this molecule in cancer physiology and therapeutic potential. Future research should be directed to explore the possibilities of therapeutic interventions targeting HERG channels while minding possible complications.
PMID: 32135169 [PubMed - as supplied by publisher]
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Activation of the Met receptor attenuates doxorubicin-induced cardiotoxicity in vivo and in vitro.
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Activation of the Met receptor attenuates doxorubicin-induced cardiotoxicity in vivo and in vitro.
Br J Pharmacol. 2020 Mar 04;:
Authors: Gallo S, Spilinga M, Albano R, Ferrauto G, Di Gregorio E, Casanova E, Balmativola D, Bonzano A, Boccaccio C, Sapino A, Comoglio PM, Crepaldi T
Abstract
BACKGROUND AND PURPOSE: Doxorubicin anti-cancer therapy is associated with cardiotoxicity, resulting from DNA damage response (DDR). Hepatocyte growth factor (HGF) protects cardiomyocytes from injury, but its administration is hampered by low biodistribution. In this study we investigated whether the activation of the HGF receptor - encoded by the Met gene - by an agonist monoclonal antibody (mAb) protects from doxorubicin-induced cardiotoxicity.
EXPERIMENTAL APPROACH: MAb (5 mg/kg) was injected in vivo into C57BL/6J mice prior to doxorubicin (three doses of 7 mg/kg). The cardiac functions were evaluated through magnetic resonance imaging (MRI) after treatment termination. Heart histological staining and mRNA levels of genes associated with heart failure (Acta1, Nppa), inflammation (IL-6) and fibrosis (Ctgf, Col1a2, Timp1, and Mmp9) were assessed. MAb (100 nM) was administered in vitro to H9c2 cardiomyoblasts before addition of doxorubicin (25 μM). DDR and apoptosis markers were evaluated by quantitative western blotting, flow cytometry and immunofluorescence. Stattic was used for pharmacological inactivation of signal transducer and activation of transcription 3 (Stat3).
KEY RESULTS: In vivo, administration of mAb alleviated doxorubicin-induced cardiac dysfunction and fibrosis. In vitro, mAb mimicked the response to HGF by (i) inhibiting histone H2AX phosphorylation at S139, (ii) quenching the expression of the DNA repair enzyme poly (ADP-ribose) polymerase 1, and (iii) reducing the proteolytic activation of caspase 3. The Met-driven cardioprotection involved, at least in vitro, the phosphorylation of Stat3.
CONCLUSION AND IMPLICATIONS: This paper shows that Met agonist mAb provides a new tool for cardioprotection against anthracycline cardiotoxicity.
PMID: 32133617 [PubMed - as supplied by publisher]
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Is there a role for remote ischemic conditioning in preventing 5-fluorouracil-induced coronary vasospasm?
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Is there a role for remote ischemic conditioning in preventing 5-fluorouracil-induced coronary vasospasm?
Cond Med. 2019 Oct;2(5):204-212
Authors: Chong J, Ho AF, Yap J, Bulluck H, Hausenloy DJ
Abstract
Cardiac ischemia associated with chemotherapy has been linked to several anti-neoplastic agents and is multifactorial in etiology. Coronary artery vasospasm is one of the most commonly reported effects of cancer therapy that can lead to myocardial ischemia or infarction. The chemotherapy agent 5-fluorouracil (5-FU) or its oral pro-drug capecitabine can result in coronary vascular endothelial dysfunction causing coronary artery spasm, and possibly coronary thrombosis. These drugs have also been shown to be associated with myocardial infarction, malignant ventricular arrhythmias, heart failure, cardiogenic shock, and sudden death. The proposed mechanisms underlying cardiotoxicity induced by 5-FU are vascular endothelial damage followed by thrombus formation, ischemia secondary to coronary artery vasospasm, direct toxicity on myocardium, and thrombogenicity. There remains a pressing need to discover novel and effective therapies that can prevent or ameliorate 5-FU associated cardiotoxicity. To this point, promising overlap has been observed between proposed remote ischemic conditioning (RIC) cardioprotective mechanisms and 5FU-associated cardiotoxic cellular pathways. RIC, in which transient episodes of limb ischemia and reperfusion (induced by inflations and deflations of a pneumatic cuff placed on the upper arm or thigh), confer both cardioprotective and vasculoprotective effects, and may therefore prevent 5-FU coronary artery spasm/cardiotoxicity. In this review, we will be discussing the following potentially therapeutic aspects of RIC in ameliorating 5-FU associated cardiotoxicity: sequential phases of 5-FU cardiotoxicity as possible targets for dual windows of cardioprotection characteristic of RIC; protective effects of RIC on endothelial function and microvasculature in relation to 5-FU induced endothelial dysfunction/microvascular dysfunction; reduction in platelet activation by RIC in the context of 5-FU induced thrombogenicity; and the utility of improvement in mitochondrial function conferred by RIC in 5-FU induced cellular toxicity secondary to mitochondrial dysfunction.
PMID: 32133437 [PubMed]
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Measurement of Ejection Fraction by Cardiac Magnetic Resonance Imaging and Echocardiography to Monitor Doxorubicin-Induced Cardiotoxicity.
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Measurement of Ejection Fraction by Cardiac Magnetic Resonance Imaging and Echocardiography to Monitor Doxorubicin-Induced Cardiotoxicity.
Int J Angiol. 2020 Mar;29(1):45-51
Authors: Tak T, Jaekel CM, Gharacholou SM, Dworak MW, Marshall SA
Abstract
Doxorubicin is a standard treatment option for breast cancer, lymphoma, and leukemia, but its benefits are limited by its potential for cardiotoxicity. The primary objective of this study was to compare cardiac magnetic resonance imaging (CMRI) versus echocardiography (ECHO) to detect a reduction in left ventricular ejection function, suggestive of doxorubicin cardiotoxicity. We studied eligible patients who were 18 years or older, who had breast cancer or lymphoma, and who were offered treatment with doxorubicin with curative intent dosing of 240 to 300 mg/m 2 body surface area between March 1, 2009 and October 31, 2013. Patients underwent baseline CMRI and ECHO. Both imaging studies were repeated after four cycles of treatment. Ejection fraction (EF) calculated by both methods was compared and analyzed with the inferential statistical Student's t test. Twenty-eight eligible patients were enrolled. Two patients stopped participating in the study before undergoing baseline CMRI; 26 patients underwent baseline ECHO and CMRI. Eight of those 26 patients declined posttreatment studies, so the final study population was 18 patients. There was a significant difference in EF pre- and posttreatment in the CMRI group ( p = 0.009) versus the ECHO group that showed no significant differences in EF ( p = NS). It appears that CMRI is superior to ECHO for detecting doxorubicin-induced reductions in cardiac systolic function. However, ECHO is less expensive and more convenient for patients because of its noninvasive character and bedside practicality. A larger study is needed to confirm these findings.
PMID: 32132816 [PubMed]
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The effect of adenosine triphosphate on sunitinib-induced cardiac injury in rats.
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The effect of adenosine triphosphate on sunitinib-induced cardiac injury in rats.
Hum Exp Toxicol. 2020 Mar 05;:960327120909874
Authors: Aldemir MN, Simsek M, Kara AV, Ozcicek F, Mammadov R, Yazıcı GN, Sunar M, Coskun R, Gulaboglu M, Suleyman H
Abstract
In this study, we aimed to show the effect of adenosine 5'-triphosphate (ATP) on sunitinib-induced cardiac injury in rats. The rats (n = 30) were divided equally into three groups as sunitinib group (SG), sunitinib plus ATP group (SAG), and healthy group (HG); 2 mg/kg ATP was injected intraperitoneally (ip) to the SAG group. Same volume normal saline as solvent was administered ip to the other two groups. After 1 h, 25 mg/kg sunitinib was applied orally via catheter to stomach in the SAG and SG groups. This procedure was repeated once daily for 5 weeks. At the end of this period, all animals were sacrificed and their cardiac tissue was removed. Malondialdehyde (MDA), total glutathione (tGSH), tumor necrosis factor α (TNF-α), and nuclear factor κB (NF-κB) levels in rats' cardiac tissues and troponin I (Tp-I) levels in rats' blood samples were evaluated. Histopathological analysis was also performed in cardiac tissues of the animals. MDA, TNF-α, NF-κB, and Tp-I levels were higher in the SG group compared to the SAG and HG groups (p < 0.001). tGSH levels of the SG group were lower than the SAG and HG groups (p < 0.001). The structure and morphology of cardiac muscle fibers and blood vessels were normal in the control group. In the SG group, obvious cardiac muscle tissue damage with dilated myofibers, locally atrophic myofibers, and congested blood vessels were observed. In the SAG group, marked amelioration in these findings was observed. We showed this for the first time that ATP administration exerts a protective effect against cardiac effects of sunitinib.
PMID: 32131635 [PubMed - as supplied by publisher]
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Protective strategies to prevent trastuzumab-induced cardiotoxicity - Authors' reply.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-01406736-TL.gif Related Articles
Protective strategies to prevent trastuzumab-induced cardiotoxicity - Authors' reply.
Lancet. 2020 02 15;395(10223):492-493
Authors: Earl HM, Hiller L, Plummer C, Miles D, Wardley AM, Cameron DA, Dunn JA
PMID: 32061290 [PubMed - indexed for MEDLINE]
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Protective strategies to prevent trastuzumab-induced cardiotoxicity.
//www.ncbi.nlm.nih.gov/corehtml/query/egifs/https:--linkinghub.elsevier.com-ihub-images-01406736-TL.gif Related Articles
Protective strategies to prevent trastuzumab-induced cardiotoxicity.
Lancet. 2020 02 15;395(10223):491-492
Authors: Guo S, Tse G, Liu T
PMID: 32061289 [PubMed - indexed for MEDLINE]
7 March 2020
14:05
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Chemotherapy-associated nonbacterial thrombotic endocarditis: A radiological mimicker of cardiac amyloidosis requiring histopathologic examination for definitive diagnosis.
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Chemotherapy-associated nonbacterial thrombotic endocarditis: A radiological mimicker of cardiac amyloidosis requiring histopathologic examination for definitive diagnosis.
Cardiovasc Pathol. 2020 Feb 11;47:107210
Authors: Sekulic M, Gupta A, Patterson A, Oliveira G, Rajagopalan S
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