Pathophysiology of cardiotoxicity from target therapy and angiogenesis inhibitors.
Maurea Nicola,Coppola Carmela,Piscopo Giovanna,Galletta Francesca,Riccio Gennaro,Esposito Emanuela,De Lorenzo Claudia,De Laurentiis Michelino,Spallarossa Paolo,Mercuro Giuseppe
Journal of cardiovascular medicine (Hagerstown, Md.)
The progress in cancer therapy and the increase in number of long-term survivors reveal the issue of cardiovascular side-effects of anticancer drugs. Cardiotoxicity has become a significant problem, and the risks of adverse cardiac events induced by systemic drugs need to be seriously considered. Potential cardiovascular toxicities linked to anticancer agents include arrhythmias, myocardial ischemia and infarction, hypertension, thromboembolism, left ventricular dysfunction, and heart failure. It has been shown that several anticancer drugs seriously affect the cardiovascular system, such as ErbB2 inhibitors, vascular endothelial growth factor (VEGF) inhibitors, multitargeted kinase inhibitors, Abelson murine leukemia viral oncogene homolog inhibitors, and others. Each of these agents has a different mechanism through which it affects the cardiovascular system. ErbB2 inhibitors block the ErbB4/ErbB2 heterodimerization pathway triggered by Neuregulin-1, which is essential for cardiomyocyte survival. VEGF signaling is crucial for vascular growth, but it also has a major impact on myocardial function, and the VEGF pathway is also essential for maintenance of cardiovascular homeostasis. Drugs that inhibit the VEGF signaling pathway lead to a net reduction in capillary density and loss of contractile function. Here, we review the mechanisms and pathophysiology of the most significant cardiotoxic effects of ErbB2 inhibitors and antiangiogenic drugs. Moreover, we highlight the role of cardioncology in recognizing these toxicities, developing strategies to prevent or minimize cardiovascular toxicity, and reducing long-term cardiotoxic effects.
10.2459/JCM.0000000000000377
An Overview on Arsenic Trioxide-Induced Cardiotoxicity.
Vineetha Vadavanath Prabhakaran,Raghu Kozhiparambil Gopalan
Cardiovascular toxicology
Arsenic trioxide (ATO) is among the first-line chemotherapeutic drugs used in oncological practice. It has shown substantial efficacy in treating patients with relapsed or refractory acute promyelocytic leukaemia. The clinical use of ATO is hampered due to cardiotoxicity and hence many patients are precluded from receiving this highly effective treatment. An alternative to this would be to use any drug that can ameliorate the cardiotoxic effects and allow exploiting the full therapeutic potential of ATO, with considerable impact on cancer therapy. Generation of reactive oxygen species is involved in a wide range of human diseases, including cancer, cardiovascular, pulmonary and neurological disorders. Hence, agents with the ability to protect against these reactive species may be therapeutically useful. The present review focuses on the beneficial as well as harmful effects of arsenic and ATO, the mechanisms underlying ATO toxicity and the possible ways that can be adopted to circumvent ATO-induced toxicity.
10.1007/s12012-018-09504-7
An update on the risk prediction and prevention of anticancer therapy-induced cardiotoxicity.
Bhave Manali,Shah Ami N,Akhter Nausheen,Rosen Steven T
Current opinion in oncology
PURPOSE OF REVIEW:Cardiotoxicity is a well established complication of anticancer therapy. As cancer survivorship and life expectancy for cancer patients improves, the morbidity and mortality of anticancer therapy-related cardiotoxicity has become more problematic. It is of utmost importance to identify patients at the highest risk for the development of cardiotoxicity and to determine strategies for prevention, early detection and treatment. RECENT FINDINGS:Clinical risk factors, biomarkers, advanced cardiac imaging and pharmacogenomics may be used to classify patients at risk for therapy-induced cardiotoxicity. A much broader armamentarium of imaging modalities for risk prediction, in addition to simple two-dimensional echocardiogram and radionucleotide angiography, has also shown clinical utility in identifying early-onset cardiotoxicity and areas of reversible myocardial injury. Exciting new research aimed at predicting cardiotoxicity and developing cardioprotective strategies may lead to changes in the administration of cardiotoxic chemotherapies. SUMMARY:Personalized assessments of the risks and benefits of therapy should be used as opposed to standardized dosing and schedules. Patients at higher risk for cardiotoxicity should receive closer monitoring, cardioprotective agents, dose adjustment or alternative regimens in an effort to reduce cardiovascular morbidity and mortality. Future research will hopefully define specific risk prediction tools and clinical protocols to prevent irreversible cardiotoxicity.
10.1097/CCO.0000000000000132
Preventing antiblastic drug-related cardiomyopathy: old and new therapeutic strategies.
Cadeddu Christian,Mercurio Valentina,Spallarossa Paolo,Nodari Savina,Triggiani Marco,Monte Ines,Piras Roberta,Madonna Rosalinda,Pagliaro Pasquale,Tocchetti Carlo G,Mercuro Giuseppe
Journal of cardiovascular medicine (Hagerstown, Md.)
Because of the recent advances in chemotherapeutic protocols, cancer survival has improved significantly, although cardiovascular disease has become a major cause of morbidity and mortality among cancer survivors: in addition to the well-known cardiotoxicity (CTX) from anthracyclines, biologic drugs that target molecules that are active in cancer biology also interfere with cardiovascular homeostasis.Pharmacological and non-pharmacological strategies to protect the cardiovascular structure and function are the best approaches to reducing the prevalence of cardiomyopathy linked to anticancer drugs. Extensive efforts have been devoted to identifying and testing strategies to achieve this end, but little consensus has been reached on a common and shared operability.Timing, dose and mode of chemotherapy administration play a crucial role in the development of acute or late myocardial dysfunction. Primary prevention initiatives cover a wide area that ranges from conventional heart failure drugs, such as β-blockers and renin-angiotensin-aldosterone system antagonists to nutritional supplementation and physical training. Additional studies on the pathophysiology and cellular mechanisms of anticancer-drug-related CTX will enable the introduction of novel therapies.We present various typologies of prevention strategies, describing the approaches that have already been used and those that could be effective on the basis of a better understanding of pharmacokinetic and pharmacodynamic CTX mechanisms.
10.2459/JCM.0000000000000382
Acetaminophen poisoning-induced heart injury: a case-based review.
Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences
PURPOSE:Acetaminophen (Paracetamol, APAP) poisoning is frequently implicated in self-harm. Cases of acetaminophen-associated cardiotoxicity are rare in relation to the number of patients with acetaminophen poisoning. A review of acetaminophen cardiotoxicity in 1996 concluded that there was no decisive evidence demonstrating that acetaminophen overdose has a cardiotoxic effect. This review study aimed to determine whether acetaminophen could induce heart injury. METHODS:We searched for keywords of acetaminophen, paracetamol, cardiotoxicity, heart injury, heart damage, myocarditis, pericarditis, myocardial infarction, and myocardial ischemia in Web of Science, PubMed, Scopus, Embase, Google Scholar, and Persian databases. The search included articles published from January 1950 to October 2018 with no language restrictions. RESULTS:The search yielded 64 citations in English; 36 of the articles were excluded as they were not relevant; 5 articles were excluded since they were duplicates, leaving 23 articles. Full-text articles of the 23 citations were obtained and reviewed. Myocardial infarction, heart dysfunction and failure, cardiac arrhythmias, pericarditis, heart cell necrosis, and sudden cardiac death were reported in acetaminophen overdose. CONCLUSIONS:Ddysrhythmias, heart failure, and various other cardiac effects could occur following acetaminophen induced hepatic failure. However, the evidence for direct injury on cardiac tissue is weak. Graphical abstract Potential mechanisms for cardiotoxicity of acetaminophen.
10.1007/s40199-019-00307-x
Anthracycline cardiotoxicity: an update on mechanisms, monitoring and prevention.
Henriksen Peter A
Heart (British Cardiac Society)
Anthracycline chemotherapy causes dose-related cardiomyocyte injury and death leading to left ventricular dysfunction. Clinical heart failure may ensue in up to 5% of high-risk patients. Improved cancer survival together with better awareness of the late effects of cardiotoxicity has led to growing recognition of the need for surveillance of anthracycline-treated cancer survivors with early intervention to treat or prevent heart failure. The main mechanism of anthracycline cardiotoxicity is now thought to be through inhibition of topoisomerase 2β resulting in activation of cell death pathways and inhibition of mitochondrial biogenesis. In addition to cumulative anthracycline dose, age and pre-existing cardiac disease are risk markers for cardiotoxicity. Genetic susceptibility factors will help identify susceptible patients in the future. Cardiac imaging with echocardiographic measurement of global longitudinal strain and cardiac troponin detect early myocardial injury prior to the development of left ventricular dysfunction. There is no consensus on how best to monitor anthracycline cardiotoxicity although guidelines advocate quantification of left ventricular ejection fraction before and after chemotherapy with additional scanning being justified in high-risk patients. Patients developing significant left ventricular dysfunction with or without clinical heart failure should be treated according to established guidelines. Liposomal encapsulation reduces anthracycline cardiotoxicity. Dexrazoxane administration with anthracycline interferes with binding to topoisomerase 2β and reduces both cardiotoxicity and subsequent heart failure in high-risk patients. Angiotensin inhibition and β-blockade are also protective and appear to prevent the development of left ventricular dysfunction when given prior or during chemotherapy in patients exhibiting early signs of cardiotoxicity.
10.1136/heartjnl-2017-312103
Prevention, Detection, and Management of Chemotherapy-Related Cardiac Dysfunction.
Abdel-Qadir Husam,Amir Eitan,Thavendiranathan Paaladinesh
The Canadian journal of cardiology
Cancer treatment-related cardiac dysfunction (CTRCD) occurs with many agents used in the treatment of cancer. This is most relevant in patients receiving cancer treatment with curative intent as opposed to those treated with a palliative intent where lifespan is more likely to be limited by the cancer diagnosis. Clinicians need to be aware of methods to prevent, detect, and manage CTRCD. This article frames an approach to CTCRD based on the American College of Cardiology/American Heart Association stages of heart failure (HF). In patients who are at risk for CTRCD (stage A HF), risk reduction methods may be warranted, including management of cardiovascular risk factors, modification of cancer treatment, and universal preventive therapy. Once cancer therapy begins, it is prudent to detect and promptly treat myocardial dysfunction (stage B HF). This can be achieved by careful monitoring during therapy using echocardiography, multigated acquisition scans, or cardiac MRI. Subclinical myocardial systolic dysfunction (ie, without a drop in ejection fraction) can be identified using either echocardiography measured peak systolic global longitudinal strain or cardiac troponin I. At present, there is insufficient evidence to institute preventive interventions based on changes in these preclinical markers. Finally, in patients with stage C/D HF, management strategies should follow existing guidelines. Advanced treatment including cardiac transplantation and mechanical circulatory support may be considered in appropriate circumstances.
10.1016/j.cjca.2016.01.028
Myocardial Injury without Electrocardiographic Changes after a Suicide Attempt by an Overdose of Glimepiride and Zolpidem: A Case Report and Literature Review.
Chou Shengpu,Ayabe Seiji,Sekine Nobuo
Internal medicine (Tokyo, Japan)
A 40-year-old diabetic man was admitted to our hospital for poor glycemic control. During hospitalization, he took 42 mg glimepiride and 50 mg zolpidem as a suicide attempt. The following day, the creatine kinase-MB fraction and troponin I levels were elevated to 112 IU/L and 8.77 ng/mL, respectively, without any electrocardiographic abnormalities. The patient recovered completely without any complications. Four weeks later, coronary computed tomography angiography and myocardial perfusion scintigraphy revealed moderate one-vessel coronary disease without the evidence of myocardial ischemia or old infarction. Cardiac-specific markers must be considered in sulfonylurea-induced hypoglycemic patients, particularly when the patient is unconscious and does not exhibit any clinical manifestations.
10.2169/internalmedicine.54.4748
Anti-cancer drugs-induced arterial injury: risk stratification, prevention, and treatment.
Gara Edit,Csikó Kristóf György,Ruzsa Zoltán,Földes Gábor,Merkely Béla
Medical oncology (Northwood, London, England)
Vascular side effects of standard chemotherapeutic drugs and novel anti-tumor agents complicate treatment cycles, increase non-cancer-related mortality rates, and decrease the quality of life in cancer survivors. Arterial thromboembolic events (ATEE) are associated with most anti-cancer medications. Previous articles have reported a variety of vascular events including ST-segment elevation myocardial infarction as one of the most severe acute arterial attacks. Cardiologists should play an early role in identifying those at high risk for vascular complications and tailor anti-thrombotic therapies in keeping with thromboembolic and bleeding risks. Early preventive steps and individualized chemotherapy may decrease anti-tumor treatment-related vascular events. Here, we aim to provide an extensive review of anti-tumor drug-induced vascular injury (DIVI), pathomechanisms, and risk stratification underlining arterial events. We give a summary of clinical manifestations, treatment options, and possible preventive measures of DIVI. Additionally, the treatment of modifiable risk factors and tailored choice of chemotherapy must be considered in all oncology patients to prevent DIVI. We propose a complex tool for ATEE risk stratification which is warranted for early prediction leading to less frequent complications in cancer patients.
10.1007/s12032-019-1295-8
Cardiovascular imaging in the diagnosis and monitoring of cardiotoxicity: cardiovascular magnetic resonance and nuclear cardiology.
Pepe Alessia,Pizzino Fausto,Gargiulo Paola,Perrone-Filardi Pasquale,Cadeddu Christian,Mele Donato,Monte Ines,Novo Giuseppina,Zito Concetta,Di Bella Gianluca
Journal of cardiovascular medicine (Hagerstown, Md.)
Chemotherapy-induced cardiotoxicity (CTX) is a determining factor for the quality of life and mortality of patients administered potentially cardiotoxic drugs and in long-term cancer survivors. Therefore, prevention and early detection of CTX are highly desirable, as is the exploration of alternative therapeutic strategies and/or the proposal of potentially cardioprotective treatments. In recent years, cardiovascular imaging has acquired a pivotal role in this setting. Although echocardiography remains the diagnostic method most used to monitor cancer patients, the need for more reliable, reproducible and accurate detection of early chemotherapy-induced CTX has encouraged the introduction of second-line advanced imaging modalities, such as cardiac magnetic resonance (CMR) and nuclear techniques, into the clinical setting. This review of the Working Group on Drug Cardiotoxicity and Cardioprotection of the Italian Society of Cardiology aims to afford an overview of the most important findings from the literature about the role of CMR and nuclear techniques in the management of chemotherapy-treated patients, describe conventional and new parameters for detecting CTX from both diagnostic and prognostic perspectives and provide integrated insight into the role of CMR and nuclear techniques compared with other imaging tools and versus the positions of the most important international societies.
10.2459/JCM.0000000000000380
Echocardiographic Assessment of Cardiotoxic Effects of Cancer Therapy.
Bottinor Wendy J,Migliore Christopher K,Lenneman Carrie A,Stoddard Marcus F
Current cardiology reports
Patients with cancer can present with difficult management issues, as the medicine can sometimes cause sequelae destructive to healthy tissue. As this population lives longer, cardiotoxic effects are beginning to emerge, but the early recognition of this signal can prove difficult, with too late a recognition leading to lifelong cardiac impairment and dysfunction. Cardio-oncology can bridge this difficulty, and echocardiography and its newer imaging abilities are proving efficacious in this population. This article will address common sequelae of cardiotoxic treatment regimens and offer recommendations for echocardiographic surveillance. We recommend echocardiography, preferably three-dimensional and strain imaging, to monitor for cardiotoxic myocardial effects before, during, and after chemotherapy with cardiotoxic drug regimens, particularly anthracycline derivatives. A reduction in left ventricular (LV) global longitudinal strain in all patients, or reduction in LV global circumferential strain or global radial strain in patients at intermediate to high risk for cardiotoxicity, despite normal LV ejection fraction warrants a clinical assessment on the benefits of continuing cardiotoxic chemotherapeutic agents. Lifelong surveillance using echocardiography for cardiotoxicity and radiation-related valvular, pericardial, and coronary artery disease is prudent.
10.1007/s11886-016-0776-z
Anthracycline-Induced Cardiotoxicity in Young Cancer Patients: The Role of Carnitine.
Armenian Saro H
Annals of nutrition & metabolism
While the increased rates of survival in childhood cancers have increased progressively in recent decades, many childhood cancer survivors will have at least one chronic health condition within 40 years of age. In this regard, cardiovascular complications have emerged as a leading cause of long-term morbidity and mortality in long-term survivors of childhood cancer, likely due to exposure to anthracycline chemotherapy, and outcomes in patients with anthracycline-related cardiomyopathy remain poor. Some progress has been made in understanding the mechanisms at the basis of anthracycline-related cardiomyopathy, which appear to involve generation of reactive oxygen species, leading to mitochondrial dysfunction, followed by myocyte apoptosis and maladaptive left ventricular remodeling. Even if several guidelines currently exist for monitoring cancer patients treated with cardiotoxic therapies who are at high risk for heart failure, much work remains to be done in finding reliable markers for screening for cardiac dysfunction. Studies from our group have identified alterations in L-carnitine in cancer survivors. While additional investigations are needed, preliminary studies suggest a role for carnitine in primary prevention (during treatment) and secondary prevention (to improve function after treatment).
10.1159/000448322
The Role of Calcium Handling Mechanisms in Reperfusion Injury.
Pittas Konstantinos,Vrachatis Dimitrios A,Angelidis Christos,Tsoucala Styliani,Giannopoulos Georgios,Deftereos Spyridon
Current pharmaceutical design
Cardiovascular diseases, such as stroke and myocardial infarction (MI) remain the major cause of death and disability worldwide. However, the mortality of MI has declined dramatically over the past several decades because of advances in medicines (thrombolytic agents, antiplatelet drugs, beta blockers, and angiotensin converting enzyme inhibitors) and approaches to restore tissue perfusion (percutaneous coronary intervention and cardiopulmonary bypass). Animal studies have been shown that these treatments have been effective in reducing acute myocardial ischemic injury and limiting MI size. The paradox is that the process of reperfusion can itself amplify cell injury and death, known as myocardial ischemia-reperfusion injury (I/R). Intensive research has uncovered several complex mechanisms of cardiomyocyte damage after reperfusion,and potential therapeutic targets for preventing I/R. Importantly, it is now recognized that excessive elevation of intracellular and mitochondrial Ca2+during reperfusion predisposes the cells to hypercontracture, proteolysis and mitochondrial failure and eventually to necrotic or apoptotic death. These enormous alterations in cytosolic Ca2+ levels are induced by the Ca2+ channels of the sarcolemma(L-Type Ca2+channels, sodium/calcium exchanger), the endoplasmic/ sarcoplasmic reticulum (SERCA ATPase) and ryanodine receptors, SOCE(store-operated calcium entry), lysosomes and others, which are modified by I/R injury. The overall goal of this review is to describe the different pathways that lead to I/R injury via Ca2+ overload, focus on recent discoveries and highlight prospects for therapeutic strategies for clinical benefit.
10.2174/1381612825666181120155953
Anthracycline Chemotherapy and Cardiotoxicity.
McGowan John V,Chung Robin,Maulik Angshuman,Piotrowska Izabela,Walker J Malcolm,Yellon Derek M
Cardiovascular drugs and therapy
Anthracycline chemotherapy maintains a prominent role in treating many forms of cancer. Cardiotoxic side effects limit their dosing and improved cancer outcomes expose the cancer survivor to increased cardiovascular morbidity and mortality. The basic mechanisms of cardiotoxicity may involve direct pathways for reactive oxygen species generation and topoisomerase 2 as well as other indirect pathways. Cardioprotective treatments are few and those that have been examined include renin angiotensin system blockade, beta blockers, or the iron chelator dexrazoxane. New treatments exploiting the ErbB or other novel pro-survival pathways, such as conditioning, are on the cardioprotection horizon. Even in the forthcoming era of targeted cancer therapies, the substantial proportion of today's anthracycline-treated cancer patients may become tomorrow's cardiac patient.
10.1007/s10557-016-6711-0
Cancer chemotherapy and cardiac arrhythmias: a review.
Tamargo Juan,Caballero Ricardo,Delpón Eva
Drug safety
Cardiovascular toxicity is a potential complication of cancer chemotherapy (CC) that increases the morbidity and mortality of cancer patients. Cardiac arrhythmias have been reported as an adverse effect of many chemotherapeutic drugs, including novel targeted therapies. The relationship between chemotherapy and arrhythmias has not been well-established and the proarrhythmogenic mechanisms remain uncertain as they can be the result of a direct electrophysiological effect or of changes in cardiac structure and function, including myocardial ischaemia and heart failure, which create an arrhythmogenic substrate. In this review we summarise available evidence of proarrhythmia induced by CC, discuss the possible mechanisms involved in this adverse effect and emphasise the importance of cardiac monitoring for the early diagnosis, intervention and surveillance of those patients more susceptible to develop proarrhythmia in an attempt to reduce the morbidity and mortality. Oncologists should be fully aware of proarrhythmia and the close collaboration between cardiologists and oncologists would result in a better cardiovascular assessment, risk stratification, cardiac monitoring and treatment during CC and during the follow-up. The final objective is to understand the mechanisms of proarrhythmia and evaluate its real incidence and clinical relevance so as to select the safest and most effective treatment for cancer patients.
10.1007/s40264-014-0258-4
[Chemotherapy-induced cardiotoxicity: Incidence, diagnosis and prevention].
Nelson-Veniard Marie,Thambo Jean-Benoit
Bulletin du cancer
Chemotherapy-induced cardiotoxicity is a major cause of morbidity and mortality in cancer survivor. The most clinically evident and best known cardiotoxicity is the anthracycline adverse effect with heart failure. Many cardiovascular adverse effects appear after cancer therapy: heart congestive failure, myocardial ischemia, hypertension, thromboembolic complications, arrhythmias and conduction disturbances. There are potential strategies to mitigate the risks of cardiac complications for cancer patients with physical examination, echocardiography and electrocardiogram. The management of the cardiotoxicity is variable.
10.1016/j.bulcan.2015.03.014
Cardiomyocyte autophagy and cancer chemotherapy.
Li Dan L,Hill Joseph A
Journal of molecular and cellular cardiology
Autophagy, an evolutionally conserved process of controlled cellular cannibalization, plays a vital role in cardiac physiology. Perturbations in cardiomyocyte autophagy contribute to the pathogenesis of a wide range of cardiac diseases, many of which culminate in heart failure. With recent advances in cancer chemotherapy and consequent improvements in cancer survival, drug-induced toxicity to the heart has assumed greater importance. As a number of prominent cellular pathways are critical to the survival of both tumor cells and heart cells, it comes as little surprise that therapies targeting those pathways have consequences in both tissues. Little is known presently about cardiomyocyte autophagy, a prominent cellular response to stress, in the setting of chemotherapy, but preliminary evidence suggests an important and context-dependent role. Dissecting the role of autophagy in "onco-cardiology" will likely yield insights into mechanisms underlying cardiomyopathy and may lead to novel means to protect the myocardium from chemotherapy-induced injury. This article is part of a Special Issue entitled "Protein Quality Control, the Ubiquitin Proteasome System, and Autophagy".
10.1016/j.yjmcc.2013.11.007
Neuregulin-1 signaling in the pathogenesis of chemotherapy-induced heart failure.
Lenneman Carrie Geisberg
Current heart failure reports
The National Cancer Institute estimates that approximately 13.7 million Americans with a history of cancer were alive on January 1, 2012. With the rising number of cancer survivors, there is an increased focus on how chemotherapy agents modulate the cardiovascular biology and cause chemotherapy-related heart failure in certain patients. Neuregulin-1 (NRG-1) is an important cardiac growth factor that is essential for normal myocardial development and maintenance. Certain chemotherapy agents perturb the normal NRG-1 signaling in the cardiovascular system and cause cardiac dysfunction and, in some cases, symptomatic heart failure. As researchers have learned the critical importance of NRG-1 within the cardiovascular system, more attention has been focused on the potential use of NRG-1 as biomarker and therapy for the treatment of heart failure. This review will highlight the biology of NRG-1 within the cardiovascular system, its role in chemotherapy-induced heart failure, and the translational potential of NRG-1 as treatment for heart failure.
10.1007/s11897-014-0193-9
Cardioprotective strategies to prevent breast cancer therapy-induced cardiotoxicity.
Trends in cardiovascular medicine
Breast cancer is the most common malignancy affecting females, with over 260,000 new cases annually and over 3.1 million survivors in the United States alone. Exposure to potentially cardiotoxic therapies, including anthracyclines, trastuzumab, and radiation therapy, coupled with host factors, place patients at increased risk for the development of cardiovascular disease (CVD) compared to non-cancer controls. Overall survival outcomes are significantly worse in patients who develop CVD, and in certain breast cancer populations, cardiovascular death exceeds the risk of cancer death in the long-term. In order to mitigate the risk of CVD, there is a growing interest in the use of cardioprotective strategies at the time of cancer therapy initiation. In this review, we present a detailed evaluation of the evidence from recently completed as well as ongoing cardio-oncology clinical trials in pharmacologic cardioprotection in breast cancer patients. We focus primarily on the potential role of dexrazoxane, alterations in anthracycline dosing or formulation, neurohormonal antagonists, beta-blockers, and combination therapy. We also discuss ongoing studies in statin cardioprotection, radiation delivery strategies, use of risk-guided strategies and the study of specific cancer populations. We close with a discussion of the ongoing needs in the field of cardio-oncology in order to advance the clinical care of patients with rigorous, evidence-based medicine.
10.1016/j.tcm.2019.01.006
Vascular Complications of Cancer Chemotherapy.
Cameron Alan C,Touyz Rhian M,Lang Ninian N
The Canadian journal of cardiology
Development of new anticancer drugs has resulted in improved mortality rates and 5-year survival rates in patients with cancer. However, many of the modern chemotherapies are associated with cardiovascular toxicities that increase cardiovascular risk in cancer patients, including hypertension, thrombosis, heart failure, cardiomyopathy, and arrhythmias. These limitations restrict treatment options and might negatively affect the management of cancer. The cardiotoxic effects of older chemotherapeutic drugs such as alkylating agents, antimetabolites, and anticancer antibiotics have been known for a while. The newer agents, such as the antiangiogenic drugs that inhibit vascular endothelial growth factor signalling are also associated with cardiovascular pathology, especially hypertension, thromboembolism, myocardial infarction, and proteinuria. Exact mechanisms by which vascular endothelial growth factor inhibitors cause these complications are unclear but impaired endothelial function, vascular and renal damage, oxidative stress, and thrombosis might be important. With increasing use of modern chemotherapies and prolonged survival of cancer patients, the incidence of cardiovascular disease in this patient population will continue to increase. Accordingly, careful assessment and management of cardiovascular risk factors in cancer patients by oncologists and cardiologists working together is essential for optimal care so that prolonged cancer survival is not at the expense of increased cardiovascular events.
10.1016/j.cjca.2015.12.023
Troponin as a cardiotoxicity marker in breast cancer patients receiving anthracycline-based chemotherapy: A narrative review.
Simões Ricardo,Silva Luciana Maria,Cruz André Luiz Valle Mussi,Fraga Vanessa Gomes,de Paula Sabino Adriano,Gomes Karina Braga
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
The approach to breast cancer has changed in recent decades due to significant advances in screening, early diagnosis, and treatment; however, the risk of cardiovascular injury induced by chemotherapy has remained similar. Anthracyclines are the most common agents used in breast cancer treatment and may lead to cardiotoxicity, which appears to have a direct relationship with accumulated dose and duration of treatment. Therefore, the use of cardiac biomarkers derived from those used in cardiac disease diagnosis has been applied to the early identification, evaluation, and cardiotoxicity monitoring during chemotherapy. Cardiac troponins (cTn) have high specificities and high sensitivity in myocardial injury and are used in the diagnosis and risk stratification of acute coronary syndromes. cTn have been validated by clinical studies in the cardiotoxicity diagnosis and prognosis in patients treated with high doses of anthracyclines alone or in combination, mainly with trastuzumab. Thus, the identification of cardiotoxicity through cTn in the preclinical phase would be crucial for the application of preventive strategies. Here, we analyzed 23 cross-sectional, prospective and retrospective studies using cTn as the biomarker of cardiotoxicity in patients with breast cancer receiving treatment with anthracyclines. Studies showed that the association of cTn with different biomarkers can contribute to the early diagnosis of cardiotoxicity; however the main evidence is that low cTn levels is related to a better outcome with a good negative predictive value (NPV). In conclusion, different studies are still necessary for the adoption of cTn as a routine clinical biomarker in patients with breast cancer receiving anthracycline treatment.
10.1016/j.biopha.2018.08.035
Chemotherapy-induced cardiomyopathy.
Higgins Angela Y,O'Halloran Thomas D,Chang James D
Heart failure reviews
Cardiomyopathy is an adverse outcome of antineoplastic drug therapy that has become increasingly relevant in the management of cancer survivors. As the efficacy of anticancer treatments has improved, long-term outcomes are altered by the development of cardiotoxicity, which may be associated with an even worse prognosis than that of the underlying malignancy. From the research into mechanisms, prevention, and treatment, the specialized field of cardio-oncology has evolved, but the recognition and appropriate management of these patients is important for the general internist and general cardiologist as well. Although antineoplastic chemotherapy can cause multiple forms of cardiotoxicity, including arrhythmia, pericardial disease, valvular dysfunction, and myocardial ischemia, in this review we will focus on chemotherapeutic agents associated with cardiomyopathies, from the anthracyclines to newer, the so-called targeted agents such as tyrosine kinase inhibitors. We also review the diagnostic modalities for chemotherapy-induced cardiomyopathy as well as the prevention and treatment strategies which may prolong the lives of those suffering from cancer.
10.1007/s10741-015-9502-y
Chemotherapy-induced cardiotoxicity: new insights into mechanisms, monitoring, and prevention.
Cadeddu Dessalvi Christian,Deidda Martino,Mele Donato,Bassareo Pier P,Esposito Roberta,Santoro Ciro,Lembo Maria,Galderisi Maurizio,Mercuro Giuseppe
Journal of cardiovascular medicine (Hagerstown, Md.)
: Chemotherapy-induced cardiotoxicity (CTX) remains a determining factor for the quality of life and mortality of patients treated with potentially cardiotoxic drugs. Considerable advances have been made in this field with increase in awareness regarding chemotherapy-induced CTX, which has changed the treatment approach to include cardiovascular risk among the first factors to be evaluated before therapy. Moreover, a better understanding of the pathophysiology of chemotherapy-induced CTX has also facilitated early identification of patients at risk with the help of new imaging technologies. The newly developed imaging tools in cardio-oncology have led to the introduction of novel parameters for evaluation of myocardial function. This, together with a renewed standardization of measurements, has increased the adherence to monitoring protocols. With respect to treatment and prevention, researchers have started focusing attention on the development of new strategies as well as new cardioprotective agents that will play a crucial role in the prevention of CTX in the near future.
10.2459/JCM.0000000000000667