Publications

Risk stratification in patients with stable ischemic heart disease is essential to guide treatment decisions. In this regard, whether coronary anatomy, physiology, or plaque morphology is the best determinant of prognosis (and driver an effective therapeutic risk reduction) remains one of the greatest ongoing debates in cardiology. In the present report, we review the evidence for each of these characteristics and explore potential algorithms that may enable a practical diagnostic and therapeutic strategy for the management of patients with stable ischemic heart disease.

We investigated the use of the CROSSER catheter, a CTO crossing device based upon high frequency mechanical vibration, as a first resort to treat patients with chronic total occlusions (CTO) while describing angiographic and computed tomography coronary angiography (CTCA) serving as predictors for success.Eighty consecutive patients were enrolled in this prospective multicentre registry of patients treated for a CTO. For 76.3% of the patients, this was the first attempt to open the CTO. Overall success rate was 75%. By conventional coronary angiography, the length of the occlusion was 26.7±14.1 mm and there was a difference in successful vs. unsuccessful cases (24.5±13.9 and 32.8±13.1, p=0.02). The presence of angulation, as defined qualitatively, was more prevalent in failed cases (60.0% vs. 32.2%, p=0.03). The mean ratio CROSSER distance within the occlusion site and length of the occlusion showed a trend towards statistical significance in successful procedures (0.56±0.90 vs. 0.30±0.34, p=0.08). During hospitalisation, two patients had a non-fatal myocardial infarction. One patient experienced delayed onset of tamponade six hours postprocedure. At 30 days, two patients had PCI in a non-treated vessel and one patient had a transient ischaemic attack. Relation to the CROSSER catheter was inconclusive.The success rate of the use of a dedicated-CTO device--the CROSSER catheter--as a first choice to open a chronic total occlusion was 75%. By multivariate analysis, in a subset of patients that were imaged with computed tomography coronary angiography, the absence of angulation was related with higher success rate.

Rupture of thin-cap fibroatheromatous plaques is a major cause of acute myocardial infarction (AMI). Such plaques can be identified in vitro by 3D intravascular palpography with high sensitivity and specificity. We used this technique in patients undergoing percutaneous intervention to assess the incidence of mechanically deformable regions. We further explored the relation of such regions to clinical presentation and to C-reactive protein levels.Three-dimensional palpograms were derived from continuous intravascular ultrasound pullbacks. Patients (n=55) were classified by clinical presentation as having stable angina, unstable angina, or AMI. In every patient, 1 coronary artery was scanned (culprit vessel in stable and unstable angina, nonculprit vessel in AMI), and the number of deformable plaques assessed. Stable angina patients had significantly fewer deformable plaques per vessel (0.6+/-0.6) than did unstable angina patients (P=0.0019) (1.6+/-0.7) or AMI patients (P<0.0001) (2.0+/-0.7). Levels of C-reactive protein were positively correlated with the number of mechanically deformable plaques (R2=0.65, P<0.0001).Three-dimensional intravascular palpography detects strain patterns in human coronary arteries that represent the level of deformation in plaques. The number of highly deformable plaques is correlated with both clinical presentation and levels of C-reactive protein. Further studies will assess the potential role of the technique to identify patients at risk of future clinical events

Intravascular ultrasound was designed to overcome the limitations of angiography, and in the process it has helped greatly with our understanding of coronary artery disease. There is no doubt that it plays an important role in contemporary interventional cardiology. In this regard, this chapter reviews the most important uses of intravascular ultrasound in current research.

No abstract is provided for this article.

Two new antagonists of platelet-activating factor (PAF), the pyrrolothiazole derivative 52770 RP and the triazolodiazepine WEB 2086, have been studied as radioligands in intact human platelets. [3H]52770 RP and [3H]WEB 2086 bound specifically to high-affinity sites with dissociation constants (Kd) of 14.8 and 6.1 nM, respectively. The maximal number of sites for [3H]52770 RP binding was approx. 15-fold higher than for [3H]PAF and [3H]WEB 2086. In addition, C16-PAF, lyso-PAF, WEB 2086 and 52770 RP had Ki values which were nearly identical for both [3H]PAF and [3H]WEB 2086, whereas only 52770 RP competed for [3H]52770 RP-binding sites. These results demonstrate that in human platelets the sites of [3H]WEB 2086 binding are identical to [3H]PAF-binding sites, whereas those of [3H]52770 RP are not. [3H]WEB 2086 appears, therefore, to be a suitable antagonist radioligand for labelling PAF receptors.

The purpose of this study was to assess the impact of body mass index (BMI) on clinical outcome of patients treated by percutaneous coronary intervention (PCI) using drug-eluting stents. Patients were stratified according to BMI as normal (<25 kg/m2), overweight (25 to 30 kg/m2), or obese (>30 kg/m2). At 5-year follow-up all-cause death, myocardial infarction, clinically justified target vessel revascularization (TVR), and definite stent thrombosis were assessed. A complete dataset was available in 7,427 patients, of which 45%, 22%, and 33% were classified according to BMI as overweight, obese, and normal, respectively. Mean age of patients was significantly older in those with a normal BMI (p <0.05). Incidence of diabetes mellitus, hypertension, and dyslipidemia increased as BMI increased (p <0.05). Significantly higher rates of TVR (15.3% vs 12.8%, p = 0.02) and early stent thrombosis (1.5% vs 0.9%, p = 0.04) were observed in the obese compared to the normal BMI group. No significant difference among the 3 BMI groups was observed for the composite of death/myocardial infarction/TVR or for definite stent thrombosis at 5 years, whereas the normal BMI group was at higher risk for all-cause death at 5 years (obese vs normal BMI, hazard ratio 0.74, confidence interval 0.53 to 0.99, p = 0.05; overweight vs normal BMI, hazard ratio 0.73, confidence interval 0.59 to 0.94, p = 0.01) in the multivariate Cox proportional hazard model. Age resulted in a linearly dependent covariate with BMI in the all-cause 5-year mortality multivariate model (p = 0.001). In conclusion, the “obesity paradox” observed in 5-year all-cause mortality could be explained by the higher rate of elderly patients in the normal BMI group and the existence of colinearity between BMI and age. However, obese patients had a higher rate of TVR and early stent thrombosis and a higher rate of other risk factors such as diabetes mellitus, hypertension, and hypercholesterolemia.

No abstract is provided for this article.

Corticosteroid resistance is a major barrier to the effective treatment of chronic obstructive pulmonary disease (COPD). Several molecular mechanisms have been proposed, such as activations of the phosphoinositide-3-kinase/Akt pathway and p38 mitogen-activated protein kinase. However, the mechanism for corticosteroid resistance is still not fully elucidated.To investigate the role of mammalian target of rapamycin (mTOR) in corticosteroid sensitivity in COPD.The corticosteroid sensitivity of peripheral blood mononuclear cells collected from patients with COPD, smokers, and nonsmoking control subjects, or of human monocytic U937 cells exposed to cigarette smoke extract (CSE), was quantified as the dexamethasone concentration required to achieve 30% inhibition of tumor necrosis factor-α-induced CXCL8 production in the presence or absence of the mTOR inhibitor rapamycin. mTOR activity was determined as the phosphorylation of p70 S6 kinase, using Western blotting.mTOR activity was increased in peripheral blood mononuclear cells from patients with COPD, and treatment with rapamycin inhibited this as well as restoring corticosteroid sensitivity. In U937 cells, CSE stimulated mTOR activity and c-Jun expression, but pretreatment with rapamycin inhibited both and also reversed CSE-induced corticosteroid insensitivity.mTOR inhibition by rapamycin restores corticosteroid sensitivity via inhibition of c-Jun expression, and thus mTOR is a potential novel therapeutic target for COPD.

Drug Prescribing for Patients with Chronic Kidney Disease in General Practice: a Cross-Sectional Study

Baseline and agonist-stimulated secretion of fucose, hexose, and protein (markers of mucus secretion) was investigated in vitro in 45 bronchial segments from 14 patients with cystic fibrosis (CF) (three after heart-lung transplant, the remainder < 4.5 h after autopsy), in 51 segments from 26 patients with carcinoma (24 resection, 2 after autopsy), and in 4 segments from 3 patients with bronchiectasis (resection). Basal rates of secretion of each mucus marker by CF bronchi were not significantly different from those by carcinoma bronchi bronchiectatic bronchi. However, rates of secretion of each marker in response to the cholinomimetic methacholine (10 microM; n = 11-18, depending on marker) and the beta 2-adrenoceptor agonist terbutaline (10 microM; n = 9-11) were significantly (p < .05) increased in carcinoma bronchi (by 50-117% above basal), but not in CF airways (n = 11-14). The secretory response to the sensory neuropeptide substance P (1 nM to 10 microM; n = 5-7) was also reduced in CF compared with carcinoma bronchi. Physiological and morphological data indicated that the reduced response by CF tissue could not be accounted for by inclusion of autopsy tissue in the study. These data suggest a defect in autonomic control of bronchial secretion in CF, not in the basal rate of secretion, but in its response to receptor stimulation.