Frequency and Types of Pathological Upper Gastrointestinal Endoscopy Findings in Clinically Healthy Individuals.

BACKGROUND AND OBJECTIVE: Beyond its application for diagnostics in patients, esophagogastroduodenoscopy (EGD) is used to assess gastrointestinal drug effects in clinical trials, where the interpretation of any pathological findings depends on the respective background variability. The objective of this analysis was to characterize the occurrence of pathological findings in the upper gastrointestinal tract in symptom-free healthy individuals. METHODS: A baseline EGD was performed in clinically healthy individuals in three clinical trials aimed to assess gastrointestinal tolerability of drugs. Pathological findings were described by type (redness, erosion, ulcer or other), number, size and location, and by clinical relevance as assessed by the endoscopist. Characteristics of volunteers were tested as potential covariates. RESULTS: A total of 294 EGDs were assessed. Characteristics of individuals were as follows: 257 (87.4%) males, age (mean ± SD) 32.0 ± 8.1 years, body weight 76.0 ± 10.6 kg, body mass index (BMI) 24.0 ± 2.5 kg/m2, 200 consumed alcohol, 250 (of 290 where this information was available) consumed caffeine and 39 (of 152) were smokers, 30 (of 151) tested positive for H. pylori. Any pathological finding was present in 79.6%. Clinically relevant findings occurred in 44.2%, mainly erosions (39.1%). Nine stomach ulcers were observed. Only age and BMI had a statistically significant relationship to overall pathological findings [age 3.4 years higher (p = 0.027), and BMI 1.6 kg/m2 higher (p < 0.001); for clinically relevant vs no findings]. CONCLUSION: Upper gastrointestinal tract mucosal lesions, including those assessed as clinically relevant, are frequent in clinically healthy individuals, impeding the assessment of causality for both disease and drug effects on gastrointestinal health.

Effective long-term control of Echinococcus multilocularis in a mixed rural-urban area in southern Germany.

Effective preventive strategies are available to control Echinococcus multilocularis in foxes in order to reduce the human infection risk. Reduction of E. multilocularis prevalence in foxes was achieved in various studies by distributing praziquantel-containing bait by hand or by aircraft in either rural or settlement areas. Here, an integrated approach is described from southern Germany (district of Starnberg). Baseline data were obtained in winter 2002/03, when the prevalence rate in the project area was 51%. Between December 2005 and December 2011, air distribution of bait in agricultural and recreational areas was combined with distribution by hand in towns and villages, in order to cover the entire fox population, with a bait density of 50 pieces / km2 (baiting area: 213 km2). In addition, a control area without anthelmintic treatment was selected. Prevalence was reduced in the baiting area to 1% by March 2007. Subsequently, from 2007 to the end of 2011, prevalence rates remained at a low level with 2.4% (2007), 2.4% (2008), 2.6% (2009), 1.2% (2010) and 0.0% (2011). In the un-baited control area the prevalence rates remained high, ranging from 19.6% to 35.1% with an average of 27.3%. During the 6 years of anthelmintic treatment, differences between baiting and control areas were highly significant (P<0.001). In the suburban and urban parts of the study area prevalence could be reduced to less than 1%, i.e. to a level below the limit of detection, which was maintained even after the measures had been discontinued. The applicability and effectiveness of anthelmintic baiting was therefore confirmed even for a heavily settled and fragmented landscape, which posed challenges for practical application of the control measures. The cost of the project ranged between € 1.70 and € 2.00 per inhabitant of the baiting area per year.

Chemogenetic Targeting of Dorsomedial Direct-pathway Striatal Projection Neurons Selectively Elicits Rotational Behavior in Mice.

The striatum of the basal ganglia is pivotal for voluntary movements and is implicated in debilitating movement disorders such as Parkinsonism and dystonia. Striatum projects to downstream nuclei through direct (dSPN) and indirect (iSPN) pathway projection neurons thought to exert opposite effects on movement. In rodent models of striatal function, unilateral dopamine deprivation induces ipsiversive rotational behavior. The dSPNs of the dorsal striatum are believed to engage distinct motor programs but underlying mechanisms remain unclear. Here, we show by employing chemogenetics [Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)] that unilateral inhibition of dorsomedial dSPNs is sufficient to selectively impair contraversive movement and elicit ipsiversive rotational behavior in mice. Adeno-associated virus (AAV) encoding Cre-dependent Gi-coupled DREADD was injected unilaterally into the dorsomedial striatum of Drd1-Cre mice, resulting in expression of the modified human M4 muscarinic receptor (hM4Di) in ∼20% of dorsostriatal dSPNs. Upon hM4Di activation, a striking positive linear correlation was found between turn ratio and viral expression, which corroborates a relationship between unilateral inhibition of dorsomedial dSPNs and rotational behavior. Bursts of ipsiversive rotations were interspersed with normal ambulation. However, partial unilateral inhibition of ∼20% of dorsostriatal dSPNs did not affect horizontal and vertical locomotion or forelimb use preference. Overall, our results substantiate a unique role of dSPNs in promoting response bias in rotational behavior and show this to be a highly sensitive measure of dSPN performance.

Soluble Ectodomain of Neuroligin 1 Decreases Synaptic Activity by Activating Metabotropic Glutamate Receptor 2.

Synaptic cell adhesion molecules represent important targets for neuronal activity-dependent proteolysis. Postsynaptic neuroligins (NLs) form trans-synaptic complexes with presynaptic neurexins (NXs). Both NXs and NLs are cleaved from the cell surface by metalloproteases in an activity-dependent manner, releasing a soluble extracellular fragment and membrane-tethered C-terminal fragment. The cleavage of NL1 depresses synaptic transmission, but the mechanism by which this occurs is unknown. Metabotropic glutamate receptor 2 (mGluR2) are located primarily at the periphery of presynaptic terminals, where they inhibit the formation of cyclic adenosine monophosphate (cAMP) and consequently suppress the release of glutamate and decrease synaptic transmission. In the present study, we found that the soluble ectodomain of NL1 binds to and activates mGluR2 in both neurons and heterologous cells, resulting in a decrease in cAMP formation. In a slice preparation from the hippocampus of mice, NL1 inhibited the release of glutamate from mossy fibers that project to CA3 pyramidal neurons. The presynaptic effect of NL1 was abolished in the presence of a selective antagonist for mGluR2. Thus, our data suggest that the soluble extracellular domain of NL1 functionally interacts with mGluR2 and thereby decreases synaptic strength.

Disappearance rate of praziquantel-containing bait around villages and small towns in southern Bavaria, Germany.

In recent years, the red fox (Vulpes vulpes) has increasingly occupied urban areas in central Europe. Meanwhile, prevalence of infection in foxes with the small fox tapeworm (Echinococcus multilocularis) has increased, thereby increasing the human risk of infection with the parasite, which causes alveolar echinococcosis. Baiting strategies to counteract E. multilocularis have been implemented in cities and the open countryside, but there are few data on the situation in villages and small towns (<10,000 inhabitants). We recorded disappearance rates of praziquantel-containing bait within villages and small towns and on settlement edges for 7 days after distribution. Disappearance rates were 89.2% in villages, 88.8% in small towns, and 91.8% in settlement edges. More than 75% of the bait was consistently taken within the first three nights. There were no significant differences in disappearance rates between years or among seasons (Cox proportional hazard model). The survival time of the bait in small towns (P=0.021) and villages (P=0.026) depended on the zone (zone 1, first row of houses bordering on open countryside; zone 2, second to fourth rows, zone 3; beyond the fifth row) in which bait was distributed. In villages, the probability of bait being eaten in zone 1 was 119% higher than it was in zone 3 (P=0.007). In small towns, the probability was 60% higher (P=0.006).

Late and very late catch-up after 90Sr/90Y beta-irradiation for the treatment of coronary in-stent restenosis.

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.

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.

CD34+CD140b+ cells and circulating CXCL12 correlate with the angiographically assessed severity of cardiac allograft vasculopathy.

AIMS: We sought to determine whether circulating vascular progenitor cells, such as endothelial progenitor cells (EPCs) or smooth muscle progenitor cells (SPCs), were associated with the severity of cardiac allograft vasculopathy (CAV). METHODS AND RESULTS: CD34(+)CD140b(+) SPCs and CD34(+)KDR(+) EPCs were measured in the peripheral circulation of 187 adult heart transplant recipients by flow cytometry. Cardiac allograft vasculopathy was quantified by angiography using a CAV-specific scoring system. Cardiac allograft vasculopathy was present in 84 patients (44.7%) and was classified as mild in 59 and severe in 25 cases. Circulating SPCs were more frequently detectable in CAV patients than in patients without CAV. The number of CD34(+)CD140b(+) cells showed a stepwise increase in patients with moderate and severe CAV. Smooth muscle progenitor cell counts were higher in patients with coronary stent implant compared with unstented patients with CAV. In contrast, peripheral CD34(+)KDR(+) EPC counts were not changed in CAV patients. Plasma CXCL12 levels correlated with the degree of CAV and SPC counts. None of the different immunosuppressive drug regimes was related to the SPC count or the CXCL12 levels. A multivariate regression analysis revealed that the SPC count was independently associated with the presence of CAV. CONCLUSION: Circulating SPCs, but not EPCs, and plasma CXCL12 concentrations are elevated in CAV patients, indicating that they play prominent roles in transplant arteriosclerosis.

Do systemic risk factors impact invasive findings from virtual histology? Insights from the international virtual histology registry.

AIMS: Cardiovascular risk factors such as elevated serum lipid levels are important in the development of coronary atherosclerosis. Radiofrequency (RF) analysis of intravascular ultrasound [IVUS, Virtual histology (VH)] offers a unique tool to study the composition of coronary atherosclerotic plaque in vivo. We used data from the multicentre VH registry to assess the association between cardiovascular risk factors and coronary plaque volume and composition. METHODS AND RESULTS: Between August 2004 and July 2006, 990 patients in 42 centres were enrolled in a prospective, multicentre, non-randomized global VH registry. Coronary artery imaging was performed by conventional IVUS and RF-IVUS. The four RF-IVUS plaque components [dense calcium (DC), necrotic core (NC), fibrous (F) tissue, and fibro fatty (FF)] were analysed in every recorded frame. The results were expressed as mean cross-sectional areas, absolute volume, and percentage of total plaque volume. Risk factor assessment included evaluation of family history of previous myocardial infarction (MI), past or current smoking, diabetes mellitus, hypertension, and the laboratory measurements. Patients with diabetes had an increased relative proportion of NC (6.47 +/- 0.28 vs. 5.86 +/- 0.14%, P = 0.037) and DC (4.58 +/- 0.27 vs. 3.90 +/- 0.14%, P = 0.017), and patients with hypertension had an increased relative proportion of FF, DC (4.35 +/- 0.16 vs. 3.57 +/- 0.17%, P = 0.02) and NC (6.24 +/- 0.17 vs. 5.60 +/- 0.19%, P = 0.01). Compared with patients with LDL-C <100 mg/dL, patients with LDL-C >160 mg/dL had higher plaque volume (342.1 +/- 26.2 vs. 318.6 +/- 10.7 mm(3)). Linear regression analysis showed a correlation between the level of HDL-C and F (r = -0.149, P < 0.01), FF (r = -0.106, P < 0.01), and NC (r = -0.90, P < 0.05). The level of LDL correlated with F (r = 0.110, P < 0.01). Patients with prior MI have an increased percentage of F (30.03 +/- 0.59 vs. 28.20 +/- 0.37%, P = 0.009). Smoking had no relevant effect on plaque composition. Treatment with acetylsalicylacid and statins reduced FF with altering plaque volume. CONCLUSION: Radiofrequency-IVUS detects marked differences in coronary plaque composition related to the risk factor profile with particular focus on lipid levels. Greater amounts of NC were associated with diabetes, hypertension, MI, and low HDL-C. The effects of treatment of changes related to plaque composition are underway.

Coronary plaque dimensions and composition by intravascular ultrasound radio frequency lesion segment analysis in stable and unstable angina patients.

AIMS: We hypothesized that the plaque composition and plaque type classification differs between acute coronary syndrome (ACS) and stable angina (SA) patients. METHODS AND RESULTS: We analyzed culprit lesion (CL) and nonculprit lesion (NCL) of ACS patients compared with target lesion (TL) and nontarget lesion (NTL) of SA patients by intravascular ultrasound radio frequency analysis in 874 lesion segments of 424 patients (ACS: 193 patients/SA: 231 patients). Comparing all lesion segments in ACS and SA patients did not show significant differences in absolute or relative plaque composition. However, necrotic core area was larger in CL versus TL (0.9+/-0.7 vs. 0.7+/-0.5 mm, P=0.005) and all plaque components were significantly higher in CL compared with NCL and TL compared with NTL, respectively. A higher amount of thin cap fibroatheroma lesions (15.2 vs. 5.1%, P<0.0001) was detected in ACS compared with SA patients. Fibrocalcific lesions were lower in ACS patients (3 vs. 10.5%, P<0.0001). CONCLUSION: The differentiation in CL/NCL of ACS and TL/NTL of SA patients revealed significant differences in plaque composition and plaque types when examined by intravascular ultrasound radiofrequency analysis. However, considerable overlap between plaque characteristics exists for ACS and SA patients.

Virtual histology.

As a luminogram, coronary angiography provides a good overview of the coronary artery tree. Using quantitative coronary measurements, the degree of coronary obstruction can be determined. The limitation of coronary angiography is that it does not provide information on the arterial wall structure and therefore cannot assess the extent of atherosclerosis. Knowledge about adaptive coronary remodelling processes as compensatory enlargement of the coronary artery has focused diagnostic interest on the non-stenotic lesions of the coronary tree. Intravascular ultrasound (IVUS) can reveal discrepancies between the extent of coronary atherosclerosis and angiography imaging by in vivo plaque imaging. Spectrum analysis of IVUS-derived radiofrequency (RF) data enables a more detailed analysis of plaque composition and morphology. Preliminary in vitro studies correlated four histological plaque components with a specific spectrum analysis of the RF data. The different components (fibrous, fibrofatty, necrotic core and dense calcium) are colour coded. Coronary tissue maps were reconstructed from RF data using IVUS-Virtual Histology (VH IVUS) software (Real-Time VH, Volcano Corporation, Rancho Cordova, California, USA). VH IVUS has the potential to detect high-risk lesions and can provide new insights into the pathophysiology of coronary artery disease. VH IVUS allows the differentiation of different lesion types based on information derived from histopathology. The in vivo specific histological analysis of coronary atherosclerosis may allow better stratification of treatment of patients with coronary artery disease.

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.

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.

Are high doses of intracoronary adenosine an alternative to standard intravenous adenosine for the assessment of fractional flow reserve?

BACKGROUND: Achievement of maximal hyperemia of the coronary microcirculation is a prerequisite for the measurement of fractional flow reserve (FFR). Intravenous adenosine is considered the standard method, but its use in the catheterization laboratory is time consuming and expensive compared with intracoronary adenosine. Therefore, this study compared different high, intracoronary doses of adenosine for the potential to achieve a maximal hyperemia equivalent to the standard intravenous route. METHODS: FFR was assessed in 50 patients with 50 intermediate lesions during cardiac catheterization. FFR was calculated as the ratio of the distal coronary pressure to the aortic pressure at hyperemia. Different incremental doses of intracoronary adenosine (60, 90, 120, and 150 microg as boli) and a standard intravenous infusion of 140 microg/kg/min were administered in a randomized fashion. RESULTS: Different incremental doses of intracoronary adenosine were well tolerated, with fewer systemic adverse effects than intravenous adenosine. At baseline, there were no significant differences for mean aortic and distal coronary pressure or heart rate in the different adenosine doses and routes. FFR decreased with increasing adenosine doses, with the lowest values observed with the 150-microg intracoronary bolus and 140-microg/kg/min dose of intravenous adenosine. All intracoronary doses, except the 150-microg bolus, resulted in mean FFR values that were significantly (P <.05) higher than FFR after the administration intravenous adenosine. Furthermore, 5 patients (10%) with a FFR value >0.75 and 3 subjects (6%) with a FFR value >0.80 who received a 60-microg intracoronary bolus reached a value below the cutoff point of 0.75 with the intravenous administration. CONCLUSIONS: This study suggests a dose-response relationship on hyperemia for intracoronary adenosine doses >60 microg. The administration of very high intracoronary adenosine boli is safe and associated with fewer systemic adverse effects than standard intravenous adenosine. However, intravenous adenosine administration with 140 microg/kg/min produced a more pronounced hyperemia than intracoronary adenosine in most patients and should be the preferred mode of application for the assessment of FFR.

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.

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.

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.