Long-Term Effects on the Lipidome of Acute Coronary Syndrome Patients.

Lipids modified by oxidative stress are key players in atherosclerosis progression. Superimposed thrombosis with subsequent closure of the coronary artery leads to the clinical manifestation of acute coronary syndrome (ACS). While several studies focusing on alterations in lipid metabolism in the acute phase have been conducted, no information is available on patients' lipidome alterations over longer time periods. In the current follow-up study, we analyzed plasma samples obtained from 17 patients three years after their ACS event (group AC). Originally, these patients were sampled 3-5 days after an index event (group B). Lipidome stability over time was studied by untargeted lipidomics using high performance liquid chromatography coupled to high resolution mass spectrometry (UHPLC-HRMS). Multi-dimensional statistics used for data processing indicated that plasmalogen lipids were the most prominent lipids separating the above patient groups and that they increased in the follow-up AC group. A similar trend was observed for lysophosphatidylethanolamine (LPE) and phosphatidylethanolamine (PE). The opposite trend was observed for two fatty acyls of hydroxy fatty acid (FAHFAs) lipids and free stearic acid. In addition, a decrease in the "classic" oxitadive stress marker, malondialdehyde (MDA), occurred during the follow-up period. Our findings present unique information about long-term lipidome changes in patients after ACS.

Incorporation of Fibrin, Platelets, and Red Blood Cells into a Coronary Thrombus in Time and Space.

We describe the internal structure, spatial organization and dynamic formation of coronary artery thrombi from ST-segment elevation myocardial infarction patients. Scanning electron microscopy (SEM) revealed significant differences among four groups of patients (<2 hours; 2-6 hours; 6-12 hours, and >12 hours) related to the time of ischemia. Coronary artery thrombi from patients presenting less than 2 hours after the infarction were almost entirely composed of platelets, with small amounts of fibrin and red blood cells. In contrast, thrombi from late presenters (>12 hours) consisted of mainly platelets at the distal end, where clotting was initiated, with almost no platelets at the proximal end, while the red blood cell content went from low at the initiating end to more than 90% at the proximal end. Furthermore, fibrin was present mainly on the outside of the thrombi and older thrombi contained thicker fibers. The red blood cells in late thrombi were compressed to a close-packed, tessellated array of polyhedral structures, called polyhedrocytes. Moreover, there was redistribution from the originally homogeneous composition to fibrin and platelets to the outside, with polyhedrocytes on the interior. The presence of polyhedrocytes and the redistribution of components are signs of in vivo clot contraction (or retraction). These results suggest why later thrombi are resistant to fibrinolytic agents and other treatment modalities, since the close-packed polyhedrocytes form a nearly impermeable seal. Furthermore, it is of particular clinical significance that these findings suggest specific disparate therapies that will be most effective at different stages of thrombus development.

Lipidomic Analysis to Assess Oxidative Stress in Acute Coronary Syndrome and Acute Stroke Patients.

Alterations in lipid metabolism mediated by oxidative stress play a key role in the process of atherosclerosis and superimposed thrombosis; these can lead to acute coronary syndrome (ACS) and acute ischemic stroke (AIS). Multiple studies have shown that the formation of atheromatous lesions is initiated by oxidation of low-density lipoproteins incorporated into the intima of the vessel wall. Here, we studied lipids in plasma samples from three cohorts: 61 patients with ACS (group A), 49 patients with AIS (group D), and 82 controls (group K). Untargeted lipidomics based on high-performance liquid chromatography coupled to mass spectrometry (UHPLC-HRMS) was employed to obtain comprehensive information on whether relationships exist between these patient categories based on lipid patterns. In addition, malondialdehyde (MDA) as a standard marker of oxidative stress was monitored. The most characteristic lipids in group K were fatty acyls of hydroxyfatty acids (FAHFAs). As expected, MDA concentrations were the lowest in group K. Our findings can better explain ongoing pathologies, both acute and chronic, with the potential for future diagnosis and treatment.

Tryptophan Metabolism, Inflammation, and Oxidative Stress in Patients with Neurovascular Disease.

Atherosclerosis is a leading cause of major vascular events, myocardial infarction, and ischemic stroke. Tryptophan (TRP) catabolism was recognized as an important player in inflammation and immune response having together with oxidative stress (OS) significant effects on each phase of atherosclerosis. The aim of the study is to analyze the relationship of plasma levels of TRP metabolites, inflammation, and OS in patients with neurovascular diseases (acute ischemic stroke (AIS), significant carotid artery stenosis (SCAS)) and in healthy controls. Blood samples were collected from 43 patients (25 with SCAS, 18 with AIS) and from 25 healthy controls. The concentrations of twelve TRP metabolites, riboflavin, neopterin (NEO, marker of inflammation), and malondialdehyde (MDA, marker of OS) were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Concentrations of seven TRP metabolites (TRP, kynurenine (KYN), 3-hydroxykynurenine (3-HK), 3-hydroxyanthranilic acid (3-HAA), anthranilic acid (AA), melatonin (MEL), tryptamine (TA)), NEO, and MDA were significantly different in the studied groups. Significantly lower concentrations of TRP, KYN, 3-HAA, MEL, TA, and higher MDA concentrations were found in AIS compared to SCAS patients. MDA concentration was higher in both AIS and SCAS group (p < 0.001, p = 0.004, respectively) compared to controls, NEO concentration was enhanced (p < 0.003) in AIS. MDA did not directly correlate with TRP metabolites in the study groups, except for 1) a negative correlation with kynurenine acid and 2) the activity of kynurenine aminotransferase in AIS patients (r = -0.552, p = 0.018; r = -0.504, p = 0.033, respectively). In summary, TRP metabolism is clearly more deregulated in AIS compared to SCAS patients; the effect of TRP metabolites on OS should be further elucidated.

Bioresorbable scaffold implantation in STEMI patients: 5 years imaging subanalysis of PRAGUE-19 study.

BACKGROUND: Bioresorbable scaffold (BRS) Absorb™ clinical use has been stopped due to higher rate of device thrombosis. Scaffold struts persist longer than 2 years in the vessel wall. Second generation devices are being developed. This study evaluates long-term invasive imaging in STEMI patients. METHODS: PRAGUE-19 study is an academic study enrolling consecutive STEMI patients with intention to implant Absorb™ BRS. A total of 83 STEMI patients between December 2012 and March 2014 fulfilled entry criteria. Coronary angiography and optical coherence tomography at 5 year follow-up was performed in 25 patients. RESULTS: Primary combined clinical endpoint (death, myocardial infarction or target vessel revascularization) occurred in 12.6% during the five-year follow-up with overall mortality 6.3%. Definite scaffold thrombosis occurred in 2 patients in the early phase after BRS implantation. Quantitative coronary angiography after 5 years demonstrated low late lumen loss of 0.11 ± 0.35 mm with binary restenosis rate of 0%. Optical coherence tomography demonstrated complete resorption of scaffold struts and mean lumen diameter of 3.25 ± 0.30 and 3.22 ± 0.49 (P = 0.73) at baseline and after 5 years, respectively. Three patients developed small coronary artery aneurysm in the treated segment. CONCLUSION: Invasive imaging results 5 years after BRS implantation in STEMI showed complete resorption of scaffold struts and stable lumen vessel diameter. Trial registration ISRCTN43696201 (retrospectivelly registred, June 7th, 2019). https://www.isrctn.com/ISRCTN43696201.

Long-term follow-up after bioresorbable vascular scaffold implantation in STEMI patients: PRAGUE-19 study update.

AIMS: Early clinical results after implantation of bioresorbable vascular scaffolds (BVS) in ST-elevation myocardial infarction (STEMI) are encouraging, but long-term data are missing. This study evaluates long-term outcome in STEMI patients with implanted BVS. METHODS AND RESULTS: The PRAGUE-19 study is an academic study enrolling consecutive STEMI patients with the intention to implant BVS. A total of 580 STEMI patients were screened between December 2012 and March 2015; 117 patients fulfilled entry criteria and BVS was successfully implanted in 114 (97%) of them. The primary combined clinical endpoint (death, reinfarction or target vessel revascularisation) occurred in 11.5% during the mean follow-up period of 730±275 days with overall mortality of 4.4%. Definite scaffold thrombosis occurred in two patients in the early phase after BVS implantation; there was no late thrombosis. Quantitative coronary angiography (10 patients) at three years demonstrated late lumen loss of 0.2±0.33 mm and optical coherence tomography showed minimal lumen area of 5.3±1.37 mm2 and neointimal hyperplasia area of 2.9±0.48 mm2. BVS struts were still visible at three years and 99.4% of them were well apposed and covered. CONCLUSIONS: Encouraging clinical and imaging results after BVS implantation in STEMI patients persist during long-term follow-up.

One-Year Clinical and Computed Tomography Angiographic Outcomes After Bioresorbable Vascular Scaffold Implantation During Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction: The PRAGUE-19 Study.

BACKGROUND: Bioresorbable vascular scaffolds (BVS) represent promising new technology, but data on their long-term outcomes in ST-segment-elevation myocardial infarction (STEMI) setting are missing. The aim was to analyze 1-year clinical and computed tomographic angiographic outcomes after BVS implantation in STEMI. METHODS AND RESULTS: PRAGUE-19 is a prospective multicenter single-arm study enrolling consecutive STEMI patients undergoing primary percutaneous coronary intervention (pPCI) with intention-to-implant BVS. A total of 343 STEMI patients were screened during 15 months enrollment period, and 70 patients (mean age 58.6±10.3 and 74% males) fulfilled entry criteria and BVS was successfully implanted in 96% of them. All patients were invited for clinical and computed tomographic angiographic control 1 year after BVS implantation. Restenosis was defined as ≥75% area stenosis within the scaffolded segment. Three events were potentially related to BVS: 1 in-stent restenosis (treated 7 months after pPCI with drug-eluting balloon), 1 stent thrombosis (treated 2 weeks after pPCI by balloon dilatation-this patient stopped all medications after pPCI), and 1 sudden death at home 9 months after pPCI. Four other patients had events definitely unrelated to BVS. Overall, 1-year mortality was 2.9%. Computed tomographic angiography after 1 year was performed in 59 patients. All BVS were widely patent, and binary restenosis rate was 2% (the only restenosis mentioned above). Mean in-scaffold minimal luminal area was 7.8±2.6 mm(2), area stenosis was 20.1±16.3%, minimal luminal diameter was 3.0±0.6 mm, and diameter stenosis was 12.8±11.1%. CONCLUSIONS: BVS implantation in STEMI is feasible and safe and offers excellent 1-year clinical and angiographic outcomes.