Serum miRNA Profile in Diabetic Patients With Ischemic Heart Disease as a Promising Non-Invasive Biomarker.

The increasing morbidity and mortality of type 2 diabetic mellitus (T2DM) patients with ischemic heart disease (IHD) highlight an urgent need to identify early biomarkers, which would help to predict individual risk of development of IHD. Here, we postulate that circulating serum-derived micro RNAs (miRNAs) may serve as potential biomarkers for early IHD diagnosis and support the identification of diabetic individuals with a predisposition to undergo IHD. We obtained serum samples from T2DM patients either with IHD or IHD-free and analysed the expression levels of 798 miRNAs using the NanoString nCounter technology platform. The prediction of the putative miRNAs targets was performed using the Ingenuity Pathway Analysis (IPA) software. Gene Ontology (GO) analysis was used to identify the biological function and signalling pathways associated with miRNA target genes. Hub genes of protein-protein interaction (PPI) network were identified by STRING database and Cytotoscape tool. Receiver operating characteristic (ROC) analysis was used to assess the diagnostic value of identified miRNAs. Real-time quantitative polymerase chain reaction (qRT-PCR) was used for nCounter platform data validation. Our data showed that six miRNAs (miR-615-3p, miR-3147, miR-1224-5p, miR-5196-3p, miR-6732-3p, and miR-548b-3p) were significantly upregulated in T2DM IHD patients compared to T2DM patients without IHD. Further analysis indicated that 489 putative target genes mainly affected the endothelin-1 signalling pathway, glucocorticoid biosynthesis, and apelin cardiomyocyte signalling pathway. All tested miRNAs showed high diagnostic value (AUC = 0.779 - 0.877). Taken together, our research suggests that circulating miRNAs might have a crucial role in the development of IHD in diabetic patients and may be used as a potential biomarker for early diagnosis.

[Complex congenital heart disease in adult complicated by endocarditis. Diagnostic difficulties]. / Zlozona wada wrodzona serca powiklana zapaleniem wsierdzia u doroslego. Trudnosci diagnostyczne.

We describe a case of a 45-year-old man admitted with symptoms of infective endocarditis on tricuspid valve. At this time complex congenital heart disease was first time diagnosed. Differential diagnosis between tetralogy of Fallot and double-chambered right ventricle is discussed. At surgical exploration tetralogy of Fallot was confirmed. The patient underwent successful total surgical correction.

[Repeated administration of t-PA and abciximab in a patient with anterior myocardial infarction--a case report]. / Ponowne podanie t-PA z abciximabem w celu utrzymania droznosci tetnicy dozawalowej w zawale sciany przedniej serca.

Repeated administration of t-PA and abciximab in a patient with anterior myocardial infarction - a case report. A case of a 40-year-old male with acute anterior myocardial infarction (MI) is presented. Due to the angiographic equipment failure, the patient did not undergo primary angioplasty and received heparin and 100 mg of t-PA. This treatment was associated with clinical and ECG signs of reperfusion, however, 30 minutes after completion of t-PA infusion, the patient developed clinical and ECG signs of re-occlusion. The decision was made to transfer the patient to a catheterisation laboratory for further invasive treatment, however, it was located 200 km from our centre. Because of that, the patient received another dose of 50 mg of t-PA and abciximab before transportation. Further course was uncomplicated and the patient underwent successful stent implantation in the other centre.

Platelet inhibition by increased tirofiban dosing during primary coronary angioplasty for ST elevation myocardial infarction.

BACKGROUND: Platelet receptor IIb/IIIa inhibition during percutaneous coronary interventions (PCI) decreases incidence of major adverse cardiac events (MACE). These effects directly result from the level of platelet inhibition. Due to existing data indicating that standard dosing of tirofiban is insufficient for optimal platelet inhibition, we proposed a novel, experimental dosing. AIM: In this study we assessed, with the use of Ultegra Rapid Platelet Function Assay (RFPA), the level of platelet inhibition with increased tirofiban dosing during primary PCI for ST elevation myocardial infarction (STEMI). METHODS: Twenty eight patients (22 males, 6 females, mean age 63 years, range 32-78 years) with STEMI were included into the study. All patients received 300 mg of aspirin, iv. heparin in a dose of 10 000 IU, which was followed by platelet receptor GP IIb/IIIa inhibitor tirofiban - 10 micro g/kg iv bolus, 0.4 micro g/kg/min for 30 min and infusion 0.1 micro g/kg/min continued for 12-24 h. Platelet function was assessed with RFPA before tirofiban administration and after 10, 30, 90 minutes as well as 8 hours from the initial dose of tirofiban. Baseline fibrinogen binding to platelet receptor IIb/IIIa was defined as PAU (platelet aggregation unit) and the effects of tirofiban on platelets were expressed as a percentage of platelet inhibition. RESULTS: During in-hospital stay, no deaths, re-infarction nor recurrences of ischaemia requiring intervention were noted. The mean total duration of tirofiban administration was 21 hours. Thrombocytopenia was not observed in any patient. Bleeding complications occurred in 5 (17.9%) patients. Blood transfusion was required in three patients. The percentages of platelet inhibition measured at the pre-specified time-points were 95%, 94%, 91% and 87%, respectively. In 32% of patients an inhibition of platelet exceeding 95%, measured 10 minutes from the onset of tirofiban infusion, was not achieved. At the same time, platelet inhibition <90% was found in only 3 (11%) patients. Eight hours from the initiation of tirofiban, platelet inhibition <70% was found in 3 (11%) patients; of them, two had platelet inhibition <95% when measured 10 minutes from the onset of therapy with tirofiban. CONCLUSIONS: 1. Increased dosing of tirofiban resulted in an enhanced platelet inhibition. 2. Optimal platelet inhibition, especially during first minutes of drug administration, was not achieved in a substantial number of patients. 3. Increased IIb/IIIa inhibitor dosing resulted in a high partial and normal baseline coronary flow in an infarct-related artery. 4. Increased tirofiban dosing resulted in a relatively high bleeding complications rate.

Myocardial perfusion assessed by contrast echocardiography correlates with angiographic perfusion parameters in patients with a first acute myocardial infarction successfully treated with angioplasty.

BACKGROUND: Angiographic flow in an epicardial artery does not define perfusion at the microvascular level. AIM: To compare myocardial contrast echocardiography (MCE) with angiographic methods of assessing microvascular reperfusion in patients with acute myocardial infarction (AMI). METHODS: One hundred consecutive patients with a first ST segment elevation myocardial infarction and single-vessel disease were successfully treated with primary percutaneous coronary intervention. Regional contrast score index (RCSI), corrected Thrombolysis In Myocardial Infarction (TIMI) frame count (cTFC), TIMI myocardial perfusion grade (TMPG) and myocardial blush grade were evaluated. RESULTS: Among 717 asynergic segments on MCE, 168 revealed a lack of perfusion. TMPG and cTFC correlated significantly with RCSI (P=0.031 and P=0.027, respectively). Myocardial blush grade did not correlate with RCSI (P=0.067). Patients with anterior AMI had significantly more segments with a perfusion defect on MCE than patients with inferior AMI (P=0.0001). CONCLUSIONS: MCE results correlate with angiographic methods of perfusion assessment such as TMPG and cTFC. Anterior AMI is associated with a greater extent of perfusion defect. MCE results correlate also with recovery of systolic left ventricular function and clinical outcome at six month follow-up.

Safety and feasibility of a novel dosing regimen of tirofiban administered in patients with acute myocardial infarction with ST elevation before primary coronary angioplasty: a pilot study.

BACKGROUND: Intravenous glycoprotein GP IIb/IIIa receptor antagonists administered to patients with acute coronary syndromes limit platelet-dependent thrombus formation and vasoconstriction and lower the complication rate of PCI. The efficacy of glycoprotein IIb/IIIa inhibitors critically depends on appropriate suppression of platelet aggregation. A growing body of evidence indicates that regimen of tirofiban used in several recent trials may be suboptimal. We investigated if a novel regimen of dosage of tirofiban administered to patients with acute myocardial infarction with ST elevation (STEMI) before primary angioplasty is safe, feasible and whether such treatment improves coronary flow in infarct-related artery. METHODS: It was an open-label, non-randomized, prospective observational study. 253 consecutive patients with STEMI, qualified to PCI were included. 104 of patients (group 1) received heparin plus tirofiban at a novel regimen (10 microg/kg bolus, followed by 0.4 microg/kg/min for 30 min and then 0.1 microg/kg/min for 12-24 hours) and the remaining 149 of the patients (group 2) received a standard dose of heparin prior to PCI. Bleeding complications were recorded. The primary end point of the study was combined TIMI 1 + 2 + 3 grade flow at the time of first contrast medium injection during angiography for primary PCI. RESULTS: Heparin was administered 50.3 +/- 58.1 minutes (group 1) or 62.3 +/- 67.3 minutes (group 2) ( p = 0.205). Tirofiban was administered for an average of 14.5 +/- 14.4 minutes before TIMI assessment (group 1). In patients treated with heparin + tirofiban the rate of combined TIMI 1 + 2 + 3 coronary flow was higher (38.4% vs. 24.8%, p = 0.020) as compared to patients treated with heparin alone. The difference in the rate of TIMI > or = 2 coronary blood flow between the groups 1 and 2 (24.0% vs. 20.1%) has not reached statistical significance ( p = 0.459). At the same time the significant difference in the rate of TIMI 1 coronary blood flow between the groups 1 and 2 was noted (14.4 vs. 4.7%, p = 0.007). In hospital mortality in the groups 1 and 2 was similar (5.3 vs. 4.8%, p = 0.838). Significant difference was noted between the groups 1 and 2 with regard to minor bleeding complications (17.3 vs. 8.7%, p = 0.041). CONCLUSION: In patients undergoing primary angioplasty for acute myocardial infarction the novel regimen of tirofiban is well tolerated and feasible, and is associated with improvement in coronary blood flow in the infarct related artery. Larger studies assessing the effects of tirofiban on clinical outcomes of patients with AMI undergoing primary angioplasty seem worthwhile.