[Show abstract][Hide abstract] ABSTRACT: Background: There is still uncertainty about the optimal strategy in patients with multivessel disease undergoing primary PCI for cardiogenic shock. Therefore we compared outcome of patients with culprit lesion only PCI and immediate multivessel PCI for cardiogenic shock in a prospective study.
Methods: We used the data of the prospective IABP-Shock II trial and included patients with primary PCI for cardiogenic shock with 2-3 vessel disease. We excluded patients with left main PCI and patients with prior coronary artery bypass surgery. Treatment with multivessel PCI or culprit lesion only PCI was left on the discretion of the operator.
Results: Between 2009 and 2011 a total of 450 patients 2-3 vessel disease were treated with primary PCI for cardiogenic shock. Of these 167 (37%) received immediate multivessel PCI while in the remaining only the culprit vessel was treated.
Baseline characteristics, procedural features and outcomes are given in the table.
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Journal of the American College of Cardiology 03/2013; 61(10). DOI:10.1016/S0735-1097(13)60102-3 · 16.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Recent data from a population-based study in children and adolescents suggest that serum thyrotropin (TSH) levels are associated with arterial blood pressure and hypertension. These results are in agreement with some but not all population-based studies in adults. Discrepancies in results might be explained by drug intake, different iodine supplies, and sizes of populations investigated. In addition, it is not clear whether an association between TSH and hypertension exists longitudinally or only cross-sectionally. Thus, our aim was to investigate cross-sectional and longitudinal associations between thyroid function and arterial blood pressure in a large consortium of cohort studies in adults.
Data from five population-based studies were pooled resulting in 17,023 individuals being available for cross-sectional and 10,048 individuals for longitudinal analyses. Associations of baseline TSH with baseline blood pressure or hypertension were analyzed by multivariable median or logistic regression models. Multivariable median or Poisson regression models were used to investigate associations of baseline TSH with five-year change in arterial blood pressure or incident hypertension.
There was a cross-sectional positive association of TSH with arterial blood pressure (p<0.001) and hypertension (odds ratio [OR]=1.76 [confidence interval (CI) 1.24-2.50], p=0.002). Likewise, hypothyroidism was associated with systolic (β=1.1 [CI 0.1-2.1], p=0.040) and diastolic blood pressure (β=1.4 [CI 0.7-2.0], p<0.001). TSH, however, was not consistently associated with a five-year change in blood pressure or incident hypertension.
High serum TSH levels were associated with current hypertension and blood pressure but not with a five-year change in blood pressure and incident hypertension. This argues for only a short-term effect of thyroid hormone levels on arterial blood pressure or a spurious association that needs further evaluation in population-based studies.
Thyroid: official journal of the American Thyroid Association 02/2013; 23(8). DOI:10.1089/thy.2012.0626 · 4.49 Impact Factor
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: Infective endocarditis is a serious disease that is often diagnosed with a considerable delay in clinical practice and therefore has a high mortality rate; therefore, early diagnosis and antibiotic treatment are extremely important. Epidemiological shifts in the age profile, new risk factors and the increasing use of intravascular prosthetic materials have led to changes in the microbial spectrum and clinical symptoms, which must be taken into account in the diagnostic efforts and therapy. Nonspecific symptoms and the increase in nosocomial endocarditis, especially in critically ill and immunocompromised patients require a high level of diagnostic expertise. With diagnostic algorithms based on guideline recommendations antibiotic treatment has to be initiated as early as possible. For patients with severe infective endocarditis a cardiac surgeon has to be involved from an early stage of the disease as in about 50 % of cases conservative antibiotic therapy alone does not alleviate the infection. Also early surgical treatment should be sought with the onset of complications. After effective treatment and patient survival there will always be an increased risk of suffering from renewed endocarditis. This is taken into account in the new recommendations of the European Society of Cardiology for the prevention of infective endocarditis.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to assess the effects of serelaxin on short-term changes in markers of organ damage and congestion and relate them to 180-day mortality in patients with acute heart failure.
Hospitalization for acute heart failure is associated with high post-discharge mortality, and this may be related to organ damage.
The Pre-RELAX-AHF (Relaxin in Acute Heart Failure) phase II study and RELAX-AHF phase III study were international, multicenter, double-blind, placebo-controlled trials in which patients hospitalized for acute heart failure were randomized within 16 h to intravenous placebo or serelaxin. Each patient was followed daily to day 5 or discharge and at days 5, 14, and 60 after enrollment. Vital status was assessed through 180 days. In RELAX-AHF, laboratory evaluations were performed daily to day 5 and at day 14. Plasma levels of biomarkers were measured at baseline and days 2, 5, and 14. All-cause mortality was assessed as a safety endpoint in both studies.
Serelaxin reduced 180-day mortality, with similar effects in the phase II and phase III studies (combined studies: N = 1,395; hazard ratio: 0.62; 95% confidence interval: 0.43 to 0.88; p = 0.0076). In RELAX-AHF, changes in markers of cardiac (high-sensitivity cardiac troponin T), renal (creatinine and cystatin-C), and hepatic (aspartate transaminase and alanine transaminase) damage and of decongestion (N-terminal pro-brain natriuretic peptide) at day 2 and worsening heart failure during admission were associated with 180-day mortality. Serelaxin administration improved these markers, consistent with the prevention of organ damage and faster decongestion.
Early administration of serelaxin was associated with a reduction of 180-day mortality, and this occurred with fewer signs of organ damage and more rapid relief of congestion during the first days after admission.
Journal of the American College of Cardiology 01/2013; 61(2):196-206. DOI:10.1016/j.jacc.2012.11.005 · 16.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Despite advances in coronary revascularization and widespread use of primary percutaneous interventions, cardiogenic shock complicating an acute ST-elevation myocardial infarction (CSMI) remains a clinical challenge with high mortality rates. Conservative management with catecholamines is associated with serious limitations, including arrhythmias, increased myocardial oxygen consumption, and inadequate circulatory support. Clinicians have therefore turned to mechanical means of circulatory support. Circulatory assist systems for CSMI can be distinguished by the method of placement (i.e. percutaneous vs. surgical), the type of circulatory support (i.e. left ventricular, right ventricular, or biventricular pressure and/or volume unloading), and whether they are combined with extracorporal membrane oxygenation (ECMO). The percutaneous assist systems most commonly used in CSMI are the intra-aortic balloon pump (IABP), venoarterial ECMO, the Impella pump, and the TandemHeart. Decades of clinical studies and experience demonstrated haemodynamic improvement, including elevation of diastolic perfusion pressure and cardiac output. Recently, the large randomized IABP-Shock II Trial did not show a significant reduction in 30-day mortality in CSMI with IABP insertion. There are no randomized study data available for ECMO use in CSMI. Both the Impella pump and the TandemHeart did not reduce 30-day mortality when compared with IABP in small randomized controlled trials (RCTs). In conclusion, despite the need for effective mechanical circulatory support in CSMI, current devices, as tested, have not been demonstrated to improve short- or long-term survival rates. RCTs testing the optimal timing of device therapy and optimal device design are needed to improve outcomes in CSMI.
European Heart Journal 01/2013; 35(3):156-167. DOI:10.1093/eurheartj/eht248 · 15.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Die infektiöse Endokarditis (IE) ist eine schwerwiegende Erkrankung, die im klinischen Alltag häufig erst mit einer erheblichen Latenz diagnostiziert wird. Nicht zuletzt deshalb ist das Mortalitätsrisiko hoch. Nach Diagnosestellung ist die zeitnahe Einleitung einer antibiotischen Therapie von herausragender Bedeutung. Epidemiologische Verschiebungen im Altersprofil, neue Risikofaktoren und die zunehmende Verwendung intravasaler prothetischer Materialien haben zu Veränderungen des Keimspektrums und des klinischen Bilds geführt, denen neue diagnostische und therapeutische Bemühungen Rechnung tragen müssen. Die in der Regel unspezifischen initialen Symptome wie auch die zunehmende Zahl nosokomialer Endokarditiden erfordern eine hohe diagnostische Kompetenz der behandelnden Ärzte. Hilfestellung bieten verschiedene diagnostische Algorithmen wie auch leitliniengestützte Empfehlungen zur antibiotischen Therapie. Bereits frühzeitig sollte ein Herzchirurg in die Behandlung einbezogen werden, da etwa in der Hälfte aller Erkrankungsfälle eine alleinige antibiotisch-konservative Therapie zu keiner Sanierung der Infektion führt. Bei Eintreten von Komplikationen sollte zeitig eine operative Therapie angestrebt werden. Nach überstandener Endokarditis haben die Patienten zeitlebens ein erhöhtes Risiko für eine erneute Endokarditis. Diesem Umstand wird in den neuen überarbeiteten Empfehlungen zur Prophylaxe der IE der Europäischen Gesellschaft für Kardiologie besonderes Gewicht verliehen.
Der Internist 01/2013; 54(1). DOI:10.1007/s00108-012-3090-x · 0.31 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Human ß-defensins are a family of antimicrobial peptides located at the mucosal surface. Both sequence multi-site variations (MSV) and copy-number variants (CNV) of the defensin-encoding genes are associated with increased risk for various diseases, including cancer and inflammatory conditions such as psoriasis and acute pancreatitis. In a case–control study, we investigated the association between MSV in DEFB104 as well as defensin gene (DEF) cluster copy number (CN), and pancreatic ductal adenocarcinoma (PDAC) and chronic pancreatitis (CP).
Two groups of PDAC (N=70) and CP (N=60) patients were compared to matched healthy control groups CARLA1 (N=232) and CARLA2 (N=160), respectively. Four DEFB104 MSV were haplotyped by PCR, cloning and sequencing. DEF cluster CN was determined by multiplex ligation-dependent probe amplification.
Neither the PDAC nor the CP cohorts show significant differences in the DEFB104 haplotype distribution compared to the respective control groups CARLA1 and CARLA2, respectively.
The diploid DEF cluster CN exhibit a significantly different distribution between PDAC and CARLA1 (Fisher’s exact test P=0.027), but not between CP and CARLA2 (P=0.867).
Different DEF cluster b CN distribution between PDAC patients and healthy controls indicate a potential protective effect of higher CNs against the disease.
BMC Research Notes 11/2012; 5(1):629. DOI:10.1186/1756-0500-5-629
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Serelaxin, recombinant human relaxin-2, is a vasoactive peptide hormone with many biological and haemodynamic effects. In a pilot study, serelaxin was safe and well tolerated with positive clinical outcome signals in patients with acute heart failure. The RELAX-AHF trial tested the hypothesis that serelaxin-treated patients would have greater dyspnoea relief compared with patients treated with standard care and placebo. METHODS: RELAX-AHF was an international, double-blind, placebo-controlled trial, enrolling patients admitted to hospital for acute heart failure who were randomly assigned (1:1) via a central randomisation scheme blocked by study centre to standard care plus 48-h intravenous infusions of placebo or serelaxin (30 μg/kg per day) within 16 h from presentation. All patients had dyspnoea, congestion on chest radiograph, increased brain natriuretic peptide (BNP) or N-terminal prohormone of BNP, mild-to-moderate renal insufficiency, and systolic blood pressure greater than 125 mm Hg. Patients, personnel administering study drug, and those undertaking study-related assessments were masked to treatment assignment. The primary endpoints evaluating dyspnoea improvement were change from baseline in the visual analogue scale area under the curve (VAS AUC) to day 5 and the proportion of patients with moderate or marked dyspnoea improvement measured by Likert scale during the first 24 h, both analysed by intention to treat. This trial is registered at ClinicalTrials.gov, NCT00520806. FINDINGS: 1161 patients were randomly assigned to serelaxin (n=581) or placebo (n=580). Serelaxin improved the VAS AUC primary dyspnoea endpoint (448 mm × h, 95% CI 120-775; p=0·007) compared with placebo, but had no significant effect on the other primary endpoint (Likert scale; placebo, 150 patients [26%]; serelaxin, 156 [27%]; p=0·70). No significant effects were recorded for the secondary endpoints of cardiovascular death or readmission to hospital for heart failure or renal failure (placebo, 75 events [60-day Kaplan-Meier estimate, 13·0%]; serelaxin, 76 events [13·2%]; hazard ratio [HR] 1·02 [0·74-1·41], p=0·89] or days alive out of the hospital up to day 60 (placebo, 47·7 [SD 12·1] days; serelaxin, 48·3 [11·6]; p=0·37). Serelaxin treatment was associated with significant reductions of other prespecified additional endpoints, including fewer deaths at day 180 (placebo, 65 deaths; serelaxin, 42; HR 0·63, 95% CI 0·42-0·93; p=0·019). INTERPRETATION: Treatment of acute heart failure with serelaxin was associated with dyspnoea relief and improvement in other clinical outcomes, but had no effect on readmission to hospital. Serelaxin treatment was well tolerated and safe, supported by the reduced 180-day mortality. FUNDING: Corthera, a Novartis affiliate company.
The Lancet 11/2012; 381(9860). DOI:10.1016/S0140-6736(12)61855-8 · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Transcoronary pacing for the treatment of bradycardias during percutaneous coronary intervention (PCI) is a useful technique in interventional cardiology. The standard technique is unipolar pacing with the guidewire in the coronary artery against a cutaneous patch electrode. We developed a novel approach for transcoronary pacing by using intravascular electrodes in different positions in the aorta in a porcine model.
Unipolar transcoronary pacing was applied in 8 pigs under general anesthesia using a standard floppy guidewire in a coronary artery as the cathode with additional insulation of the guidewire by a monorail angioplasty balloon. Intravascular electrodes positioned in the aorta thoracalis and the aorta abdominalis served as indifferent anodes. The efficacy of transcoronary pacing with intravascular anodal electrodes was assessed by measurement of threshold and impedance data and the magnitude of the epicardial electrogram in comparison to unipolar transvenous pacing using the same indifferent anodal electrodes. Transcoronary pacing with the guidewire-balloon combination using indifferent intravascular electrodes was effective in all cases. Transcoronary pacing thresholds obtained against the indifferent coil electrodes in the aorta thoracalis (0.8 ± 0.5 V) and in the aorta abdominalis (0.8 ± 0.5 V) were similar to those obtained with unipolar transvenous pacing (0.7 ± 0.3 V and 0.6 ± 0.2 V, respectively), whereas the tip-electrode in the aorta thoracalis serving as indifferent anode produced significantly higher pacing thresholds (guidewire, 2.8 ± 2.6 V; transvenous lead, 1.5 ± 0.8 V). The lower pacing threshold of the coil-electrodes was associated with significantly lower impedance values (aorta thoracalis, 285 ± 63 ohm; aorta abdominalis, 294 ± 61 ohm) as compared to the tip-electrode in the aorta thoracalis (718 ± 254 ohm). The amplitude of the epicardial electrogram acquired by the intracoronary guidewire was without significant differences between the indifferent electrodes.
Transcoronary pacing in the animal model using a standard guidewire with balloon insulation and intravascular indifferent electrodes is depending on the optimal configuration of the anodal electrode. The use of intravascular coil electrodes with a sufficient surface area can produce 100% capture at thresholds comparable to transvenous pacing. Therefore, technical integration of these coil electrodes into the access sheath or the guiding catheter with respect to handling these tools in daily clinical practice in the catheterization laboratory could further facilitate the transcoronary pacing approach.
The Journal of invasive cardiology 09/2012; 24(9):451-5. · 0.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In current international guidelines, intraaortic balloon counterpulsation is considered to be a class I treatment for cardiogenic shock complicating acute myocardial infarction. However, evidence is based mainly on registry data, and there is a paucity of randomized clinical trials.
In this randomized, prospective, open-label, multicenter trial, we randomly assigned 600 patients with cardiogenic shock complicating acute myocardial infarction to intraaortic balloon counterpulsation (IABP group, 301 patients) or no intraaortic balloon counterpulsation (control group, 299 patients). All patients were expected to undergo early revascularization (by means of percutaneous coronary intervention or bypass surgery) and to receive the best available medical therapy. The primary efficacy end point was 30-day all-cause mortality. Safety assessments included major bleeding, peripheral ischemic complications, sepsis, and stroke.
A total of 300 patients in the IABP group and 298 in the control group were included in the analysis of the primary end point. At 30 days, 119 patients in the IABP group (39.7%) and 123 patients in the control group (41.3%) had died (relative risk with IABP, 0.96; 95% confidence interval, 0.79 to 1.17; P=0.69). There were no significant differences in secondary end points or in process-of-care measures, including the time to hemodynamic stabilization, the length of stay in the intensive care unit, serum lactate levels, the dose and duration of catecholamine therapy, and renal function. The IABP group and the control group did not differ significantly with respect to the rates of major bleeding (3.3% and 4.4%, respectively; P=0.51), peripheral ischemic complications (4.3% and 3.4%, P=0.53), sepsis (15.7% and 20.5%, P=0.15), and stroke (0.7% and 1.7%, P=0.28).
The use of intraaortic balloon counterpulsation did not significantly reduce 30-day mortality in patients with cardiogenic shock complicating acute myocardial infarction for whom an early revascularization strategy was planned. (Funded by the German Research Foundation and others; IABP-SHOCK II ClinicalTrials.gov number, NCT00491036.).
New England Journal of Medicine 08/2012; 367(14):1287-96. DOI:10.1056/NEJMoa1208410 · 55.87 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background:
Severe infections play an important role in the emergency department (ED) and early risk stratification is essential. We compared the prognostic value of APACHE II, SOFA, and MEDS scores, and the biomarkers C-reactive protein (CRP), procalcitonin (PCT), and interleukin 6 (IL-6).
We performed a prospective observational study. Patients aged 18 years or older with a severe infection, from whom blood cultures were taken, were included.
Two hundred and eleven patients were included. The 30-day mortality rate was 8.5%. All scores and biomarkers showed significant area under the curve (AUC) values of receiver operating characteristic curve analysis for death within 30 days: 0.801 for APACHE II, 0.785 for MEDS, 0.708 for SOFA, 0.693 for CRP, 0.651 for PCT, and 0.716 for IL-6. For treatment in an ICU and need for mechanical ventilation, these parameters had significant AUC values, too. For renal replacement therapy, only APACHE II, SOFA, and PCT showed significant AUC values. According to the trend observed, the AUC values were highest for the APACHE II score.
All investigated parameters have a predictive value in patients with an infection in the ED. According to the trend observed, the APACHE II score seems to have the best discriminative power. Use of the APACHE II score already at the time of admission to the ED may be useful for stratifying patients at risk for ICU treatment, thereby using the same score in the ED and the ICU.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The IABP SHOCK trial was designed as a morbidity-based randomized controlled trial to determine the effect of intraaortic balloon pulsation (IABP) in patients with infarct-related cardiogenic shock (CS). The primary endpoint was the change in the APACHE II score over a 4-day period. The prospective hypothesis was that adding IABP therapy to "standard care" would reduce CS-triggered multiorgan dysfunction syndrome (MODS). The primary endpoint showed no difference between conventionally managed cardiogenic shock patients and those with additional IABP support. In an inflammatory marker substudy, we analyzed the prognostic value of the cytokines interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), macrophage inflammatory protein-1β (MIP-1β), granulocyte-colony stimulating factor (G-CSF), and monocyte chemoattractant protein-1β (MCP-1β). We also investigated the influence of IABP support, age, and gender on cytokine levels. DESIGN: The inflammatory marker substudy of the prospective, randomized, controlled, open label IABP SHOCK Trial (ClinicalTrials.gov ID NCT00469248). MATERIALS AND METHODS: A prospective, randomized, single-center study in a 12-bed intensive care unit at a university hospital was performed. A total of 40 consecutive patients were enrolled. The observational period was 96 h. RESULTS: The investigated cytokines showed a significant contribution in the prediction of mortality. Initial (on admission) and maximal cytokine levels during the observational period showed a similar predictive power. Patients with elevated levels of pro- and antiinflammatory cytokines had a higher risk of dying. The maximal level measured over the observation period in the hospital was also suited to identify the survivors. Close correlations between maximal cytokine levels resulted in the choice of only one independent marker (MIP-1β) into the multivariate model (OR 1.024, 95% CI 1.005-1.043). Initial cytokine levels were also suitable to predict the survivors; the risk of death significantly increases with increasing IFN-γ level (OR 1.119, 95% CI 1.005-1.246). Cytokine levels were not affected by the presence of IABP support. Age (< 75 or > 75 years) and gender did not have a clinically relevant effect on INF-γ, TNF-α, MIP-1β, G-CSF, and MCP-1 in CS patients. CONCLUSION: The inflammatory response in patients with myocardial infarction complicated by CS, as reflected by the inflammatory markers INF-γ, TNF-α, MIP-1β, G-CSF, and MCP-1β, have been shown to be of prognostic value in estimating clinical outcome.
[Show abstract][Hide abstract] ABSTRACT: Stroke and other thromboembolic events are mainly caused by emboli from heart, aorta and other arteries. In this paper we describe a group of 5 middle-aged patients suffering from emboli caused by large thrombi in the aorta. Since the development of giant thrombi under high flow conditions in the aorta is a pathophysiological process which is not well understood, a model of flow distribution by numerically simulating the Navier-Stokes equation for an incompressible fluid was generated. This model simulated how such thrombi may develop in the aorta. We hypothesize that large thrombi issuing from the aortic vessel wall represent a underestimated entity in middleaged persons and are probably overlooked as the cause of stroke or other embolic events in some cases.
Journal of Thrombosis and Thrombolysis 07/2012; 35(2). DOI:10.1007/s11239-012-0775-x · 2.17 Impact Factor