Effects of genetic factors to stent thrombosis due to clopidogrel resistance after coronary stent placement.

Stent thrombosis (ST) is considered as a multifactorial problem which is mostly occurs due to clopidogrel resistance. It may be due to some CYP450 enzyme deficiencies which play role in clopidogrel metabolism. Therefore the aim of this study is to detect the mutations in CYP2C19 and CYP2C9 genes which may cause ST, and to investigate the relation between other risk factors and ST. 50 individuals who have stent thrombosis and 50 individuals who haven't got any complication were enrolled as patient and control group respectively. *2,*3,*4,*5,*17 mutations in CYP2C19 gene and *2 ve *3 mutations in CYP2C9 gene were investigated with RT-PCR. Clopidogrel and aspirin resistance were investigated with multiple electrode platelet aggregometry. Results were evaluated statistically. CYP2C19*2 mutation was found statistically higher in patients (% 18), whereas CYP2C19*17 was found statistically higher in controls (% 36)(p<0.05). Additionally, it was found that patients who have clopidogrel and/or aspirin resistance also have CYP2C19*1/*2 or CYPC19*2/*2 genotype. These relations were also found statistically significant. (p=0,000005 for clopidogrel resistance and p=0,000059 for aspirin resistance). In conclusion, it was suggested that there is a relation between CYP2C19*2 mutations and ST due to clopidogrel resistance, and CYP2C19*17 may have a protective role in this process. The use of novel and more potent drug or high clopidogrel maintenance dosing before stent implantation may be beneficial treatment options for antiplatelet therapy in CYP2C19*2 carriers.

Relationship between ACE gene polymorphism and ischemic chronic heart failure in Turkish population.

BACKGROUND: Angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism has been associated with the development of left ventricular hypertrophy, myocardial infarction, and remodeling. However, little is known about its role in ischemic chronic heart failure (CHF). We investigated the relationship between ACE gene I/D polymorphism and ischemic CHF and its influence on exercise capacity. METHODS: ACE gene I/D polymorphism was analyzed in 209 Turkish patients with coronary artery disease (CAD) undergoing coronary angiography. ACE genotype distributions were examined in 84 consecutive patients with ischemic CHF, functional capacity class II-IV to New York Heart Association and left ventricular ejection fraction (LVEF) < 40% and 125 consecutive patients with stable angina pectoris and LVEF > or = 40%. Furthermore the results of the cardiopulmonary exercise testing (CPX) in each ACE genotype were compared in medically treated ischemic CHF patients (n = 84). RESULTS: ACE genotype distributions were similar between the patients with and without symptomatic CHF in CAD. The odds ratios were 0.95 for D homozygotes (p > 0.05) and 0.98 for the D allele (p > 0.05). In patients with ischemic CHF the differences in CPX findings were statistically not significant in ACE D/D, I/D and I/I genotypes (peak oxygen consumptions 13.7 +/- 4.6; 14.6 +/- 5.1 and 14.5 +/- 5.0 ml/kg/min, respectively (p >0.05). CONCLUSIONS: In this study population, there was no evidence that ACE gene I/D polymorphism plays a role in the development of CHF in CAD or any influence on exercise capacity in treated patients with ischemic CHF.

Angiographic and scintigraphic (perfusion and electrocardiogram-gated SPECT) correlates of clinical presentation in unstable angina.

BACKGROUND: Braunwald classification can be used as a measure of the acuteness or severity of clinical presentation of unstable angina. Gating perfusion images might provide additional information to that obtained from angiography, allowing correlations between the coronary anatomy and extent of myocardium at risk via simultaneous perfusion/function assessment. HYPOTHESIS: The aim of this study was to determine the relation between the highest levels of the Braunwald classification (class III = rest angina within 48 h of presentation; class C = postinfarction angina; class c = refractory angina) and the angiographic findings, and the extent ofperfusion and segmental wall motion abnormalities using technetium-99m ((99m)Tc) sestamibi-gated single-photon emission computed tomography (SPECT) imaging. METHODS: The study group consisted of 86 patients with unstable angina who underwent rest gated (99m)Tc sestamibi SPECT imaging and coronary angiography. Perfusion was graded on a 5-point scale (0 = normal; 4 = absent uptake) and wall motion on a 4-point scale (0 = akinesia/dyskinesia; 3 = normal) using the 20 segment model. Perfusion (PI) and wall motion indices (WMI) were calculated by adding the score of all segments and dividing this by 20. The localization, the degree of stenosis, and the morphology of the culprit lesion were assessed. Multivariate analysis was performed to identify the independent predictors of class III, C, and c angina. RESULTS: Perfusion index was higher and WMI was lower in classes III, C, and c than in classes < III, < C, and < c, respectively (all p < 0.001). Class III angina was associated with PI (p <0.0001), WMI (p< 0.0001), complex morphology (p = 0.01), and decreased Thrombolysis in Myocardial Infarction (TIMI) flow (p = 0.002); class C angina with PI (p < 0.0001), WMI (p< 0.0001), intracoronary thrombus (p = 0.007), and decreased TIMI flow (p = 0.003); and class c angina with PI (p = 0.005) and WMI (p = 0.006). CONCLUSION: The highest levels of the Braunwald classification are associated with a greater size and intensity of myocardial perfusion and wall motion abnormalities and with the angiographic findings of complex morphology, intracoronary thrombus, and decreased TIMI flow.

Relation of plasma lipoprotein(a) with myocardial viability and left ventricular performance in survivors of myocardial infarction.

Previous studies have reported that high serum lipoprotein(a) levels may be responsible for total occlusion of the infarct-related artery via inhibition of intrinsic fibrinolysis during acute myocardial infarction. We evaluated whether this would result in a greater extent of myocardial necrosis and impaired left ventricular function in patients with high lipoprotein(a) levels. Sixty-eight patients with prior myocardial infarction, who were not receiving thrombolytic therapy underwent coronary angiography and stress-redistribution-reinjection Tl-201 scintigraphy. Antegrade TIMI flow in the infarct-related artery was lower (1.54 +/- 1.14 vs 2.15 +/- 1.05; p = 0.03) and the collateral index was higher (1.3 +/- 1.0 vs 0.8 +/- 0.9; p = 0.07) in patients with high lipoprotein(a) levels (> 30 mg/dl) compared to those with low lipoprotein(a) levels (< or = 30 mg/dl). Regional wall motion score index was lower (0.8 +/- 0.8 vs 1.4 +/- 0.5; p = 0.008) and global ejection fraction was higher (46 +/- 10% vs 40 +/- 11%; p = 0.03) in patients with low lipoprotein(a) levels. On SPECT images, the number of non-viable defects was higher in patients with high lipoprotein(a) levels (4.0 +/- 2.5 vs 1.9 +/- 1.3; p = 0.0002), whereas the number of viable defects was higher in those with low lipoprotein(a) levels (2.5 +/- 1.8 vs 1.5 +/- 1.3; p = 0.02). We conclude that high lipoprotein(a) levels may prolong the occlusion of infarct-related artery during acute myocardial infarction and lead to a greater extent of myocardial necrosis and impaired left ventricular function.

Assessment of viable myocardium and prediction of postoperative improvement in left ventricular function in patients with severe left ventricular dysfunction by quantitative planar stress-redistribution-reinjection 201-T1 imaging.

A noninvasive approach to determine viable but asynergic myocardium will be clinically significant in identifying patients with coronary artery disease and severe left ventricular dysfunction who will benefit most from coronary bypass surgery. Accordingly, 12 patients (mean ejection fraction 0.32 +/- 0.03) underwent quantitative planar stress-redistribution-reinjection thallium scintigraphy and radionuclide ventriculography before and 8 weeks after revascularization for viability and segmental and global left ventricular function assessment, respectively. Reinjection scan showed new fill-in in 63% of segments without redistribution. Postoperative improvement in perfusion and function of asynergic segments were significantly better in viable compared to nonviable segments (P < 0.001, P < 0.01, respectively) with a strong correlation between improvement in 201-T1 uptake and function (P < 0.001). When adequacy of revascularization was considered, the predictive value of a positive preoperative viability test for functional improvement was 83%. Finally, mean ejection fraction and global wall motion score increased significantly after revascularization for the group as a whole (0.32 +/- 0.03 to 0.44 +/- 0.04, P < 0.001 and 24.08 +/- 2.90 to 33.16 +/- 3.32, P < 0.001, respectively). Thus, preoperative quantitative planar stress-redistribution-reinjection thallium imaging detects viable but asynergic segments which improve function postoperatively and may be valuable in selection of patients with severe left ventricular dysfunction for revascularization.

Platelet lymphocyte adherence in children after surgery.

There is limited data on the importance of the adherence phenomenon of platelets to lymphocytes. In the present study rosette formation and agglutination of lymphocytes with autologous platelets were observed in children after surgery. Lymphocytes and platelets were separated by 'Lymphoprep' solutions from heparinized blood. Platelet-lymphocyte agglutinates were prepared in the presence of inactivated fetal calf serum and were counted on slides. Platelet-lymphocyte agglutinates were found to be significantly elevated during the first post-operative day. It is concluded that the enhancement of platelet adhesiveness to lymphocytes may be due to anaesthesia.