Bridge to operation with the GPIIb/IIIa inhibitor abciximab in high-risk coronary patients.

BACKGROUND: Glycoprotein-IIb/IIIa inhibitors are now frequently used in the cardiological treatment of high-risk coronary patients even if the patient is considered suitable for surgical intervention. However, there is no consensus whether GPIIb/IIIa inhibitors should be stopped before operation because of an increased risk of bleeding or if surgery should even be delayed until the anticoagulating effect subsides. METHODS: From June 2002 to August 2003 140 patients who had to undergo primary aorto-coronary bypass for ongoing myocardial ischemia were enrolled in the present study. The patients received either clopidogrel, aspirin and heparin or additionally abciximab until operation. RESULTS: Although the intraoperative need for blood products was higher in the abciximab group, there was no significant difference in postoperative blood loss. The hemodynamic situation of the abciximab patients after the operation was better compared to the other groups. 30-day mortality was not increased when compared to the elective control group (6.7 % vs. 6.1 %). CONCLUSION: The GPIIb/IIIa inhibitor abciximab can be safely used as a bridge to operation and results in a better hemodynamic outcome in high-risk coronary patients while reducing the incidence of major ischemic events.

Intravascular electric impedance spectroscopy of atherosclerotic lesions using a new impedance catheter system.

Newer techniques are required to identify atherosclerotic lesions that are prone to rupture. Electric impedance spectroscopy (EIS) can characterize biological tissues by measuring the electrical impedance over a frequency range. We tested a newly designed intravascular impedance catheter (IC) by measuring the impedance of different stages of atherosclerosis induced in an animal rabbit model. Six female New Zealand White rabbits were fed for 17 weeks with a 5% cholesterol-enriched diet to induce early forms of atherosclerotic plaques. All aortas were prepared from the aortic arch to the renal arteries and segments of 5-10 mm were marked by ink spots. A balloon catheter system with an integrated polyimide-based microelectrode structure was introduced into the aorta and the impedance was measured at each spot by using an impedance analyzer. The impedance was measured at frequencies of 1 kHz and 10 kHz and compared with the corresponding histomorphometric data of each aortic segment.Forty-four aortic segments without plaques and 48 segments with evolving atherosclerotic lesions could be exactly matched by the histomorphometric analysis. In normal aortic segments (P0) the change of the magnitude of impedance at 1 kHz and at 10 kHz (|Z|(1 kHz) - |Z|(10 kHz), = ICF) was 208.5 +/- 357.6 Omega. In the area of aortic segments with a plaque smaller than that of the aortic wall diameter (PI), the ICF was 137.7 +/- 192.8 Omega. (P 0 vs. P I; p = 0.52), whereas in aortic segments with plaque formations larger than the aortic wall (PII) the ICF was significantly lower -22.2 +/- 259.9 Omega. (P0 vs. PII; p = 0.002). Intravascular EIS could be successfully performed by using a newly designed microelectrode integrated onto a conventional coronary balloon catheter. In this experimental animal model atherosclerotic aortic lesions showed significantly higher ICF in comparison to the normal aortic tissue.

Diagnostic value of stress echocardiography for the detection of restenosis after PTCA.

Stress echocardiography (SE) has become a widely accepted clinical tool for the non-invasive diagnosis of coronary artery disease (CAD). Previous studies have confirmed that SE has superior diagnostic value compared to exercise ECG testing. SE has also emerged as a cost-effective alternative to nuclear imaging techniques in patients where symptoms and/or conventional ECG stress testing have provided ambiguous results. Several studies have investigated the value of SE to detect significant restenosis after PTCA. However, in these studies, different methods have been used to induce cardiovascular stress such as physical exercise by bicycle or treadmill, pharmacologic stress testing (with dipyridamole or dobutamine) or transoesphageal atrial pacing. This review evaluates the published database of SE to detect restenosis in patients after successful PTCA. It includes 13 studies with a total of 989 patients performed at 3-6 months after the primary intervention. The diagnostic value, utility and limitations of SE is presented and discussed. The data show that SE has a high diagnostic value for detecting significant restenosis after PTCA. Mean sensitivity of SE was 74% (CI 69-79%), mean specificity was 87% (CI 84-89%). The positive predictive value (PPV) of SE was 83%, the overall negative predictive value (NPV) 97%. We conclude that, in the follow-up of patients after PTCA, SE has distinct advantages over other non-invasive methods and is a recommended method for the detection of those to be considered for repeat angiography.

Drotrecogin alfa (activated) inhibits NF-kappa B activation and MIP-1-alpha release from isolated mononuclear cells of patients with severe sepsis.

OBJECTIVE AND DESIGN: Non-anticoagulant biological activities, such as anti-inflammatory and anti-apoptotic mechanisms of action, have been suggested for recombinant human activated protein C (rhAPC; drotrecogin alfa (activated)). However, these mechanisms are much less characterized and understood than rhAPC's anticoagulant activity. Aim of the study was to determine the effect of rhAPC on the activity of the pro-inflammatory transcription factor nuclear factor kappa B (NF-kappaB) in mononuclear cells isolated from septic patients and to characterize an effect downstream from NF-kappaB activation, such as the release of the NF-kappaB-controlled chemokine Macrophage Inflammatory Protein-1-alpha (MIP-1-alpha). SUBJECTS: Peripheral blood was obtained from 13 septic patients and from 8 healthy controls. METHODS: Mononuclear cells were isolated by Ficoll-Paque density gradient centrifugation and were incubated with or without rhAPC (10 microg/ml) for 2 h for the measurement of NF-kappaB activity in cell lysates or alternatively for 6 h for the determination of MIP-1-alpha levels in supernatants. NF-kappaB activity was measured by an ELISA-based assay directed against the p50 and the p65 subunit of NF-kappaB. RESULTS: RhAPC, at supra-pharmacological concentration (10 microg/ml), significantly inhibited NF-kappaB activity and the release of MIP-1-alpha ex vivo in isolated mononuclear cells from patients with severe sepsis. In mononuclear cells of healthy subjects, however, rhAPC did not change NF-kappaB activity. Basal NF-kappaB activity early in severe sepsis was not predictive for survival. CONCLUSIONS: RhAPC at supra-pharmacological concentration (10 microg/ml) inhibits the activity of NF-kappaB in ex vivo isolated mononuclear cells of septic patients as well as the release of MIP-1-alpha, a proinflammatory chemokine regulated by NF-kappaB. These findings may represent immunomodulatory pathways by which rhAPC exerts specific anti-inflammatory activity in vitro in addition to its known anticoagulant and profibrinolytic activity and should be further investigated in an in vivo setting.

Paradoxical coronary embolism causing non-ST segment elevation myocardial infarction in a case of pulmonary embolism.

We describe the case of a 61-year-old woman who simultaneously suffered a pulmonary embolism and a myocardial infarction due to paradoxical coronary artery embolism. Transesophageal echocardiography with injection of agitated hydroxyethyl starch revealed a patent foramen ovale. Thrombophlebistis of the left saphenous vein with extension of thrombus into the femoral vein could be identified as the source of embolism. Paradoxical coronary embolism is an underrecognized cause of MI. Diagnosis is particularly difficult, when MI and PE coincide, because of the similarity in clinical signs and symptoms of both entities. A high level of clinical suspicion and echocardiography, especially if performed soon after presentation, can be the clue to early diagnosis of PDE.

Incidence and electrophysiological characteristics of spontaneous ventricular tachyarrhythmias in high risk coronary patients and prophylactic implantation of a defibrillator.

OBJECTIVES: To assess the incidence and electrophysiological characteristics of spontaneous ventricular tachyarrhythmias after implantable cardioverter-defibrillator (ICD) implantation for primary prevention. DESIGN: Prospective observational study. PATIENTS: 41 consecutive patients, who fulfilled MADIT (multicenter automatic defibrillator implantation trial) I criteria, except for suppressibility by procainamide, and who received a prophylactic ICD. INTERVENTIONS: Subpectoral implantation of an ICD. MAIN OUTCOME MEASURES: Incidence of ventricular tachyarrhythmias and their electrophysiological characteristics with respect to timing of the arrhythmia, tachyarrhythmia cycle length, mode of termination, and clinical relevance. RESULTS: During a mean (SD) follow up of 30 (21) months 18 of 41 (43.9%) patients experienced 142 appropriate ICD treatments. The mean (SD) time to first event was 9.6 (15.1) months. One patient had ventricular fibrillation (VF), 12 patients ventricular tachycardia (VT), and five both VT and VF. The mean (SD) cycle length of monomorphic VT was 306 (42) ms. Of 142 episodes, 117 (82.3%) were terminated by antitachycardia pacing and another 25 (17.6%) by ICD discharges. Cumulative survival of hypothetical death, defined as treated VT with a cycle length < 260 ms or VF, was 83.2% after one year and 78.4% after two years. CONCLUSIONS: Patients with a left ventricular ejection fraction < 35%, a history of myocardial infarction, non-sustained VT, and inducible VT/VF are at high risk of VT/VF early after implantation. Therefore, implantation of a tiered treatment defibrillator seems to be justified.

Expression and activity of matrix metalloproteinase-2 in calcific aortic stenosis.

Calcific aortic stenosis is the main heart valve disease in the elderly, leading to massive focal calcification and thickening of the valve cusps. Matrix metalloproteinases (MMPs) are thought to contribute to this process. Therefore, the study assessed the expression of the gelatinases MMP-2 and MMP-9 and the endogenous tissue inhibitor of metalloproteinase (TIMP)-2 as well as the gelatinolytic activity in normal and stenotic valves. Human tricuspid aortic valves with and without calcific aortic stenosis were studied by immunohistochemistry for MMP-2, MMP-9 and TIMP-2. The gelatinolytic activity in native valve sections was assessed by gelatin in situ zymography with or without addition of the MMP activator p-aminophenymercuric acetate (APMA). Staining intensities for MMP-2 and TIMP-2 were elevated in stenotic valves as compared to controls. Minor staining of MMP-9 was present exclusively in stenotic valves. The morphologic distribution of gelatinolytic activity was comparable to the staining pattern of MMP-2, and since MMP-9 immunostaining demonstrated only a low number of positive cells, the observed gelatinolytic activity is likely due to MMP-2. Gelatinolytic activity was low in normal valves but significantly increased by the MMP activator APMA. In contrast, stenotic valves showed a strong basal gelatinolytic activity that could not be significantly enhanced by APMA suggesting that MMP-2 is present as a latent pro-enzyme in normal valves and activated in stenotic valves. Thus, MMP-2 might be involved in the matrix remodeling during calcific aortic stenosis.

[Expansion of the Multilink-Tristar stent after direct implantation and predilatation: comparison of clinical, angiography and intravascular ultrasound parameters]. / Expansion des Multilink-Tristar-Stents nach direkter Implantation und Vordilatation: Vergleich klinischer, angiographischer und intravasaler sonographischer Parameter.

Coronary stenting has become the primary therapeutic option for many coronary lesions. As opposed to conventional stenting the advantages of direct stenting are a reduction of procedural time, radiation exposure and costs. However, data about the incidence of in-stent restenosis are so far not available. It was the aim of this prospective study to compare the expansion of the Multilink stent after direct stenting and predilatation by quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). Between January 2000 and June 2001, 82 patients were assigned to direct stenting (46 lesions) or predilatation (40 lesions) in lesions of coronary arteries > 3 mm. The procedural success rate was 92% in patients undergoing direct stenting. The baseline clinical characteristics were similar in both groups. The comparison of the angiographic data shows that direct stenting was performed in lesions with a lower degree of stenosis (71 +/- 12% vs 79 +/- 11%, p = 0.01) and that significantly shorter stents were used (14.4 +/- 3.0 vs 17.8 +/- 4.1 mm, p = 0.0007). The mean stenosis length was not significantly different in either group (10.5 +/- 3.4 vs 11.7 +/- 4.3 mm, n.s.). The QCA data after stent implantation show no differences of either implantation technique. Stent expansion was assessed by IVUS estimation of the proximal, distal and minimal in stent area. The minimal in-stent area (9.53 +/- 3.23, mm2 vs 8.65 +/- 1.96 mm2, n.s.) and the stent symmetry index (0.88 vs 0.88 n.s.) were not different in either patient group. These results indicate that in this subset of selected coronary lesions > 3 mm, elective stent implantation with and without predilatation effectively can achieve comparable stent expansion as assessed by QCA and IVUS. In comparison to conventional stent implantation stents, which were implanted without predilatation, were significantly shorter to cover the same lesion length.

[Differential thoracic pain diagnosis. An internal medicine challenge]. / Differenzialdiagnose des Thoraxschmerzes. Eine internistische Herausforderung.

In the event of chest pain developing, the task of initial evaluation must be either to confirm and treat an acute life-threatening condition, or to exclude it. The diagnosis of a harmless functional disorder can be established only after the exclusion of a number of cardiovascular, pulmonary or gastrointestinal conditions, as also infection or malignancy. Such an approach often requires cooperation with orthopedic surgeons, general surgeons, psychiatrists and also pain specialists.

[Rapid assessment of thoracic pain. Is it a myocardial infarct?]. / Brustschmerzabklärung im Eiltempo. Ist es ein Herzinfarkt?

The high mortality rate of acute myocardial infarction underline the importance of this entity in the differential diagnosis of acute chest pain. Medical history, clinical presentation, ECG, biochemical markers of myocardial injury and imaging techniques are used to establish a correct diagnosis. Myocardial infarction can be divided into ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction. In the case of ST-segment elevation myocardial infarction thrombolytic therapy or percutaneous transluminal coronary angioplasty should be instituted as soon as possible. In patients without persistent ST-segment elevation biochemical markers of myocardial damage, especially troponin T and troponin I, are of major importance for risk stratification. Patients with elevated troponin levels should be treated with GPIIb/IIIa antagonists and early intervention.

Role of vessel size as a predictor for the occurrence of in-stent restenosis in patients with diabetes mellitus.

Intracoronary stents have been shown to reduce the rate of restenosis when compared with balloon angioplasty, but in-stent restenosis continues to be an important clinical problem. It was therefore the aim of this registry to identify procedural and angiographic predictors for the occurrence of in-stent restenosis. We analyzed 368 patients with 421 lesions who underwent coronary stent implantation between January 1998 and February 2000. Indications for the placement of a coronary stent were severe dissections (37%), suboptimal angiographic results (38%), restenotic lesions (20%), and graft lesions (4%). Angiographic follow-up was obtained in 270 patients (73%) with 293 lesions after 6 months. Clinical and angiographic variables were analyzed by univariate and multivariate models for the ability to predict the occurrence of in-stent restenosis, defined as a diameter stenosis >50%. In-stent restenosis was angiographically documented in 67 patients and 68 lesions (23%). Under all tested variables the reference luminal diameter before stent implantation (p = 0.006) and diabetes mellitus (p = 0.023) were identified as independent predictors for the occurrence of in-stent restenosis. The comparison of diabetic and nondiabetic patients according to vessel size revealed a 2 times higher rate of in-stent restenosis in small vessels (44% vs 23%, p = 0.002), whereas in vessels >3.0 mm the rate of in-stent restenosis was not significantly different between the 2 groups. In this registry, the clinical variable diabetes and the procedural variable reference vessel size were independent predictors for the occurrence of in-stent restenosis. In these patients, the rate of in-stent restenosis was as high as 45%.

In-hospital mortality of elderly patients with acute myocardial infarction: data from the MITRA (Maximal Individual Therapy in Acute Myocardial Infarction) registry.

BACKGROUND: Advanced age remains one of the principal determinants of mortality in patients with acute myocardial infarction (AMI). HYPOTHESIS: The aim of this study was to determine the in-hospital outcome of elderly (> 75 years) patients with AMI who were admitted to hospitals participating in the national MITRA (Maximal Individual Therapy in Acute Myocardial Infarction) registry. METHODS: MITRA is a prospective, observational German multicenter registry investigating current treatment modalities for patients presenting with AMI. All patients with AMI admitted within 96 h of onset of symptoms were included in the MITRA registry. MITRA was started in June 1994 and ended in January 1997. This registry comprises 6,067 consecutive patients with a mean age of 65 +/- 12 years, of whom 1,430 (17%) were aged > 75 years. Patients were compared with respect to patient characteristics, prehospital delays, early treatment strategies, and clinical outcome. RESULTS: In the elderly patient population, the prehospital delay was 210 min, which was significantly longer than that for younger patients (155 min, p = 0.001). Although the incidence of potential contraindications for the initiation of thrombolysis was almost equally distributed between the two age groups (8.7 vs. 8.2%, p = NS), elderly patients (> 75 years) received reperfusion therapy less frequently (35.9 vs. 64.6%) than younger patients. Mortality increased with advanced age and was 26.4% for all patients aged > 75 years. If reperfusion therapy was initiated, in-hospital mortality was 21.8 versus 28.9% in patients aged > 75 years (p = 0.001) and 29.4 versus 38.5% in patients aged > 85 years (p = 0.001). CONCLUSION: In this registry, elderly patients with AMI had a much higher in-hospital mortality than that expected from randomized trials. In MITRA, the mortality reduction with reperfusion therapy was found to be highest in the very elderly patient population.

[Use of Abciximab in threatening vascular occlusion after PTCA]. / Einsatz von Abciximab bei drohendem Gefässverschluss nach PTCA.

UNLABELLED: The administration of GP IIb/IIIa antagonists has been shown to be effective in reducing myocardial infarction and cardial death when given before PTCA. This prospective study was performed to determine the efficacy of abciximab in a bail-out situation to manage threatened or acute vessel closure. METHODS: Acute or threatened vessel closure was observed in 104 (5.5%) out of 1903 consecutive patients treated with PTCA in our institution. Of the 104 patients 46 (44%) were treated for unstable angina (CCS IV). Abciximab was administered in bail-out situations in a dosage of 0.25 mg/kg given as a bolus, which was followed by an intravenous infusion of 10 micrograms/min over 12 hours. Repeat PTCA was performed shortly after the administration of the abciximab bolus. After the procedure, the sheath was left in place and control angiography was carried out 24 h later. RESULTS: In 100 of the 104 patients TIMI flow III could be restored by abciximab therapy and RePTCA. In 4 patients an additional stent implantation was necessary due to persistent flow limitation. One day post PTCA, early follow-up angiography demonstrated patency of all vessels except two. In-hospital events occurred in 4 patients. Three of these patients underwent emergency CABG due to subacute vessel closure a few hours after PTCA and died during or directly after surgery. Follow-up after one year included clinical status and control angiography of the target vessel. During long-term follow-up, MACE occurred in 15 patients (2 MI, 8 CABG and 5 RePTCA). CONCLUSION: The results of this prospective trial demonstrate the efficacy of abciximab therapy in bail-out situations occurring during or early after PTCA. The use of abciximab in bail-out situations appears clinically beneficial. Further studies have to compare the efficacy of this approach with prophylactic abciximab treatment.

The impact of untreated coronary dissections on acute and long-term outcome after intravascular ultrasound guided PTCA.

AIM: Vessel size adapted PTCA results in the use of larger balloons with an increased incidence of severe vascular dissections. The aim of our trial was (a) to evaluate the effect of severe dissections on the acute outcome and (b) to study the natural history of dissections after 1 year. METHODS AND RESULTS: One hundred and seventy-eight patients with 195 lesions underwent vessel size adapted PTCA using intravascular ultrasound. Clinical and angiographic 1 year follow-up was obtained for all patients. Intravascular ultrasound was performed before PTCA to measure the external elastic membrane diameter at the lesion site so that the balloon size could be adopted (external elastic membrane-10%) and post-interventionally to determine the procedural success and the incidence of intracoronary dissections. Stent implantation was reduced to persistently flow limiting dissections (TIMI I, II). Dissections were detected by intravascular ultrasound in 128/195 (66%) lesions (by angiography in 111/195 [58%] lesions) and classified by intravascular ultrasound criteria into four groups: group I: no dissection (67 lesions [34%]), group II: mild dissections (21 lesions [11%]), group III: medium dissections (19 lesions [10%]) and group IV: severe dissections (88 lesions [45%]). Because of threatened vessel closure, GPIIb/IIIa antagonists were used in eight (4.5%) patients and a stent was implanted in two (1. 1%) patients. The cumulative event rate after 1 year was 12% and the global angiographic restenosis rate was 19%. The post-interventional evidence of severe dissections was associated with a decrease in clinical events during long-term follow up (group I: 13 events [19%] vs group IV: seven events [7%];P=0.03). This was also true for the occurrence of restenosis which was significantly lower in patients with severe dissections (group I: 19 [28%] lesions vs group IV:10 [11%] lesions;P=0.01). CONCLUSIONS: According to the theory of 'therapeutic dissections', our data suggest that substantial dissections following PTCA, which do not diminish antegrade blood flow, do not lead to an increase in acute or long-term events. The natural history of vessel injury seems to provide favourable wound healing without increase of restenosis. Thus, stenting for treatment of large dissections without flow limitation does not seem to be mandatory.

Angiotensin I-converting enzyme gene polymorphism, coronary artery disease and myocardial infarction. An angiographically controlled study.

OBJECTIVES: We investigated the association between insertion/deletion polymorphism of the angiotensin I-converting enzyme (ACE) gene, the presence and extent of coronary artery disease, and myocardial infarction. BACKGROUND: The D allele of the ACE gene has been associated with coronary artery disease and myocardial infarction, but this association has been challenged in epidemiological studies. METHODS: Nine hundred and sixty-nine men and 341 women undergoing coronary angiography were studied. The ACE genotypes were assessed by polymerase chain reaction from genomic deoxyribonucleic acid, homozygosity for the D allele was controlled using an insertion-specific primer. Coronary artery disease was defined by angiographic criteria, the extent of coronary artery disease by the number of coronary arteries with >/=50% lumen narrowing. RESULTS: The ACE genotypes did not differ in terms of age, sex, body mass index, blood pressure, plasma lipids or lipoproteins. We found no association between the ACE genotypes and coronary artery disease (odds ratio, 95% confidence interval in DD genotypes for coronary artery disease in men 0.97, 0.70-1.36; in women 1.56, 0.95-2.57), extent of coronary artery disease (men 1.17, 0.85-1.61; women 1.24, 0.65-2.34), or myocardial infarction among the patients with coronary artery disease (men 1.07, 0.78-1.48; women 0.95, 0.50-1.76). The ACE genotype was not associated with coronary artery disease or myocardial infarction in hypertensives (n=771; odds ratio for coronary artery disease 0.93, 0.65-1.34; odds ratio for myocardial infarction 0.94, 0.66-1.33), or in patients

Extent, determinants and clinical importance of pressure recovery in patients with aortic valve stenosis.

AIMS: In experimental studies the recovery of pressure distal to stenotic valve orifices has been well described. We evaluated the extent, determinants, and clinical importance of pressure recovery in patients with aortic valve stenosis. METHODS AND RESULTS: The study was performed in 37 patients with aortic valve stenosis, in whom cardiac catheterization was performed and left ventricular and aortic pressures were determined using a high-fidelity multi-tip micromanometer catheter. To register the pressure waveforms accurately the catheter was positioned so that the proximal micromanometer was in the left ventricle, the second at the site of minimal pressure in the vena contracta, and the third (the most distal) in the ascending aorta 16 cm further downstream. The amount of pressure recovery within the ascending aorta was up to 44% of the maximal pressure drop. The index pressure recovery was directly correlated to the Gorlin-derived aortic valve area (r=0.80) and indirectly correlated to the ratio of aortic valve area and the cross-sectional area of the ascending aorta. CONCLUSIONS: This clinical study confirmed experimental data, that index pressure recovery is dependent on the ratio of the effective valve area and the cross-sectional area of the ascending aorta. Pressure recovery may need to be considered in patients with mild to moderate aortic stenosis and with a small cross-sectional area of the ascending aorta.