[Troponins as biomarkers for myocardial injury and myocardial infarction]. / Troponine als Biomarker bei Myokardschaden und Myokardinfarkt.

Elevation of cardiac troponins above the 99th percentile of a healthy reference population is established as a marker for myocardial cell damage and is crucial for the diagnosis of myocardial infarction. In addition, corresponding clinical evidence of acute myocardial ischemia i.e. symptoms, changes in the electrocardiogram (ECG), wall motion abnormalities or suggestive angiographic findings are required for the diagnosis of myocardial infarction. Using modern highly sensitive assays myocardial infarction can be detected more frequently and earlier. On the other hand myocardial infarction can be ruled out with a higher diagnostic accuracy. Cardiac troponins are specific for myocardial cell damage but not for myocardial infarction and can be elevated in numerous other disease states. In these cases myocardial injury can be diagnosed independently of myocardial ischemia. Typical dynamics with rise and fall of troponin levels can distinguish acute myocardial injury (e. g. pericarditis/myocarditis and pulmonary embolism) from chronic myocardial injury (e. g. cardiomyopathy). Clinically, highly sensitive troponin assays are currently recommended in addition to the 0/3 h and 0/1 h algorithms for rapid inclusion or exclusion of myocardial infarction.

[Acute coronary syndrome with ST-elevation]. / Akutes Koronarsyndrom mit ST­Strecken-Hebung.

The current guidelines of the European Society of Cardiology have up-dated and confirmed the role of a primary percutaneous coronary intervention (PCI) as the preferred reperfusion therapy in patients with acute coronary syndrome and ST-elevation. The establishment of regional network structures for implementation of this reperfusion strategy is recommended and described. Primary PCI should preferably be carried out via the transradial route and should include the implantation of modern drug-eluting stents. In most cases of coronary multivessel disease, primary PCI should be limited to the treatment of the infarcted artery. Routine mechanical thrombus aspiration during primary PCI is no longer recommended. Recommendations for a specific anti-thrombotic and secondary prophylactic medication after primary PCI are highlighted.

[Acute coronary syndrome without ST-elevation (NSTE-ACS)]. / Akutes Koronarsyndrom ohne ST-Hebung (NSTE-ACS).

The timing of an invasive diagnosis and treatment strategy in patients with an acute coronary syndrome without ST-elevation (NSTE-ACS) depends on the patient's risk profile. In addition to the clinical symptoms, ST/T alterations in the resting ECG as well as an increase and kinetics of troponin are of crucial importance in this setting. For the majority of patients the highly sensitive troponin enables a rapid rule in or rule out strategy of a non-ST-segment elevation myocardial infarction (NSTEMI) with a 0/3 h algorithm. An even faster 0/1 h algorithm is increasingly being used; however, troponin only helps to identify patients with NSTEMI. Troponin-negative patients can still suffer from unstable angina pectoris. A dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASS) and an ADP receptor antagonist should be initiated in the acute phase and continued for 12 months, irrespective of the initial treatment strategy, e.g. percutaneous coronary intervention (PCI), bypass surgery or conservative treatment. In patients with a high bleeding risk a duration of 6 months only may be considered, whereas in patients with a high risk of ischemia the DAPT might be prolonged for up to 36 months.

Polymorphisms of the tumor necrosis factor-alpha (TNF) and the TNF-alpha converting enzyme (TACE/ADAM17) genes in relation to cardiovascular mortality: the AtheroGene study.

Tumor necrosis factor (TNF) is a major cytokine involved in inflammatory reaction and a mortality predictor in patients with coronary artery disease (CAD). Plasma levels of soluble TNF (sTNF) depend on the rate of its synthesis but also on its shedding from cell surface, a mechanism mainly regulated by the TNF alpha converting enzyme (TACE or ADAM17). We investigated the relationship between ADAM17 and TNF polymorphisms, circulating levels of shed ADAM17 substrates (sTNF, sTNFR1 and sTNFR2), and cardiovascular risk in a prospective cohort of CAD patients. Five tag single-nucleotide polymorphisms (SNPs) of the ADAM17 gene as well as four previously described TNF SNPs were genotyped in the Atherogene Study composed of 1,400 CAD patients among which 136 died from a cardiovascular (CV) cause. sTNF, sTNFR1, and sTNFR2 concentrations were all significantly elevated in patients with future CV death, independently of other clinical/biological variables. While none of the studied TNF SNPs was associated with sTNF, sTNFR1, nor sTNFR2 levels, the ADAM17 -154A allele was found associated with a 14% increase of sTNF levels as compared to the -154C allele (p = 0.0066). Moreover, individuals carrying the 747Leu allele displayed a borderline increased risk of future cardiovascular death [odds ratio, 2.06 (1.05-4.04), p = 0.03]. These results suggest a role of ADAM17 in the regulation of sTNF plasma levels and identifies ADAM17 gene as a candidate for CAD. Tumor necrosis factor (TNF) is a major cytokine involved in inflammatory reaction and a mortality predictor in patients with coronary artery disease (CAD). We have studied the association of ADAM17 and TNF polymorphisms with circulating levels of shed ADAM17 substrates (sTNF, sTNFR1 and sTNFR2) and with cardiovascular risk in a large population of individuals with CAD (Atherogene Study, n = 1,400). Two newly identified polymorphisms, obtained by a systematic sequencing of the ADAM17 gene, C-154A and Ser747leu, slightly influence respectively sTNF plasma levels and the risk of cardiovascular death.

Prognostic value of plasma tissue factor and tissue factor pathway inhibitor for cardiovascular death in patients with coronary artery disease: the AtheroGene study.

BACKGROUND: Tissue factor (TF) and its specific inhibitor, tissue factor pathway inhibitor (TFPI), are important contributors to the initiation of the coagulation process. OBJECTIVES: To compare plasma levels of soluble TF (sTF) and free-TFPI (f-TFPI) between patients with stable angina pectoris (SAP) and acute coronary syndrome (ACS) and to assess the impact of the two variables on long-term prognosis. PATIENTS/METHODS: Patients with SAPs (n = 1146) and acute coronary syndrome (n = 523) from the AtheroGene study were included and followed for 2.3 years. Because of the strong impact of unfractionated heparin (UFH) on f-TFPI levels, but not on sTF levels, patients having received UFH before blood drawing were excluded from the analyses on f-TFPI (n = 226). RESULTS: On admission, no significant differences in sTF levels were observed between SAP and ACS patients. By comparison to patients with stable angina, f-TFPI levels significantly increased in patients with acute unstable angina and further increased in patients presenting with non-ST-elevation myocardial infarction and ST-elevation myocardial infarction (P < 10(-4)). Among the 1669 individuals with a coronary artery disease, 56 died from a cardiovascular cause. In prospective analyses, high sTF levels were independently associated with an increased risk of cardiovascular death in individuals with ACS (fully adjusted hazard ratio associated with one quartile increase = 2.06; 95% confidence interval 1.24-3.45; P = 0.006) but not in those with SAP (hazard ratio = 1.07; 95% confidence interval 0.78-1.46; P = 0.67). In SAP and ACS patients, high f-TFPI levels were not independently associated with an increased risk of cardiovascular death. CONCLUSIONS: Plasma sTF levels were predictive of cardiovascular mortality in individuals with ACS, whereas f-TFPI levels were associated with the severity of myocardial damage on admission but were not independently related to outcome.

Haemostatic factors and the risk of cardiovascular death in patients with coronary artery disease: the AtheroGene study.

OBJECTIVE: To get a better insight into the role of hemostasis in coronary artery disease (CAD), we assessed the impact of von Willebrand factor (vWF), fibrinogen, thrombin-antithrombin (TAT) complexes, D-dimers, and plasmin-antiplasmin (PAP) complexes on the risk of cardiovascular event in a prospective cohort of CAD patients. METHODS AND RESULTS: The prospective Atherogene cohort includes 1057 individuals with an angiographically proven coronary artery disease at baseline. After a median follow-up of 6.6 years, 135 individuals died from a cardiovascular cause and 97 had a nonfatal cardiovascular event. Higher levels of all 5 hemostatic markers at baseline were associated with an increased risk of cardiovascular death, but not of nonfatal event. Except for vWF, these associations remained significant after adjustment for conventional cardiovascular risk factors and C-reactive protein (CRP) levels (P for trend according to increasing tertiles=0.20, 0.011, 0.026, 0.019, and 0.01 for vWF, fibrinogen, TAT, D-Dimer, and PAP, respectively). When including the 5 hemostatic markers in a stepwise Cox regression analysis where conventional risk factors and CRP were forced into the model, fibrinogen and D-dimers remained independently associated with the risk of cardiovascular death. Adjusted hazard ratios (95% CI) associated with one SD increase of fibrinogen and D-dimers were 1.27 (1.04 to 1.55) and 1.29 (1.09 to 1.53), respectively. CONCLUSIONS: In patients with coronary artery disease, fibrinogen and D-dimer levels are independent predictors of subsequent cardiovascular death. Our data support a role of impaired coagulation/fibrinolysis process in the complications of coronary artery disease.

Long-term cost-effectiveness of clopidogrel in patients with acute coronary syndrome without ST-segment elevation in Germany.

Patients with acute coronary syndrome without ST-segment elevation receiving clopidogrel in addition to acetylsalicylic acid (ASA) showed a 20% risk reduction in comparison to patients receiving ASA monotherapy (CURE trial). Economic models for assessing the impact on costs exist for several countries but not for Germany on a long-term basis. The objective of this model adaptation is to assess the long-term economic impact of clopidogrel taken in addition to ASA in Germany. A Markov model with six states [at risk, first year with stroke, following years with stroke, first year with new myocardial infarction (MI), following years with MI, and death] was adapted for Germany. Model outcome was life-years saved. Effects of 1-year treatment were calculated based on the CURE trial. Resource use for the different health states was based on published data, which included costs for drugs, outpatient care, hospitalization, rehabilitation and nursing. Risk data for MI and stroke were based on Swedish data and validated for the German adaptation. The model calculates lifetime costs and survival length. Costs were estimated from the payers' perspective. A series of one-way sensitivity analyses was conducted (follow-up costs, discount rates). The Markov analysis predicts a survival of 8.89years in the placebo treatment group and 9.02 years in the clopidogrel treatment group. The cumulated costs were euro 8,548 and euro 8,953, respectively. The incremental cost-effectiveness ratio (ICER) was euro 3,113 for each life-year saved. The model was robust regarding variations in key parameters in the sensitivity analysis, resulting in a range of ICER from euro 1,338 to euro 9,322. Our results are in line with the results for other healthcare systems. Adding clopidogrel to ASA for patients with acute coronary syndrome without ST-segment elevation generated an additional life-year saved at a comparably low value of euro 3,113. One-year treatment with clopidogrel is a cost-effective treatment option in patients with acute coronary syndrome from the perspective of a third-party payer in Germany.

The predictive value of different equations for estimation of glomerular filtration rate in patients with coronary artery disease - Results from the AtheroGene study.

BACKGROUND: Impaired renal function leads to dramatically increased risk for the development and progression of coronary artery disease (CAD). Therefore we aimed to assess the predictive value of different equations for estimated glomerular filtration rate (eGFR) in CAD-patients. METHODS: From the AtheroGene study 2135 patients were included. eGFR was calculated using the 4-variable Modification of Diet in Renal Disease (4MDRD) equation for serum creatinine (sCr), the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation for sCr and cystatin C (CysC) each alone, and in combination (CysC/sCr). eGFR was assessed regarding the combined outcome of cardiovascular death and non-fatal myocardial infarction and regarding complex CAD represented by a SYNTAX score ≥23. Median follow-up was 4.3years. RESULTS: Only the CKD-EPI equation using CysC could differentiate between eGFR >90ml/min/1.73m(2) vs. eGFR 60-90ml/min/1.73m(2) according to the occurrence of an endpoint event (log-rank test p=0.009). In the Cox regression analysis only eGFR calculated by CKD-EPI equation for CysC (Hazard ratio per 1 standard deviation (HR) 1.27 (95% CI 1.07-1.50); p=0.007) and for CysC/sCr (HR 1.22 (95% CI 1.02-1.46); p=0.026) were predictive regarding the outcome after adjustment for cardiovascular risk factors and Nt-proBNP. Furthermore, only eGFR calculated by CKD-EPI equation for CysC (odds ratio (OR) 1.57 (95% CI 1.36-1.78); p<0.001) and for CysC/sCr (OR 1.32 (95% CI 1.13-1.53); p<0.001) were significantly associated with a SYNTAX score ≥23. CONCLUSION: In patients with CAD the CKD-EPI equation for CysC and for CysC/sCr provided the best predictive value regarding the prognosis and the severity of CAD.

Double-blind study of the safety of clopidogrel with and without a loading dose in combination with aspirin compared with ticlopidine in combination with aspirin after coronary stenting : the clopidogrel aspirin stent international cooperative study (CLASSICS).

BACKGROUND: Combination therapy with the ADP receptor antagonist ticlopidine plus aspirin has emerged as standard care after coronary stenting. Clopidogrel, a new ADP receptor antagonist, has greater molar potency than ticlopidine and better safety/tolerability. METHODS AND RESULTS: Patients (n=1020) were randomized after successful stent placement and initiated on a 28-day regimen of either (1) 300-mg clopidogrel loading dose and 325 mg/d aspirin on day 1, followed by 75 mg/d clopidogrel and 325 mg/d aspirin; (2) 75 mg/d clopidogrel and 325 mg/d aspirin; or (3) 250 mg BID ticlopidine and 325 mg/d aspirin. The primary end point consisted of major peripheral or bleeding complications, neutropenia, thrombocytopenia, or early discontinuation of study drug as the result of a noncardiac adverse event during the study-drug treatment period. The primary end point occurred in 9.1% of patients (n=31) in the ticlopidine group and 4.6% of patients (n=31) in the combined clopidogrel group (relative risk 0.50; 95% CI 0.31 to 0.81; P=0.005). Overall rates of major adverse cardiac events (cardiac death, myocardial infarction, target lesion revascularization) were low and comparable between treatment groups (0.9% with ticlopidine, 1.5% with 75 mg/d clopidogrel, 1.2% with the clopidogrel loading dose; P=NS for all comparisons). CONCLUSIONS: The safety/tolerability of clopidogrel (plus aspirin) is superior to that of ticlopidine (plus aspirin) (P=0.005). The 300-mg loading dose was well tolerated, notably with no increased risk of bleeding. Secondary end point data are consistent with the hypothesis that clopidogrel and ticlopidine have comparable efficacy with regard to cardiac events after successful stenting.

Circulating cell adhesion molecules and death in patients with coronary artery disease.

BACKGROUND: Vascular cell adhesion molecule (VCAM)-1, intercellular adhesion molecule (ICAM)-1, and E-selectin mediate adhesion and transmigration of leukocytes to the vascular endothelial wall and may promote plaque growth and instability. In a prospective study, we evaluated the effect of soluble adhesion molecules on the risk of future cardiovascular events among patients with angiographically documented coronary artery disease (CAD). Methods and Results- -We obtained baseline samples from a prospective cohort of 1246 patients with CAD. Besides various markers of inflammation, soluble VCAM-1 (sVCAM-1), sICAM-1, and sE-selectin were determined. Follow-up information on cardiovascular events was obtained (mean, 2.7; maximum, 4.1 years). Independently higher levels of sVCAM-1 (1932 versus 1128 ng/mL; P<0.0001), sICAM-1 (353 versus 287 ng/mL; P=0.015), and sE-selectin (81 versus 63 ng/mL; P=0.003) were observed in patients with future death from cardiovascular causes. In a multivariate model, fatal risk was 2.1-fold (1.1 to 4.0) higher in patients within the top quartile of baseline sVCAM-1 concentrations compared with lower quartiles. This association was present independent of general inflammatory response as reflected by low or high C-reactive protein (hs-CRP) levels. In a model that simultaneously controlled for all inflammatory and soluble adhesion markers determined, only sVCAM-1 remained independently significant for future fatal cardiovascular events, with a 2.8-fold increase in risk (P=0.003). CONCLUSIONS: Soluble adhesion molecules sVCAM-1, sICAM-1, and sE-selectin were significantly related to future death from cardiovascular causes among patients with documented CAD. Especially sVCAM-1 added to the predictive value of classic risk factors and hs-CRP in determining the risk of future cardiovascular death.

Impact of viral and bacterial infectious burden on long-term prognosis in patients with coronary artery disease.

BACKGROUND: The number of infectious pathogens to which an individual has been exposed (infectious burden) may correlate with coronary artery disease (CAD). In a prospective study, we evaluated the effect of 8 pathogens and the aggregate pathogen burden on the risk for future fatal cardiac events among patients with angiographically documented CAD. Methods and Results-In 1018 patients, IgG or IgA antibodies to herpes simplex virus types 1 and 2, cytomegalovirus, Epstein-Barr virus, Haemophilus influenzae, Chlamydia pneumoniae, Mycoplasma pneumoniae, and Helicobacter pylori were determined. Moreover, highly sensitive C-reactive protein was measured. Follow-up information on cardiovascular events was obtained (mean 3.1 years, maximum 4.3 years). Seropositivities to Epstein-Barr virus (P=0.001), H pylori (P=0.002), and herpes simplex virus type 2 (P=0.045) were independently associated with the future risk of cardiovascular death. An increasing number for pathogen burden was significantly predictive of the long-term prognosis (P<0.0001). Infectious burden divided into 0 to 3, 4 or 5, and 6 to 8 seropositivities was associated with an increasing mortality of 3.7%, 7.2%, and 12.6%, respectively. Patients seropositive to >5 pathogens compared with those seropositive to <4 pathogens had a 5.1 (1.4 to 18.3) higher risk of future cardiac death. This result was mainly driven by the pathogen burden of seropositivities to Herpesviridae (P<0.0001). The prognostic impact of total or viral pathogen burden was independent of the C-reactive protein level. CONCLUSIONS: These results support the hypothesis that the number of infectious pathogens to which an individual has been exposed independently contributes to the long-term prognosis in patients with documented CAD.

Cardioprotective effects of the Na(+)/H(+) exchange inhibitor cariporide in patients with acute anterior myocardial infarction undergoing direct PTCA.

BACKGROUND: Activation of Na(+)/H(+) exchange in myocardial ischemia and/or reperfusion leads to calcium overload and myocardial injury. Experimental studies have shown that Na(+)/H(+) exchange inhibitors can attenuate Ca(2+) influx into cardiomyocytes. We therefore performed a multicenter, randomized, placebo-controlled clinical trial to test the hypothesis that inhibition of Na(+)/H(+) exchange limits infarct size and improves myocardial function in patients with acute anterior myocardial infarction (MI) treated with direct PTCA. METHODS AND RESULTS: One hundred patients were randomized to receive placebo (n=51) or a 40-mg intravenous bolus of the Na(+)/H(+) exchange inhibitor cariporide (HOE 642) (n=49) before reperfusion. Global and regional left ventricular functions were analyzed by use of paired contrast left ventriculograms performed before and 21 days after PTCA and myocardial enzymes (ie, creatine kinase ¿CK, CK-MB, and LDH) as markers for myocardial tissue injury were evaluated. At follow-up, the ejection fraction was higher (50% versus 40%; P<0.05) and the end-systolic volume was lower (69.0 versus 97.0 mL; P<0.05) in the cariporide group. Significant improvements in some indices of regional wall motion abnormalities were observed, such as the percentage of chords with hypokinesis < -2 SD (P=0.045) and the severity of hypokinesis in the border zone of the infarct region (P=0.052). In addition, CK, CK-MB, or LDH release was significantly reduced in the cariporide patients. CONCLUSIONS: Our findings suggest that inhibition of Na(+)/H(+) exchange by cariporide may attenuate reperfusion injury and thereby improve the recovery from left ventricular dysfunction after MI.

Cytomegalovirus infection with interleukin-6 response predicts cardiac mortality in patients with coronary artery disease.

BACKGROUND: Prospective data relating previous exposure to cytomegalovirus (CMV) to the risk of cardiac mortality are controversial. We investigated the effect of previous exposure to CMV infection on the risk of future cardiac disease-related death in relation to an underlying inflammatory response. METHODS AND RESULTS: coronary angiography was performed in 1134 subjects, and 989 patients with documented coronary artery disease were studied prospectively. CMV-IgG titers and interleukin (IL)-6 levels were measured before angiography. Increasing titers of CMV correlated with the elevation of IL-6 levels (P<0.001) after adjustment for possible confounders. All patients were followed up for a median of 3.1 years (maximum 4.3 years). During follow-up, 96 patients died, 70 of cardiac disease. Overall, CMV seropositivity was not related to cardiac mortality after adjustment for confounding variables (P=0.19). In contrast, in patients with elevated IL-6 levels (>/=11.9 pg/mL, median level), CMV seropositivity was independently associated with a 3.2-fold (95% CI 1.4 to 7.3, P=0.007) increase in risk of future cardiac death, whereas in individuals without IL-6 elevation, previous CMV infection had no effect on cardiac mortality. CONCLUSIONS: MV seropositivity in patients with an inflammatory response is independently associated with future cardiac mortality, whereas this association is lost in patients who do not demonstrate an inflammatory response. These data support the hypothesis that the atherosclerotic effects of CMV are mediated through an underlying inflammatory response.

Abciximab facilitates the rate and extent of thrombolysis: results of the thrombolysis in myocardial infarction (TIMI) 14 trial. The TIMI 14 Investigators.

BACKGROUND: The TIMI 14 trial tested the hypothesis that abciximab, the Fab fragment of a monoclonal antibody directed to the platelet glycoprotein (GP) IIb/IIIa receptor, is a potent and safe addition to reduced-dose thrombolytic regimens for ST-segment elevation MI. METHODS AND RESULTS: Patients (n=888) with ST-elevation MI presenting <12 hours from onset of symptoms were treated with aspirin and randomized initially to either 100 mg of accelerated-dose alteplase (control) or abciximab (bolus 0.25 mg/kg and 12-hour infusion of 0.125 microg. kg-1. min-1) alone or in combination with reduced doses of alteplase (20 to 65 mg) or streptokinase (500 000 U to 1.5 MU). Control patients received standard weight-adjusted heparin (70-U/kg bolus; infusion of 15 U. kg-1. h-1), whereas those treated with a regimen including abciximab received low-dose heparin (60-U/kg bolus; infusion of 7 U. kg-1. h-1). The rate of TIMI 3 flow at 90 minutes for patients treated with accelerated alteplase alone was 57% compared with 32% for abciximab alone and 34% to 46% for doses of streptokinase between 500 000 U and 1.25 MU with abciximab. Higher rates of TIMI 3 flow at both 60 and 90 minutes were observed with increasing duration of administration of alteplase, progressing from a bolus alone to a bolus followed by either a 30- or 60-minute infusion (P<0.02). The most promising regimen was 50 mg of alteplase (15-mg bolus; infusion of 35 mg over 60 minutes), which produced a 76% rate of TIMI 3 flow at 90 minutes and was tested subsequently in conjunction with either low-dose or very-low-dose (30-U/kg bolus; infusion of 4 U. kg-1. h-1) heparin. TIMI 3 flow rates were significantly higher in the 50-mg alteplase plus abciximab group versus the alteplase-only group at both 60 minutes (72% versus 43%; P=0.0009) and 90 minutes (77% versus 62%; P=0.02). The rates of major hemorrhage were 6% in patients receiving alteplase alone (n=235), 3% with abciximab alone (n=32), 10% with streptokinase plus abciximab (n=143), 7% with 50 mg of alteplase plus abciximab and low-dose heparin (n=103), and 1% with 50 mg of alteplase plus abciximab with very-low-dose heparin (n=70). CONCLUSIONS: Abciximab facilitates the rate and extent of thrombolysis, producing early, marked increases in TIMI 3 flow when combined with half the usual dose of alteplase. This improvement in reperfusion with alteplase occurred without an increase in the risk of major bleeding. Substantial reductions in heparin dosing may reduce the risk of bleeding even further. Modest improvements in TIMI 3 flow were seen when abciximab was combined with streptokinase, but there was an increased risk of bleeding.

Intravascular ultrasound after low and high inflation pressure coronary artery stent implantation.

OBJECTIVES: We sought to characterize the differences seen after low or high pressure coronary artery stent deployment as assessed by intravascular ultrasound. BACKGROUND: Until 1992, the success of stent deployment was assessed by angiographic criteria only, but in 1993 the procedure was expanded to include postprocedural single-use intravascular ultrasound imaging. Ultrasound criteria for successful stent deployment were 1) symmetry, 2) minimal lumen diameter > 3.0 mm, 3) no echo-free spaces between the stent and the vessel, and 4) no uncovered dissections. METHODS: We used mechanical 4.8F or 3.5F 20- or 30-MHz monorail single-use intravascular ultrasound catheters. RESULTS: Fifty-two patients were included, 28 treated in 1991 and 1992 (group A) and 24 treated in 1993 or 1994 (group B); 87% of patients underwent elective stent implantation. The number of echocardiographic studies per patient increased from 1 +/- 0.1 (mean +/- SD) in group A to 2.0 +/- 0.85 in group B. Mean maximal balloon size increased from 3.3 +/- 0.33 to 3.73 +/- 0.24 mm and maximal inflation pressure from 6.9 +/- 1.1 to 15.8 +/- 2.4 bar (p < 0.001). The eccentricity index was 0.915 +/- 0.04 in group B versus 0.87 +/- 0.05 in group A. Minimal lumen diameter measured by echocardiography increased from 2.55 +/- 0.41 mm in group A to 3.14 +/- 0.37 mm in group B. The final mean values per cross-sectional area as a percent of calculated balloon area were similar in group A (67.5 +/- 23%) and group B (66.5 +/- 22.9%). No major acute complications occurred in either group; subacute thrombosis developed in two patients, both in group A. CONCLUSIONS: Intravascular ultrasound data confirm that high pressure stent deployment leads to increased minimal lumen area. Despite high pressure stent deployment, homogeneous stent geometry and optimal stent expansion were not observed in all patients.

Percutaneous transluminal coronary angioplasty after thrombolytic therapy: a prospective controlled randomized trial.

In 162 patients with acute transmural myocardial infarction, combined intravenous and intracoronary thrombolytic therapy with streptokinase was initiated. In vessels that remained occluded, mechanical recanalization was performed with a 3F recanalization catheter (group I, n = 79) or a 4F Grüntzig balloon catheter (group II, n = 83). After reperfusion, intracoronary streptokinase was administered superselectively. After termination of streptokinase infusion, angioplasty was performed only in patients in group II. There was no difference between the groups in relation to sex, age, infarct location, creatine kinase levels and time between onset of symptoms and start of treatment. Initial coronary angiography showed an open vessel in 27 (34%) of 79 patients in group I and 21 (25%) of 83 patients in group II. The final reperfusion rate was 90% (71 of 79) in group I and 86% (71 of 83) in group II. Angioplasty was attempted in 69 of the 71 patients in group II with a success rate of 65% and an occlusion rate of 3%. During the hospital stay, reocclusion occurred in 14 (20%) of 71 patients in group I. After thrombolytic therapy, coronary luminal narrowing in group I was 75 +/- 17% in patients without and 87 +/- 6% in patients with reocclusion (p less than 0.05). In group II, reocclusion was found in 10 (14%) of 71 patients. After angioplasty, the degree of coronary stenosis in group II was reduced from 82 +/- 12 to 51 +/- 30% (p less than 0.001). Reocclusion was found in 3 (7%) of the 45 patients with successful angioplasty and in 7 (32%) of the 22 patients with unsuccessful angioplasty (p less than 0.01). Improvement in regional left ventricular function was observed only in patients from group II with anterior myocardial infarction. In conclusion, by combined medical and mechanical recanalization, the rate of coronary reperfusion can be increased and infarct time shortened, providing the possibility of full revascularization by angioplasty, with improvement of regional wall motion and reduction of the rate of reocclusion.

Recombinant hirudin (HBW 023) prevents troponin T release after coronary angioplasty in patients with unstable angina.

OBJECTIVES: This study was performed to evaluate the efficacy of peri-interventional treatment with recombinant hirudin (r-hirudin [HBW 023]) compared with heparin in the prevention of troponin T release in patients with unstable angina. BACKGROUND: Percutaneous transluminal coronary angioplasty in patients with unstable angina is associated with a high risk of acute thrombotic complications. METHODS: Serial troponin T measurements were performed in 61 patients with unstable angina during the 48-h observation period after coronary angioplasty of the ischemia-related lesion. Patients were randomly assigned to peri-interventional intravenous treatment with either r-hirudin (dosage group I: 0.3-mg/kg body weight bolus, 0.12 mg/kg per h for 24 h; dosage group II: 0.5-mg/kg bolus, 0.24 mg/kg per h for 24 h) or heparin (150-IU/kg bolus, 20 IU/kg per h for 24 h). All patients received acetylsalicylic acid before coronary angiography. After 24 h, patients received a constant low dose infusion of either hirudin (0.04 mg/kg per h) or heparin (7 IU/kg per h) for another 24 h. The power of the study to detect a decrease in abnormal troponin T levels from 60% (heparin group) to 20% (combined r-hirudin groups) was 88%. RESULTS: Serial troponin T measurements revealed two peaks within the 48 h after coronary angioplasty in the heparin but not the hirudin groups. An elevated serum troponin T concentration (> 0.2 ng/ml) within 48 h of coronary angioplasty was found in 9 (24%) of 38 patients in the hirudin groups (5 [25%] of 20 in dosage group I; 4 [22%] of 18 in dosage group II) compared with 11 (58%) of 19 in the heparin group (p = 0.01). We observed major cardiac events (death, myocardial infarction, abrupt vessel closure) in 1 (4.8%) of 21 patients in dosage group I, 1 (5.3%) of 19 in dosage group II and 3 (14.3%) of 21 in the heparin group (p = 0.33). CONCLUSIONS: In this pilot trial, hirudin appears to be superior to heparin in preventing troponin T release after coronary angioplasty.

Association between P-selectin gene polymorphisms and soluble P-selectin levels and their relation to coronary artery disease.

P-selectin is a cellular adhesion molecule that mediates the interaction of activated endothelial cells or platelets with leukocytes. Increased levels of soluble P-selectin have been reported in various cardiovascular disorders. We measured serum soluble P-selectin levels as well as 3 polymorphisms of the P-selectin gene (C-2123G, A-1969G, and Thr715Pro) in a large cohort of patients with documented coronary artery disease (n=869) and a healthy control group (n=334). The 3 P-selectin polymorphisms were strongly associated with P-selectin levels and altogether explained 7.3% and 18.6% of the P-selectin variability in patients and controls, respectively. Genotype distributions did not significantly differ between patients and controls. P-selectin levels were increased in patients younger than 55 years of age compared with controls (135.2 vs 114.3 ng/mL, P<0.01). On the contrary, patients older than 65 years of age had significantly lower P-selectin levels than did controls (121.5 vs 134.7 ng/mL, P<0.02). In intermediate age groups, P-selectin levels did not significantly differ between the 2 groups. In conclusion, this study revealed a strong association between P-selectin gene polymorphisms and serum P-selectin levels and a complex age-dependent relation between soluble P-selectin levels and coronary artery disease, which suggests that this molecule might have different roles in the atherothrombotic process.

Are morphological or functional changes in the carotid artery wall associated with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus, or herpes simplex virus infection?

BACKGROUND AND PURPOSE: Chronic infection with Chlamydia pneumoniae, Helicobacter pylori, cytomegalovirus (CMV), and herpes simplex virus (HSV) has been implicated in the pathogenesis of atherosclerosis. The carotid intima-media thickness (IMT) can be taken to indicate early atherosclerosis, the presence of a carotid stenosis is a marker of a manifest carotid atherosclerosis, and an increase in arterial stiffness is used as marker of structural and functional changes in an atherosclerotic vessel wall. METHODS: In 504 patients (75% men; mean age 62.9 [SD 10] years), we measured the IMT and the elastic pressure modulus (EP; n=445) of the common carotid artery and the prevalence of a internal or external carotid artery stenosis. Blood samples were taken, and antibodies against C pneumoniae, H pylori, CMV, and HSV types 1 and 2 were evaluated. Statistical evaluation was performed with regression procedures and multivariate logistic regression analyses. RESULTS: Seropositivity for C pneumoniae was an independent predictor for a combined end point of highest category of IMT and carotid artery stenosis (OR 1.8, 95% CI 1.1 to 3.1; adjusted) for IgG titers. Independently, CMV increased the risk for the combined end point (OR 1.7, 95% CI 1.1 to 2.8; adjusted) for IgG titers and for IgA titers (OR 2.3, 95% CI 1.1 to 4. 9; adjusted). We found a significant correlation between IgG antibodies against CMV and EP; HSV type 2 IgG titers were associated with IMT and carotid stenosis, but the latter results were no longer significant after adjustment. There was no association with H pylori or HSV type 1. CONCLUSIONS: We found a significant association of IgG antibodies against C pneumoniae and CMV with early and advanced carotid atherosclerosis. CMV was also correlated to functional changes of the carotid artery, but this could not be confirmed after adjustment.