Distribution of hepatitis C virus in circulating blood components from blood donors.

BACKGROUND AND OBJECTIVES: Current nucleic acid tests (NAT) for blood donor screening use plasma as the test sample and, consequently, cannot detect virions bound to blood cells of infected donors. Hepatitis C virus (HCV) RNA and infectious virions have been detected in association with the cellular components of blood of patients with active liver disease; however, studies comparing HCV viral loads in whole blood and plasma have generated contradictory results. The aim of this study was to investigate the distribution of HCV in different compartments of the peripheral blood from HCV-infected blood donors, which may differ from that observed in patients with HCV-associated liver disease. MATERIALS AND METHODS: Hepatitis C virus-positive donor specimens were identified by NAT and antibody testing. HCV RNA was extracted from samples of whole blood and their corresponding components (RBC and plasma). Viral RNA was quantified by real-time qRT-PCR. RESULTS: Hepatitis C virus was present in all blood components from infected donors from which RNA could be amplified. For the majority of samples, plasma (34/46) had the highest detectable concentration of HCV RNA, and RBC (37/46) had the lowest. Specimens with negative NAT and positive antibody assays also produced qRT-PCR negative results. CONCLUSION: These results indicate that including the RBC fraction in the tested sample will not increase assay sensitivity. Although 10% of the specimens had a higher viral load in whole blood, there was no significant overall increase in sensitivity to justify changes in the specimen format. Thus, plasma specimens are well suited for blood donor screening for HCV.

Evidence of prolonged inflammation in unstable angina and non-Q wave myocardial infarction.

OBJECTIVES: This study was designed to document the inflammatory response up to one year after acute presentation with unstable angina (UA) and non-Q wave infarction (NQMI) as reflected by the expression of soluble cell adhesion molecules (CAMs). BACKGROUND: Coronary plaque inflammation is a key component in the pathogenesis of acute coronary syndromes. Cell adhesion molecules are critical mediators of the inflammatory process. Soluble forms of these molecules are detectable in serum and are elevated acutely in patients with UA and NQMI. METHODS: Patients presenting with UA and NQMI had serum samples taken at presentation and then after three, six and 12 months. A control group of similar age and gender distribution was used for comparison. Levels of soluble inter-cellular adhesion molecule-1, vascular cell adhesion molecule-1, endothelial-selectin and platelet-selectin were measured using an ELISA technique. RESULTS: We studied 91 patients (M/F = 73/18, mean age 62 +/- 11 years, 56 UA and 35 NQMI) and 24 controls (M/F = 18/6, mean age 56 +/- 12 years). Levels of all four soluble CAMs were significantly elevated in both UA and NQMI patients at presentation, three and six months in comparison with controls. Levels in UA and NQMI groups fell between six and 12 months after initial presentation. CONCLUSIONS: The results suggest that the inflammatory stimulus triggering expression of CAMs is sustained for up to six months after presentation with either UA or NQMI and then returns toward control values over the following six months.

Adhesion molecules in nonrheumatic aortic valve disease: endothelial expression, serum levels and effects of valve replacement.

OBJECTIVES: We studied the expression of intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and endothelial selectin (E-selectin) on aortic valve endothelium in patients undergoing valve replacement. We also assessed the relation between serum levels and endothelial expression and also the changes in serum levels following surgery. BACKGROUND: Nonrheumatic aortic valve disease is believed to be a degenerative condition. Increased tissue and soluble adhesion molecule levels are described in inflammatory conditions. METHODS: Aortic valves from 22 surgical (16 bicuspid, 6 tricuspid) and 6 autopsy (4 normal, 2 thickened) cases were studied by immunohistochemistry. Soluble adhesion molecules were measured in peripheral blood preoperatively, and at 6 and 18 months postoperatively, and compared with controls. RESULTS: The majority of the surgically removed tricuspid and bicuspid valves expressed adhesion molecules (E-selectin, 75% and 100%; ICAM-1, 75% and 80%; VCAM-1, 69% and 60%, respectively). The normal postmortem valves did not express these, while the diseased ones did. Endothelial expression of E-selectin correlated strongly with serum levels (r = 0.695, p = 0.004). Soluble E-selectin levels were significantly higher at baseline compared with controls (p = 0.017) and fell significantly at 18 months postoperatively (p = 0.005). CONCLUSIONS: Adhesion molecule expression on diseased valves supports an inflammatory component in "degenerative" aortic valve disease. The diseased valves may be the main source of elevated soluble E-selectin in this condition as blood levels correlate with endothelial expression and blood levels fall at 18 months postoperatively.

Early temporal expression of soluble cellular adhesion molecules in patients with unstable angina and subendocardial myocardial infarction.

Inflammation is increasingly considered to be involved in the pathogenesis of acute coronary syndromes. We documented persistent elevation in the levels of soluble ICAM-1 and soluble VCAM-1 and a decrease in the levels of soluble E-selectin in the first 72 hours of acute presentation in patients with unstable angina and subendocardial myocardial infarction.

Impact of preexisting statin use on adhesion molecule expression in patients presenting with acute coronary syndromes.

Of 147 patients admitted with acute coronary syndromes, 17 were taking statins at the time of presentation. These were matched with 17 subjects not taking statins. We found that statin therapy was associated with lower levels of sP-selectin, a marker of platelet and vascular endothelial activation. This provides further insight into the extralipid effect of statins in clinical practice and may help explain the greater-than-expected benefits of statin therapy in ischemic heart disease.

Helicobacter pylori serology in patients with angiographically documented coronary artery disease.

We studied the relation between angiographically defined coronary artery disease and serologic evidence of Helicobacter pylori infection in 488 patients undergo ing elective coronary angiography. There was no association between Helicobacter pylori infection and coronary artery disease (odds ratio 1.3, 95% confidence interval 0.83 to 2.16).

Restenosis following elective implantation of single Palmaz-Schatz stents in de-novo lesions in native vessels.

BACKGROUND: Restenosis is the main limitation of long-term success after coronary angioplasty. Intracoronary stent implantation may reduce restenosis by producing a larger initial lumen and eliminating recoil. The objective of this study was to determine the frequency of and features associated with restenosis after elective single Palmaz-Schatz stent implantation in de-novo lesions in native vessels. METHODS: Eighty consecutive patients were studied. Angiographic follow-up was performed in 79 out of 80 (99%) 6.5 +/- 3.4 months after the procedure. Angiographic measurements were performed using an automated computerized quantitative angiographic analysis system. RESULTS: Restenosis (> or = 50% stenosis) at follow-up occurred in 26 out of 79 patients (33%). The frequency of complex lesion morphology was higher (50% versus 19% American College of Cardiology/American Heart Association classification B2; P = 0.005), the reference vessel diameter larger (3.0 +/- 0.5 mm versus 2.8 +/- 0.6 mm, P = 0.049), and the lesion length longer (10.9 +/- 3.5 mm versus 8.5 +/- 3.5 mm, P = 0.009) in the restenosis group compared with the non-restenosis group. The population was divided into three groups according to the reference vessel diameter: (1) greater than 3.0 mm (n = 27), (2) 2.5-3.0 mm (n = 29), and (3) less than 2.5 mm (n = 22). One patient was excluded from this subgroup analysis because of difficulty in determining the reference vessel diameter before the procedure. The restenosis rates were 52%, 37%, and 11%, respectively, for the three groups (P = 0.02). The relative acute gain was greater in the smaller vessels, (0.66 in the < 2.5 mm vessels, 0.53 in the 2.5-3.0 mm vessels, and 0.48 in the > 3.0 mm vessels; P = 0.006). This was associated with a relative oversizing of the final stent balloon in the smaller vessels (balloon-to-vessel ratio of 1.33 in the vessels < 2.5 mm diameter, 1.16 in the 2.5-3.0 mm vessels, and 0.98 in the > 3.0 mm vessels; P = 0.001). CONCLUSION: The frequency of restenosis in single electively implanted Palmaz-Schatz stents in de-novo lesions in native vessels was 33%. The degree of restenosis was lower in smaller vessels, in which a better initial result was associated with relative oversizing of the final stent balloon. More aggressive dilation within the stented segment may result in a lower restenosis rate.

Reciprocal activation of leukocyte-endothelial adhesion molecules in acute coronary syndromes.

BACKGROUND: The acute coronary syndromes are associated with an intense inflammatory response and sustained leukocyte activation. This inflammatory state has been correlated with an adverse prognosis, but the source of this inflammation remains controversial, with evidence that it may arise either from the coronary vasculature or from the systemic endothelium. METHODS: Levels of soluble cell adhesion molecules, and of their respective monocyte cell surface ligands, were measured in the peripheral serum of 21 patients presenting with acute coronary syndromes. Soluble intercellular adhesion molecule-1 and soluble vascular cell adhesion molecule-1 were measured by enzyme linked immunosorbent assay and expression of the monocyte integrins CD11b (Mac-1) and CD49d (VLA-4) was measured by direct immunofluorescence using flow cytometry. RESULTS: High levels of the monocyte receptor CD11b (531 vs. 345 MFI, P<0.01), and its soluble intercellular adhesion molecule-1 (329 vs. 232 ng/ml, P<0.01), were noted in patients with acute coronary syndromes compared to healthy controls. CONCLUSIONS: Reciprocal activation of monocyte receptor ligands and endothelial adhesion molecules was found in the peripheral blood of patients with acute coronary syndromes. This may indicate a coordinated state of pro-inflammatory upregulation with widespread activation of both leukocytes and endothelium and suggests a systemic rather than local source for inflammation in acute coronary disease.

Relationship between intracoronary and peripheral expression of soluble cell adhesion molecules.

BACKGROUND: Elevated levels of soluble cell adhesion molecules (sCAMs) have been reported in various coronary artery disease processes. The principle stimulus for expression of sCAMs is believed to be an inflamed atherosclerotic plaque within the coronary vessel. The relationship between levels of sCAMs in the coronary circulation and the peripheral circulation has not been defined. The primary aim of this study was to define the relationship between levels of sCAMs sampled from the systemic circulation and from the coronary circulation. We also set out to document the acute expression of soluble CAMs following coronary angioplasty with or without stent implantation. METHODS: The coronary sinus was cannulated in patients undergoing LAD angioplasty. Samples were drawn from left coronary ostium (LCO) and coronary sinus (CS) and femoral vein simultaneously before, immediately after and 4 h after the PTCA procedure. Levels of sICAM-1, sVCAM-1, sE-selectin and sP-selectin were measured using ELISA technique. RESULTS: 10 patients (7 male/3 female, 61+/-11 y) entered the study. There was no significant difference in the levels of sICAM-1, sVCAM-1, sE-selectin and sPselectin whether sampled from left coronary ostium, coronary sinus or femoral vein at all time points. There was no significant change in the acute expression of sICAM-1, sVCAM-1 and sE-selectin following coronary angioplasty. Levels of sP-selectin fell significantly during the PTCA procedure (142+/-7 ng/ml to 64+/-6 ng/ml, P<0.001) but then rose again after 4 h and returned toward baseline levels at 24 h. CONCLUSION: Levels of soluble CAMs sampled in the systemic circulation directly reflect levels in the coronary circulation. Coronary angioplasty results in rapid fall in levels of sP-selectin which returns to normal within 24 h following the procedure.

Experience of immediate stenting, perfusion balloon and secondary stenting in failed angioplasty.

OBJECTIVE: To present a comparative analysis of the immediate and short term experience of stent implantation as the initial treatment for failed angioplasty (immediate stenting) with the staged approach of prolonged inflation with a perfusion balloon followed by stent implantation if prolonged inflation was unsuccessful (secondary stenting). DESIGN: Retrospective analysis of the outcome of 90 consecutive patients from a single institution undergoing one of these treatment strategies for failed angioplasty. INTERVENTIONS AND MAIN RESULTS: The initial treatment for failed angioplasty was prolonged inflation with a perfusion balloon in 59 and immediate stent implantation in 31 patients. Angiographic success (less than 50% residual and normal flow) was achieved in 24 of 59 (41%) with the perfusion balloon (mean duration of inflation 12.2 +/- 8.3 mins) and in 30 of 31 (97%) with immediate stent implantation (P = 0.0001). Of the 35 patients in whom the perfusion balloon was unsuccessful secondary stenting was attempted in 27, with angiographic success in 24 (89%). Stent thrombosis occurred in four (13%) of the immediate stent group and in three (13%) of the secondary stent group. Acute ischemia compatible with vessel occlusion occurred in one (4%) of the perfusion balloon alone group following an initially successful result. One month following the procedure, 23 (72%) of the patients treated with perfusion balloon alone, 26 (84%) of the immediate stent group and 21 (78%) of the secondary stent group had a successful outcome and were free from major complications. CONCLUSION: Immediate stent implantation and the staged approach of prolonged inflation with a perfusion balloon followed by secondary stent implantation if prolonged inflation was unsuccessful yielded similar results.

Inflammatory markers as predictors of clinical outcome in acute coronary syndromes.

Inflammation is a critical pathogenic component in acute coronary syndromes. As a consequence the potential use of inflammatory markers as predictors of clinical outcome in acute coronary syndromes has been investigated. This review outlines the pathology underlying acute coronary syndromes and reviews the published data on inflammatory markers in acute coronary syndromes.

Audit of acute myocardial infarctions at Saint James's Hospital, Dublin, from 1996 to 1999.

Saint James' Hospital is a 650-bed tertiary referral hospital. An audit was performed of acute transmural myocardial infarctions for the years 1996 to 1999 inclusive. On average there were 2043 cardiology admissions annually, 9.8% of all hospital admissions. Acute transmural myocardial infarction was diagnosed in 178 patients annually, and was less common during the summer. The figure of 72% receiving revascularisation therapy (thrombolysis 67%, primary angioplasty 5%) compares favourably with 35% in 1992. The main reason for not receiving thrombolysis was late presentation (15%) with contraindications present in only 5%. The case fatality rate was 16% confirming the higher mortality in clinical practice than that of thrombolytic trials. The prescription of aspirin or warfarin (99%) and betablockers (67%) was in line with international trials. The use of angiotensin converting enzyme inhibitors (34%) and statins (28%) is similar to other studies but less than would be expected according to trial evidence.

An unusual cause of abrupt vessel closure.

A 60 year old woman presented with chest pain. An ECG showed ST depression across the anterior leads and lateral T wave inversion and angiography showed a significant proximal circumflex lesion. After percutaneous intervention to the circumflex artery she had a cardiac arrest and died. Postmortem examination found a stent blocked with a combination of thrombus and a tangle of translucent material. Embolic coronary artery occlusion is well described but this is the first report of embolisation of material arising from the lining of the guiding catheter as the cause.

Alterations in reference vessel diameter following intracoronary stent implantation: important consequences for restenosis based on percent diameter stenosis.

The scaffolding effect of stent implantation has the potential to alter vascular geometry and dimensions. The objective of this study was to determine the impact of intracoronary stent implantation on the reference vessel diameter and the consequences of this on the frequency of restenosis applying the binary definitions of restenosis based on percent diameter stenosis. Routine angiographic follow-up was performed in 79/80 consecutive patients who had a single elective Palmaz-Schatz stent implanted in denovo lesions in native coronary arteries 6.5 +/- 3.4 mo after the index procedure. Complete quantitative angiographic follow-up was available in 78 (98%). The mean reference vessel diameter was 2.9 +/- 0.6 mm preprocedure, increased to 3.1 +/- 0.5 mm immediately poststent implantation and was 2.6 +/- 0.6 mm at follow-up (F = 6.45, P = 0.0001, ANOVA for repeated measures). In view of the varying reference vessel diameter, percent diameter stenosis postangioplasty and at follow-up was determined by two methods: (1) automatically by the quantitative coronary angiographic analysis system and (2) by expressing the minimal luminal diameter postangioplasty and at follow-up as a function of the original preprocedural reference vessel diameter. The restenosis rate was significantly greater for all definitions of restenosis when the minimal luminal diameter was determined as a function of the original preprocedure reference vessel diameter (e.g., 34% vs. 18% for the > or = 50% criterion, P = 0.018). Stent implantation results in alterations in reference vessel diameter, which have important consequences for the frequency of restenosis presented as a binary variable based on percent diameter stenosis.

Inflammation in acute coronary syndromes.

Extensive evidence supports a pathogenic role for both local and systemic inflammation in acute coronary syndromes. However, several important questions remain unanswered. Is the observed inflammatory process a precursor or a consequence of coronary plaque rupture? Is the inflammatory component of unstable coronary disease a potential therapeutic target? Finally, do infectious agents have a pathogenic role in coronary atherosclerosis and acute coronary syndromes?

Thrombosis and restenosis after stenting in failed angioplasty: comparison with elective stenting.

The results of Palmaz-Schatz stent implantation in failed angioplasty in 60 consecutive patients were compared with those of elective stent implantation in 100 consecutive patients. Stent implantation was successful in all of the failed group and in 99% of the elective. Stent thrombosis occurred in 16.7% of the failed group and 2% of the elective (p = 0.001). In the failed angioplasty group, stent thrombosis was associated with a greater frequency of preprocedure complex morphology (40% vs 12% in the nonthrombosis group, p = 0.05), persistent uncovered dissection after stenting (60% vs 14%, p = 0.004), and greater residual stenosis (39.9% +/- 25.3% vs 24.9% +/- 13.08%, p = 0.008) after stenting. Vessel patency was reestablished by angioplasty in 5 of 10 with stent thrombosis. Of these 5 patients, however, 2 suffered repeat stent thrombosis; 1 died suddenly four months later; and restenosis occurred in the remaining 2. Follow-up angiography was performed in 98% of the elective group at 6.3 +/- 2.6 months and 96% of the failed angioplasty group at 6.4 +/- 2.1 months. Restenosis (> or = 50% stenosis) occurred in 32% of the elective group and 50% of the failed angioplasty group (p = 0.041). Multiple logistic regression analysis identified multiple stent implantation (F = 6.75, p = 0.01) and triple-vessel disease (F = 3.46, p = 0.06) as independent positive predictors of restenosis. In conclusion, stent implantation in cases of failed angioplasty could be performed with a success similar to that of elective stent implantation but was associated with a greater frequency of stent thrombosis and restenosis.

Aggressive clinical pattern of angina at restenosis following coronary angioplasty in unstable angina.

The frequency, clinical pattern, and timing of recurrent angina following successful single-lesion percutaneous transluminal coronary angioplasty (PTCA) was assessed in a consecutive group of 104 patients with stable angina and in 85 with unstable angina. In addition, the relationship between lesion morphology and angiographic features and the pattern of recurrent angina was determined. Restenosis, defined as recurrence of symptoms with > 50% stenosis at the site of PTCA, occurred in 25 (24%) of the stable group and in 23 (27%) of the unstable group (p = NS). The pattern of angina at repeat presentation was aggressive in nature in 8% of the stable group and in 48% of the unstable group (p = 0.002). The time interval between the recurrence of symptoms and repeat coronary angiogram or PTCA was longer in the nonaggressive group than in the aggressive group, 16 +/- 12.1 and 5 +/- 6.8 weeks, respectively (p < 0.003). The key factors predicting the recurrent angina pattern identified by multiple logistic regression analysis were the angina status pre-PTCA (p = 0.001) and the presence of double-vessel disease (p = 0.01). An aggressive pattern of angina at the time of restenosis is frequent in patients with unstable angina at the time of PTCA, and close post-PTCA surveillance is necessary in these patients.

Occupancy of the internal and external pools of glycoprotein IIb/IIIa following abciximab bolus and infusion.

The internal pool of GPIIb/IIIa, which is expressed upon platelet activation, may be inaccessible to inhibition by GPIIb/IIIa antagonists. To determine the occupancy of the internal and external pools of GPIIb/IIIa and platelet function following an abciximab bolus and infusion, 15 patients undergoing elective percutaneous transluminal coronary angioplasty were administered abciximab as a bolus and 36-h infusion. GPIIb/IIIa receptor number and occupancy in resting and TRAP-6 (20 microM)-activated samples (to expose the internal pool of GPIIb/IIIa) was quantified using a monoclonal antibody-based assay. Antibody binding was quantified by flow cytometry and platelet inhibition by light transmittance aggregation and by the rapid platelet function analyser (Accumetrics, San Diego, CA). The target of >80% receptor occupancy (range 82--99% occupancy) of the external pool of GPIIb/IIIa was achieved in all patients at 3 min. Receptor occupancy of the combined internal and external pools of GPIIb/IIIa was less, ranging from 75 to 93% and again was maximal at 3 min. Platelet aggregation was markedly inhibited to 20 microM ADP (maximal, 11 +/- 2% of baseline), but less so to 5 microM TRAP-6 (maximal, 36 +/- 25% of baseline). Following discontinuation of the drug, there was a gradual fall in receptor occupancy over 15 days coinciding with the disappearance of abciximab from the platelet surface. Maximum inhibition of platelet function and receptor occupancy of the external pool of GPIIb/IIIa occurs within 3 min of an abciximab bolus and infusion. However, some internal receptors that are expressed by potent agonists are not occupied, which may explain the incomplete inhibition of platelet aggregation.