Publications

Background The new, less shortening, self-expanding Wallstent is characterized by longitudinal flexibility, a protective membrane, a low profile, and a customized range of diameters (3.5 to 6.0 mm). The recent modification of the braiding angle of the Wallstent has resulted in a new device with less shortening on expansion and a concomitant reduction in radial force. We hypothesized that the enforced mechanical remodeling produced by the selection of an oversized Wallstent might result in improved accommodation of subsequent reactive intimal hyperplasia and prevention of chronic recoil of the vessel. Methods and Results To prove this hypothesis, we recently implanted 44 new, less shortening Wallstents in 35 native coronary arteries in 35 patients with acute or threatened closure after balloon angioplasty, according to a strategy of oversizing of Wallstent diameter and complete coverage of the lesion length. The initial and 6-month follow-up angiograms were analyzed with a computer-based quantitative coronary angiography (QCA) system. Acute gain (minimal luminal diameter [MLD] post minus MLD pre) and late loss (MLD post minus MLD at follow-up) were examined. Stent deployment was successful in 44 of 44 attempts (100%). Nominal stent diameter used was 1.40 mm larger than the maximal vessel diameter. One patient (3%) with a dilated but unstented lesion proximal to the stented segment sustained a subacute occlusion on day 1 associated with myocardial infarction. Event-free survival at 30 days after stent implantation was 97% (34 of 35 patients). Of the 34 patients eligible for 6-month angiographic follow-up, 3 who were asymptomatic declined repeat angiography. MLD (and percent diameter stenosis [% DS]) changed from 0.83±0.50 mm (72%) pre through 3.06±0.48 mm (15%) post to 2.27±0.74 mm (28%) at follow-up. Acute gain was 2.23±0.63 mm, and late loss was 0.78±0.61 mm. Angiographic restenosis (>50% DS) was observed in 5 of 31 patients (16%) at 6 months, all of whom underwent repeat angioplasty. Thus, the overall event-free survival at 6-month follow-up was 83% (29 of 35 patients). Conclusions The oversized Wallstent implantation with complete coverage of the lesion length conveyed a favorable 6-month clinical and angiographic outcome. The large acute gain obtained by the Wallstent afforded greater accommodation of the subsequent late loss. The enforced mechanical remodeling by oversized new Wallstents may result in prevention of acute and chronic recoil of the vessel wall and subsequently a lower restenosis rate at follow-up.

Background Histologic experimental studies have reported incomplete neointimal healing in overlapping with respect to nonoverlapping segments in drug-eluting stents (DESs), but these observations have not been confirmed in human coronary arteries hitherto. On the contrary, angiographic and optical coherence tomography studies suggest that DES overlap elicits rather an exaggerated than an incomplete neointimal reaction. Methods Optical coherence tomography studies from 2 randomized trials including sirolimus-eluting, biolimus-eluting, everolimus-eluting, and zotarolimus-eluting stents were analyzed at 9- to 13-month follow-up. Coverage in overlapping segments was compared versus the corresponding nonoverlapping segments of the same stents, using statistical pooled analysis. Results Forty-two overlaps were found in 31 patients: 11 in sirolimus-eluting stents, 3 in biolimus-eluting stents, 17 in everolimus-eluting stents, and 11 in zotarolimus-eluting stents. The risk ratio of incomplete coverage was 2.35 (95% CI 1.86-2.98) in overlapping versus nonoverlapping segments. Thickness of coverage in overlaps was only 85% (95% CI 81%-90%) of the thickness in nonoverlaps. Significant heterogeneity of the effect was observed, especially pronounced in the comparison of thickness of coverage (I 2 = 90.31). Conclusions The effect of overlapping DES on neointimal inhibition is markedly heterogeneous: on average, DES overlap is associated with more incomplete and thinner coverage, but in some cases, the overlap elicits an exaggerated neointimal reaction, thicker than in the corresponding nonoverlapping segments. These results might help to understand why overlapping DES is associated with worse clinical outcomes, both in terms of thrombotic phenomena and in terms of restenosis and revascularization.

Background Bifurcation PCI is associated with a lower rate of procedural success, especially in multivessel disease patients. We aimed to determine the impact of bifurcation treatment on 2‐years clinical outcomes when a state‐of‐the‐art PCI strategy (heart team decision‐making using the SYNTAX score II, physiology guided coronary stenosis assessment, thin strut bioresorbable polymer drug‐eluting stent, and intravascular ultrasound guidance) is followed. Methods Three‐vessel disease patients enrolled in the SYNTAX II trial ( n = 454) were categorized in patients with (a) ≥1 treated bifurcation ( n = 126), and (b) without bifurcation ( n = 281). The primary endpoint was the occurrence of major adverse cardio and cerebrovascular events (MACCE—a composite of all‐cause death, stroke, any myocardial infarction, or any revascularization) at 2 years. Secondary endpoints were the occurrence of target lesion failure (TLF) defined as cardiac death, target‐vessel myocardial infarction and ischemia‐driven target lesion revascularization, and the individual components of the composite primary endpoint, as well as stent thrombosis. Results A total of 145 bifurcation were treated in 126 patients. At 2 years, MACCE occurred in 75/407 patients (20.7% for bifurcation versus 17.5% for nonbifurcation, hazard ratio [HR] of 1.28, CI95% 0.78–2.08, p = .32). TLF presented a trend toward higher occurrence in bifurcation (16.8% vs. 10.8%, HR 1.75, CI95% 0.99–3.09, p = .053). Definite stent thrombosis did not differ at 2‐year between groups (0.8% for the bifurcation vs. 0.7% for the nonbifurcation, p = .92). Conclusion Bifurcation treatment in patients with three‐vessel disease undergoing state‐of‐the‐art PCI had similar event rate of MACCE but was associated with a trend toward higher incidence of TLF compared with nonbifurcation lesions.

We have determined the expression of phosphodiesterase (PDE) 7A1 and PDE7A2 in human cells that have been implicated in the pathogenesis of chronic obstructive pulmonary disease and asthma. Messenger RNA transcripts were detected by RT-PCR in T lymphocytes, monocytes, neutrophils, airway and vascular smooth muscle cells, lung fibroblasts, epithelial cells, and cardiac myocytes. Human epithelial, T cell, eosinophil, and lung fibroblast cell lines were also positive for PDE7A1 and PDE7A2 mRNA transcripts. By Western immunoblot analyses the amount of PDE7A1 was greatest in T cell lines, peripheral blood T lymphocytes, epithelial cell lines, airway and vascular smooth muscle cells, lung fibroblasts, and eosinophils but was not detected in neutrophils. In contrast, PDE7A2 protein, which was identified in human cardiac myocytes, was not found in any of the other cell types investigated. Immunoconfocal analyses showed that PDE7A was expressed in neutrophils and alveolar macrophages. As the expression of PDE7A mirrors the distribution of PDE4 we speculate that this enzyme could be a target for novel anti-inflammatory drugs.

Epithelial cells play a critical role in airway inflammation and have the capacity to produce many inflammatory mediators, including bioactive lipids and proinflammatory cytokines. Intracellular levels of cAMP and cGMP are important in the control of inflammatory cell function. These cyclic nucleotides are inactivated via a family of phosphodiesterase (PDE) enzymes, providing a possible site for drug intervention in chronic inflammatory conditions. We studied the expression of PDE activity in an epithelial cell line (A549) and in primary human airway epithelial cells (HAECs). We measured PDE function using specific inhibitors to identify the PDE families present and used RT-PCR to elucidate the expression of PDE isogenes. Both A549 cells and HAECs predominantly expressed PDE4 activity, with lesser PDE1, PDE3, and PDE5 activity. RT-PCR identified HSPDE4A5 and HSPDE4D3 together with HSPDE7. Inhibition of PDE4 and PDE3 reduced secretion by these cells. Epithelial PDE may be an important target for PDE4 inhibitors in the development of the control of asthmatic inflammation, particularly when delivered via the inhaled route.

We have recently completed an observing program with the Australia Telescope Compact Array towards massive star formation regions traced by 6.7 GHz methanol maser emission. We found the molecular cores could be separated into groups based on their association with/without methanol maser and 24 GHz continuum emission. Analysis of the molecular and ionised gas properties suggested the cores within the groups may be at different evolutionary stages. In this contribution we derive the column densities and temperatures of the cores from the NH3 emission and investigate if this can be used as an indicator of the relative evolutionary stages of cores in the sample. The majority of cores are well fit using single-temperature large velocity gradient models, and exhibit a range of temperatures from ~10 K to >200 K. Under the simple but reasonable assumption that molecular gas in the cores will heat up and become less quiescent with age due to feedback from the powering source(s), the molecular gas kinetic temperature combined with information of the core kinematics seems a promising probe of relative core age in the earliest evolutionary stages of massive star formation.

Background/Introduction coronary revascularization in patients with de novo three-vessel coronary artery disease (3VD) without Left Main disease can be performed by either PCI or CABG after objective Heart Team consensus. In the ongoing Multivessel TALENT trial (NCT04390672)1, the intended multivessel PCI is performed using DES with ultrathin struts and biodegradable polymers under the guidance of quantitative flow ratio (QFR) and intracoronary imaging with IVUS or OCT. Purpose The Logistic Clinical SYNTAX score (logSYNTAX) to predict 2-year all-cause mortality after PCI was developed in 15,883 patients treated in the GLOBAL LEADERS trial and externally validated in 10,100 patients. This study aims to predict 2-year all-cause mortality after intended multivessel PCI in the currently enrolled trial population to identify patients who should be considered high risk. Methods and results We performed an interim analysis in the first consecutive 781 patients of the ongoing Multivessel TALENT Trial aimed to enrol 1550 patients. Thirteen clinical predictors are used in the logSYNTAX score: SYNTAX I-score, presence of 3VD and/or LM disease, age, creatinine clearance in mL/min, LVEF, BMI, serum hemoglobin level(g/dL), the White Blood Cell Count (WBC, in 109 cells/L) and the presence of COPD, PVD, diabetes mellitus, current smoking and/or a history of stroke. LVEF and BMI have additional squared terms to adjust for non-linear associations with all-cause mortality. The predicted mortality was estimated using the survival function developed in the GLOBAL LEADERS trial. We considered patients high-risk if the estimated risk was above the 3rd quartile. In 563 patients, all thirteen predictors necessary for 2-year mortality prediction were available. Median 2-year all-cause mortality of 1.9% (1.09-3.82; IQR2.73). 142 patients (25%) with an increased estimated 2-year mortality risk (>3.8%) due to higher prevalence of the aforementioned predictors; higher median age [75 (9.0) vs. 67 (12.0), p <0.001], a lower median LVEF [55% (20) vs. 94% (35.5), p <0.001] and a higher median SYNTAX score [26.0 (13.5) vs. 20.0(11.0), p <0.001]. A complete overview of predictors can be found in table 1. High age, an impaired LVEF, and an increased anatomical SYNTAX-I score were the main contributors to high mortality in this study cohort (see figure 1). Conclusion(s) In 563 patients, the median predicted 2-year all-cause mortality was 1.9%. Nevertheless, a non-neglectable amount of patients were estimated to be at increased risk for all-cause 2-year mortality. Accurate prediction by knowledge of aforementioned predictors is pivotal for appropriate mortality risk prediction to segregate high-risk patients with 3VD for individual decision-making on coronary revascularization, even if surgical revascularization is no option, and guide optimal treatment with use of intravascular imaging to achieve an optimal PCI result.Table 1Figure 1