Publications

At present most systems used for three-dimensional (3D) reconstruction's of two-dimensional intracoronary ultrasound (ICUS) images are based on an image acquisition with a pull-back device which withdraws the catheter with a constant speed, not taking account of cardiac motion and coronary dynamics/pulsation. Cyclic changes of the vessel dimensions and the movement of the catheter inside the vessel result in artifacts and inaccuracies of quantitative analysis. Furthermore, most systems in use for this kind of analysis applications store the ICUS image data on video tape for off-line analysis, which results in quality loss. To overcome these limitations and to achieve a rapid on-line analysis without quality loss resulting from unnecessary A/D-conversions, ECG-gated acquisition and direct digitisation of ICUS images was performed on-line.

Objective: The role of oral immunosuppressive therapy (OIT) to prevent restenosis after percutaneous coronary intervention (PCI) and stenting is still controversial. This study evaluates the impact of oral administration of prednisone or sirolimus to prevent restenosis. Methods: We conducted a meta-analysis of trials in which PCI-patients were randomized to bare metal stents (BMS) plus OIT (BMS + OIT group) versus BMS or drug-eluting stents alone (BMS/DES group). Primary endpoints were target lesion revascularization and death/myocardial infarction (MI). Secondary endpoints were death, MI, stent thrombosis and in-stent late lumen loss. Hazard ratio and weighted geometric mean difference [95% confidence intervals] served as summary statistics. Results: Individual data of seven trials (1246 patients [BMS + OIT, n = 608 versus BMS/DES, n = 638] with 1456 coronary lesions) were merged. At a median follow-up of 360 days, BMS + OIT versus BMS/DES significantly reduced the risk of revascularization (0.49 [0.24–0.98], P = 0.04). In particular, BMS + OIT reduced the risk of revascularization (0.38 [0.21–0.67], P < 0.001) and late lumen loss (−0.39 mm [−0.67, −0.11], P < 0.001) as compared with BMS alone. BMS + OIT versus BMS/DES showed a similar risk of death/MI (0.67 [0.29–1.53], P = 0.34), death (0.82 [0.25–2.69], P = 0.71), MI (0.58 [0.24–1.39], P = 0.22) and stent thrombosis (0.43 [0.10–1.87], P = 0.26). Conclusion: In patients undergoing PCI the use of BMS and oral immunosuppressive therapy reduces the risk of revascularization as compared with BMS alone but not as compared with DES alone, while these therapies display a similar risk of death/MI. The advantage of adding oral immunosuppressive therapy to BMS is due to a lower risk of restenosis as compared with BMS alone.

Physiological assessment of coronary artery disease (CAD) has become one of the cornerstones of decision making for myocardial revascularization, with a large body of evidence supporting the benefits of using fractional flow reserve and other pressure-based indexes for functional assessment of coronary stenoses. Furthermore, physiology allows the identification of specific vascular dysfunction mechanisms in patients without obstructive CAD. Currently, more than 10 modalities of functional coronary assessment are available, although the overall adoption of these physiological tools, of either intracoronary or image-based nature, is still low. In this paper the authors review these modalities of functional coronary assessment according to their timing of use: outside the catheterization laboratory, in the catheterization laboratory prior to the percutaneous coronary intervention (PCI), and in the catheterization laboratory during or after PCI. The authors discuss how the information obtained can be used in setting the indication for PCI, in planning and guiding the procedure, and in documenting the final functional result of the intervention. The advantages and limitations of each modality in each setting are discussed. Furthermore, the key value of intracoronary physiology in diagnosing mechanisms of microcirculatory dysfunction, which account for the presence of ischemia in many patients without obstructive CAD, is revisited. On the basis of the opportunities generated by the multiplicity of diagnostic tools described, the authors propose an algorithmic approach to physiological coronary investigations in clinical practice, with the key aims of: 1) avoiding unneeded revascularization procedures; 2) improving procedural PCI and long-term outcomes in patients with obstructive CAD; and 3) diagnosing vascular dysfunction mechanisms that can be effectively treated in patients with NOCAD. The authors believe that such structured approach may also contribute to the wider adoption of available technologies for functional assessment of patients with CAD.

Objectives This study sought to evaluate late recoil of a novel bioabsorbable everolimus-eluting coronary stent (BVS), which is composed of a poly-L-lactic acid backbone, coated with a bioabsorbable polymer containing everolimus. Background Little is known about the mechanical behavior of bioabsorbable polymer stents after deployment in diseased human coronary arteries. Methods The study population consisted of 16 patients, who were treated with elective BVS implantation for single de novo native coronary artery lesions and were followed at 6 months. All patients underwent an intravascular ultrasound examination at post-procedure and follow-up. A total of 484 paired cross-sectional areas (CSAs) were acquired and analyzed. Late absolute stent recoil was defined as stent area at post-procedure (X) − stent area at follow-up (Y). Late percent stent recoil was defined as (X − Y)/X × 100. In each CSA, plaque morphology was assessed qualitatively and classified as calcific, fibronecrotic, or fibrocellular plaque. Results Late absolute and percent recoil of the BVS was 0.65 ± 1.71 mm2 (95% confidence interval [CI]: 0.49 to 0.80 mm2) and 7.60 ± 23.3% (95% CI: 5.52% to 9.68%). Calcified plaques resulted in significantly less late recoil (0.20 ± 1.54 mm2 and 1.97 ± 22.2%) than fibronecrotic plaques (1.03 ± 2.12 mm2 and 12.4 ± 28.0%, p = 0.001 and p = 0.001, respectively) or fibrocellular plaque (0.74 ± 1.48 mm2 and 8.90 ± 19.8%, p = 0.001 and p = 0.001, respectively). Conclusions The BVS shrank in size during the follow-up period. The lesion morphology of stented segments might affect the degree of late recoil of the BVS. (ABSORB Everolimus Eluting Coronary Stent System First in Man Clinical Investigation; NCT00300131)

No abstract is provided for this article.

Background and Objectives: The burden of chronic obstructive pulmonary disease (COPD) disproportionately affects patients in low to middle-income countries. Although the Theophylline and Steroids in COPD Study (TASCS) showed no clinical benefit from administering low-dose theophylline and prednisone in COPD patients compared to placebo, it was hypothesized that those with elevated blood eosinophil counts would receive clinical benefit from the intervention. Methods: This was a post-hoc analysis of the TASCS dataset – a double-blinded, placebo-controlled trial conducted in patients with moderate–severe COPD in China. Participants were allocated 1:1:1 to low-dose oral theophylline (100mg bd) and prednisone (5mg qd; PrT), theophylline (100mg bd) and prednisone-matched placebo (TP), or double-matched placebo (DP) groups and followed-up for 48 weeks. A baseline count of ≥ 300 eosinophils/μL blood was categorized as elevated/eosinophilic, and the primary outcome was the annualized moderate-severe exacerbation rate. Results: Of 1487 participants eligible for analysis, 325 (22%) were eosinophilic. These participants were predominantly male (82%), had a mean (SD) age of 64 (± 8) years and a predicted forced expiratory volume in 1s (FEV 1 ) of 43% (± 16). The annualized moderate–severe exacerbation rate was significantly higher in the PrT group compared to the pooled results of the TP and DP groups (incidence rate ratio = 1.6; ([95% CI 1.06– 1.76]) p = 0.016). Changes in spirometry values and reported disease impact scores (St. George’s Respiratory Questionnaire and COPD Assessment Test) at week 48 were not significantly different between groups. Conclusion: Combination low-dose theophylline and prednisone was associated with a significant increase in the annual moderate-severe exacerbation rate in participants with a blood eosinophil count ≥ 300 cells/μL compared to placebo. Keywords: eosinophil, COPD, clinical trial, China, theophylline, prednisone

Everolimus has been successfully tested in humans using both an erodable and a durable polymer in small previous studies.This single blind multi-centre non-inferiority randomised (3:1) controlled trial evaluated the safety and performance of the XIENCE V Everolimus Eluting Coronary Stent System (XIENCE V EECSS) versus the TAXUS Paclitaxel Eluting Coronary Stent System (TAXUS(R) PECSS) in the treatment of patients with a maximum of two de novo native coronary artery lesions located in two different epicardial vessels. Three hundred patients with evidence of myocardial ischaemia were allocated to stent implantation with an everolimus-eluting stent (n=223) or a paclitaxel-eluting stent (n=77). Suitable lesions had a diameter stenosis of <50-99%, a length of <28 mm, and a reference vessel diameter between 2.5 mm and 4.25 mm. The primary endpoint was in-stent late loss (LL) at 180 days. Percentage in-stent volume obstruction (%VO) was measured by intravascular ultrasound (IVUS) in a subset of 152 patients. Clinical secondary endpoints included ischaemia driven major adverse cardiac events (ID-MACE) at 180 days.At 6 months, the in-stent LL was 0.11+/-0.27 mm in the everolimus-eluting stent arm, as compared to 0.36+/-0.39 mm in the paclitaxel-eluting stent arm (p<0.0001). Percentage VO in the everolimus-eluting stent arm was 2.5+/-4.7% versus 7.4+/-7.0% in the paclitaxel-eluting stent arm (p<0.0001). Hierarchical MACE was 2.7% (6/222) in the everolimus-eluting stent arm vs. 6.5% (5/77) in the paclitaxel-eluting stent arm.This non-inferiority randomised trial not only met its primary endpoint, but also demonstrated the superiority of the everolimus-eluting stent over the paclitaxel-eluting stent in terms of in-stent late loss.

We investigate the accuracy of a new software system (C‐THV, Paieon) designed to calculate the optimal projection (OP) view for transcatheter aortic valve implantation (TAVI) based on two aortograms, and its agreement with the operator's choice. An optimal fluoroscopic working view projection with all three aortic cusps depicted in one line, is crucial during TAVI. In our institution selection of the OP is based on multislice computed tomography (MSCT). Seventy‐three consecutive patients referred for TAVI were divided into two groups. For the first group (53 patients, retrospective cohort) we compared the OP views estimated by C‐THV with the ones estimated by MSCT. For the second group (20 patients, prospective cohort), we compared the OP views estimated by C‐THV with the operator's choice during TAVI. For the retrospective cohort, the mean absolute difference (mean ± SD) between C‐THV and MSCT was 6.6 ± 4.9 degrees. In 77% of the cases the mean difference between C‐THV and MSCT was &lt;10 degrees. For the prospective cohort, the mean absolute difference (mean ± SD) between C‐THV and the operator's choice was 5.5 ± 3.4 degrees. A mean difference of &lt;10 degrees was found in 90% of the cases. In this study we found that the C‐THV software estimated the OP view for TAVI with good accuracy. The level of agreement between C‐THV and either the MSCT or the operator's choice was deemed satisfactory, with the vast majority of observed differences being &lt;10 degrees. © 2010 Wiley‐Liss, Inc.

Sirolimus-eluting stents (SESs) have been shown to decrease restenosis compared with bare metal stents (BMSs). Currently, there are limited data on the long-term efficacy of these devices in a real-world patient population. Furthermore, the potential of a late restenotic phenomenon has not yet been excluded. From April to October 2002, 508 consecutive patients with de novo lesions exclusively treated with SESs were enrolled and compared with 450 patients treated with BMSs in the preceding 6 months (control group). Patients in the SES group more frequently had multivessel disease and type C lesions, received more stents, and had more bifurcation stenting. After 3 years, the cumulative incidence of major adverse cardiac events (comprising death, myocardial infarction, and target vessel revascularization) was significantly lower in the SES group compared with the pre-SES group (18.9% vs 24.7%, hazards ratio 0.73, 95% confidence interval 0.56 to 0.96, p = 0.026). The 3-year risk of target lesion revascularization was 7.5% in the SES group versus 12.6% in the pre-SES group (hazards ratio 0.57, 95% confidence interval 0.38 to 0.87, p = 0.01). In conclusion, the unrestricted use of SESs is safe and superior to the use of BMSs. The beneficial effects, reported after 1 and 2 years in reducing major adverse cardiac events, persisted with no evidence of a clinical late restenotic “catch-up” phenomenon.

Background Studies on the inflammatory process in the large airways of patients with mild/moderate COPD have shown a prevalent T lymphocyte and macrophage infiltration of the bronchial mucosa. However, bronchial inflammation in more severe disease has not been extensively studied. Objective The aim of the present study was to characterize the lymphocyte infiltration in the bronchial mucosa of subjects with severe, compared to mild, COPD, and to examine the relationship between airflow limitation and T lymphocyte numbers in the bronchial mucosa. Methods We examined bronchial biopsies obtained from nine smokers with severe airflow limitation, nine smokers with mild/moderate airflow limitation and 14 smokers with normal lung function. Immunohistochemical methods on cryostat sections were used to assess the number of CD3 + , CD4 + , CD8 + cells and the number of CD3 + cells coexpressing the chemokine receptor CCR5 (CCR5 + CD3 + ) in the subepithelium. Results Subjects with severe COPD had lower numbers of CD3 + , CD8 + and CCR5 + CD3 + cells than mild/moderate COPD ( P &lt; 0.012, P &lt; 0.02 and P &lt; 0.02, respectively) and control smokers ( P &lt; 0.015, P &lt; 0.005 and P &lt; 0.015, respectively). In subjects with airflow limitation the number of CD3 + and CD8 + cells was inversely correlated with the degree of airway obstruction ( r = 0.59, P &lt; 0.015 and r = 0.52, P &lt; 0.032, respectively). Conclusions Bronchial inflammation in severe COPD is characterized by lower numbers of CD3 + and CD8 + cells and decreased numbers of CD3 + cells coexpressing the chemokine receptor CCR5. T lymphocyte infiltration is inversely correlated with the degree of airflow limitation.

In some species serotonin (5-HT) has been shown to act as a central modulator of the cough reflex. To investigate whether serotonergic mechanisms influence the control of the human cough reflex, we have induced cough responses before and during infusions of 5-HT; its precursor 5-hydroxytryptophan (5-HTP), which, in contrast to 5-HT, crosses the blood-brain barrier; and saline control. At the start of each study day, eight normal male volunteers were challenged with a single inhalation of a solution lacking chloride ions (0.15 M sodium bicarbonate) and a single breath of capsaicin during a sham infusion. After 3 h they received repeat cough challenges during experimental infusions of 5-HT, 5-HTP, or saline control, which were given randomly and single blind. Heart rate, respiratory rate, and blood pressure were measured before, during, and after each infusion. Both 5-HT and 5-HTP reduced cough responses to the chloride-deficient solution (P = 0.035 and P = 0.017, respectively) with respect to saline control, whereas neither infusion reduced responses to capsaicin. 5-HT caused a transient increase in heart rate that was not observed with a similar dose of 5-HTP or saline (P < 0.01). Respiratory rate and blood pressure were not affected by experimental infusions but rose during cough challenge. We conclude that 5-HT exerts an inhibitory influence over the human cough reflex at peripheral and possibly central sites.

A retrospective review of cardiac events occurring in all patients who underwent attempted coronary angioplasty in the first 5 years of our experience (1980-1985) was undertaken. Follow-up data were obtained from the civil registry, hospital records, patient, family, and referring physician. Patient survival curves were constructed and the outcome of women and men was compared. Eight hundred fifty-six patients, 172 women and 684 men with a mean age of 60.0 and 55.3 years, respectively, underwent attempted coronary angioplasty with an overall procedural success rate of 82%, 77.7% in women and 83.1% in men. Follow-up data were obtained in 837 patients (97.8%) with a mean period of 9.6 years (range 0-13.3 years). The estimated 10 year survival in women was identical to men [79%, 95% confidence interval (CI) 72.6–85.4% vs. 78%, 95% CI 74.6–81.4%] as was the 10 year event-free survival (men 36%, 95% CI 32.0–40.0% vs. women 37%, 95% CI 29.2-44.8%), with a similar proportion of major cardiac events—death, myocardial infarction, coronary artery bypass surgery, and repeat angioplasty. When women were matched to men for age and previous myocardial infarction, factors found to be associated with an adverse outcome, there was no significant difference. Additionally, outcome was compared after patients were matched for maximum nominal balloon size as an estimate of vessel size, with no significant difference between women and men. At follow-up, women complained of significantly more anginal symptoms than men (59.2% vs. 44.0%, P < 0.05) and took significantly more antianginal medication. © 1996 Willey-Liss, Inc.

No abstract is provided for this article.

Background Dyspnea represents a drug adverse effect reported with a higher frequency for ticagrelor, as compared with other P2Y12 antagonists. The impact of dyspnea on clinical outcomes has not been yet evaluated in the context of aspirin-free therapies after percutaneous coronary intervention (PCI). Purpose The study aimed to evaluate the incidence of dyspnea and its associations with demographic characteristics and clinical outcomes in patients undergoing PCI treated with ticagrelor either as monotherapy or as a part of a dual antiplatelet therapy (DAPT) in the GLOBAL LEADERS cohort. Methods This is a sub-analysis of the randomized all-comer GLOBAL LEADERS study (n=15991), comparing the experimental strategy of ticagrelor monotherapy following one-month DAPT after PCI with the reference strategy of 12-month DAPT followed by 12-month aspirin monotherapy. The incidence of dyspnea reported as adverse event (AE) and its relation to demographic characteristics and 2-year clinical outcomes was evaluated (intention-to-treat analysis). Multivariable Cox proportional hazards models were performed, including randomized treatment and incidence of first dyspnea event as a time-dependent covariate. The primary endpoint was a composite of 2-year all-cause mortality or centrally adjudicated, new Q-wave myocardial infarction (MI). Patient-oriented clinical endpoints (POCE) comprised all-cause death, any stroke, MI or revascularization, whereas net adverse clinical events (NACE) included POCE and Bleeding Academic Research Consortium (BARC)-defined bleeding type 3 or 5. Results Overall, dyspnea was reported as an AE in 2101 patients (13.2%) up to two years of follow-up, with a higher frequency in the experimental arm (16.4%) as compared with the reference group (11.1%) (hazard ratio [HR]1.70, 95% confidence interval [CI] 1.56–1.86, p=0.001). Predictors of dyspnea AE up to 2 years by multivariate analyses were: chronic obstructive pulmonary disease (HR1.71, 95% CI 1.56–1.87, p=0.001), female gender (HR1.31, 95% CI 1.18–1.44, p=0.001), hypertension (HR1.31, 95% CI 1.19–1.44, p=0.001, prior coronary artery bypass grafting (HR1.30, 95% CI 1.10–1.54, p=0.003), left ventricle ejection fraction below 40% (HR1.22, 95% CI 1.04–1.42, p=0.012), presentation with acute coronary syndrome (HR1.19, 95% CI 1.09–1.29, p=0.001) and body mass index (≥27kg/m2) (HR1.17, 95% CI 1.08–1.28, p=0.001). In patients who reported dyspnea AE, the two-year rates of the efficacy and safety endpoints in the experimental and reference arm were: for the primary endpoint 3.4% vs. 4.3% (p adjusted=0.807), for POCE 15.8% vs. 17.6% (p adjusted=0.218), for NACE 17.2% vs. 19.6% (p adjusted=0.082), for BARC 3 or 5 type bleeding 17.2% vs. 19.6% (p adjusted=0.082), respectively. Conclusions The occurrence of dyspnea AE up to two years after PCI appeared not to affect the safety of the experimental treatment strategy of 23-month ticagrelor monotherapy following one-month DAPT after PCI. Acknowledgement/Funding Study founded by European Cardiovascular Research Institute, which received unrestricted grants from Biosensors Int., AstraZeneca, Medicines Company.