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.

BACKGROUND:Late vessel failure by restenosis or thrombosis is a potential limitation of drug-eluting stent implantation.METHODS:We conducted a prospective 5-year clinical evaluation following implantation of sirolimus-eluting Cypher stents for in-stent restenosis regardless of the patient's symptomatic status. A complete 5-year follow-up is reported for 192 consecutive patients.RESULTS:The cumulative rate of death was 5.2%, of cardiac death was 4.2%, of nonfatal myocardial infarction was 4.2%, of definite stent thrombosis was 1.0%, of probable stent thrombosis was 1.0%, of possible stent thrombosis was 2.1%, of target lesion revascularization was 9.4%, of target vessel revascularization was 13.5%, and of major adverse cardiovascular events (death of all causes, nonfatal myocardial infarction, and repeat revascularization; major adverse cardiovascular event) was 22.9%, respectively.CONCLUSION:These results, of a comparably large series, indicate that the implantation of sirolimus-eluting Cypher stents for the treatment of coronary in-stent restenosis is effective and safe and associated with a stable clinical course in the very long term.

Since late vessel failure has been speculated as a significant limitation of vascular brachytherapy (VBT), we conducted a prospective clinical evaluation at 6, 12, 24, 36 and 60 months follow-up after irradiation with (90)Sr/(90)Y for in-stent restenosis (ISR) regardless of the patient's symptomatic status. Complete five-year follow-up is reported for 104 consecutive patients. The cumulative rate of death was 13.5% (6 months: 0.96%; 12 months: 2.88%; 24 months: 4.81%; 36 months: 7.69%), of acute myocardial infarction 4.81% (2.88%; 4.81%; 4.81%; 4.81%), of late thrombotic occlusion 4.81% (3.85%; 4.81%; 4.81%; 4.81%), of target lesion revascularization (TLR) 27.9% (8.65%; 12.5%; 17.3%; 21.2%), of target vessel revascularization (TVR) 43.3% (12.5%; 19.2%; 22.1%; 29.8%), and of all major adverse cardiovascular events (MACE) 61.5% (16.3%; 26.9%; 31.7%; 42.3%), respectively. Considered that the annual incidence of TVR after the first year following drug-eluting stenting for in-stent restenosis has been reported as approximately 3% per year, an incidence of 5.8% per year following VBT of our study population clearly indicates a more pronounced, delayed and, even in the fifth year after the index procedure, ongoing restenotic process following beta-irradiation of in-stent restenotic lesions associated with clinically relevant adverse cardiovascular events.

Intravascular ultrasound radiofrequency analysis (IVUS-RF) characterizes plaque components as necrotic core (NC) and dense calcium (DC). The aim of this study was to perform an IVUS-RF derived analysis of the lesion segment profile in acute coronary syndrome (ACS) patients. Therefore, we compared the site of the minimum lumen area—cross sectional area (mla-CSA) with the worst lesion site—CSA (ws-CSA) defined by the maximum NC site.

BACKGROUND:Cardiac allograft vasculopathy (CAV) is the major limitation in survival of patients after heart transplantation. Cardiac allograft vasculopathy is angiographically silent in the early phase after operation. Intravascular ultrasound (IVUS) is a more sensitive method to detect the early stages of CAV and provides information about its development. Recent IVUS studies demonstrated a rapid progression of CAV within the first year after transplantation as a predictor of morbidity and mortality.OBJECTIVES:This study assessed the plaque composition of early atherosclerosis in transplant patients by radiofrequency analysis.METHODS:Coronary angiography and IVUS with Virtual Histology (VH) software (Real-Time VH, Volcano Corp, Rancho Cordova, CA) were used to assess 18 patients early after heart transplantation (1.71 +/- 0.47 months). The plaque composition was determined by IVUS radiofrequency data analysis. Tissue maps were reconstructed from radiofrequency data using VH-IVUS software. The VH-IVUS acquisition was performed with standardized IVUS (EagleEye catheter; 2.9 F/20 MHz; Volcano Corp) and the VH-IVUS console (Volcano Corp).RESULTS:Coronary angiography did not show any wall irregularities. Intravascular ultrasound demonstrated donor-transmitted atherosclerosis in 6 of 18 patients (33.33%). The incidence, amount of plaque burden, and plaque composition was significantly related to donor age. By VH-IVUS analysis, the plaque composition consisted mainly of fibrotic tissue.CONCLUSIONS:Donor-transmitted coronary atherosclerosis is present early after heart transplantation and cannot be detected by coronary angiography. VH-IVUS gives detailed information about the plaque distribution and the plaque composition.

Eine regelmäßige Ischämiediagnostik ist bei Patienten nach Herztransplantation (HTX) von besonderer Bedeutung. Unter Zuhilfenahme transpulmonaler Ultraschallkontrastmittel (KM) können praktisch alle HTX Patienten mittels Dobutamin-Stressechokardiografie (DSE) mit ausreichender Bildqualität untersucht werden. Die Sicherheit der KM-Gabe während der DSE konnte bereits gezeigt werden, die vorliegende Studie untersucht den Langzeitverlauf bei Patienten nach nativer und KM-unterstützter DSE.

Unter Zuhilfenahme transpulmonaler Ultraschallkontrastmittel (KM) können praktisch alle Patienten mit Indikation für einen Ischämietest mittels Stressechokardiografie mit ausreichender Bildqualität untersucht werden. Eine Diskussion über deren Sicherheit führte zur vorliegenden Studie, die die Komplikationsraten des nativen Dobutamin-Stressechokardiogramms (DSE) und des KM-unterstützten DSE bei herztransplantierten (HTX) und nicht herztransplantierten Patienten vergleicht.

In-stent restenosis is the limiting entity following coronary stent implantation. It is associated with significant morbidity and cost and thus represents a major clinical and economical problem. Worldwide, approximately 250 000 in-stent restenotic lesions per year have to be dealt with. The pathophysiology of instent restenosis is multifactorial and comprises inflammation, smooth muscle cell migration and proliferation and extracellular matrix formation, all mediated by distinct molecular pathways. Instent restenosis has been recognised as very difficult to manage, with a repeat restenosis rate of 50% regardless of the mechanical angioplasty device used. Much more favourable results were reported for the adjunctive irradiation of the in-stent restenotic lesion, with a consistent reduction of the incidence of repeat in-stent restenosis by 50%. Data from the first clinical trials on drug-eluting stents for the treatment of in-stent restenosis have shown very much promise yielding this strategy likely to become the treatment of choice. This review outlines the histological and molecular findings of the pathophysiology, the epidemiology, the predictors and the diagnostic work-up of in-stent restenosis and puts emphasis on the various treatment options for its prevention and therapy.

Background: The survival of heart transplant patients is limited by cardiac allograft vasculopathy (CAV). Intravascular ultrasound (IVUS) and IVUS-derived radiofrequency plaque composition analysis (IVUS-RF) provide further information about the process of coronary atherosclerosis.Methods: In this study we aimed to assess the time-dependent differences in disease progression in patients with CAV. Fifty-six patients were divided into three groups according to time interval after transplantation (Group I: 1 to 3 months, 18 patients; Group II, 1 to 5 years, 20 patients; Group III: 5 to 15 years, 18 patients).Results: IVUS-RF revealed time-dependent increase s in all plaque components. The largest increase was shown for fibrotic, fibrofatty and necrotic tissue between Groups I and II. Dense calcium area increased uniformly in all groups. IVUS-RF-derived plaque type analysis revealed predominantly fibrotic plaques in all groups with a decrease of frequency over time. Fibrolipidic and fibrotic-calcific plaques increased uniformly. High-risk lesions, such as thick-cap fibroatheromas (FAs), increased in Groups I and II and decreased in Group III. Thin-cap FAs were detected only in Group III.Conclusions: IVUS-RF, as compared with gray-scale IVUS, provides better detailed information about the development of CAV by plaque morphology and composition analysis in different stages after heart transplantation. Serial IVUS-RF analysis in these patients may improve the stratification of heart transplant recipients.

Background Invasive coronary angiography (ICA) alone fails to accurately select patients with intermediate stenoses who should be treated by percutaneous coronary intervention (PC]). Previous studies have demonstrated the usefulness of fractional flow reserve (FFR) for identifying patients in whom deferring an intended PC] would be more beneficial than performing the planned procedure. The long-term safety of FFR-based therapy stratification, however, remains unknown. Therefore, the aim of this study was to retrospectively evaluate the long-term safety of an FFR-based therapy stratification in patients with intermediate coronary lesions detected by ICA.Methods We included 56 patients presenting with a 50% to 75% angiographic stenosis by visual assessment on ICA, with negative, inconclusive, or no stress test, and in whom the intended PCI was deferred based on the result of the FFR measurement (ie, FFR >= 0.75). The occurrence of major adverse cardiac events during a 5-year follow-up period was recorded.Results A complete 5-year follow-up was available in all patients. Mean follow-up was 1868 +/- 380 days. During follow-up, 16 events (1 cardiac death, 4 noncardiac deaths, 11 revascularization procedures) occurred. The combined rate of cardiac death and nonfatal myocardial infarction was 1.8% over 5 years. Nine PCI procedures (5 target vessel, 4 nontarget vessel) were performed during follow-up based on objective signs of ischemia. The angina status was not different between inclusion and the 5-year follow-up.Conclusion Deferring PCI in patients without critical reduction in FFR may be a safe option during long-term follow-up.

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 mm(2); 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.

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.

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 mu m 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.