
Sebastian PhilippElbe Kliniken · Department of Cardiology
Sebastian Philipp
Priv.-Doz. Dr. med.
About
83
Publications
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3,103
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Introduction
Clinical trials in CHF and coronary interventions
Additional affiliations
October 2009 - present
Elbeklinikum Stade
Description
- Clinical Research
January 2006 - September 2009
January 2006 - December 2009
Publications
Publications (83)
Background
The present study aimed to develop a simple dosing score when starting the cardiac glycoside digitoxin in heart failure with reduced ejection fraction (HFrEF) employing first data from the randomized, double-blinded DIGIT-HF trial.
Methods and results
In DIGIT-HF, digitoxin was started with a dose of 0.07 mg once daily (o.d.) in all pat...
Objective:
Left ventricular assist device (LVAD) implantation with concomitant Dor plasty is only reported anecdotally. We herein aimed to describe our experience with LVAD and concomitant Dor procedures and describe long-term outcomes of this special subset of heart failure patients.
Methods:
Between January/2010 and December/2018, 144 patients r...
Aims
Despite recent advances in the treatment of chronic heart failure (HF), mortality and hospitalizations still remain high. Additional therapies to improve mortality and morbidity are urgently needed. The efficacy of cardiac glycosides – although regularly used for HF treatment – remains unclear. DIGIT‐HF was designed to demonstrate that digitox...
Background
Current retrospective evidence suggests similar clinical and superior hemodynamic outcomes of the Sorin Freedom Solo stentless aortic valve (SFS) (LivaNova PLC, London, UK) compared to the Carpentier Edwards Perimount stented aortic valve (CEP) (Edwards Lifesciences Inc., Irvine, California, USA). To date, no reports exist describing cas...
Right ventricular failure (RVF) may still occur despite the benefits of minimally-invasive left ventricular assist device (MI-LVAD) implantation. Our center strategy aims to avoid aggressive postoperative inotrope use by utilizing mechanical support to facilitate RV recovery and adaptation. We herein report first outcomes of patients with minimally...
Over the last decade the number of heart transplantations declined and the number of implanted left ventricular assist devices (LVAD) markedly increased. Accordingly, common intensive care interventions rise and present their own challenges, especially due to the necessary anticoagulation regimen. One of these procedures is percutaneous dilatation...
Background:
Microalbuminuria (MAU) is defined as an urinary albumin excretion rate between 20-200 mg/l or 30-300 mg/day. It is a surrogate marker for endothelial dysfunction and is independently associated with atherosclerotis in diabetic and in non-diabetic patients. We assessed the prevalence of MAU in non-diabetic patients who presented with UA...
Novel bare metal stents with improved stent design may become a viable alternative to drug-eluting stents in certain patient groups, particularly, when long-term dual antiplatelet therapy should be avoided.
The ENERGY registry aimed to assess the safety and benefits of a cobalt-chromium thin strut bare metal stent with a passive coating in a large...
BACKGROUND: Mineralocorticoid antagonists improve survival among patients with chronic, severe systolic heart failure and heart failure after myocardial infarction. We evaluated the effects of eplerenone in patients with chronic systolic heart failure and mild symptoms. METHODS: In this randomized, double-blind trial, we randomly assigned 2737 pati...
Introduction: Matrix reorganization and collagen formation have been suggested to be responsible for cardiac remodeling. Recently, Hypoxia Inducible Factors (HIF) has been shown to be also involved. To differentiate the pathogenesis of cardiac remodeling we used two different prolyl 4-hydroxylase (P4H) inhibitors, FG 0041 known for its potential in...
Neointimal hyperplasia is one of the key components of the restenotic process. The aim of this study was to evaluate the efficacy and safety of a microbubble delivery of c-myc antisense peptide in reducing restenosis after coronary stenting in de novo stenosis with intravascular ultrasound. A Multi-Link Zeta bare metal stent was implanted in de nov...
BACKGROUND: Mineralocorticoid antagonists improve survival among patients with chronic, severe systolic heart failure and heart failure after myocardial infarction. We evaluated the effects of eplerenone in patients with chronic systolic heart failure and mild symptoms. METHODS: In this randomized, double-blind trial, we randomly assigned 2737 pati...
BACKGROUND: Mineralocorticoid antagonists improve survival among patients with chronic, severe systolic heart failure and heart failure after myocardial infarction. We evaluated the effects of eplerenone in patients with chronic systolic heart failure and mild symptoms. METHODS: In this randomized, double-blind trial, we randomly assigned 2737 pati...
Cardiovascular complications are a major cause of morbidity and mortality in chronic renal failure (CRF) patients. Chronic anemia is a complication of CRF and a cardiovascular risk factor per se. It was the aim of the present study to clarify whether uremia and anemia are additive or supra-additive with respect to cardiovascular alterations.
Thirty...
N-terminal-pro brain natriuretic peptide (NT-proBNP) is a useful cardiac marker that is also influenced by renal dysfunction. It was our objective to assess the relationship between NT-proBNP concentrations in plasma and worsening renal function, and to attempt adjustment of NT-proBNP for renal dysfunction in a prospective, stratified multi-center...
Cardiovascular risk factors such as elevated serum lipid levels are important in the development of coronary atherosclerosis. Radiofrequency (RF) analysis of intravascular ultrasound [IVUS, Virtual histology (VH)] offers a unique tool to study the composition of coronary atherosclerotic plaque in vivo. We used data from the multicentre VH registry...
A 63-year-old white man with a 6-month history of progressive exertional dyspnea was referred for evaluation. In 1997, he presented an episode of unconsciousness as first symptom of a cardiac disease. In 2003, arterial hypertension, as well as atrioventricular block Mobitz type I, was diagnosed. A worsening of the biventricular heart failure over t...
Renal artery stenosis (RAS) is both a common and progressive disease and its prevalence in patients > 65 years is 6.8%. In patients with known or suspected atherosclerosis undergoing coronary angiography, a frequency of even 11-23% is reported in the literature. Despite this high prevalence, there is an ongoing discussion about the indications for...
Renal artery stenosis (RAS) is both a common and progressive disease and its prevalence in patients > 65 years is 6.8%. In patients with known or suspected atherosclerosis undergoing coronary angiography, a frequency of even 11–23% is reported in the literature. Despite this high prevalence, there is an ongoing discussion about the indications for...
Background: Although the use of drug-eluting stents has been shown to limit neointimal hyperplasia, currently available DES may adversely affect re-endothelialization, possibly precipitating late cardiac events. The aim of this study was to evaluate the efficacy and safety of a microbubble delivery of c-myc antisense peptide in preventing restenosi...
Background: Cardiovascular risk factors have an impact on coronary atherosclerosis evolution. However, there is only limited information about the relationship between risk and atherosclerotic plaque as measured invasively by Intravascular Ultrasound Radiofrequency (IVUS-RF) analysis. The Aim of this study was to assess the impact of cardiovascular...
Cardiac marker release after percutaneous coronary interventions (PCI) reflects myocardial necrosis which is usually the result of periprocedural (micro)embolization of atherothrombotic debris and associated with impaired left ventricular function and adverse outcome.
In this prospective study, we examined 55 patients treated by direct stenting of...
More and more patients are treated with antiplatelet drugs today. In this context a sufficient inhibition of platelet aggregation, on the one hand, is of essential importance to the efficiency of prophylaxis of myocardial and cerebral infarction and to avoiding thrombosis of drug-eluting stents. On the other hand, this medication can result in an i...
Balloon aortic valvuloplasty (BAV), introduced since almost 20 years, has experienced a revival for its use in the treatment of elderly patients with severe calcified aortic stenosis that are associated with high operative risk and co-morbidities. This is due to the introduction of new balloon catheters and techniques. This study reports about 75 s...
A 57-year-old man presented with a sudden onset of chest pain, which suggested the possibility of myocardial infarction. Coronary angiography revealed a myocardial bridge in the left anterior descending coronary artery. The myocardial bridge decreased the diameter of the artery substantially during systole (Panel A, with arrow pointing to myocardia...
Wir berichten
über die iatrogene Perforation
eines Pulmonalarterienastes bei
einer 84-jährigen Patientin nach
Aortenklappenvalvuloplastie und
das nachfolgende Krisenmanagement
mit Restitutio ad integrum.
Die Perforation verursachte eine
intrapulmonale Hämorrhagie mit
drohender Asphyxie. Die Ursache
wurde rasch erkannt und die Blutung
durch Repositi...
Intravascular ultrasound (IVUS) is the "state-of-the-art" technique for imaging and analyzing coronary plaque extent and composition. Despite small-sized IVUS catheters complications are possible during the procedure such as acute coronary dissection, perforation, and vessel thrombosis. The authors report the case of an acute dissection of the righ...
Intravascular ultrasound (IVUS) is the “state-of-the-art” technique for imaging and analyzing coronary plaque extent and composition. Despite small-sized IVUS catheters complications are possible during the procedure such as acute coronary dissection, perforation, and vessel thrombosis. The authors report the case of an acute dissection of the righ...
Although protein kinase C (PKC) plays a key role in ischemic preconditioning (IPC), the actual mechanism of that protection is unknown. We recently found that protection from IPC requires activation of adenosine receptors during early reperfusion. We, therefore, hypothesized that PKC might act to increase the heart's sensitivity to adenosine. IPC l...
In recent years, intravascular ultrasound (IVUS) has evolved as an important adjunct to angiography, providing insights that are significantly altering conventional paradigms in diagnosis and therapy. However, major drawbacks in the use of IVUS relied on the fact that a heavy console had to be moved from lab to lab, and extensive time for set up an...
We previously reported that pharmacological preconditioning of rabbit hearts with acetylcholine involves activation of phosphatidylinositol 3-kinase (PI3-K) through transactivation of the epidermal growth factor receptor (EGFR). Transactivation is thought to be initiated by cleavage of membrane-bound pro-heparin-binding EGF-like growth factor (HB-E...
Pressure overload leads to myocardial remodelling with collagen accumulation, left ventricular hypertrophy (LVH), neurohormonal activation and myocardial dysfunction. Prolyl 4-hydroxylases (P4H) are involved in collagen maturation. Inhibition of P4H has been shown to prevent LV remodelling and improve survival post-myocardial infarction.
To evaluat...
Calcified aortic stenosis is the predominant valve disease. Patients affected are most commonly elderly people, who often show associated comorbidities like reduced left ventricular function, impaired renal function, and pulmonary hypertension. The risk of open-heart surgery is elevated. Balloon aortic valvuloplasty enables a reduction of symptoms,...
Die kalzifizierte Aortenklappenstenose ist der häufigste Herzklappenfehler. Die Betroffenen sind ältere Menschen, die häufig zusätzlich Komorbiditäten wie linskventrikuläre Dysfunktion, eingeschränkte Nierenfunktion und pulmonale Hypertonie aufweisen. Das operative Risiko ist erhöht. Mit der perkutanen Aortenklappenvalvuloplastie können eine Sympto...
We investigated whether atrial natriuretic peptide (ANP) given just prior to reperfusion reduces infarction in rabbit hearts and whether protection is related to activation of protein kinase G (PKG). Isolated rabbit hearts were subjected to a 30-min period of regional ischemia; treated hearts received a 20-min infusion of ANP (0.1 microM) starting...
Prolyl hydroxylase domain-containing enzymes (PHD) hydroxylate a proline residue that controls the degradation of hypoxia inducible factor (HIF). Hypoxia inhibits this hydroxylation thus increasing HIF levels. HIF is upregulated in ischemic tissues, growing tumors and in nonischemic, mechanically stressed myocardium. Pharmacological inhibition of p...
Ischemic postconditioning protects the reperfused heart from infarction, and this protection is dependent on the occupancy of adenosine receptors. We further explored the role of adenosine receptors in this salvage.
In situ rabbit hearts underwent 30 min of regional ischemia and 3 h of reperfusion, and postconditioning was effected with four cycles...
Acetylcholine (ACh) and opioid receptor agonists trigger the preconditioned phenotype through sequential activation of the epidermal growth factor (EGF) receptor, phosphatidylinositol 3-kinase (PI3-K), Akt, and nitric oxide synthase (NOS), and opening of mitochondrial (mito) K(ATP) channels with the generation of reactive oxygen species (ROS). Alth...
Protection from a prolyl hydroxylase domain-containing enzyme (PHD) inhibitor, desferoxamine (DFO), was recently reported to be dependent on production of reactive oxygen species (ROS). Ischemic preconditioning triggers the protected state by stimulating nitric oxide (NO) production to open mitochondrial ATP-sensitive K+ (mitoK(ATP)) channels, gene...
Research efforts have focused on ways to attenuate deleterious consequences of coronary occlusion in humans. However, clinical research is hampered by the inability to measure morphological, biochemical and molecular changes produced by interventions. Accordingly, a variety of experimental models have been used. However, selection of the particular...
The importance of anaemia in chronic heart failure was highlighted recently by different cohort studies. The aim of this study was to assess the prevalence of anaemia and its relationship to renal function, left ventricular function and symptoms of heart failure.
We surveyed cases of patients admitted to the Department of Cardiology during 22 conse...
Bradykinin and acetylcholine (ACh) trigger preconditioning by ATP-sensitive K(+) (K(ATP)) channel-dependent production of reactive oxygen species (ROS). Recent evidence suggests that ROS production may in turn be influenced by cGMP-dependent protein kinase (PKG). This study utilized DT-2 and DT-3 peptides, highly specific membrane-permeable blocker...
Protection from postconditioning has been documented in in situ animal models and it has been proposed that it is targeting circulating leukocytes. We therefore tested whether postconditioning can protect leukocyte-free, buffer-perfused rabbit hearts. Infarct size was measured with triphenyltetrazolium staining. In control hearts undergoing 30 min...
The presence of apoptotic cell death in cardiac myocytes is now well established and the contribution of apoptosis for the development of heart failure has been suggested. However, the mechanism responsible for the induction of apoptosis remains unclear. The present study was designed to investigate the involvement of Fas and caspase 3 in the trans...
In the rabbit heart, bradykinin and ACh trigger preconditioning by a mechanism involving ATP-sensitive potassium channel-dependent production of reactive oxygen species (ROS). Recent evidence indicates that the pathway by which bradykinin causes ROS generation includes nitric oxide synthase (NOS) and protein kinase G (PKG). On the other hand, Akt w...
Hypoxia-inducible factor (HIF)-1alpha and -2alpha are key regulators of the transcriptional response to hypoxia and pivotal in mediating the consequences of many disease states. In the present work, we define their temporo-spatial accumulation after myocardial infarction and systemic hypoxia. Rats were exposed to hypoxia or underwent coronary arter...
While ACE-inhibitors have proven their prognostic benefit in many hypertension studies, a new approach has been proposed by inhibiting neutral endopeptidase, which degrades natriuretic peptides. The combined inhibition of ACE and endopeptidase was named "vasopeptidase-inhibition" and tested in several trial. Though effective in lowering blood press...
Nachdem die ACE-Hemmer in den letzten Jahren in immer weiteren Indikationsfeldern günstige prognostische Effekte zeigen konnten, wurden die Inhibition der neutralen Endopeptidase und die dadurch bewirkte Aktivierung der natriuretischen Peptide lange Zeit als ein zusätzlicher sinnvoller Ansatz gesehen. Insbesondere die gleichzeitige Inhibition von A...
Bradykinin (BK) mimics ischemic preconditioning by generating reactive oxygen species (ROS). To identify intermediate steps that lead to ROS generation, rabbit cardiomyocytes were incubated in reduced MitoTracker Red stain, which becomes fluorescent after exposure to ROS. Fluorescence intensity in treated cells was expressed as a percentage of that...
Trotz mehrerer größerer klinischer Studien sind heute ACE-Hemmer immer noch Medikament der ersten Wahl bei der Behandlung der Herzinsuffizienz. AT1-Antagonisten sind den ACE-Hemmern dabei nicht überlegen - weder bei der Behandlung der chronischen Herzinsuffizienz noch bei der akuten Herzinsuffizienz im Rahmen eines Myokardinfarktes. Obwohl die Glei...
The endothelin (ET-1) system is activated in chronic heart failure (CHF). Whether, what type, and what degree of selective ET blockade is clinically beneficial is unknown. We investigated hemodynamic and neurohumoral effects of 3 weeks of treatment with various dosages of the orally available ET(A) antagonist darusentan in addition to modern standa...
The enzyme neutral endopeptidase (NEP; EC 3.4.24.11) cleaves several vasoactive peptides such as the atrial natriuretic peptide (ANP). ANP is a hormone of cardiac origin with diuretic and natriuretic actions. Despite elevated circulating levels of ANP, congestive heart failure (CHF) is characterized by progressive sodium and water retention. In ord...
In heart failure, the cGMP to natriuretic peptide ratio is decreased and infusion of atrial natriuretic peptide (ANP) induces less cGMP generation. The ratio of the second messenger cGMP to plasma concentrations of ANP or brain natriuretic peptide (BNP) correlates with the effectiveness of natriuretic peptides. It was investigated whether blockade...
Growth hormone (GH) application is a new strategy in the treatment of heart failure. However, clinical and experimental investigations have shown contradictory effects of GH on cardiac performance. We tested the hypothesis that GH could improve cardiac and renal function in volume overload-induced heart failure. The effect of 4 weeks of GH treatmen...
Is heart failure an endocrine disease? Historically, congestive heart failure (CHF) has often been regarded as a mechanical and haemodynamic condition. However, there is now strong evidence that the activation of neuroendocrine systems, like the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system, as well as the activation of...
Adrenomedullin (AM) is a peptide hormone with vasodilating and natriuretic properties. AM plasma concentrations are elevated in heart failure. Whether cardiac AM-mRNA synthesis is increased in heart failure is not known. We measured AM-mRNA/GAPDH-mRNA in all four heart chambers in compensated and overt heart failure in rats with two different sizes...
We tested the hypothesis that low-density lipoprotein (LDL) and its acetylated form influence surface expression of vascular adhesion molecules on human endothelial cells. Vascular adhesion molecule surface expression was assessed with flow cytometry on cultured endothelial cells with a modified enzyme-linked immunosorbent assay. LDL acetylation wa...
Low-density lipoproteins (LDLs) stimulate cytosolic calcium ([Ca++]i) in endothelial cells. To elucidate the mechanisms of this response, we compared the effects of low-density lipoprotein (LDL) with those of thrombin, a known endothelial cell agonist. [Ca++]i was measured in cultured endothelial cells from human umbilical veins. Both spectrofluoro...
[Mikrofiche-Ausg.]. Berlin, Humboldt-Univ., Diss., 1996.
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