Differential prognostic accuracy of right ventricular dysfunction, the Seattle heart failure model and the MAGGIC score in patients with severe mitral regurgitation undergoing the MitraClip® procedure.

BACKGROUND: MitraClip ® (MC) is an established procedure for severe mitral regurgitation (MR) in patients deemed unsuitable for surgery.Right ventricular dysfunction (RVD) is associated with a higher mortality risk. The prognostic accuracy of heart failure risk scores like the Seattle heart failure model (SHFM) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score in pts undergoing MC with or without RVD has not been investigated so far. METHODS: SHFM and MAGGIC score were calculated retrospectively. RVD was determined as tricuspid annular plane systolic excursion (TAPSE) ≤15 mm. Area under receiver operating curves (AUROC) of SHFM and MAGGIC were performed for one-year all-cause mortality after MC. RESULTS: N = 103 pts with MR III° (73 ± 11 years, LVEF 37 ± 17%) underwent MC with a reduction of at least I° MR. One-year mortality was 28.2%.In Kaplan-Meier analysis, one- year mortality was significantly higher in RVD-pts (34.8% vs 2.8%, p = 0.009).Area under the Receiver Operating Characteristic (AUROC) for SHFM and MAGGIC were comparable for both scores (SHFM: 0.704, MAGGIC: 0.692). In pts without RVD, SHFM displayed a higher AUROC and therefore better diagnostic accuracy (SHFM: 0.776; MAGGIC: 0.551, p < 0.05). In pts with RVD, MAGGIC and SHFM displayed comparable AUROCs. CONCLUSION: RVD is an important prognostic marker in pts undergoing MC. SHFM and MAGGIC displayed adequate over-all prognostic power in these pts. Accuracy differed in pts with and without RVD, indicating higher predictive power of the SHFM score in pts without RVD.

[Pulmonary artery pressure sensor for ambulatory assessment of ventricular filling pressure in advanced heart failure : What should be considered for the follow-up care?] / Pulmonalarterieller Drucksensor zur ambulanten Beurteilung des ventrikulären Füllungsdrucks bei fortgeschrittener Herzinsuffizienz : Was ist bei der Nachsorge zu beachten?

BACKGROUND: Patients with advanced heart failure suffer from frequent hospitalizations. Noninvasive hemodynamic telemonitoring for assessment of pulmonary filling pressure has been shown to reduce hospitalizations. In this article, our experience with possible control intervals and the standardization of the follow-up care of hemodynamic telemonitoring is reported. METHODS: A literature search and our own experience in the follow-up care concerning the implantable pulmonary artery pressure sensor for noninvasive hemodynamic telemonitoring in patients with advanced heart failure are presented. RESULTS: For standardized follow-up care of heart failure patients with hemodynamic monitoring a specialized team consisting of a heart failure nurse and heart failure physician is essential. These teams should ideally work based on a unique standard operating procedure (SOP) to ensure standardized control intervals and a standardized approach to classical hemodynamic changes. However, all therapeutic recommendations have to be prescribed by a physician and must be modified if individually appropriate. CONCLUSION: Optimized follow-up care for hemodynamically guided heart failure management requires the implementation of novel structures in the German health care system in order to transfer the clinical benefit from clinical trials into daily routine.

[Implantable sensors for outpatient assessment of ventricular filling pressure in advanced heart failure : Which telemonitoring design is optimal?] / Implantierbare Sensoren zur ambulanten Beurteilung des ventrikulären Füllungsdrucks bei fortgeschrittener Herzinsuffizienz : Welches Telemonitoring-Design ist optimal?

INTRODUCTION: Patients with advanced heart failure suffer from frequent hospitalizations. Non-invasive hemodynamic telemonitoring for assessment of ventricular filling pressure has been shown to reduce hospitalizations. We report on the right ventricular (RVP), the pulmonary artery (PAP) and the left atrial pressure (LAP) sensor for non-invasive assessment of the ventricular filling pressure. METHODS: A literature search concerning the available implantable pressure sensors for noninvasive haemodynamic telemonitoring in patients with advanced heart failure was performed. RESULTS: Until now, only implantation of the PAP-sensor was able to reduce hospitalizations for cardiac decompensation and to improve quality of life. The right ventricular pressure sensor missed the primary endpoint of a significant reduction of hospitalizations, clinical data using the left atrial pressure sensor are still pending. CONCLUSION: The implantation of a pressure sensor for assessment of pulmonary artery filling pressure is suitable for reducing hospitalizations for heart failure and for improving quality of life in patients with advanced heart failure.

Suspected involvement of EPTFE membrane in sterile intrathoracic abscess and pericardial empyema in a multi-allergic LVAD recipient: a case report.

Device-related infections in recipients of left ventricular assist devices (LVAD) have been recognized as a major source of morbidity and mortality. They require a high level of diagnostic effort as part of the overall burden resulting from infectious complications in LVAD recipients. We present a multi-allergic patient who was treated for persistent sterile intrathoracic abscess formation and pericardial empyema following minimally invasive LVAD implantation including use of a sheet of e-polytetrafluoroethylene (ePTFE) membrane to restore pericardial integrity. Sterile abscess formation and pericardial empyema recurred after surgical removal until the ePTFE membrane was removed, suggesting that in disposed patients, ePTFE may be related to sterile abscess formation or sterile empyema.

[Regenerative therapy in cardiology: how distant is it from reality?]. / Regenerative Therapien in der Kardiologie: Wie weit entfernt von der Praxis?

During acute myocardial infarction, ischemia causes progressive loss of contractile tissue. Subsequently, structural changes lead to left ventricular remodeling finally resulting in the development of heart failure. In addition to an optimal reperfusion and pharmacologinal post-infarction therapy, increased neovascularization and regeneration of cardiomyocytes could reduce or even abolish the ongoing left ventricular remodeling processes within the infarct area. Experimental studies have demonstrated that transplantation of adult progenitor cells leads to increased neovascularization, reduced fibrosis and, therefore, increased left ventricular function after acute myocardial infarction. In contrast to current treatment strategies, progenitor cell therapy offers a new regenerative approach for myocardial tissue. Initial clinical studies have demonstrated, apart from safety and feasibility of intracoronary infusion of adult autologous progenitor cells, a significant improvement of left ventricular function, geometry and vascularization in patients with acute myocardial infarction receiving intracoronary infusion of progenitor cells. However, in patients with chronic ischemic cardiomyopathy, the improvement in contractility is less pronounced. Finally, whether intracoronary infusion of adult progenitor cells can also reduce morbidity and mortality due to heart failure, remains to be investigated.

Normalization of coronary blood flow in the infarct-related artery after intracoronary progenitor cell therapy: intracoronary Doppler substudy of the TOPCARE-AMI trial.

BACKGROUND: Coronary microvascular dysfunction contributes to infarct extension and poor prognosis after an acute myocardial infarction (AMI). Recently, progenitor cell application has been demonstrated to improve neovascularization and myocardial function after experimental myocardial infarction. Therefore, we investigate coronary blood flow regulation in patients after AMI treated with intracoronary progenitor cell therapy. METHODS AND RESULTS: In the TOPCARE-AMI trial, patients received either bone marrow-derived or circulating progenitor cells into the infarct-related artery 3-7 days after AMI. The present substudy investigates in 40 patients coronary blood flow regulation at the time of progenitor cell therapy and at 4-month follow-up by i.c. Doppler in the infarct artery as well as a reference vessel. At the initial measurement, coronary flow reserve (CFR) was reduced in the infarct artery compared to the reference vessel (median 2.5 vs. 3.4, p<0.001). At 4-month follow-up, intracoronary progenitor cell therapy was associated with a normalization of CFR in the infarct artery (median 3.9 vs. reference vessel 3.8, p=0.15). CFR also improved in the reference vessel, but mechanisms were different: reference vessel increase in CFR was secondary to an increased basal vascular resistance, probably due to reduced need for hypercontractility. In contrast, in the infarct artery, adenosine-induced minimal vascular resistance profoundly decreased, indicating an increased maximal coronary vascular conductance capacity. In addition, in a non-randomized matched control group (n=8), minimal vascular resistance in the infarct artery was significantly elevated compared to progenitor cell treated patients 4 months after AMI (p=0.012). CONCLUSIONS: Intracoronary progenitor cell therapy after AMI is associated with complete restoration of coronary flow reserve due to a substantial improvement of maximal coronary vascular conductance capacity. The clinical importance of improved microcirculation by progenitor cell therapy in patients after AMI has to be established in further randomized trials.

Infarct remodeling after intracoronary progenitor cell treatment in patients with acute myocardial infarction (TOPCARE-AMI): mechanistic insights from serial contrast-enhanced magnetic resonance imaging.

BACKGROUND: Experimental and initial clinical studies suggest that transplantation of circulating blood- (CPC) or bone marrow-derived (BMC) progenitor cells may beneficially affect postinfarction remodeling processes after acute myocardial infarction (AMI). To relate functional characteristics of the infused cells to quantitative measures of outcome at 4-month follow-up, we performed serial contrast-enhanced MRI and assessed the migratory capacity of the transplanted progenitor cells immediately before intracoronary infusion. METHODS AND RESULTS: In 28 patients with reperfused AMI receiving either BMCs or CPCs into the infarct artery 4.7+/-1.7 days after AMI, serial contrast-enhanced MRI performed initially and after 4 months revealed a significant increase in global ejection fraction (from 44+/-10% to 49+/-10%; P=0.003), a decrease in end-systolic volume (from 69+/-26 to 60+/-28 mL; P=0.003), and unchanged end-diastolic volumes (122+/-34 versus 117+/-37 mL; P=NS). Infarct size, measured as late enhancement (LE) volume, decreased significantly, from 46+/-32 to 37+/-28 mL (P<0.05). There was a significant correlation between the reduction in LE volume and global ejection fraction improvement. The migratory capacity of transplanted cells as assessed ex vivo toward a gradient of vascular endothelial growth factor for CPCs and stromal cell derived factor-1 for BMCs was closely correlated with the reduction of LE volume. By multivariate analysis, migratory capacity remained the most important independent predictor of infarct remodeling. CONCLUSIONS: Analysis of serial contrast-enhanced MRI suggests that intracoronary infusion of adult progenitor cells in patients with AMI beneficially affects postinfarction remodeling processes. The migratory capacity of the infused cells is a major determinant of infarct remodeling, disclosing a causal effect of progenitor cell therapy on regeneration enhancement.

[Coronary stent implantation in elderly patients: acute and long-term results]. / Koronare Stentimplantation bei alten Patienten. Akutergebnisse und Langzeitverlauf.

UNLABELLED: The number of elderly patients with coronary heart disease is rapidly growing. Morbidity, related with PTCA is increased in elderly patients, presumably because of the more complex adverse baseline characteristics. However, it has not been firmly elucidated whether routine use of coronary stents is associated with a more favourable outcome in this population. Therefore, we investigated the influence of age on acute procedural success, rate of restenosis (quantitative coronary angiography) and major cardiovascular events (death/myocardial infarction [MI]) 6 months after intra-coronary stent implantation in 1306 patients. Patients were categorised into < 65 years (n = 709),65-75 years (n = 443) and >75 years (n= 154). RESULTS: Older patients had a higher amount of multivessel disease (p < 0.001) and a lower left ventricular ejection fraction (p < 0.001). Nevertheless, the rate of acute success and restenosis were comparable between the different age groups. In contrast, older patients had significantly more adverse clinical events during long-term followup. (Death/MI < 65 years 3.0%, 65-75 years 3.9%, > 75 years 7.8%, p = 0.02). However, by multivariate analysis age was no longer an independent predictor of adverse clinical events (p = 0.26), which were predominantly determined by coexisting impaired left ventricular function (p < 0.001). CONCLUSION: After proper judgement of the clinical situation, coronary stent implantation should be considered in selected elderly patients. Thus, advanced age as a solely factor should not be regarded as a contraindication for coronary stent implantation.

Insulin-mediated stimulation of protein kinase Akt: A potent survival signaling cascade for endothelial cells.

Insulin exerts potent antiapoptotic effects in neuronal cells and has been suggested to promote angiogenesis. Therefore, we investigated whether insulin inhibits tumor necrosis factor-alpha (TNF-alpha)-induced apoptosis in human umbilical vein endothelial cells (HUVECs). Because insulin has been shown to stimulate the protein kinase Akt, we investigated whether activation of Akt contributes to the apoptosis-suppressive effect of insulin and characterized the downstream signaling pathway. Incubation with insulin dose-dependently prevented apoptosis induced by TNF-alpha (50 ng/mL). The extent of apoptosis suppression by insulin was similar to the effect of vascular endothelial growth factor. Pharmacological inhibition of Akt activation or overexpression of a dominant-negative Akt mutant prevented the antiapoptotic effect of insulin. Furthermore, we investigated the effect of TNF-alpha on Akt phosphorylation by Western blot analysis with the use of a phosphospecific Akt antibody. Incubation of HUVECs with TNF-alpha induced a marked dephosphorylation of Akt. Insulin counteracted this TNF-alpha-induced dephosphorylation of Akt. Furthermore, we investigated the downstream signaling events. Akt has been shown to mediate its apoptosis-suppressive effects via phosphorylation of Bad or caspase-9. However, incubation with insulin did not lead to enhanced phosphorylation of Bad at Ser 136 or Ser 112. In contrast, insulin inhibited caspase-9 activity and prevented caspase-9-induced apoptosis. Mutation of the Akt site within caspase-9 significantly reduced the apoptosis-suppressive effect of insulin. The present study demonstrates an important role for insulin-mediated Akt activation in the prevention of endothelial cell apoptosis, which may importantly contribute to cell homeostasis and the integrity of the endothelium. In endothelial cells, Akt seems to mediate its antiapoptotic effect, at least in part, via phosphorylation of caspase-9 rather than Bad.

Physiology, phylogenetic relationships, and ecology of filamentous sulfate-reducing bacteria (genus desulfonema)

Microscopy of organic-rich, sulfidic sediment samples of marine and freshwater origin revealed filamentous, multicellular microorganisms with gliding motility. Many of these neither contained sulfur droplets such as the Beggiatoa species nor exhibited the autofluorescence of the chlorophyll-containing cyanobacteria. A frequently observed morphological type of filamentous microorganism was enriched under anoxic conditions in the dark with isobutyrate plus sulfate. Two strains of filamentous, gliding sulfate-reducing bacteria, Tokyo 01 and Jade 02, were isolated in pure cultures. Both isolates oxidized acetate and other aliphatic acids. Enzyme assays indicated that the terminal oxidation occurs via the anaerobic C(1) pathway (carbon monoxide dehydrogenase pathway). The 16S rRNA genes of the new isolates and of the two formerly described filamentous species of sulfate-reducing bacteria, Desulfonema limicola and Desulfonema magnum, were analyzed. All four strains were closely related to each other and affiliated with the delta-subclass of Proteobacteria. Another close relative was the unicellular Desulfococcus multivorans. Based on phylogenetic relationships and physiological properties, Strains Tokyo 01 and Jade 02 are assigned to a new species, Desulfonema ishimotoi. A new, fluorescently labeled oligonucleotide probe targeted against 16S rRNA was designed so that that it hybridized specifically with whole cells of Desulfonema species. Filamentous bacteria that hybridized with the same probe were detected in sediment samples and in association with the filamentous sulfur-oxidizing bacterium Thioploca in its natural habitat. We conclude that Desulfonema species constitute an ecologically significant fraction of the sulfate-reducing bacteria in organic-rich sediments and microbial mats.

Fluid shear stress stimulates phosphorylation of Akt in human endothelial cells: involvement in suppression of apoptosis.

Fluid shear stress alters the morphology and function of the endothelium by activating several kinases. Furthermore, shear stress potently inhibits apoptosis of endothelial cells. Since activation of Akt kinase has been shown to prevent cell death, we investigated the effects of shear stress on Akt phosphorylation. To test the hypothesis that shear stress interacts with the Akt kinase pathway, human umbilical venous endothelial cells were exposed to laminar shear stress (15 dyne/cm2). Western blotting with specific antibodies against the phosphorylated Akt demonstrated a time-dependent stimulation of Akt phosphorylation by shear stress with a maximal increase up to 6-fold after 1 hour of shear stress exposure. The stimulation of Akt phosphorylation by shear stress thereby seemed to be mediated by the phosphoinositide 3-OH kinase (PI3K), as evidenced by the significant inhibition of shear stress-induced Akt phosphorylation by the PI3K inhibitors wortmannin (20 nmol/L) and Ly294002 (10 micromol/L). In addition, pharmacological inhibition of P13K reduced the antiapoptotic effect of shear stress against growth factor depletion-induced apoptosis. Most important, overexpression of a dominant-negative Akt mutant significantly inhibited the apoptosis-suppressive effect of shear stress against serum depletion-induced apoptosis, thus indicating the direct involvement of shear stress-induced Akt phosphorylation for inhibition of endothelial cell apoptosis. These results define a novel shear stress-stimulated signal transduction pathway, namely, activation of the serine/threonine kinase Akt, which may contribute to the profound changes in endothelial morphology and function by shear stress.

Root colonization of different plants by plant-growth-promoting Rhizobium leguminosarum bv. trifolii R39 studied with monospecific polyclonal antisera.

Monospecific polyclonal antisera raised against Rhizobium leguminosarum bv. trifolii R39, a bacterium which was isolated originally from red clover nodules, were used to study the colonization of roots of leguminous and nonleguminous plants (Pisum sativum, Lupinus albus, Triticúm aestivum, and Zea mays) after inoculation. Eight weeks after inoculation of soil-grown plants, between 0.1 and 1% of the total bacterial population in the rhizospheres of all inoculated plants were identified as R. leguminosarum bv. trifolii R39. To characterize the associative colonization of the nonleguminous plants by R.leguminosarum bv. trifolii R39 in more detail, a time course study was performed with inoculated roots of Z. mays. R. leguminosarum bv. trifolii R39 was found almost exclusively in the rhizosphere soil and on the rhizoplane 4 weeks after inoculation. Colonization of inner root tissues was detected only occasionally at this time. During the process of attachment of R. leguminosarum bv. trifolii R39 to the rhizoplane, bacterial lipopolysaccharides were overexpressed, and this may be important for plant-microbe interaction. Fourteen weeks after inoculation, microcolonies of R. leguminosarum bv. trifolii R39 were detected in lysed cells of the root cortex as well as in intracellular space of central root cylinder cells. At the beginning of flowering (18 weeks after inoculation), the number of R. leguminosarum bv. trifolii R39 organisms decreased in the rhizosphere soil, rhizoplane, and inner root tissue.

Direct examination of subgingival plaque from a diseased periodontal site using confocal laser scanning microscopy (CLSM).

Material taken directly from a periodontal site was investigated using immunofluorescence, acridine orange staining and confocal laser scanning microscopy (CLSM). Porphyromonas gingivalis was tracked by a specific polyclonal antibody and its pronounced occurrence in inflamed as compared to non-inflamed areas was demonstrated. Further accompanying microorganisms were counterstained with acridine orange which could provide information on the viability of individual cells. Optical sections by laser microscopy revealed the spatial arrangement of the investigated material. The combination of specific staining and CLSM allows a detailed microbiological investigation of clinical material obtained directly without cultivation.

Molecular evidence for association between the sphingobacterium-like organism "Candidatus comitans" and the myxobacterium Chondromyces crocatus.

Seven strains of the myxobacterium Chondromyces crocatus, isolated from widely separated geographic regions, were investigated for the presence of an associate gram-negative, rod-shaped companion bacterium that is phylogenetically related to the genus Sphingobacterium and has been named "Candidatus comitans" (C. A. Jacobi, E. Stackebrandt, H. Reichenbach, and B. J. Tindall, Int. J. Syst. Bacteriol. 46:119-122, 1996). Five of the Chondromyces strains were found to be associated with a companion bacterium, and one strain lost its companion during the study. A 16S ribosomal DNA (16S rDNA) clone library was generated for each Chondromyces culture. Sequence similarity was > 99.1% for all but one strain of C. crocatus and all but one strain of "Candidatus comitans". The three analyzed 16S rDNA clone sequences of the companion of Cm c7 indicated that this companion strain is slightly less related to the other companion strains. The association between the companion and the myxobacterium including the sporangioles was determined by in situ hybridization with fluorescently labeled rRNA probes and scanning confocal laser microscopy. Based on these results, there are indications that the companion strains may survive environmental stress by inclusion in the aggregates and in the sporangioles of the myxobacterium.

In Situ Localization of Azospirillum brasilense in the Rhizosphere of Wheat with Fluorescently Labeled, rRNA-Targeted Oligonucleotide Probes and Scanning Confocal Laser Microscopy.

The colonization of wheat roots by Azospirillum brasilense was used as a model system to evaluate the utility of whole-cell hybridization with fluorescently labeled, rRNA-targeted oligonucleotide probes for the in situ monitoring of rhizosphere microbial communities. Root samples of agar- or soil-grown 10- and 30-day-old wheat seedlings inoculated with different strains of A. brasilense were hybridized with a species-specific probe for A. brasilense, a probe hybridizing to alpha subclass proteobacteria, and a probe specific for the domain Bacteria to identify and localize the target bacteria. After hybridization, about 10 to 25% of the rhizosphere bacteria as visualized with 4(prm1),6-diamidino-2-phenylindole (DAPI) gave sufficient fluorescence signals to be detected with rRNA-targeted probes. Scanning confocal laser microscopy was used to overcome disturbing effects arising from autofluorescence of the object or narrow depth of focus in thick specimens. This technique also allowed high-resolution analysis of the spatial distribution of bacteria in the rhizosphere. Occurrence of cells of A. brasilense Sp7 and Wa3 was restricted to the rhizosphere soil, mainly to the root hair zone. C-forms of A. brasilense were demonstrated to be physiologically active forms in the rhizosphere. Strain Sp245 also was found repeatedly at high density in the interior of root hair cells. In general, the combination of fluorescently labeled oligonucleotide probes and scanning confocal laser microscopy provided a very suitable strategy for detailed studies of rhizosphere microbial ecology.

The use of immunological methods to detect and identify bacteria in the environment.

Immunological detection methods have become increasingly important in microbial ecology for the tracking of specific microorganisms and for community analysis. For a reliable application of these techniques, the monoclonal antibodies or polyclonal antisera used have to fulfill several quality criteria. Cross reactivity, cellular localization of the antigenic determinant, affinity characteristics and the expression of the antigenic determinant at environmental conditions have to be determined. Immunological methods can be used for the identification, quantification and enrichment of specific bacteria in extracts as well as for the visualization of cells in situ. The sensitivity of advanced immunological methods can be compared to PCR techniques. Using image processing of epifluorescence micrographs or confocal laser scanning microscopy, the immunofluorescence approach can now be applied to study complex environmental samples.

In situ analysis of microbial consortia in activated sludge using fluorescently labelled, rRNA-targeted oligonucleotide probes and confocal scanning laser microscopy.

Activated sludge flocs are complex consortia of various micro-organisms. The community structures of samples taken from municipal sewage treatment plants were characterized using fluorescently labelled, 16S and 23S rRNA-targeted oligonucleotide probes in combination with confocal scanning laser microscopy (CSLM). In comparison with conventional epifluorescence microscopy, CSLM considerably improved the capability to visualize directly the spatial distribution of defined bacterial populations inside the sludge flocs. Analyses could be performed at high resolution undisturbed by problems such as autofluorescence or limited spatial resolution in thick samples. In addition, CSLM was used to analyse some structural properties of paraformaldehyde-fixed activated sludge flocs, such as floc size and homogeneity. Typical floc sizes were found to be in the range between 5 and 50 microns. Whereas most of the flocs were completely colonized by bacteria, there were also examples of flocs containing gas bubbles or particles in the interior.

[Chronic disseminated histiocytosis X. A case with unusual liver involvement]. / Chronische disseminierte Histiocytosis X. Ein Fall mit ungewöhnlicher Leberbeteiligung.

A chronic disseminated histiocytosis X of a 37-year-old patient is reported on. Besides the classical Hand-Schüller-Christian-trias the involvement of central parts of the liver with jaundice and cholangitis was predominant.