Observational study of inflammatory profiles in patients with ST-elevation myocardial infarction stratified by plaque erosion or rupture identified by optical coherence tomography: The Plaque Erosion Pilot Study

Background Plaque erosion is responsible for 30–40% of ST-elevation myocardial infarction (STEMI) cases, but the underlying cause is unknown. Autopsy studies suggest that inflammatory infiltrates are less abundant in erosion compared to plaque rupture, which suggests that other pathological mechanisms are important. So far, different inflammatory profiles have not been demonstrated in vivo. Objectives We sought to characterise the inflammatory profiles of plaque rupture and plaque erosion in patients with STEMI undergoing primary percutaneous coronary intervention (PPCI). Methods Forty STEMI patients undergoing PPCI with less than six hours of chest pain were recruited in a single-centre observational study. Blood samples were taken from the infarct-related artery and a peripheral artery. Culprit plaques were imaged using optical coherence tomography (OCT) before PCI and classified by three blinded observers as ruptured fibrous cap (RFC) or intact fibrous cap (IFC). The expression profiles of 102 cytokines were measured using an array, and comparisons of the two pathological groups were performed using the Significance Analysis of Microarrays (SAM) methodology. Significant cytokines were validated with enzyme-linked immunosorbent assay (ELISA) and this was confirmed statistically using Wilcoxon rank-sum tests. Thrombectomy samples were analysed for differential mRNA expression using real-time polymerase chain reaction (RT-PCR). Results Twenty-three lesions were classified as RFC (58%), fifteen as IFC (38%) and two were undefined (4%). Overall, 12% (12/102) of cytokines were differentially expressed in both coronary and peripheral plasma. We selected the most significant differences and confirmed that IFC was associated with preferential expression of epidermal growth factor (EGF) (coronary samples: SAM adjusted P < 0.001; ELISA IFC 7.42 vs RFC 6.63 log2 pg/ml, P = 0.036) and Thrombospondin-1 (TSP-1) (coronary samples: SAM adjusted P = 0.03; ELISA IFC 10.4 vs RFC 8.65 log2 ng/ml, P = 0.0041). Interferon-inducible T-cell alpha chemoattractant (I-TAC) was preferentially expressed in RFC (coronary samples: SAM adjusted P <0.001; ELISA IFC 10.2 vs RFC 10.8 log2 pg/ml; P = 0.042). Thrombectomy mRNA demonstrated significantly elevated EGF expression in IFC (P = 0.0264) and I-TAC in RFC (P = 0.0007), but no differences in expression of TSP-1. Conclusions Distinct inflammatory profiles for RFC and IFC are demonstrable in coronary plasma and thrombectomy specimens in STEMI patients. IFC is associated with elevated intracoronary EGF and TSP-1. These results may help to further understand the pathophysiology of plaque erosion and to potentially tailor future treatment strategies. (Chandran S, Watkins J, Abdul-Aziz A, Shafat M, Calvert PA, Bowles KM, et al. Inflammatory differences in plaque erosion and rupture in patients with ST-segment elevation myocardial infarction. J Am Heart Assoc. 2017 May 3;6(5).

Inflammatory Differences in Plaque Erosion and Rupture in Patients With ST‐Segment Elevation Myocardial Infarction

Background: Plaque erosion causes 30% of ST‐segment elevation myocardial infarctions, but the underlying cause is unknown. Inflammatory infiltrates are less abundant in erosion compared with rupture in autopsy studies. We hypothesized that erosion and rupture are associated with significant differences in intracoronary cytokines in vivo. Methods and Results: Forty ST‐segment elevation myocardial infarction patients with <6 hours of chest pain were classified as ruptured fibrous cap (RFC) or intact fibrous cap (IFC) using optical coherence tomography. Plasma samples from the infarct‐related artery and a peripheral artery were analyzed for expression of 102 cytokines using arrays; results were confirmed with ELISA. Thrombectomy samples were analyzed for differential mRNA expression using quantitative real‐time polymerase chain reaction. Twenty‐three lesions were classified as RFC (58%), 15 as IFC (38%), and 2 were undefined (4%). In addition, 12% (12 of 102) of cytokines were differentially expressed in both coronary and peripheral plasma. I‐TAC was preferentially expressed in RFC (significance analysis of microarrays adjusted P<0.001; ELISA IFC 10.2 versus RFC 10.8 log2 pg/mL; P=0.042). IFC was associated with preferential expression of epidermal growth factor (significance analysis of microarrays adjusted P<0.001; ELISA IFC 7.42 versus RFC 6.63 log2 pg/mL, P=0.036) and thrombospondin 1 (significance analysis of microarrays adjusted P=0.03; ELISA IFC 10.4 versus RFC 8.65 log2 ng/mL, P=0.0041). Thrombectomy mRNA showed elevated I‐TAC in RFC (P=0.0007) epidermal growth factor expression in IFC (P=0.0264) but no differences in expression of thrombospondin 1. Conclusions: These results demonstrate differential intracoronary cytokine expression in RFC and IFC. Elevated thrombospondin 1 and epidermal growth factor may play an etiological role in erosion

Application of unsaturated shear strength properties in slope stability analysis

It is very important to study applications of unsaturated soil properties in slope stability analysis due to the additional shear strength an unsaturated soil possesses. Shear strength of an unsaturated soil is strongly related to the amount of water in the voids of the soil, and therefore to the matric suction. It is postulated that the shear strength of an unsaturated soil should also bear a relationship to the soil-water characteristic curve. In this thesis, the effect of unsaturated shear strength properties on stability of slopes is investigated by analysing for the stability of hypothetical cut slopes. The effect of the position of water table below the failure surface of hypothetical cut slopes were analysed using Slope/w software for different water table positions for three different cut slope angles. For this work, analyses were done by replacing the cohesion by the apparent cohesion values. Apparent cohesion values were increased by increasing the depth of water table and increasing the effect of negative pore water pressure. Different apparent cohesion values corresponding to the different percentage of negative hydrostatic pressures were utilized. Spreadsheets prepared by a previous research were used to analyse the hypothetical cut slopes by the Modified Janbu’s Method of slices for unsaturated soils. The negative pore water pressure could be directly taken into account in this method, and the Factors of Safety (FOS) derived by this method are compared with the results from SLOPE/W software. Variation of FOS with slope angle and position of water table are investigated. The parametric study done here gives an insight into the problem of landslides. Lowering of the Water Table is been to increase the FOS against sliding failure, as expected

Percutaneous device closure of paravalvular leak

Background: Paravalvular leak (PVL) occurs in 5% to 17% of patients following surgical valve replacement. Percutaneous device closure represents an alternative to repeat surgery. Methods: All UK and Ireland centers undertaking percutaneous PVL closure submitted data to the UK PVL Registry. Data were analyzed for association with death and major adverse cardiovascular events (MACE) at follow-up. Results: Three hundred eight PVL closure procedures were attempted in 259 patients in 20 centers (2004-2015). Patient age was 67±13 years; 28% were female. The main indications for closure were heart failure (80%) and hemolysis (16%). Devices were successfully implanted in 91% of patients, via radial (7%), femoral arterial (52%), femoral venous (33%), and apical (7%) approaches. Nineteen percent of patients required repeat procedures. The target valve was mitral (44%), aortic (48%), both (2%), pulmonic (0.4%), or transcatheter aortic valve replacement (5%). Preprocedural leak was severe (61%), moderate (34%), or mild (5.7%) and was multiple in 37%. PVL improved postprocedure (