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20 pages, 7169 KiB  
Review
The Role of Advanced Cardiovascular Imaging Modalities in Cardio-Oncology: From Early Detection to Unravelling Mechanisms of Cardiotoxicity
by Isabella Leo, Mahesh Vidula, Giandomenico Bisaccia, Maria Cristina Procopio, Roberto Licordari, Maria Perotto, Giulia La Vecchia, Nikolaos Miaris, Paco E. Bravo and Chiara Bucciarelli-Ducci
J. Clin. Med. 2023, 12(15), 4945; https://doi.org/10.3390/jcm12154945 - 27 Jul 2023
Cited by 2 | Viewed by 1730
Abstract
Advances in cancer therapies have led to a global improvement in patient survival rates. Nevertheless, the price to pay is a concomitant increase in cardiovascular (CV) morbidity and mortality in this population. Increased inflammation and disturbances of the immune system are shared by [...] Read more.
Advances in cancer therapies have led to a global improvement in patient survival rates. Nevertheless, the price to pay is a concomitant increase in cardiovascular (CV) morbidity and mortality in this population. Increased inflammation and disturbances of the immune system are shared by both cancer and CV diseases. Immunological effects of anti-cancer treatments occur with both conventional chemotherapy and, to a greater extent, with novel biological therapies such as immunotherapy. For these reasons, there is growing interest in the immune system and its potential role at the molecular level in determining cardiotoxicity. Early recognition of these detrimental effects could help in identifying patients at risk and improve their oncological management. Non-invasive imaging already plays a key role in evaluating baseline CV risk and in detecting even subclinical cardiac dysfunction during surveillance. The aim of this review is to highlight the role of advanced cardiovascular imaging techniques in the detection and management of cardiovascular complications related to cancer treatment. Full article
(This article belongs to the Section Cardiovascular Medicine)
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53 pages, 1273 KiB  
Systematic Review
New Insights in the Era of Clinical Biomarkers as Potential Predictors of Systemic Therapy-Induced Cardiotoxicity in Women with Breast Cancer: A Systematic Review
by Alexia Alexandraki, Elisavet Papageorgiou, Marina Zacharia, Kalliopi Keramida, Andri Papakonstantinou, Carlo M. Cipolla, Dorothea Tsekoura, Katerina Naka, Ketti Mazzocco, Davide Mauri, Manolis Tsiknakis, Georgios C. Manikis, Kostas Marias, Yiola Marcou, Eleni Kakouri, Ifigenia Konstantinou, Maria Daniel, Myria Galazi, Effrosyni Kampouroglou, Domen Ribnikar, Cameron Brown, Georgia Karanasiou, Athos Antoniades, Dimitrios Fotiadis, Gerasimos Filippatos and Anastasia Constantinidouadd Show full author list remove Hide full author list
Cancers 2023, 15(13), 3290; https://doi.org/10.3390/cancers15133290 - 22 Jun 2023
Cited by 5 | Viewed by 3036
Abstract
Cardiotoxicity induced by breast cancer therapies is a potentially serious complication associated with the use of various breast cancer therapies. Prediction and better management of cardiotoxicity in patients receiving chemotherapy is of critical importance. However, the management of cancer therapy-related cardiac dysfunction (CTRCD) [...] Read more.
Cardiotoxicity induced by breast cancer therapies is a potentially serious complication associated with the use of various breast cancer therapies. Prediction and better management of cardiotoxicity in patients receiving chemotherapy is of critical importance. However, the management of cancer therapy-related cardiac dysfunction (CTRCD) lacks clinical evidence and is based on limited clinical studies. Aim: To provide an overview of existing and potentially novel biomarkers that possess a promising predictive value for the early and late onset of CTRCD in the clinical setting. Methods: A systematic review of published studies searching for promising biomarkers for the prediction of CTRCD in patients with breast cancer was undertaken according to PRISMA guidelines. A search strategy was performed using PubMed, Google Scholar, and Scopus for the period 2013–2023. All subjects were >18 years old, diagnosed with breast cancer, and received breast cancer therapies. Results: The most promising biomarkers that can be used for the development of an alternative risk cardiac stratification plan for the prediction and/or early detection of CTRCD in patients with breast cancer were identified. Conclusions: We highlighted the new insights associated with the use of currently available biomarkers as a standard of care for the management of CTRCD and identified potentially novel clinical biomarkers that could be further investigated as promising predictors of CTRCD. Full article
(This article belongs to the Section Systematic Review or Meta-Analysis in Cancer Research)
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17 pages, 1902 KiB  
Review
PCSK9 Inhibitors in Cancer Patients Treated with Immune-Checkpoint Inhibitors to Reduce Cardiovascular Events: New Frontiers in Cardioncology
by Vincenzo Quagliariello, Irma Bisceglia, Massimiliano Berretta, Martina Iovine, Maria Laura Canale, Carlo Maurea, Vienna Giordano, Andrea Paccone, Alessandro Inno and Nicola Maurea
Cancers 2023, 15(5), 1397; https://doi.org/10.3390/cancers15051397 - 22 Feb 2023
Cited by 19 | Viewed by 3686
Abstract
Cancer patients treated with immune checkpoint inhibitors (ICIs) are exposed to a high risk of atherosclerosis and cardiometabolic diseases due to systemic inflammatory conditions and immune-related atheroma destabilization. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key protein involved in metabolism of low-density [...] Read more.
Cancer patients treated with immune checkpoint inhibitors (ICIs) are exposed to a high risk of atherosclerosis and cardiometabolic diseases due to systemic inflammatory conditions and immune-related atheroma destabilization. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key protein involved in metabolism of low-density lipoprotein (LDL) cholesterol. PCSK9 blocking agents are clinically available and involve monoclonal antibodies, and SiRNA reduces LDL levels in high-risk patients and atherosclerotic cardiovascular disease events in multiple patient cohorts. Moreover, PCSK9 induces peripheral immune tolerance (inhibition of cancer cell- immune recognition), reduces cardiac mitochondrial metabolism, and enhances cancer cell survival. The present review summarizes the potential benefits of PCSK9 inhibition through selective blocking antibodies and siRNA in patients with cancer, especially in those treated with ICIs therapies, in order to reduce atherosclerotic cardiovascular events and potentially improve ICIs-related anticancer functions. Full article
(This article belongs to the Section Molecular Cancer Biology)
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5 pages, 200 KiB  
Editorial
Clinical Management of Long-Term Survivors after Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma
by Alessia Bari, Chiara Gerardi, Eleonora Allocati, Agata Puzzovivo, Vitaliana De Sanctis, Alessandra Tucci, Monica Balzarotti, Silvia Franceschetti, Francesco Merli, Attilio Guarini, Guido Gini and Carla Minoia
Cancers 2022, 14(23), 5960; https://doi.org/10.3390/cancers14235960 - 2 Dec 2022
Cited by 1 | Viewed by 1473
Abstract
Compared to other patients suffering from hematological malignancies, classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients have a long life expectancy when in complete remission at the end of first, or sometimes second, line treatments [...] Full article
(This article belongs to the Special Issue Lymphoma Survivorship)
22 pages, 7426 KiB  
Article
Combination of Spirulina platensis, Ganoderma lucidum and Moringa oleifera Improves Cardiac Functions and Reduces Pro-Inflammatory Biomarkers in Preclinical Models of Short-Term Doxorubicin-Mediated Cardiotoxicity: New Frontiers in Cardioncology?
by Vincenzo Quagliariello, Manuela Giovanna Basilicata, Giacomo Pepe, Raffaele De Anseris, Annabella Di Mauro, Giosuè Scognamiglio, Giuseppe Palma, Vincenzo Vestuto, Simona Buccolo, Antonio Luciano, Massimiliano Barbieri, Francesca Bruzzese, Carlo Maurea, Rossella Pumpo, Carmine Ostacolo, Pietro Campiglia, Massimiliano Berretta and Nicola Maurea
J. Cardiovasc. Dev. Dis. 2022, 9(12), 423; https://doi.org/10.3390/jcdd9120423 - 28 Nov 2022
Cited by 13 | Viewed by 3005
Abstract
Anthracyclines are essential adjuvant therapies for a variety of cancers, particularly breast, gastric and esophageal cancers. Whilst prolonging cancer-related survival, these agents can induce drug-related cardiotoxicity. Spirulina, Reishi (Ganoderma lucidum) and Moringa are three nutraceuticals with anti-inflammatory effects that are currently [...] Read more.
Anthracyclines are essential adjuvant therapies for a variety of cancers, particularly breast, gastric and esophageal cancers. Whilst prolonging cancer-related survival, these agents can induce drug-related cardiotoxicity. Spirulina, Reishi (Ganoderma lucidum) and Moringa are three nutraceuticals with anti-inflammatory effects that are currently used in cancer patients as complementary and alternative medicines to improve quality of life and fatigue. We hypothesize that the nutraceutical combination of Spirulina, Reishi and Moringa (Singo) could reduce inflammation and cardiotoxicity induced by anthracyclines. Female C57Bl/6 mice were untreated (Sham, n = 6) or treated for 7 days with short-term doxorubicin (DOXO, n = 6) or Singo (Singo, n = 6), or pre-treated with Singo for 3 days and associated with DOXO for remaining 7 days (DOXO–Singo, n = 6). The ejection fraction and radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100, Fujifilm, Tokyo, Japan). The myocardial expressions of NLRP3, DAMPs (galectin-3 and calgranulin S100) and 13 cytokines were quantified through selective mouse ELISA methods. Myocardial fibrosis, necrosis and hypertrophy were analyzed through immunohistochemistry (IHC). Human cardiomyocytes were exposed to DOXO (200 nM) alone or in combination with Singo (at 10, 25 and 50 µg/mL) for 24 and 48 h. Cell viability and inflammation studies were also performed. In preclinical models, Singo significantly improved ejection fraction and fractional shortening. Reduced expressions of myocardial NLRP3 and NF-kB levels in cardiac tissues were seen in DOXO–Singo mice vs. DOXO (p < 0.05). The myocardial levels of calgranulin S100 and galectin-3 were strongly reduced in DOXO–Singo mice vs. DOXO (p < 0.05). Immunohistochemistry analysis indicates that Singo reduces fibrosis and hypertrophy in the myocardial tissues of mice during exposure to DOXO. In conclusion, in the preclinical model of DOXO-induced cardiotoxicity, Singo is able to improve cardiac function and reduce biomarkers involved in heart failure and fibrosis. Full article
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22 pages, 2620 KiB  
Review
Cardiotoxicity Induced by Immune Checkpoint Inhibitors: What a Cardio-Oncology Team Should Know and Do
by Concetta Zito, Roberta Manganaro, Giuliana Ciappina, Calogera Claudia Spagnolo, Vito Racanelli, Mariacarmela Santarpia, Nicola Silvestris and Scipione Carerj
Cancers 2022, 14(21), 5403; https://doi.org/10.3390/cancers14215403 - 2 Nov 2022
Cited by 10 | Viewed by 3278
Abstract
Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic scenario for several malignancies. However, they can be responsible for immune-related adverse events (irAEs), involving several organs, with a pooled incidence ranging between 54% and 76%. The frequency of cardiovascular system involvement is <1%. Among [...] Read more.
Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic scenario for several malignancies. However, they can be responsible for immune-related adverse events (irAEs), involving several organs, with a pooled incidence ranging between 54% and 76%. The frequency of cardiovascular system involvement is <1%. Among the cardiovascular irAEs, myocarditis is the most common and the most dangerous but other, less common manifestations of ICI-related cardiotoxicity include pericardial disease, arrhythmias, Takotsubo-like syndrome, and acute myocardial infarction, all of which remain poorly explored. Both oncologists and cardiologists, as well as the patients, should be aware of the possible occurrence of one or more of these complications, which in some cases are fatal, in order to implement effective strategies of cardiac surveillance. In this review, we summarize the latest studies and recommendations on the pathogenesis, clinical manifestation, diagnosis, and management of ICI-related cardiotoxicity in order to realize a complete and updated overview on the main aspects of ICI-related cardiotoxicity, from surveillance to diagnosis to management, useful for both oncologists and cardiologists in their clinical practice. In particular, in the first part of the review, we realize a description of the pathogenetic mechanisms and risk factors of the main cardiovascular irAEs. Then, we focus on the management of ICI-related cardiotoxicity by analyzing five main points: (1) identifying and evaluating the type and severity of the cardiotoxicity; (2) deciding whether to withhold ICI therapy; (3) initiating steroid and immunosuppressive therapy; (4) starting conventional cardiac treatment; and (5) restarting ICI therapy. Finally, we discuss the existing evidence on surveillance for ICI-related cardiotoxicity and propose a surveillance strategy for both short- and long-term cardiotoxicity, according to the most recent guidelines. Full article
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16 pages, 877 KiB  
Review
Treatment Options in AF Patients with Cancer; Focus on Catheter Ablation
by Silvia Garibaldi, Michela Chianca, Iacopo Fabiani, Michele Emdin, Marcello Piacenti, Claudio Passino, Alberto Aimo, Antonella Fedele, Carlo Maria Cipolla and Daniela Maria Cardinale
J. Clin. Med. 2022, 11(15), 4452; https://doi.org/10.3390/jcm11154452 - 30 Jul 2022
Cited by 6 | Viewed by 3818
Abstract
Longer life expectancy along with advancements in cancer and atrial fibrillation (AF) therapies and treatment strategies have led to an increase in the number of individuals with both diseases. As a result, the complicated management of these patients has become crucial, necessitating individualised [...] Read more.
Longer life expectancy along with advancements in cancer and atrial fibrillation (AF) therapies and treatment strategies have led to an increase in the number of individuals with both diseases. As a result, the complicated management of these patients has become crucial, necessitating individualised treatment that considers the bi-directional relationship between these two diseases. On the one hand, giving appropriate pharmaceutical therapy is exceptionally difficult, considering the recognised thromboembolic risk posed by AF and malignancy, as well as the haemorrhagic risk posed by cancer. The alternative pulmonary vein isolation (PVI) ablation, on the other hand, has been inadequately explored in the cancer patient population; there is yet inadequate data to allow the clinician to unambiguously select patients that can undertake this therapeutic intervention. The goal of this review is to compile the most valuable data and supporting evidence about the characteristics, care, and therapy of cancer patients with AF. Specifically, we will evaluate the pharmaceutical options for a proper anticoagulant therapy, as well as the feasibility and safety of PVI in this population. Full article
(This article belongs to the Special Issue New Insights into Atrial Fibrillation)
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10 pages, 592 KiB  
Brief Report
Echocardiography Monitoring during Anthracycline Administration in Hodgkin and Non-Hodgkin’s Lymphoma: The Tei Index Evaluation
by Agata Puzzovivo, Agnese Maria Fioretti, Carla Minoia, Roberta Villoni, Santa Carbonara, Giusi Graziano, Fabio Pavone, Attilio Guarini and Stefano Oliva
J. Pers. Med. 2022, 12(2), 290; https://doi.org/10.3390/jpm12020290 - 16 Feb 2022
Cited by 2 | Viewed by 1956
Abstract
Anthracyclines are widely employed in lymphoma’s chemotherapy and has been shown to induce heart failure. Echocardiographic parameters of left ventricular (LV) systolic function are usually used to monitor the cardiac side effects during and after anthracyclines treatment. The measurement of theTei index could [...] Read more.
Anthracyclines are widely employed in lymphoma’s chemotherapy and has been shown to induce heart failure. Echocardiographic parameters of left ventricular (LV) systolic function are usually used to monitor the cardiac side effects during and after anthracyclines treatment. The measurement of theTei index could anticipate the onset of LV dysfunction. The aim of this study was to evaluate the performance of the delta Tei index for the early detection of cardiac toxicity in a prospective population of anthracycline-treated lymphoma patients. Our preliminary data suggest that the Tei index may predict the risk for cardiotoxicity in this subset of patients earlier than LV ejection fraction alteration. Full article
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30 pages, 1133 KiB  
Systematic Review
Late Cardiological Sequelae and Long-Term Monitoring in Classical Hodgkin Lymphoma and Diffuse Large B-Cell Lymphoma Survivors: A Systematic Review by the Fondazione Italiana Linfomi
by Stefano Oliva, Agata Puzzovivo, Chiara Gerardi, Eleonora Allocati, Vitaliana De Sanctis, Carla Minoia, Tetiana Skrypets, Attilio Guarini and Guido Gini
Cancers 2022, 14(1), 61; https://doi.org/10.3390/cancers14010061 - 23 Dec 2021
Cited by 7 | Viewed by 3343
Abstract
Cardiotoxicity represents the most frequent cause with higher morbidity and mortality among long-term sequelae affecting classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients. The multidisciplinary team of Fondazione Italiana Linfomi (FIL) researchers, with the methodological guide of Istituto di Ricerche [...] Read more.
Cardiotoxicity represents the most frequent cause with higher morbidity and mortality among long-term sequelae affecting classical Hodgkin lymphoma (cHL) and diffuse large B-cell lymphoma (DLBCL) patients. The multidisciplinary team of Fondazione Italiana Linfomi (FIL) researchers, with the methodological guide of Istituto di Ricerche Farmacologiche “Mario Negri”, conducted a systematic review of the literature (PubMed, EMBASE, Cochrane database) according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in order to analyze the following aspects of cHL and DLBCL survivorship: (i) incidence of cardiovascular disease (CVD); (ii) risk of long-term CVD with the use of less cardiotoxic therapies (reduced-field radiotherapy and liposomal doxorubicin); and (iii) preferable cardiovascular monitoring for left ventricular (LV) dysfunction, coronary heart disease (CHD) and valvular disease (VHD). After the screening of 659 abstracts and related 113 full-text papers, 23 publications were eligible for data extraction and included in the final sample. There was an increased risk for CVD in cHL survivors of 3.6 for myocardial infarction and 4.9 for congestive heart failure (CHF) in comparison to the general population; the risk increased over the years of follow-up. In addition, DLBCL patients presented a 29% increased risk for CHF. New radiotherapy techniques suggested reduced risk of late CVD, but only dosimetric studies were available. The optimal monitoring of LV function by 2D-STE echocardiography should be structured according to individual CV risk, mainly considering as risk factors a cumulative doxorubicine dose >250 mg per square meter (m2) and mediastinal radiotherapy >30 Gy, age at treatment <25 years and age at evaluation >60 years, evaluating LV ejection fraction, global longitudinal strain, and global circumferential strain. The evaluation for asymptomatic CHD should be offered starting from the 10th year after mediastinal RT, considering ECG, stress echo, or coronary artery calcium (CAC) score. Given the suggested increased risks of cardiovascular outcomes in lymphoma survivors compared to the general population, tailored screening and prevention programs may be warranted to offset the future burden of disease. Full article
(This article belongs to the Special Issue Lymphoma Survivorship)
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25 pages, 3474 KiB  
Review
Role of Cardiac Biomarkers in Cancer Patients
by Gennaro Carmine Semeraro, Carlo Maria Cipolla and Daniela Maria Cardinale
Cancers 2021, 13(21), 5426; https://doi.org/10.3390/cancers13215426 - 29 Oct 2021
Cited by 26 | Viewed by 4474
Abstract
In patients with cancer—and especially some specific subtypes—the heart can be pathologically affected due to the direct action of the tumor or its secretion products or due to the toxicity of some oncological treatments. Cardiac biomarkers have been investigated as inexpensive and easily [...] Read more.
In patients with cancer—and especially some specific subtypes—the heart can be pathologically affected due to the direct action of the tumor or its secretion products or due to the toxicity of some oncological treatments. Cardiac biomarkers have been investigated as inexpensive and easily accessible tools for prediction, early diagnosis, monitoring, or prognosis of various forms of cancer-related cardiac diseases. However, their clinical usefulness was not always clearly demonstrated in every area of cardioncology. For the identification of anthracycline related cardiotoxicity in the very early stages troponins proved to be more efficient detectors than imaging methods. Nevertheless, the lack of a standardized dosage methodology and of cardiotoxicity specific thresholds, do not yet allow to outline the precise way to employ them in clinical routine and to incorporate them into appropriate diagnostic or managing algorithms. Cardiac biomarkers proved also effective in patients with primary cardiac amyloidosis, in which both troponins and natriuretic peptides were able to predict adverse outcome, and carcinoid heart disease, where a precise diagnostic cut-off for N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was identified to screen patients with valvular involvement. Likewise, NT-proBNP proved to be an excellent predictor of postoperative atrial fibrillation (POAF). On the contrary, evidence is still not sufficient to promote the routine use of cardiac biomarkers to early diagnose myocarditis due to immune check points inhibitors (ICIs), radiotherapy induced cardiotoxicity and cardiac complications related to androgenetic deprivation. In this review we present all the evidence gathered so far regarding the usefulness and limitations of these relatively inexpensive diagnostic tools in the field of cardio-oncology. Full article
(This article belongs to the Special Issue Bio-Pathological Markers in the Diagnosis and Therapy of Cancer)
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17 pages, 1842 KiB  
Review
Atrial Fibrillation after Lung Cancer Surgery: Prediction, Prevention and Anticoagulation Management
by Gennaro Carmine Semeraro, Carlo Ambrogio Meroni, Carlo Maria Cipolla and Daniela Maria Cardinale
Cancers 2021, 13(16), 4012; https://doi.org/10.3390/cancers13164012 - 9 Aug 2021
Cited by 10 | Viewed by 3987
Abstract
Atrial fibrillation (AF) is a common complication of the early postoperative period of various types of surgery, including that for lung cancer. Although induced by the homeostatic alterations related to surgery, there is evidence that it is not a mere stand-alone transitory event, [...] Read more.
Atrial fibrillation (AF) is a common complication of the early postoperative period of various types of surgery, including that for lung cancer. Although induced by the homeostatic alterations related to surgery, there is evidence that it is not a mere stand-alone transitory event, but it represents a relevant complication of surgery, bearing considerable prognostic consequences. Different methods have therefore been explored to predict the occurrence of postoperative atrial fibrillation (POAF) and prevent it. In particular, the age among clinical factors, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP), as a marker, have proven to be good predictors, and the use of beta-blockers or amiodarone in primary prevention seems to reduce its incidence significantly. There is growing evidence that POAF significantly increases the risk of stroke and global mortality in the long term; therefore, it should be managed in the same way as spontaneous atrial fibrillation. In this review, we will present the strongest evidence found so far and the most recent findings regarding the management of POAF, with a special focus on patients undergoing thoracic surgery for lung cancer. Full article
(This article belongs to the Special Issue Surgical Treatment of Lung Cancer)
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2 pages, 157 KiB  
Editorial
Redox and Nitrosative Signaling and Stress
by Claudia Penna
Antioxidants 2020, 9(12), 1237; https://doi.org/10.3390/antiox9121237 - 7 Dec 2020
Viewed by 1403
Abstract
In this Special Issue, redox/nitrosative signaling has been considered in several aspects of cardiosciences and oncology, namely cardioncology [...] Full article
(This article belongs to the Special Issue Redox and Nitrosative Signaling and Stress)
15 pages, 1296 KiB  
Review
Characteristics, Management, and Outcomes of Acute Coronary Syndrome Patients with Cancer
by Valentina Milazzo, Nicola Cosentino, Jeness Campodonico, Claudia Lucci, Daniela Cardinale, Carlo M. Cipolla and Giancarlo Marenzi
J. Clin. Med. 2020, 9(11), 3642; https://doi.org/10.3390/jcm9113642 - 12 Nov 2020
Cited by 19 | Viewed by 2731
Abstract
Patients with cancer are at increased risk of cardiovascular disease, with a reported prevalence of acute coronary syndrome (ACS) ranging from 3% to 17%. The increased risk of ACS in these patients seems to be due to the complex interaction of shared cardiovascular [...] Read more.
Patients with cancer are at increased risk of cardiovascular disease, with a reported prevalence of acute coronary syndrome (ACS) ranging from 3% to 17%. The increased risk of ACS in these patients seems to be due to the complex interaction of shared cardiovascular risk factors, cancer type and stage, and chemotherapeutic and radiotherapy regimens. The management of ACS in patients with cancer is a clinical challenge, particularly due to cancer’s unique pathophysiology, which makes it difficult to balance thrombotic and bleeding risks in this specific patient population. In addition, patients with cancer have largely been excluded from ACS trials. Hence, an evidence-based treatment for ACS in this group of patients is unknown and only a limited proportion of them is treated with antiplatelets or invasive revascularization, despite initial reports suggesting their beneficial prognostic effects in cancer patients. Finally, cancer patients experiencing ACS are also at higher risk of in-hospital and long-term mortality as compared to non-cancer patients. In this review, we will provide an overview on the available evidence of the relationship between ACS and cancer, in terms of clinical manifestations, possible underlying mechanisms, and therapeutic and prognostic implications. Full article
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25 pages, 2094 KiB  
Review
SARS-CoV-2 Infection and Cardioncology: From Cardiometabolic Risk Factors to Outcomes in Cancer Patients
by Vincenzo Quagliariello, Annamaria Bonelli, Antonietta Caronna, Gabriele Conforti, Martina Iovine, Andreina Carbone, Massimiliano Berretta, Gerardo Botti and Nicola Maurea
Cancers 2020, 12(11), 3316; https://doi.org/10.3390/cancers12113316 - 10 Nov 2020
Cited by 28 | Viewed by 3970
Abstract
The coronavirus disease-2019 (COVID-19) is a highly transmissible viral illness caused by SARS-CoV-2, which has been defined by the World Health Organization as a pandemic, considering its remarkable transmission speed worldwide. SARS-CoV-2 interacts with angiotensin-converting enzyme 2 and TMPRSS2, which is a serine [...] Read more.
The coronavirus disease-2019 (COVID-19) is a highly transmissible viral illness caused by SARS-CoV-2, which has been defined by the World Health Organization as a pandemic, considering its remarkable transmission speed worldwide. SARS-CoV-2 interacts with angiotensin-converting enzyme 2 and TMPRSS2, which is a serine protease both expressed in lungs, the gastro-intestinal tract, and cardiac myocytes. Patients with COVID-19 experienced adverse cardiac events (hypertension, venous thromboembolism, arrhythmia, myocardial injury, fulminant myocarditis), and patients with previous cardiovascular disease have a higher risk of death. Cancer patients are extremely vulnerable with a high risk of viral infection and more negative prognosis than healthy people, and the magnitude of effects depends on the type of cancer, recent chemotherapy, radiotherapy, or surgery and other concomitant comorbidities (diabetes, cardiovascular diseases, metabolic syndrome). Patients with active cancer or those treated with cardiotoxic therapies may have heart damages exacerbated by SARS-CoV-2 infection than non-cancer patients. We highlight the cardiovascular side effects of COVID-19 focusing on the main outcomes in cancer patients in updated perspective and retrospective studies. We focus on the main cardio-metabolic risk factors in non-cancer and cancer patients and provide recommendations aimed to reduce cardiovascular events, morbidity, and mortality. Full article
(This article belongs to the Collection The Impact of COVID-19 Infection in Cancer)
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22 pages, 4568 KiB  
Article
NLRP3 as Putative Marker of Ipilimumab-Induced Cardiotoxicity in the Presence of Hyperglycemia in Estrogen-Responsive and Triple-Negative Breast Cancer Cells
by Vincenzo Quagliariello, Michelino De Laurentiis, Stefania Cocco, Giuseppina Rea, Annamaria Bonelli, Antonietta Caronna, Maria Cristina Lombari, Gabriele Conforti, Massimiliano Berretta, Gerardo Botti and Nicola Maurea
Int. J. Mol. Sci. 2020, 21(20), 7802; https://doi.org/10.3390/ijms21207802 - 21 Oct 2020
Cited by 51 | Viewed by 4927
Abstract
Hyperglycemia, obesity and metabolic syndrome are negative prognostic factors in breast cancer patients. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. However, ICIs are associated with immune-related adverse events involving cardiotoxicity. We aimed to study if hyperglycemia [...] Read more.
Hyperglycemia, obesity and metabolic syndrome are negative prognostic factors in breast cancer patients. Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment, achieving unprecedented efficacy in multiple malignancies. However, ICIs are associated with immune-related adverse events involving cardiotoxicity. We aimed to study if hyperglycemia could affect ipilimumab-induced anticancer efficacy and enhance its cardiotoxicity. Human cardiomyocytes and estrogen-responsive and triple-negative breast cancer cells (MCF-7 and MDA-MB-231 cell lines) were exposed to ipilimumab under high glucose (25 mM); low glucose (5.5 mM); high glucose and co-administration of SGLT-2 inhibitor (empagliflozin); shifting from high glucose to low glucose. Study of cell viability and the expression of new putative biomarkers of cardiotoxicity and resistance to ICIs (NLRP3, MyD88, cytokines) were quantified through ELISA (Cayman Chemical) methods. Hyperglycemia during treatment with ipilimumab increased cardiotoxicity and reduced mortality of breast cancer cells in a manner that is sensitive to NLRP3. Notably, treatment with ipilimumab and empagliflozin under high glucose or shifting from high glucose to low glucose reduced significantly the magnitude of the effects, increasing responsiveness to ipilimumab and reducing cardiotoxicity. To our knowledge, this is the first evidence that hyperglycemia exacerbates ipilimumab-induced cardiotoxicity and decreases its anticancer efficacy in MCF-7 and MDA-MB-231 cells. This study sets the stage for further tests on other breast cancer cell lines and primary cardiomyocytes and for preclinical trials in mice aimed to decrease glucose through nutritional interventions or administration of gliflozines during treatment with ipilimumab. Full article
(This article belongs to the Special Issue New Prognostic and Predictive Markers in Cancer Progression)
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