Effetti cardiotossivi precoci e tardivi del trattamento con Epirubicina. Valutazione con marker biochimici ed ecocardiografia Tissue Doppler.

Our study was carried out in a group of epirubicin(Epi)-treated patients with cancer at different sites with the aim of detecting early preclinical changes, that are predictive of the risk of heart failure. All subjects underwent conventional echocardiography, as well as tissue Doppler imaging (TDI) with Strain (ε) and Strain Rate (SR). Moreover, echocardiographic changes identified during the Epi treatment were compared with inflammatory and oxidative stress laboratory markers. Thirty-one patients (age 59±14 yrs) with histologically confirmed tumors at different sites, scheduled to be treated with an Epi-based chemotherapy regimen were enrolled. We prospectively evaluated the acute (one week after) and late effects (3, 6, 12 and 18 months of follow-up) of Epi administration. A significant impairment of the systolic LV function was observed at epirubicin dose 200 mg/m2: this was shown by a reduction of the SR peak in comparison to baseline. This reduction persisted statistically significant throughout the treatment and follow-up, up to 18 months when the Sm reduction became significant. Levels of IL-6, sIL-6R and ROS increased significantly at 200 mg/m2 and IL-6 persisted high at 300 and 400 mg/m2 Epi dose returning within baseline values during follow-up. A significant inverse correlation between ΔSR and both the increase of IL-6 and ROS was observed. The multiple regression analysis showed that both IL-6 and ROS variables were independent and strongly predictive of ΔS

Contractile reserve in systemic sclerosis patients as a major predictor of global cardiac impairment and exercise tolerance

Several studies have evidenced high prevalence of myocardial systolic and diastolic dysfunction among patients with systemic sclerosis (SSc). Exercise echocardiography has shown a diagnostic and prognostic role in identifying early left ventricular (LV) dysfunction in several myocardial pathological settings. The aim of our study was to evaluate early signs of LV impairment under exercise and their correlation to patient's exercise tolerance. Forty-five patients (age 60.4 ± 10.3 years) with SSc and 20 age and sex comparable controls were enrolled in the study. All patients underwent clinical evaluation, 2D echocardiography associated with Tissue Doppler and speckle tracking to evaluate LV deformation indexes, and an exercise echocardiography to evaluate left ventricle contractile reserve (LVCR) and exercise pulmonary pressures. Finally, a 6-minute walking test (6MWT) to evaluate exercise tolerance was also performed. Compared to controls, SSc patients showed an impaired diastolic function (E/E' 10.9 ± 3.7 vs 8.36 ± 2.01; p < 0.01) associated with larger left atrial dimensions (LAVI 28.4 ± 8.7 vs 19.3 ± 4.6 mL/m2; p < 0.01). During exercise echocardiography, a reduced global longitudinal strain at peak exercise (S-GLS) was highlighted compared to controls (15.7 ± 3.6 vs 18.2 ± 2.2; p = 0.001). A S-GLS cutoff <18 %, identified by ROC analysis, identified SSc patients with a reduced diastolic function, exercise tolerance at the 6MWT and higher pulmonary pressures. Our data show that in SSc patients a reduced LVCR characterizes the patients with a more extensive cardiovascular impairment in terms of LV diastolic function, pulmonary pressures and exercise tolerance. These data underline the importance of exercise echocardiography for the preclinical screening of the LV impairment in this population

Metabolomic Profiles on Antiblastic Cardiotoxicity: New Perspectives for Early Diagnosis and Cardioprotection

Antiblastic drugs-induced cardiomyopathy remains a relevant cause of morbidity and mortality, during and after chemotherapy, despite the progression in protective therapy against cardiovascular diseases and myocardial function. In the last few decades, many groups of researchers have focused their attention on studying the metabolic profile, first in animals, and, subsequently, in humans, looking for profiles which could be able to predict drug-induced cardiotoxicity and cardiovascular damage. In clinical practice, patients identified as being at risk of developing cardiotoxicity undergo a close follow-up and more tailored therapies. Injury to the heart can be a consequence of both new targeted therapies, such as tyrosine kinase inhibitors, and conventional chemotherapeutic agents, such as anthracyclines. This review aims to describe all of the studies carried on this topic of growing interest

Early impairment of contractility reserve in patients with insulin resistance in comparison with healthy subjects

Background: Insulin resistance (IR) is currently considered a crucial cardiovascular (CV) risk factor, which seems to play a dominant role in the evolution toward cardiac and vascular impairment. Early IR-induced cardiac dysfunction can be assessed by Doppler-derived myocardial systolic strain rate (SR) index, measured at baseline and after dobutamine stress echocardiography (DSE).Methods: Thirty IR patients (HOMA-IR = 7 ± 5.2, age 52.6 ± 2.1 years), and 20 healthy, age and sex matched controls were studied. IR had been diagnosed in all patients in the 3 months preceding the study. Dobutamine echocardiography was performed in all subjects to exclude ischemic heart disease, and left ventricular contractile reserve (LVCR) was then assessed. LVCR was evaluated as an increase in the peak of an average longitudinal SR, measured in the basal and mid segments of 2 and 4 chamber ventricular walls.Results: No significant differences between the 2 groups were revealed by baseline echocardiography. In contrast, after DSE a significant decrease of Delta SR was found in the IR group in comparison to the controls (0.54 ± 0.31 s-1vs 1.14 ± 0.45 s-1; p < 0.0001).Conclusions: Our results show that IR, even if isolated and arising within a short time period, not only represents the initial phase of future diabetes, but may adversely affect heart function, as evidenced by the depressed LVCR. Our data strengthen the need for attention to be paid to IR state and for an early therapeutic approach

Epicardial fat volume assessed with cardiac magnetic resonance imaging in patients with Takotsubo cardiomyopathy

Purpose: The aims of our study were to investigate with cardiovascular magnetic resonance (CMR) the role of Epicardial Fat Volume (EFV) and distribution in patients with Takotsubo cardiomyopathy (TTC). Moreover, we explored EFV in patients with TTC and related this to comorbidities, cardiac biomarkers, and cardiac function. Methods: This retrospective study performed CMR scans in 30 consecutive TTC patients and 20 healthy controls. The absolute amount of EFV was quantified in consecutive short-axis cine stacks through the modified Simpson's rule. In addition, the left atrio-ventricular groove (LV) and right ventricle (RV) Epicardial Fat Thickness (EFT) were measured as well. Besides epicardial fat, LV myocardial strain parameters and T2 mapping measurements were obtained. Results: TTC patients and controls were of comparable age, sex, and body mass index. Compared to healthy controls, patients with TTC demonstrated a significantly increased EFV, epicardial fat mass, and EFV indexed for body 7surface area (p&nbsp;=&nbsp;0.005; p&nbsp;=&nbsp;0.003; p&nbsp;=&nbsp;0.008; respectively). In a multiple regression model including age, sex, BMI, atrial fibrillation, and dyslipidemia, TTC remained an independent association with EFV (p&nbsp;=&nbsp;0.008). Global T2 mapping and Global longitudinal strain in patients with TTC were correlated with EFV (r&nbsp;=&nbsp;0.63, p&nbsp;=&nbsp;0.001, and r&nbsp;=&nbsp;0.44, p&nbsp;=&nbsp;0.02, respectively). Conclusion: Patients with TTC have increased EFV compared to healthy controls, despite a similar body mass index. The amount of epicardial fat was associated with CMR markers of myocardial inflammation and subclinical contractile dysfunction

Metabolomic approach to profile functional and metabolic changes in heart failure

Heart failure (HF) is characterized by a series of adaptive changes in energy metabolism. The use of metabolomics enables the parallel assessment of a wide range of metabolites. In this study, we appraised whether metabolic changes correlate with HF severity, assessed as an impairment of functional contractility, and attempted to interpret the role of metabolic changes in determining systolic dysfunction

Effects of metformin and exercise training, alone or in association, on cardio-pulmonary performance and quality of life in insulin resistance patients

BACKGROUND: Metformin (MET) therapy exerts positive effects improving glucose tolerance and preventing the evolution toward diabetes in insulin resistant patients. It has been shown that adding MET to exercise training does not improve insulin sensitivity. The aim of this study was to determine the effect of MET and exercise training alone or in combination on maximal aerobic capacity and, as a secondary end-point on quality of life indexes in individuals with insulin resistance. METHODS: 75 insulin resistant patients were enrolled and subsequently assigned to MET (M), MET with exercise training (MEx), and exercise training alone (Ex). 12-weeks of supervised exercise-training program was carried out in both Ex and MEx groups. Cardiopulmonary exercise test and SF-36 to evaluate Health-Related Quality of Life (HRQoL) was performed at basal and after 12-weeks of treatment. RESULTS: Cardiopulmonary exercise test showed a significant increase of peak VO2 in Ex and MEx whereas M showed no improvement of peak VO2 (∆ VO2 [CI 95%] Ex +0.26 [0.47 to 0.05] l/min; ∆ VO2 MEx +0.19 [0.33 to 0.05] l/min; ∆ VO2 M -0.09 [-0.03 to -0.15] l/min; M vs E p < 0.01; M vs MEx p < 0.01; MEx vs Ex p = ns). SF-36 highlighted a significant increase in general QoL index in the MEx (58.3 ± 19 vs 77.3 ± 16; p < 0.01) and Ex (62.1 ± 17 vs 73.7 ± 12; p < 0.005) groups. CONCLUSIONS: We evidenced that cardiopulmonary negative effects showed by MET therapy may be counterbalanced with the combination of exercise training. Given that exercise training associated with MET produced similar effects to exercise training alone in terms of maximal aerobic capacity and HRQoL, programmed exercise training remains the first choice therapy in insulin resistant patients

The Echocardiographic Parameters of Systolic Function Are Associated with Specific Metabolomic Fingerprints in Obstructive and Non-Obstructive Hypertrophic Cardiomyopathy

The purpose of this study was to assess whether metabolomics, associated with echocardiography, was able to highlight pathophysiological differences between obstructive (OHCM) or non-obstructive (NOHCM) hypertrophic cardiomyopathy. Thirty-one HCM patients underwent standard and advanced echocardiography; a plasma sample was collected for metabolomic analysis. Results. Patients with OHCM compared with subjects with NOHCM had higher values of 2DLVEF (66.5 ± 3.3% vs. 60.6 ± 1.8%, p &lt; 0.01), S wave (7.6 ± 1.1 vs. 6.3 ± 0.7 cm/s, p &lt; 0.01) and 3D global longitudinal strain (17.2 ± 4.2%, vs. 13.4 ± 1.3%, p &lt; 0.05). A 2-group PLS-Discriminant Analysis was performed to verify whether the two HCM groups differed also based on the metabolic fingerprint. A clear clustering was shown (ANOVA p = 0.014). The most discriminating metabolites resulted as follows: in the NOHCM Group, there were higher levels of threitol, aminomalonic acid, and sucrose, while the OHCM Group presented higher levels of amino acids, in particular those branched chains, of intermediates of glycolysis (lactate) and the Krebs cycle (fumarate, succinate, citrate), of fatty acids (arachidonic acid, palmitoleic acid), of ketone bodies (2-OH-butyrate). Our data point out a different systolic function related to a specific metabolic activity in the two HCM phenotypic forms, with specific metabolites associated with better contractility in OHCM