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

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.

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

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.

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.

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.

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

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.

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

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.

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

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.

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

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.

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.

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.

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.

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.

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

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.

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

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.

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

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.

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

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.

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

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)(-).

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

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.

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

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.