Publications

The volume, morphology and composition of atherosclerotic plaque play an important role in coronary artery disease and in long-term outcome of coronary interventions and pharmaceutical strategies. Intracoronary ultrasound (ICUS) provides real-time cross-sectional imaging of vessel wall structures. In-vitro and in-vivo studies have shown that ICUS can identify the general composition of the plaque by assigning different grey levels to different tissue types. Ultrasound scanners use 256 grey levels, whereas the human eye can only discriminate 32. Therefore, computer-assisted grey level interpretation (labelling) and measurement can help identify different tissue types present in the plaque and track changes over time. This paper covers a new research tool that facilitates this and that provides an objective quantitative analysis parameter for the segmentation of plaque into four different tissue types.

No abstract is provided for this article.

The incidence of major complications after percutaneous coronary angioplasty (PTCA) of a totally occluded artery was assessed retrospectively. A total of 1649 PTCA procedures were analyzed. After exclusion of procedures for acute myocardial infarction or total occlusion that resulted from restenosis, 90 patients were selected. Forty-four patients (49%) had stable angina and 46 (51%) had unstable angina. The estimated duration of occlusion was 87 ± 78 days in patients with stable angina, as compared with 10 ± 8 days in patients with unstable angina (p < 0.001). Abrupt vessel closure during PTCA occurred only in patients with unstable angina (0% versus 17%, p < 0.05). The major complication rate was 2.5% in the stable angina group, and 20% in unstable angina group (p < 0.01). This rate was also significantly higher than the complication rate of 8% observed in 442 procedures that were performed during the same period in patients with the unstable angina and nonocclusive stenosis (p < 0.01). Patients with unstable angina who undergo PTCA of a totally occluded artery represent a subset at high risk for major complications.

No abstract is provided for this article.

<strong>Objectives:</strong> The aim of the present analysis is to compare the quantitative angiographic aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) among three balloon-expandable valves. <strong>Background:</strong> Quantitative videodensitometric aortography is an objective, accurate, and reproducible tool for adjudication of AR following TAVI. <strong>Methods:</strong> This is a retrospective corelab analysis, independent from industry, of aortograms from patients treated with TAVI using the balloon-expandable Myval transcatheter heart valve (THV) (Meril Life Sciences Pvt. Ltd., India), Sapien 3, and XT THVs (Edwards Lifesciences, Irvine, CA, USA). The study comprised of 108 analyzable aortograms from consecutive patients in a multicenter European registry who underwent Myval THV implantation. The results of quantitative assessment of AR in the Sapien 3 THV (n = 397) and Sapien XT THV (n = 239) were retrieved from a published pooled database. <strong>Results:</strong> The Myval THV had the lowest proportion of patients with moderate or severe angiographic quantitative AR (2.8%) compared to the Sapien 3 THV (8.3%; p = 0.049) and Sapien XT THV (10.9%; p = 0.012). Furthermore, the Myval THV had the lowest mean angiographic quantitative AR (6.3 ± 6.3%), followed by Sapien 3 THV (7.6 ± 7.1%) and Sapien XT THV (8.8 ± 7.5%), and it was significantly lower than that of the Sapien XT THV (p = 0.006), but not significantly different from Sapien 3 THV (p = 0.246). <strong>Conclusion:</strong> The Myval THV, in comparison with other BEV's analyzed in our database, showed a lower occurrence of moderate or severe AR after TAVI. These results should be confirmed in prospective cohorts of randomized patients with head-to-head THV comparisons.

We have investigated the relationship between changes in T-cell activation in the bronchial mucosa, airway responsiveness and eosinophilic inflammation in sensitized Brown-Norway rats exposed to ovalbumin (OVA). Rats sensitized intraperitoneally with OVA and exposed to OVA aerosol 21 days later showed an enhanced increase in lung resistance (RNL) to acetylcholine (P < 0.05), and a significant increase in the number of eosinophils, neutrophils and lymphocytes in bronchoalveolar lavage fluid (BAL) (P < 0.05), compared with sensitized but saline-exposed controls. There was a significant increase in cells expressing the T-cell activation marker CD25 (P < 0.05) and the numbers of CD8+ T cells (P < 0.05), but not in the numbers of CD2+ and CD4+ cells. Eosinophil counts in airway submucosal tissue, as assessed by staining with BMK-13; a monoclonal antibody that binds to eosinophil major basic protein (MBP), were increased in rats receiving sensitization and exposure to OVA compared with naive controls (P < 0.002). There were significant positive correlations between the increase in RL to acetylcholine and the numbers of CD25+ (r = 0.92, P < 0.001), CD4+ (r = 0.77, P < 0.05), CD8+ (r = 0.71, P < 0.05) and MBP+ (r = 0.72, P < 0.03) cells in the OVA-sensitized and exposed group, but not in saline-exposed or naive animals. The number of MBP+ cells also correlated with CD25 expression (r = 0.71, P < 0.05). We conclude that airway hyper-responsiveness and inflammatory cell infiltration caused by OVA exposure of sensitized animals is associated with the presence of activated T cells in the airway mucosa. CD8+ T cells may play a role in the regulation of events leading to eosinophil inflammation and airway hyper-responsiveness.

<b>Introduction:</b> Exacerbations can occur even in mild asthma. The risk of exacerbations can be reduced with as-needed budesonide/formoterol (BUD/FORM) or BUD maintenance+as-needed terbutaline vs as-needed terbutaline alone (SYGMA 1; NCT02149199). <b>Aims and Objectives:</b> This <i>post-hoc</i> analysis of SYGMA 1 examined the NNT with as-needed BUD/FORM or BUD maintenance to have an additional patient (pt) free from a severe or moderate/severe exacerbation over 1 year. <b>Methods:</b> SYGMA 1 was a 52-week, double-blind trial of pts with mild asthma randomised to placebo bid+terbutaline 0.5mg as needed (n=1277), placebo bid+as-needed BUD/FORM 200/6µg (n=1277) or BUD 200µg bid+as-needed terbutaline (n=1282). The NNT for as-needed BUD/FORM and BUD maintenance vs as-needed terbutaline after 1 year of treatment were compared. <b>Results:</b> When compared with as-needed terbutaline, treating 16 pts with as-needed BUD/FORM, or 17 pts with maintenance BUD, for 1 year, prevented 1 additional pt having a severe exacerbation, reducing to 9 and 10 pts, respectively, for moderate/severe exacerbations (Table). <b>Conclusions:</b> The numbers needed to treat for a year with as-needed BUD/FORM to prevent one pt having a severe or moderate/severe exacerbation vs as-needed terbutaline were comparable to BUD maintenance, regardless of pre-study treatment, supporting a role for these therapies in mild asthma.

No abstract is provided for this article.

Background The efficacy and safety of ticagrelor monotherapy in elderly patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) or stable coronary artery disease (CAD) has not been evaluated. Purpose To evaluate the efficacy and safety of ticagrelor monotherapy following 1-month dual antiplatelet therapy (DAPT) after PCI in relation to age and clinical presentation in the GLOBAL LEADERS study cohort. Methods This is a subanalysis of the randomized multicentre GLOBAL LEADERS study, comparing the experimental strategy of 23-month ticagrelor monotherapy after 1 month of ticagrelor and aspirin with the reference strategy of 12-month DAPT followed by 12-month aspirin monotherapy in 15991 patients undergoing PCI. Patients were categorized into elderly and very elderly according to a pre-specified cut-off of 75 years and a post-hoc defined cut-off of 80 years. Impact of age and clinical presentation (ACS versus stable CAD) on clinical outcome at 2 years was evaluated. The primary endpoint was a composite of all-cause mortality or nonfatal, centrally adjudicated, new Q-wave myocardial infarction. Results In the overall elderly (&gt;75 years) population (n=2565), primary endpoint occurred in 7.2% of patients in the experimental group and in 9.4% of patients in the reference group (p=0.041) at 2 years (p int =0.23). Elderly patients in the experimental group had a lower rate of definite stent thrombosis (ST) (0.2% vs. 0.9%, p=0.043, p int=0.03), definite or probable ST (0.4 vs. 1.3%, p=0.015, p int=0.01) and a numerically higher rates of BARC 3 or 5 type bleeding (5.0% vs. 3.9%, p=0.192, p int=0.06), when compared to the reference arm. Among elderly patients presenting with ACS both treatment groups did not differ in the rates of primary endpoint (9.1% vs. 10.8%, p=0.367) and BARC 3 or 5 type bleeding (4.7% vs. 5.7%, p=0.458), whereas among elderly patients with stable CAD the experimental strategy was associated with numerically lower rates of the primary endpoint (5.7% vs. 8.4%, p=0.046) (p int =0.42) and a higher rate of BARC 3 or 5 type bleedings (5.3% vs. 2.6%, p=0.012) (p int =0.02) at 2 years. Exploratory analyses among very elderly (≥80 years) patients (n=1169) indicated no significant differences between treatment groups in the rates of the primary endpoint (10.2% vs. 11.7% p=0.411, p int=0.940) and BARC 3 or 5 type bleeding (6.0% vs. 5.3%, p=0.630, p int=0.514) at 2 years. Conclusions The efficacy and safety of the experimental treatment strategy of 23-month ticagrelor monotherapy after 1-month DAPT following PCI was not identified as age-dependent. Among elderly patients the anti-ischemic benefit was derived at the expense of increased rate of BARC 3 or 5 type bleeding in stable CAD subgroup, but not in ACS subgroup. Acknowledgement/Funding European Clinical Research Institute, which received unrestricted grants from Biosensors International, AstraZeneca, and the Medicines Company.

Aims:The aim of this substudy was to determine the five-year correlates of non-TV-related adverse events (AE) in STEMI patients included in the EXAMINATION trial. Methods and results:The EXAMINATION trial randomised 1,498 STEMI patients to bare metal or everolimus-eluting stent implantation.In this substudy, patients were analysed according to non-TV-related AE, defined as the composite of either non-TV revascularisation (non-TVR) or non-TV-related myocardial infarction (MI).At five-year follow-up, 125 patients (8.3%) exhibited 136 non-TV-related AE (124 [8.3%] non-TVR, 12 [0.8%]non-TV-related MI), accounting for 47.1% of 289 non-fatal cardiac events overall.These patients had a higher incidence of diabetes mellitus (p<0.001),arterial hypertension (p=0.032),previous MI (p=0.073),multivessel disease (p<0.001), and incomplete revascularisation (p=0.049), and a lower rate of ST-segment resolution >70% (p=0.042) as compared to the rest.At Cox analysis, previous MI (HR 1.872, 95% CI: 1.004-3.489;p=0.048), incomplete revascularisation (HR 1.746, 95% CI: 1.029-2.963;p=0.039) and diabetes (HR 1.942, 95% CI: 1.292-2.919;p=0.001) were independent correlates of non-TVrelated AE. Conclusions:In STEMI patients undergoing primary percutaneous coronary intervention, previous MI, incomplete revascularisation and diabetes resulted in being independent correlates of five-year non-TVrelated AE.