Theodor Baars

Vasoconstrictor Potential of Coronary Aspirate From Patients Undergoing Stenting of Saphenous Vein Aortocoronary Bypass Grafts and Its Pharmacological Attenuation

Rationale: Stent implantation into atherosclerotic plaques releases, apart from particulate debris, soluble substances that contribute to impaired microvascular perfusion. Objective: To quantify the release of vasoconstrictors and to determine the efficacy of coronary dilators to attenuate their action. Methods and Results: Using a distal protection/aspiration device, coronary arterial blood was retrieved before and during stenting in 22 patients with severe saphenous vein aorto-coronary bypass stenoses. The release of catecholamines, endothelin, serotonin, thromboxane B2, and tumor necrosis factor (TNF)&agr; was measured. The response of rat mesenteric arteries with intact (+E) and denuded (−E) endothelium to aspirate plasma was normalized to that by KCl. Responses to selective receptor blockade, adenosine, nitroprusside, and verapamil against the aspirate-induced constriction were determined. The coronary arterial plasma withdrawn before stenting induced 21±5% and the aspirate plasma after stenting induced 95±8% of maximum KCl-induced vasoconstriction. Serotonin, thromboxane B2, and TNF&agr; release into aspirate plasma increased by 1.9±0.2 &mgr;mol/L, 25.6±3.1 pg/mL, and 19.7±6.1 pg/mL, respectively, during stenting. The aspirate-induced vasoconstriction was largely antagonized by selective serotonin receptor blockade, with little further antagonism by additional thromboxane receptor blockade. TNF&agr; did not induce constriction per se but potentiated the constriction with serotonin and the thromboxane-analog U-46619 in arteries +E. The concentrations to induce half-maximal vasodilation were comparable for nitroprusside (+E, 3.3×10−8; −E, 1.9×10−8 mol/L) and verapamil (+E, 8.3×10−8; −E, 7.8×10−8 mol/L), and the vasoconstriction was eventually eliminated. The vasodilator response to adenosine was dependent on functional endothelium and weaker. Conclusion: Serotonin is the main coronary vasoconstrictor after stenting, and thromboxane and TNF&agr; somewhat potentiate the serotonin response. Nitroprusside and verapamil are more potent than adenosine to attenuate the aspirate plasma-induced vasoconstriction, and they are not dependent on functional endothelium.

Coronary aspirate TNFα reflects saphenous vein bypass graft restenosis risk in diabetic patients

BackgroundPatients with diabetes mellitus (DM) have an increased risk for periprocedural complications and adverse cardiac events after percutaneous coronary intervention. We addressed the potential for coronary microvascular obstruction and restenosis in patients with and without DM undergoing stenting for saphenous vein bypass graft (SVG) stenosis under protection with a distal occlusion/aspiration device.MethodsSVG plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Percent diameter stenosis was determined from quantitative coronary angiography before, immediately after and 6 months after stent implantation. Coronary aspirate was retrieved during stent implantation and divided into particulate debris and plasma. Total calcium, several vasoconstrictors, and tumor necrosis factor (TNF)α in particulate debris and coronary aspirate plasma were determined.ResultsPatients with and without DM had similar plaque volume, but larger necrotic core and greater particulate debris release in patients with than without DM (20.3±2.7 vs. 12.7±2.6% and 143.9±19.3 vs. 75.1±10.4 mg, P<0.05). The TNFα concentration in particulate debris and coronary aspirate plasma was higher in patients with than without DM (15.9±6.6 vs. 5.1±2.4 pmol/mg and 2.2±0.7 vs. 1.1±0.2 pmol/L, P<0.05), whereas total calcium and vasoconstrictors were not different. Patients with DM had a greater percent diameter stenosis 6 months after stent implantation than those without DM (22.17±5.22 vs. 6.34±1.11%, P<0.05). The increase in TNFα immediately after stent implantation correlated with restenosis 6 months later (r=0.69, P<0.05).ConclusionIn diabetics, particulate debris and coronary aspirate plasma contained more TNFα, which might reflect the activity of the underlying atherosclerotic process.Trial registrationURL: http://www.clinicaltrials.gov/ct2/results?term=NCT01430884; unique identifier: NCT01430884

Aspirate from human stented native coronary arteries vs. saphenous vein grafts: more endothelin but less particulate debris

Stent implantation into atherosclerotic coronary arteries releases particulate debris and soluble substances that contribute to impaired microvascular perfusion. Here we addressed the potential for microvascular obstruction in patients with stenotic native right coronary arteries (nRCA) compared with saphenous vein grafts on right coronary arteries (SVG-RCA). We enrolled symptomatic, male patients with stable angina pectoris and a flow-limiting stenosis in their nRCA or SVG-RCA (n = 18/18). Plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Coronary aspirate was retrieved during stent implantation under protection with a distal occlusion/aspiration device and divided into particulate debris and plasma. The release of catecholamines, endothelin, serotonin, thromboxane B2, and tumor necrosis factor-α was measured. The response of rat mesenteric arteries with intact (+E) and denuded (-E) endothelium to aspirate plasma (without and with selective endothelin receptor blockade) was normalized to that by potassium chloride (KClmax = 100%). Plaque volume and composition were not different between nRCA and SVG-RCA. There was less particulate debris (65 ± 8 vs. 146 ± 23 mg; P < 0.05) and more endothelin release (5.8 ± 0.8 vs. 1.3 ± 0.7 pg/ml; P < 0.05) in nRCA than in SVG-RCA, whereas the release of the other mediators was not different. Aspirate from nRCA induced stronger vasoconstriction than that from SVG-RCA [nRCA, 78 ± 6% (+E)/84 ± 5% (-E); SVG-RCA, 59 ± 6% (+E)/68 ± 3% (-E); P < 0.05 nRCA vs. SVG-RCA], which was attenuated by a nonspecific endothelin and a specific endothelin receptor A antagonist. Thus coronary aspirate from stented nRCA is characterized by less debris but more endothelin and stronger vasoconstrictor response than that from SVG-RCA.

Release of Intracoronary Microparticles during Stent Implantation into Stable Atherosclerotic Lesions under Protection with an Aspiration Device

Objective Stent implantation into atherosclerotic coronary vessels impacts on downstream microvascular function and induces the release of particulate debris and soluble substances, which differs qualitatively and quantitatively between native right coronary arteries (RCAs) and saphenous vein grafts on right coronary arteries (SVG-RCAs). We have now quantified the release of microparticles (MPs) during stent implantation into stable atherosclerotic lesions and compared the release between RCAs and SVG-RCAs. Methods In symptomatic, male patients with stable angina and a stenosis in their RCA or SVG-RCA, respectively (n = 14/14), plaque volume and composition were analyzed using intravascular ultrasound before stent implantation. Coronary aspirate was retrieved during stent implantation with a distal occlusion/aspiration device and divided into particulate debris and plasma. Particulate debris was weighed. Platelet-derived MPs (PMPs) were distinguished by flow cytometry as CD41+, endothelium-derived MPs (EMPs) as CD144+, CD62E+ and CD31+/CD41-, leukocyte-derived MPs as CD45+, and erythrocyte-derived MPs as CD235+. Results In patients with comparable plaque volume and composition in RCAs and SVG-RCAs, intracoronary PMPs and EMPs were increased after stent implantation into their RCAs and SVG-RCAs (CD41+: 2729.6±645.6 vs. 4208.7±679.4 and 2355.9±503.9 vs. 3285.8±733.2 nr/µL; CD144+: 451.5±87.9 vs. 861.7±147.0 and 444.6±74.8 vs. 726.5±136.4 nr/µL; CD62E+: 1404.1±247.7 vs. 1844.3±378.6 and 1084.6±211.0 vs. 1783.8±384.3 nr/µL, P<0.05), but not different between RCAs and SVG-RCAs. Conclusion Stenting in stable atherosclerotic lesions is associated with a substantial release not only of PMPs, but also of EMPs in RCAs and SVG-RCAs. Their release does not differ between RCAs and SVG-RCAs. Trial Registration ClinicalTrials.gov NCT01430884

Myocardial injury during transfemoral transcatheter aortic valve implantation: an intracoronary Doppler and cardiac magnetic resonance imaging study

AIMS Myocardial injury reflected by a post-procedural increase of serum troponin I (TnI) occurs frequently during transcatheter aortic valve implantation (TAVI). It is potentially caused by intraprocedural hypotension, periprocedural coronary microembolisation and post-procedural (para)valvular leakages (PVLs). We invasively assessed coronary flow dynamics including coronary flow velocity reserve (CFVR), embolic high-intensity transient signals (HITS) as well as rapid pacing induced hypotension and post-procedural PVLs to determine their contribution to post-procedural TnI increases. METHODS AND RESULTS In 15 transfemoral TAVI patients, TnI was measured serially, and cardiac MRIs with late gadolinium enhancement (LGE) were performed pre- and post-interventionally. There were no significant correlations between coronary flow dynamics, CFVR and the area under the curve (AUC) of TnI over 72 hours. Despite the detection of HITS in all patients and during all procedural steps, there was also no correlation between the amount of HITS and the AUC of TnI. However, there were positive correlations between the duration of rapid pacing as well as the time of subsequent blood pressure recovery and the AUC of TnI. Both LGE and more than mild PVL were observed in a single case only. CONCLUSIONS Myocardial injury after TAVI appears to be related more to hypoperfusion-induced ischaemia than to periprocedural microembolisation.

In Acute Myocardial Infarction Liver Parameters Are Associated With Stenosis Diameter

AbstractDetection of high-risk subjects in acute myocardial infarction (AMI) by noninvasive means would reduce the need for intracardiac catheterization and associated complications. Liver enzymes are associated with cardiovascular disease risk. A potential predictive value for liver serum markers for the severity of stenosis in AMI was analyzed.Patients with AMI undergoing percutaneous coronary intervention (PCI; n = 437) were retrospectively evaluated. Minimal lumen diameter (MLD) and percent stenosis diameter (SD) were determined from quantitative coronary angiography. Patients were classified according to the severity of stenosis (SD ≥ 50%, n = 357; SD < 50%, n = 80). Routine heart and liver parameters were associated with SD using random forests (RF). A prediction model (M10) was developed based on parameter importance analysis in RF.Age, alkaline phosphatase (AP), aspartate aminotransferase (AST), and MLD differed significantly between SD ≥ 50 and SD < 50. Age, AST, alanine aminotransferase (ALT), and troponin correlated significantly with SD, whereas MLD correlated inversely with SD. M10 (age, BMI, AP, AST, ALT, gamma-glutamyltransferase, creatinine, troponin) reached an AUC of 69.7% (CI 63.8–75.5%, P < 0.0001).Routine liver parameters are associated with SD in AMI. A small set of noninvasively determined parameters can identify SD in AMI, and might avoid unnecessary coronary angiography in patients with low risk. The model can be accessed via http://stenosis.heiderlab.de.

Calcium antagonists in myocardial ischemia/reperfusion—update 2012

SummaryThe present article briefly reviews the processes underlying excitation–contraction coupling in cardiomyocytes and vascular smooth muscle cells, their perturbations during reversible and irreversible myocardial ischemia and reperfusion, notably the pathogenetic role of increased intracellular calcium concentrations, and finally the beneficial effects of calcium antagonists on the impairment of coronary vasomotor tone, on cardiac contractile dysfunction and on myocardial infarction.ZusammenfassungDie vorliegende Übersicht charakterisiert kurz die grundlegenden Prozesse der elektromechanischen Kopplung in Kardiomyozyten und glatten Gefäßmuskelzellen, ihre Veränderungen bei reversibler und irreversibler myokardialer Ischämie und Reperfusion, insbesondere die pathogenetische Funktion der erhöhten intrazellulären Kalziumkonzentration, sowie schließlich die protektiven Wirkungen von Kalziumantagonisten auf den gestörten koronaren Vasomotorentonus, die kontraktile Dysfunktion und die myokardiale Infarktausprägung.

Compensation of feature selection biases accompanied with improved predictive performance for binary classification by using a novel ensemble feature selection approach

MotivationBiomarker discovery methods are essential to identify a minimal subset of features (e.g., serum markers in predictive medicine) that are relevant to develop prediction models with high accuracy. By now, there exist diverse feature selection methods, which either are embedded, combined, or independent of predictive learning algorithms. Many preceding studies showed the defectiveness of single feature selection results, which cause difficulties for professionals in a variety of fields (e.g., medical practitioners) to analyze and interpret the obtained feature subsets. Whereas each of these methods is highly biased, an ensemble feature selection has the advantage to alleviate and compensate for such biases. Concerning the reliability, validity, and reproducibility of these methods, we examined eight different feature selection methods for binary classification datasets and developed an ensemble feature selection system.ResultsBy using an ensemble of feature selection methods, a quantification of the importance of the features could be obtained. The prediction models that have been trained on the selected features showed improved prediction performance.

Aspirate from human stented saphenous vein grafts induces epicardial coronary vasoconstriction and impairs perfusion and left ventricular function in rat bioassay hearts with pharmacologically induced endothelial dysfunction

Stent implantation into aortocoronary saphenous vein grafts (SVG) releases particulate debris and soluble vasoactive mediators, for example, serotonin. We now analyzed effects of the soluble mediators released into the coronary arterial blood during stent implantation on vasomotion of isolated rat epicardial coronary artery segments and on coronary flow and left ventricular developed pressure in isolated perfused rat hearts. Coronary blood was retrieved during percutaneous SVG intervention using a distal occlusion/aspiration protection device in nine symptomatic patients with stable angina pectoris and a flow‐limiting SVG stenosis. The blood was separated into particulate debris and plasma. Responses to coronary plasma were determined in isolated rat epicardial coronary arteries and in isolated, constant pressure‐perfused rat hearts (±nitric oxide synthase [NOS] inhibition and ±serotonin receptor blockade, respectively). Coronary aspirate plasma taken after stent implantation induced a stronger vasoconstriction of rat epicardial coronary arteries (52 ± 8% of maximal potassium chloride induced vasoconstriction [% KClmax = 100%]) than plasma taken before stent implantation (12 ± 8% of KClmax); NOS inhibition augmented this vasoconstrictor response (to 110 ± 15% and 24 ± 9% of KClmax). Coronary aspirate plasma taken after stent implantation reduced in isolated perfused rat hearts only under NOS inhibition coronary flow by 17 ± 3% and left ventricular developed pressure by 25 ± 4%. Blockade of serotonin receptors abrogated these effects. Coronary aspirate plasma taken after stent implantation induces vasoconstriction in isolated rat epicardial coronary arteries and reduces coronary flow and left ventricular developed pressure in isolated perfused rat hearts with pharmacologically induced endothelial dysfunction.

Influence of stent implantation on erythrocyte aggregation in human native coronary arteries and saphenous vein grafts

Stent implantation into atherosclerotic coronary vessels induces the release of particulate debris and soluble vasoactive substances, which impair downstream microvascular function. Microvascular perfusion, however, is also determined by hemorheological parameters. We therefore analyzed now changes in erythrocyte (RBC) aggregation in coronary arterial blood during stent implantation.