Daniela Di Lisi

Chemotherapy-induced cardiotoxicity: role of the tissue Doppler in the early diagnosis of left ventricular dysfunction.

Cardiotoxicity is a common complication of chemotherapy. The aim of this study was to assess the cardiotoxicity of anticancer drugs using tissue Doppler imaging. A prospective study was carried out using patients with early breast cancer (72 women, median age: 57±12 year) and other inclusion and exclusion criteria. Inclusion criteria were treatment with epirubicin, trastuzumab, fluorouracil, cyclophosphamide, taxotere, and taxolo; left ventricular ejection fraction (LVEF) of more than 50%; and absence of important pathologies. Exclusion criteria were presence of known heart disease, earlier exposure to mediastinal irradiation, and earlier chemotherapy. On the basis of treatment, patients were divided into five groups: A=fluorouracil–epirubicin–cyclophosphamide (FEC), B=FEC+trastuzumab, C=trastuzumab, D=FEC+taxotere, and E=FEC+taxol+trastuzumab. Cardiological evaluation including electrocardiogram and echocardiogram was carried out at baseline, 3 months, and 6 months after the start of chemotherapy in all patients. The Doppler patterns were integrated with other echo parameters (tissue Doppler). Significant changes (P <0.05) in the echo parameters of the tissue Doppler were observed in treated patients during follow-up but not in LVEF. In conclusion, the tissue Doppler is more sensitive than standard Doppler in the study of diastolic function and LVEF in the study of systolic function. The tissue Doppler should integrate conventional echocardiography in the study of left ventricular function in patients treated with anticancer drugs. It is very important to reduce the risk of cardiovascular complications, especially heart failure, in breast cancer survivors.

Anticancer therapy-induced vascular toxicity: VEGF inhibition and beyond

Cardiotoxicity induced by chemotherapeutic agents and radiotherapy is a growing problem. In recent years, an increasing number of new drugs with targeted action have been designed. These molecules, such as monoclonal antibodies and tyrosine kinase inhibitors, can cause different type of toxicities compared to traditional chemotherapy. However, they can also cause cardiac complications such as heart failure, arterial hypertension, QT interval prolongation and arrhythmias. Currently, a field of intense research is the vascular toxicity induced by new biologic drugs, particularly those which inhibit vascular endothelial growth factor (VEGF) and its receptor (VEGF-R) and other tyrosine kinases. In this review, we aim at focusing on the problem of vascular toxicity induced by new targeted therapies, chemotherapy and radiotherapy, and describe the main mechanisms and emphasizing the importance of early diagnosis of vascular damage, in order to prevent clinical complications.

From molecular mechanisms to clinical management of antineoplastic drug-induced cardiovascular toxicity: A translational overview

Significance: Antineoplastic therapies have significantly improved the prognosis of oncology patients. However, these treatments can bring to a higher incidence of side-effects, including the worrying cardiovascular toxicity (CTX). Recent Advances: Substantial evidence indicates multiple mechanisms of CTX, with redox mechanisms playing a key role. Recent data singled out mitochondria as key targets for antineoplastic drug-induced CTX; understanding the underlying mechanisms is, therefore, crucial for effective cardioprotection, without compromising the efficacy of anti-cancer treatments. Critical Issues: CTX can occur within a few days or many years after treatment. Type I CTX is associated with irreversible cardiac cell injury, and it is typically caused by anthracyclines and traditional chemotherapeutics. Type II CTX is generally caused by novel biologics and more targeted drugs, and it is associated with reversible myocardial dysfunction. Therefore, patients undergoing anti-cancer treatments should be closely monitored, and patients at risk of CTX should be identified before beginning treatment to reduce CTX-related morbidity. Future Directions: Genetic profiling of clinical risk factors and an integrated approach using molecular, imaging, and clinical data may allow the recognition of patients who are at a high risk of developing chemotherapy-related CTX, and it may suggest methodologies to limit damage in a wider range of patients. The involvement of redox mechanisms in cancer biology and anticancer treatments is a very active field of research. Further investigations will be necessary to uncover the hallmarks of cancer from a redox perspective and to develop more efficacious antineoplastic therapies that also spare the cardiovascular system.

Timely recognition of cardiovascular toxicity by anticancer agents: a common objective of the pharmacologist, oncologist and cardiologist.

Both conventional and new anticancer drugs can frequently cause adverse cardiovascular effects, which can span from subclinical abnormalities to serious life-threatening and sometimes fatal events. This review examines the principal basic and clinical elements that may be of profit to identify, prevent and treat such toxicities. Clearly, the accomplishment of such objectives requires the strong commitment and cooperation of different professional figures including, but not limited to, pharmacologists, oncologists and cardiologists. The aspect of anticancer drug cardiotoxicity seems to be somehow underestimated, mainly due to inadequate reporting of adverse reactions from oncology drugs in the post-marketing setting. Thus, the implementation of pharmacovigilance is indispensable to rapidly and fully assess the safety of newer agents in real-life patients.

Large left ventricular metastasis in patient with liposarcoma.

: Metastases to the heart and pericardium are rare. We present a 44-year-old male with pleural dedifferentiated liposarcoma and multiple metastases, with no previous cardiological history and/or cardiac symptoms. A transthoracic echocardiogram during the advanced stage of disease showed a lobulated, large and mobile mass, with homogeneous echogenicity, attached to the basal posterior wall of the left ventricle via a broad base and with intracavitary growth. This mass extends to inferolateral and inferoseptal wall of the left ventricle.

Cardiovascular risk profile of patients with psoriasis

The aim of this study was to assess the cardiovascular risk profile of patients with psoriasis compared to patients without psoriasis. A case-control assay was performed using 143 cases (psoriasis patients) and 104 controls (patients without psoriasis). We assessed the presence of hypertension, lipid profile (HDL, triglycerides), diabetes, and body mass index in both cases and controls. Psoriasis patients showed an unfavorable cardiovascular risk profile and a higher risk of cardiovascular events and metabolic syndrome than patients without psoriasis.

Cardiovascular Damage Induced by Anti-VEGF Therapy

Vascular endothelial growth factor (VEGF) plays an important role in maintaining the regular homeostasis of vascular walls. VEGF binds its receptor (VEGFR) promoting the regular survival and function of endothelial cells. Anti-VEGF and anti-VEGFR drugs inhibit the action of VEGF and VEGFR. These drugs can cause cardiovascular toxic effects such as arterial hypertension, thromboembolism, myocardial ischemia and heart failure. The monoclonal antibody bevacizumab and tyrosine kinase inhibitors (sorafenib, sunitinib, pazopanib, regorafenib, axitinib, cabozantinib, ponatinib) are the main inhibitors of VEGF, VEGFR and other tyrosine kinases. In this chapter we will illustrate the cardiovascular toxic effects of these drugs, their mechanism of action, strategy to early diagnose and treat these complications. We will also illustrate strategy to prevent cardiovascular toxicity. It is important to know cardiovascular toxic effect of these drugs widely used in oncological field, to avoid the development of severe future complications.

Cardiovascular Damage Induced by Anti-BCR-ABL TKIs

Anti-BCR-ABL TKIs (tyrosine kinase inhibitors) are drugs that inhibit BCR ABL tyrosine. They are used especially in the treatment of hematological cancer and gastrointestinal stromal tumors (GIST). Anti-BCR-ABL TKIs include first (imatinib), second (nilotinib, dasatinib, bosutinib) and third-generation drugs (ponatinib). Especially second- and third-generation drugs can cause cardiovascular complications such as arterial thrombosis, myocardial ischemia, peripheral arterial diseases, QTc prolongation, and pulmonary hypertension. Nilotinib and ponatinib can cause thrombotic arterial events with various mechanisms. Particularly dasatinib can cause pulmonary hypertension. Compared to conventional chemotherapy, myocardial dysfunction was found in a smaller number of cases. In this chapter, we will illustrate cardiovascular adverse effects induced by anti-BCR-ABL TKIs, the main mechanisms that could explain such effects, and the influence played by cardiovascular risk factors. It is essential for both cardiologists and oncologists to know these issues in order to develop appropriate monitoring and apply preventive strategies to avoid the occurrence of toxicity and the need of any premature interruption of the antineoplastic treatment.

Thrombus-like small apical fibroma in patient with left ventricular dysfunction and thrombophilia: An unusual presentation

Fibroma is a primary benign cardiac tumor and it could be congenital since it usually manifests at birth or in early childhood. In the pediatric population, it constitutes the second (17%) primary cardiac tumor after rabdomyoma (67%). However, it may be occasionally detected in adolescents and adults. Fibroma usually arises in the ventricles, intramurally, and not infrequently is associated with calcific central core degeneration. Histologically, fibroma is a connective tissue tumor derived from fibroblasts, which consists of bundles of spindle-shaped and regular cells mingling with collagen and elastic fibers, insinuating themselves between myocytes in periphery. In most cases it is clinically silent, but occasionally it can be revealed by cardiac insufficiency (21%), chest pain (3.5%), arrhythmia (13%), and even sudden death. It is in fact the most common neoplastic cause of life-threatening arrhythmias. Cardiac magnetic resonance (CMR) plays an important role in the diagnosis. In our case, we describe an unusual imaging presentation of thrombuslike small apical fibroma in a patient with left ventricular dysfunction, thrombophilia, and previous pulmonary embolism. A 42-year-old man with arterial hypertension, smoking status, and family history of cardiovascular diseases was hospitalized for acute chest pain. Electrocardiogram on admission showed sinus rhythm with deep negative T wave in the precordial leads from V4 to V6. Echocardiogram showed moderate left ventricular dilatation with global hypokinesia and moderate left ventricular systolic dysfunction [left ventricular ejection fraction (LVEF) 39%]. An enhanced left ventricular apical trabeculation was also described. In the suspicion of an acute coronary syndrome, the patient underwent coronary angiography, which documented only some

Assessment of No-Reflow Phenomenon by Myocardial Blush Grade and Pulsed Wave Tissue Doppler Imaging in Patients with Acute Coronary Syndrome.

Background: No-reflow phenomenon is a complication of myocardial revascularization and it is associated with a worse prognosis. Materials and Methods: A prospective study was carried out enrolling patients with acute myocardial infarction (64 patients, 49 male and 15 female, median age 64.9 ± 10.61 years), both STEMI and NSTEMI, who underwent myocardial revascularization with percutaneous coronary intervention (PCI). TIMI flow and Myocardial Blush Grade (MBG) were assessed at baseline (T0), in addition to tissue Doppler imaging (TDI) and electrocardiogram. Cardiological evaluation was also performed at T1 (one month after PCI) and T2 (every year after revascularization for a mean follow-up of 24.9 months ± 6.93 months). Patients were divided into two groups on the basis of MBG. Results: In the present study, we found at T1 a significant association between MBG and dyslipidemia (P = 0,038) and NYHA class and MBG (P = 0,040), among clinical variables and cardiovascular risk factors. Moreover, a statistically significant relationship was observed between MBG and a new echocardiographic index of systolic and diastolic dysfunction, the EAS index measured with tissue Doppler imaging (P = 0,013). At T2, the EAS parameter was also significantly impaired in patients with reduced MBG, compared to patients with normal MBG (P = 0,003). Conclusions: This study demonstrates that the combined evaluation of systolic and diastolic dysfunction by EAS index, according to the literature, could detect a subclinical ventricular dysfunction due to a perfusion defect. Therefore, EAS index could be a useful parameter to be measured in the follow-up of patients undergoing revascularization.