Ursula Müller-Werdan

Martin Luther University Halle-Wittenberg, Halle-on-the-Saale, Saxony-Anhalt, Germany

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Publications (158)393.84 Total impact

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    ABSTRACT: In critically ill patients regulation of heart-rate is often severely disturbed. Interaction of bacterial endotoxin (lipopolysaccharide, LPS) with hyperpolarization-activated cyclic nucleotide-gated cation-(HCN)-channels may interfere with heart-rate regulation. Here, we analyze the effect of LPS, the HCN-channel blocker ivabradine or Ca(2+) -channel blockers (nifedipine, verapamil) on pacemaking in spontaneously beating neonatal rat cardiomyocytes (CM) in vitro. In vivo, we analyze telemetrically the effect of LPS on the heart-rate of adult CD1-mice with and without autonomic blockade. LPS (100 ng/ml) and ivabradine (5 μg/ml) reduced the beating-rate of CM by 20.1 and 24.6%, respectively. Coincubation of CM with both, LPS and ivabradine, did not further reduce the beating-rate, indicating interaction of both compounds with HCN-channels, while coincubation with Ca(2+-) channel blockers and LPS caused additive beating-rate reduction. In CD1-mice with an active autonomic-nervous-system, injection of LPS (0.4 mg/kg) expectedly resulted in increased heart-rate. However, if the autonomic nervous system was blocked by propranolol and atropine, in line with the in vitro data, LPS induced a significant reduction of heart-rate, which was not additive to ivabradine. The in vivo and in vitro results indicate that endotoxin interacts with HCN-channels of cardiomyocytes. Thus, LPS indirectly sensitizes HCN-channels for sympathetic activation (tachycardic-effect), and in parallel directly inhibits channel activity (bradycardic-effect). Both effects may contribute to the detrimental effects of septic cardiomyopathy and septic autonomous dysfunction. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.
    Clinical and Experimental Pharmacology and Physiology 04/2015; DOI:10.1111/1440-1681.12415 · 2.41 Impact Factor
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    ABSTRACT: The anti-anginal efficacy of ivabradine is well established. We describe a post hoc analysis in the ADDITIONS database to investigate effectiveness and tolerability of ivabradine in combination with beta-blocker in patients with angina who have had a percutaneous coronary intervention (PCI). ADDITIONS was a non-interventional, multicenter prospective study including 2,330 patients with stable angina. In addition to beta-blocker, patients were treated with ivabradine in approved dosages for 4 months. We divided the population according to whether they had previously had a PCI or not, and explored the effect of ivabradine on heart rate, number of weekly angina attacks, frequency of nitrate consumption, as well as quality of life (QoL) and tolerability. Data were available for 2,319 patients, of whom 51.4% had previously had a PCI. There was no difference in the effect of ivabradine on mean heart rate between patients with a previous PCI [64.4 ± 7.6 beats per minute (bpm)] than those without (66.8 ± 8.5 bpm) at 4 months (both P < 0.0001). Similarly, the number of angina attacks decreased from 1.9 ± 2.4 to 0.5 ± 1.5 per week in patients with a previous PCI and 1.5 ± 2.0 to 0.3 ± 1.0 per week in patients without a previous PCI (both P < 0.0001). The frequency of nitrate consumption fell from 2.7 ± 3.7 to 1.0 ± 1.9 per week and 1.8 ± 2.8 to 0.6 ± 1.5 per week (both P < 0.0001) in patients with and without a previous PCI, respectively. There was no difference in the improvements in Canadian Cardiovascular Society class of angina, QoL, and physicians' assessment of effectiveness and tolerability between patients with a previous PCI and those without. Ivabradine is an effective and well-tolerated anti-anginal treatment in patients with stable angina after PCI. Ivabradine reduced the frequency of weekly angina attacks and nitrate consumption, led to an improvement in Canadian Cardiovascular Society class and a substantial improvement in the QoL of stable angina patients.
    Advances in Therapy 02/2015; DOI:10.1007/s12325-015-0182-8 · 2.44 Impact Factor
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    ABSTRACT: Abstract BACKGROUND: Clinical trials have proven the anti-anginal and anti-ischemic efficacy of the pacemaker current inhibitor ivabradine in combination with beta-blockers in patients with stable angina pectoris (AP). This retrospective subgroup analysis of the ADDITIONS study evaluated the effectiveness and tolerability of ivabradine combined with beta-blockers, and its effects on angina symptoms and quality of life in elderly patients ≥ 75 years in everyday practice. METHODS: In the non-interventional, multicenter, prospective, open-label ADDITIONS study 2330 patients with stable AP of different age groups were treated with a flexible dose of ivabradine twice daily in addition to beta-blockers for 4 months. Heart rate (HR), number of angina attacks, nitrate consumption, tolerance, and quality of life (QoL) were evaluated. A subgroup analysis was performed, focusing on 479 patients (21%) ≥ 75 years. RESULTS: In these 479 patients ≥ 75 years ivabradine (mean dose 11.61 ± 3.18 mg per day) after 4 months of treatment reduced HR by 19.2 ± 11.6 bpm to 65.4 ± 8.3 bpm. The average number of angina attacks per week was decreased by 1.6 ± 1.8 to 0.4 ± 1.3 and the average consumption of short-acting nitrates per week was reduced by 2.2 ± 3.2 to 0.6 ± 1.8 units (both p < 0.0001). There was a marked shift in Canadian Cardiovascular Society (CCS) grade distribution with most patients (57%) now classified as CCS grade I, and 42% as CCS grades II and III. This was accompanied by an improvement in EQ-5D QoL index to 0.75 ± 0.22 (p < 0.0001). Tolerability of ivabradine treatment was rated by the physicians as “very good/good” for 72%/28% of elderly patients. CONCLUSIONS: In daily clinical practice, addition of ivabradine to beta-blockers was effective in reducing HR, angina attacks and nitrate consumption in elderly patients (≥ 75 years) with stable angina pectoris. In addition, a marked improvement of CCS symptom scores and QoL was demonstrated. Treatment was generally well tolerated.
    Experimental Gerontology 11/2014; 59:34-41. DOI:10.1016/j.exger.2014.09.002 · 3.53 Impact Factor
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    ABSTRACT: BACKGROUND: Clinical trials have proven the anti-anginal and anti-ischemic efficacy of the pacemaker current inhibitor ivabradine in combination with beta-blockers in patients with stable angina pectoris (AP). This retrospective subgroup analysis of the ADDITIONS study evaluated the effectiveness and tolerability of ivabradine combined with beta-blockers, and its effects on angina symptoms and quality of life in elderly patients ≥ 75 years in everyday practice. METHODS: In the non-interventional, multicenter, prospective, open-label ADDITIONS study 2330 patients with stable AP of different age groups were treated with a flexible dose of ivabradine twice daily in addition to beta-blockers for 4 months. Heart rate (HR), number of angina attacks, nitrate consumption, tolerance, and quality of life (QoL) were evaluated. A subgroup analysis was performed, focusing on 479 patients (21%) ≥ 75 years. RESULTS: In these 479 patients ≥ 75 years ivabradine (mean dose 11.61 ± 3.18 mg per day) after 4 months of treatment reduced HR by 19.2 ± 11.6 bpm to 65.4 ± 8.3 bpm. The average number of angina attacks per week was decreased by 1.6 ± 1.8 to 0.4 ± 1.3 and the average consumption of short-acting nitrates per week was reduced by 2.2 ± 3.2 to 0.6 ± 1.8 units (both p < 0.0001). There was a marked shift in Canadian Cardiovascular Society (CCS) grade distribution with most patients (57%) now classified as CCS grade I, and 42% as CCS grades II and III. This was accompanied by an improvement in EQ-5D QoL index to 0.75 ± 0.22 (p < 0.0001). Tolerability of ivabradine treatment was rated by the physicians as “very good/good” for 72%/28% of elderly patients. CONCLUSIONS: In daily clinical practice, addition of ivabradine to beta-blockers was effective in reducing HR, angina attacks and nitrate consumption in elderly patients (≥ 75 years) with stable angina pectoris. In addition, a marked improvement of CCS symptom scores and QoL was demonstrated. Treatment was generally well tolerated.
    Experimental Gerontology 11/2014; 59:34-41. · 3.53 Impact Factor
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    ABSTRACT: Objectives: Inflammation is essential for atherogenesis. Cholesterol, a cardiovascular risk factor, may activate inflammation in the vessel wall during this process. Cytokine-mediated interactions of human monocytes with vascular smooth muscle cells (SMCs) may perpetuate this process. Methods: We investigated the capacity of the cholesterol metabolite 25-hydroxycholesterol to induce inflammatory mediators in cocultures of freshly isolated monocytes with SMCs. We determined the role of interleukin-(IL)-1 in this interaction using qPCR, bioassays, ELISA and western blot. Cocultures with SMC to monocyte ratios from 1:4 to 1:20 were tested. Results: In separate SMC and monocyte cultures (monocultures) 25-hydroxycholesterol only poorly activated IL-1, IL-6 and MCP-1 production, whereas LPS stimulated much higher cytokine levels than unstimulated cultures. In contrast, cocultures of SMCs and monocytes stimulated with 25-hydroxycholesterol produced hundredfold higher cytokine levels than the corresponding monocultures. Blocking experiments with IL-1-receptor antagonist showed that IL-1 decisively contributed to the 25-hydroxycholesterol-induced synergistic IL-6 and MCP-1 production. The presence of intracellular IL-1β precursor, released mature IL-1β, and caspase-1 p10 indicated that the inflammasome was involved in this process. Determination of IL-1-mRNA in Transwell experiments indicated that the monocytes are the major source of IL-1, which subsequently activates the SMCs, the primary source of IL-6 in the coculture. Conclusion: Taken together, these interactions between local vessel wall cells and invading monocytes may multiply cholesterol-triggered inflammation in the vessel wall, and IL-1 may play a key role in this process. The data also indicate that lower cholesterol levels than expected from monocultures may suffice to initiate inflammation in the tissue. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.
    Atherosclerosis 10/2014; 237(2):443-452. DOI:10.1016/j.atherosclerosis.2014.10.002 · 3.97 Impact Factor
  • Atherosclerosis 08/2014; 235(2):e89. DOI:10.1016/j.atherosclerosis.2014.05.235 · 3.97 Impact Factor
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    ABSTRACT: Die kardiovaskulären Erkrankungen zählen zu den häufigsten stationären Behandlungsanlässen älterer Menschen. Dennoch finden die Besonderheiten geriatrischer Patienten in der akutstationären Versorgung bisher kaum Beachtung. Ziel dieser Untersuchung war die deskriptive Darstellung klinischer Versorgungsverläufe geriatrischer und nichtgeriatrischer Patienten mit akutem Myokardinfarkt (AMI).Im Rahmen einer Vollerhebung wurden 83 Patientenakten aus dem Jahr 2009 im Hinblick auf pflegerische, therapeutische sowie sozialberatende und medizinische Maßnahmen untersucht. Die retrospektive Dokumentenanalyse stützt sich auf die Daten der kardiologischen Fachabteilung eines Universitätsklinikums. Die Eingruppierung in geriatrische und nichtgeriatrische Patienten erfolgte anhand einer im Vorfeld entwickelten Kriterienliste.Es konnten 48 geriatrische und 35 nichtgeriatrische Patienten identifiziert werden. Es zeigten sich bei den geriatrischen Patienten ein umfassender pflegerischer und therapeutischer Unterstützungsbedarf, eine hohe Komplikationshäufigkeit und lange Verweildauer sowie Besonderheiten bezüglich des Entlassungsorts.Aufgezeigt wurden die komplexen Problemstellungen und besonderen Versorgungsbedürfnisse geriatrischer Patienten mit akutem Myokardinfarkt. Diese vulnerable Patientengruppe sollte in der Akutversorgung stärker Beachtung finden. Weiterführende Studien mit einem prospektiven Ansatz sind notwendig, um die spezifischen Bedürfnisse geriatrischer Patienten in der Akutversorgung zu erfassen.
    Zeitschrift für Gerontologie + Geriatrie 01/2014; 47(1). · 1.02 Impact Factor
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    ABSTRACT: We investigated the relationship of impaired autonomic function and severity of illness in chronic heart failure (CHF) and multiple-organ dysfunction syndrome (MODS) as an end stage of CHF. Furthermore, we assessed the link of parasympathetic modulation of the heart rate and inflammatory activation in CHF and MODS. Sixty-five patients admitted for worsening of CHF were retrospectively enrolled in this study. In addition, 65 age- and sex-matched patients with pronounced MODS were assigned for comparison of autonomic function and C-reactive protein in patients with CHF or MODS, respectively. Heart rate variability (HRV) parameters of the time and frequency domain as markers of autonomic function were analyzed from 24-hour Holter electrocardiograms. The more pronounced the severity of illness as expressed by the Acute Physiology and Chronic Health Evaluation score, the more the HRV was impaired. This effect was particularly seen for overall variability (SD of RR intervals) and HRV parameters characterizing the parasympathetic modulations of the heart rate (high, very low frequency power). C-reactive protein levels as markers of inflammation were inversely related to high and very low frequencies. Our results allow for speculation that autonomic dysfunction in CHF indicates a beginning of uncoupled interorgan communication potentially leading to MODS as characterized by disruption of communication between the organs.
    Journal of critical care 12/2013; DOI:10.1016/j.jcrc.2013.12.015 · 2.19 Impact Factor
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    ABSTRACT: Depressed heart rate variability in severe inflammatory diseases can partially be explained by the lipopolysaccharide (LPS)-dependent modulation of cardiac pacemaker channels. Recently, we showed that LPS inhibits pacemaker current in sino-atrial node cells and in HEK293 cells expressing cloned pacemaker channels, respectively. The present study was designed to verify whether this inhibition involves LPS-dependent intracellular signaling and to identify structures of LPS responsible for pacemaker current modulation. We examined the effect of LPS on the activity of human hyperpolarization-activated cyclic nucleotide-gated channel 2 (hHCN2) stably expressed in HEK293 cells. In whole-cell recordings bath-application of LPS decreased pacemaker current (IhHCN2) amplitude. The same protocol had no effect on channel activity in cell-attached patch recordings, where channels are protected from the LPS-containing bath solution. This demonstrates that LPS has to interact directly with or close to the channel protein. After cleavage of LPS into lipid A and the polysaccharide chain, neither of them alone impaired IhHCN2, suggesting that modulation of channel activity critically depends on the integrity of the entire LPS molecule. We furthermore showed that β-cyclodextrin interfered with LPS-dependent channel modulation predominantly via scavenging of lipid A, thereby abrogating the capability of LPS to intercalate into target cell membranes. We conclude that LPS impairs IhHCN2 by a local mechanism that is restricted to the vicinity of the channels. Furthermore, intercalation of lipid A into target cell membranes is a prerequisite for the inhibition that is suggested to depend on direct interaction of the LPS polysaccharide chain with cardiac pacemaker channels.
    The Journal of Physiology 12/2013; 592(6). DOI:10.1113/jphysiol.2013.268540 · 4.54 Impact Factor
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    ABSTRACT: Patients with infective endocarditis (IE) form a heterogeneous group, ranging from those who are successfully treated with no adverse events, to those with severe complications and a high mortality. In this Review, we highlight pathogen-host interactions and the mechanisms underlying various risk factors for patients with IE. A temporal trend in the pattern of IE has been observed in high-income countries within the past 5 decades, with patients contracting IE at an increasingly old age, and a growing incidence of health-care-associated staphylococcal IE. Consequently, prevention strategies should no longer focus on prophylaxis of streptococcal bacteraemia during dental procedures, but instead encourage a more-general approach to reduce the incidence of health-care-associated IE. Much knowledge has been gained about the mechanisms of vegetation formation, growth, and embolization on damaged or inflamed cardiac valves, and on cardiac devices. Improved understanding of these mechanisms will help to combat the increasing problem of antimicrobial resistance. Two mechanisms of IE should increasingly be the focus of future research: the role of immunosenescence in elderly patients with IE, particularly after transcatheter aortic valve implantation, and the mechanisms that trigger septic shock, a condition that leads to a substantial increase in the risk of death in patients with IE.
    Nature Reviews Cardiology 11/2013; DOI:10.1038/nrcardio.2013.174 · 10.15 Impact Factor
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    ABSTRACT: BACKGROUND: Although cardiovascular diseases belong to the most frequent causes of inpatient treatment of older people the specific characteristics of geriatric patients in the acute care unit still receive marginal attention. The aim of this study was the descriptive representation of clinical health care processes of geriatric and non-geriatric patients with acute myocardial infarction. PATIENTS AND METHODS: Using a retrospective document analysis 83 medical patient records were examined with regard to nursing, therapeutic as well as medical measures and social counseling. The classification in geriatric and non-geriatric patients was based on a predefined list of criteria. RESULTS: In the study a total of 48 geriatric and 35 non-geriatric patients could be identified. There was a comprehensive need for support of nursing and therapeutic care, a high frequency of complications and a long length of stay as well as specifics concerning the place of discharge in geriatric patients. CONCLUSIONS: Complex problems and special care needs of geriatric patients with acute myocardial infarction were shown. This vulnerable group of patients should be given more attention in acute care. Further investigations with a prospective character are necessary in order to detect the specific needs of geriatric patients in acute care.
    Zeitschrift für Gerontologie + Geriatrie 06/2013; 47(1). DOI:10.1007/s00391-013-0490-z · 1.02 Impact Factor
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    ABSTRACT: INTRODUCTION: In sepsis, the reduced systemic vascular resistance (SVR) can lead to a compensatory increase in cardiac output (CO). This may mimic a normal cardiac function although there is already a sepsis-induced myocardial depression. On a cohort of patients with septic multi-organ dysfunction syndrome, we have recently developed a method to correlate the actual CO to the afterload (estimated by SVR) and introduced the parameter "afterload-related cardiac performance" (ACP), which indicates if the rise of CO is adequate for the particular SVR. In this present study it was to be investigated, if ACP can reveal septic cardiomyopathy in patients with community-acquired sepsis in the early state soon after admission to the emergency department (ED), and if there is a prognostic relevance of septic cardiomyopathy defined by ACP. Results were compared to cardiac index (CI) and cardiac power index (CPI). METHODS: Adults presenting at the ED with sepsis were included. ACP, CI and CPI were calculated at the time of admission, after 24, and 72 h. They were correlated to severity of disease and the prognostic values were analyzed. RESULTS: A total of 141 patients were included. Only ACP was significantly influenced by severity of sepsis, whereas CI and CPI were not. ACP was the only hemodynamic parameter predicting mortality: nonsurvivors had lower ACP values at the time of admission to the ED (66.9 vs. 88.9 %, p < 0.05) and ACP predicted non-survival with an AUC value of 0.72, p = 0.003. Cardiac impairment defined by an ACP value of 80 % or below determined worse prognosis. CONCLUSIONS: Septic cardiomyopathy occurs already at the early stage of disease and is of prognostic relevance. It might be recognized best, if cardiac function is correlated to afterload.
    Clinical Research in Cardiology 06/2013; 102(10). DOI:10.1007/s00392-013-0584-z · 4.17 Impact Factor
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    ABSTRACT: Various strategies have been devised to reduce the clinical consequences of myocardial infarction including acute medical care, revascularization, stem cell transplantations and, more recently, prevention of cardiomyocyte cell death. Activation of embryonic signaling pathways is a particularly interesting option to complement these strategies and to improve the functional performance and survival rate of cardiomyocytes. Here, we have concentrated on Bone Morphogenetic Protein 2 (BMP-2), which induces ectopic formation of beating cardiomyocytes during development in the mesoderm and protects neonatal cardiomyocytes from ischemia-reperfusion injury.In a mouse model of acute myocardial infarction an i.v.-injection of BMP-2 reduced infarct size in mice when given after LAD-ligation. BMP-2 treated mice are characterized by a reduced rate of apoptotic cardiomyocytes both in the border zone of the infarcts and in the remote myocardium. In vitro, BMP2 increases the frequency of spontaneously beating neonatal cardiomyocytes and the contractile performance under electrical pacing at 2 Hz and at the same time preserves cellular ATPstores and decreases the rate of apoptosis despite the increased workload. BMP-2 specifically induced phosphorylation of Smad1/5/8 proteins and protects adult cardiomyocytes from long-lasting hypoxia-induced cellular damage and oxidative stress without activation of the cardiodepressant TGFß-pathway.Our data suggest that BMP-2 treatment may have considerable therapeutic potential in individuals with acute and chronic myocardial ischemia by improving the contractility of cardiomyocytes and preventing cardiomyocyte cell death.
    Shock (Augusta, Ga.) 01/2013; DOI:10.1097/SHK.0b013e318289728a · 2.73 Impact Factor
  • Intensiv- und Notfallbehandlung 01/2013; 38(10):173-198. DOI:10.5414/IBX00405
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    ABSTRACT: BACKGROUND: The aim of this study was to investigate factors influencing mortality after percutaneous coronary intervention (PCI) in patients aged ≥ 75 years compared to younger patients. PATIENTS AND METHODS: A total of 1,809 coronary heart disease (CHD) patients after PCI with stent implantation in our hospital were assessed. Kaplan-Meier analyses with log-rank test and Cox regression analyses were performed on three predefined models concerning primary endpoint of all-cause mortality. Model 1 was a univariate analysis of the influence of age dichotomized by age 75 years on the primary endpoint. Model 2 included age and classical cardiovascular risk factors (CVRFs, e.g., body mass index (BMI), smoking, diabetes, and hypertension). Model 3 consisted of age, classical CVRFs, and additional factors (e.g., medication; hemoglobin, peripheral arterial disease (PAD), low-density lipoprotein cholesterol (LDL-C) and creatinine levels, and left ventricular ejection fraction (LVEF)). RESULTS: In the mean follow-up of 137 ± 61 weeks 375 patients died. Age ≥ 75 years was significantly related to mortality in all models. In model 3, previous stroke, PAD, diabetes, elevated levels of serum creatinine, and increased LDL-C were related to elevated mortality, higher hemoglobin levels, and LVEF > 50% were associated with decreased mortality in all patients and in patients < 75 years. In patients ≥ 75 years arterial hypertension was associated with poor outcome (hazard ratio (HR) 7.989, p = 0.040), previous antiplatelet therapy showed reduced mortality (HR 0.098, p = 0.039). CONCLUSION: Although risk factors such as previous stroke, PAD, diabetes, renal insufficiency, and anemia were predictors for death in all patients and patients < 75 years, in the elderly only arterial hypertension increased, whereas treatment with platelet inhibitors decreased mortality.
    Zeitschrift für Gerontologie + Geriatrie 04/2012; DOI:10.1007/s00391-012-0338-y · 1.02 Impact Factor
  • Dr. M. Meisel, S. Nuding, U. Müller-Werdan
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    ABSTRACT: Das standardisierte geriatrische Basisassessment bildet die funktionellen Einschränkungen des betagten Patienten valide ab. Weniger präzise gelingt die Prognoseabschätzung älterer Menschen mittels der Instrumente zur kardiovaskulären und zur präoperativen Risikobewertung oder durch die intensivmedizinischen Organversagenscores. Eine Anpassung und Weiterentwicklung der Scoresysteme könnte diese Unschärfe beheben.
    02/2012; 107(1). DOI:10.1007/s00063-011-0029-2
  • M Meisel, S Nuding, U Müller-Werdan
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    ABSTRACT: The standard geriatric basic assessment validly presents the functional limitations of elderly patients. The prognosis estimation of elderly people is less precise using the instruments for cardiovascular and preoperative risk evaluation or by the intensive care medicine scores on organ failure. An adaptation and further development of score systems could clarify these vague areas.
    02/2012; 107(1):29-31.
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    ABSTRACT: Several clinical trials have demonstrated the antianginal and anti-ischemic efficacy of ivabradine in combination with beta-blocker in patients with stable angina pectoris. The ADDITIONS (PrActical Daily efficacy anD safety of Procoralan(®) In combinaTION with betablockerS) study evaluated the efficacy, safety, and tolerability of ivabradine added to beta-blocker, and its effect on angina symptoms and quality of life in routine clinical practice. This non-interventional, multicenter, prospective study included 2,330 patients with stable angina pectoris treated with a flexible dose of ivabradine twice daily in addition to beta-blocker for 4 months. The parameters recorded included heart rate, number of angina attacks, nitrate consumption, tolerance, and quality of life. After 4 months ivabradine (mean dose 12.37 ± 2.95 mg/day) reduced heart rate by 19.4 ± 11.4 to 65.6 ± 8.2 bpm (p < 0.0001). The number of angina attacks was reduced by 1.4 ± 1.9 per week (p < 0.0001), and nitrate consumption by 1.9 ± 2.9 U per week (p < 0.0001). At baseline (i.e., on beta-blocker), half of the patients (51%) were classified as Canadian Cardiovascular Society (CCS) grade II; 29% were CCS grade I. After 4 months' treatment with ivabradine, most of the patients were CCS grade I (68%). The EQ-5D index improved by 0.17 ± 0.23 (p < 0.0001). The overall efficacy of ivabradine was considered by the physicians as "very good" (61%) or "good" (36%) in most patients. Suspected adverse drug reactions were documented in 14 patients; none were severe. In daily clinical practice, combining ivabradine with beta-blocker not only reduces heart rate, number of angina attacks, and nitrate consumption, but also improves the quality of life in patients with stable angina pectoris.
    Clinical Research in Cardiology 01/2012; 101(5):365-73. DOI:10.1007/s00392-011-0402-4 · 4.17 Impact Factor
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    ABSTRACT: To study the association between baseline heart rate and outcome in patients with multiple organ dysfunction (MODS) as well as the course of heart rate over the first 4 days during MODS. Prospective observational study in 89 patients with MODS, defined as an APACHE-II score ≥20. Baseline heart rate (HR(0)) was determined over a 60-minute period at the time of MODS diagnosis. 28-day all-cause mortality was the primary endpoint of the study, a fall of the APACHE-II score by 4 points or more from day 0 to day 4 constituted the secondary endpoint. Hazard ratios for heart rate of 90 beats per minute (bpm) or greater relative to less than 90 bpm were calculated using Cox proportional hazards model and adjusted for confounding variables. Median baseline heart rate was 83 bpm in survivors and 92 bpm in non-survivors (p = 0.048). 28-day mortality was 32 and 61% in patients with HR(0) < 90 bpm and HR(0) ≥ 90 bpm, respectively. The adjusted hazard ratio for 28-day mortality was 2.30 (95% confidence interval 1.21-4.36, p = 0.001) for HR(0) ≥ 90 bpm relative to HR(0) < 90 bpm. No correlation was found between baseline heart rate and the secondary endpoint. From day 0 to day 4, heart rate remained elevated in all patients, as well as in survivors and non-survivors. A heart rate ≥90 bpm at the time of MODS diagnosis is an independent risk factor for increased 28-day mortality. As in patients with cardiovascular conditions such as coronary heart disease or chronic heart failure, heart rate might constitute a target for heart rate-lowering therapy in the narrow initial treatment window of MODS.
    Clinical Research in Cardiology 11/2011; 101(2):139-47. DOI:10.1007/s00392-011-0375-3 · 4.17 Impact Factor
  • U. Müller-Werdan, T. Klöss, M. Meisel
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    ABSTRACT: Bei alten Patienten müssen in der intensivmedizinischen Therapie der Akuterkrankung auch spezifische medizinische Probleme wie die Folgen der Organalterung, Komorbidität oder geriatrische Syndrome berücksichtigt werden. Hierbei sind insbesondere Instrumente zum geriatrischen Assessment hilfreich. Geriatrie und Intensivmedizin leisten bisher jeweils komplementäre Beiträge zur Behandlung schwerstkranker Hochbetagter. Eine engere fachliche Verzahnung der beiden Disziplinen könnte zur Bewältigung der vielen offenen Fragen und drängenden Probleme einen erheblichen Mehrwert zugunsten der Versorgung hochbetagter Kranker leisten. For elderly patients specific medical problems, such as the consequences of aging organs, comorbidities or geriatric syndromes must be considered in the intensive care treatment of acute diseases. Under these circumstances special instruments for geriatric assessment are particularly useful. Up to now geriatrics and intensive care medicine have made complementary contributions in the treatment of severely ill elderly patients. A closer interdisciplinary cooperation of the two disciplines could be of substantial beneficial value in the care of the sick and elderly to overcome the many open questions and pressing problems. SchlüsselwörterGeriatrie–Intensivmedizin–Homöostenose–Delir–Immunseneszenz KeywordsGeriatrics–Intensive care unit–Homoeostenosis–Delirium–Immunosenescence
    09/2011; 106(1):10-15. DOI:10.1007/s00063-011-00242-5

Publication Stats

2k Citations
393.84 Total Impact Points

Institutions

  • 1970–2014
    • Martin Luther University Halle-Wittenberg
      • • Institute for Physiological Chemistry
      • • Clinic for Internal Medicine III
      • • Institut für Humangenetik und Medizinische Biologie
      • • Clinic for Ophthalmology
      • • Institute for Pathology
      Halle-on-the-Saale, Saxony-Anhalt, Germany
  • 2004–2013
    • Universitätsklinikum Halle (Saale)
      Halle-on-the-Saale, Saxony-Anhalt, Germany
  • 2010–2012
    • Diakonissenkrankenhaus Dessau
      Dessau, Saxony-Anhalt, Germany
  • 1995–1996
    • Ludwig-Maximilians-University of Munich
      • Department of Internal Medicine I
      München, Bavaria, Germany