Ticagrelor effectively inhibits platelet aggregation in comatose survivors of cardiac arrest undergoing primary percutaneous coronary intervention treated with mild therapeutic hypothermia.

BACKGROUND: Mild therapeutic hypothermia (MTH) is believed to reduce the effectiveness of antiplatelet drugs. Effective dual-antiplatelet therapy after percutaneous coronary intervention (PCI) is mandatory to avoid acute stent thrombosis. The effectiveness of ticagrelor in MTH-treated out-of-hospital cardiac arrest (OHCA) survivors is still a matter of debate. The aim of the study was to evaluate the impact of MTH on the platelet-inhibitory effect of ticagrelor in comatose survivors of OHCA treated with primary PCI. METHODS: Eighteen comatose survivors of OHCA with acute coronary syndrome undergoing immediate PCI treated with MTH were compared with 14 patients with uncomplicated primary myocardial infarction after PCI, matched for gender and age, in a prospective, single-center, observational study. Platelet aggregation was evaluated using VerifyNow P2Y12 point-of-care testing at 3 time points: admission (T0), during MTH (T1), and 48-72 h after rewarming (T2). RESULTS: Ticagrelor effectively inhibits platelet aggregation in OHCA patients subjected to MTH and in all patients in the control group. The effectiveness of ticagrelor did not differ between the MTH group and the control group (p = 0.581). In 2 cases in the MTH population, the platelet response to ticagrelor was inadequate, and in one of them it remained insufficient during the re-warming phase. There was no stent thrombosis in these patients. CONCLUSIONS: The present study confirmed the effectiveness of ticagrelor to inhibit platelets in myocardial infarction patients after OHCA treated with primary PCI undergoing hypothermia. The use of cooling was not associated with an increased risk of stent thrombosis.

Thin-cap fibroatheroma and increased coronary intima-media thickness are associated with an altered balance of arginine metabolites.

INTRODUCTION: Arginase inhibition increases plasma citrulline and citrulline / ornithine (C/O) ratio, and reduces plasma ornithine and ornithine / arginine (O/A) ratio in an animal model of myocardial infarction (MI). OBJECTIVES: We hypothesized that the presence of thin­cap fibroatheroma (TCFA) in the culprit lesion and increased non­culprit intima­media thickness of an infarct­related artery (IRA) are associated with an altered balance of arginine metabolites. PATIENTS AND METHODS: Arginine and its metabolites were measured using liquid chromatography and tandem mass spectrometry in 100 consecutive MI patients upon admission and at 6­month follow­up. TCFA and adjacent to culprit lesion proximal and distal 10­mm segments were assessed with optical coherence tomography in the acute phase. Twenty five patients without coronary lesions on angiography served as controls. RESULTS: The C/O ratio increased 5.33 times (P <0.001), while the O/A ratio decreased 2.53 times (P <0.001) at the 6­month follow­up, as compared with the acute phase of MI. The patients with (n = 75) vs without (n = 25) TCFA had lower C/O ratio by 29% (P = 0.003), while the mean intima­media diameter of adjacent non­culprit region correlated with the follow­up O/A ratio (R = 0.337; P = 0.003). In a multivariable analysis, a higher acute phase C/O ratio was associated with a lower risk of TCFA presence (odds ratio, 0.978; 95% CI, 0.962-0.994; P = 0.006), whereas a higher follow­up O/A ratio correlated with larger intima­media diameter of the adjacent segments (ß coefficient, 0.227; 95% CI for ß coefficient, 0.045-0.409; P = 0.018). CONCLUSIONS: Enhanced arginase activity over nitric oxide synthase following ischemia was associated with the presence of TCFA in the culprit lesion, while a similar metabolic shift in the chronic phase correlated with a greater thickness of the intima­media in the adjacent non­culprit IRA segments.

Ezetimibe combined with simvastatin compared with simvastatin alone results in a greater suppression of oxidative stress and enhanced fibrinolysis in patients after acute coronary events.

We compared the effect of simvastatin versus simvastatin combined with ezetimibe on hemostasis and inflammation after acute coronary events [acute coronary syndromes (ACS)]. In an investigator-initiated, double-blind, placebo-controlled, randomized study, patients with ACS were assigned to 40 mg/d of simvastatin + 10 mg/d of ezetimibe (n = 26) or 40 mg/d of simvastatin + placebo (n = 28) administered for 2 months. Markers of coagulation (prothrombin fragments 1.2, thrombin-antithrombin complexes, free tissue factor pathway inhibitor), fibrinolysis [plasminogen activator inhibitor-1, clot lysis time (CLT)], platelet activation (soluble CD40 ligand, ß-thromboglobulin, thromboxane B2), oxidative stress [8-iso-prostaglandin F2α (8-iso-PGF2α)], and inflammation (interleukin-6, interleukin-18, and interleukin-1ß) were measured within the first 12 hours of ACS and at 1 and 2 months of therapy. A final analysis comprised 20 patients in the simvastatin + ezetimibe group and 26 patients in the simvastatin + placebo group. Both groups were similar with regard to demographics, risk factors, medications, and routine laboratory results. Inflammatory, coagulation, and platelet markers did not differ between both treatment groups at all time points. Reductions in low-density lipoprotein cholesterol, CLT, plasminogen activator inhibitor-1, and 8-iso-PGF2α were significantly greater (by 10%, 8.7%, 17.5%, and 22.4%) in the simvastatin + ezetimibe group after 1 month, with further decreases in CLT and 8-iso-PGF2α at 2 months (all P < 0.05). These changes were not associated with lipid and inflammatory parameters. In conclusion, compared with simvastatin alone, simvastatin + ezetimibe results in a greater suppression of oxidative stress and enhanced fibrinolysis in patients with ACS, indicating that ezetimibe might exert cholesterol-independent actions in humans (NCT00725829).

Elevated concentrations of Nɛ-homocysteinyl-lysine isopeptide in acute myocardial infarction: links with ADMA formation.

BACKGROUND: A homocysteine (Hcy) metabolite, thioester Hcy-thiolactone, whose reaction with protein lysine residues affords N-homocysteinylated proteins, has been implicated in cardiovascular disease. Proteolytic turnover of N-homocysteinylated proteins generates the isopeptide Nɛ-homocysteinyl-lysine (N-Hcy-Lys). METHODS: We determined N-Hcy-Lys in serum and a NO syntase inhibitor asymmetric dimethylarginine (ADMA), as well as symmetric dimethylarginine (SDMA) and glutathione in plasma by high performance liquid chromatography in 52 consecutive patients with acute myocardial infarction (AMI) recruited within the first 12 h following onset of chest pain. Associations of N-Hcy-Lys with markers of thrombin generation, oxidative stress, enhanced inflammation, fibrinolysis, and autoantibodies against homocysteinylated proteins were also analyzed. RESULTS: N-Hcy-Lys concentrations, detectable in 45 (86.5%) patients (>0.1 µmol/L), were 127.3% higher compared with healthy controls. N-Hcy-Lys correlated with ADMA (r=0.50; p<0.001), SDMA (r=0.43; p<0.01), glutathione (r=0.37; p<0.05), fibrinogen (r=0.39; p<0.01) and plasminogen activator inhibitor-1 (r=0.32; p<0.05), but not with plasma total Hcy, anti-N-Hcy-protein autoantibodies, vitamin B(12), folate, interleukin-6, plasma thrombin-antithrombin (TAT) complexes, prothrombin fragments F1+2 or 8-isoprostaglandin F(2α) a marker of oxidative stress. CONCLUSIONS: N-Hcy-Lys is increased in AMI patients and its formation is linked with the nitric oxide synthase inhibitor ADMA.

Thrombus aspiration followed by direct stenting: a novel strategy of primary percutaneous coronary intervention in ST-segment elevation myocardial infarction. Results of the Polish-Italian-Hungarian RAndomized ThrombEctomy Trial (PIHRATE Trial).

BACKGROUND: Previous studies with thrombectomy showed different results, mainly due to use of thrombectomy as an additional device not instead of balloon predilatation. The aim of the present study was to assess impact of aspiration thrombectomy followed by direct stenting. METHODS: Patients with ST elevation myocardial infarction (STEMI) <6 hours from pain onset and occluded infarct-related artery in baseline angiography were randomized into aspiration thrombectomy followed by direct stenting (TS, n = 100) or standard balloon predilatation followed by stent implantation (n = 96). The primary end point of the study was the electrocardiographic ST-segment elevation resolution >70% (STR > 70%) 60 minutes after primary angioplasty (percutaneous coronary intervention [PCI]). Secondary end points included angiographic myocardial blush grade (MBG) after PCI, combination of STR > 70% immediately after PCI and MBG grade 3 (optimal myocardial reperfusion), Thrombolysis In Myocardial Infarction flow after PCI, angiographic complications, and in-hospital major adverse cardiac events. RESULTS: Aspiration thrombectomy success rate was 91% (crossing of the lesion with thrombus reduction and flow restoration). There was no significant difference in STR ≥ 70% after 60 minutes (53.7% vs 35.1%, P = .29). STR > 70% immediately after PCI (41% vs 26%, P < .05), MBG grade 3 (76% vs 58%, P < .03), and optimal myocardial reperfusion (35.1% vs 11.8%, P < .001) were more frequent in TS. There was no difference in between the groups in 6-month mortality (4% vs 3.1%, P = .74) and reinfarction rate (1% vs 3.1%, P = .29). CONCLUSIONS: Aspiration thrombectomy and direct stenting is safe and effective in STEMI patients with early presentation (<6 hours). The angiographic parameters of microcirculation reperfusion and ECG ST-segment resolution directly after PCI were significantly better in thrombectomy group despite the lack of the difference in ST-segment resolution 60 minutes after PCI.

[Primary percutaneous coronary intervention with DES implantation after Bentall de Bono procedure; late in-stent restenosis after DES implantation]. / Pierwotna angioplastyka z implantacja stentuuwalniajacego lek po operacji Bentall De Bono;pózna restenoza w stencie uwalniajacym lek.

We report a case of acute coronary syndrome in a 58 year-old man with a history of double Bentall De Bono procedure (redo due to endocarditis). During the second operation, both main native coronary arteries were anastomosed end-to-end to aortic prosthesis using short vein graft insertions. Four months later the patient presented to the CCU with unstable angina. Computed tomography-scan suggested bilateral ostial stenoses. Percutaneous coronary intervention of the left proximal anastomosis was performed with DES. 14 months later the patient was treated with in-(DES) DES implantation.

Elevated levels of 8-iso-prostaglandin F2alpha in acute coronary syndromes are associated with systemic and local platelet activation.

INTRODUCTION: Oxidative stress is an important causative factor in atherosclerosis. Isoprostanes are derivatives of arachidonate oxidized by reactive oxygen species (ROS). Oxidized lipids are markers of oxidative stress, important mediators of atherosclerosis, and activators of platelets. 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha) is a stable isoprostane and reliable marker of oxidative stress in vivo. OBJECTIVES: The aim of the study was to determine the level of oxidative stress in acute coronary syndromes (ACS) and its correlations with the para meters of hemo stasis. PATIENTS AND METHODS: Fourty-nine patients aged 46 to 76 years, including 28 with ACS and 25 with stable coronary artery disease (CAD), were enrolled to the study. The levels of 8-iso-PGF2alpha, soluble CD40 ligand (sCD40L), P-selectin (P-sel), beta-thromboglobulin, and the thrombin-antithrombin complex (TAT) in the plasma of venous blood were determined. A microvascular injury model was also used to evaluate TAT generation and sCD40L levels in blood collected every 60 seconds at the site of standardized microvascular injury. RESULTS: 8-iso-PGF2alpha levels were significantly higher in ACS compared to CAD patients (363.2 +/-45.94 vs. 328.2 -/+31.96 pg/ml, P = 0.011) and correlated with venous plasma levels of P-sel and beta-thromboglobulin in the ACS (r = 0.66; P = 0.0005 and r = 0.62; P = 0.001, respectively) and CAD groups (r = 0.46; P = 0.02 and r = 0.49; P = 0.01, respectively). In the microvascular injury model, the maximum concentrations of sCD40L in the ACS group were associated with plasma 8-iso-PGF2alpha levels (r = 0.50, P = 0.01). No correlations between 8-iso-PGF2alpha and markers of thrombin generation in venous blood and microvascular injury model were observed. CONCLUSIONS: Plasma levels of 8-iso-PGF2alpha are significantly higher in ACS compared with stable CAD and correlate with platelet activation.