Bonni Syeda

Intracoronary Thrombectomy With the X-Sizer Catheter System Improves Epicardial Flow and Accelerates ST-Segment Resolution in Patients With Acute Coronary Syndrome A Prospective, Randomized, Controlled Study

Background—In patients with acute coronary syndrome (ACS), percutaneous coronary intervention (PCI) may cause thrombus dislodgment followed by reduced flow and impaired microcirculatory function. We prospectively compared conventional PCI to a strategy of additional pretreatment using the X-sizer thrombectomy system. Methods and Results—Sixty-six patients (51 [77%] men; 54.9±9.9 years) with ACS (49 with ST-elevation infarction [STEMI]) and suspected intracoronary thrombus were randomized 1:1 to pretreatment with X-sizer and conventional PCI alone. Various aspects of epicardial flow and microvascular function were studied. Baseline data were similar in both groups. Postprocedural TIMI 3 flow was obtained in 90% of X-sizer–treated patients and in 84% of controls (NS); however, corrected TIMI frame count was lower in X-sizer– treated patients (18.3±10.2 versus 24.7±14.1;P <0.05). No significant group differences were observed in final coronary flow reserve, myocardial blush grade, and myocardial dye intensity. In STEMI, the sum of ST elevation was significantly lower in X-sizer–treated patients immediately after (2.78±3.05 versus 6.15±6.32 mm;P <0.03) and 6 hours after (2.17±2.31 versus 4.14±3.7 mm;P <0.05) intervention. ST-segment resolution >50% was observed in 83% of X-sizer–treated patients and in 52% of controls (P <0.03). Multivariate analysis identified X-sizer treatment as the single independent predictor of ST-segment resolution >50% (OR 4.35; 95% CI, 1.13 to 16.9;P <0.04). Major adverse cardiac events after 30 days occurred in 2 patients in each group. Conclusions—In ACS with suspected thrombus, pretreatment with the X-sizer catheter system improves epicardial flow and accelerates ST-segment resolution compared with conventional PCI alone.

Arterial compliance: a diagnostic marker for atherosclerotic plaque burden?

BACKGROUND Previous studies have shown atherogenesis to be related with increased vessel stiffness. Measures of the arterial compliance can be performed noninvasively from pressure pulse contour analysis of arterial waveforms. In this prospective study we aimed to analyze to what extent vessel compliance can reflect the angiographic coronary artery status. METHODS Large and small arterial elasticity indices (LAEI in milliliters per mm Hg x 10 and SAEI in milliliters per mm Hg x 100) were measured in 151 patients on the radial artery with the PulseWave Sensor HDI device. All patients were classified into diffuse-coronary artery disease (CAD) (defined as stenosis length >15 mm), focal-CAD (defined as stenosis length between 1 and 15 mm), or no-CAD. RESULTS We found both LAEI and SAEI to be reduced in the diabetic group (LAEI: 11.2 +/- 2.9 v 13.4 +/- 4.5, P =.006; SAEI: 3.7 +/- 1.6 v 4.7 +/- 2.4, P =.01). Inverse association was seen between age and LAEI (r = -0.41; P <.001) and SAEI (r = -0.38; P <.001). No-CAD was found in 31 patients, focal-CAD in 64 patients, and diffuse-CAD in 56 patients. Mean LAEI were 13.8 +/- 3.5, 13.7 +/- 4.7, and 11.3 +/- 3.5 in the groups no-CAD, focal-CAD, and diffuse-CAD, respectively (P =.004), (no-CAD versus diffuse-CAD: P =.04; focal-CAD versus diffuse-CAD: P =.009). Respective SAEI values were 5.6 +/- 2.5, 5.0 +/- 2.1, and 3.1 +/- 1.6 (P <.001), (no-CAD versus diffuse-CAD: P <.001; focal-CAD versus diffuse-CAD: P <.001). Multivariate analysis revealed SAEI (P <.001), hypercholesterolemia (P =.005), systolic blood pressure (BP) (P <.001), mean arterial BP (P <.001), pulse pressure (P =.003), and male gender (P =.001) to be diagnostic markers of the type of vessel disease. CONCLUSIONS Compliance measurements may be used for identification of patients with diffuse atherosclerotic processes of the coronary arteries.

Detection of High-grade Stenoses With Multislice Computed Tomography in Heart Transplant Patients

BACKGROUND Post-transplant follow-up of heart transplant patients consists of repeated coronary angiography, which is associated with high costs, discomfort and risk. We sought to determine whether multislice computed tomography (MSCT) permits the exclusion or progression of coronary artery disease in heart transplant patients. METHODS MSCT scanning (Philips CT MX 8000 IDT) and invasive coronary angiography were performed on 66 consecutive heart transplant patients. One hundred milliliters of non-ionic iodinated contrast medium was applied for CT angiography. For MSCT analysis, coronary arteries and side branches with a diameter > or =1.5 mm were assessed for the presence of luminal narrowing of >70%. MSCT results were compared with those of quantitative coronary angiography analysis. RESULTS Ten patients (17%) had one significant stenosis, whereas 3 patients (5%) had 2-vessel disease and none had 3-vessel disease. MSCT was performed successfully on 60 patients enrolled in our analysis. Forty-two of 44 patients (95%) who were estimated to be fully evaluable for MSCT were correctly classified. On per-segment-based analysis, sensitivity, specificity and positive and negative predictive values were 59%, 94%, 91% and 99.43%, respectively. After exclusion of unevaluable segments, sensitivity and specificity increased to 71% and 99.86%, respectively. On per-patient-based analysis, sensitivity, specificity and positive and negative predictive values were 88%, 97%, 88% and 97%, respectively, in evaluable transplant recipients. CONCLUSIONS MSCT with its high specificity and high negative predictive value allows the exclusion of significant coronary artery vasculopathy in evaluable patients. From the clinical point of view, this might spare additional invasive coronary angiography in heart transplant patients.

Ivabradine Versus Metoprolol for Heart Rate Reduction Before Coronary Computed Tomography Angiography

Several studies have demonstrated the correlation of heart rate (HR) and image quality in coronary computed tomography angiography. Beta-blocker administration is critical because of its negative inotropic effect. Ivabradine is a selective HR-lowering agent that exclusively inhibits the I(f) current in sinoatrial node cells without having any effect on cardiac contractility or atrioventricular conduction. A total of 120 patients were randomized to oral premedication with ivabradine 15 mg or metoprolol 50 mg. HR and blood pressure (BP) were measured before the administration of premedication and immediately before coronary computed tomographic angiography. The mean time between premedication administration and follow-up was 108 ± 21.5 minutes for ivabradine and 110 ± 22.2 minutes for metoprolol (p = NS). When comparing groups, there were no significant differences in reduction of HR (-11.83 ± 8.6 vs -13.20 ± 7.8 beats/min, p = NS) and diastolic BP (-5.05 ± 14.2 mm Hg vs -4.08 ± 10.8 mm Hg, p = NS), whereas the decrease of systolic BP was significantly lower in patients who received ivabradine compared to those in the metoprolol group (-3.95 ± 13.6 vs -13.65 ± 17.3 mm Hg, p <0.001). In the subgroup of patients who were receiving long-term β-blocker therapy, significantly stronger HR reduction was achieved with ivabradine (-13.19 ± 5.4 vs -10.04 ± 6.0 beats/min, p <0.05), while the decrease in systolic BP was less (-2.00 ± 13.6 vs -15.04 ± 20.8 mm Hg, p <0.05) compared to metoprolol. In conclusion, ivabradine decreases HR before coronary computed tomographic angiography sufficiently, with significantly less depression of systolic BP compared to metoprolol.

Mechanism of lumen gain during coronary stent deployment in diabetic patients compared with non-diabetic patients.

BackgroundDiabetic patients show an increased incidence of restenosis after coronary angioplasty than non-diabetic patients. This may be because of differences in the mechanism of lumen gain during coronary revascularization in this population cohort. DesignThis study analyses the mechanism of lumen gain during coronary stent deployment in diabetic patients compared with non-diabetic patients with intravascular ultrasound (IVUS). MethodsIVUS images were obtained prior to and after revascularization in 26 diabetic and 97 non-diabetic patients. The external elastic membrane cross-sectional area (EEM) and lumen cross-sectional area (LA) were measured. Plaque area (PA) was calculated as EEM minus LA. Differences between pre- and post-LA (ΔLA), EEM (ΔEEM) and PA (ΔPA) were calculated. ResultsPre-interventional PA (diabetic patients: 12.4 ± 4.4 mm2 compared with non-diabetic patients: 10.7 ± 3.6 mm2, P = 0.04) and pre-interventional EEM (15.5 ± 4.4 mm2 compared with 13.6 ± 3.7 mm2 respectively, P = 0.02) were larger in the diabetic group. Postinterventional PA (10.2 ± 3.2 mm2 compared with 8.0 ± 3.4 mm2, P = 0.004) was also larger and postinterventional LA (6.3 ± 2.2 mm2 compared with 7.4 ± 2.4 mm2 P = 0.04), ΔEEM (0.9 ± 1.8 mm2 compared with 1.8 ± 1.8 mm2 P = 0.04) and ΔLA (3.1 ± 1.6 mm2 compared with 4.2 ± 2.2 mm2, P = 0.03) were smaller in the diabetic group. The diabetic group exhibited longer lesion lengths (P = 0.04) and a higher inflation pressure was used during revascularization in this patient cohort (P = 0.02). ConclusionDiabetic patients have less reduction of PA during revascularization and because the vessel wall cannot be stretched outwards despite higher inflation pressure, postinterventional LA remains smaller than in the non-diabetic population cohort. This might be a rudiment for consideration of different treatment strategies such as cutting balloon or atherectomy prior to stenting in this population group in order to achieve better procedural outcome.

Time course of prothrombotic and proinflammatory substance release after intracoronary stent implantation

We hypothesized that restenosis after coronary stenting is predicted by elevated levels of markers of thrombus formation and inflammation. Plasma levels of representative markers of inflammation, the thrombin and plasmin activation systems and adhesion molecules were measured in 59 patients with stable angina pectoris before, immediately after and 6 hours (h), 12 h, 24 h, one month and six months after elective stent implantation (radioactive phosphorus-32 stents/RSs/ n = 16, bare-metal stents/BMSs/ n = 43). All patients underwent clinical and angiographic follow-up (FUP) six months after stenting. RSs had significantly higher angiographic severity of restenosis than BMSs (47.1 +/- 20.1% vs. 27.6 +/- 22.0%, p = 0.003). Repeated measures ANOVA revealed significant differences between the BMS and RS groups as regards the increases in plasma levels of vascular cell adhesion molecule-1 (VCAM-1, p = 0.022), plasminogen activator inhibitor-1 (PAI-1, p = 0.047), tissue-type plasminogen activator (tPA, p = 0.047) and CD40 ligand (CD40L, p = 0.038). tPA levels tended to increase immediately after stenting in both groups, whereas the PAI-1 level one month after stenting was elevated significantly only in the RS group. In the RS group, the plasma levels of CD40L were increased at 24 h and six months after stenting, and the VCAM-1 level rose immediately after stenting and remained high during the FUP. Multivariate analysis on pooled laboratory data of both groups revealed elevated levels of VCAM-1 at 12 h and at six months as significant predictors of the severity of stent restenosis. In conclusion, the process of inflammation and thrombosis occurring after coronary interventions seems to be prolonged and enhanced in patients with high-grade restenosis at the follow up.

Amino-Terminal Pro-B-Type Brain Natriuretic Peptide: Screening for Cardiovascular Disease in the Setting of Alcoholism

AIMS N-terminal pro-BNP (NtBNP) has attracted attention as a biomarker for heart failure. The aims of our study are (a) to characterize the role of NtBNP as a biological marker in the setting of alcoholism; (b) to describe potential gender differences with respect to NtBNP; (c) to correlate NtBNP with other clinical and haemodynamic variables. METHODS We examined 83 alcohol-dependent patients according to International Classification of Disease 10th Revision (ICD-10) and Diagnostic and Statistical Manual of Mental Disorders Fourth Edition (DSM-IV; 59 males and 24 females, age: 50 ± 10.5 years) referred to the department of psychiatry for alcohol withdrawal therapy. In these patients, we determined NtBNP, markers of alcohol abuse and transthoracic echocardiography to determine systolic left ventricular ejection fraction (EF). These measurements were repeated after alcohol withdrawal. RESULTS At Day 1 of alcohol withdrawal, 43 patients (52%; 27 males and 16 females) had elevated NtBNP levels (394.4 ± 438.7 pg/ml) despite normal EF (64.7 ± 6.2%). After withdrawal therapy (16.6 ± 7.8 days), NtBNP decreased significantly (228.6 ± 251.2 pg/ml; P < 0.01), despite unchanged EF (65.0 ± 5.8%; P = ns). This was the case in both males and females (328.9 ± 235.5 to 216.7 ± 194.3 pg/ml; P < 0.05 vs. 492.7 ± 635.7 to 246.6 ± 327.7 pg/ml; P < 0.05). Elevated NtBNP levels were related significantly to the history of arterial hypertension (P < 0.05). CONCLUSION This study highlights the fact that NtBNP can be elevated in the setting of alcoholism. The elevation in NtBNP is unrelated to EF and is reversible after alcohol withdrawal. We suggest a subclinical detrimental effect of alcohol abuse on cardiac function.

Long-Term Outcome of Combined (Percutaneous Intramyocardial and Intracoronary) Application of Autologous Bone Marrow Mononuclear Cells Post Myocardial Infarction: The 5-Year MYSTAR Study.

Objective The long-term (5-year) outcome of early (3–6 weeks after acute myocardial infarction [AMI], BM-MNC Early group) and late (3–4 months after AMI, BM-MNC Late group) combined (percutaneous intramyocardial and intracoronary) delivery of autologous bone marrow mononuclear cells (BM-MNCs) was evaluated in patients with ejection fractions (EF) between 30–45% post-AMI. Methods Major adverse cardiac and cerebrovascular events (MACCE) and hospitalization were recorded. Left (LV) and right (RV) ventricular function were measured by transthoracic echocardiography. Cardiac magnetic resonance imaging (MRI) and myocardial single photon emission computed tomography was performed in a subgroup of patients. Pre-cell therapy myocardial voltage values of treated areas (assessed by NOGA mapping) were correlated with clinical outcome. Results Five-year MACCE incidences (7.4%. vs 24.1%) and the composite of all adverse events (11.1% vs 27.6%) were not different between the Early and Late treatment groups. The significant LV-EF increase at 1-year follow-up was preserved at the 5-year control (from baseline to 5-year: 5.3%, 95% CI:0.5–10.1, and 5.7%, 95% CI:1.7–9.6, p<0.05 in the Early and Late groups, respectively), with no significant changes between 1- and 5-year follow-ups. Similarly, RVEF increased significantly from baseline to the 5-year follow-up (Early group: 5.4%, 95% CI:1.0–9.6; and Late group: 8.4%, 95% CI:4.5–12.3). Lower baseline levels of myocardial viability of the treated cardiac area (6.3±2.4 vs 8.2±3.0 mV, p<0.05) were associated with incidence of MACCE. Conclusions Percutaneous combined delivery of autologous BM-MNCs is feasible and safe after 5 years, and may result in sustained improvement of cardiac function at 5 years in patients with low EF post-AMI (Clinicaltrials.gov NCT01395212).

Preclinical randomised safety, efficacy and physiologic study of the silicon dioxide inert-coated Axetis and bare metal stent: short-, mid- and long-term outcome.

AIMS To evaluate the short-, mid- and long-term safety, efficacy and vascular physiology of Axetis silicon dioxide (SiO2, abrading the micropores) inert-coated stent implantation in a randomised preclinical setting. METHODS AND RESULTS Coronary arteries of domestic pigs were randomised to receive either Axetis or BMS (same design) stents with one-, three- and six-month follow-up (FUP), controlled by coronary angiography, optical coherence tomography (OCT), intravascular ultrasound (IVUS) and histology (n=32). The time-dependent vasomotor reaction of coronary arteries to stenting was measured using modified myography (n=12). Complete endothelialisation of the Axetis stent was confirmed by OCT, IVUS and histology at one-month FUP. Histopathology revealed continuous healing of the vessel wall with a gradual reduction of inflammation and fibrin score during the six-month FUP in both stent types. Significantly smaller neointimal area and %area stenosis were measured in Axetis stents compared with BMS at each FUP time point. Vascular reactivity measurements showed significantly better endothelium-dependent vasodilation of stented arteries with Axetis implantation. CONCLUSIONS Implantation of the Axetis SiO2-coated stent resulted in a significantly better safety, efficacy and vessel physiology profile compared with BMS of the same design with a continuous decrease in vessel inflammation during the six-month FUP.

Assessment of the Safety and Efficacy of the Novel Tetrapeptide ITF-1697 on Infarct Size after Primary PTCA in Acute Myocardial Infarction

AbstractObjective and design:ITF-1697 is a chemically modified LYS-Pro tetrapeptide that corresponds to sequence 113–116 of C-reactive protein. Previous studies have demonstrated significant anti-ischaemic and antithrombotic activity of this tetrapeptide. The aim of this prospective, randomised, double-blind study in patients with acute myocardial infarction undergoing coronary revascularisation was to investigate the safety and efficacy of prolonged intravenous (IV) infusion of ITF-1697 at different doses on reduction of infarct size, as assessed by radionuclide imaging. Patients and methods:Injection of technetium-99m (Tc99m) was followed by injection of ITF-1697 or placebo bolus and 24-hour infusion in patients with acute myocardial infarction. Percutaneous transluminal coronary angioplasty (PTCA) was performed and succeeded by radionuclide imaging. A second Tc99m injection and radionuclide imaging was performed 7 days after the PTCA or at hospital discharge. The primary efficacy variable was set as the ratio between the myocardial salvage (size of the initial perfusion defect minus the final size of the infarct) and the initial area at risk (myocardial salvage index). Twenty-three patients were included in the study protocol, of whom nine were randomised to the ITF-1967 dose 1 group (loading dose 55 μg/kg IV, infusion 0.5 μg/kg/min for 24 hours), a further nine to the ITF-1697 dose 2 group (loading dose 110 μg/kg IV, infusion 1.0 μg/kg/min for 24 hours), and the remaining five to the placebo group. Results: The defined safety variables (adverse events, laboratory parameters, vital signs and clinical outcome) exhibited no relationship to the application of ITF-1697. Comparison of myocardial salvage index revealed no statistical difference within the three groups (p = 0.65). Hypothesis testing on the myocardial salvage as well as the empirical and bias-correct confidence intervals (CIs) revealed significant differences between the ITF-1697 dose 2 group and the placebo group (95% CI 2.75, 18.07). Conclusion: The application of the tetrapeptide ITF-1697 during acute myocardial infarction to reduce infarct size was found to be feasible and safe in this pilot trial.