Publications by authors named "Karl Theisen"

28 Publications

  • Page 1 of 1

Sirolimus-eluting stent implantation versus beta-irradiation for the treatment of in-stent restenotic lesions: clinical and ultrasound results from a randomised trial.

EuroIntervention 2011 Jan;6(6):687-94

Department of Cardiology, Heart and Diabetes Center North Rhine-Westphalia, Bad Oeynhausen, Germany.

Aims: Recent trials with different designs indicated that drug-eluting stents may be superior to vascular brachytherapy (VBT) for the treatment of in-stent restenosis (ISR). We performed a randomised, double-centre, clinical, quantitative coronary angiographic (QCA) and intravascular ultrasound (IVUS) acute and 3-years comparison of 90Sr/90Y-VBT and sirolimus-eluting stent implantation (SES) for ISR.

Methods And Results: Ninety-one (91) consecutive patients were included. By QCA, SES led to a higher acute gain (2.08 ± 0.41 mm vs. 1.54 ± 0.70 mm, p < 0.0001), higher postprocedural minimum lumen diameter (2.76 ± 0.39 mm vs. 2.39 ± 0.52 mm; p < 0.0001), lower late lumen loss at follow-up (0.09 ± 0.29 vs. 0.39 ± 0.79 mm, p = 0.042), and a higher net lumen gain of the target lesion (2.05 ± 0.51 vs 1.18 ± 1.08 mm, p < 0.0001). By IVUS, the smaller acute gain following VBT was the result of residual intima hyperplasia, the intima hyperplasia formation following SES was extremely low, and the edge-effect was virtually absent after SES, respectively. At 6-month follow-up, both the angiographic restenosis rate (4.7 vs. 22.7%; p < 0.0001) and target lesion revascularisation rate (2.3 vs. 10.4%; p = 0.025) were lower in SES. Importantly, SES showed a stable clinical course at 3-year follow-up while VBT was associated with a sustained incidence of target vessel failure (11.6 vs. 46.7%; p < 0.0001).

Conclusions: SES for ISR is associated with superior QCA, IVUS and clinical results at 6-month and 3-year of follow-up when compared with VBT.
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http://dx.doi.org/10.4244/EIJV6I6A117DOI Listing
January 2011

Randomized comparison of dexamethasone-eluting stents with bare metal stent implantation in patients with acute coronary syndrome: serial angiographic and sonographic analysis.

Am Heart J 2007 Jun;153(6):979.e1-8

Department of Medicine, Division of Cardiology, Medizinische Klinik und Poliklinik-Innenstadt, Ludwig-Maximilians-Universität, Munich, Germany.

Aims: The aim of this study is to compare the anti-inflammatory effect of the dexamethasone preloaded stent (Dexamet, Abbott, Galway, Ireland) with the bare metal stent (BMS; BiodivYsio, Biocompatibles Cardiovascular LTD, Galway, Ireland) in patients with acute coronary syndrome (ACS) assessed by angiographic (QCA) and intracoronary ultrasound (ICUS).

Methods And Results: One hundred twenty patients with ACS were randomly assigned to revascularization using the Dexamet stent (n = 60) or BMS (n = 60). Serial QCA analysis and ICUS analysis were performed during long-term follow-up (2.9 F; 20 MHz transducer; Volcano Corp, Brussels, Belgium). Power calculations were performed for QCA-derived differences of lumen loss. In addition, statistical analysis was performed (SPSS for Windows 12.0.1). The target lesion revascularization rate was lower in the Dexamet group (10 [16.67%] vs 20 [33.33%] patients; P = .031). The QCA revealed improved lumen restoration in the Dexamet stent group (lumen loss, 0.55 +/- 0.65 vs 1.07 +/- 0.92 mm [P = .001]; loss index, 0.20 +/- 0.23 vs 0.46 +/- 0.42 [P < .001]). The ICUS revealed greater neointimal proliferation in the BMS versus the Dexamet stent group (3.36 +/- 1.03 vs 3.05 +/- 1.38 mm2; P < .001). Death (n = 1) and the number of total occlusions of the stent segment (n = 1) were identical in both groups.

Conclusion: Dexamet stents, in comparison with the BMS stents, reduced the target lesion revascularization rate in patients with ACS and lead to better lumen restoration during long-term follow-up.
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http://dx.doi.org/10.1016/j.ahj.2007.03.032DOI Listing
June 2007

Diagnostic accuracy of optical coherence tomography and intravascular ultrasound for the detection and characterization of atherosclerotic plaque composition in ex-vivo coronary specimens: a comparison with histology.

Coron Artery Dis 2006 Aug;17(5):425-30

Department of Cardiology, Division of Internal Medicine, Institute for Clinical Radiology, University of Munich, Germany, and Department of Radiology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.

Background: Both intravascular ultrasound and optical coherence tomography have been purported to accurately detect and characterize coronary atherosclerotic plaque composition. The aim of our study was to directly compare the reproducibility and diagnostic accuracy of optical coherence tomography and intravascular ultrasound for the detection and characterization of coronary plaque composition ex vivo as compared with histology.

Methods And Results: Intravascular ultrasound (20 MHz) and optical coherence tomography imaging was performed in eight heart specimens using motorized pullback. Standard histology using hematoxylin-eosin and van Gieson staining was performed on 4 mum thick slices. Each slice was divided into quadrants and accurately matched cross-sections were analyzed for the presence of fibrous, lipid-rich, and calcified coronary plaque using standard definitions for both intravascular ultrasound and optical coherence tomography and correlated with histology. After exclusion of 145/468 quadrants, we analyzed the remaining 323 quadrants with excellent image quality in each procedure. Optical coherence tomography demonstrated a sensitivity and specificity of 91/88% for normal wall, 64/88% for fibrous plaque, 77/94% for lipid-rich plaque, and 67/97% for calcified plaque as compared with histology. Intravascular ultrasound demonstrated a sensitivity and specificity of 55/79% for normal wall, 63/59% for fibrous plaque, 10/96% for lipid-rich plaque, and 76/98% for calcified plaque. Both intravascular ultrasound and optical coherence tomography demonstrated excellent intraobserver and interobserver agreement (optical coherence tomography: kappa=0.90, kappa=0.82; intravascular ultrasound: kappa=0.87, kappa=0.86).

Conclusion: Optical coherence tomography is superior to intravascular ultrasound for the detection and characterization of coronary atherosclerotic plaque composition, specifically for the differentiation of noncalcified, lipid-rich, or fibrous plaque.
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http://dx.doi.org/10.1097/00019501-200608000-00005DOI Listing
August 2006

Cardiac magnetic resonance perfusion imaging for the functional assessment of coronary artery disease: a comparison with coronary angiography and fractional flow reserve.

Eur Heart J 2006 Jun 23;27(12):1465-71. Epub 2006 May 23.

Department of Cardiology, Division of Internal Medicine, University of Munich Germany.

Aims: Cardiac magnetic resonance perfusion imaging (CMRI) is a promising technique for non-invasive measurement of myocardial perfusion reserve. Fractional flow reserve (FFR) is an established invasive method for functional assessment of coronary artery disease (CAD). To prospectively assess the diagnostic value of CMRI for the detection of haemodynamically significant coronary lesions, compared with coronary angiography (CA) and FFR.

Methods And Results: Forty-three patients with suspected or known CAD underwent CA, CMRI, and FFR measurement. First pass magnetic resonance perfusion examination was performed during hyperaemia (140 microg/kg/min adenosine over 6 min) and at rest. One hundred and twenty-nine perfusion territories were assessed by semi-quantitative evaluation of signal intensity-time curves using the myocardial perfusion reserve index (MPRI) [upslope(stress(corrected))/upslope(rest(corrected))]. Perfusion territories were categorized as normal (coronary stenosis < or = 50%), intermediate (stenosis > 50% and FFR > 0.75), or severe (stenosis > 50% and FFR < or = 0.75 or total occlusion). MPRI values (+/-SD) were significantly different between the three categories [normal, 2.2 +/- 0.5 vs. intermediate, 1.8 +/- 0.5 (P = 0.005) and intermediate vs. severe, 1.2 +/- 0.3 (P < 0.001)]. An MPRI cut-off value of 1.5 (derived from receiver operating characteristics analysis) distinguished haemodynamically relevant (severe) from non-relevant (normal and intermediate) stenoses with a sensitivity of 88% (CI 74-100%) and a specificity of 90% (CI 84-96%).

Conclusion: In contrast to earlier studies that compared CMRI with morphological examination (CA) alone, the present study compared CMRI with CA plus a standard invasive functional assessment (FFR) and demonstrated that CMRI is able to distinguish haemodynamically relevant from non-relevant coronary lesions with a high sensitivity and specificity and may therefore contribute to clinical decision-making.
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http://dx.doi.org/10.1093/eurheartj/ehl039DOI Listing
June 2006

Comparison of Tc-99m sestamibi SPECT with fractional flow reserve in patients with intermediate coronary artery stenoses.

J Nucl Cardiol 2005 Nov-Dec;12(6):645-54

Department of Nuclear Medicine, University of Munich, Munich, Germany.

Background: Myocardial single photon emission computed tomography (SPECT) is an established noninvasive method for the assessment of the functional significance of coronary artery stenoses. Intracoronary pressure measurements to determine fractional flow reserve (FFR) are increasingly performed during coronary angiography whenever an immediate decision regarding possible intervention is required. We hypothesized that the regional summed difference score (SDSr), reflecting reversible perfusion defects in the myocardial supply area of the FFR target vessel, would be the best predictor of an abnormal FFR in patients without prior myocardial infarction. Otherwise, a regional summed stress score (SSSr) should be the best predictor of an abnormal FFR in patients with prior myocardial infarction for different patient subgroups with coronary artery disease.

Methods And Results: In this study 50 patients (mean age, 65 +/- 9.1 years; 18 women) with coronary artery disease and a 50% to 75% coronary stenosis (target vessel) were prospectively investigated. Dobutamine myocardial SPECT was performed as a single-day stress/rest protocol by use of technetium 99m sestamibi. For image interpretation, semiquantitative analysis was conducted by calculating SSSr and SDSr. Within 8 (+/-14.9) days, coronary angiography was performed and FFR was calculated by use of a pressure wire (normal FFR, > or = 0.75). The mean FFR of all patients was 0.78 +/- 0.14. Of 50 patients, 17 had an FFR lower than 0.75 in the target vessel. Receiver operating characteristic analysis identified an SDSr of 1 or greater and an SSSr of 3 or greater as the best threshold values for predicting ischemic FFR. Sensitivity, specificity, and negative and positive predictive values of SDSr and SSSr for the detection of FFR values lower than 0.75 in the target vessel were 80%, 76%, 53%, and 92%, respectively, and 70%, 93%, 78%, and 90%, respectively, in patients without prior myocardial infarction and 57%, 50%, 67%, and 40%, respectively, and 100%, 50%, 78%, and 100%, respectively, in patients with prior myocardial infarction. Weak correlation was found between the single values of FFR with both SDSr and SSSr for the different patient subgroups.

Conclusion: Among the dobutamine myocardial scintigraphy variables studied, SDSr was the best predictor of an abnormal FFR (cutoff value of 0.75) in patients without prior myocardial infarction. As assumed, SSSr was the best predictor of an abnormal FFR in patients with prior myocardial infarction in the target region.
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http://dx.doi.org/10.1016/j.nuclcard.2005.07.006DOI Listing
January 2006

Three-year clinical follow-up after strontium-90/yttrium-90 beta-irradiation for the treatment of in-stent coronary restenosis.

Am J Cardiol 2005 Nov 30;96(10):1399-403. Epub 2005 Sep 30.

Division of Cardiology, Department of Medicine, Medizinische Klinik und Poliklinik, University Hospital Campus Innenstadt, Munich, Germany.

Because late vessel failure has been speculated as a possible limitation of vascular brachytherapy, we conducted a prospective clinical evaluation at 6, 12, 24, and 36 months of follow-up after irradiation with strontium-90/yttrium-90 for in-stent restenosis, regardless of the patient's symptomatic status. We report complete 3-year follow-up data for 106 consecutive patients. The cumulative rate of death at 6, 12, 24, and 36 months was 0.9%, 0.9%, 0.9%, and 1.9% respectively. The corresponding rates for acute ST-elevation myocardial infarction were 2.8%, 4.7%, 4.7%, and 4.7%, respectively. The cumulative rate of late thrombotic occlusion at 6, 12, 24, and 36 months was 3.8%, 4.7%, 4.7%, and 4.7%, respectively. The corresponding rates of target lesion revascularization and target vessel revascularization were 8.5% and 12.3% (p = 0.046), 14.2% (p = 0.157) and 18.0% (p = 0.046), 12.3% and 18.9% (p = 0.008), and 21.7% (p = 0.083) and 29.2% (p = 0.005), respectively. The cumulative rate of all major adverse cardiovascular events at 6, 12, 24, and 36 months was 16.1%, 24.5% (p = 0.003), 27.4% (p = 0.083), and 35.8% (p = 0.003), respectively. In conclusion, these results indicate a delayed and, even in the third year after the index procedure, continued restenotic process after beta irradiation of in-stent restenotic lesions.
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http://dx.doi.org/10.1016/j.amjcard.2005.06.087DOI Listing
November 2005

Application, feasibility, and efficacy of a combined intravascular ultrasound and stent delivery system: results from a prospective multicenter trial.

J Interv Cardiol 2005 Oct;18(5):367-74

Department of Cardiology, Division of Internal Medicine, University of Munich, Germany.

Background: Intravascular ultrasound (IVUS) is the reference method for in vivo assessment of vessel dimensions and coronary plaque composition, which can influence device selection as well as stent sizing.

Objectives: The objective of this prospective multicenter-study was to test the application, safety, and feasibility of a new combined IVUS and stent delivery system.

Methods: A total of 32 patients with planned direct stent implantation under IVUS guidance were included in the study. Procedural as well as angiographical and IVUS characteristics of the stent implantation with the combined IVUS and stent delivery system were assessed and compared to a historical control cohort where IVUS-guided stenting was performed with a separate IVUS catheter.

Results: Direct stent placement was successfully performed in all patients and no malfunctions of the system were noted. A post-interventional IVUS assessment was possible in 27 (87%) of the 31 patients. The IVUS information led to a change in therapeutic strategy in 16 (50%) of the 32 patients. In the study group, both the procedural time and the amount of contrast dye were significantly lower than in the historical IVUS-guided stenting control group. A clinical 12-month follow-up revealed a 89% event-free survival and a target vessel revascularization rate of 7%.

Conclusion: The use of a combined IVUS and stent delivery device is safe, easy to handle, and can provide helpful additional information to guide a percutaneous coronary interventions procedure. Beyond angiography, these informations had significant impact on the interventional strategy in these patients, which resulted in a low rate of major adverse cardiac events. The concept of combining IVUS information and a stent delivery system may be increasingly attractive with evolving imaging modalities like virtual histology or a combination with drug-eluting stents.
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http://dx.doi.org/10.1111/j.1540-8183.2005.00075.xDOI Listing
October 2005

Sirolimus-eluting stent implantation and beta-irradiation for the treatment of in-stent restenotic lesions: comparison of underlying mechanisms of acute gain and late loss as assessed by volumetric intravascular ultrasound.

Am Heart J 2005 Aug;150(2):351-7

Cardiology Division, Hospital of the Ludwig-Maximilians-University of Munich, Munich, Germany.

Background: The aim of the study was to compare the angioplasty mechanisms of drug (sirolimus)-eluting stent (DES) implantation and vascular brachytherapy (VBT) for the treatment of in-stent restenosis (ISR) as assessed by intravascular ultrasound (IVUS).

Methods: We performed IVUS in 53 patients (28 DES, 25 VBT) before and after angioplasty of ISR and at 6-month follow-up. Cross-sectional areas of the external elastic membrane, the stent, and the lumen were measured. Plaque + media, peristent plaque, and intimal hyperplasia areas were calculated, respectively.

Results: Clinical and IVUS baseline characteristics did not differ between groups at baseline. After the index procedure, the lumen at the stent site was smaller in the DES group (DES 6.7 +/- 2.0 mm2 vs VBT 7.5 +/- 2.2 mm2, P = .042). Because of less intimal hyperplasia (DES 0.2 +/- 0.5 mm2 vs VBT 0.7 +/- 0.7 mm2, P = .043), the lumen dimensions revealed no difference between groups at follow-up (DES 6.5 +/- 2.3 mm2 vs VBT 6.8 +/- 2.2 mm2, P = .374). At the reference site, the index procedure led to a similar increase of plaque + media (DES 0.9 +/- 0.9 mm2 vs VBT 0.6 +/- 1.2 mm2, P = .150). At follow-up, the plaque + media was significantly smaller in the DES group (DES 8.0 +/- 6.6 mm2 vs VBT 9.9 +/- 7.8 mm2, P = .013).

Conclusions: Drug-eluting stent for the treatment of ISR more effectively inhibits neointima formation when compared with VBT. Yet insufficient stent expansion might be a reason for device failure and should be avoided. At the reference site, lumen loss by an increased plaque burden, as has been well recognized following VBT, is not present with DES.
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http://dx.doi.org/10.1016/j.ahj.2004.09.041DOI Listing
August 2005

Comparison of acute and long-term results and underlying mechanisms from sirolimus-eluting stent implantation for the treatment of in-stent restenosis and recurrent in-stent restenosis in patients in whom intracoronary radiation failed as assessed by intravascular ultrasound.

Am J Cardiol 2004 Oct;94(7):917-21

Cardiology Division, Medizinische Poliklinik-Innenstadt, University of Munich, Munich, Germany.

In-stent restenosis (ISR), especially after vascular brachytherapy, is a therapeutic challenge. Sirolimus-eluting stent implantation is a promising new option for the treatment of patients with ISR. The efficacy of sirolimus-eluting stent implantation for the treatment of patients with their first episodes of ISR and with recurrent ISR due to the failure of vascular brachytherapy was compared using intravascular ultrasound imaging.
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http://dx.doi.org/10.1016/j.amjcard.2004.06.028DOI Listing
October 2004

Immediate effects of n-3 fatty acid infusion on the induction of sustained ventricular tachycardia.

Lancet 2004 May;363(9419):1441-2

Kardiologie Medizinische Poliklinik, Klinikum der Universität München, 80336 Munich, Germany.

Increased consumption of n-3 fatty acids reduces mortality from sudden cardiac death, indicating that such acids have anti-arrhythmic effects. We did electrophysiological testing in ten patients with implanted cardioverter defibrillators who were at high risk of sudden cardiac death. To assess their immediate effects on the induction of sustained ventricular tachycardia, n-3 fatty acids were infused. Such tachycardia was not induced in five of seven patients. Our findings show that infusion of n-3 polyunsaturated fatty acids does not induce arrhythmia, but did result in a reduction of sustained ventricular tachycardia in some patients.
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http://dx.doi.org/10.1016/S0140-6736(04)16105-9DOI Listing
May 2004

Evolution of angiographic restenosis rate and late lumen loss after intracoronary beta radiation for in-stent restenotic lesions.

Am J Cardiol 2004 Apr;93(7):836-42

Cardiology Division, Department of Medicine, Medizinische Klinik und Poliklinik-Innenstadt, University Hospital, Munich, Germany.

The aim of this study was to investigate the time course of angiographic restenosis rate and late loss after successful percutaneous coronary intervention and vascular brachytherapy with beta-irradiation using strontium-90/yttrium-90 in 98 patients who were prospectively enrolled into a quantitative angiographic and clinical follow-up protocol at 6, 12, and 24 months after the index procedure, regardless of their symptom status. Actuarial restenosis rates measured 11.2 +/- 5% at 6 months of follow-up, 24.5 +/- 5% at 12 months, and 28.5 +/- 6% at 24 months, respectively. Late loss of the stent segment during the first 6 months measured 0.38 +/- 0.40 mm (6 to 12 months: 0.25 +/- 0.38 mm; 12 to 24 months: 0.16 +/- 0.32 mm), of the injured segment 0.27 +/- 0.21 mm (6 to 12 months: 0.21 +/- 0.26 mm; 12 to 24 months: 0.13 +/- 0.24 mm), of the irradiated segment 0.18 +/- 0.29 mm (6 to 12 months: 0.19 +/- 0.31 mm; 12 to 24 months: 0.11 +/- 0.27 mm), and of the analysis segment 0.18 +/- 0.36 mm (6 to 12 months: 0.17 +/- 0.29 mm; 12 to 24 months: 0.11 +/- 0.20 mm). Restenosis after angioplasty and beta-irradiation of in-stent restenotic lesions is not complete within 6 months but is sustained with a gradual decrease over 24 months.
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http://dx.doi.org/10.1016/j.amjcard.2003.12.020DOI Listing
April 2004

Impact of barotrauma on acute and late angiographic and clinical outcomes following angioplasty and beta-irradiation of coronary in-stent restenotic lesions.

J Invasive Cardiol 2004 Jan;16(1):14-9

Cardiology Division, Medizinische Poliklinik Innenstadt, University Hospital, Munich, Germany.

Introduction: The aim of this study was to prospectively evaluate the impact of different degrees of vessel barotrauma on the acute and 1-year clinical and angiographic outcomes of percutaneous coronary intervention (PCI) and adjunctive vascular brachytherapy (VBT) with 90Sr/90Y for in-stent restenotic lesions (ISR) in 118 patients.

Methods And Results: Sixty consecutive patients were treated according to an aggressive PCI strategy (group 1); fifty-eight were treated non-aggressively (group 2). Irradiation was performed with a manual afterloader. Clinical and angiographic baseline characteristics did not differ between groups. Group 1 yielded a higher acute lumen gain (2.3 +/- 1.2 mm versus 1.7 +/- 1.3 mm; p=0.005) and a higher prevalence of additional stent implantation (48.3% versus 22.4%; p=0.003). At follow-up, net gain (1.8 +/- 0.7 mm versus 1.4 +/- 0.8 mm; p=0.102) was equalized by a higher late loss in group 1 (0.6 +/- 0.8 mm versus 0.3 +/- 0.7 mm; p=0.036). Remaining target vessel late loss, due to edge effects, was considerably higher in group 1 than in group 2 (0.5 +/- 0.8 mm versus 0.2 +/- 0.5 mm; p<0.001), leading to a higher rate of binary angiographic restenosis (23.3% versus 6.9%; p=0.013) and target vessel revascularization (16.7% versus 5.2%; p=0.046). After excluding patients who received additional stents, the angiographic differences between groups were attenuated.

Conclusion: Our study does not support the use of oversized balloons and high inflation pressures for the treatment of ISR when combined with VBT. Additional stent implantation combined with VBT carries a high risk of repeat revascularization in the setting of ISR and should be avoided.
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January 2004

Transcatheter closure of a ruptured ventricular septum following inferior myocardial infarction and cardiogenic shock.

Catheter Cardiovasc Interv 2003 Oct;60(2):224-8

Cardiology Division, Medizinische Poliklinik-Innenstadt, University of Munich, Munich, Germany.

Elective transcatheter closure of congenital septal defects has emerged as a valuable method, but the clinical experience on occlusion of ventricular septal rupture after myocardial infarction is very limited. We report a case of fatal outcome in a patient with inferior myocardial infarction and cardiogenic shock despite technically successful transcatheter closure of a large complex ventricular septal defect.
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http://dx.doi.org/10.1002/ccd.10616DOI Listing
October 2003

Differential regulation of xanthine and NAD(P)H oxidase by hypoxia in human umbilical vein endothelial cells. Role of nitric oxide and adenosine.

Cardiovasc Res 2003 Jun;58(3):638-46

Medizinische Poliklinik Innenstadt, Ludwig-Maximilians-University Munich, Ziemssenstrasse 1, 80336, Munich, Germany.

Objectives: Although in tissue injury following hypoxia/reoxygenation (H/R) an increased endothelial formation of superoxide anions (O(2)(-)) plays an important role, it is still not fully understood which of the potential enzymatic sources of endothelial O(2)(-) are crucially involved. In this study, we particularly examined the activities of NAD(P)H oxidase and xanthine oxidase (XO) after 8 h of exposure to mild hypoxia. We further studied whether enzyme activities can be modified by NO and adenosine during hypoxic treatment.

Methods And Results: In human umbilical vein endothelial cells O(2)(-) production was measured immediately after exposure to hypoxia ('early reoxygenation') or after 2 h of reoxygenation at normoxic conditions ('late reoxygenation'). In the early reoxygenation phase the O(2)(-) production was attenuated by 28.5% while it was enhanced by 58.2% after late reoxygenation. Using specific inhibitors of NAD(P)H oxidase and XO, gp91ds-tat and oxypurinol, respectively, we show that the constitutively active NAD(P)H oxidase was blocked following hypoxia while XO was activated. The presence of NO during hypoxia had no effect on NAD(P)H oxidase activity but it significantly inhibited the activation of XO. Inhibition of XO activation was, at least in part, caused by the release of adenosine from endothelial cells which induces an increased formation of NO by its A1 and A2 receptors.

Conclusion: Our results indicate that during exposure to mild hypoxia for 8 h, a change in the enzymatic source of endothelial O(2)(-) occurs: a prolonged inhibition of NAD(P)H oxidase was found while an enhanced activity of XO occurs in the reoxygenation phase. These results suggest that different strategies of antioxidant therapy should be taken into consideration in oxidative stress related to chronic hypoxia when compared to normoxic atherosclerotic tissues with an activated vascular NAD(P)H oxidase as the main source of O(2)(-).
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http://dx.doi.org/10.1016/s0008-6363(03)00262-1DOI Listing
June 2003

Fractional flow reserve predicts major adverse cardiac events after coronary stent implantation.

Z Kardiol 2002 ;91 Suppl 3:132-6

Dept. of Cardiology, Medizinische Klinik-Innenstadt, University of Munich, Ziemssenstr. 1 80336 Munich, Germany.

Objectives: Determination of fractional flow reserve (FFR) allows the functional assessment of coronary stenoses before and after an intervention. Preliminary data suggest that a FFR > or = 0.94 is associated with an excellent clinical outcome after stent implantation. However, these results were limited both by the number of patients included and the use of non-contemporary stent designs. We sought to determine the prognostic value of FFR measurements in a large patient cohort undergoing coronary stent implantation.

Methods: Eighty-nine consecutive patients were enrolled in whom a stent implantation was performed and a pressure wire was used as a guide wire. Patients were followed for at least 6 months. Death, myocardial infarction (MI) and target vessel revascularization (TVR) were considered cardiac events. A FFR > or = 0.94 was regarded as an optimal functional result.

Results: A complete follow-up was available in all patents. Pre-interventional FFR increased from 0.66 +/- 0.16 to 0.95 +/- 0.05 (p < 0.0001) after stent implantation. Sixteen (18%) events occurred during follow-up including 10 (11.2%) TVR. Final FFR was significantly higher in patients without compared to patients with an event (0.92 +/- 0.06 vs. 0.96 +/- 0.05, p < 0.003). By univariate analysis, the presence of diabetes mellitus, left ventricular function, residual diameter stenosis and final FFR were associated with a worse clinical outcome. In the multivariate analysis, only the final FFR and left ventricular function remained as significant predictors for cardiac events (relative risk, 3.50; 95% CI: 1.29-9.52, P < 0.014, and 0.97; 95% CI: 0.93-1.00, p = 0.047).

Conclusion: These results demonstrate in a nonselected patient cohort a strong correlation between FFR values after coronary stenting and subsequent cardiac events. Further studies have to investigate whether outcome after stenting might be improved by guiding the procedure with a pressure guide wire.
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http://dx.doi.org/10.1007/s00392-002-1324-yDOI Listing
March 2003

Safety of FFR-based treatment strategies: the Munich experience.

Z Kardiol 2002 ;91 Suppl 3:115-9

Medizinische Klinik der Universität München-Innenstadt Ziemssenstr. 1 80336 München, Germany.

Fractional flow reserve (FFR) as a new technique for physiological assessment of coronary stenoses could identify patients with CAD in whom the deferral of an intended PCI was more beneficial than performing the planned procedure. It is up to now unknown whether a FFR-based therapy stratification is also safe in patients with multivessel disease and complex coronary lesions. This study demonstrates in 71 symptomatic patients with predominantly multivessel disease and angiographically intermediate coronary lesions that patients do not benefit from PCI procedures in terms of overall survival, target vessel patency or clinical symptoms during 12 month follow-up if FFR is above 0.75.
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http://dx.doi.org/10.1007/s00392-002-1321-1DOI Listing
March 2003

Influence of stent design and deployment technique on neointima formation and vascular remodeling.

Z Kardiol 2002 ;91 Suppl 3:98-102

Abteilung Kardiologie Medizinische Klinik Klinikum der Ludwig-Maximilians-Universität München-Innenstadt Ziemssenstrasse 1 80336 München, Germany.

A variety of different stent types is available for the treatment of coronary stenosis. However, in-stent restenosis remains the major limitation for the use of these devices. Intracoronary ultrasound (ICUS) in addition to coronary angiography provides precise measurements of coronary wall dimensions during stent implantation and of intimal hyperplasia during follow-up. The extent of coronary injury during stent implantation was shown to play an important role in neointima formation. It is characterized by endothelial exposure, intima laceration, and media permeation. Stent-induced coronary injury has been considered to depend on stent design and stent strut size with consecutive deep wall laceration. ICUS analysis showed a correlation between the stent design and the amount of neointimal tissue proliferation. The role of adventitial remodeling in the process of restenosis is discussed controversially. Post-procedural stent expansion may provoke adventitial remodeling. The stent design and stenting strategy determines the extent of peri- and post-procedural coronary injury. Post-procedural coronary morphologic changes and changes of the stent geometry depend upon the stent design. Beside further modifications as the use of drug-eluting stents the decrease of stent-related vessel injury should be an important criterion for the development of future stent design.
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http://dx.doi.org/10.1007/s00392-002-1317-xDOI Listing
March 2003

Serial intravascular ultrasound analysis after intracoronary beta-radiation in long in-stent restenotic lesions.

Z Kardiol 2002 ;91 Suppl 3:17-22

Medizinische Klinik Klinikum der Ludwig-Maximilians-Universität München-Innenstadt Ziemssenstrasse 1 80336 München, Germany.

In-stent restenosis (ISR) represents the major limitation of stent implantation. Treatment, although of relative technical ease, is unsatisfactory due to the high incidence of recurrent restenosis. Long ISR lesions are especially prone to restenosis. Vascular brachytherapy (VBT) has emerged as a powerful adjunct therapeutic modality to treat ISR. However, VBT may be less effective in very long, diffuse ISR lesions. The present study investigated serial changes of the extent and distribution of neointima formation after beta-radiation as assessed by intravascular ultrasound (IVUS). Following interventional procedures of long ISR in 30 patients, a 40 mm or 60 mm non-centered 90Sr/90Y seed train was used for VBT. Serial (post radiation (PR) and follow-up (FU)) quantitative coronary angiography (QCA) measurements of minimal lumen diameter (MLD) and late lumen loss (LLL) and intravascular ultrasound measurements (IVUS) of cross-sectional areas of the lumen (L-CSA), stent (S-CSA) and intimal hyperplasia (IH-CSA) were performed and compared with historic controls. LLL (0.34 +/- 0.27 mm; p = 0.196), mean decrease of L-CSA (-1.0 +/- 0.8 mm2; p = 0.024) and mean increase of IH-CSA (0.5 +/- 1.3 mm2; p = 0.038) in long ISR were comparable with previously reported results of short ISR. In conclusion the average changes of lumen and intimal hyperplasia after beta-radiation of long ISR are similar to those of short ISR.
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http://dx.doi.org/10.1007/s00392-002-1303-3DOI Listing
March 2003

Crucial role of local peroxynitrite formation in neutrophil-induced endothelial cell activation.

Cardiovasc Res 2003 Mar;57(3):804-15

Division of Cardiology, Medizinische Klinik Innenstadt, Ludwig-Maximilians-University Munich, Germany.

Introduction And Methods: The reaction of superoxide anions and NO not only results in a decreased availability of NO, but also leads to the formation of peroxynitrite, the role of which in the cardiovascular system is still discussed controversially. In cultured human endothelial cells, we studied whether there is a significant interaction between endothelial NO and neutrophil-derived superoxide anions in terms of endothelial peroxynitrite formation. We particularly studied whether a significantly higher redox-stress can be found in those endothelial cells directly adjacent to an activated neutrophil.

Results: A considerable part of the 2,7-dihydrodichlorofluoresceine signal in endothelial cells was due to oxidation by peroxynitrite. Providing superoxide radicals by enzymatic source or by the neutrophil respiratory burst increased the fluorescence, which was attenuated by blockade of endothelial NO-synthase, suggesting that peroxynitrite was formed from neutrophil- or extracellular enzyme-derived superoxide and endothelial NO. Considerably higher fluorescence intensity was observed in endothelial cells in direct neighborhood to a neutrophil. This was particularly pronounced in the presence of a NO-donor and was accompanied by a strong activation of NF-kappaB and increased expression of E-selectin in these cells.

Conclusion: Endothelial cells adjacent to neutrophils may have elevated levels of peroxynitrite that result in an increased expression of adhesion molecules. Such cells might represent a preferential site for adhesion and migration of additional neutrophils when simultaneously high concentrations of NO and neutrophil-derived superoxide are present.
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http://dx.doi.org/10.1016/s0008-6363(02)00786-1DOI Listing
March 2003

Coronary Doppler measurements do not predict progression of cardiac allograft vasculopathy: analysis by serial intracoronary Doppler, dobutamine stress echocardiography, and intracoronary ultrasound.

J Heart Lung Transplant 2002 Aug;21(8):902-5

Department of Cardiology, Medizinische Klinik-Innenstadt, University of Munich, Germany.

Coronary flow velocity reserve (CFVR) (maximum/baseline flow velocity, 16 microg adenosine) was compared with dobutamine stress echocardiography (DSE) (5 to 40 microg/kg/min) to assess the progression of angiographically silent cardiac allograft vasculopathy (CAV). As a reference for the morphologic assessment of CAV, serial intracoronary ultrasound (ICUS) measurements were performed. An increase in CFVR could be observed in all transplant patients despite morphologic or functional progression of CAV or non-progressive CAV as assessed by ICUS or DSE. Thus, serial intracoronary Doppler flow analysis is not useful to predict morphologic or functional progression of CAV.
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http://dx.doi.org/10.1016/s1053-2498(01)00416-8DOI Listing
August 2002

NAD(P)H oxidase-dependent platelet superoxide anion release increases platelet recruitment.

Blood 2002 Aug;100(3):917-24

Institute of Physiology and the Department of Internal Medicine, Ludwig-Maximilians-University Munich, Schillerstr 44, 80336 Munich, Germany.

Platelets, although not phagocytotic, have been suggested to release O. Since O-producing reduced nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) oxidases can be specifically activated by certain agonists and are found in several nonphagocytotic tissues, we investigated whether such an enzyme is the source of platelet-derived O. We further studied which agonists cause platelet O release and whether platelet-derived O influences thrombus formation in vitro. Collagen, but not adenosine 5'-diphosphate (ADP) or thrombin, increased O formation in washed human platelets. This was a reduced nicotinamide adenine dinucleotide (NADH)-dependent process, as shown in platelet lysates. Consistent with a role of a platelet, NAD(P)H oxidase expression of its subunits p47(phox) and p67(phox) and inhibition of platelet O formation by diphenylene-iodoniumchloride (DPI) and by the specific peptide-antagonist gp91ds-tat were observed. Whereas platelet-derived O did not influence initial aggregation, platelet recruitment to a preformed thrombus following collagen stimulation was significantly attenuated by superoxide dismutase (SOD) or DPI. It was also inhibited when ADP released during aggregation was cleaved by the ectonucleotidase apyrase. ADP in supernatants of collagen-activated platelets was decreased in the presence of SOD, resulting in lower ADP concentrations available for recruitment of further platelets. Exogenous O increased ADP- concentrations in supernatants of collagen-stimulated platelets and induced irreversible aggregation when platelets were stimulated with otherwise subthreshold concentrations of ADP. These results strongly suggest that collagen activation induces NAD(P)H oxidase-dependent O release in platelets, which in turn enhances availability of released ADP, resulting in increased platelet recruitment.
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http://dx.doi.org/10.1182/blood.v100.3.917DOI Listing
August 2002

Stent design-related coronary artery remodeling and patterns of neointima formation following self-expanding and balloon-expandable stent implantation.

Catheter Cardiovasc Interv 2002 Aug;56(4):478-86

Department of Cardiology, Medizinische Klinik-Innenstadt, University Hospital, Munich, Germany.

The self-expanding Wallstent (WS) and balloon-expandable Palmaz-Schatz stents (PS) display different mechanical and dynamical stent properties. We analyzed the impact of the respective stent design on coronary wall geometry using quantitative coronary angiography (QCA) and intracoronary ultrasound (ICUS) measurements. Serial measurements were performed within the stent and within reference segments of 50 patients (25 WS, 25 PS). Relative changes for each parameter in both stent designs were calculated (Mann-Whitney U-test; 95% CI). The luminal net gain in WS was not significantly higher in WS compared with PS (1.63 +/- 1.11 vs. 1.44 +/- 0.63 mm; P = 0.2554). The respective loss indexes were also similar (0.38 +/- 0.42 vs. 0.36 +/- 0.23; P = 0.8578). The WS segments showed significant postinterventional stent expansion with positive vessel remodeling. The neointima formation was significantly higher in WS segments (4.23 +/- 2.07 vs. 2.22 +/- 2.22 mm(2)). The coronary wall morphology and stent geometry after 6.5 +/- 1.2 months are related to the stent design. In WS segments, the neointima formation was balanced by postinterventional stent expansion, resulting in a comparable relative lumen loss in both stent types. The respective stent design had no impact on the vessel reference segments.
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http://dx.doi.org/10.1002/ccd.10249DOI Listing
August 2002

Images in cardiovascular medicine. Septal course of the left main coronary artery originating from the right sinus of valsalva.

Circulation 2002 Mar;105(12):1511-2

Cardiology Division, Medizinische Klinik-Innenstadt, University of Munich, University Hospital, Munich, Germany.

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http://dx.doi.org/10.1161/hc1202.104523DOI Listing
March 2002

The role of tacrolimus (FK506)-based immunosuppression on bone mineral density and bone turnover after cardiac transplantation: a prospective, longitudinal, randomized, double-blind trial with calcitriol.

Transplantation 2002 Feb;73(4):547-52

Medizinische Klinik, Klinikum Innenstadt, Department of Cardiology, Ludwig-Maximilians University, 80336 Munich, Germany.

Background: Tacrolimus (FK506) is a new immunosuppressive drug in organ transplantation that has demonstrated experimentally to be more deleterious on bone mineral metabolism than cyclosporine. The purpose of this clinical study was to evaluate the effects of a tacrolimus-based immunosuppression on the skeleton and to investigate in a prospective, longitudinal, randomized, double-blind, study the effect of 0.25 microg calcitriol (1,25-dihydroxyvitamin D3) versus placebo in the prevention of bone loss and fracture rate after heart transplantion (HTx).

Methods: A total of 53 patients (5 female, 48 male, mean age: 53+/-11 years) were randomized to the study medication. Basic therapy included calcium and sex hormone replacement in hypogonadism. Bone mineral density of the lumbar spine (LS) and femoral neck (FN) were performed at baseline, after 12 and 24 months. Biochemical indexes of mineral metabolism were measured every 3 months.

Results: Overall bone mineral density (BMD) was significantly decreased after HTx (T-score-LS: 89+/-13%; FN: 88+/-14%). LS-BMD (% change in g/cm2) increased significantly within the study period in the calcitriol group (12 months: 7.1+/-8.1%, P<0.01; 24 months: 14.0+/-10.1%, P<0.01) and showed a positive trend in the placebo group (12 months: 4.5+/-9.3%, NS; 24 months: 6.2+/-8.0%, NS). FN-BMD in the calcitriol group was stable (12 months: -2.1+/-4.2%; NS; 24 months: -0.9+/-3.2%, NS). FN-BMD in the placebo group decreased significantly within the first 12 month follow-up period (-7.3+/-5.4; P<0.05) and stabilized within 2 years (-8.0+/-4.1%; P < 0.05). Fracture incidence was low during the study interval (first year: 5.0%, second year: 0%). Bone resorption markers decreased significantly during calcitriol therapy.

Conclusions: High dose tacrolimus-based immunosuppressive regimen is associated with a rapid bone loss early after cardiac transplantation. Beyond the first 6 months after HTx, calcium, vitamin D, and hormone supplementation in hypogonadism lead sufficiently to bone mineral recovery. Besides immunosuppression, both concomitant hypogonadism and secondary hyperparathyroidism play a major role for the bone loss and should be therefore monitored and treated adequately. Low dose calcitriol should be substituted for at least 2 years as additional antiresorptive therapy.
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http://dx.doi.org/10.1097/00007890-200202270-00010DOI Listing
February 2002