Patterns of activation and deposition of platelets exposed to the polymeric surface of the paclitaxel eluting stent.

The interaction of platelets with the polymeric surface of drug eluting stents has not been fully described in the literature. Our aim was to analyze the patterns of activation and deposition of platelets exposed to two different stent platforms; (a) the polymeric surface of the paclitaxel eluting stent (Taxus((R)) stent, PES,) and (b) the metallic surface of a stent with identical structural design (Express((R)) stent, BMS). Platelet activation was tested by deploying stents in an in vitro flow chamber model. Anticoagulated blood of 25 healthy volunteers was circulated (flow rate 10 ml/min for 60 min) into the flow chamber system. P-selectin expression, glycoprotein IIb/IIIa activation (PAC-1 binding) and platelet-monocyte complexes (PMC) formation were evaluated at 0, 10, 30 and 60 min. Surface platelet deposition was assessed by surface electron microscopy in stents implanted in the in vitro system for 60 min and in stents implanted in normal porcine coronary arteries for 24 h. Platelet activation evaluation showed a higher P-Selectin expression (92.9% of baseline in PES versus 68.3 % in BMS, P = 0.01) and higher PMC formation (125.7 % of baseline in PES versus 75.6% in BMS, P < 0.01) in the PES compared to the BMS control group. PAC-1 binding levels did not differ among groups. In the in vitro study, SEM analysis of the stent surface showed no statistical differences on platelet deposition between the groups. In addition, presence of proteinaceous material was more frequently seen on the BMS group (moderate to complete coverage = 80% in BMS versus 26% in PES, P < 0.01). In the in vivo study, complete platelet coverage was similar between groups (PES = 7% versus BMS = 8%, P = NS). However, there was an overall trend towards less platelet deposition on the BMS surface (mild and moderate coverage = 83%, 9% in BMS versus 49%, 44% in PES, P < 0.001 for both) but thrombus formation was not observed in either group. The polymeric surface of the PES appears to induce a higher degree of platelet activation and deposition compared to the BMS surface. The biological implications of these findings on the patterns of vascular healing need to be further studied in vivo. Condensed Abstract The interaction of human platelets with the surface of drug eluting stents has not been fully characterized. Patterns of platelet activation and adhesion were evaluated in vitro and in vivo after exposing platelets to the surface of the paclitaxel-eluting stent and identical bare metal stent. The degree of PMC formation and P-selectin expression was increased in PES compared to BMS. In the in vivo study, complete platelet coverage was similar between groups. There was an overall trend towards less platelet deposition on the BMS surface, however, thrombus formation was not observed on either surface. The polymeric surface of the PES appears to induce a higher degree of platelet activation and deposition compared to the BMS surface.

B-type natriuretic peptide (BNP) and proBNP: role of emerging markers to guide therapy and determine prognosis in cardiovascular disorders.

Over the last decade, one group of neurohormonal markers, including atrial natriuretic peptide (ANP), N-terminal pro-ANP, B-type natriuretic peptide (BNP), and N-terminal proBNP, has generated much interest in the evaluation and management of heart failure and acute coronary syndrome. There has been so much literature on the subject, especially concerning BNP and proBNP, that it leaves us confused at times about what the literature has to say about these markers. In this article, we have made an honest attempt to examine all the available literature in relation to the impact of BNP and proBNP on cardiovascular disease and present it to the reader in an assimilated fashion.

Comparison and co-relation of invasive and noninvasive methods of ejection fraction measurement.

BACKGROUND: Accurate estimation of left ventricular ejection fraction (LVEF) has assumed great significance in the era of automatic implantable cardioverter defibrillators (AICDs), and a low EF may be one of the sole deciding factor in determining AICD implantation in certain patient populations. AIM: There are various methods, invasive and noninvasive, which can help calculate EF. We sought to conduct a retrospective study comparing EF estimation by invasive (angiography) and noninvasive methods [MUGA (multiple-gated acquisition), echocardiography (echo), single-photon emission computed tomography (SPECT)] in 5,558 patients in our hospital from 1995-2004. METHODS AND RESULTS: EF was estimated by > or = 1 method (angiography, MUGA, echo, SPECT) within a one-month period. Values for the four tests in 5,558 patients were as follows: angiography mean 46.2, range 20-75, standard deviation (SD) 13.1; MUGA mean 45.7, range 20-70, SD 11.6; echo mean 45.7, range 22-70, SD 11.2; and SPECT mean 54.4, range 30-75, SD 11.9. Excellent positive correlations were found among all four tests as follows: angiography and MUGA, correlation coefficient (r) = 0.97, angiography and echo r = 0.96, angiography and SPECT r = 0.94, MUGA and echo r = 0.97, MUGA and SPECT r = 0.94, and echo and SPECT r = 0.94. Values for SPECT were significantly higher than for angiography, echo and MUGA (p < 0.001). The arithmetic difference between angiography and MUGA (mean 0.50, range -5.0-5.0) and the arithmetic difference between angiography and echo (mean 0.52, range -5.0-15.0) were similar (p = 0.59). The arithmetic difference between SPECT and angiography (mean 8.2, range -15.0-20.0) was significantly larger than the arithmetic difference between angiography and echo (p < 0.001). CONCLUSIONS: All the four methods used to estimate EF corelate well with each other. However, values estimated during stress testing by SPECT overestimate EF and are significantly higher as compared to MUGA, echo and angiography. Estimation of EF by MUGA, echo or angiography should be preferred over SPECT, especially when that patient warrants intervention. We conclude that the overestimation of EF by SPECT may deprive some deserving patients of the survival benefit afforded by ICD.

Platelet reactivity in patients with subacute stent thrombosis compared with non-stent-related acute myocardial infarction.

BACKGROUND: Recent case control studies suggest that patients with subacute stent thrombosis (SAT) have increased platelet reactivity. However, SAT often presents as acute myocardial infarction (AMI), which is also associated with augmented platelet activation. We therefore compared platelet reactivity in patients with SAT and patients with AMI unrelated to stenting. METHODS: We identified 20 patients with SAT, 20 patients with ST-elevation AMI who underwent primary percutaneous coronary intervention (PCI), and 20 patients who underwent stenting without SAT occurrence (stable control group). Platelet function was measured > or = 3 days after PCI in the SAT (repeat procedure) and AMI groups and > or = 3 months after stenting in the stable group. All patients received aspirin and clopidogrel. Platelet reactivity was evaluated by aggregation in response to 5 and 20 micromol/L of adenosine diphosphate and 1.5 mmol/L arachidonic acid, and by flow cytometric determination of P-selectin and glycoprotein IIb/IIIa activation. RESULTS: Clinical characteristics were similar among the groups. Platelet testing was performed 4.9 +/- 1.7, 3.1 +/- 0.3, and 108 +/- 22 days after PCI in the SAT, AMI, and stable groups, respectively. The SAT group had higher platelet aggregation and activation markers than the stable group. However, platelet aggregation and activation was very similar in the SAT and AMI groups. CONCLUSIONS: Patients with SAT have increased platelet reactivity, compared with patients who do not develop SAT following stenting. However, the augmented platelet reactivity does not appear to differ from patients with AMI unrelated to stenting. This study highlights the need for large prospective studies to determine whether platelet hyperreactivity increases the risk of SAT.