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Background/Introduction Acute stress-induced cardiomyopathy, also known as Takotsubo Syndrome (TTS), was originally classified as a benign disease. Nowadays, this assumption has changed, especially in its long-term outcome, due to TTS clinical presentation, that often mirrors the acute myocardial infarction (MI) phenotype. Current knowledge already delineate clinical features distinctive of TTS and MI patients, however, diagnosis requires multiple, expansive, and invasive medical examinations. Moreover, concerning the biological panorama, very slight is known and the lack of a tailored therapy is resented. Therefore, a biological profile for this clinical category could provide easier and less invasive diagnostic tools, leading edge towards novel therapeutic pathways. Purpose The aim of the study is to perform a biological profile of the TTS group compared to the ST Segment Elevation Myocardial Infarction (STEMI) in order to explore the molecular peculiarities attendant the pathophysiologic mechanisms. Methods We performed a gene expression array on two groups of pooled cDNA from peripheral blood mononuclear cells, from TTS (n=11) and STEMI (n=19) patients. We conducted gene expression validations for each enrolled patient through qPCR. Results Our preliminary data displayed several differences in gene expression levels of a grand number of cell adhesion signaling molecule between the two groups. As shown in figure 1, three gene were more expressed in TTS group: Nitric Oxide Synthase 3, also known as endothelial NOS (NOS3; p=0.002), Superoxide dismutase 1 (SOD1; p=0.03) and transferrin receptor (TFRC; p=0.005). Meanwhile, five gene displayed a higher expression in STEMI patients compared to TTS: phospholipase A2 Group 7 (PLA2G7; p=0.04), Galectin 8 (LGALS8; p=0.02), Intercellular Adhesion Molecule 1 (ICAM1; p=0.002), Hyaluronidase 2 (HYAL2; p=0.01) and Hyaluronan Receptor (CD44; p=0.0002). Conclusions The earliest results of this study led us to focus on fewer genes related to endothelial and oxidative stress pathways. TTS is habitually triggered by intense emotional or physical stress. Indeed, our results showed how TTS patients present higher expression of NOS3, SOD1 and TFRC, all components involved in the oxidative stress pathways. In STEMI patients, top expressed genes, such as HYAL2, CD44 and ICAM1, are all associated with extracellular matrix turnover, likely due to the presence of a stenotic plaque and the consequent endothelial derangement. The uncovering of diagnostic biomarkers in TTS might improve the early, non-invasive, stratification of this group of patients, thus facilitating novel and personalized therapeutics design. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): The present study was supported by the Italian National Project Grant PRIN 2017.

Funding Acknowledgements Type of funding sources: None. Background High-flow nasal cannulae oxygen therapy (HFNCOT) represents a better tolerated alternative to non-invasive pressure support ventilation (NIPSV) for acute cardiogenic pulmonary edema (ACPE) treatment. However, there are still few data on the effect of HFNCOT on cardiac function and hemodynamic. Purpose To assess and compare the effects of NIPSV and HFNCOT in ACPE setting on right ventricular (RV) systolic function and on indices of cardiac filling and output, as measured by echocardiography. Methods This is a cross-over controlled study, enrolling 15 consecutive patients admitted to our Cardiovascular Intensive Care Unit for ACPE and hypoxaemic, normo/hypocapnic acute respiratory failure, with P/F ratio < 200. Each patient received NIPSV, followed by HFNCOT. Full echocardiographic assessment and blood gas analysis (BGA) were performed 40 minutes from onset of each ventilation modality, respectively before NIPSV to HFNCOT switch and before HFNCOT interruption. In particular, RV function parameters, together with RV and atrial strain, were prospectively collected. Results In spite of not significant changes in BGA, RV function was significantly improved under HFNCOT, as compared to NIPSV, as assessed by the following parameters: tricuspid annular plane excursion (TAPSE) (P = 0.001), RV S’ wave (P = 0.007), RV fractional area change (RVFAC) (P = 0.006). Strain analysis confirmed the significant improvement in RV function, with free wall global longitudinal strain (GLS) and free wall and septum GLS significantly higher under HFNCOT, as compared to NIPSV (-21% vs -18% P Conclusions NIPSV significantly affect RV function making more complex the management of patients presenting with ACPE. In this setting, HFNCOT represents a valuable alternative, providing similar respiratory outcomes while preserving good right ventricle performance.

Background Coronary microvascular obstruction (MVO) is a noxious condition frequently occurring in patients with ST-elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI). However, multiple mechanisms are involved in the pathogenesis of MVO and not yet fully understood. Recent studies suggested that perilipin 2 (PLIN2) may play an important role in lipid metabolism of macrophages resident in atherosclerotic plaques along with a role in enhancing oxidative stress. Purpose To study the association between PLIN2 and MVO in STEMI patients undergoing primary PCI. We also assessed the role of PLIN2 to predict future major cardiovascular events (MACEs). Methods STEMI patients undergoing primary PCI were enrolled. PLIN2 was dosed within 24 hours from admission in peripheral blood monocytes. MVO was assessed using TIMI flow grade and myocardial blush grade on coronary angiogram after PCI, and patients were stratified accordingly (MVO or noMVO). Major adverse cardiac events (defined as a composite of cardiac death, non-fatal myocardial infarction, re-admission for heart failure and target vessel revascularization) were assessed at clinical follow-up. Results Among 100 STEMI patients (mean age, 65.2±12.0 years, 81 males), 33 (33.0%) had MVO. Patients with MVO were older, had higher troponin I peak, C-reactive protein and lower left ventricular ejection fraction on admission. Patients with MVO had significantly higher levels of PLIN2 (1.03±0.28 vs. 0.90±0.16, p=0.019) compared to noMVO patients. Age [OR (95% CI) per year, 1.045 (1.005–1.087), p=0.026] and PLIN2 [OR (95% CI) per unit, 16.606 (2.027–136.030), p=0.009] were associated with MVO at univariate logistic regression analysis. However, only PLIN2 levels [OR (95% CI) per unit, 12.325 (1.446–105.039), p=0.033] were independently associated with MVO at multivariate analysis. Follow up data were available for 76 patients (76%). After a mean follow up of 182.2±126.6 days, 13 MACEs occurred. Patients with MVO had more MACEs [9 (37.5%) vs. 4 (7.7%), p Conclusions In STEMI patients undergoing primary PCI, PLIN2 was independently associated with MVO. PLIN2 was an independent predictor of MACEs at clinical follow-up. These findings suggest that PLIN2 may represent a promising therapeutic target, opening the avenue towards novel therapeutic approaches for MVO. Funding Acknowledgement Type of funding source: None

Background PLATO study showed that Ticagrelor (Ti) significantly reduced the rate of death from vascular causes, myocardial infarction or stroke without a significant increase of major bleeding vs Clopidogrel (Cl). Previous studies demonstrated the stronger direct anti-platelet effect of Ti versus Cl. Few data exist about the indirect anti-platelet properties and pleiotropic effects, eventually involved in the positive effect of Ti on acute coronary syndrome (ACS) outcome. Aim As Ti has multiple pleiotropic effects, we sought to assess whether the different outcome of Ti versus Cl in NSTE-ACS patients could be explained, at least in part, by different modulation of circulating microRNA (miRNA). The primary endpoint was to characterize the effect of the two different P2Y12 inhibitors on miRNA expression. Secondary endpoint was to correlate miRNA profile to clinical outcome. Methods Thirty-one patients with a diagnosis of NSTE-ACS were enrolled in this study. Patients were randomized for Ti or Cl assumption before undergoing PCI. Clinical characteristics were homologues between Ti and Cl groups. Blood samples were drawn at different time point (T0, T1 and T2) to test miRNA modulation and stability (T0, at baseline; T1, three hours after drug administration; T2, twenty-four hours after coronarography). Plasma RNA was extracted and pooled for microarray PCR based panel of ninety miRNA analysis. MiRNA expression was normalized on the global mean of each patient. Levels of circulating miRNAs were compared using statistical tests, assuming significance at P Results A panel of seven circulating miRNAs associated with atherosclerosis, thrombosis and inflammation were selected for validation (miR-652-3p; miR-26-5p; miR-25-3p; miR-let7c; miR-155-5p; miR-222-3p; miR-223-3p). Microarray analysis showed an opposite modulation of most miRNAs at T0, T1 and T2 in patients with Cl or Ti treatment. In particular, Cl group showed an upregulation of most miRNAs, while Ti administration caused their down-regulation. Of the seven miRNA selected for validation, miR-652-3p, expression at T1 showed a significantly modulation in patients in Cl treatment compared to Ti (T1 Cl 2,637±1,092, T1 Ti 0,660±0,171; p=0.03). MiRNA-652-3p has a validated pro-atherogenic role. On five-years follow, an higher rate (40%) of cardiovascular events (new ACS, recurrent ischemia and stent thrombosis) was reported in the Cl group compare to Ti. Indeed, no one death or bleeding occurred. Conclusion This data suggest that Ti has a protective role down-regulating pro-atherogenic and pro-thrombotic miRNAs (miR-652-3p, miR-let7c, miR-223-3p, miR-155-5p) and promoting the expression of anti-atherogenic miRNAs (miR-25-3p) when compared to Cl. This may contribute to explain the positive effect on clinical outcome of Ti. Although the small number of patients, this pilot study gives another evidence about the multiple positive pleiotropic effect of Ti. Figure 1. miRNA 652-3p expression Funding Acknowledgement Type of funding source: None

Background The imbalance between protective and harmful bacteria in the microbial communities leads to a non-physiological condition, known as “dysbiosis”. In the last decade, several studies have suggested that gut microbiota can contribute to the development and progression of various disease including cardiovascular disease through metabolism-mediated pathways. The production and the release of bacterial metabolites, including Trimethylamine N-oxide (TMAO), can affect host health acting to distant organs. Purpose The aim of the present study was to explore the gut microbiota and the levels of TMAO in patients with stable angina (SA) and acute coronary syndrome (ACS) with or without elevation of the ST segment, respectively STEMI and NSTEMI, and in control subjects. Methods Feces were obtained from ACS (n=31) and SA (n=23) patients and controls (n=24). Genomic DNA was isolated using the QIamp DNA Stool Mini Kit. Samples were subjected to 16S rRNA gene V3–V4 region sequencing by an Illumina MiSeq TM platform. A combination of software packages QIIME and VSEARCH was used to generate a biological observation matrix (BIOM) at different taxonomic levels (from phylum to genus). The BIOM was analysed using the Web-based program MicrobiomeAnalyst. β-diversity between groups was obtained by weighted UniFrac distance metric analysis. Serum TMAO levels were measured with a UPLC-MS/MS mass spectrometry in SA and ACS patients. Results β-diversity analysis showed a different bacterial composition in SA and ACS patients and controls ([PERMANOVA] F-value: 1.9706; R-squared: 0.050567; p-value Conclusion These results, taken together, suggest that gut microbiota and its derived metabolites might play an essential role in the progression of atherosclerosis and in coronary plaque instability. Funding Acknowledgement Type of funding source: Other. Main funding source(s): Linea D1 Università Cattolica del Sacro Cuore

Patients with ischaemic heart disease and low ejection fraction (EF) are at increased risk of sudden death. MADIT (Multicenter Automated Defibrillator Implantation Trial) II has shown that implantable cardioverter-defibrillators (ICDs) reduce the risk of death by 31% at two years in patients with previous myocardial infarction and EF < 30%.1 The absolute risk reduction over an average follow up of 20 months, however, was only 5.6%. In addition, the high prevalence of patients who have had a myocardial infarction with EF ⩽ 30% makes the cost of this strategy high. This has led to an ongoing search for reliable markers of future episodes of life-threatening ventricular tachycardia (VT) or ventricular fibrillation (VF) to identify a higher-risk subgroup in which ICD therapy can be more beneficial and cost effective. The difficulty in predicting major ventricular arrhythmias probably reflects a limited understanding of their complex mechanisms. This is particularly true for patients who have had a myocardial infarction and with LV dysfunction, in whom myocardial ischaemia may trigger major ventricular arrhythmias. C reactive protein (CRP) concentration has been shown to be raised both in subjects studied …

Superoxide dismutase (SOD) activity and reduced glutathione (GSH) content in erythrocytes (RBC) of uremic patients on chronic dialysis were determined. Specific SOD activity and GSH content were found lower in RBC from uremic patients before hemodialysis compared to normal RBC; after hemodialysis, the specific activity of SOD and GSH content were significantly increased.

It has been suggested that performance in an industrial inspection task can be improved by rapidly alternating images of the item to be inspected and a perfect item onto the visual field of the inspector. Such a blink inspection system was evaluated for a complex item (a printed circuit board which could contain three flaws) and a simple item (a blank field which could contain one flaw) using eight student subjects for each of five inspection conditions. Three groups, one using blink inspection and two control groups, inspected circuit boards; two groups (one blink and one control) inspected blank fields. Search time was improved by blink inspection for the circuit boards and with different defects showing different degrees of improvement. Only one type of defect showed both reduced search times and reduced errors. For blank fields, performance was worse under blink inspection. Subjects showed a consistent tendency to terminate their search for defects in a logical manner, with stopping time related to search difficulty. Measures of heart rate mean and variability were taken as a pilot study to measure task stress. There was little evidence from the heart rate measures that the task was stressful.

C-reactive protein (CRP), the prototypic acute phase reactant and a sensitive marker of inflammation, consistently predicts new coronary events, including myocardial infarction and death, in patients with ischemic heart disease. The data are very consistent with regard to the long-term outcome, but in many studies are also significant for in-hospital events. The predictive value of CRP is, in the majority of the studies, independent of and additive to that of the troponins. Moreover recent data suggest that CRP may be a reliable marker of the risk of restenosis after percutaneous coronary interventions and that its levels can be modulated by statins. Taken together, all these data suggest that CRP, probably with different cut-offs, should be used as a marker of risk and as a guide to therapy in patients hospitalized for acute coronary syndromes and in outpatients suffering from ischemic heart disease.