Cardio-oncology rehabilitation: are we ready?

Cardio-oncology rehabilitation (CORE) is not only an essential component of cancer rehabilitation but also a pillar of preventive cardio-oncology. Cardio-oncology rehabilitation is a comprehensive model based on a multitargeted approach and its efficacy has been widely documented; when compared with an 'exercise only' programme, comprehensive CORE demonstrates a better outcome. It involves nutritional counselling, psychological support, and cardiovascular (CV) risk assessment, and it is directed to a very demanding population with a heavy burden of CV diseases driven by physical inactivity, cancer therapy-induced metabolic derangements, and cancer therapy-related CV toxicities. Despite its usefulness, CORE is still underused in cancer patients and we are still at the dawning of remote models of rehabilitation (tele-rehabilitation). Not all CORE is created equally: a careful screening procedure to identify patients who will benefit the most from CORE and a multidisciplinary customized approach are mandatory to achieve a better outcome for cancer survivors throughout their cancer journey. The aim of this paper is to provide an updated review of CORE not only for cardiologists dealing with this peculiar population of patients but also for oncologists, primary care providers, patients, and caregivers. This multidisciplinary team should help cancer patients to maintain a healthy and active life before, during, and after cancer treatment, in order to improve quality of life and to fight health inequities.

Atherosclerosis and the Bidirectional Relationship between Cancer and Cardiovascular Disease: From Bench to Bedside-Part 1.

Atherosclerosis, a complex metabolic-immune disease characterized by chronic inflammation driven by the buildup of lipid-rich plaques within arterial walls, has emerged as a pivotal factor in the intricate interplay between cancer and cardiovascular disease. This bidirectional relationship, marked by shared risk factors and pathophysiological mechanisms, underscores the need for a comprehensive understanding of how these two formidable health challenges intersect and influence each other. Cancer and its treatments can contribute to the progression of atherosclerosis, while atherosclerosis, with its inflammatory microenvironment, can exert profound effects on cancer development and outcomes. Both cancer and cardiovascular disease involve intricate interactions between general and personal exposomes. In this review, we aim to summarize the state of the art of translational data and try to show how oncologic studies on cardiotoxicity can broaden our knowledge of crucial pathways in cardiovascular biology and exert a positive impact on precision cardiology and cardio-oncology.

ANMCO POSITION PAPER: cardio-oncology in the COVID era (CO and CO).

The COVID-19 pandemic and its impact on patients with cancer and cardiovascular disease have confirmed the particular vulnerability of these populations. Indeed, not only a higher risk of contracting the infection has been reported but also an increased occurrence of a more severe course and unfavourable outcome. Beyond the direct consequences of COVID-19 infection, the pandemic has an enormous impact on global health systems. Screening programmes and non-urgent tests have been postponed; clinical trials have suffered a setback. Similarly, in the area of cardiology care, a significant decline in STEMI accesses and an increase in cases of late presenting heart attacks with increased mortality and complication rates have been reported. Health care systems must therefore get ready to tackle the 'rebound effect' that will likely show a relative increase in the short- and medium-term incidence of diseases such as heart failure, myocardial infarction, arrhythmias, and cardio- and cerebrovascular complications. Scientific societies are taking action to provide general guidance and recommendations aimed at mitigating the unfavourable outcomes of this pandemic emergency. Cardio-oncology, as an emerging discipline, is more flexible in modulating care pathways and represents a beacon of innovation in the development of multi-specialty patient management. In the era of the COVID-19 pandemic, cardio-oncology has rapidly modified its clinical care pathways and implemented flexible monitoring protocols that include targeted use of cardiac imaging, increased use of biomarkers, and telemedicine systems. The goal of these strategic adjustments is to minimize the risk of infection for providers and patients while maintaining standards of care for the treatment of oncologic and cardiovascular diseases. The aim of this document is to evaluate the impact of the pandemic on the management of cardio-oncologic patients with the-state-of-the-art knowledge about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease (COVID-19) in order to optimize medical strategies during and after the pandemic.

Crizotinib-induced cardiotoxicity: the importance of a proactive monitoring and management.

Crizotinib is a multitarget tyrosine kinase inhibitor and it represents the standard of care in patients with anaplastic lymphoma kinase translocated non-small-cell lung cancer. Crizotinib is generally well tolerated and the most frequent adverse events include gastrointestinal effects, visual disorders, edema, fatigue and liver enzyme abnormalities. However, due to the increasing clinical experience with crizotinib, other toxicities are emerging, such as Q-wave T-wave interval prolongation and bradycardia. In the current review we will focus on the management of crizotinib-related cardiotoxicity.

The Conundrum of Cancer-Associated Thrombosis: Lesson Learned from Two Intriguing Cases and Literature Review.

The correlation between cancer and venous thromboembolism (VTE) is solid, whereas the knowledge about cancer-related arterial thromboembolism (ATE) still needs a deeper investigation to clarify its pathogenesis. We describe two cases that represent useful hints for a comprehensive review of the thrombotic issue. A 75-year-old man with advanced rectal cancer treated with fluoropyrimidines suffered two catheter-related VTE events managed according to current guidelines. There was no indication for "extended" anticoagulant therapy for him, but during antithrombotic wash-out and fluoropyrimidines plus panitumumab regimen, he suffered a massive right coronary artery (RCA) thrombosis. Another patient with no cardiovascular (CV) risk factors and affected by advanced bladder cancer was treated with a platinum-containing regimen and suffered an acute inferior myocardial infarction 2 days after chemotherapy administration. He was successfully treated with primary Percutaneous Transluminal Coronary Angioplasty of RCA, discontinuing platinum-based therapy. Our observations raise the issue of cancer-associated thrombosis (CAT) complexity and the potential correlation between arterial and venous thrombotic events. Moreover, physicians should be aware of the thrombotic risk associated with anticancer therapies, suggesting that an appropriate prophylaxis should be considered.

[ANMCO Position paper in collaboration with ITACARE-P: Cardio-oncology rehabilitation. Are we ready?] / Position paper ANMCO in collaborazione con ITACARE-P: Riabilitazione cardio-oncologica. "Are we ready?".

Cardio-oncology rehabilitation (CORE) is not only an essential component of cancer rehabilitation, but also a pillar of preventive cardio-oncology. CORE is a comprehensive model based on a multitargeted approach and its efficacy has been widely documented; when compared to an "exercise only" program, comprehensive CORE demonstrates a better outcome. It involves nutritional counseling, psychological support and cardiovascular risk assessment, and it is directed to a very demanding population with a heavy burden of cardiovascular diseases driven by physical inactivity, cancer therapy-induced metabolic derangements and cancer therapy-related cardiovascular toxicities. Despite its usefulness, CORE is still underused in cancer patients and we are still at the dawning of remote models of rehabilitation (telerehabilitation). Not all cardio-oncology rehabilitation is created equal: a careful screening procedure to identify patients who will benefit the most from CORE and a multidisciplinary customized approach are mandatory to achieve a better outcome for cancer survivors throughout their cancer journey.The aim of this position paper is to provide an updated review of CORE not only for cardiologists dealing with this peculiar patient population, but also for oncologists, primary care providers, patients and caregivers. This multidisciplinary team should help cancer patients to maintain a healthy and active life before, during and after cancer treatment, in order to improve quality of life and to fight health inequities.

Role of preeclampsia-related angiogenic factors in sunitinib cardiotoxicity: two cases and review of the literature.

Sunitinib is a multi-targeted tyrosine kinase inhibitor widely used in clear cell renal carcinoma and in imatinib-resistant gastrointestinal stromal tumors. Sunitinib-associated cardiotoxicity has been recognized and includes hypertension, left ventricular dysfunction and congestive heart failure; nevertheless, few data exist in the literature regarding the role of preeclampsia-related angiogenic factors in sunitinib cardiotoxicity. We report a case of sunitinib-induced severe left ventricular dysfunction that occurred in a hypertensive woman with metastatic renal carcinoma and a history of preeclampsia, and a case of sunitinib-induced preeclampsia-like syndrome in a normotensive patient with an imatinib-resistant gastrointestinal stromal tumor. Our experience confirms that inhibition of angiogenic factors to treat cancer is a novel challenge for the oncologist and requires the cardiologist's support.

Corrigendum: Immune checkpoint inhibitor therapy increases systemic SDF-1, cardiac DAMPs Fibronectin-EDA, S100/Calgranulin, galectine-3, and NLRP3-MyD88-chemokine pathways.

[This corrects the article DOI: 10.3389/fcvm.2022.930797.].

Corrigendum: Cardio-oncology in the COVID Era (Co & Co): The never-ending story.

[This corrects the article DOI: 10.3389/fcvm.2022.821193.].

Corrigendum: Cancer survivorship at heart: a multidisciplinary cardio-oncology roadmap for healthcare professionals.

[This corrects the article DOI: 10.3389/fcvm.2023.1223660.].

Cancer survivorship at heart: a multidisciplinary cardio-oncology roadmap for healthcare professionals.

In cancer, a patient is considered a survivor from the time of initial diagnosis until the end of life. With improvements in early diagnosis and treatment, the number of cancer survivors (CS) has grown considerably and includes: (1) Patients cured and free from cancer who may be at risk of late-onset cancer therapy-related cardiovascular toxicity (CTR-CVT); (2) Patients with long-term control of not-curable cancers in whom CTR-CVT may need to be addressed. This paper highlights the importance of the cancer care continuum, of a patient-centered approach and of a prevention-oriented policy. The ultimate goal is a personalized care of CS, achievable only through a multidisciplinary-guided survivorship care plan, one that replaces the fragmented management of current healthcare systems. Collaboration between oncologists and cardiologists is the pillar of a framework in which primary care providers and other specialists must be engaged and in which familial, social and environmental factors are also taken into account.

An ELIME assay for the rapid diagnosis of coeliac disease.

Coeliac disease (CD) is a gluten-induced autoimmune enteropathy found in genetically susceptible subjects. Because of the high number of undetected cases, rapid and cheaper screening methods are needed. Currently, the CD diagnosis involves the detection of anti-transglutaminase IgA antibodies (anti-tTG IgA) in blood serum through the use of ELISA systems with confirmation by histology of the intestinal mucosa. A new, rapid magneto-electrochemical immunosensor for CD diagnosis has been developed and applied to serum sample analysis. The system uses magnetic beads coated with tTG antigen to detect anti-tTG antibodies in positive serum samples and an alkaline phosphatase-conjugated anti-human IgA as label. An electrochemical readout, using magnetized screen-printed electrodes coupled with a portable instrument, is made after the addition of α-naphtyl phosphate, which is enzymatically converted into the electrochemically active α-naphthol product. The work involved the following considerations: (1) optimization of analytical parameters; (2) recovery evaluation, adding known concentrations of anti-tTG IgA to "blank" sera; (3) analysis of 107 blood serum samples; (4) calculation of the ROC curve, resulting in a cut-off of 1.0 U/ml, 100% of clinical sensitivity and 98.36% of clinical specificity; evaluation of the agreement between electrochemical and ELISA kit values (r (2) of 0.943). The system developed could be an useful tool for a correct and rapid CD diagnosis. This method is simple, cheap, rapid, and suitable for screening analyses performed outside of the classical diagnostic laboratory.

Anal metastasis from breast cancer: a case report and review of the literature.

Breast cancer usually metastasizes towards the lymph nodes, lung, bone, liver or brain; metastatic gastrointestinal involvement is rare and anal metastases are extremely rare. Necroscopic studies report a 6-18% incidence of extra-hepatic gastrointestinal metastases, and the most frequent sites of the GI tract involved are the stomach and the small intestine. We report a case with anal metastasis from breast cancer and a review of the associated literature.

Immune checkpoint inhibitor therapy increases systemic SDF-1, cardiac DAMPs Fibronectin-EDA, S100/Calgranulin, galectine-3, and NLRP3-MyD88-chemokine pathways.

Background: Immune checkpoint inhibitors (ICIs) have significantly changed the oncology clinic in recent years, improving survival expectations in cancer patients. ICI therapy have a broad spectrum of side effects from endocrinopathies to cardiovascular diseases. In this study, pro-inflammatory and pro-fibrotic effects of short-term ICIs therapy in preclinical models were analyzed. Methods: Firstly, in a human in vitro model, human cardiomyocytes co-cultured with hPBMC were exposed to ICIs (with CTLA-4 or PD-1 blocking agents, at 200 nM) for 72 h. After treatment, production of DAMPs and 12 cytokines were analyzed in the supernatant through colorimetric and enzymatic assays. C57/Bl6 mice were treated with CTLA-4 or PD-1 blocking agents (15 mg/kg) for 10 days. Before (T0), after three days (T3) and after treatments (T10), ejection fraction, fractional shortening, radial and longitudinal strain were calculated by using bidimensional echocardiography (Vevo 2100, Fujfilm). Fibrosis, necrosis, hypertrophy and vascular NF-kB expression were analyzed through Immunohistochemistry. Myocardial expression of DAMPs (S100- Calgranulin, Fibronectin and Galectine-3), MyD88, NLRP3 and twelve cytokines have been analyzed. Systemic levels of SDF-1, IL-1ß, and IL-6 were analyzed before, during and after ICIs therapy. Results: Radial and longitudinal strain were decreased after 10 days of ICIs therapy. Histological analysis of NF-kB expression shows that short-term anti-CTLA-4 or anti-PD-1 treatment increased vascular and myocardial inflammation. No myocardial hypertrophy was seen with the exception of the pembrolizumab group. Myocardial fibrosis and expression of galectin-3, pro-collagen 1-α and MMP-9 were increased after treatment with all ICIs. Both anti-CTLA-4 or anti-PD-1 treatments increased the expression of DAMPs, NLRP3 inflammasome and MyD88 and induced both in vitro and in vivo the secretion of IL-1ß, TNF-α and IL-6. Systemic levels of SDF-1, IL-1ß and IL-6 were increased during and after treatment with ICIs. Conclusions: Short therapy with PD-1 and CTLA-4 blocking agents increases vascular expression of NF-kB, systemic SDF-1, IL-1ß, IL-6 levels and myocardial NLRP3, MyD88 and DAMPs expression in preclinical models. A pro-inflammatory cytokine storm was induced in myocardial tissues and in cultured cardiac cells after ICIs therapy. The overall picture of the study suggests new putative biomarkers of ICIs-mediated systemic and myocardial damages potentially useful in clinical cardioncology.

Corrigendum: Cardio-Oncology in the COVID Era (Co & Co): The Never Ending Story.

[This corrects the article DOI: 10.3389/fcvm.2022.821193.].

Cardio-Oncology in the COVID Era (Co & Co): The Never Ending Story.

The pathophysiology of some non-communicable diseases (NCDs) such as hypertension, cardiovascular disease (CVD), diabetes, and cancer includes an alteration of the endothelial function. COVID-19 is a pulmonary and vascular disease with a negative impact on patients whose damaged endothelium is particularly vulnerable. The peculiar SARS-CoV-2-induced "endothelitis" triggers an intriguing immune-thrombosis that affects both the venous and arterial vascular beds. An increased liability for infection and an increased likelihood of a worse outcome have been observed during the pandemic in patients with active cancer and in cancer survivors. "Overlapping commonalities" between COVID-19 and Cardio-Oncology have been described that include shared phenotypes of cardiovascular toxicities such as left ventricular dysfunction, ischemic syndromes, conduction disturbances, myocarditis, pericarditis and right ventricular failure; shared pathophysiologic mechanisms such as inflammation, release of cytokines, the renin-angiotensin-aldosterone-pathway, coagulation abnormalities, microthrombosis and endothelial dysfunction. For these features and for the catalyst role of NCDs (mainly CVD and cancer), we should refer to COVID-19 as a "syndemic." Another challenging issue is the persistence of the symptoms, the so-called "long COVID" whose pathogenesis is still uncertain: it may be due to persistent multi-organ viral attacks or to an abnormal immune response. An intensive vaccination campaign is the most successful pharmacological weapon against SARS-CoV-2, but the increasing number of variants has reduced the efficacy of the vaccines in controlling SARS-CoV-2 infections. After a year of vaccinations we have also learned more about efficacy and side-effects of COVID-19 vaccines. An important byproduct of the COVID-19 pandemic has been the rapid expansion of telemedicine platforms across different care settings; this new modality of monitoring cancer patients may be useful even in a post pandemic era. In this paper we analyze the problems that the cardio-oncologists are facing in a pandemic scenario modified by the extensive vaccination campaign and add actionable recommendations derived from the ongoing studies and from the syndemic nature of the infection.

Women at heart: Introducing gender cardio-oncology.

As cardio-oncology imposed itself as the reference specialty for a comprehensive cardiovascular approach to all patients with cancer, a more specific and careful cardiac evaluation of women entering their journey into cancer care is needed. Gender medicine refers to the study of how sex-based biological and gender-based socioeconomic and cultural differences influence people's health. Gender-related aspects could account for differences in the development, progression, and clinical signs of diseases as well as in the treatment of adverse events. Gender also accounts for major differences in access to healthcare. As for medicine and healthcare in general, gender-related characteristics have gained significance in cardio-oncology and should no longer be neglected in both clinical practice and research. We aimed to review the most relevant cardiovascular issues in women related to the cardio-oncology approach to offer a specific gender-related point of view for clinicians involved in the care process for both cancer and cardiovascular disease.