Martin Höher

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.

A randomized trial of elective stenting after balloon recanalization of chronic total occlusions

OBJECTIVES The aim of this study was to assess the role of Wiktor stent implantation after recanalization of chronic total coronary occlusions with regard to the clinical and angiographic outcome after six months. BACKGROUND Beside the common use of stents in clinical practice, the number of stent indications proven by randomized trials is still limited. METHODS Eighty-five patients with a thrombolysis in myocardial infarction grade 0 chronic coronary occlusion were examined. After standard balloon angioplasty, the patients were randomly assigned to stent implantation, or percutaneous transluminal coronary angioplasty (PTCA) alone (no further intervention). Quantitative coronary angiography was performed at baseline and after six months. RESULTS The minimal lumen diameter did not differ immediately after recanalization (stent group 1.61 +/- 0.30 mm vs. PTCA group 1.65 +/- 0.36 mm), and increased after stent implantation to 2.51 +/- 0.41 mm. After six months, the stent group still had a significantly greater lumen (1.57 +/- 0.59 vs. 1.06 +/- 0.90 mm; p < 0.01) and a significantly lower restenosis and reocclusion rate (32% and 3%) compared with the PTCA group (64% and 24%); restenosis analysis according to treatment was 72% (PTCA) versus 29% (stent, p < 0.01). Late loss was equal in both groups. At follow-up, the stent patients had a better angina class (p < 0.01), and fewer cardiac events (p < 0.03). A meta-analysis including this trial and three other controlled trials with the Palmaz-Schatz stent showed concordant results. CONCLUSIONS Stent implantation after reopening of a chronic total occlusion provides a better angiographic result, corresponding to a better clinical outcome with fewer recurrence of symptoms and reinterventions after six months.

Intracoronary β-Irradiation With a Liquid 188Re-Filled Balloon Six-Month Results From a Clinical Safety and Feasibility Study

Background—Coronary irradiation is a new concept to reduce restenosis. We evaluated the feasibility and safety of intracoronary irradiation with a balloon catheter filled with 188Re, a liquid, high-energy β-emitter. Methods and Results—Irradiation with 15 Gy at 0.5-mm tissue depth was performed in 28 lesions after balloon dilation (n=9) or stenting (n=19). Lesions included 19 de novo stenoses, 4 occlusions, and 5 restenoses. Irradiation time was 515±199 seconds in 1 to 4 fractions. There were no procedural complications. One patient died of noncardiac causes at day 23. One asymptomatic patient refused 6-month angiography. Quantitative angiography after intervention showed a reference diameter of 2.77±0.35 mm and a minimal lumen diameter of 2.36±0.43 mm. At 6-month follow-up, minimal lumen diameter was 1.45±0.88 mm (late loss index 0.57). Target lesion restenosis rate (>50% in diameter) was low (12%; 3 of 26). In addition, we observed 9 stenoses at the proximal or distal end of the irradiation zone, potent...

Corticosteroid agents inhibit proliferation of smooth muscle cells from human atherosclerotic arteries in vitro.

We studied the in vitro effect of steroid agents on smooth muscle cells from human atherosclerotic arteries. Recent advances in the understanding of the biology of restenosis indicate that restenosis is predominantly caused by a multifactorial stimulation of smooth muscle cell proliferation. Primary stenosing plaque material of 24 patients (aged 63 +/- 14 years) and restenosing plaque material of 7 patients (aged 65 +/- 9 years) was selectively extracted from femoral arteries by the Simpson atherectomy device. Cells were isolated by enzymatic disaggregation and identified as smooth muscle cells by positive reaction with smooth muscle alpha-actin. The steroid agents prednisolone (0.0075-750 micrograms/ml), hydrocortisone (0.0125-1250 micrograms/ml), and dexamethasone (0.0004-40 micrograms/ml) were added to the cultures. Six days after seeding the cells were trypsinized and the cell number was measured by a cell counter. All three steroid agents exhibited a significant antiproliferative effect on smooth muscle cell proliferation. At high concentrations of hydrocortisone, cytoskeletal elements of smooth muscle cells such as actin, microtubules, and vimentin, were largely altered. Our data indicate that the proliferation of smooth muscle cells from human atherosclerotic arteries in vitro can be inhibited by steroid agents and thus may open the way for local post-angioplasty treatment strategies.

The future of cardiovascular imaging and non-invasive diagnosis A joint statement from the European Association of Echocardiography, the Working Groups on Cardiovascular Magnetic Resonance, Computers in Cardiology, and Nuclear Cardiology of the European Society of Cardiology, the European Association of Nuclear Medicine and the Association for European Paediatric Cardiology

Advances in medical imaging now make it possible to investigate any patient with cardiovascular disease using multiple methods which vary widely in their technical requirements, benefits, limitations, and costs. The appropriate use of alternative tests requires their integration into joint clinical diagnostic services where experts in all methods collaborate. This statement summarises the principles that should guide developments in cardiovascular diagnostic services.

Complement and Dilated Cardiomyopathy: A Role of Sublytic Terminal Complement Complex-Induced Tumor Necrosis Factor-α Synthesis in Cardiac Myocytes

Dilated cardiomyopathy is a syndrome characterized by cardiac enlargement and impaired systolic function of the heart. Tumor necrosis factor (TNF)-alpha, a pleiotropic cytokine, seems to play a central role in the progression of dilated cardiomyopathy. Recent data suggest that ongoing inflammation in the myocardium may, in many cases, contribute to the development of disease. Chronic generation of autoantibodies to myocardial antigens or, in some cases, viral infection are pathobiologically involved. Although both antibodies and some viruses activate the complement system, the role of innate immunity in dilated cardiomyopathy has as yet not been investigated systematically. In this study we demonstrate by analysis of myocardial biopsies from 28 patients that C5b-9, the terminal membrane attack complex of complement, accumulates in human myocardium in dilated cardiomyopathy. C5b-9 significantly correlates with immunoglobulin deposition and myocardial expression of TNF-alpha. In vitro, C5b-9 attack on cardiac myocytes induces nuclear factor (NF)-kappaB activation as well as transcription, synthesis, and secretion of TNF-alpha. We conclude that chronic immunoglobulin-mediated complement activation in the myocardium may contribute in part to the progression of dilated cardiomyopathy via C5b-9-induced TNF-alpha expression in cardiac myocytes.

Endovascular brachytherapy for the prevention of restenosis after angioplasty.

Abstract.Restenosis is an unsolved clinical and financial limitation of angioplasty. Local irradiation is a new approach for the reduction of restenosis. Several animal studies have demonstrated the effective inhibition of arterial neointimal proliferation by percutaneous or endovascular irradiation. High-dose-rate irradiation from gamma and beta sources can be applied from radioactive wires or seeds and from liquid beta-emitter-filled balloon catheters. Dosimetric calculations have been performed for all relevant radionuclides. An effective dose can be applied within 10 min to the treated arteries. Beta-emitters are characterized by a low tissue penetration, which simplifies radiation protection but complicates the achievement of a homogeneous dose distribution without centring of the irradiation source. Gamma-emitters are characterized by deep tissue penetration and delivery of almost the same dose to all vessel layers; however, considerable care with regard to radiation protection of the environment is required if gamma-emitters are used. The liquid-filled balloon ensures a homogeneous dose delivery due to the self-centring irradiation source but entails the possibility of radioactivity incorporation in the event of balloon rupture. The most attractive radionuclide for this purpose is rhenium-188, which is available from the 188W/188Re generator system. Radiation exposure after accidental incorporation can be limited by chelation with mercaptoacetyltriglycine or by subsequent oral administration of perchlorate. Initial clinical trials have demonstrated the feasibility of the various irradiation techniques and yielded encouraging results. The use of unsealed radioactivity in a balloon catheter involves the nuclear medicine physician in this new field of therapy. This review discusses the concepts, the radiotracers and the results of animal experiments and early clinical trials in the field of endovascular irradiation employed as a possible means to prevent restenosis after angioplasty.

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.)

De-noising of high-resolution ECG signals by combining the discrete wavelet transform with the Wiener filter

In this study the authors applied a combination of the discrete wavelet transform and the Wiener filter to the noise-reduction of high-resolution ECG signals. The procedure is optimal in the least squares sense in that it separates a signal from additive noise. It was compared to a popular de-noising algorithm by Donoho (1993) on artificially generated signals and on a high-resolution ECG signal corrupted by noise.