Papers by Christopher Adlbrecht
BACKGROUND: Advancing age is associated with a greater prevalence of coronary artery disease in h... more BACKGROUND: Advancing age is associated with a greater prevalence of coronary artery disease in heart failure with reduced ejection fraction and with a higher risk of complications after coronary artery bypass grafting (CABG). Whether the efficacy of CABG compared with medical therapy (MED) in patients with heart failure caused by ischemic cardiomyopathy is the same in patients of different ages is unknown.
P . b . b . 0 2 Z 0 3 1 1 0 5 M , V e r l a g s p o s t a m t : 3 0 0 2 P u r k e r s d o r f , E... more P . b . b . 0 2 Z 0 3 1 1 0 5 M , V e r l a g s p o s t a m t : 3 0 0 2 P u r k e r s d o r f , E r s c h e i n u n g s o r t : 3 0 0 3 G a b l i t z Indexed in EMBASE/Excerpta Medica/Scopus www.kup.at/kardiologie Member of the ESC-Editors' Club Member of the Offizielles Organ des Österreichischen Herzfonds
European Journal of Cardiovascular Prevention & Rehabilitation, 2012
Background: In primary care, identification of patients who are at risk of major adverse events i... more Background: In primary care, identification of patients who are at risk of major adverse events is of great importance. At the same time identifying individuals who are at very low risk and do not need further diagnostic workup and therapy is also important and may help to correctly allocate scarce healthcare resources. Aim: This study evaluated amino-terminal pro B-natriuretic peptide (NT-proBNP) as a risk marker in primary care patients with hypertension, diabetes, clinically suspected heart failure (HF), history of coronary artery disease or myocardial infarction. Methods and results: A prospective observational study was conducted in 1203 primary care patients. The primary endpoint, time to all-cause hospitalisation, was reached in 282 (24%) individuals within 12 months. Of all variables analysed, only NT-proBNP (HR 1.001 [1.000-1.001], p < 0.001) and age (HR 1.018 [1.007-1.028], p ¼ 0.001) were of independent predictive value in a stepwise Cox regression analysis regarding all-cause hospitalisation. Neither systolic dysfunction nor signs and symptoms of HF added independent information to predict outcome. The negative predictive value (NPV) increased depending on the specificity of the endpoint (NPV was 86% for all-cause, 98% for cardiac and 100% for HF-related hospitalisation for 125 pg/ml). Positive predictive value and NPV were superior for NT-proBNP compared to clinical signs and symptoms of HF at every cut-point between 100 and 500 pg/ml. Conclusion: NT-proBNP levels predicted clinical events in primary care patients at risk. NPVs were excellent in this high risk population, proving NT-proBNP measurement a safe diagnostic tool.
Circulation, 2007
Background-Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by intraluminal... more Background-Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by intraluminal thrombus organization and fibrous obliteration of pulmonary arteries. Recently, associated medical conditions such as splenectomy, ventriculoatrial shunt for the treatment of hydrocephalus, permanent central intravenous lines, inflammatory bowel disease, and osteomyelitis were found to be associated with the development of CTEPH. The study aim was to define the impact of these novel risk factors on survival.
Arteriosclerosis, Thrombosis, and Vascular Biology, 2008
Objective-Acute pulmonary emboli usually resolve within 6 months. However, in 0.1% to 5% of cases... more Objective-Acute pulmonary emboli usually resolve within 6 months. However, in 0.1% to 5% of cases thrombus transforms into fibrous masses. If vascular obstruction is severe, the resulting condition is chronic thromboembolic pulmonary hypertension (CTEPH). Patients who carry ventriculo-atrial (VA-) shunts for the treatment of hydrocephalus and report a history of shunt infection are at an increased risk for CTEPH. Because CTEPH lacks traditional plasmatic risk factors for venous thromboembolism, we hypothesized that delayed thrombus resolution rather than abnormal coagulation is important, and that bacterial infection would be important for this misguidance. Methods and Results-Human CTEPH thromboemboli were harvested during pulmonary endarterectomy. The effects of Staphylococcal infection on thrombus organization were examined in a murine model of stagnant-flow venous thrombosis. Staphylococcal DNA, but not RNA, was detected in 6 of 7 thrombi from VA shunt carriers. In the mouse model, staphylococcal infection delayed thrombus resolution in parallel with upregulation of transforming growth factor (TGF) beta and connective tissue growth factor. Conclusions-In the present work, we propose a mechanism of disease demonstrating that infection with Staphylococci enhances fibrotic vascular remodeling after thrombosis, resulting in misguided thrombus resolution. Thrombus infection appears to be a trigger in the evolution of CTEPH. (Arterioscler Thromb Vasc Biol. 2008;28:000-000.)
Clinical Science, 2012
Thrombotic occlusion of an epicardial coronary artery on the grounds of atherosclerotic plaque is... more Thrombotic occlusion of an epicardial coronary artery on the grounds of atherosclerotic plaque is considered the ultimate step in AMI (acute myocardial infarction). However, the precise pathophysiological mechanisms underlying acute coronary occlusion are not fully understood. We have analysed proteomic profiles of systemic plasma and plasma derived from the site of coronary plaque rupture of non-diabetic patients with STEMI (ST-segment elevation myocardial infarction). Label-free quantification of MS/MS (tandem MS) data revealed differential regulation of complement cascade components and a decrease in anti-thrombotic PEDF (pigment epitheliumderived factor) between CS (culprit site)-derived plasma and systemic plasma. PEDF, which is known to have a protective role in atherothrombosis, was relatively decreased at the CS, with a level of expression inverse to local MMP-9 (matrix metalloproteinase-9) activity. CS plasma displayed enhanced proteolytic activity towards PEDF. Proteomics of coronary thrombus aspirates indicate that PEDF processing is associated with coronary plaque rupture.
Thrombosis and Haemostasis, Sep 1, 2009
Atherosclerotic plaque rupture with subsequent mural thrombus formation is considered the main ev... more Atherosclerotic plaque rupture with subsequent mural thrombus formation is considered the main event compromising epicardial flow in acute myocardial infarction (AMI). However, the precise mechanisms underlying acute coronary occlusion are unknown. We compared the proteomic profiles of systemic plasma and plasma derived from the site of thrombus formation of patients with AMI by two-dimensional gel electrophoresis and ELISA. We identified a local activation of the complement system, with selective accumulation of the complement activator C-reactive protein (CRP) and the downstream complement effectors C3a and C5a. CRP in coronary thrombus co-localised with C1q and C3 immunoreactivities, suggesting classical complement activation. In vitro, coronary thrombus derived plasma enhanced neutrophil chemotaxis in a C5a dependent fashion. In vivo, neutrophil accumulation at the site of thrombus formation paralleled the time delay from symptom onset to first balloon inflation or aspiration, and was correlated with C5a and enzymatic infarct size. We present the first direct evidence for localised complement activation in acute coronary thrombi. Our data indicate that local complement effectors amplify the vascular occlusion process in AMI by enhanced neutrophil recruitment.
CHEST Journal, 2005
Bosentan, an oral endothelin (ET)-A/ET-B receptor antagonist, is effective in the treatment of pu... more Bosentan, an oral endothelin (ET)-A/ET-B receptor antagonist, is effective in the treatment of pulmonary arterial hypertension. To investigate the safety and efficacy of bosentan therapy in patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Case series. Pulmonary Hypertension Unit of the Medical University of Vienna, Austria. Sixteen patients (9 women and 7 men; mean age +/- SD, 70 +/- 13 years). Off-label bosentan treatment over 6 months. Changes from baseline in liver enzymes, New York Heart Association (NYHA) functional class, 6-min walking distance (6-MWD), and serum amino-terminal pro-brain natriuretic peptide (proBNP). After 6 months, NYHA functional class improved by one class in 11 patients. Mean 6-MWDs increased from 299 +/- 131 m at baseline to 391 +/- 110 m at 6 months (p = 0.01). In parallel, proBNP decreased from 3,365 +/- 2,923 to 1,755 +/- 1,812 pg/mL (p = 0.01). Neither aspartate aminotransferase (25 +/- 2 U/L vs 25 +/- 2 U/L, p = 0.25) nor alanine aminotransferase (23 +/- 12 U/L vs 24 +/- 9 U/L, p = 0.57) changed significantly. Limitations of the study were uncontrolled design and small sample size. Our study suggests a beneficial effect of the oral dual ET receptor antagonist bosentan in patients with inoperable CTEPH, urging the need for a randomized, placebo-controlled trial.
Thrombosis and Haemostasis, 2007
Acutec oronarys yndrome is characterized by compromised blood flowa tt he epicardial andm icrovas... more Acutec oronarys yndrome is characterized by compromised blood flowa tt he epicardial andm icrovascular levels.Weh ave previously shownthat thrombectomyinST-elevation myocardial infarction (STEMI) acceleratesS T-segment resolution, possibly by preventing distal embolization.We hypothesized that thrombusc onstituents contribute to microcirculatoryd ysfunction. Therefore, we analyzed the molecular and cellular composition of acute coronaryt hrombi, and correlatedv asoconstrictive mediators with themagnitude of ST-segment resolutionwithin one hour of percutaneous coronaryi ntervention( PCI). Fresh coronarythrombi were retrievedin35consecutiveSTEMI patients who were treatedw ith the X-Sizer thrombectomyc atheter,and thrombus cell counts and vasoconstrictorc oncentrations were assessed.Tw elve-leadECG recordings were analyzed priort oa nd one hour after PCI.Concentration of en-
Circulation Research, 2014
A cute coronary syndrome (ACS) is among the leading causes of death. 1 However, precise pathomech... more A cute coronary syndrome (ACS) is among the leading causes of death. 1 However, precise pathomechanisms of acute coronary occlusion and atherothrombosis are still not well understood. Circulating leukocytes, particularly monocytes, play a central role in atherothrombosis. 2,3 The role of neutrophils (polymorphonuclear cells [PMNs]) in coronary thrombosis is less explored, although systemic PMN counts are among the most robust predictors of acute coronary events 4 and impact outcomes. We have previously shown PMN accumulation in coronary thrombi, and PMNs have been described in thrombi recovered during surgical thrombectomies and open repair of abdominal aortic aneurysms. 7 PMNs hold powerful effector mechanisms, particularly by the formation of neutrophil extracellular traps (NETs). On activation, PMNs release their nuclear content into the extracellular space to engulf and isolate pathogens. 8 NETs are composed of chromatin, which consists of DNA segments wound in sequence around 8 histone protein cores, and other granule proteins, exerting potent proinflammatory, cytotoxic, and prothrombotic effects. 9,10 Rationale: Mechanisms of coronary occlusion in ST-elevation acute coronary syndrome are poorly understood. We
Thrombosis and Haemostasis, 2009
Atherosclerotic plaque rupture with subsequent mural thrombus formation is considered the main ev... more Atherosclerotic plaque rupture with subsequent mural thrombus formation is considered the main event compromising epicardial flow in acute myocardial infarction (AMI). However, the precise mechanisms underlying acute coronary occlusion are unknown. We compared the proteomic profiles of systemic plasma and plasma derived from the site of thrombus formation of patients with AMI by two-dimensional gel electrophoresis and ELISA. We identified a local activation of the complement system, with selective accumulation of the complement activator C-reactive protein (CRP) and the downstream complement effectors C3a and C5a. CRP in coronary thrombus co-localised with C1q and C3 immunoreactivities, suggesting classical complement activation. In vitro, coronary thrombus derived plasma enhanced neutrophil chemotaxis in a C5a dependent fashion. In vivo, neutrophil accumulation at the site of thrombus formation paralleled the time delay from symptom onset to first balloon inflation or aspiration, and was correlated with C5a and enzymatic infarct size. We present the first direct evidence for localised complement activation in acute coronary thrombi. Our data indicate that local complement effectors amplify the vascular occlusion process in AMI by enhanced neutrophil recruitment.
A106. CHRONIC THROMBOEMBOLIC PULMONARY HYPERTENSION: BENCH TO BEDSIDE, 2011
European Journal of Clinical Investigation, 2010
Background Current data appear in favour of thrombectomy for ST-elevation myocardial infarction (... more Background Current data appear in favour of thrombectomy for ST-elevation myocardial infarction (STEMI). However, information on long-term outcome after thrombectomy is limited. We performed a retrospective long-term study to assess the risk of cardiac re-hospitalizations and survival after discharge from the index hospitalization for STEMI.
Circulation, Oct 31, 2006
Thrombosis and Haemostasis, 2005
Chronic thromboembolic pulmonaryh ypertension (CTEPH) is characterizedb yo rganized thromboemboli... more Chronic thromboembolic pulmonaryh ypertension (CTEPH) is characterizedb yo rganized thromboemboli that obstruct the pulmonaryv ascular bed. AlthoughC TEPH is as erious complication of acute symptomaticp ulmonary embolismi n4 %o f cases,s igns,s ymptomsa nd classical riskf actors forv enous thromboembolism arelacking.Theaim of the presentstudy was to identifym edical conditions conferringa ni ncreasedr isko f CTEPH.W ep erformedac ase-control-study comparing 109
Thrombosis and Haemostasis, 2003
Results show that CTEPH patients had higher FVIII levels than controls (233±83IU/dl versus 123±40... more Results show that CTEPH patients had higher FVIII levels than controls (233±83IU/dl versus 123±40IU/dl, p<0.0001) and PAH patients (158±61IU/dl, p<0.0001). Plasma FVIII one year after surgery (212±94IU/dl) was statistically unchanged compared with preoperative values (FVIII: 226±88IU/dl, n=25). FVIII>230IU/dl was more prevalent in CTEPH patients (41%) than in controls (5%, p<0.0001) and PAH patients (22%, p=0.022). We can conclude that elevated plasma FVIII is the first prothrombotic factor identified in a large proportion of CTEPH patients.
European Journal of Clinical Investigation, 2012
Background Recent studies show associations between inorganic phosphate and risk of heart failure... more Background Recent studies show associations between inorganic phosphate and risk of heart failure in the general population as well as between fibroblast growth factor 23 (FGF-23) and outcome in coronary heart disease. This study was carried out to assess whether circulating levels of inorganic phosphate and FGF-23, a new central hormone in mineral bone metabolism, predict outcome in systolic heart failure.
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Papers by Christopher Adlbrecht