Eralp Tutar

Elevated Whole-Blood Tissue Factor Procoagulant Activity as a Marker of Restenosis After Percutaneous Transluminal Coronary Angioplasty and Stent Implantation

Background—Experimental data suggest that tissue factor (TF) may induce neointimal hyperplasia after arterial injury. In this study, we investigated the hypothesis that elevated levels of TF in the circulation contribute to the development of restenosis after percutaneous transluminal coronary angioplasty (PTCA) or stent implantation. Methods and Results—Whole-blood TF procoagulant activity (TF-PCA) was measured using a previously described assay before, at 3 hours after, and at 24 hours after the intervention in 61 patients with stable angina undergoing PTCA (n=20) or stent implantation (n=41). Coronary angiography was performed 4 to 6 months after the intervention, and luminal narrowing ≥50% was defined as restenosis. Whole-blood TF-PCA levels did not correlate with intracellular monocyte tumor necrosis factor-&agr; expression, a marker of activation of these cells. Baseline levels and time course of whole-blood TF-PCA after the intervention were compared in patients who did or did not subsequently develop restenosis. Whole-blood TF-PCA levels did not change significantly in the 24 hours after either intervention. However, in both the PTCA and stent groups, initial TF-PCA was significantly higher in patients who subsequently developed restenosis (P =0.018 and 0.039 compared with those who did not develop restenosis for PTCA and stent groups, respectively). Conclusions—Higher baseline values of whole-blood TF-PCA may be a predictor of restenosis after PTCA and stent implantation.

Echocardiographic evaluation of left ventricular diastolic function in chronic cor pulmonale

In this study we hoped to understand the abnormalities of left ventricular filling dynamics in chronic cor pulmonale. Our findings showed a severe left ventricular diastolic impairment, directly related to a progressive increase in pulmonary hypertension itself, as expressed by correlation analysis between systolic pulmonary artery pressure and the following parameters: transmitral flow velocity in early/late diastole ratio (r = -0.69, p <0.001), isovolumic relaxation time (r = 0.54, p = 0.001), and transmitral flow velocity in early diastole (r = -0.59, p <0.01).

Restenosis after Transluminal Coronary Angioplasty: A Risk Factor Analysis

Background: Restenosis after percutaneous transluminal coronary angioplasty (PTCA) is a major problem limiting the long-term efficacy of the procedure. The purpose of this study was to determine whether risk factors such as cigarette smoking, diabetes mellitus, hypertension or hypercholesterolaemia correlate with restenosis after PTCA. We also studied the relationship between a history of previous myocardial infarction and the extent of coronary artery disease (single-, two- or three-vessel) with restenosis after coronary angioplasty. Methods: A total of 360 patients underwent successful PTCA. Follow-up coronary angiograms were performed in 181 patients after a mean ± SD period of 6 ± 4 months. Results: The restenosis rate was 49%. We divided the patients into two groups: 89 patients with restenosis (8 women and 81 men) and 92 patients with no restenosis (14 women and 78 men). Age, sex, a history of cigarette smoking, diabetes mellitus and a history of previous myocardial infarction were not associated with restenosis. Serum levels of triglyceride were also unrelated to the restenosis rate. Restenosis was associated with hypertension, low levels of high-density-lipoprotein cholesterol, high levels of low-density-lipoprotein cholesterol and high total cholesterol levels (P < 0.001). Patients with two-vessel or multivessel disease had significantly higher restenosis rates than patients with single-vessel disease (P < 0.001). Conclusion: Patients with hyperlipidaemia, hypertension and multi-vessel disease appear to be at higher risk of recurrent restnosis.

A Stepwise Approach to the Treatment of Amiodarone-Induced Thyrotoxicosis

Amiodarone-induced thyrotoxicosis (AIT) is a complex therapeutic challenge. Two major forms have been described: type I and type II. Methimazole (MMI) and potassium perchlorate (KCLO(4)) is the treatment of choice for the former, whereas corticosteroids are used for the latter. However, mixed forms appear frequently and it is not easy to prescribe corticosteroids because of side effects. The present study investigated the validity of a stepwise therapeutic approach to AIT. Twenty patients with AIT were given 30-50 mg/d of MMI and 1000 mg/d of KCLO(4) initially for a month. Euthyroidism or a significant decrease in serum thyroid hormone levels could be achieved in 12 of the patients (7 with type I, 5 type II). Prednisolone, 40-48 mg/d was added for the 8 nonresponding patients (7 type I, 1 type II) and euthyroidism was achieved in all. The prednisolone dose was decreased when free thyroxine (T(4)) levels normalized, and MMI was titrated, maintaining euthyroidism until urinary iodine excretion normalized. Mixed forms of AIT may prevail in iodine-deficient areas. Initial classification of the patients may cause unnecessary corticosteroid use in a substantial number of patients with AIT. A stepwise approach is feasible; however, when the patient is gravely ill, MMI, KCLO(4), and prednisolone could be prescribed simultaneously.

The effects of L-carnitine treatment on left ventricular function and erythrocyte superoxide dismutase activity in patients with ischemic cardiomyopathy

We studied the effects of l‐carnitine on left ventricular systolic function and the erythrocyte superoxide dismutase activity in 51 patients with ischemic cardiomyopathy. They all previously were under the treatment of angiotensin‐converting enzyme inhibitor, digitalis and diuretics. Patients were randomized into two groups. In group I (n = 31), 2 g/day l‐carnitine was added to therapy. l‐Carnitine was not given to the other 20 patients (Group II). In group I (mean age 64.3 ± 7.8 years), 27 of the patients were men, and four were women. In group II (mean age 66.2 ± 8.7 years), 17 of the patients were men, and three were women. Twenty age‐matched healthy subjects (mean age: 60.1 ± 5.3 years) constituted the control group. In each group, left ventricular ejection fraction (LVEF) by echocardiography and red cell superoxide dismutase activity by spectrophotometric method were measured initially and after 1 month of randomisation. Compared with normal healthy subjects (n = 20), patients (n = 51) had significantly higher red cell SOD activity (5633 ± 1225 vs. 3202 ± 373 U/g Hb, P < 0.001). At the end of 1 month of l‐carnitine therapy, red cell SOD activity showed an increase in group I (5918 ± 1448 to 7218 ± 1917 U/g Hb, P < 0.05). In group II, red cell SOD activity showed no significant change after 1 month of randomisation (5190 ± 545 to 5234 ± 487 U/g Hb, P = 0.256). One month after randomisation there was a significant increase in LVEF in both groups I and II (37.8–42.3%, P < 0.001 in group I; 41.5–43.8%, P < 0.001 in group II). The improvement in LVEF was more significant in the l‐carnitine group (4.5% vs. 2.3%, P < 0.01). We conclude that, as a sign of increased free radical production, superoxide dismutase activity was further increased in patients with l‐carnitine treatment. l‐Carnitine treatment in combination with other traditional pharmacological therapy might have an additive effect for the improvement of left ventricular function in ischemic cardiomyopathy.

Relation between the insertion/deletion polymorphism of the angiotensin I converting enzyme gene and restenosis after coronary stenting.

Background Observations with intravascular ultrasound demonstrated that neointimal hyperplasia is the predominant factor responsible for in-stent restenosis. Experimental data suggest that angiotensin I converting enzyme (ACE) plays a role in the thickening of neointima after balloon denudation. Insertion/deletion (I/D) polymorphism of the ACE gene is significantly associated with plasma level of ACE and subjects with D/D genotype have significantly higher plasma levels of ACE than normal. Objective To investigate whether this polymorphism influences the risk of restenosis after coronary stenting. Methods We genotyped 158 patients who had undergone single-vessel coronary stenting for the ACE I/D polymorphism. Results Of the 158 patients, 56 (35%) had the D/D genotype, 71 (45%) had the I/D genotype and 31(20%) had the I/I genotype. Prevalences of genotypes were compatible with Hardy-Weinberg equilibrium and distributions of ACE genotype among patients and 132 healthy controls from the same geographic area did not differ. At follow-up (after a median duration of 5.4 months), overall rates of angiographic restenosis and of revascularization of target lesion (RTL) were 32.3 and 22.8%, respectively. Of 51 patients with angiographic restenosis, 31 (60.8%) had focal and 20 (39.2%) had diffuse patterns of restenosis. Diffuse in-stent restenosis was significantly more prevalent among patients with D/D genotype (P= 0.016). Multiple stepwise logistic regression analysis identified ACE I/D polymorphism as the independent predictor of angiographic restenosis and RTL. Relative risk of angiographic restenosis was 6.29 [95% confidence interval (CI), 1.80–22.05, P= 0.0004] for D/D genotype and 3.88 (95% CI 1.11–13.12, P= 0.029) for I/D genotype, whereas relative risk of RTL was 7.44 (95% CI 1.60–34.58, P= 0.01) for D/D genotype and 3.88 (95% CI 0.083–18.15, P= 0.085) for I/D genotype. Conclusions The ACE I/D polymorphism is significantly associated with risk of angiographic and clinical restenosis after coronary stenting. Angiographic pattern of restenosis is also significantly associated with I/D polymorphism, diffuse type being more prevalent among subjects with D/D genotype.

Increase in soluble E-selectin level after PTCA and stent implantation: a potential marker of restenosis

BACKGROUND E-Selectin is expressed only on activated endothelial cells, and may be used as a marker of endothelial activation. The relationship between soluble form of E-selectin (sE-selectin) and development of restenosis after balloon angioplasty (PTCA) is controversial, and there are no data for after stent implantation. We evaluated the role of serially measured sE-selectin levels in predicting the development of restenosis after PTCA and stent implantation. METHODS In sixty-one patients with stable angina pectoris who underwent PTCA (n=20) or stent implantation (n=41), peripheral blood samples were taken just before (baseline), at 3 and at 24 h after the intervention. sE-Selectin levels were measured by ELISA. Coronary angiography was repeated at 4-6 months after the intervention, and > or =50% stenosis at the site of the intervention was regarded as restenosis. Levels and time course of sE-selectin after the intervention were compared in patients with and those without restenosis. RESULTS sE-Selectin levels of the patients with and those without restenosis were similar at each of the three measurements, and significantly increased after the intervention both in the PTCA and stent groups (P<0.001 for both groups). Posthoc analysis showed that sE-selectin levels increased significantly at 3 h after PTCA (P=0.024) and stent implantation (P=0.018), and did not change thereafter in patients with restenosis. In the nonrestenotic group, sE-selectin did not change significantly in the 24 h following PTCA, however, a significant difference was observed only by comparing the values at baseline with those at 24 h after stent implantation (P=0.021). CONCLUSIONS A substantial increase in sE-selectin levels early (at 3 h) after PTCA and stent implantation may predict development of restenosis.

Exercise performance in patients with dilated cardiomyopathy: relationship to resting left ventricular function

Relationship between maximal exercise tolerance and resting indexes of left ventricular systolic and diastolic function were evaluated in 35 men, aged 55.1 +/- 10.4 years, with dilated cardiomyopathy. Clinical diagnosis of dilated cardiomyopathy was confirmed with M-mode echocardiography (M-mode echocardiographic end-diastolic dimension >55 mm, fractional shortening <25%, increased E point septal separation). Coronary angiography was considered mandatory for exclusion of patients with coronary artery disease. Patients with mitral regurgitation (> or =grade 2) and rhythm other than sinus were excluded. According to the functional classification of New York Heart Association 6 patients were in class I, 11 in class II, 12 in class III and 6 in class IV. Left ventricular ejection fraction (LVEF), stroke volume (SV) and left ventricular end-diastolic pressure (LVEDP) were measured with contrast angiography. Peak early (VE) and late (VA) transmitral filling velocities and their ratio (E/A), isovolumetric relaxation time (IRT) and deceleration time (DT) were computed from pulsed wave Doppler echocardiograms. On completion of all resting measurements, patients underwent symptom limited upright treadmill exercise testing using a modified Naughton protocol and maximal exercise performance metabolic equivalent work load (NETS) was calculated from the speed, incline and length of time at the stage using standard tables to make interpatient comparisons. Significant correlation has been found between NYHA class and METS (r= -0.77, P<0.001). However NYHA class II and NYHA class III patients were found to have similar METS (P=0.317). Patients were further divided into two groups on the basis of exercise data. Group I consisted of 22 patients with relatively preserved exercise tolerance (> or =4 METS) and Group II included 13 patients with impaired exercise tolerance (> or =4 METS). This arbitrary classification was based upon previously described survival differences in these two groups. There were no differences between two groups in terms of age, gender distribution (all were male), heart rate and arterial blood pressure. LVEF, LVEDP, stroke volume, VE, VA, E/A, IRT and DT were also similar between two groups. Strong positive correlation was observed between LVEDP and VE (r=0.74) while IRT and VA negatively correlated with LVEDP (r= -0.77 and r= -0.81 respectively) but neither of resting indexes of left ventricular systolic and diastolic function showed significant correlation with METS and exercise duration.

Overcoming Aspirin Resistance with Loading Clopidogrel Earlier in Elective Percutaneous Coronary Intervention

We aimed to analyze the clinical effect of clopidogrel loading time on adverse cardiovascular events among patients with aspirin resistance. Recurrent adverse events may still occur despite dual antiplatelet therapy after coronary stenting. Aspirin resistance is one of the possible reasons of this trouble. Optimal antiplatelet strategy for coronary stenting is unknown among patients with aspirin resistance. A total of 980 patients scheduled for elective coronary stenting were enrolled and allocated into two groups according to the loading time of clopidogrel more or less than 6 hours before coronary intervention (early- or late-loaded groups, respectively). Aspirin resistance was determined according to the urinary levels of 11-dehydrothromboxane B2. Overall 240 patients who were allocated to early- and late-loaded groups were identified as aspirin resistant according to the urinary levels of 11-dehydrothromboxane B2. After a follow-up period of 12 months major adverse cardiac events were observed among 16 patients (13.9%) in the early-loaded group and 30 patients (25.8%) in the late-loaded group (p = 0.02). Early loading of clopidogrel was an independent predictor of lower rate of cardiac events (hazard ratio = 0.46 [0.32-0.76, 95% confidence interval], p = 0.001). The rates of bleeding events and periprocedural myocardial infarction were similar in early- and late-loaded groups. The current study demonstrated that loading of clopidogrel earlier than 6 hours before elective coronary stenting among aspirin-resistant patients was associated with increased benefits for ischemic events with similar bleeding rates.

Left atrial appendage function in patients with different pacing modes

Many studies suggest that patients who receive a ventricular pacemaker have a higher incidence of systemic thromboembolism compared to patients receiving a physiological pacemaker. However, the exact mechanism regarding the etiology of thromboembolism remains unclear. We evaluated the left atrial appendage (LAA) functions, using multiplane transesophageal echocardiography (TEE), in patients with different pacing modes. In order to evaluate the ejection fraction (EF), peak emptying (V(E)) and filling (V(F)) flow velocities of the LAA by TEE, we studied 31 patients (mean age 63+/-18.5 years) who had been paced for 5.0+/-2.9 years. Patients with atrial fibrillation, left ventricular dysfunction and mitral valve disease were excluded. The pacing indications were complete atrioventricular block (AVB) in 19 patients (9 VVI, 10 VDD or DDD) and sick sinus syndrome (SSS) in 12 patients (5 VVI, 7 DDD). Mean EF, V(E) and V(F) of the LAA were significantly lower in all patients with ventricular pacing (25.5+/-15.6%, 30.4+/-15.6 cm/s and 29. 1+/-19.2 cm/s, respectively) compared to those with physiologic pacing (48.5+/-16.9%, 59.6+/-16.3 cm/s, 57.9+/-18.5 cm/s, respectively) (P<0.01 in all). When patients were further classified with respect to underlying heart disease whether they had SSS or AVB, all measurements of the LAA (EF, V(E) and V(F)) in both subgroup of patients with SSS and AVB were found significantly lower in those with ventricular pacing than in those with physiologic pacing (Tables 3 and 4). This decrease, especially in LAA flow, was much greater in those with SSS (Mean V(E) and V(F) <20 cm/s). In a patient paced with VVI for SSS, a thrombus was detected within the LAA cavity. In conclusion, these results suggest that the pacing modality appeared to influence the LAA functions in paced patients. Patients with asynchronous ventricular pacing modes had a significantly higher incidence of depressed LAA functions than did patients with physiological pacing, especially more marked in patients with sick sinus syndrome. This may be a factor responsible for increased risk of thrombus formation and thromboembolic events in this patient population.