Cardio-oncology: Gaps in Knowledge, Goals, Advances, and Educational Efforts.

Over the past 20 years, cancer treatments have become more effective, leading to significant improvements in survival rates. However, anticancer drugs can have several possible cardiovascular side effects; in particular, the development of left ventricular dysfunction with chemoradiation therapy can negatively affect patients' cardiac outcome, and can limit anticancer treatments. This is an ongoing issue that will continue to persist, due to the ongoing development of new antitumor agents with potential cardiotoxic effects, and the prolonged life expectancy of long-term cancer survivors. Thus, the need for cooperation between oncologists and cardiologists in the management of cancer patients has led to the development of a new medical discipline-cardio-oncology-where the issue of cardiotoxicity is a topic of intense interest and research. However, several issues remain-the proper definition and diagnosis of cardiotoxicity, as well as monitoring and treatment strategies. In this review, the current advances in cardio-oncology, limitations of current approaches, and future research fields will be discussed.

Using biomarkers to predict and to prevent cardiotoxicity of cancer therapy.

INTRODUCTION: Cardiotoxicity is a common complication that may compromise the clinical effectiveness of anticancer therapy. The current standard for monitoring cardiac function detects cardiotoxicity only when a functional impairment has already occurred, not allowing for any early preventive strategy. Areas covered: A novel approach, based on the use of biomarkers has recently emerged, resulting in a very effective tool for early, real-time identification, and monitoring of cardiotoxicity. In particular, cardiac troponin elevation during chemotherapy allows to identify patients more prone to develop myocardial dysfunction and cardiac events. In these patients, use of angiotensin-converting enzyme inhibitors, such as enalapril, has shown to be effective in improving clinical outcomes, giving the chance for cardioprotective strategies in a selected population. The authors reviewed the currently available data about the role of biomarkers in this setting. Expert commentary: Early identification of patients at high risk of cardiotoxicity by cardiac biomarkers - in particular troponin - provides a rationale for targeted preventive strategies against cancer therapy-induced left ventricular dysfunction and its associated clinical complications, with the advantage of limiting prophylactic therapy only to a restricted number of patients. Although the major international oncologic societies encourage this approach, some limitations to a routinely use of biomarkers still exist.

Curing Cancer, Saving the Heart: A Challenge That Cardioncology Should Not Miss.

Advances in oncologic therapies have led to considerable improvements in prognosis and survival. However, these improvements may ultimately be diminished by the increase of cardiovascular side effects. Typically, both conventional and new antitumoral therapies may induce asymptomatic or symptomatic left ventricular dysfunction. Its development still remains a major deterrent that may compromise clinical effectiveness of cancer treatment, independently of the oncologic prognosis, having a serious impact on the patient's survival and quality of life. Hence, prevention of cardiotoxicity remains a crucial topic both for cardiologists and oncologists. Many strategies to mitigate the risk of cardiotoxicity have been developed, including cardiac function monitoring, limitation of chemotherapy doses, use of anthracycline analogues and cardioprotectants, and early detection of cardiotoxicity by biomarkers, followed by prophylactic intervention in selected high risk patients. We reviewed the currently available approaches which have been demonstrated to be effective in preventing or limiting cancer drug-induced cardiotoxicity.

Growth properties of cardiac stem cells are a novel biomarker of patients' outcome after coronary bypass surgery.

BACKGROUND: The efficacy of bypass surgery in patients with ischemic cardiomyopathy is not easily predictable; preoperative clinical conditions may be similar, but the outcome may differ significantly. We hypothesized that the growth reserve of cardiac stem cells (CSCs) and circulating cytokines promoting CSC activation are critical determinants of ventricular remodeling in this patient population. METHODS AND RESULTS: To document the growth kinetics of CSCs, population-doubling time, telomere length, telomerase activity, and insulin-like growth factor-1 receptor expression were measured in CSCs isolated from 38 patients undergoing bypass surgery. Additionally, the blood levels of insulin-like growth factor-1, hepatocyte growth factor, and vascular endothelial growth factor were evaluated. The variables of CSC growth were expressed as a function of the changes in wall thickness, chamber diameter and volume, ventricular mass-to-chamber volume ratio, and ejection fraction, before and 12 months after surgery. A high correlation was found between indices of CSC function and cardiac anatomy. Negative ventricular remodeling was not observed if CSCs retained a significant growth reserve. The high concentration of insulin-like growth factor-1 systemically pointed to the insulin-like growth factor-1-insulin-like growth factor-1 receptor system as a major player in the adaptive response of the myocardium. hepatocyte growth factor, a mediator of CSC migration, was also high in these patients preoperatively, as was vascular endothelial growth factor, possibly reflecting the vascular growth needed before bypass surgery. Conversely, a decline in CSC growth was coupled with wall thinning, chamber dilation, and depressed ejection fraction. CONCLUSIONS: The telomere-telomerase axis, population-doubling time, and insulin-like growth factor-1 receptor expression in CSCs, together with a high circulating level of insulin-like growth factor-1, represent a novel biomarker able to predict the evolution of ischemic cardiomyopathy following revascularization.

Polymorphonuclear neutrophils and instability of the atherosclerotic plaque: a causative role?

OBJECTIVE: The aim of this review is to examine the role of polymorphonuclear neutrophils (PMNs) in the evolution of atherosclerosis. INTRODUCTION: While the role of PMNs in the evolution of atherosclerosic process has failed until recently to attract much attention, a body of research carried out over the last decade has disclosed the unexpectedly complex behavior of these cells, unraveling an unexpected key role for PMNs in the onset and progression of atheroma. METHODS: A PubMed database search was performed for studies providing evidences on the role of PMNs in the development and progression of atherosclerotic lesion. RESULTS AND CONCLUSIONS: Activated PMNs were shown to produce and release reactive oxygen species, inflammatory leukotrienes and proteolytic lysosomal enzymes, directly inducing vascular damage. Activated PMNs also secrete myeloperoxidase, involved in lipoprotein oxidation. PMNs have a finite lifespan and typically die through apoptosis, which thus represents a counter-regulatory mechanism limiting the toxic potential of these short-lived, terminally differentiated cells. Dysregulation of this process probably contributes to the pathogenesis and progression of several inflammatory diseases. Moreover, high circulating levels of PMN-platelet aggregates have been reported in patients with clinical atherosclerosis, and recent studies suggest that these aggregates may play a role in vascular response to injury. It has been suggested that this heterotypic interaction between platelets and leukocytes might represent a link between hemostasis/thrombosis and the inflammatory response.

[Myeloperoxidase as possible diagnostic and prognostic marker of acute coronary syndrome]. / Il ruolo della mieloperossidasi come marker diagnostico e prognostico nella cardiopatia ischemica.

Myeloperoxidase (MPO) is an enzyme stored in azurophilic granules of polymorphonuclear neutrophils and macrophages and released into extracellular fluid during inflammatory processes. Several studies have shown its involvement into oxidative stress and inflammation. Recently, MPO has been considered its role as a possible marker of plaque instability and a useful tool for the prognostic evaluation of patients with coronary artery disease. Aim of this review is to provide an overview of patophysiological, analytical and clinical characteristics of MPO and to summarize the evidence about its usefulness as diagnostic and prognostic marker in the setting of acute coronary syndrome.

Inflammatory markers, cholesterol and statins: pathophysiological role and clinical importance.

Statins are one of the most important medications in cardio-vascular diseases since they block cholesterol synthesis by inhibiting the 3-hydroxy-3-methylglutaryl coenzyme A reductase and thus reduce low density lipoprotein concentrations. In the last years, numerous pleiotropic properties of statins have been described, beyond their well-known lipid lowering function. In particular, they are able to modulate inflammation, which plays a pivotal role in the atherosclerotic process. Several trials have shown a direct correlation between statin therapy and lower C-reactive protein concentrations. Moreover, a large body of pathophysiological studies has demonstrated that statins lower cytokine concentrations and inhibit recruitment, migration and cell adhesion to endothelium by attenuating chemokine production. They also inhibit inflammatory pathways regulated by proteins as Ras and Rho, and increase nitric oxide production which exerts a protective effect on endothelium. In addition to reducing inflammation in coronary atherosclerosis, statins also have beneficial effects in chronic inflammatory and autoimmune diseases, such as psoriasis, and they could induce clinical improvement. Statins seem to exert benefits even in settings of infection. These results suggest that initiating and monitoring statin therapy on the basis of inflammatory markers, in particular C-reactive protein, may improve cardiovascular prevention and treatment.

Inflammatory biomarkers and coronary heart disease: from bench to bedside and back.

Inflammation plays a pivotal role in all stages of atherosclerosis from endothelial dysfunction and plaque formation to plaque destabilization and disruption. Inflammatory biomarkers, originally studied to better understand the pathophysiology of atherosclerosis, have generated increasing interest among clinicians, because of their utility in the challenging problems of diagnosis and risk assessment of patients with suspected or proved coronary heart disease. Moreover, in fascinating perspective, they could be used as therapeutic target, counteracting initiation, progression, and development of complications of atherosclerosis. In this review, we will provide an overview of the more promising inflammatory biomarkers, focusing on their utility and limitations in the clinical setting.

[Relation of C-reactive protein and coronary heart disease. Current knowledges]. / Ruolo della proteina C-reattiva nella patologia coronarica. Attuali conoscenze.

Originally meant as a marker of inflammation in coronary heart disease (CHD), C reactive protein (CRP) is becoming an important tool in the clinical management of CHD patients. Several studies, and in particular the recent JUPITER trial, confirm its feasibility in intermediate risk patients; furthermore, according to last evidence, CRP could be a target for new therapeutic strategies.

Different apparent prognostic value of hsCRP in type 2 diabetic and nondiabetic patients with acute coronary syndromes.

BACKGROUND: C-reactive protein (CRP) is an established prognostic marker in acute coronary syndromes (ACS); however, no study has specifically addressed its prognostic role in type 2 diabetes with ACS. We evaluated the prognostic role of CRP separately in diabetic and nondiabetic patients with ACS. METHODS: We enrolled 251 patients with unstable angina and measured serum concentrations of high sensitivity (hs)CRP. Ninety-seven patients underwent coronary angiography with evaluation of atherosclerotic disease severity and extent by Bogaty score. Assessed endpoint was the combined occurrence of myocardial infarction (MI) and death at 1 year. RESULTS: No significant differences were found in hs-CRP between patients with and without diabetes. By Cox regression, hsCRP was not associated with 1-year follow-up events in diabetic patients but was strongly associated with events in nondiabetic patients (P = 0.0012). Coronary angiography exhibited a higher extent index in patients with diabetes than in those without (P = 0.04). hsCRP concentrations were not associated with angiographic atherosclerotic burden. By Cox analysis, hsCRP and extent score were associated with events in patients who underwent coronary angiography (P < 0.001 and P = 0.034, respectively). In nondiabetic patients, hsCRP was the only predictor of events at 1-year follow-up (P < 0.001), whereas in diabetic patients, hsCRP was not associated with events and a weak association was observed for extent score (P = 0.06). CONCLUSIONS: Our study suggests that different pathophysiological mechanisms may be responsible for MI and death in unstable angina patients with or without diabetes and that severity of coronary artery disease plays a major role in diabetes (and inflammation in the absence of diabetes).

Biomarkers in Acute Coronary Syndrome.

BACKGROUND: Evaluation of patients who present to the hospital with acute undifferentiated chest pain or other symptoms and signs suggestive of Acute Coronary Syndrome (ACS) is often a clinical challenge. The initial assessment, requiring a focused history (including risk factors analysis), a physical examination, an electrocardiogram (EKG) and serum cardiac marker determination, is time-consuming and troublesome. Recent investigations have indicated that increases in biomarkers of necrosis, inflammation, ischemia and myocardial stretch may provide earlier assessment of overall patient risk, help in identifying the adequate diagnostic and therapeutic management for each patient and allow for prevention of substantial numbers of new events. APPROACH AND CONTENT: The purpose of this review is to provide an overview of the characteristics of several biomarkers that may have potential clinical utility to identify ACS patients. Patho-physiology, analytical and clinical characteristics have been evaluated for each marker, underlying the properties for potential routine clinical use. SUMMARY: The biomarkers discussed in this review are promising and might lead to improved diagnosis and risk stratification of patients with ACS, however their clinical application requires further studies. It is important to define their clinical role as diagnostic markers, their predictive value and the specificity, standardization and detection limits of the assays.