HDL Subclasses and the Distribution of Paraoxonase-1 Activity in Patients with ST-Segment Elevation Acute Myocardial Infarction.

The aim of this multicentric study was to assess the impacts of oxidative stress, inflammation, and the presence of small, dense, low-density lipoproteins (sdLDL) on the antioxidative function of high-density lipoprotein (HDL) subclasses and the distribution of paraoxonase-1 (PON1) activity within HDL in patients with ST-segment elevation acute myocardial infarction (STEMI). In 69 STEMI patients and 67 healthy control subjects, the lipoproteins' subclasses were separated using polyacrylamide gradient (3-31%) gel electrophoresis. The relative proportion of sdLDL and each HDL subclass was evaluated by measuring the areas under the peaks of densitometric scans. The distribution of the relative proportion of PON1 activity within the HDL subclasses (pPON1 within HDL) was estimated using the zymogram method. The STEMI patients had significantly lower proportions of HDL2a and HDL3a subclasses (p = 0.001 and p < 0.001, respectively) and lower pPON1 within HDL3b (p = 0.006), as well as higher proportions of HDL3b and HDL3c subclasses (p = 0.013 and p < 0.001, respectively) and higher pPON1 within HDL2 than the controls. Independent positive associations between sdLDL and pPON1 within HDL3a and between malondialdehyde (MDA) and pPON1 within HDL2b were shown in the STEMI group. The increased oxidative stress and increased proportion of sdLDL in STEMI are closely related to the compromised antioxidative function of small HDL3 particles and the altered pPON1 within HDL.

Oxidative Stress and Inflammatory Markers PTX3, CypA, and HB-EGF: How Are They Linked in Patients With STEMI?

We investigated circulating levels of inflammatory biomarkers pentraxin-3 (PTX3), cyclophilin A (CypA), and heparin-binding epidermal growth factor-like growth factor (HB-EGF); oxidative stress; and antioxidant status markers in the patients with ST-segment elevation acute myocardial infarction (STEMI) to better understand a relationship between inflammation and oxidative stress. We examined the impact of oxidative stress on high values of inflammatory parameters. The study included 87 patients with STEMI and 193 controls. We observed a positive correlation between PTX3 and HB-EGF (ρ = 0.24, P = .027), CyPA, and sulfhydryl (SH) groups (ρ = 0.25, P = .026), and a negative correlation between PTX3 and SH groups (ρ = -0.35, P = .001) in patients with STEMI. To better understand the effect of the examined parameters on the occurrence of high concentrations of inflammatory parameters, we grouped them using principal component analysis. This analysis identified the 4 most contributing factors. Optimal cutoff values for discrimination of patients with STEMI from controls were calculated for PTX3 and HB-EGF. An independent predictor for PTX3 above the cutoff value was a "metabolic-oxidative stress factor" comprised of glucose and oxidative stress marker prooxidant-antioxidant balance (odds ratio = 4.449, P = .030). The results show that higher PTX3 values will occur in patients having STEMI with greater metabolic and oxidative stress status values.

Circulating levels of inflammatory parameters pentraxin-3, cyclophilin and heparin-binding epidermal growth factor-like growth factor in patients with ST-elevation myocardial infarction.

Inflammatory biomarkers - pentraxin-3 (PTX3), cyclophilin A (CypA) and heparin-binding epidermal growth factor-like growth factor (HB-EGF) were examined in patients with ST-segment elevation myocardial infarction (STEMI) undergoing revascularization with primary percutaneous coronary intervention (pPCI) and stent implanting. Investigated parameters were compared between patients with and without obstructive coronary artery disease (CAD). In addition, their changes were tested in circulation before and immediately after pPCI. The study group consisted of 81 STEMI patients. Patients were classified in the STEMI-CAD group if they had significant obstructive CAD or in MINOCA group if they had no significant stenosis. In STEMI-CAD patients inflammatory parameters were determined prior to and after pPCI intervention. Immediately after pPCI, in STEMI-CAD patients levels of PTX3 were significantly lower (1.52 vs. 2.17 µg/L, p < .001), while the levels of HB-EGF (14.61 vs. 12.03 pg/L, p < .001) and CyPA (15.95 vs. 8.62 µg/L, p < .001) were significantly higher compared to levels before pPCI. STEMI-CAD patients had lower PTX3 values 2.17 µg/L (1.55-5.10 µg/L) than MINOCA patients 5.06 µg/L (2.77-6.7 µg/L), p = .046. Diagnostic accuracy of PTX3 for discrimination MINOCA from STEMI-CAD patients was low (area under receiver operating characteristic curve = 0.770). Evaluation of PTX3 values may be helpful in the understanding of MINOCA aetiology but they couldn't distinguish stenosis severity in STEMI patients. Inflammatory biomarkers significantly changed after pPCI but the possibility of clinical use of these biomarkers needs to be evaluated in a larger prospective study.

Influence of manual thrombus aspiration on left ventricular diastolic function in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention.

INTRODUCTION: Data on effects of thrombus aspiration on left ventricular diastolic function in ST-elevation myocardial infarction (STEMI) population are scarce. OBJECTIVE: We sought to compare echocardiographic indices of the diastolic function and outcomes in STEMI patients treated with and without manual thrombus aspiration, in an academic, high-volume percutaneous coronary intervention (PCI) center. METHODS: A total of 433 consecutive patients who underwent primary PCI in 2011-2012 were enrolled in the study. Patients were not eligible for the study if they already suffered a myocardial infarction, had been previously revascularized, received thrombolytics, presented with cardiogenic shock, had significant valvular disease, atrial fibrillation or had previously implanted pacemaker. Comprehensive echocardiogram was performed within 48 hours. During follow-up patients'status was assessed by an office visit or telephone interview. RESULTS: Patients treated with thrombus aspiration (TA+, n=216) had similar baseline characteristics as those without thrombus aspiration (TA-, n = 217). Groups had similar total ischemic time (319 ± 276 vs. 333 ± 372 min; p = 0.665), but TA+ group had higher maximum values of troponin I (39.5 ± 30.5 vs. 27.6 ± 26.9 ng/ml; p < 0.001). The echocardiography revealed similar left ventricular volumes and systolic function, but TA+ group had significantly higher incidence of E/e' > 15, as a marker of severe diastolic dysfunction' (TA+ 23.1% vs. TA- 15.2%; p = 0.050). During average follow-up of 14 ± 5 months, major adverse cardiac/cerebral events occurred at the similar rate (log rank p = 0.867). CONCLUSION: Thrombus aspiration is associated with a greater incidence of severe diastolic dysfunction in unselected STEMI patients treated with primary PCI, but it doesn't influence the incidence of major adverse cardiovascular events.

Favorable outcomes in octogenarians treated with bioresorbable polymer drug-eluting stent.

AIM: As a result of a higher prevalence of comorbidities, elderly adults are often underrepresented in clinical trials, and more often experience complications during percutaneous coronary intervention. Our aim was to evaluate clinical outcomes of patients older than 80 years, compared with their younger counterparts, when bioresorbable polymer biolimus A9 drug-eluting stent is used for their treatment. METHODS: The prospective, observational e-Nobori registry was created to validate the safety and efficacy of bioresorbable polymer drug-eluting stent in unselected patients. The primary end-point of the study was freedom from target lesion failure defined as a composite of cardiac death, target vessel-related myocardial infarction and clinically-driven target lesion revascularization at 1 year. RESULTS: There were 781 (7.8%) octogenarians, they were less frequently male (62% vs 77%; P < 0.0001) and more often presented as acute coronary syndrome (44% vs 39%; P = 0.0182). The index percutaneous coronary intervention success was lower in the elderly patients (98% vs 99%; P = 0.0398). One-year follow up was completed for 97% of the elderly patients and 99% of the younger patients. The difference in target lesion failure (3.33% vs 2.83%; log-rank P = 0.0114) was mainly driven by increased mortality in octogenarians (3.73% vs 1.47%; P < 0.0001). Elderly patients had more bleeding and vascular complications (2.67% vs 1.05%; P = 0.0001). CONCLUSIONS: Despite advanced age, multiple comorbidities and complexity of treated lesions, clinical outcomes are favorable in octogenarians treated by bioresorbable polymer biolimus A9 drug-eluting stent. Geriatr Gerontol Int 2016; 16: 1246-1253.

Reduced sirolimus systemic exposure and improved bioresorbable polymer properties: new allies for the treatment of patients with coronary artery disease.

This prospective, first-in-man, open-label multicenter study sought to assess the pharmacokinetics of sirolimus after Ultimaster drug-eluting stent implantation (coated with sirolimus and bioabsorbable co-polymer) in patients with de novo coronary artery disease (the TCD-10023 PK study). The primary endpoint was sirolimus concentration in peripheral whole blood at 28 days after stent implantation. In addition, safety, tolerability, therapeutic outcome and vasomotor response after stent implantation were studied. Twenty patients were enrolled in the study. Blood samples for the measurements of sirolimus concentration were collected at eight time points during first 48 h, at 7 days and 28 days after stent implantation. Patients underwent 6-month angiographic and up to 12 months clinical follow-up. At 28 days, only two of 20 patients had sirolimus concentrations above lower limit of quantification (20.0 pg/mL). The highest sirolimus blood concentration was 105 pg/mL. The median maximum concentration was 36.8 pg/mL (range 22.9-41.5 pg/mL) for stent 3.0 × 15 mm and 87.2 pg/mL (range 60.0-105.0 pg/mL) for 3 × 28 mm stent. The median systemic exposure, as measured by the area under the time-concentration curve, was 8.3 ng h/mL (range 6.47-28.0 ng h/mL). At 6 months, endothelial function was well preserved, and up to 12 months, there were no signs of sirolimus toxicity nor any other safety concerns. Our results demonstrate that implantation of Ultimaster stent resulted in almost nondetectable sirolimus in blood after 28 days. These findings were translated into exceptional safety profile, without any sign of systemic toxicity.