Thorsten Nusser

Pioglitazone Reduces Neointima Volume After Coronary Stent Implantation A Randomized, Placebo-Controlled, Double-Blind Trial in Nondiabetic Patients

Background— Restenosis requiring reintervention limits the long-term success after coronary stent implantation. Thiazolidinediones, like pioglitazone or rosiglitazone, are oral antidiabetic drugs with additional antirestenotic properties. In a randomized, placebo-controlled, double-blind trial, we examined the effect of 6-month pioglitazone therapy on neointima volume after coronary stenting in nondiabetic coronary artery disease patients. Methods and Results— Fifty nondiabetic patients after coronary stent implantation were randomly assigned to pioglitazone (30 mg daily; pio) or placebo (control) treatment in addition to standard therapy, and neointima volume was assessed by intravascular ultrasound at the 6-month follow-up. Both groups were comparable with regard to baseline characteristics, angiographic lesion morphology, target vessel, and length of the stented segment. In addition, there were no statistical differences in minimal lumen diameter before and after intervention, as well as reference diameter after stent implantation. In this study population of nondiabetic patients, pio treatment did not significantly change fasting blood glucose, fasting insulin, or glycosylated hemoglobin levels, as well as lipid parameters. In contrast, pio treatment significantly reduced neointima volume within the stented segment, with 2.3±1.1 mm3/mm in the pio group versus 3.1±1.6 mm3/mm in controls (P=0.04). Total plaque volume (adventitia-lumen area) was significantly lower at follow-up in the pio group (11.2±3.2 mm3/mm) compared with controls (13.2±4.2 mm3/mm; P=0.04). Moreover, the binary restenosis rate was 3.4% in the pio group versus 32.3% in controls (P<0.01). Conclusions— Thus, 6-month treatment with pio significantly reduced neointima volume after coronary stent implantation in nondiabetic patients. These data bolster the hypothesis that antidiabetic thiazolidinediones, in addition to their metabolic effects, exhibit direct antirestenotic effects in the vasculature.

Reduction of Major Adverse Cardiac Events With Intracoronary Compared With Intravenous Bolus Application of Abciximab in Patients With Acute Myocardial Infarction or Unstable Angina Undergoing Coronary Angioplasty

Background—In patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty, abciximab reduces major adverse cardiac events (MACE). Clinical trials have studied intravenous administration only. Intracoronary bolus application of abciximab causes very high local drug concentrations and may be more effective. We studied whether intracoronary bolus administration of abciximab is associated with a reduced MACE rate compared with the standard intravenous bolus application. Methods and Results—We stratified 403 consecutive patients with acute myocardial infarction or unstable angina undergoing coronary angioplasty according to the type of application of abciximab. A 20-mg bolus of abciximab was given intravenously in 109 patients and intracoronarily in 294 patients. There were no differences between the groups with regard to diabetes mellitus, cardiogenic shock, successful intervention, or preprocedural and postprocedural TIMI flow. At 30 days, the incidence of MACE (death, myocardial infarction, urgent revascularization) was significantly lower in the patients with intracoronary compared with intravenous administration of abciximab (10.2% versus 20.2%;P <0.008), which was independent from stenting in multivariate analysis. The effect was most pronounced in patients with preprocedural TIMI 0/1 flow (MACE: intracoronary 11.8% versus intravenous 27.5%, P <0.002; n=273). Conclusions—In patients with acute myocardial infarction or unstable angina undergoing emergency coronary angioplasty, intracoronary bolus application of abciximab is associated with a reduction of MACE compared with the standard intravenous bolus application of abciximab. Prospective, randomized trials are warranted to further assess intracoronary application of abciximab.

Results of Intracoronary Stem Cell Therapy After Acute Myocardial Infarction

To assess the effect of autologous bone-marrow cell (BMC) therapy in patients with acute myocardial infarction in a rigorous double-blind, randomized, placebo-controlled trial. Patients with reperfusion >6 hours after symptom onset were randomly assigned in a 2:1 ratio to receive intracoronary BMC or placebo therapy 5 to 7 days after symptom onset. The patients were stratified according to age, acute myocardial infarction localization, and left ventricular (LV) function. Rigorous double-blinding was ensured using autologous erythrocytes for the placebo preparation that was visually indistinguishable from the active treatment. Serial cardiac magnetic resonance imaging studies were performed before study therapy and after 1, 3, and 6 months. The primary end point was the difference in the LV ejection fraction from baseline to 6 months. The secondary end points included changes in the LV end-diastolic and end-systolic volume indexes and infarct size. A total of 42 patients were enrolled (29 in the BMC group and 13 in the placebo group) in the integrated pilot phase. A mean of 381 x 10(6) mononuclear BMCs were administered. The baseline clinical and cardiac magnetic resonance imaging parameters did not differ. Compared to baseline, the difference in LV ejection fraction for the placebo group versus BMC group was 1.7 +/- 6.4% versus -0.9 +/- 5.5% at 1 month, 3.1 +/- 6.0% versus 1.9 +/- 4.3% at 3 months, and 5.7 +/- 8.4% versus 1.8 +/- 5.3% at 6 months (primary end point; not significant). No difference was found in the secondary end points between the 2 groups, including changes in infarct size or LV end-diastolic and end-systolic volume indexes. In conclusion, in this rigorous double-blind, randomized, placebo-controlled trial, we did not observe an evidence for a positive effect for intracoronary BMC versus placebo therapy with respect to LV ejection fraction, LV volume indexes, or infarct size.

Comparison of the slow-release polymerbased paclitaxel-eluting Taxus-Express stent with the bare-metal Express stent for saphenous vein graft interventions

SummaryBackgroundThe paclitaxel-eluting Taxus-Express stent is superior regarding angiographic and clinical outcome compared with its bare-metal platform for lesions in native coronary arteries. We studied the potential impact of the Taxus-Express stent in comparison with its bare-metal counterpart for treatment of lesions in saphenous vein grafts (SVGs). Furthermore, a metaanalysis was performed regarding use of drug-eluting (DES) vs bare-metal stents (BMS) in SVG lesions.MethodsWe analyzed 13 consecutive patients who underwent percutaneous revascularization in SVG lesions using the slowrelease, paclitaxel-eluting Taxus- Express stent. These lesions were balanced with 26 patients with SVG lesions treated with the baremetal Express stent (BMS) in the preceding period. Angiographic follow-up was performed after 6 months, clinical follow-up after 6 and 12 months.ResultsThere were no statistically significant differences regarding clinical, procedural and angiographic parameters pre and post intervention. Binary restenoses occurred significantly less in the Taxus group compared with the BMS group (0% vs 34.6%; p=0.016). This translated into a significantly lower occurrence of major adverse cardiac events (death, Q-wave myocardial infarction, repeat target vessel revascularization) in the Taxus group compared with the BMS group at the 6-month (0% vs 26.9%, p=0.039) and 12-month follow-up (7.7% vs 38.5%, p=0.045). Multivariate predictors for freedom of binary restenosis were the reference diameter pre intervention and treatment with Taxus stents. Metaanalysis including 280 DES and 256 BMS patients revealed an odds ratio of 0.34 (95% confidence interval 0.21–0.54) for MACE and 0.26 (95% confidence interval 0.16–0.44) for target vessel revascularizations, both favoring DES.ConclusionsWe conclude that the use of the slow-release Taxus-Express stent has the potential to be superior regarding angiographic and clinical outcome compared with its bare-metal counterpart for treatment of SVG lesions within a 12-month follow-up. A large, randomized trial including a long follow-up period is now required to prove the results of the metaanalysis.

Myocardial biopsy findings and gadolinium enhanced cardiovascular magnetic resonance in dilated cardiomyopathy

In some patients suffering from dilated cardiomyopathy (DCM) magnetic resonance imaging (MRI) shows late gadolinium enhancement with variable distribution. Myocardial biopsies in DCM reveal a chronic myocardial inflammatory process in almost 50% and myocardial persistence of adenoviral or enteroviral genome in about 15% of the patients.

Assessment of myocardial perfusion for detection of coronary artery stenoses by steady-state, free-precession magnetic resonance first-pass imaging.

Objective: To evaluate the diagnostic impact of magnetic resonance imaging (MRI) first-pass perfusion using steady-state, free-precession (SSFP) sequences with parallel imaging (SENSE) for detection of coronary stenoses. Design: Prospective observational study. Setting: University hospital, cardiac MRI and catheterisation laboratories. Patients and methods: 228 patients were examined with coronary angiography and MRI (1.5 T Intera CV). A three-slice, short-axis SSFP perfusion scan with a saturation prepulse was performed during infusion of adenosine and at rest followed by myocardial scar (late enhancement) imaging. Gadolinium-DTPA was given at 0.1 mmol/kg body weight. Perfusion images were visually assessed. Analysis for myocardial hypoperfusion was done according to patient group and according to vessel. Results: Sensitivity, specificity and accuracy of MRI first-pass perfusion for detection of a coronary artery stenosis (>50% luminal narrowing) in the total patient group were 93.0%, 85.7%, 91.2% and for a significant lesion (>70% luminal narrowing) 96.1%, 72.0%, 88.2%, respectively. Based on 536 coronary artery territories without myocardial scar, the sensitivity of MRI perfusion analysis for detection of a significant lesion was for the left anterior descending artery 91.4%, for the circumflex artery 81.6% and for the right coronary artery 65.1% (p<0.001). Conclusions: MRI first-pass perfusion analysis using an SSFP sequence with three myocardial slices was a highly accurate diagnostic method for detection of coronary artery stenoses. This MRI technique can be included in daily practice and has the potential to guide the indication for invasive coronary angiography.

Intracoronary β-irradiation with a rhenium-188-filled balloon catheter: a randomized trial in patients with de novo and restenotic lesions ☆

Background Restenosis requiring reintervention is the main limitation of coronary angioplasty. Intracoronary irradiation reduces neointimal proliferation. We studied the efficacy of a self‐centering liquid rhenium‐188‐filled balloon catheter for coronary &bgr;‐brachytherapy. Methods and Results After successful coronary angioplasty with or without stenting, 225 patients (71% de novo lesions) were randomly assigned to receive 22.5 Gy intravascular &bgr;‐irradiation in 0.5‐mm tissue depth (n=113) or to receive no additional intervention (n=112). Clinical and procedural data did not differ between the groups except a higher rate of stenting in the control group (63%) compared with the rhenium‐188 group (45%, P<0.02). After 6 months of follow‐up, late loss was significantly lower in the irradiated group compared with the control group, both of the target lesion (0.11±0.54 versus 0.69±0.81 mm, P<0.0001) and of the total segment (0.22±0.67 versus 0.70±0.82 mm, P<0.0001). This was also evident in the subgroup of patients with de novo lesions and independent from stenting. Binary restenosis rates were significantly lower at the target lesion (6.3% versus 27.5%, P<0.0001) and of the total segment (12.6% versus 28.6%, P<0.007) after rhenium‐188 brachytherapy compared with the control group. Target vessel revascularization rate was significantly lower in the rhenium‐188 (6.3%) compared with the control group (19.8%, P=0.006). Conclusions Intracoronary &bgr;‐brachytherapy with a rhenium‐188 liquid‐filled balloon is safe and efficiently reduces restenosis and revascularization rates after coronary angioplasty. (Circulation. 2003;107:3022‐3027.)

Catheter-Based Delivery of Fluid Paclitaxel for Prevention of Restenosis in Native Coronary Artery Lesions After Stent Implantation

BACKGROUND Stents eluting antiproliferative drugs reduce the incidence of restenosis but delay healing of the vascular wall. We assessed the safety and efficacy of catheter-based local delivery of fluid paclitaxel in patients with coronary de novo stenoses after implantation of a bare metal stent. METHODS AND RESULTS We conducted a prospective, randomized trial comparing the local delivery of fluid paclitaxel after bare metal stent implantation (group I) with the implantation of a bare metal stent (group II) and the implantation of a paclitaxel-eluting stent (group III) in 204 patients. The primary end point was in-stent late lumen loss. Secondary end points included binary restenosis rate >50%, minimal lumen diameter, diameter stenosis, and a composite clinical end point (major adverse cardiac events and revascularization of the target lesion) 6 months after intervention. At 6 months, angiography showed an in-stent late lumen loss of 0.61+/-0.44 mm in group I versus 0.99+/-0.72 mm in group II (I versus II, P=0.0006) and 0.44+/-0.48 mm in group III (noninferiority of I versus III, P=0.023). The 1-sided 95% CI for the true difference of the means of in-stent late lumen loss in groups I and III was -infinity to 0.3174188. The cumulative overall rate of major cardiac events was 13.4% in group I, 26.8% in group II, and 14.9% in group III. Target lesion revascularization rate was 13.4% (group I), 22.1% (group II), and 13.4% (group III). CONCLUSIONS Additional antiproliferative treatment of de novo lesions in native coronary arteries with catheter-based delivery of fluid paclitaxel after bare metal stenting was safe and significantly reduced neointimal proliferation, restenosis, and clinical events compared with bare metal stent implantation alone.

Myocardial Perfusion Reserve in Cardiovascular Magnetic Resonance: Correlation to Coronary Microvascular Dysfunction

The present study examined the association of myocardial perfusion reserve index (MPRI) in cardiovascular magnetic resonance (CMR) with coronary microvascular dysfunction (CMD) and serum levels of markers of inflammation or endothelial activation. Twelve patients with typical angina pectoris without coronary artery disease were enrolled in this study, and CMR perfusion was analyzed using a steady-state-free-precession sequence with 3 short axis slices per heartbeat during first pass of 0.025 mmol Gadolinium-DTPA/kg body weight. The upslope of myocardial signal intensity curves was used to calculate MPRI. CMD was assessed by intracoronary Doppler flow measurement and biplane angiography. Both MPRI and CMD were assessed during endothelium-independent stimulation with intravenous adenosine and during endothelium-dependent stimulation with intracoronary infusion of acetylcholine. Serum values of soluble CD40 ligand (sCD40L), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), soluble intercellular adhesion molecule-1 (sICAM-1), and C-reactive protein (CRP) were measured. Impaired MPRI correlated significantly with a decrease in coronary blood flow reserve after both endothelium-dependent (p = 0.033) and endothelium-independent (p = 0.022) stimulation. Serum levels above the median of all normal ranged biomarkers sCD40L, TNF-alpha, IL-6, sICAM-1 and CRP were associated with an impaired MPRI for stimulation with adenosine as well as acetylcholine. In multivariable analyses, sCD40L (p < 0.001) and TNF-alpha (p = 0.011) were significantly associated with a decrease in MPRI on adenosine, as were TNF-alpha (p = 0.016) and sICAM-1 (p = 0.022) for a decrease in MPRI on acetylcholine. MPRI on adenosine significantly correlated with MPRI on acetylcholine (p < 0.001). Therefore, the present study demonstrates safety and feasibility of an intracoronary infusion of acetylcholine during CMR perfusion analysis, thus allowing direct assessment of endothelial dependent vasomotor function at the myocardial level by CMR. Furthermore, we show that an impaired myocardial perfusion reserved in CMR is associated with established biomarkers of early atherosclerosis and significantly correlated with CMD. CMR combined with adenosine could be proposed as a non-invasive tool to evaluate CMD.

Magnetic resonance imaging to assess acute changes in atrial and ventricular parameters after transcatheter closure of atrial septal defects

To evaluate acute changes in atrial and ventricular parameters by the use of cardiac magnetic resonance imaging (MRI) in patients with percutaneous transcatheter atrial septal defects (ASD) closure.