Background Experimental studies suggest that mural thrombus may be involved in postangioplasty restenosis. The aim of our study was to examine the role of angiographically identifiable thrombus in the clinical situation. Methods and Results The study population comprised 2950 patients (3583 lesions). The presence of angiographically identifiable thrombus either before or after the procedure was defined as the presence of a generalized haziness or filling defect within the arterial lumen. Restenosis was assessed by both a categorical (>50% diameter stenosis at follow-up) and a continuous approach (absolute and relative losses). The study population included 160 lesions with and 3423 lesions without angiographically identifiable thrombus. The categorical restenosis rate was significantly higher in lesions containing angiographically identifiable thrombus: 43.1% versus 34.4%, P <.01; relative risk, 1.449; CI, 1.051 to 1.997. The absolute and relative losses were also higher in lesions containing angiographically identifiable thrombus (absolute loss, 0.43±0.66 versus 0.32±0.52; relative loss, 0.16±0.26 versus 0.13±0.21; both P <.05). The higher restenosis in these lesions was due primarily to an increased incidence of occlusion at follow-up angiography in this group: 13.8% versus 5.7%, P <.001. When lesions that went on to occlude by the time of follow-up angiography were excluded from the analysis, the restenosis rate between the two groups was similar by both the categorical (34.1% versus 30.4%, P =NS; relative risk, 1.183; CI, 0.824 to 1.696) and continuous (absolute loss, 0.23±0.46 versus 0.24±0.42, P =NS; relative loss, 0.09±0.17 versus 0.09±0.16, P =NS) approaches. Conclusions Our results indicate that the presence of angiographically identifiable thrombus at the time of the angioplasty procedure is associated with higher restenosis. The mechanism by which this occurs is through vessel occlusion at follow-up angiography. Measures aimed at improving outcome in this group of patients should be focused in this direction.
The role of extracellular signal‐regulated kinase (ERK)‐1 and ERK‐2 in controlling histamine‐induced tone in bovine trachealis was investigated. PD 098059, an inhibitor of mitogen‐activated protein kinase kinase (MKK)‐1, had no effect on the histamine concentration‐response relationship that described contraction. However, in the presence of EGTA, PD 098059 produced a parallel 5 fold rightwards shift of the histamine concentration‐response curve without reducing the maximum response. The β 2 ‐adrenoceptor agonist, procaterol, also displaced the histamine‐concentration response curve to the right but the effect was much greater than that evoked by PD 098059, non‐competitive and seen in the absence and presence of EGTA. A low basal level of pERK‐1 and pERK‐2 was always detected in untreated trachealis, which was significantly higher in EGTA‐treated tissues and inhibited by PD 098059 and procaterol. Histamine markedly enhanced the phosphorylation of ERK‐1 and ERK‐2 by a mechanism that was also enhanced by EGTA and significantly attenuated by procaterol and PD 098059. Neither cholera toxin nor Sp ‐8‐Br‐cAMPS mimicked the ability of procaterol to dephosphorylate ERK. Similarly, neither pertussis toxin (PTX) nor Rp ‐8‐Br‐cAMPS, an inhibitor of cyclic AMP‐dependent protein kinase (PKA), affected basal pERK levels or antagonized the inhibitory effect of procaterol. These data implicate the MKK‐1/ERK signalling cascade in Ca 2+ ‐independent, histamine‐induced contraction of bovine trachealis. In addition, the ability of procaterol to dephosphorylate ERK in an Rp ‐8‐Br‐cAMPS‐ and PTX‐insensitive manner suggests that this may contribute to the anti‐spasmogenic activity of β 2 ‐adrenoceptor agonists by activating a novel PKA‐independent pathway. British Journal of Pharmacology (2000) 131 , 981–989; doi: 10.1038/sj.bjp.0703663
A damaged myocardium cannot effectively regenerate and repair itself subsequent to either acute or chronic pathologic insult. The emerging field of cell transplantation has attempted to address some of the issues and has progressed from preclinical studies to proof-of-concept clinical studies conducted in humans. Different cell types are being researched, including autologous skeletal muscle-derived myoblasts, bone marrow-derived mesenchymal stem cells and autologous bone marrow-derived stem cells. Other ongoing efforts are seeking to promote homing of bone marrow-g g derived cells to convert to cardiomyocytes in the myocardium, enhancement of the ability of cardiomyocytes to replicate and efforts to derive pluripotent stem cells from human blastocysts. While a variety of other cell types such as embryonic cardiomyocytes and embryonic stem cells have been investigated through preclinical studies, they have not progressed to clinical applications, for logistic and ethical reasons. The goal of any such therapy is to restore both an angiogenic and a muscular component to the myocardium by replacing damaged, fibrous scar tissue with compliant, elastic muscle tissue that would convert an akinetic or dyskinetic scar into tissue that augments systolic and diastolic function. The unique ability of skeletal muscle-derived stem cells (myoblasts) to form myotubes within the infarcted zones of the heart has led to the promotion of early pilot studies in humans.1-5 A secondary benefit would be that the compliance of the scar would be modified such that the pathologic remodeling process would be altered and would progress towards the baseline normal state.6-8 The challenge of replacing a large amount of dysfunctional and necrotic tissue is immense, and the ability to deliver, retain and engraft cells into a mechanically disadvantaged and neurohormonally altered environment has yet to be adequately addressed.
Objectives This study assessed the ability of the SYNTAX score (SXscore) to stratify risk in patients treated with percutaneous coronary intervention (PCI) using zotarolimus-eluting or everolimus-eluting stents. Background The SXscore can identify patients treated with PCI who are at highest risk of adverse events. Methods The SXscore was calculated prospectively in 2,033 of the 2,292 patients enrolled in the RESOLUTE All Comers study (RESOLUTE III All Comers Trial: A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention). Clinical outcomes in terms of a patient-oriented composite endpoint (POCE) of all-cause death, myocardial infarction (MI), and repeat revascularization; the individual components of POCE; target lesion failure (TLF) (a composite of cardiac death, target-vessel MI, and clinically driven target lesion revascularization); and stent thrombosis were subsequently stratified according to SXscore tertiles: SXscoreLOW ≤9 (n = 698), 9 <SXscoreMID ≤17 (n = 676); SXscoreHIGH >17 (n = 659). Results At 12-month follow-up, rates of POCE, MI, repeat revascularization, TLF, and the composite of death/MI were all significantly higher in patients in the highest SXscore tercile. Rates of stent thrombosis were all highest in the SXscoreHIGH tertile (p > 0.05). After multivariate adjustment, the SXscore was identified as an independent predictor of POCE, MI, repeat revascularization, and TLF (p < 0.05 for all). At 12-month follow-up, the SXscore, ACEF score, and Clinical SXscore had C-statistics of 0.57, 0.78, and 0.67, respectively, for mortality and of 0.62, 0.56, 0.63, respectively, for POCE. No significant between-stent differences were observed for TLF or POCE in any of the SXscore tertiles. Conclusions The SYNTAX score is able to stratify risk amongst an all-comers population treated with PCI with second-generation drug-eluting stents (DES); however, improvements can be made with the inclusion of clinical variables. (RESOLUTE III All Comers Trial: A Randomized Comparison of a Zotarolimus-Eluting Stent With an Everolimus-Eluting Stent for Percutaneous Coronary Intervention; NCT00617084)
No abstract is provided for this article.
