Malte Kelm

Endotracheal intubation (ET) in intensive care unit (ICU) patients is regarded as more challenging than elective intubations in the operating room. Despite challenging conditions in ICU, trainees are often the initial operators performing ET. Because nonanesthesiologist intensivists with limited experience in ET run most of the nonsurgical ICUs, it is of exceptional importance to identify patients with predictable difficult ET in advance to prepare for a difficult airway scenario and thus avoid severe complications. In this prospective, observational, single-center study, we used a truncated MACOCHA score to evaluate intubation performance of nonanesthesiologist ICU trainees in an interdisciplinary medical ICU. We show that (a) ET could be performed safely and without fatal complications in all cases; (b) the MACOCHA score is feasible on a nonanesthesiologist ICU; (c) a truncated MACOCHA score of at least 8 predicts failure of ICU trainees; and (d) availability of an ear, nose, and ...

The hemodynamic vascular consequences of implanting left ventricular assist devices (LVADs) have not been studied in detail. We investigated the effect of LVAD implantation compared with heart transplant (HTx) on microvascular and macrovascular function in patients with end-stage heart failure and evaluated whether microparticles may play a role in LVAD-related endothelial dysfunction. Vascular function was assessed in patients with end-stage heart failure awaiting HTx, patients who had undergone implantation of a continuous-flow centrifugal LVAD, and patients who had already received a HTx. Macrovascular function was measured by flow-mediated vasodilation (FMD) using high-resolution ultrasound of the brachial artery. Microvascular function was assessed in the forearm during reactive hyperemia using laser Doppler perfusion imaging and pulsed wave Doppler. Age-matched patients without heart failure and without coronary artery disease (CAD) (healthy control subjects) and patients with stable CAD served as control subjects. Circulating red blood cell (CD253(+)), leukocyte (CD45(+)), platelet (CD31(+)/CD41(+)), and endothelial cell (CD31(+)/CD41(-), CD62e(+), CD144(+)) microparticles were determined by flow cytometry and free hemoglobin by enzyme-linked immunosorbent assay. FMD and microvascular function were significantly impaired in patients with end-stage heart failure compared with healthy control subjects and patients with stable CAD. LVAD implantation led to recovery of microvascular function, but not FMD. In parallel, increased free hemoglobin was observed along with red and white cell microparticles and endothelial and platelet microparticles. This finding indicates destruction of blood cells with release of hemoglobin and activation of endothelial cells. HTx and LVAD implantation led to similar improvements in microvascular function. FMD increased and microparticle levels decreased in patients with HTx, whereas shear stress during reactive hyperemia was similar in patients with LVADs and patients with HTx. Our data suggest that LVAD support leads to significant improvements in microvascular perfusion and hemodynamics. However, destruction of blood cells may contribute to residual endothelial dysfunction potentially by increasing nitric oxide scavenging capacity.

Dual atrioventricular nodal non-re-entrant tachycardia (DAVNNT), also known as 'double fire', has recently received more attention since it was demonstrated to mimic more common arrhythmias such as atrial premature beats, atrial fibrillation, and ventricular tachycardia. This is important, since mistaken differential diagnoses and the resulting therapeutic decisions have severe consequences for affected patients. DAVNNT is characterized by conduction characteristics of the atrioventricular (AV) node that leads to a double antegrade conduction of one sinoatrial nodal activity via the slow and fast AV nodal pathways. As a result, the most significant hint from an electrocardiogram (ECG) is a P wave followed by two narrow QRS complexes. Although DAVNNT is rather a rare arrhythmia, it now appears to be more common than previously thought. To date, 68 cases including 3 small single-centre observational studies accumulated over the last 5 years have demonstrated the feasibility and safety of radiofrequency catheter ablation for DAVNNT. Catheter ablation treats this arrhythmia effectively by modifying or eliminating slow pathway function. Here, we review the current state of DAVNNT knowledge systematically and address current challenges presented by this 'ECG chameleon from the AV node'.

To assess the benefits and risks of short term (<12 months) or extended (>12 months) dual antiplatelet therapy (DAPT) versus standard 12 month therapy, following percutaneous coronary intervention with drug eluting stents. Meta-analysis of randomised controlled trials. PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, Scopus, Web of Science, Cochrane Library, and major congress proceedings, searched from 1 January 2002 to 16 February 2015. Trials comparing short term (<12 months) or extended (>12 months) DAPT regimens with standard 12 month duration of therapy. Primary outcomes were cardiovascular mortality, myocardial infarction, stent thrombosis, major bleeding, and all cause mortality. 10 randomised controlled trials (n=32 287) were included. Compared to 12 month DAPT, a short term course of therapy was associated with a significant reduction in major bleeding (odds ratio 0.58 (95% confidence interval 0.36 to 0.92); P=0.02) with no significant ...

Nitric oxide (NO) is constitutively produced and released from the endothelium and several blood cell types by the isoform 3 of the NO synthase (NOS3). We have shown that NO protects against myocardial ischemia/reperfusion (I/R) injury and that depletion of circulating NOS3 increases within 24h of ischemia/reperfusion the size of myocardial infarction (MI) in chimeric mice devoid of circulating NOS3. In the current study we hypothesized that circulating NOS3 also affects remodeling of the left ventricle following reperfused MI. To analyze the role of circulating NOS3 we transplanted bone marrow of NOS3-/- and wild type (WT) mice into WT mice, producing chimerae expressing NOS3 only in vascular endothelium (BC-/EC+) or in both, blood cells and vascular endothelium (BC+/EC+). Both groups underwent 60 min of coronary occlusion in a closed-chest model of reperfused MI. During the 3 weeks post MI, structural and functional LV remodeling was serially assessed (24h, 4d, 1w, 2w and 3w) by e...

Patients with anemia show a negative outcome in percutaneous coronary intervention, transcatheter aortic valve replacement and cardiac surgery. The impact of anemia on periprocedural major adverse cardiac and cerebrovascular events (MACCE) and mortality in patients undergoing treatment of severe mitral regurgitation (MR) with percutaneous mitral valve repair using the MitraClip® system is not known. To assess whether percutaneous mitral valve repair with the MitraClip® system is safe and effective in patients with anemia. 80 patients with severe and moderate-to-severe MR were included in this open-label observational single-center study. Anemia was prevalent in 51.3% of patients (n=41). MitraClip® devices were successfully implanted in 97.6% (n=40) of patients with anemia and in 97.4% (n=38) of patients without anemia (p=0.971). Periprocedural MACCE occurred in 4.9% (n=2) of patients with anemia and 5.1% (n=2) of patients without anemia (p=0.959). Thirty-day mortality was 2.4% (n=1)...

Patients with diabetes mellitus show a negative outcome in percutaneous coronary intervention, aortic valve replacement and cardiac surgery. The impact of diabetes on patients undergoing treatment of severe mitral regurgitation (MR) using the MitraClip system is not known. We therefore sought to assess whether percutaneous mitral valve repair with the MitraClip system is safe and effective in patients with diabetes mellitus. We included 58 patients with severe and moderate-to-severe MR in an open-label observational single-center study. Ninteen patients were under oral medication or insulin therapy for type II diabetes mellitus. MitraClip devices were successfully implanted in all patients with diabetes and in 97.4% (n = 38) of patients without diabetes (p = 0.672). Periprocedural major cardiac adverse and cerebrovascular events (MACCE) occurred in 5.1% (n = 2) of patients without diabetes whereas patients with diabetes did not show any MACCE (p = 0.448). 30-day mortality was 1.7% (...

To characterize the safety and efficacy of deep sedation (DS) as compared to general anaesthesia (GA) in percutaneous mitral valve repair (PMVR) using the MitraClip system. PMVR with the MitraClip system has emerged as a therapeutic alternative to surgical valve repair in high-risk patients. The PMVR procedure is typically performed under GA. Due to their high surgical risk, avoidance of GA in many of those patients would be desirable. In an open-label observational study 21 patients with severe mitral regurgitation were randomized to either GA or DS using propofol. Primary endpoints of this comparison were related to safety with rate of conversion from DS to GA, bleeding, aspiration, and pneumonia. Secondary endpoints were related to efficacy with procedural, in-hospital, and mid-term outcome at 1 month. All clips have been implanted successfully in both groups. No conversion from DS to GA was necessary. Four patients undergoing GA suffered from upper respiratory tract infections a...

Red blood cells (RBC) have been considered almost exclusively as a transporter of metabolic gases and nutrients for the tissues. It is an accepted dogma that RBCs take up and inactivate endothelium-derived NO via rapid reaction with oxyhemoglobin to form methemoglobin and nitrate, thereby limiting NO available for vasodilatation. Yet it has also been shown that RBCs not only act as "NO sinks", but exert an erythrocrine function - i.e an endocrine function of RBC - by synthesizing, transporting and releasing NO metabolic products and ATP, thereby potentially controlling systemic NO bioavailability and vascular tone. Recent work from our and others laboratory demonstrated that human RBCs carry an active type 3, endothelial NO synthase (eNOS), constitutively producing NO under normoxic conditions, the activity of which is compromised in patients with coronary artery disease. In this review we aim to discuss the potential role of red cell eNOS in RBC signaling and function, an...

Aging leads to a number of disadvantageous changes in the cardiovascular system. Deterioration of vascular homoeostasis with increase in oxidative stress, chronic low-grade inflammation, and impaired nitric oxide bioavailability results in endothelial dysfunction, increased vascular stiffness, and compromised arterial-ventricular interactions. A chronic dietary supplementation with the micronutrient nitrate has been demonstrated to improve vascular function. Healthy dietary patterns may regulate gene expression profiles. However, the mechanisms are incompletely understood. The changes that occur at the gene expression level and transcriptional profile following a nutritional modification with nitrate have not been elucidated. To determine the changes of the vascular transcriptome, we conducted gene expression microarray experiments on aortas of old mice, which were treated with dietary nitrate. Our results highlight differentially expressed genes overrepresented in gene ontology categories. Molecular interaction and reaction pathways involved in the calcium-signaling pathway and the detoxification system were identified. Our results provide novel insight to an altered gene-expression profile in old mice following nitrate supplementation. This supports the general notion of nutritional approaches to modulate age-related changes of vascular functions and its detrimental consequences.

Objectives: While nitric oxide (NO) is a potent vasodilator already in the nM range, a cGMP-independent negative inotropic effect is observed at higher concentrations. Since inhibition of creatine kinase (CK) by NO-induced nitrosylation has been proposed as a possible 31 mechanism of action, we measured the flux through CK in the intact heart. Methods: In saline perfused, paced guinea pig

Sulfide (H2S/HS(-)) has been demonstrated to exert an astounding breadth of biological effects, some of which resemble those of nitric oxide (NO). While the chemistry, biochemistry and potential pathophysiology of the cross-talk between sulfide and NO have received considerable attention lately, a comparable assessment of the potential biological implications of an interaction between nitrite and sulfide is lacking. This is surprising inasmuch as nitrite is not only a known bioactive oxidation product of NO, but also efficiently converted to S-nitrosothiols in vivo; the latter have been shown to rapidly react with sulfide in vitro, leading to formation of S/N-hybrid species including thionitrite (SNO(-)) and nitrosopersulfide (SSNO(-)). Moreover, nitrite is used as a potent remedy against sulfide poisoning in the clinic. The chemistry of interaction between nitrite and sulfide or related bioactive metabolites including polysulfides and elemental sulfur has been extensively studied i...

The aim of this meta-analysis was to compare the 30-day safety and efficacy of bivalirudin with those of heparin with or without routine administration of a glycoprotein IIb/IIIa inhibitor (GPI) in patients with acute coronary syndrome (ACS). Bivalirudin has been a mainstay of anticoagulation in patients with ACS compared with heparin. The extent to which trial results have been affected by the coadministration of heparin with a GPI, however, remains unclear. A total of 13 randomized, controlled trials involving 24,605 patients were included. There was no significant difference in 30-day mortality or myocardial infarction rate with bivalirudin compared with heparin with or without routine GPI administration. A reduction of 30-day major bleeding was observed with bivalirudin compared with heparin that was significant when GPI was routinely administered (odds ratio [OR]: 0.52, 95% confidence interval [CI]: 0.45 to 0.60), p < 0.001) but not with provisionally administered GPI (OR: 0...

Inorganic nitrate and nitrite from endogenous or dietary sources are metabolized in vivo to nitric oxide (NO) and other bioactive nitrogen oxides. The nitrate-nitrite-NO pathway is emerging as an important mediator of blood flow regulation, cell signaling, energetics and tissue responses to hypoxia. The latest advances in our understanding of the biochemistry, physiology and therapeutics of nitrate, nitrite and NO were discussed during a recent 2-day meeting at the Nobel Forum, Karolinska Institutet in Stockholm.

Early identification of acute respiratory distress syndrome (ARDS) and forceful implementation of standardized therapy algorithms are the mandatory basis of an effective therapy to improve patient outcome. Recently, a new definition of ARDS was implemented, which simplified the diagnostic criteria for ARDS. Evidence-based therapies are rare, but some cornerstone interventions can be recommended. Lung-protective ventilation with high positive end-expiratory pressure and low tidal volume and early prone positioning in severe cases improve survival rate. We here present an integrated "Düsseldorf hands-on translation" in the form of a "one-page" standard operating procedure in order to fasten and standardize both diagnosis and therapeutic algorithms on an intensive care unit.

Pulmonary vein isolation (PVI) as a cornerstone for catheter ablation of atrial fibrillation (AF) remains a complex and time-consuming procedure. To assess feasibility, safety, and acute efficacy of a novel irrigated multielectrode ablation catheter guided by an electroanatomic mapping system for PVI in patients with paroxysmal AF. Twenty-five consecutive patients (60 ± 10 years) with paroxysmal AF underwent PVI by using a novel decapolar mapping and ablation catheter (nMARQ catheter, Biosense Webster Inc, Diamond Bar, CA). Ablation was guided by electroanatomic mapping allowing radiofrequency (RF) energy delivery in the antral region of pulmonary veins (PVs) from 10 irrigated electrodes simultaneously. The day after ablation, cardiac magnetic resonance imaging was performed routinely in order to assess for potential acute PV stenosis. Overall, 97 of 97 (100%) targeted PVs could be isolated with a mean of 27 ± 11 RF applications and a mean total burning time of 15 ± 6 minutes per patient. The total procedure time from femoral vein access to catheter withdrawal was 110 ± 31 minutes, including a mean total fluoroscopy time of 23 ± 9 minutes. On average, 6 ± 3 RF impulses with a maximum of 25 W were applied per vein. After a short learning curve, procedure, fluoroscopy, and total burning times decreased to 94 ± 16, 16 ± 3, and 9 ± 2 minutes, respectively (P < .05). Entrance and exit blocks could be verified by placing the ablation catheter into 90 of 97 (93%) PVs in 18 of 25 (72%) patients. No procedure-related complications were observed, especially no acute PV stenosis could be detected. The use of a novel irrigated multielectrode ablation system for PVI is feasible and safe, resulting in acute isolation of all targeted PVs with no complications and short procedure times. Sustainability of these initial results has to be confirmed in long-term efficacy and follow-up trials.