Publications

OBJECTIVE To study the relation between moderate coronary dissections, coronary flow velocity reserve (CFVR), and long term outcome. METHODS 523 patients undergoing balloon angioplasty and sequential intracoronary Doppler measurements were examined as part of the DEBATE II trial (Doppler endpoints balloon angioplasty trial Europe). After successful balloon angioplasty, patients were randomised to stenting or no further treatment. Dissections were graded at the core laboratory by two observers and divided into four categories: none, mild (type A-B), moderate (type C), severe (types D to F). Patients with severe dissections (n = 128) or without available reference vessel CFVR (n = 139) were excluded. The remaining 256 patients were divided into two groups according to the presence (group A, n = 45) or absence (group B, n = 211) of moderate dissection. RESULTS Following balloon angioplasty, there was no difference in CFVR between the two groups. At 12 months follow up, a higher rate of major adverse cardiac events was observed overall in group A than in group B (10 (22%) v 23 (11%), p = 0.041). However, the risk of major adverse events was similar in the subgroups receiving balloon angioplasty (group A, 6 (19%) v group B, 16 (16%), NS). Among group A patients, the adverse events risk was greater in those randomised to stenting (odds ratios 6.603 v 1.197, p = 0.046), whereas there was no difference in risk if the group was analysed according to whether the CFVR was < 2.5 or ⩾ 2.5 after balloon angioplasty. CONCLUSIONS Moderate dissections left untreated result in no increased risk of major adverse cardiac events. Additional stenting does not improve the long term outcome.

Technologies in interventional Cardiology have evolved from balloon to mechanical ablation, atherectomy, stenting, and brachytherapy to current drug eluting interventional strategies. New challenges are to develop techniques that not only prevent restenosis, but also promote vascular and endothelial healing after (balloon) injury. Endothelial healing approaches range from preventing endothelial injury to restoring endothelial function and reendothelialization by pharmacotherapy and cell therapy. These novel healing strategies warrant further exploration as they may represent an alternative to drug-eluting stent approaches.

No abstract is provided for this article.

In human embryonic lung fibroblasts, transforming growth factor-beta 1 (TGF-beta 1) induced a time-dependent down-regulation of M2 muscarinic receptor binding sites as measured with the nonselective hydrophilic ligand [3H]N-methylscopolamine (NMS). This down-regulation was slow, with 58% loss of all receptors after 24 hr of treatment. The affinity of [3H]NMS for the remaining sites was unaltered by TGF-beta 1. The loss in [3H]NMS binding was accompanied by reduced adenylyl cyclase activity and functional desensitization of M2 muscarinic receptors. Northern blot analyses showed a 72% decrease in the steady state levels of m2 muscarinic receptor mRNA after 24-hr TGF-beta 1 treatment. Recovery of m2 muscarinic receptor mRNA after TGF-beta 1 treatment was slow, with a half-life of approximately 8 hr. There was no effect of TGF-beta 1 on the m2 muscarinic receptor mRNA half-life measured in the presence of actinomycin D, but the rate of m2 muscarinic receptor gene transcription measured with nuclear run-on assay was reduced by 50%, indicating reduced gene transcription. Cycloheximide (10 micrograms/ml) pretreatment abolished the TGF-beta 1 effect, indicating that de novo protein synthesis was required for receptor downregulation. In summary, we have shown that TGF-beta 1 induced desensitization and down-regulation of M2 muscarinic receptor protein and gene that was mediated through reduction in the rate of m2 receptor gene transcription.

The effect of sulfonated shale oil fractions on the oxidative burst and the mobilization of intracellular calcium in purified guinea pig peritoneal macrophages was investigated in vitro. Three sulfonated shale oil fractions of varying boiling range, No. 1 = R = 1269 (powder, sodium salt of sulfonated shale oil dark), No. 2 = R 3269 (watery solution, sodium salt of sulfonated shale oil pale, Ichthyol hell), No. 3 = R 2069 (watery solution, ammonium salt of sulfonated shale oil dark, Ichthyol) were investigated. Two of three compounds dose-dependently inhibited leukotriene (LT) B4-induced Ca++ mobilization with complete inhibition at 10 mumol/l. The phorbol ester-stimulated generation of superoxide anion was dose-dependently inhibited by all three compounds with an optimal concentration of 1 to 10 mumol/l and maximal inhibition of 34.7, 39 and 38%. High concentrations of the compounds promoted the release of superoxide anion into the buffer medium. The LTB4-stimulated generation of hydrogen peroxide was also dose-dependently inhibited by all three compounds with maximal inhibition of 34, 40 and 32% with an optimal concentration of 100 mumol/l. Our observations support the hypothesis that sulfonated shale oil fractions are capable of modulating inflammatory responses through inhibition of inflammatory cell functions.

Objectives The aim of this study was to compare outcomes after transfemoral transcatheter aortic valve implantation with the Medtronic CoreValve (MCV) versus the Edwards SAPIEN/SAPIEN XT transcatheter heart valve (ESV) for severe aortic stenosis. Background No large matched comparison study has been conducted so far evaluating both commercially available devices. Methods The data from databases of 4 experienced European centers were pooled and analyzed. Due to differences in baseline clinical characteristics, propensity score matching was performed. Study objectives were Valve Academic Research Consortium outcomes at 30 days and 1 year. Results In total, 793 patients were included: 453 (57.1%) treated with the MCV and 340 (42.9%) with the ESV. After propensity matching, 204 patients were identified in each group. At 30 days, there were no differences in all-cause mortality (MCV, 8.8% vs. ESV, 6.4%; hazard ratio [HR]: 1.422; 95% confidence interval [CI]: 0.677 to 2.984; p = 0.352), cardiovascular mortality (MCV, 6.9% vs. ESV, 6.4%; HR: 1.083; 95% CI: 0.496 to 2.364; p = 0.842), myocardial infarction (MCV, 0.5% vs. ESV, 1.5%; HR: 0.330; 95% CI: 0.034 to 3.200; p = 0.339), stroke (MCV, 2.9% vs. ESV, 1.0%; HR: 3.061; 95% CI: 0.610 to 15.346; p = 0.174), or device success (MCV, 95.6% vs. ESV, 96.6%; HR: 0.770; 95% CI: 0.281 to 2.108; p = 0.611). Additionally, there were no differences in major vascular complications (MCV, 9.3% vs. ESV, 12.3%; HR: 0.735; 95% CI: 0.391 to 1.382; p = 0.340) or life-threatening bleeding (MCV, 13.7% vs. ESV, 8.8%; HR: 1.644; 95% CI: 0.878 to 3.077; p = 0.120). MCV was associated with more permanent pacemakers (22.5% vs. 5.9%; HR: 4.634; 95% CI: 2.373 to 9.050; p < 0.001). At 1 year, there were no differences in all-cause (MCV, 16.2% vs. ESV, 12.3%; HR: 1.374; 95% CI: 0.785 to 2.407; p = 0.266) or cardiovascular (MCV, 8.3% vs. ESV, 7.4%; HR: 1.145; 95% CI: 0.556 to 12.361; p = 0.713) mortality. Conclusions No differences between the 2 commercially available transfemoral transcatheter aortic valve implantation devices were observed at the adjusted analysis in Valve Academic Research Consortium outcomes except for the need for permanent pacemakers with the MCV.

No abstract is provided for this article.

Adjunct high-pressure balloon inflations following the delivery of oversized self-expandable Wallstents may affect their implied late, postprocedural self-expansion. Consequently, we examined 15 “Magic” Wallstents, which were implanted following a strategy of stent oversizing and subsequent adjunct high-pressure balloon inflations (16 ± 2 atm; all ≥12 atm). The excellent radiographic visibility of this stent permitted reliable quantitative coronary angiographic measurement of both lumen and stent dimensions (before and after stenting, and at follow-up). At follow-up, extent and distribution of in-stent neointimal proliferation were evaluated with volumetric intravascular ultrasound. Between postintervention and follow-up examination, mean stent diameter increased from 3.7 ± 0.4 to 4.2 ± 0.4 mm (p <0.0001); there was no significant difference in late stent expansion between proximal, mid-, and distal stent subsegments. Late stent expansion showed a significant (reverse) relation to maximum balloon size (r = −0.56, p <0.04), but not with follow-up lumen size or late lumen loss. On average, 52 ± 18% of the stent was filled with neointimal ingrowth; neointimal volume/cm stent length was 64 ± 22 mm3. Both late stent expansion (r = 0.36, p <0.02) and maximum balloon pressure (r = 0.41, p <0.001) were related to neointimal volume/cm stent but not to follow-up lumen size. Thus, despite high-pressure implantation, Wallstents showed significant late self-expansion, which resulted in larger stent dimensions at follow-up that assisted in accommodating in-stent neointimal proliferation. Conversely, late stent expansion had a significant relation to the extent of in-stent neointimal ingrowth. Beneficial and disadvantageous effects of the late stent expansion appear to be balanced, because a relation to late lumen loss or follow-up lumen dimensions was not found to be present.

The latest generation of multislice spiral computed tomography (MSCT) scanners is capable of noninvasive coronary angiography. We evaluated its diagnostic accuracy to detect stenotic coronary artery disease (CAD). In 53 patients with suspected CAD, contrast-enhanced MSCT and conventional angiography were performed. The CT data were acquired within a single breathhold, and isocardiophasic slices were reconstructed by means of retrospective electrocardiographic gating. Coronary segments of ≥2 mm in diameter, measured by quantitative angiography, were evaluated. In 70% of the 358 available segments, image quality was regarded as adequate for assessment. The overall sensitivity, specificity, and positive and negative predictive values to detect ≥50% stenotic lesions in the assessable segments were 82% (42 of 51 lesions), 93% (285 of 307 nonstenotic segments), and 66% and 97%, respectively, regarding conventional quantitative angiography as the gold standard. Proximal segments were assessable in 92%, and distal segments and side branches in 71% and 50%, respectively. Including the undetected lesions in nonassessable segments, overall sensitivity decreased to 61% but remained 82% for lesions in proximal coronary segments. MSCT correctly predicted absent, single, or multiple lesions in 55% of patients. Thus, despite potentially high image quality, current MSCT protocols offer only reasonable diagnostic accuracy in an unselected patient group with a high prevalence of CAD.