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Biomedical subjects

Gerhard Steinbeck

Publications and source records attributed to Gerhard Steinbeck.

At least 19 recordsLinked to original sources

Assessment of collateralized myocardium with Cardiac Magnetic Resonance (CMR): transmural extent of infarction but not angiographic collateral vessel filling determines regional function and perfusion in collateral-dependent myocardium.

BACKGROUND: Angiographic collateral vessel filling is limited to evaluate collateral-dependent myocardium. We hypothesize, that quantitative assessment of regional myocardial function, perfusion and viability with Cardiac Magnetic Resonance (CMR) adds complementary information to angiography of collateralized myocardium. METHODS: CMR was performed in 30 patients with one chronic occluded coronary artery and no further flow limiting stenosis to assess transmural extend of infarction (TEI), resting perfusion and perfusion during adenosine-induced hyperemia and regional wall thickening (RWT) in collateral-dependent and antegradely-perfused myocardium. Collateral vessels were evaluated by angiography and the Rentrop grade (0-3). RESULTS: In 15 patients with < 50% TEI in collateral-dependent myocardium resting perfusion (1.08+/-0.22 ml/min/g), hyperemia (2.21+/-0.73 ml/min/g) and RWT (4.0+/-2.6 mm) were similar to antegradely-perfused myocardium (rest 1.14+/-0.20 and hyperemia 2.46+/-0.82 ml/min/g, RWT 4.3+/-1.7 mm). In 15 patients with > or = 50% TEI in collateral-dependent myocardium resting perfusion and hyperemia as well as RWT were significantly lower (rest 0.84+/-0.19, p<0.001 and hyperemia 1.34+/-0.43 ml/min/g, p<0.001; RWT 1.0+/-1.0 mm, p<0.0001) compared to antegradely-perfused myocardium. There was an inverse correlation between TEI and resting or hyperemic perfusion or RWT. In contrary, resting perfusion and hyperemia as well as RWT in collateral-dependent myocardium were not different between patients with good (2-3) compared to patients with poor Rentrop grade (0-1). There was no correlation between TEI and Rentrop grade. CONCLUSION: Function and perfusion in collateral-dependent myocardium are preserved, if transmural extent of infarction is limited (< 50%). This is independent of their angiographic collateral vessel filling. Thus, CMR adds complementary information to angiographic standard assessment of collateral vessels.

Aged↗

Identification of a common gene expression signature in dilated cardiomyopathy across independent microarray studies.

OBJECTIVES: This study was designed to identify a common gene expression signature in dilated cardiomyopathy (DCM) across different microarray studies. BACKGROUND: Dilated cardiomyopathy is a common cause of heart failure in Western countries. Although gene expression arrays have emerged as a powerful tool for delineating complex disease patterns, differences in platform technology, tissue heterogeneity, and small sample sizes obscure the underlying pathophysiologic events and hamper a comprehensive interpretation of different microarray studies in heart failure. METHODS: We accounted for tissue heterogeneity and technical aspects by performing 2 genome-wide expression studies based on cDNA and short-oligonucleotide microarray platforms which comprised independent septal and left ventricular tissue samples from nonfailing (NF) (n = 20) and DCM (n = 20) hearts. RESULTS: Concordant results emerged for major gene ontology classes between cDNA and oligonucleotide microarrays. Notably, immune response processes displayed the most pronounced down-regulation on both microarray types, linking this functional gene class to the pathogenesis of end-stage DCM. Furthermore, a robust set of 27 genes was identified that classified DCM and NF samples with >90% accuracy in a total of 108 myocardial samples from our cDNA and oligonucleotide microarray studies as well as 2 publicly available datasets. CONCLUSIONS: For the first time, independent microarray datasets pointed to significant involvement of immune response processes in end-stage DCM. Moreover, based on 4 independent microarray datasets, we present a robust gene expression signature of DCM, encouraging future prospective studies for the implementation of disease biomarkers in the management of patients with heart failure.

Antibody Formation↗

Autologous bone marrow stem cell mobilization induced by granulocyte colony-stimulating factor after subacute ST-segment elevation myocardial infarction undergoing late revascularization: final results from the G-CSF-STEMI (Granulocyte Colony-Stimulating Factor ST-Segment Elevation Myocardial Infarction) trial.

OBJECTIVES: The purpose of this investigator-driven, prospective, randomized, double-blinded, placebo-controlled phase II study was to compare the effects of granulocyte colony-stimulating factor (G-CSF) on the improvement of myocardial function in patients undergoing delayed percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Experimental and early clinical studies suggest that transplantation of stem cells improves cardiac regeneration and neovascularization after acute myocardial infarction. Most investigators have utilized either a direct injection or intracoronary infusion of bone marrow-derived cells, but early cytokine-mediated mobilization of stem cells has been reported to show similar improvement in cardiac function. METHODS: Forty-four patients with late revascularized subacute STEMI were treated either with G-CSF or placebo over 5 days after successful PCI. Primary end points were change of global and regional myocardial function from baseline (1 week after PCI) to 3 months after PCI assessed by magnetic resonance imaging (MRI). Secondary end points consisted of characterization of mobilized stem cell populations, assessment of safety parameters up to 12 months including 6-month angiography, as well as myocardial perfusion assessed by MRI. RESULTS: Global myocardial function from baseline (1 week after PCI) to 3 months improved in both groups, but G-CSF was not superior to placebo (Delta(ejection fraction) 6.2 +/- 9.0 vs. 5.3 +/- 9.8%, p = 0.77). A slight but non-significant improvement of regional function occurred in both groups. Granulocyte colony-stimulating factor resulted in mobilization of endothelial progenitor cell populations and was well tolerated with a similar rate of target lesion revascularization from in-stent restenosis. In both groups major adverse cardiovascular events occurred in a comparable frequency. Granulocyte colony-stimulating factor resulted in significant improvement of myocardial perfusion 1 week and 1 month after PCI. CONCLUSIONS: Granulocyte colony-stimulating factor treatment after PCI in subacute STEMI is feasible and relatively safe. However, patients do not benefit from G-CSF when PCI is performed late. Granulocyte colony-stimulating factor results in improved myocardial perfusion of the infarcted area, which may reflect enhanced neovascularization.

Angioplasty, Balloon, Coronary↗

[German Competence Network on Atrial Fibrillation (AFNET). A nationwide cooperation for better research and patient care].

The Atrial Fibrillation Competence Network is an interdisciplinary national research network funded by the Federal Ministry of Education and Research (BMBF). The aim of the network--founded in 2003--is to improve the treatment of atrial fibrillation, the most common clinically important arrhythmia of the heart. A decentralized patient registry has been established. This registry, which comprises the manifestation, diagnostics and therapy of atrial fibrillation in Germany, is being used as a data basis for epidemiologic clinical studies. Epidemiologic projects are being conducted to study, e.g., the prevalence of atrial fibrillation as well as the occurrence of complications. Four multicenter clinical trials have been started to optimize pharmacological treatments (ANTIPAF trial, Flec-SL trial), preventive pacing (BACE-PACE trial) and catheter-based ablation (GAP-AF trial). Other clinical projects are being conducted to study the risk of neurologic complications and to develop new diagnostic imaging techniques. Experimental basic research projects are focusing on different aspects of atrial remodeling in order to find out in which way the molecular mechanisms can be manipulated by new methods of treatment. First results are presented.

Atrial Fibrillation↗

Ablation for atrioventricular nodal reentrant tachycardia with a prolonged PR interval during sinus rhythm: the risk of delayed higher-degree atrioventricular block.

INTRODUCTION: Delayed higher-degree atrioventricular (AV) block can develop after slow pathway ablation for AV nodal reentrant tachycardia with a preexisting first-degree AV block. Retrograde fast pathway ablation is considered as an alternative approach for patients with a markedly prolonged PR interval and no demonstrable anterograde fast pathway function at baseline. This study aimed to determine the long-term reliability of AV conduction after retrograde fast pathway ablation in comparison to slow pathway ablation in patients with AV nodal reentrant tachycardia and a first-degree AV block at baseline. METHODS AND RESULTS: Among 43 patients with AV nodal reentrant tachycardia and a prolonged PR interval (defined as >or=200 msec), 10 patients without demonstrable dual pathway physiology underwent ablation of the retrograde fast pathway, and 33 patients with dual pathway physiology underwent slow pathway ablation. Persisting intraprocedural second- or third-degree AV block requiring pacemaker implantation occurred in one patient (10%) after retrograde fast pathway ablation and in one patient (3%) after slow pathway ablation. During the long-term follow-up of 61 +/- 39 months after retrograde fast pathway ablation, no delayed second- or third-degree AV block occurred, and the PR interval remained unchanged (308 +/- 60 msec vs 304 +/- 52 msec). During the follow-up of 37 +/- 25 months after slow pathway ablation, a delayed complete heart block developed in two patients, and a second-degree AV block developed in two patients. Three patients aged 66, 75, and 76 years died suddenly of unknown cause 4, 16, and 48 months following slow pathway ablation, respectively. CONCLUSIONS: Slow pathway ablation was associated with a significant risk of a delayed higher-degree AV block in patients with AV nodal reentrant tachycardia and a prolonged PR interval at baseline. Retrograde fast pathway ablation for patients with a first-degree AV block and no demonstrable dual pathway physiology was associated with a higher intraprocedural risk of complete AV block but did not result in the development of higher-degree AV block during the long-term follow-up of up to 9 years.

Aged↗

Accuracy of 64-slice computed tomography to classify and quantify plaque volumes in the proximal coronary system: a comparative study using intravascular ultrasound.

OBJECTIVES: We evaluated the accuracy of a new 64-slice computed tomography (CT) scanner, compared with intravascular ultrasound, to visualize atherosclerosis in the proximal coronary system. BACKGROUND: Noninvasive determination of plaque composition and plaque burden may be important to improve risk stratification. METHODS: In 20 patients, a 64-slice CT scan (Sensation 64, Siemens Medical Solutions, Forchheim, Germany) and an intravascular ultrasound investigation of vessels without stenosis >50% was performed. Diagnostic image quality with 64-slice CT was obtained in 36 vessels in 19 patients. RESULTS: In these vessels, which were divided in 3-mm sections, 64-slice CT enabled a correct detection of plaque in 54 of 65 (83%) sections containing noncalcified plaques, 50 of 53 (94%) sections containing mixed plaques, and 41 of 43 (95%) sections containing calcified plaques. In 192 of 204 (94%) sections, atherosclerotic lesions were excluded correctly. In addition, 64-slice CT enabled the visualization of 7 of 10 (70%) sections revealing a lipid pool and could identify a spotty calcification pattern in 27 of 30 (90%) sections. The correlation coefficient to determine plaque volumes per vessel was r2 = 0.69 (p < 0.001) with an underestimation of mixed and noncalcified plaque volumes (p < 0.03) and a trend to overestimate calcified plaque volumes by 64-slice CT. The interobserver variability to determine plaque volumes was 37%. Interobserver agreement to identify atherosclerotic sections was good (Cohen's kappa coefficient = 0.75). CONCLUSIONS: We conclude that 64-slice CT reveals encouraging results to noninvasively detect different types of coronary plaques located in the proximal coronary system. The ability to determine plaque burden currently is hampered by mainly an insufficient reproducibility.

Coronary Angiography↗

Highly purified omega-3 fatty acids for secondary prevention of sudden cardiac death after myocardial infarction-aims and methods of the OMEGA-study.

INTRODUCTION: During the last decades a large body of data has been accumulated indicating omega-3 fatty acids to exert beneficial effects on the prognosis of patients with cardiovascular disease. Especially, omega-3 fatty acids are regarded to be effective in reducing the risk of sudden cardiac death after acute myocardial infarction. However, treatment of acute myocardial infarction and secondary prevention considerably have been improved within the past years including early revascularization by PCI, the routine use of beta-blockers, statins and ACE-inhibitors as well as cardiac rehabilitation for improving life style measures. To date, there exists no controlled randomized trial testing the prognostic effect of omega-3 fatty acids after acute myocardial infarction in a double blind regimen under the conditions of modern treatment of myocardial infarction. MATERIALS AND METHODS: The present study therefore evaluates the effect of highly purified omega-3 fatty acid ethylesters (omega-3-acid ethyl esters 90=Zodin) on the rate of sudden cardiac death within 1 year after acute myocardial infarction. Secondary endpoints are total mortality, non-fatal cardiovascular events, rhythm abnormalities in holter monitoring and depression score. RESULT AND CONCLUSION: The recruitment-period started in October 2003 and is expected to last until December 2006. The results of the study are therefore expected for the beginning of 2008, when all patients will have completed the 12-months follow up-period.

Death, Sudden, Cardiac↗

Effects of corticotropin-releasing hormone (CRH) on monocyte function, mediated by CRH-receptor subtype R1 and R2: a potential link between mood disorders and endothelial dysfunction?

Psychosocial factors have been reported to be independently associated with coronary heart disease (CHD). Though corticotropin-releasing hormone (CRH) is the major hormone activated during adaptive responses to stressful stimuli, the undergoing pathophysiological mechanism related to stress-induced endothelial dysfunction is still poorly understood. This study sought to investigate the effects of extrahypothalamic CRH on monocyte/endothelium adhesion. Second we elucidate the influence of CRH on monocytic endothelin-1 (ET-1) and nitric oxide (NO) release and the receptors involved. Cell adhesion was determined using an adhesion assay, MAC-1 expression by flow cytometry. ET-1/NO release were quantified via ELISA or fluorometrically, monocytic CRH-receptors were confirmed by mRNA. Corticotropin-releasing hormone induced a significant time- and concentration-dependent increase of cell adhesion as well as monocytic MAC-1 expression; endothelial ICAM-1 and VCAM-1 expression was not altered. In addition, corticotropin-releasing hormone significantly increased monocytic ET-1 release whereas nitric oxide release was decreased. The effect was abolished by the selective CRH-receptor antagonist astressin. Our findings support the importance of peripherally circulating corticotropin-releasing hormones, by influencing specific homeostatic properties of monocytes. Our data may provide a novel concept of how specific CRH-receptor antagonists may prevent CRH (stress)-related endothelial dysfunction up to cardiovascular complications.

CD11b Antigen↗

Substrate in the interventricular septum for left ventricular and right ventricular outflow tract tachycardia: ablation from the right side of the septum.

Simultaneous epicardial and endocardial mapping demonstrated that in a substantial number of ventricular tachycardias (VTs) endocardial, intramural, and epicardial structures are involved in the substrate of the reentrant circuits. Both right and left ventricular breakthrough has also been described during VT originating in the interventricular septum. We report the case of a patient with a nonischemic left ventricular aneurysm presenting with a left ventricular outflow tract (LVOT) tachycardia and a right ventricular outflow tract (RVOT) tachycardia. Mapping from the anterior interventricular vein and the endocardium of the RVOT revealed mid-diastolic potentials at the epicardium of the LVOT and the endocardium of RVOT, where the criteria of central isthmus sites could be demonstrated. Ablation targeting an isolated late potential during sinus rhythm in RVOT eliminated both the LVOT tachycardia and the RVOT tachycardia. In this patient with a nonischemic left ventricular aneurysm, the substrate of a LVOT tachycardia and RVOT tachycardia is described, and successful catheter ablation of the right and left ventricular tachycardia from the septal wall of RVOT is reported.

Adult↗

Hemodynamic and vascular effects of ventricular sourcing by stent-based ventricle to coronary artery bypass in patients with multivessel disease undergoing coronary artery bypass surgery.

BACKGROUND: The hemodynamic and vascular effects of ventricular sourcing by a stent-based (VSTENT, Percardia) left ventricle-to-coronary artery bypass were studied in a patient subgroup of the European multicenter ADVANTAGE study (ADjunctive treatment with the VCAB/VSTENT myocardial implANT system in coronary Artery bypass Graft patiEnts). METHODS AND RESULTS: Twelve patients who underwent VSTENT implantation in addition to coronary artery bypass surgery were studied up to 12 months after the procedure. The VSTENT was implanted distal to a hemodynamically relevant coronary artery stenosis. Coronary flow velocity was assessed at rest and during dobutamine stress. Intraoperative VSTENT implantation was successful in 11 of 12 patients. Early postoperative angiograms showed patent VSTENT in 8 of 11 patients, with predominantly systolic flow distal to the VSTENT. Coronary flow velocity reserve induced by dobutamine stress was 1.7+/-0.1 (P=0.006). VSTENT patency at 2- to 6-month follow-up was present in 5 of 11 patients, with concomitant VSTENT stenosis in 4 of those 5. In all patients, coronary flow velocity increased 3- to 4-fold proximal to the VSTENT, which was associated with a moderate degree of arterial remodeling. Except for target vessel reintervention (n=5), no other major adverse events were observed in 11 of 12 patients. One patient died on the second postoperative day, though the cause was probably not related to the VSTENT implantation. CONCLUSIONS: VSTENT implantation seems to be safe in the mid-term follow-up and leads to a predominantly systolic coronary flow pattern in the vessel supplied by the VSTENT, with a flow reserve similar or close to that seen with conventional bypass. VSTENT patency rate, however, was unacceptably low at 3- to 6-month follow-up and needs to be improved.

Aged↗

Quantification of obstructive and nonobstructive coronary lesions by 64-slice computed tomography: a comparative study with quantitative coronary angiography and intravascular ultrasound.

OBJECTIVES: The aim of the present study was to determine the diagnostic accuracy of 64-slice computed tomography (CT) to identify and quantify atherosclerotic coronary lesions in comparison with catheter-based angiography and intravascular ultrasound (IVUS). BACKGROUND: Currently, the ability of multislice CT to quantify the degree of coronary artery stenosis and dimensions of coronary plaques has not been evaluated. METHODS: We included 59 patients scheduled for coronary angiography due to stable angina pectoris. A contrast-enhanced 64-slice CT (Senation 64, Siemens Medical Solutions, Forchheim, Germany) was performed before the invasive angiogram. In a subset of 18 patients, IVUS of 32 vessels was part of the catheterization procedure. RESULTS: In 55 of 59 patients, 64-slice CT enabled the visualization of the entire coronary tree with diagnostic image quality (American Heart Association 15-segment model). The overall correlation between the degree of stenosis detected by quantitative coronary angiography compared with 64-slice CT was r = 0.54. Sensitivity for the detection of stenosis <50%, stenosis >50%, and stenosis >75% was 79%, 73%, and 80%, respectively, and specificity was 97%. In comparison with IVUS, 46 of 55 (84%) lesions were identified correctly. The mean plaque areas and the percentage of vessel obstruction measured by IVUS and 64-slice CT were 8.1 mm2 versus 7.3 mm2 (p < 0.03, r = 0.73) and 50.4% versus 41.1% (p < 0.001, r = 0.61), respectively. CONCLUSIONS: Contrast-enhanced 64-slice CT is a clinically robust modality that allows the identification of proximal coronary lesions with excellent accuracy. Measurements of plaque and lumen areas derived by CT correlated well with IVUS. A major limitation is the insufficient ability of CT to exactly quantify the degree of stenosis.

Aged↗

Functional profiling of human atrial and ventricular gene expression.

The purpose of our investigation was to identify the transcriptional basis for ultrastructural and functional specialization of human atria and ventricles. Using exploratory microarray analysis (Affymetrix U133A+B), we detected 11,740 transcripts expressed in human heart, representing the most comprehensive report of the human myocardial transcriptome to date. Variation in gene expression between atria and ventricles accounted for the largest differences in this data set, as 3.300 and 2.974 transcripts showed higher expression in atria and ventricles, respectively. Functional classification based on Gene Ontology identified chamber-specific patterns of gene expression and provided molecular insights into the regional specialization of cardiomyocytes, correlating important functional pathways to transcriptional activity: Ventricular myocytes preferentially express genes satisfying contractile and energetic requirements, while atrial myocytes exhibit specific transcriptional activities related to neurohumoral function. In addition, several pro-fibrotic and apoptotic pathways were concentrated in atrial myocardium, substantiating the higher susceptibility of atria to programmed cell death and extracellular matrix remodelling observed in human and experimental animal models of heart failure. Differences in transcriptional profiles of atrial and ventricular myocardium thus provide molecular insights into myocardial cell diversity and distinct region-specific adaptations to physiological and pathophysiological conditions. Moreover, as major functional classes of atrial- and ventricular-specific transcripts were common to human and murine myocardium, an evolutionarily conserved chamber-specific expression pattern in mammalian myocardium is suggested.

Animals↗

Reprogramming of the human atrial transcriptome in permanent atrial fibrillation: expression of a ventricular-like genomic signature.

Atrial fibrillation is associated with increased expression of ventricular myosin isoforms in atrial myocardium, regarded as part of a dedifferentiation process. Whether reexpression of ventricular isoforms in atrial fibrillation is restricted to transcripts encoding for contractile proteins is unknown. Therefore, this study compares atrial mRNA expression in patients with permanent atrial fibrillation to atrial mRNA expression in patients with sinus rhythm and to ventricular gene expression using Affymetrix U133 arrays. In atrial myocardium, we identified 1434 genes deregulated in atrial fibrillation, the majority of which, including key elements of calcium-dependent signaling pathways, displayed downregulation. Functional classification based on Gene Ontology provided the specific gene sets of the interdependent processes of structural, contractile, and electrophysiological remodeling. In addition, we demonstrate for the first time a prominent upregulation of transcripts involved in metabolic activities, suggesting an adaptive response to increased metabolic demand in fibrillating atrial myocardium. Ventricular-predominant genes were 5 times more likely to be upregulated in atrial fibrillation (174 genes upregulated, 35 genes downregulated), whereas atrial-specific transcripts were predominantly downregulated (56 genes upregulated, 564 genes downregulated). Overall, in fibrillating atrial myocardium, functional classes of genes characteristic of ventricular myocardium were found to be upregulated (eg, metabolic processes), whereas functional classes predominantly expressed in atrial myocardium were downregulated (eg, signal transduction and cell communication). Therefore, dedifferentiation with adoption of a ventricular-like signature is a general feature of the fibrillating atrium.

Atrial Fibrillation↗

Common variants in myocardial ion channel genes modify the QT interval in the general population: results from the KORA study.

Altered myocardial repolarization is one of the important substrates of ventricular tachycardia and fibrillation. The influence of rare gene variants on repolarization is evident in familial long QT syndrome. To investigate the influence of common gene variants on the QT interval we performed a linkage disequilibrium based SNP association study of four candidate genes. Using a two-step design we analyzed 174 SNPs from the KCNQ1, KCNH2, KCNE1, and KCNE2 genes in 689 individuals from the population-based KORA study and 14 SNPs with results suggestive of association in a confirmatory sample of 3277 individuals from the same survey. We detected association to a gene variant in intron 1 of the KCNQ1 gene (rs757092, +1.7 ms/allele, P=0.0002) and observed weaker association to a variant upstream of the KCNE1 gene (rs727957, +1.2 ms/allele, P=0.0051). In addition we detected association to two SNPs in the KCNH2 gene, the previously described K897T variant (rs1805123, -1.9 ms/allele, P=0.0006) and a gene variant that tags a different haplotype in the same block (rs3815459, +1.7 ms/allele, P=0.0004). The analysis of additive effects by an allelic score explained a 10.5 ms difference in corrected QT interval length between extreme score groups and 0.951 of trait variance (P<0.00005). These results confirm previous heritability studies indicating that repolarization is a complex trait with a significant heritable component and demonstrate that high-resolution SNP-mapping in large population samples can detect and fine map quantitative trait loci even if locus specific heritabilities are small.

Adult↗

Visualising noncalcified coronary plaques by CT.

Due to a rapid improvement of the new generation submillimetre multislice CT-technology noninvasive tomographic imaging of the coronary vessel wall has become reality. First clinical studies have shown the ability in particular of 16-slice CT to determine plaque burden, plaque composition and compensatory vessel-wall remodelling. These novel findings already constitute an important step forward to assess coronary atherosclerosis noninvasively in a detailed manner which opens promising new opportunities for a better understanding and riskstratification of coronary atherosclerosis. Current limitations, mainly the insufficient accuracy to detect small lesions in distal coronary segments, might be overcome by improved spatial and temporal resolution of the new generation scanners operating with 64 and more detectors.

Contrast Media↗