Oxidative stress and inflammation: determinants of anthracycline cardiotoxicity and possible therapeutic targets

Chemotherapy with anthracycline-based regimens remains a cornerstone of treatment of many solid and blood tumors but is associated with a significant risk of cardiotoxicity, which can manifest as asymptomatic left ventricular dysfunction or overt heart failure. These effects are typically dose-dependent and cumulative and may require appropriate screening strategies and cardioprotective therapies in order to minimize changes to anticancer regimens or even their discontinuation. Our current understanding of cardiac damage by anthracyclines includes a central role of oxidative stress and inflammation. The identification of these processes through circulating biomarkers or imaging techniques might then be helpful for early diagnosis and risk stratification. Furthermore, therapeutic strategies relieving oxidative stress and inflammation hold promise to prevent heart failure development or at least to mitigate cardiac damage, although further evidence is needed on their efficacy, either alone or as part of combination therapies with neurohormonal antagonists, which are the current adopted standard

Cardiac magnetic resonance findings in patients with type 1 myotonic dystrophy

Abstract Funding Acknowledgements Type of funding sources: None. Background Heart disease is a major determinant of prognosis in type 1 myotonic dystrophy (DM1), second only to respiratory complications. Cardiac imaging, possibly including cardiac magnetic resonance (CMR), is recommended in patients with DM1. However, limited information is available on CMR findings and their prognostic significance in DM1. Methods We identified all patients with DM1 evaluated from 2009 to 2020 in a CMR laboratory with an established collaboration with a Neuromuscular Disorder Unit. Results Thirty-four patients were retrieved (21 males, aged 45 ± 12). At the time of CMR examination, 97% had neuromuscular symptoms (mean duration 16 ± 13 years), 12 (35%) presented with atrioventricular block (n = 11 1st degree, n = 1 2nd degree type 1), 15 (44%) with intraventricular conduction disturbances (n = 5 left bundle branch block, n = 5 right bundle branch block, n = 3 left anterior fascicular block, n = 2 other non-specific intraventricular conduction delay), 4 (12%) with atrial fibrillation or flutter. No patient had a device. At CMR, 5 (15%) patients had left ventricular (LV) systolic dysfunction (LV ejection fraction [LVEF] <50%) and 5 (15%) a depressed right ventricular (RV) function (RVEF <50%). Compared to age- and sex-specific reference values for our laboratory, 12 (35%) patients showed a decreased LV end-diastolic volume index (LVEDVi), 7 (21%) a decreased LV mass index (LVMi), and 29 (83%) a decreased LVMi/LVEDVi ratio. Nine (26%) patients had mid-wall late gadolinium enhancement (LGE, mean extent 4.5 ± 2.0% of LVM; n = 8 septal, n = 4 inferolateral, n = 2 inferior, n = 1 anterolateral), and 14 (40%) some areas of fatty infiltration (n = 9 involving the LV, n = 13 the RV). Native T1 in the interventricular septum (1,041 ± 53 ms) approached the upper reference limit (1,089 ms), and the extracellular volume was slightly increased (33 ± 2%, reference values <30%). Over a median follow-up of 3.3 years (interquartile interval 1.6-4.7), 2 (6%) patients died, one for infectious and respiratory complications and the other for unknown causes, 5 (15%) patients underwent pacemaker implantation for conduction disturbances, and 4 (12%) had a documentation of high-risk (Lown class ≥4) ventricular ectopic beats (VEBs). Among all CMR variables collected, higher values of LVMi/LVEDVi ratio emerged as univariate predictor of all-cause death (p = 0.044). At logistic regression analysis, anteroseptal wall thickness was associated with the need for pacemaker implantation (p = 0.028), while LGE mass was associated with high-risk VEBs (p = 0.026). Conclusions Patients with DM1 display several structural and functional cardiac abnormalities, with variable degrees of cardiac muscle hypotrophy, fibrosis and fatty infiltration. The possibility to predict the need for pacemaker implantation, ventricular arrhythmias and all-cause or cardiovascular mortality should be verified in larger cohorts

Influence of cardiac phase on myocardial native T1 values by a segmental approach

Abstract Funding Acknowledgements Type of funding sources: None. Background. Native T1 values are usually assessed in the end-diastole to minimize motion artifacts while the systolic data acquisition offers the advantage of a thicker myocardium, with reduced partial-volume effects. Higher myocardial T1 values have been detected in diastole at both 1.5T and 3T but the dependence of this difference on myocardial segments or gender has not been fully explored. Aim. We provided a systematic comparison of myocardial native T1 values in diastole and systole, by considering separately myocardial segments and dividing males and females. Methods. Sixty-one healthy subjects (46.0 ± 14.1 years, 32 males) underwent CMR at 1.5T (Signa Artist; GE Healthcare). Three short-axis slices of the left ventricle acquired in diastole and systole using a Modified Look–Locker Inversion Recovery sequence. Image analysis was performed with a commercially available software package. T1 value was assessed in all 16 myocardial segments and global value was the mean. Results. Table 1 shows the comparison between T1 values calculated from maps obtained in diastole and systole. Systolic T1 values were significantly lower in the basal anterolateral segment, in all medium segments except for the medium inferior segment, and in all apical segments. The percentage difference between diastolic and systolic T1 values was considered to compensate for the higher T1 values in females, and a significantly higher value was detected in females for the majority of medium segments, for all apical segments, and for the global value. Conclusion. The diastolic-systolic discrepancy was more pronounced for the females and at the apical level, supporting the hypothesis that, besides the physiologic variations in myocardial blood volume during the cardiac cycle, the partial volume-effect may be a strong additional contributing factor. Native T1 values should be obtained always in the same cardiac phase to avoid a potential bias in the discrimination between healthy and pathologically affected myocardium

Implementation of an epicardial implantable MEMS sensor for continuous and real-time postoperative assessment of left ventricular activity in adult minipigs over a short- and long-term period

The sensing of left ventricular (LV) activity is fundamental in the diagnosis and monitoring of cardiovascular health in high-risk patients after cardiac surgery to achieve better short- and long-term outcome. Conventional approaches rely on noninvasive measurements even if, in the latest years, invasive microelectromechanical systems (MEMS) sensors have emerged as a valuable approach for precise and continuous monitoring of cardiac activity. The main challenges in designing cardiac MEMS sensors are represented by miniaturization, biocompatibility, and long-term stability. Here, we present a MEMS piezoresistive cardiac sensor capable of continuous monitoring of LV activity over time following epicardial implantation with a pericardial patch graft in adult minipigs. In acute and chronic scenarios, the sensor was able to compute heart rate with a root mean square error lower than 2 BPM. Early after up to 1 month of implantation, the device was able to record the heart activity during the most important phases of the cardiac cycle (systole and diastole peaks). The sensor signal waveform, in addition, closely reflected the typical waveforms of pressure signal obtained via intraventricular catheters, offering a safer alternative to heart catheterization. Furthermore, histological analysis of the LV implantation site following sensor retrieval revealed no evidence of myocardial fibrosis. Our results suggest that the epicardial LV implantation of an MEMS sensor is a suitable and reliable approach for direct continuous monitoring of cardiac activity. This work envisions the use of this sensor as a cardiac sensing device in closed-loop applications for patients undergoing heart surgery

Biological response of an in vitro human 3D lung cell model exposed to brake wear debris varies based on brake pad formulation

Wear particles from automotive friction brake pads of various sizes, morphology, and chemical composition are significant contributors towards particulate matter. Knowledge concerning the potential adverse effects following inhalation exposure to brake wear debris is limited. Our aim was, therefore, to generate brake wear particles released from commercial low-metallic and non-asbestos organic automotive brake pads used in mid-size passenger cars by a full-scale brake dynamometer with an environmental chamber simulating urban driving and to deduce their potential hazard in vitro. The collected fractions were analysed using scanning electron microscopy via energy-dispersive X-ray spectroscopy (SEM-EDS) and Raman microspectroscopy. The biological impact of the samples was investigated using a human 3D multicellular model consisting of human epithelial cells (A549) and human primary immune cells (macrophages and dendritic cells) mimicking the human epithelial tissue barrier. The viability, morphology, oxidative stress, and (pro-)inflammatory response of the cells were assessed following 24 h exposure to similar to 12, similar to 24, and similar to 48 A mu g/cm(2) of non-airborne samples and to similar to 3.7 A mu g/cm(2) of different brake wear size fractions (2-4, 1-2, and 0.25-1 A mu m) applying a pseudo-air-liquid interface approach. Brake wear debris with low-metallic formula does not induce any adverse biological effects to the in vitro lung multicellular model. Brake wear particles from non-asbestos organic formulated pads, however, induced increased (pro-)inflammatory mediator release from the same in vitro system. The latter finding can be attributed to the different particle compositions, specifically the presence of anatase.Web of Science9272351233

Correlation between global longitudinal peak systolic strain and coronary artery disease severity as assessed by the angiographically derived SYNTAX score

In this study, we investigate the correlation between reduced global longitudinal peak systolic strain (GLPSS) and the SYNTAX score (SS) in patients undergoing coronary angiography.We examined 71 patients undergoing both echocardiogram and coronary angiography within 15 days. All patients had normal global and/or regional wall motion on resting echocardiogram. We calculated GLPSS using two-dimensional speckle-tracking echocardiography. SS was calculated for each group of patients based on the presence and/or the severity of coronary artery disease (CAD): no CAD on angiogram (n=10, control group), low SS (n=36, SS<22) and high SS (n=25, SS≥22). We hypothesised that GLPSS at rest is inversely correlated with the angiographically derived SS.Age, sex and most of the risk factors were equally distributed among the groups. There was a significant inverse correlation between GLPSS and SS values (r(2)=0.3869, P<0.001). This correlation was weaker in the low-SS group (r(2)=0.1332, P<0.05), whereas it was lost in the high-SS group (r(2)=0.0002, P=NS). Receiver operating characteristic curve analysis identified that the optimal cut-off for the detection of high-SS patients was 13.95% (sensitivity=71%, specificity=90%, P<0.001).The results of our study suggest that GLPSS might be promising for the detection of patients with high SYNTAX score on coronary angiogram. There is an inverse correlation between resting GLPSS and SS as assessed by coronary angiography. In patients with the highest SS, however, the correlation with GLPSS was less significant