Publications

Annexin I (lipocortin 1) is abundant in lung secretions. Concentrations rise after oral glucocorticoid, but the effect of inhaled budesonide on annexin I release is unknown. Extracellular annexin I in bronchoalveolar lavage fluid (BALF) from 11 asthmatic patients was unaffected by inhaled budesonide (800 microgramgs twice daily for 4 wk; mean after budesonide, 110 ng/mg albumin; after placebo, 107 ng/mg albumin). Rat alveolar macrophages (AMs) and alveolar epithelial type II (ATII) cells were cultured alone and with budesonide or dexamethasone. Mean basal concentrations of cellular (3.5 ng/10(6) AMs; 4.4 ng/10(6) ATII cells) and secreted (1. 4 ng/10(6) AMs; 1.8 ng/10(6) ATII cells) annexin I were similar in AMs and ATII cells. Although budesonide subdued annexin I secretion from both cell types, dexamethasone stimulated annexin I release. Annexin I release from ATII cells peaked at 10(-7) M dexamethasone but at 10(-3) M dexamethasone from AMs. Thus, at low concentrations of dexamethasone, ATII cells probably contribute more annexin I to respiratory tract secretions than AMs, although at high concentrations, both cells probably contribute. The study demonstrates previously undescribed differences between glucocorticoids and between AMs and ATII cells with respect to annexin I regulation.

Objectives We sought to assess the relationship between completeness of revascularization and adverse events at one year in the ARTS (Arterial Revascularization Therapies Study) trial. Background There is uncertainty to what extent degree of completeness of revascularization, using up-to-date techniques, influences medium-term outcome. Methods After consensus between surgeon and cardiologist regarding the potential for equivalence in the completeness of revascularization, 1,205 patients with multivessel disease were randomly assigned to either bypass surgery or stent implantation. All baseline and procedural angiograms and surgical case-record forms were centrally assessed for completeness of revascularization. Results Of 1,205 patients randomized, 1,172 underwent the assigned treatment. Complete data for review were available in 1,143 patients (97.5%). Complete revascularization was achieved in 84.1% of the surgically treated patients and 70.5% of the angioplasty patients (p < 0.001). After one year, the stented angioplasty patients with incomplete revascularization showed a significantly lower event-free survival than stented patients with complete revascularization (i.e., freedom from death, myocardial infarction, cerebrovascular accident and repeat revascularization) (69.4% vs. 76.6%; p < 0.05). This difference was due to a higher incidence of subsequent bypass procedures (10.0% vs. 2.0%; p < 0.05). Conversely, at one year, bypass surgery patients with incomplete revascularization showed only a marginally lower event-free survival rate than those with complete revascularization (87.8% vs. 89.9%). Conclusions Complete revascularization was more frequently accomplished by bypass surgery than by stent implantation. One year after bypass, there was no significant difference in event-free survival between surgically treated patients with complete revascularization and those with incomplete revascularization, but patients randomized to stenting with incomplete revascularization had a greater need for subsequent bypass surgery.

No abstract is provided for this article.

To determine the impact of Rheolytic thrombectomy (RT) on the clinical and angiographic outcome of patients with ST-elevation myocardial infarction (STEMI) and large thrombus burden (LTB).Two hundred sixty-six consecutive patients who presented from April 2002 until December 2004 with STEMI and LTB were retrospectively analyzed. LTB was defined as definite presence of thrombus with the greatest dimension greater > or = 2 vessel diameters by visual assessment. RT, as well as the interventional procedure and the peri-procedural pharmacological therapy, was at the discretion of the operator. All patients were followed for major adverse cardiac events (MACE) defined as death, non-fatal myocardial infarction (MI) and infarct-related artery revascularization. Pre- and post-procedural thrombolysis in myocardial infarction (TIMI) flow and thrombus burden as well as myocardial blush, distal embolization and no reflow were also determined.Complete follow-up was available in all patients; mean duration was 17 +/- 8.7 months. RT was used in 75 patients (28.2%). Stents were implanted in 251 (94.4%) patients; drug-eluting stents in 210 (84.6%) patients (15.5% sirolimus-eluting stents and 69.1% paclitaxel-eluting stents). The 2-year cumulative survival and MACE-free survival were higher in the RT compared to the non-RT group (92% vs. 82.7%, p = 0.051 and 87.7% vs. 69.9%, p = 0.004, respectively). Post-procedure indices (TIMI 3 flow, absence of thrombus and myocardial blush grade 3) of angiographic outcome were significantly better in the RT group. RT was an independent predictor of MACE (HR: 0.45, 95% CI: 0.22-0.93, p = 0.03).RT significantly improves the clinical and angiographic outcome of patients with STEMI and large thrombus burden.

Background The optimal revascularisation strategy for patients with left main coronary artery disease is uncertain. We therefore aimed to evaluate long-term outcomes for patients treated with percutaneous coronary intervention (PCI) with drug-eluting stents versus coronary artery bypass grafting (CABG). Methods In this individual patient data meta-analysis, we searched MEDLINE, Embase, and the Cochrane database using the search terms “left main”, “percutaneous coronary intervention” or “stent”, and “coronary artery bypass graft*” to identify randomised controlled trials (RCTs) published in English between database inception and Aug 31, 2021, comparing PCI with drug-eluting stents with CABG in patients with left main coronary artery disease that had at least 5 years of patient follow-up for all-cause mortality. Two authors (MSS and BAB) identified studies meeting the criteria. The primary endpoint was 5-year all-cause mortality. Secondary endpoints were cardiovascular death, spontaneous myocardial infarction, procedural myocardial infarction, stroke, and repeat revascularisation. We used a one-stage approach; event rates were calculated by use of the Kaplan-Meier method and treatment group comparisons were made by use of a Cox frailty model, with trial as a random effect. In Bayesian analyses, the probabilities of absolute risk differences in the primary endpoint between PCI and CABG being more than 0·0%, and at least 1·0%, 2·5%, or 5·0%, were calculated. Findings Our literature search yielded 1599 results, of which four RCTs—SYNTAX, PRECOMBAT, NOBLE, and EXCEL—meeting our inclusion criteria were included in our meta-analysis. 4394 patients, with a median SYNTAX score of 25·0 (IQR 18·0–31·0), were randomly assigned to PCI (n=2197) or CABG (n=2197). The Kaplan-Meier estimate of 5-year all-cause death was 11·2% (95% CI 9·9–12·6) with PCI and 10·2% (9·0–11·6) with CABG (hazard ratio 1·10, 95% CI 0·91–1·32; p=0·33), resulting in a non-statistically significant absolute risk difference of 0·9% (95% CI −0·9 to 2·8). In Bayesian analyses, there was an 85·7% probability that death at 5 years was greater with PCI than with CABG; this difference was more likely than not less than 1·0% (<0·2% per year). The numerical difference in mortality was comprised more of non-cardiovascular than cardiovascular death. Spontaneous myocardial infarction (6·2%, 95% CI 5·2–7·3 vs 2·6%, 2·0–3·4; hazard ratio [HR] 2·35, 95% CI 1·71–3·23; p<0·0001) and repeat revascularisation (18·3%, 16·7–20·0 vs 10·7%, 9·4–12·1; HR 1·78, 1·51–2·10; p<0·0001) were more common with PCI than with CABG. Differences in procedural myocardial infarction between strategies depended on the definition used. Overall, there was no difference in the risk of stroke between PCI (2·7%, 2·0–3·5) and CABG (3·1%, 2·4–3·9; HR 0·84, 0·59–1·21; p=0·36), but the risk was lower with PCI in the first year after randomisation (HR 0·37, 0·19–0·69). Interpretation Among patients with left main coronary artery disease and, largely, low or intermediate coronary anatomical complexity, there was no statistically significant difference in 5-year all-cause death between PCI and CABG, although a Bayesian approach suggested a difference probably exists (more likely than not <0·2% per year) favouring CABG. There were trade-offs in terms of the risk of myocardial infarction, stroke, and revascularisation. A heart team approach to communicate expected outcome differences might be useful to assist patients in reaching a treatment decision. Funding No external funding.

Background — Radioactive stents with an activity of 0.75 to 12 μCi have shown &gt;40% edge restenosis due to neointimal hyperplasia and negative remodeling. This trial evaluated whether radioactive Cold Ends stents might resolve edge restenosis by preventing remodeling at the injured extremities. Methods and Results — The 25-mm long (15-mm radioactive center and 5-mm nonradioactive ends) Cold Ends stents had an activity of 3 to 12 μCi at implantation. Forty-three stents were implanted in 43 patients with de novo native coronary artery disease. Two procedural, 1 subacute, and 1 late stent thrombosis occurred. A restenosis rate of 22% was observed with a shift of the restenosis, usually occurring at the stent edges of radioactive stents, into the Cold Ends stents. The most severe restenosis occurred at the transition zone from radioactive to nonradioactive segments, a region located in dose fall-off. Conclusion — Cold Ends stents did not resolve edge restenosis.

The inhibitory role of endothelium‐derived relaxing factor was studied in both rat and human pulmonary arteries in vitro by inhibiting its synthesis with the L‐arginine analogue N G ‐monomethyl‐ l ‐arginine ( l ‐NMMA). In rat pulmonary arteries, l ‐NMMA pretreatment (10–300 μ m ) dose‐dependently inhibited acetylcholine‐induced relaxation (which is endothelium‐dependent). N G ‐monomethyl‐ d ‐arginine ( d ‐NMMA, 100 μ m ) was without effect, l ‐Arginine, but not d ‐arginine, dose‐dependently reversed this inhibition. l ‐NMMA had no effect on relaxation induced by sodium nitroprusside. In human small pulmonary arteries l ‐NMMA (100 μ m ) pretreatment similarly inhibited the acetylcholine‐induced relaxation but had no effect on the sodium nitroprusside‐induced relaxation. In both rat and human pulmonary arteries, l ‐NMMA, but not d ‐NMMA, always caused contraction of preconstricted tissues whereas it had no effect on baseline tone. In the rat this contraction was completely prevented by prior treatment with l ‐arginine. l ‐NMMA (100 μ m ) pretreatment mimicked the effect of endothelium removal on phenylephrine‐induced vasoconstriction, both resulting in an increase in tension development at each concentration of phenylephrine. This enhancement was greatest at low concentrations of phenylephrine but was still present even at the highest concentrations. Pretreatment with l ‐NMMA (100 μ m ) also significantly increased the responses to single doses of phenylephrine. These results suggest that endothelium‐derived relaxing factor from endothelial cells both mediates the relaxation response to acetylcholine and also acts as a physiological brake against vasoconstriction in pulmonary vessels.

No abstract is provided for this article.

No abstract is provided for this article.

Background: Fractional flow reserve (FFR) is a reliable tool for the functional assessment of coronary stenoses. FFR computed tomography (CT) derived (FFR CT ) has shown to be accurate, but its clinical usefulness in patients with complex coronary artery disease remains to be investigated. The present study sought to determine the impact of FFR CT on heart team’s treatment decision-making and selection of vessels for revascularization in patients with 3-vessel coronary artery disease. Methods: The trial was an international, multicenter study randomizing 2 heart teams to make a treatment decision between percutaneous coronary interventions and coronary artery bypass grafting using either coronary computed tomography angiography or conventional angiography. The heart teams received the FFR CT and had to make a treatment decision and planning integrating the functional component of the stenoses. Each heart team calculated the anatomic SYNTAX score, the noninvasive functional SYNTAX score and subsequently integrated the clinical information to compute the SYNTAX score III providing a treatment recommendation, that is, coronary artery bypass grafting, percutaneous coronary intervention, or equipoise coronary artery bypass grafting-percutaneous coronary intervention. The primary objective was to determine the proportion of patients in whom FFR CT changed the treatment decision and planning. Results: Overall, 223 patients were included. Coronary computed tomography angiography assessment was feasible in 99% of the patients and FFR CT analysis in 88%. FFR CT was available for 1030 lesions (mean FFR CT value 0.64±13). A treatment recommendation of coronary artery bypass grafting was made in 24% of the patients with coronary computed tomography angiography with FFR CT . The addition of FFR CT changed the treatment decision in 7% of the patients and modified selection of vessels for revascularization in 12%. With conventional angiography as reference, FFR CT assessment resulted in reclassification of 14% of patients from intermediate and high to low SYNTAX score tertile. Conclusions: In patients with 3-vessel coronary artery disease, a noninvasive physiology assessment using FFR CT changed heart team’s treatment decision-making and procedural planning in one-fifth of the patients. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02813473.

No abstract is provided for this article.

Objectives We examined outcomes according to lesion preparation strategy (LPS) in patients with left main coronary artery (LMCA) percutaneous coronary intervention (PCI) in the EXCEL trial. Background The optimal LPS for LMCA PCI is unclear. Methods We categorized LPS hierarchically (high to low) as: (a) rotational atherectomy (RA); (b) cutting or scoring balloon (CSB); (c) balloon angioplasty (BAL); and d) direct stenting (DIR). The primary endpoint was 3‐year MACE; all‐cause death, stroke, or myocardial infarction. Results Among 938 patients undergoing LMCA PCI, RA was performed in 6.0%, CSB 9.5%, BAL 71.3%, and DIR 13.2%. In patients treated with DIR, BAL, CSB, and RA, respectively, there was a progressive increase in SYNTAX score, LMCA complex bifurcation, trifurcation or calcification, number of stents, and total stent length. Any procedural complication occurred in 10.4% of cases overall, with the lowest rate in the DIR (7.4%) and highest in the RA group (16.1%) ( p trend = .22). There were no significant differences in the 3‐year rates of MACE (from RA to DIR: 17.9%, 20.2%, 14.5%, 14.7%; p = .50) or ischemia‐driven revascularization (from RA to DIR: 16.8%, 10.8%, 12.3%, 14.2%; p = .65). The adjusted 3‐year rates of MACE did not differ according to LPS. Conclusions The comparable 3‐year outcomes suggest that appropriate lesion preparation may be able to overcome the increased risks of complex LMCA lesion morphology.