Mustafa Kilickap

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.

Effect of losartan on circulating Tnfα levels and left ventricular systolic performance in patients with heart failure

Background Tumor necrosis factor alpha (TNFα) plays an important role in the pathophysiology of heart failure. Recent studies have shown a beneficial effect of losartan in these patients. However, the effect of losartan on TNFα levels in heart failure has not yet been studied. We evaluated the effect of losartan on circulating TNFα levels and ejection fraction (EF) in patients with congestive heart failure. Methods Forty patients with heart failure and EF ≤ 40% were enrolled into the study. All of the patients have been given diuretic and digitalis therapy. Twenty patients were given losartan (50 mg/d) (Group I, 10 women, 10 men, 12 dilated cardiomyopathy, 8 ischemic heart disease, mean age 64.9 ± 8.9), and another 20 patients were not given losartan because of hypotension or renal dysfunction (Group II, 13 men, 7 women, 10 dilated cardiomyopathy, 10 ischemic heart disease, mean age 61.2 ±10.5). EF was measured at the initial evaluation and on the fifteenth day of the therapy by echocardiographic examination using an acoustic quantification method. Circulating TNFα levels were also measured at the initial evaluation and on the fifteenth day of therapy by the ELISA method. Results Losartan significantly increased EF and decreased TNFα (EF increased from 29.4 ± 7.3% to 36.0 ± 8.5%, P < 0.001, and TNFα decreased from 39.2 ± 37.4 pg/ml to 27.0 ± 30.0 pg/ml, P < 0.05). Changes in TNFα levels and EF were not found to be correlated (r=−0.28, P=0.24). However, in the control group, EF and TNFα levels were similar at baseline and at the fifteenth day (EF 31.4 ± 8.1% vs 31.7 ± 7.8%, P=0.1, and TNFα 91.5 ± 86.0 pg/ml vs 110.0 ± 80.7 pg/ml, P=0.1, respectively). Conclusions Losartan improves left ventricular systolic function and decreases TNFα level. The decreased TNFα level seems to be independent of EF.

Five-year follow-up after transepicardial implantation of autologous bone marrow mononuclear cells to ungraftable coronary territories for patients with ischaemic cardiomyopathy

OBJECTIVE Cell therapy for patients with ischaemic cardiomyopathy (IC) is still an open issue. We aimed to assess the long-term safety and therapeutic potency of autologous bone marrow mononuclear cell (ABMMNC) implantation into ungraftable coronary artery (UCA) territories in patients with IC. METHODS Bone marrow was aspirated from the iliac crest, and transepicardial ABMMNC implantation (n=25, 24 men, aged 57+/-7 years) as an adjunct to coronary artery bypass grafting (CABG) was performed into an area of reversible ischaemia within the territory of UCA (1.29+/-0.09 x 10(9) ABMMNCs). Control group (n=25, 23 men, aged 59+/-7 years) underwent incomplete CABG due to poor target vessel graftability. The study protocol consisted of coronary angiography, stress echocardiography, nuclear imaging and Holter monitoring at baseline and follow-up. The mean follow-up time was 988+/-423 days. RESULTS There was no difference between the groups regarding postoperative complications and outcome. Overall 5-year survival for the ABMMNC group was 79+/-10%, and 71+/-12% for the controls (p=0.48). Left ventricular ejection fraction (LVEF) at baseline was 24.8+/-3.7 versus 25.9+/-3.1 in the ABMMNC group and the controls, respectively. After 6 months, mean global LVEF increased to 36.3+/-7.4 (p<0.001) versus 31.4+/-4.1 (p=0.001), respectively. A significant difference was noted in delta LVEF between the groups (p<0.001, 95% confidence interval (CI): 3.4-8.9) at 6 months, and (p=0.001, 95% CI: 2.0-7.4) at 1 year. Accordingly, perfusion scores in UCA segments detected by single-photon emission computed tomography (SPECT) improved with ABMMNC therapy to 18.0+/-24.4 from 7.1+/-25.7 (p=0.001 vs control UCA segments). CONCLUSION Cellular therapy for IC within UCA could augment myocardial perfusion and contractility but does not improve overall survival. No adverse events were detected after cell therapy at mid-term follow-up.

Hyperhomocysteinemia and Restenosis

Objective This study was undertaken to assess the effect of plasma homocysteine level on angiographic restenosis 6 months after coronary angioplasty. Methods The plasma homocysteine level was measured in 100 consecutive patients at the time of coronary angioplasty, 56 patients who attended a 6-month follow-up angiogram being enrolled to the study; the 44 patients without a control coronary angiogram were not enrolled. Patients with and without angiographic restenosis were designated as groups A (n = 34) and B (n = 22) respectively. Results The baseline demographic (groups A and B), angiographic (groups A and B) and procedural characteristics were similar in both groups. The mean plasma homocysteine level (SD) was 15.2 (7.7) and 11.1 (2.5) μmol/l in groups A and B respectively (P = 0.007; 95% CI −6.9 to −1.1). With respect to the plasma homocysteine level, the upper and the lower thirds were compared by binary logistic regression (the lower third homocysteine level being < 10.6 μmol/l and the upper third homocysteine level > 14.1 μmol/l). The angiographic restenosis rate for the lower and upper tertiles was 47.4% and 89.5% respectively (P = 0.01; OR = 9.4; 95% CI 1.6−52.7). After adjustment for age and sex, the statistical significance did not change (P = 0.013; OR = 9.43; 95% CI 1.6-54.9). Even after adjustment for age, sex, smoking, hypertension, hypercholesterolemia, and diabetes mellitus, there was a statistically significant difference between the upper and lower tertiles (P = 0.008; OR = 41.3; 95% CI 2.6-635). Conclusion Increased plasma homocysteine level and diabetes mellitus were independent risk factors for angiographic restenosis after percutaneous transluminal coronary angioplasty and coronary stenting.

Behçet's disease with right ventricle thrombus and bilateral pulmonary artery aneurysms--a case report.

Behçet’s disease is currently recognized as a multisystemic disease that may present with vascular, cutaneous, pulmonary, neurologic, rheumatologic, gastrointestinal, and genitourinary manifestations. Despite this multiplicity, cardiac involvement and also the coexistence of bilateral pulmonary arterial aneurysms are rare. An interesting case is presented here with intracardiac thrombi and bilateral pulmonary arterial aneurysms that showed clinical regression with immunosuppressive therapy.

Good Collaterals Predict Viable Myocardium

The authors undertook this study to see whether highly developed coronary collaterals at an area shed by a totally occluded coronary artery predicts myocardial viability. Percutaneous coronary intervention (PCI) of a totally occluded coronary artery has been debated since its introduction. It is recommended to search for viable myocardium before opening a totally occluded coronary artery; however, there is no practical yet sensitive method of assessing myocardial viability in the catheterization laboratory. Forty-seven consecutive patients (12 women, 25.5%; 35 men, 74.5%), each with 1 totally occluded coronary artery, were prospectively enrolled to the study. After the diagnostic coronary angiography, all patients underwent dobutamine stress echocardiography to determine viable myocardium at the territory of the totally occluded coronary artery, and the status of angiographic coronary collaterals was assessed. Patients were then divided into 2 groups according to the presence (Group A) or absence (Group B) of viable myocardium by stress echocardiography. Eighteen patients (38.3%) had viable myocardium (Group A) in the area shed by the totally occluded coronary artery and 29 patients (61.7%) had nonviable myocardium (Group B). The incidences of significant coronary collateral circulation to the viable (Group A) and nonviable (Group B) areas were 66.7% (12 patients) and 20.7% (6 patients), respectively (p = 0.002). Logistic regression analysis was used to evaluate the independent factors for viable myocardium, and only significant coronary collateral circulation was found to be an independent factor for the detection of viable myocardium (p = 0.006, OR 16.7, 95% CI 2.25 to 124.4). The sensitivity and specificity of good collateral circulation for the detection of viable myocardium were 75% and 65.7%, respectively. The positive predictive and negative predictive values of the good coronary collateral circulation in detecting viable myocardium were 75% and 79%, respectively. The authors conclude that good coronary collaterals have a high sensitivity and positive predictive value for the prediction of viability as shown by dobutamine echocardiography, and only by assessing the coronary collateral circulation can one decide for percutaneous coronary revascularization, if not for coronary artery bypass surgery.

Value of Tissue Doppler Myocardial Velocities of Tricuspid Lateral Annulus for the Diagnosis of Right Heart Failure in Patients with COPD

Objective: Aim of this study was to investigate the value of systolic indices of tricuspid valve annular motion measured by tissue Doppler imaging for the diagnosis right ventricular failure in patients with chronic obstructive pulmonary disease (COPD). Methods: Patients with COPD with right heart failure symptoms and/or right ventricular dilatation were enrolled for the study. The control group consisted of age and sex matched patients referred to the echocardiography laboratory who had normal echocardiographic examination. Tricuspid valve annulus peak systolic velocity and myocardial acceleration during isovolumic contraction were recorded by tissue Doppler imaging. Results: IVA and Sa wave velocities were found to be significantly decreased in patients with right ventricular failure. For the prediction of right heart failure IVA <3.8 m/sec2 had 91% sensitivity, 80% specificity, 90% positive predictive value (PPV), and 82% negative predictive value (NPV) and Sa wave velocity <9.2 cm/sec had 80% sensitivity, 62% specificity, 75% PPV, and 68% NPV. Conclusion: Tricuspid valve annular velocities measured by tissue Doppler imaging especially IVA, offer potential diagnostic value for the diagnosis of right heart failure in patients with COPD.

Facilitation of radial artery cannulation by periradial subcutaneous administration of nitroglycerin.

PURPOSE To determine whether subcutaneous administration of nitroglycerin mixed with local anesthetic agent results in effective vasodilation of the radial artery, and whether this technique improves access time and decreases complications. MATERIALS AND METHODS This prospective study consisted of two consecutive investigations. In the first (n = 30), only local anesthetic agent (prilocaine 2%) was injected into one arm, and local anesthetic agent plus 500 microg nitroglycerin was injected into the other arm. Radial artery diameters before and after injections were measured by ultrasonography. In the second, 33 patients received local anesthetic agent (prilocaine 2%) plus 500 microg nitroglycerin (group A) and 30 received only local anesthetic agent (group B) to determine whether the addition of nitroglycerin would improve radial artery access time, duration of angiography, perception of arterial pulse (ie, pulse score), number of punctures before successful cannulation, and complication rates. RESULTS In the first investigation, radial artery diameter increased significantly in the nitroglycerin-treated arm (2.3 mm +/- 0.4 vs 2.9 mm +/- 0.5; P = .05). In the second, there were no significant differences between groups with respect to age, sex, duration of angiography, and number of punctures before cannulation. However, the pulse score increased and radial artery access time improved significantly after addition of nitroglycerin (79% vs 10% [P < .001] and 75 sec +/- 47 vs 132 sec +/- 100 [P = .005], respectively). Radial artery spasm and thrombosis were less frequently observed in group A, albeit to an insignificant extent (P = .39 and P = .49, respectively). CONCLUSIONS Subcutaneous administration of nitroglycerin significantly increased radial artery diameter, which can lead to facilitation of catheterization of the radial artery for arteriography and interventions.

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.

The relationship between angiotensin converting enzyme gene I/D polymorphism and qt dispersion in patients with hypertrophic cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) is characterized by disorganized myocardial architecture, and may cause ventricular arrhythmias and sudden death. The angiotensin-converting enzyme (ACE) with two deletion alleles (DD genotype) has been proposed to be associated with increased myocardial collagen content. We evaluated QT dispersion (QTd), which reflects regional differences in ventricular repolarization, in HCM patient and controls among the three different ACE genotypes. Materials and methods: Sixty-three patients with HCM and 20 healthy subjects were included in the study. QT parameters were measured from 12 lead electrocardiograms. ACE genotypes were determined from the DNA extracted from peripheral blood by a polymerase chain reaction (PCR) method. QT parameters were compared among the three ACE genotypes both in HCM patients and controls. Results: Median ages were similar in HCM and control groups. QTd and corrected QTd (QTcd) were significantly greater in the HCM group compared with the controls. The frequencies of each genotype were similar in both groups. Although QTd and QTcd did not differ among the three genotypes in the control subjects, they were significantly greater in patients with DD genotype compared with other genotypes in the HCM group. Conclusion: QTd and QTcd are increased in patients with HCM, especially in those with the DD genotype.