Jürgen Barmeyer

Acute and chronic tissue response to coronary stent implantation: pathologic findings in human specimen.

OBJECTIVES The aim of our study was to analyze the cellular components of neointimal tissue regeneration after coronary stenting. BACKGROUND High restenosis rates are a major limiting factor of coronary stenting. To reduce the occurrence of restenoses, more insights into the mechanisms leading to proliferation and expression of extracellular matrix are necessary. METHODS Twenty-one autopsy cases with coronary stents implanted 25 h to 340 days before death were studied. The stented vessel segments were analyzed postmortem by light microscopy and immunohistochemical staining. RESULTS In the initial phase stents are covered by a thin multilayered thrombus. Alpha-actin-positive smooth muscle cells (SMCs) are found as the main cellular component of the neointimal tissue. Later (>6 weeks) extracellular matrix increases and fewer SMCs can be found. In every phase the SMC layers are loosely infiltrated by inflammatory cells (T lymphocytes). In the early postinterventional phase all endothelial cells are destroyed. The borderline between the vessel lumen and the vascular wall is constituted by a thin, membranous thrombus. Six weeks after stenting, SMCs form the vessel surface. Complete reendothelialization is first found 12 weeks after stenting. CONCLUSIONS Stent integration is a multifactorally triggered process with proliferating SMCs generating regenerative tissue. In the early phase predominantly thrombotic material can be observed at the site of stenting, followed by the invasion of SMCs, T lymphocytes and macrophages. The incidence of delayed reendothelializations and the occurrence of deep dissections may be associated with excessive SMC hyperplasia.

SEGMENTATION OF 3D INTRAVASCULAR ULTRASONIC IMAGES BASED ON A RANDOM FIELD MODEL

Segmentation of intravascular ultrasound images provides important information about the degree of vessel obstruction as well as about the shape and size of plaques. To address the problems of inter- and intra-observer variances associated with conventional manual tracing, a fully automated segmentation was developed. The algorithm is based on the optimisation of a maximum a posteriori estimator, implementing the Rayleigh distribution of speckle and a priori information about the contours. Within 3D image sets, additional information by the blood flow resulting in a decorrelation of the pixels within the luminal boundary is used to initialise the segmentation. To accelerate the estimation, dynamic programming was used. The segmentation algorithm was realised as a Windows 95 application on a Pentium II/233 MHz and delivered reliable and reproducible results independent of the catheter position and the total image brightness (except overflow). In contrast, contours drawn by two physicians for an evaluation of 29 clinical cases showed large intra- and inter-observer variances. In vivo images were acquired with a 20 MHz transducer array (EndoSonics InVision). Comparison with the contours drawn by the physicians and histology demonstrates the potential of the segmentation algorithm.

Aerobic Capacity in Rate Modulated Pacing

Whether heart rate or AV synchrony is the most important factor for an increase in aerobic capacity was evaluated in a comparative study between sinus bradycardia, VVIR, DDD, and DDDR stimulation. Sixteen patients (mean age 67 years) with chronotropic incompetence and impJanted DDDR pacemaker (Telectronics META 1250) were randomly studied by cardiopulmonary exercise testing. All patients were exercised to their anaerobic threshold (ATJ with the following heart rates: DDD 84 ± 3, WIR 110 ± 5, and DDDR 116 ± 6 beats/min. Mean oxygen uptake (VO2, mL/kg per min) at AT was 7.4 ± 0.3 in DDD and WIR modes. A 12% increase was measured in DDDR mode (8.3 ± 0.4). Compared to VVIR work capacity in the DDDR mode was improved by 17% (41 vs 48 W/min). In patients with isolated sinus node disease (n = 9) the increase of VO2 and work capacity at AT during DDDR mode was more pronounced (16% and 20%, respectively, compared to VVIR). In patients with intermittent second or third degree AV block (n = 7) the differences between the pacing modes were not significant. This might partly be due to a lesser degree of chronotropic incompetence in this subgroup. In conclusion only the conjunction of heart rate increase and preservation of AV synchrony provides a significant improvement in aerobic capacity during exercise.

Hyperfibrinogenemia increases the risk of cardiac events after coronary artery stenting

Abstract Primary success rates, and the angiographic and clinical outcome after percutaneous coronary intervention, are influenced by many different factors. Clinical features and morphologic characteristics of the target lesion are important. Also, interventionally caused endothelial trauma may trigger atherogenetic and procoagulatory factors leading to intraluminal thrombosis. The study population consisted of 228 consecutive, unselected patients with symptomatic coronary artery disease or exercise-induced myocardial ischemia and coronary artery stenoses eligible for percutaneous intervention. We analyzed different clinical, morphological, and laboratory (total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, triglycerides, fibrinogen) features in those patients with adverse cardiac events (stent thrombosis, myocardial infarction, urgent target vessel revascularization, death) after primary successful coronary artery stenting, compared with a control group without adverse events. In the group with adverse cardiac events we found a significantly higher level of fibrinogen compared with the control group. Other laboratory data and clinical characteristics were not significantly different between the two groups. The study shows a possible association between hyperfibrinogenemia and adverse cardiac events after intracoronary stenting. In clinical practice, the potential role of elevated levels of fibrinogen in an unfavorable outcome after percutaneous coronary interventions should be considered when planning coronary artery stenting.

Comparison of the efficacy and safety of aspirin alone with coumadin plus aspirin after provisional coronary stenting: final and follow-up results of a randomized study.

BACKGROUND The antithrombotic benefit of the conventional treatment with coumadin after coronary stenting is limited by bleeding complications. However, the superiority of an antiplatelet therapy with aspirin alone compared with coumadin plus aspirin has not been proven by randomized studies. The efficacy and safety of treatment with aspirin alone in comparison to coumadin plus aspirin were evaluated in this randomized study. METHODS Out of 164 patients aged 59.7 +/- 9.2 years, 79 patients were randomly assigned to receive 100 mg aspirin daily (group A) and 85 patients randomly assigned to coumadin plus aspirin (group CA) after provisional coronary stenting with a high-pressure technique. The primary end point was defined as the absence of death, subacute closure of the target vessel, myocardial infarction, urgent coronary bypass surgery, repeated coronary angioplasty, and peripheral vascular complications requiring transfusion or surgery. High-pressure inflation technique was used, but ultrasound guidance was not. RESULTS During hospitalization (median 8 days), 135 patients (82. 3%) were free of events (A, 84.8%; CA, 80.8%; P =.42). Eleven (6.7%) subacute closures occurred (A, 10.1%; CA, 3.5%; P =.09); 2 of them were lethal in the aspirin group. Emergency bypass surgery was performed in 1 patient in each group. Peripheral vascular complications were observed in 13 patients (7.9%) (A, 1.3%; CA, 14. 1%; P <.01). At 3-month follow-up, 15 (9.1%) elective revascularization procedures (A, 7.6%; CA, 10.6%; P =.51) were performed. CONCLUSION Aspirin alone at the low dose of 100 mg administered or the combination of coumadin and aspirin after high-pressure coronary stenting does not prevent adverse clinical events when ultrasound guidance is not used.

Two-Dimensional Echocardiographic Assessment of Right Cardiac Pressure Overload in Patients with Chronic Obstructive Airway Disease

Two-dimensional echocardiography was used to estimate right cardiac pressure overload in patients with chronic obstructive airway disease. Area measurements of the four heart chambers were carried out from the apical four-chamber view. Additionally, the respiratory behaviour of the inferior vena cava was examined from the subcostal view. A good apical imaging of the four-chamber view for area measurement was obtained in 44 out of 48 patients with chronic obstructive airway disease. The respiratory behaviour of the inferior vena cava was investigated from the subcostal view in 38 patients. Within 8 days after echocardiography, right cardiac catheterization was carried out in order to measure pulmonary artery and right atrial mean pressures and to determine pulmonary vascular resistance. A good correlation was found between pulmonary artery mean pressure and the following echocardiographic parameters: area index (area/body surface) of the two right heart cavities (r = 0.83), right-to-left ventricular area ratio (r = 0.82) and right-to-left cardiac area ratio (ratio between the added areas of both right heart cavities on the one side and the added areas of both left heart cavities on the other; r = 0.82). Correlation between these parameters and pulmonary vascular resistance (r = 0.71, 0.66 and 0.71, respectively) and between the right atrial mean pressure and the right atrial area index was less close (r = 0.64). On the other hand, the respiratory behaviour of the inferior vena cava proved to be highly specific but not very sensitive in predicting a pathological right atrial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Relationship Between Atrioventricular Delay and Oxygen Consumption in Patients with Sick Sinus Syndrome: Relevance to Rate Responsive Pacing

To develop a dromotropic‐controlled rate adaptive algorithm for patients with sick sinus syndrome (SSS) and intact AV conduction, 14 pacemaker patients with SSS underwent cardiopulmonary exercise testing (CPX). During exercise, the pacemaker was programmed in an AAT mode without rate adaptation, whereby 3 patients developed supraventricular arrhythmia and 11 patients kept sinus rhythm. Chronotropic incompetence (CI) at heart rate (HR) < 95 beats/min at the anaerobic threshold (AT) was found in five patients. In patients with chronotropic competence (CC), the HR increase was significantly greater than in CI patients (rest: 73.2 ± 12.6 vs. 64.2 ± 4.0 beats/min; AT:101.2 ± 6.2 vs. 82.0 ± 5.1 beats/min; peak: 135.2 ± 10.7 vs. 103.2 ± 10.9 beats/min). There was no significant difference in the AVD between CC and CI patients (rest: 167.7 ± 38.6 vs. 170.8 ± 22.5 ms, AT: 156.2 ± 30.7 vs. 163.6 ± 21.6 ms, peak: 144.7 ± 29.0 vs. 152.4 ± 15.0 ms). The correlation coefficient between HR increase and VO2 was +1.0 and between AVD decrease and VO2– 1.0 in both groups. An increase in pacing rate from 75 beats/min to 120 beats/min without exercise (overpacing) led to a prolongation of the AV interval of about 30.6 ± 14.2 ms. Based on this closed loop control with negative feedback, a dromotropic rate adaptive algorithm for patients with SSS and intact AV conduction could be developed.

Influence of the pacing rate on the atrioventricular conduction time during aerobic and anaerobic exercise: basic concepts for a dromotropically controlled rate responsive pacemaker.

The dromotropic pacemaker concept needs a rate responsive algorithm in which the pacing rate is controlled by the atrioventricular conduction time (AVCT). To develop basic concepts for such a rate responsive algorithm, the influence of the pacing rate on the AVCT was investigated. Seven patients (62 ± 7.8 years) with sick sinus syndrome and intact atrioventricular conduction underwent two cardiopulmonary exercise tests (CPX) on a treadmill. According to the determination of the anaerobic threshold (AT) and the patients maximum capacity in the first incremental CPX the work rate for two exercise levels below and above the AT were chosen for the second constant workload CPX. The calculation of the optimal pacing rate (HRopt) was based on the oxygen uptake (VO2) during exercise after reaching steady‐state conditions. According to the increase of the V2 from 14.8 ± 2.3 mL/min per kilogram during aerobic work (38.3 ± 16.0 W) to 19.4 ± 4.7 mL/min per kilogram during anaerobic work (80.6 ± 32.3 W), the HRopt was calculated to be 98.6 ± 6.9 beats/min and 116.4 ± 4.7 beats/min. Starting from HRopt, the pacing rate was increased (overpacing) and decreased (underpacing) by about 5 beats/min every minute. At optimal pacing rate the AVCT decreased significantly from 233.0 ± 30.5 ms during aerobic work and to 226.4 ± 27.3 ms during anaerobic work (P < 0.05). Whereas overpacing induced a significant prolongation of the AVCT during aerobic work (4.17 ± 1.78 ms per 10 beats/min) and anaerobic work (3.84 ± 1.60 ms per 10 beats/min), underpacing yielded a significant shortening of the AVCT by about 4.49 ± 2.64 ms per 10 beats/min during aerobic work and 4.75 ± 1.87 ms per 10 beats/min during anaerobic work (P < 0.01). The slopes of the regression lines of the relationship between AVCT and pacing rate were not significantly different. Based on the reciprocal relationship of heart rate (HR) and AVCT, basic concepts may be established for a dromotropic rate responsive algorithm.

Korrelationen von Herzfrequenz und AV-Zeit zum Leistungsgrad: Bedeutung für das dromotrope Schrittmacherkonzept

EINLEITUNG: Ziel der sogenannten frequenzadaptiven Herzschrittmachertherapie ist eine Simulation der nervalen Steuerung des supraventrikulären Erregungsleitungssystems, um den Kreislaufapparat möglichst schnell an die körperliche Belastung anzupassen. Bei Erkrankungen des Sinusknotens (SSS) mit chronotroper Inkompetenz und ungestörter atrioventrikulärer (AV) Leitung wurde das Konzept entwickelt, die Erregungsleitungsverzögerung im AV-Knoten als Meßgröße für den Belastungsgrad zu nutzen und daraus die erforderliche Stimulationsfrequenz zu errechnen [1]. Eine objektive Beurteilung des Belastungsgrades ist durch die Messung der Atemgase unter Belastung (Spiroergometrie) möglich. Hierbei kann respiratorisch die anaerobe Schwelle bestimmt werden [2].

Beam compression of multistatic intravascular ultrasound data by an adaptive kernel function

To improve the image quality of intravascular ultrasound (IVUS) systems, which is among others limited by a poor lateral or angular resolution, a reconstruction in the Fourier domain based on beam compression by matched filtering offers the major advantage to consume far less acquisition and computation time. The reconstruction can be performed on 1/7/sup th/ of the raw signals acquired with an EndoSonics In-Vision/sup TM/ system by a simple 2D multiplication with a Kernel function in the Fourier domain. In the past, a simplified monostatic Kernel function was introduced. By applying an adaptive multistatic Kernel function accounting for different transmitting and receiving elements the lateral resolution can be further improved. Simulation and experimental results are discussed to find a useful selection of signals to process with respect to computation time. Reconstruction results obtained in a human coronary artery show the effectiveness of the algorithm.