[Fatigue, breathlessness and chest pain in a 31-year-old man with schizoaffective disorder]. / Müdigkeit, Kurzatmigkeit und Brustschmerz bei einem 31-jährigen Mann mit schizoaffektiver Störung.

BACKGROUND: Clozapine is an alternative antipsychotic medication used to control symptoms of schizophrenia and to reduce risks of suicidal behavior in patients who did not adequately respond to standard medication. Due to severe side effects including cardiomyopathy and myocarditis its clinical use is limited. CASE REPORT: A 31-year-old man of east European descent presented to the emergency medical department with fatigue, shortness of breath and chest pain. Due to a schizoaffective disorder he was treated with clozapine and lithium. Echocardiography revealed severely impaired left ventricular systolic function. After exclusion of coronary artery disease by coronary angiography an endomyocardial biopsy was performed according to the guidelines. This confirmed the clinically suspected toxic cardiomyopathy. Therefore, antipsychotic treatment was immediately changed and state of the art heart failure medication was started resulting in a clear improvement of left ventricular function. CONCLUSION: In patients treated with clozapine or lithium and clinical signs of heart failure, toxic cardiomyopathy should be considered.

Heart rate variability for rapid risk stratification of emergency patients with malignant disease.

INTRODUCTION: Neoplasms are the second most common diseases in western countries. Many patients with malignant diseases repeatedly present themselves in the emergency department (ED). Due to limited capacities, appropriate risk stratification strategies for cancer patients have to be developed. This study assesses if deceleration capacity (DC) of heart rate as a parameter of heart rate variability predicts mortality in emergency patients with malignant diseases. METHODS: Prospectively, 140 adults with different entities of malignant diseases who presented in the medical ED were included. Primary and secondary endpoints were intrahospital mortality and mortality within 180 days, respectively. We calculated DC from short-term ECG readings of the surveillance monitors. Additionally, the Modified Early Warning Score (MEWS) and laboratory parameters such as white blood cells (WBC), lactate dehydrogenase, serum hemoglobin, and serum creatinine were determined. RESULTS: The median age of the patients was 65 ± 14 years. 19.3% of the patients died within the hospital stay and 57.9% died within 180 days. DC and WBC were independent predictors of intrahospital death reaching a hazard ratio (HR) of 0.79 (95% confidence interval (CI) 0.63-0.993, p = 0.043) and of 1.00 (95% CI 1.00-1.00, p = 0.003), respectively. DC and serum creatinine independently predicted death within 180 days (HR 0.90, 95% CI 0.82-0.98, p = 0.023 and HR 1.41, 95% CI 1.05-1.90, p = 0.018, respectively). CONCLUSION: Deceleration capacity of heart rate is suitable for rapid risk assessment of emergency patients with malignant diseases.

Insertable cardiac monitors after cryptogenic stroke--a risk factor based approach to enhance the detection rate for paroxysmal atrial fibrillation.

BACKGROUND AND PURPOSE: Recently, the CRYSTAL AF trial detected paroxysmal atrial fibrillation (AF) in 12.4% of patients after cryptogenic ischaemic stroke (IS) or cryptogenic transient ischaemic attack (TIA) by an insertable cardiac monitor (ICM) within 1 year of monitoring. Our aim was (i) to assess if an AF risk factor based pre-selection of ICM candidates would enhance the rate of AF detection and (ii) to determine AF risk factors with significant predictive value for AF detection. METHODS: Seventy-five patients with cryptogenic IS/TIA were consecutively enrolled if at least one of the following AF risk factors was present: a CHA2DS2-VASc score ≥4, atrial runs, left atrium (LA) size >45 mm, left atrial appendage (LAA) flow ≤0.2 m/s, or spontaneous echo contrast in the LAA. The electrocardiographic and echocardiographic criteria were chosen as they have been repeatedly reported to predict AF; the same applies for four of the six items of the CHA2DS2-VASc score. The study end-point was the detection of one or more episodes of AF (≥2 min). RESULTS: Seventy-four patients underwent implantation of an ICM; one patient had AF at the date of implantation. After 6 months, AF was detected in 21/75 patients (28%), after 12 months in 25/75 patients (33.3%). 92% of AF episodes were asymptomatic. LA size >45 mm and the presence of atrial runs were independently associated with AF detection [hazard ratio 3.6 (95% confidence interval 1.6-8.4), P = 0.002, and 2.7 (1.2-6.7), P = 0.023, respectively]. CONCLUSIONS: The detection rate of AF is one-third after 1 year if candidates for an ICM after cryptogenic IS/TIA are selected by AF risk factors. LA dilation and atrial runs independently predict AF.

Efficacy and safety of zero-fluoroscopy ablation for supraventricular tachycardias. Use of optional contact force measurement for zero-fluoroscopy ablation in a clinical routine setting.

BACKGROUND: Conventional catheter ablation of cardiac arrhythmias is associated with radiation risks for patients and laboratory personnel. Widespread use of zero-fluoroscopic catheter ablation in clinical routine is limited by safety concerns. This study investigated the feasibility of zero-fluoroscopy catheter ablation using a three-dimensional mapping system and optional catheter contact force technology for an all-comers collective. PATIENTS AND METHODS: The study comprised 184 patients; 91 patients, including 29 pediatric patients, underwent a zero-fluoroscopic electrophysiology (EP) study using the EnSite NavX system with real-time visualization of all electrodes. These patients were matched to a control group, which was treated using fluoroscopy in the same period. Inclusion criteria were documented supraventricular tachycardia or a history of symptomatic paroxysmal supraventricular tachycardia. Transseptal access, if necessary, was achieved under transesophageal echocardiographic guidance for ablation of left-sided arrhythmias. Radiofrequency (using optional contact force measurement) or a cryotechnique was used for ablation. RESULTS: We observed no major acute complications. There were no significant differences between the two groups in the follow-up period. CONCLUSION: Zero-fluoroscopic catheter ablation is generally feasible in right-sided cardiac arrhythmias. Safety concerns regarding left atrial substrates or children can be overcome with optional real-time contact force measurement.

Is the diagnostic yield of myocardial stress perfusion MRI impaired by three-vessel coronary artery disease?

BACKGROUND: Three-vessel coronary artery disease (CAD) comes along with globally reduced myocardial perfusion potentially restricting the demarcation of regional hypoperfusion in stress perfusion cardiac magnetic resonance imaging (MRI). PURPOSE: To evaluate whether stress perfusion cardiac MRI is capable of detecting myocardial hypoperfusion in patients with 3-vessel CAD reliably. MATERIAL AND METHODS: Two hundred and five patients with symptoms of CAD were included. The examination protocol comprised imaging of myocardial perfusion at stress (0.14 mg/kg/min adenosine for 4 min) using a 2D saturation recovery gradient echo sequence after administration of gadobutrol (0.1 mmol/kg body weight). Perfusion sequences were assessed qualitatively by two experienced observers. Coronary angiography served as standard of reference. RESULTS: Sensitivity and specificity for hemodynamically relevant stenoses in patients with 0-, 1-, 2-, 3-vessel coronary artery disease were 100%/91%, 91%/73%, 90%/71%, 92%/64%; positive/negative predictive value, 67%/100%, 91%/73%, 83%/81%, 93%/58%; diagnostic accuracy, 93%/87%/83%/87%, respectively. The negative predictive value in patients with 3-vessel CAD was lower than in patients with 0- and 2-vessel CAD and the specificity lower than in patients with no CAD whereas the positive predictive value was higher than in patients with no CAD. The other proportions did not differ significantly between the groups. CONCLUSION: The diagnostic value of stress perfusion cardiac MRI in patients with 3-vessel CAD is comparable to results in patients with 1- or 2-vessel CAD. In the rare event that stress perfusion images do not depict regional hypoperfusion in patients with severe 3-vessel CAD, myocardial ischemia could be identified by reduced semi-quantitative perfusion parameters.

Differential MMP-9 activity in CD34⁺progenitor cell-derived foam cells from diabetic and normoglycemic patients.

BACKGROUND: Upon coincubation with platelet aggregates, CD34(+) progenitor cells have the potential to differentiate into foam cells. There is evidence that progenitor cells from diabetic and nondiabetic patients have different properties, which may affect the patients' prognosis. In this study we investigated an in vitro model of foam cell formation based on patient-derived CD34(+) progenitor cells. We analyzed the growth characteristics as well as the M-CSF-release and matrix metalloproteinase (MMP) synthesis from CD34(+) progenitor cell-derived foam cells originating from diabetic and nondiabetic patients. METHODS AND RESULTS: Bone marrow samples were obtained from 38 patients who were elected for thoracic surgery. CD34(+) progenitor cells from diabetic and nondiabetic patients were isolated and incubated with platelets from healthy volunteers. Foam cell formation was confirmed by immunostaining (CD68) and quantified by light microscopy. Whereas the absolute number of foam cells was not affected, the negative slope in the growth curve was seen significantly later in the diabetic group. In supernatants derived from"diabetic" CD34(+) progenitor cells, MMP-9 was significantly enhanced, whereas MMP-2 activity or M-CSF-release was not affected significantly. CONCLUSION: In a coculture model of CD34(+) progenitor cells with platelets, we show for the first time that"diabetic" CD34(+) progenitor cells exhibit functional differences in their differentiation to foam cells concerning growth characteristics and release of MMP-9.

Combination of high on-treatment platelet aggregation and low deaggregation better predicts long-term cardiovascular events in PCI patients under dual antiplatelet therapy.

High on-treatment platelet reactivity is associated with short-term major cardiovascular (CV) events in patients undergoing percutaneous coronary intervention (PCI). Maximum and final aggregation assessed by light transmission aggregometry (LTA) have both been used to predict short-term outcome after PCI, however their long-term prognostic impact remains controversial. There is currently no information regarding the prognostic role of deaggregation and its added value in combination with established aggregation parameters. About 1279 patients with symptomatic coronary artery disease (CAD) undergoing PCI were enrolled in this monocentric study. On-treatment platelet aggregation under clopidogrel maintenance therapy, as well as deaggregation was determined by maximum and final aggregation (5 min after adding of the agonist). Deaggregation was defined as slope of the tangent between Aggmax +0.5 min. Primary endpoints were the composite of myocardial infarction, stroke, and CV death or stent thrombosis according to the ARC criteria. Low deaggregation, defined as values in the lowest tertile (<1.5), was more frequent in patients with acute coronary syndromes (ACS) compared to patients with stable angina pectoris (SAP), ACS: 29.6% vs. SAP: 22.0%, p = 0.001. The combination of high on-treatment platelet reactivity, defined by the upper tertile of Aggmax and low deaggregation, was associated with significantly increased risk for combined long-term CV events. The combination of low deaggregation and high on-treatment platelet reactivity is associated with higher risk for recurrent events in patients with CAD undergoing PCI. Thus, deaggregation might be a more sensitive parameter providing added value in terms of risk prediction for long-term recurrent CV events in relation with established aggregation parameters.

Expression of stromal-cell-derived factor-1 (SDF-1): a predictor of ischaemic stroke?

BACKGROUND AND PURPOSE: Platelet stromal-cell-derived factor-1 (SDF-1) plays a pivotal role in angiogenesis and the regeneration of ischaemic tissue through the regulation of haematopoietic progenitor cells and is upregulated at the sites of vascular injury and platelet activation. Thus, SDF-1 has recently been discussed as a predictor in ischaemic diseases such as acute myocardial infarction. However, no clinical data pertinent to the investigation of the platelet SDF-1 expression in patients with stroke are available. METHODS: We consecutively evaluated 196 patients who were admitted to the stroke unit with symptoms suspected for stroke. Surface expression of the platelet activation markers (P-selectin and GPIb) and the expression of platelet-bound SDF-1 were determined by two-colour whole blood flow cytometry. RESULTS: Patients with transient ischaemic attack (TIA) as well as with ischaemic stroke showed similar levels of SDF-1 expression on hospital admission compared with patients with non-ischaemic (NI) events and with 30 healthy controls (TIA (mean fluorescence intensity±SD): 31.5±18.2 vs. NI: 26.4±15.7; P=0.361; stroke: 28.7±19.8 vs. NI; P=0.943; control: 26.1±11.3; P>0.05 compared with all). Platelet SDF-1 expression showed a trend with the severity of stroke according to National Institute of Health Stroke Scale score (r=0.125; P=0.085), but significantly correlated with the peak levels of C-reactive protein (r=0.218; P=0.002) and with the levels of platelet activation (P-selectin: r=0.389; P=0.001). Multifactorial analysis of covariance revealed a significant influence on platelet SDF-1 expression by smoking (P=0.019). CONCLUSIONS: Platelet SDF-1 surface expression did not show any significant difference in patients with TIA and ischaemic stroke compared with patients with NI events. Thus, single biomarker evaluation of platelet SDF-1 surface expression is not helpful to predict ischaemic stroke.

[Long-term outcome after dialysis-dependent renal failure on the intensive care unit]. / Langzeitergebnis nach akutem dialysepflichtigem Nierenversagen auf einer internistischen Intensivstation.

BACKGROUND: Acute kidney injury (AKI) is a common and serious complication of acute life-threatening diseases. OBJECTIVES: The aim of this study was to investigate the effect of acute renal failure on mortality in intensive care patients, the need for renal replacement therapy at discharge, and the effect on long-term mortality. MATERIAL AND METHODS: Evaluation of 118 patient cases with dialysis-dependent acute renal failure between November 2016 and December 2017 admitted to a medical intensive care unit (ICU) at the University Hospital Tübingen, Germany. Dialysis at discharge and 1­year mortality were defined as the primary endpoints. The secondary endpoint was need for continuous renal replacement after 18 months. RESULTS: In 118 patients, renal replacement modality by means of hemodialysis became necessary. A mortality rate of 45.8% (54/118) was found in patients requiring dialysis. Of the 64 surviving dialysis-dependent patients, 35.9% were still dependent on renal replacement therapy at the time of discharge. The 1­year mortality rate was significantly higher in patients that still required dialysis at the time of discharge (p = 0.004). At 18-month follow-up, seven patients (10.9%) were still on renal replacement therapy. At this time, dialysis was significantly more frequent in patients with dialysis at the time of discharge than in dialysis-free patients (7.1% vs. 71.4%, p = 0.001). CONCLUSION: Severe episodes of AKI requiring renal replacement therapy in the setting of an ICU are associated with increased mortality 1 year after discharge and an increased requirement for renal replacement 18 months after discharge.

Expression of platelet glycoprotein VI is associated with transient ischemic attack and stroke.

BACKGROUND AND PURPOSE: Platelet collagen receptor glycoprotein VI (GPVI) contributes significantly to platelet adhesion and thrombus formation. We aimed to investigate GPVI in patients presenting with symptoms of acute cerebrovascular disease and to define GPVI as biomarker for acute stroke. METHODS: We consecutively evaluated 205 patients, who admitted the stroke unit with symptoms for stroke. Surface expression of the platelet activation markers (GPVI, CD62P, GPIb) was determined by two-color whole blood flow cytometry. RESULTS: Patients with transient ischemic attack (TIA) (n = 18; 8.8%) as well as with stroke (n = 133; 64.9%) showed a significantly enhanced GPVI expression (mean fluorescence intensity +/- SD) on admission compared to patients with non-ischemic (NI) events (n = 54; 26.3%) (TIA: 20.9 +/- 7.1 vs. NI: 16.2 +/- 3.9; P = 0.002; stroke: 20.4 +/- 5.7 vs. NI; P = 0.002). Neither CD62P nor GPIb surface expression showed a significant difference. Logistic regression analysis revealed that on admission GPVI was associated with stroke independent of conventional laboratory markers such as C-reactive protein, blood glucose, and creatine kinase. Using a receiver operating characteristic curve on GPVI, we have determined the cut off value of 18.2 for stroke. Thus, patients with enhanced GPVI expression levels (>or=18.2) had a 2.4-fold relative risk for stroke. Patients with elevated platelet GPVI expression level had a poorer clinical outcome in cumulative event-free survival for stroke, myocardial infarction, and cerebro-/cardiovascular death at 3-month follow-up (log rank; P = 0.045). CONCLUSIONS: These findings indicate that platelet GPVI surface expression is significantly enhanced in patients with TIA and stroke compared to patients with NI events. Determination of platelet-specific GPVI may be useful as an early biomarker for cerebral ischemia.

Individualized antiplatelet therapy: what can a clinical score contribute?

Safeguarding of antiplatelet drug efficacy represents a cornerstone for the optimal treatment of patients with symptomatic coronary artery disease requiring coronary interventions. This means a challenge to modern cardiology since there has been cumulative evidence, that response to common oral antiplatelet therapy is a highly variable phenomenon underlying various mechanisms. It is known, that particular risk groups exhibit a high residual platelet aggregability (RPA) despite conventional antiplatelet therapy. Additionally, a relevant association between high RPA and recurrent ischaemic events after PCI exists. Individualization of antiplatelet therapy by dose increase or alternative application of novel P2Y12-receptor antagonists might lead to improved cardiovascular outcome in patients with poor responsiveness to conventional antiplatelet therapy. Identification of risk patients who might benefit from tailored therapy by increased net benefit without excess of major bleedings means a challenge. Clinical risk scores might help in the process of risk stratification and therapeutic decision. Subsequently, literature on risk assessment for antiplatelet drug responsiveness and different strategies will be discussed to identify patients who might benefit from personalized antiplatelet strategies.

The Residual Platelet Aggregation after Deployment of Intracoronary Stent (PREDICT) score.

BACKGROUND: Recent studies suggest a high interindividual variability of response to clopidogrel associated with adverse cardiovascular outcome. Different clinical factors are considered to influence a persistent residual platelet aggregation (RPA) despite conventional antiplatelet therapy. OBJECTIVES: To investigate clinical factors that affect RPA after 600-mg clopidogrel loading in a large unselected cohort of patients with symptomatic CAD. METHODS: The study population included a consecutive cohort of 1,092 patients treated with coronary stenting for stable angina and acute coronary syndromes (ACS). Residual platelet activity was assessed by ADP (20 micromol L(-1))-induced platelet aggregation >or= 6 h after LD. Eleven clinical factors were included in the primary analysis. RESULTS: In multivariate regression analysis increased RPA was significantly influenced by ACS, reduced LV-function, diabetes mellitus, renal failure (creatinine > 1.5 mg dL(-1)), and age > 65 years. In a factor-weighed model the risk for high RPA increased with higher score levels (OR for patients with a score of 1-3, 1.21, 95% CI 0.7-2.1; score 4-6, OR 2.0, 95% CI 1.17-3.5; P = 0.01; score 7-9, OR 3.3, 95% CI 1.8-6.0). During a 30-day follow-up the incidence of major adverse events was higher in patients with RPA in the upper tertile (4.8% vs. 2.5% in the 2nd and 1.5% in the 1st tertile; P < 0.05). CONCLUSIONS: The PREDICT score provides a good tool to estimate residual platelet activity after clopidogrel LD by easily available patient details. Additionally, we demonstrate its association with short-term outcome. Thus, patients with a high score may benefit from intensified antiplatelet therapy by improved platelet inhibition and risk reduction for thromboischemic events.

Ligand bridging mediates integrin alpha IIb beta 3 (platelet GPIIB-IIIA) dependent homotypic and heterotypic cell-cell interactions.

The aggregation of cells bearing recombinant integrin alpha IIb beta 3 (platelet GPIIb-IIIa) has been analyzed by two-color flow cytometry. As in normal platelets, aggregation requires functional alpha IIb beta 3, "activation" of alpha IIb beta 3, and fibrinogen (fg) binding to alpha IIb beta 3. Cellular aggregation required that both interacting cells express functional alpha IIb beta 3, because a binding defective mutant, alpha IIb beta 3 (D119----Y), failed to support interaction with wild type alpha IIb beta 3-bearing cells. In addition, cells bearing resting alpha IIb beta 3 were incorporated into aggregates formed by cells bearing a constitutively active mutant, alpha IIb beta 3 (beta 1-2), indicating that only one of the cells in an interacting pair must be activated. Finally, heterotypic interactions occurred between cells bearing activated alpha IIb beta 3 and cells bearing alpha V beta 3, a fg-binding integrin present on endothelial and tumor cells. Thus, ligand bridging between fg-binding integrins represents a mechanism of cell-cell interaction, cells bearing resting alpha IIb beta 3 (e.g., resting platelets) may be incorporated into aggregates formed by cells bearing activated alpha IIb beta 3, and alpha IIb beta 3 mediates heterotypic interactions with cells bearing other fg receptors.

Platelets, inflammation and atherosclerosis.

An expanding body of evidence continues to build on the role of platelets as initial actors in the development of atherosclerotic lesions. Platelets bind to leukocytes and endothelial cells, and initiate monocyte transformation into macrophages. Platelets internalize oxidized phospholipids and promote foam cell formation. Platelets also recruit progenitor cells to the scene that are able to differentiate into foam cells or endothelial cells depending on conditions. Platelets tip the scales in the initiation, development and total extent of atherosclerotic lesions.

beta(3)A-integrin downregulates the urokinase-type plasminogen activator receptor (u-PAR) through a PEA3/ets transcriptional silencing element in the u-PAR promoter.

Migration of cells requires interactions with the extracellular matrix mediated, in part, by integrins, proteases, and their receptors. Previous studies have shown that beta(3)-integrin interacts with the urokinase-type plasminogen activator receptor (u-PAR) at the cell surface. Since integrins mediate signaling into the cell, the current study was undertaken to determine if in addition beta(3)-integrin regulates u-PAR expression. Overexpression of beta(3)-integrin in CHO cells, which are avid expressers of the receptor, downregulated u-PAR protein and mRNA expression. The u-PAR promoter (-1,469 bp) that is normally constitutively active in CHO cells was downregulated by induced beta(3)-integrin expression. A region between -398 and -197 bp of the u-PAR promoter was critical for beta(3)-integrin-induced downregulation of u-PAR promoter activity. Deletion of the PEA3/ets motif at -248 bp substantially impaired the ability of beta(3)-integrin to downregulate the u-PAR promoter, suggesting that the PEA3/ets site acts as a silencing element. An expression vector encoding the transcription factor PEA3 caused inhibition of the wild-type but not the PEA3/ets-deleted u-PAR promoter. The PEA3/ets site bound nuclear factors from CHO cells specifically, but binding was enhanced when beta(3)-integrin was overexpressed. A PEA3 antibody inhibited DNA-protein complex formation, indicating the presence of PEA3. Downregulation of the u-PAR promoter was achieved by the beta(3)A-integrin isoform but not by other beta(3)-integrin isoforms and required the cytoplasmic membrane NITY(759) motif. Moreover, overexpression of the short but not the long isoform of the beta(3)-integrin adapter protein beta(3)-endonexin blocked u-PAR promoter activity through the PEA3/ets binding site. Thus, besides the physical interaction of beta(3)-integrin and u-PAR at the cell surface, beta(3) signaling is implicated in the regulation of u-PAR gene transcription, suggesting a mutual regulation of adhesion and proteolysis receptors.

[MR stress perfusion for the detection of flow-limiting stenoses in symptomatic patients with known coronary artery disease and history of stent implantation]. / MR-Stressperfusion zur Vorhersage flusslimitierender Stenosen bei symptomatischen Patienten mit bekannter KHK nach Stentimplantation.

PURPOSE: The aim of the present study was to determine the correlation of myocardial perfusion MR imaging (MPMRI) and coronary angiography for the detection of flow-limiting stenosis in symptomatic patients with known coronary artery disease and a history of intervention. MATERIALS AND METHODS: MPMRI was performed in 51 symptomatic patients (44 male, 64.7 +/- 9.5 years) with known coronary artery disease and a history of stent implantation (between 5 years and 2 weeks prior to MRI). Malperfused myocardial regions were correlated with findings of coronary angiography. A stenosis of > 70% was regarded as hemodynamically significant. RESULTS: In MPMRI 37 patients (73%) showed a stress induced perfusion deficit. In 35 of these patients coronary angiography revealed a stenosis of > 70 %. A total of 38 patients (75%) showed stenoses of > 70%. MPMRI yielded a sensitivity of 92% with a specificity of 85 %. The positive predictive value was 95 % and negative predictive value was 79%. The assignment of malperfused segments to coronary artery territories was carried out according to the standardized myocardial model of the American Heart Association (sensitivity/specificity was 59/85% for RCA, 79/81% for LAD and 54/68 % for LCX). CONCLUSION: MPMRI is a suitable non-invasive method for detecting flow-limiting coronary artery stenoses in patients with a history of stent implantation.

[Platelet activation in acute coronary syndrome and interventional therapy]. / Aktivierungszustand der Thrombozyten beim akuten Koronarsyndrom und in der interventionellen Therapie.

Platelets play a critical role in formation of coronary thrombosis. An enhanced systemic platelet activation plays a significant role in the acute coronary syndrome. Despite better interventional techniques and better concomitant pharmacological therapy, the degree of platelet activation contributes significantly to prognosis and postinterventional event rate. Residual platelet activation after intervention is often associated with an enhanced initial platelet activation prior interventional treatment. An effective antiplatelet therapy is of utmost importance for the acute therapy and for secondary prevention in patients undergoing coronary interventions or with acute coronary syndrome. The efficacy of the antithrombotic therapy determines the long term prognosis in these patients.

Point-of-care testing of cardiac autonomic function for risk assessment in patients with suspected acute coronary syndromes.

BACKGROUND: Impaired cardiac autonomic function has been linked to adverse outcomes in patients with acute coronary syndromes (ACS) but is not included in clinical risk models. This is the first study to investigate whether point-of-care testing of cardiac autonomic function by means of short-term deceleration capacity (DC) of heart rate improves risk assessment in patients with suspected ACS. METHODS: 1821 patients with suspected ACS were prospectively enrolled if they were older than 17 years and in sinus rhythm. Short-term DC was automatically assessed from monitor recordings at hospital admission. The Global Registry of Acute Coronary Events (GRACE) score was used as gold standard risk predictor. Primary endpoint was the composite of intrahospital and 30-day mortality. Secondary endpoint was 180-day mortality. RESULTS: Of the 1,821 patients with suspected ACS, 28 (1.5%) and 60 (3.3%) reached the primary and secondary endpoints, respectively. DC was a highly significant predictor of both endpoints, yielding areas under the curve (AUC) of 0.784 (95% CI 0.714-0.854) and 0.781 (0.727-0.832) (p < 0.001 for both), respectively. Implementing DC into the GRACE-risk model leads to a significant increase of the C-statistics from 0.788 (0.703-0.874) to 0.825 (0.750-0.900; p < 0.01 for difference) and from 0.814 (0.759-0.864) to 0.851 (0.808-0.889; p < 0.01 for difference) for the primary and secondary endpoints, respectively. Stratification by dichotomized DC was especially powerful in patients with GRACE score <140. CONCLUSIONS: In patients with suspected ACS, point-of-care testing of cardiac autonomic function by means of DC is feasible and improves risk assessment by the GRACE score. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov NCT01486589.

[The role of platelets for the pathophysiology of acute coronary syndromes]. / Die Rolle der Thrombozyten in der Pathophysiologie des akuten Koronarsyndroms.

Cardiovascular diseases, especially ischaemic heart disease, are actually the most frequent causes of death in the Western world and represent a central challenge for modern research and medicine. The pathophysiology of ischaemic heart disease is based upon the development and biological remodelling of atherosclerotic plaques. Mainly at late stages, but also in the early phase of atherosclerosis, rupture of the atherosclerotic plaque occurs and may lead to the clinical manifestation of acute coronary syndromes, including unstable angina pectoris, non-transmural or transmural myocardial infarction. Next to inflammation mediating cells like monocytes, platelets play an essential role at early and late stages of atherosclerotic disorders. This review summarizes the basic pathophysiological mechanism of platelet adhesion and secretion, the molecular steps involved in platelet mediated thrombus formation in the atherosclerotic microenvironment and the role of platelet accumulation in reperfused myocardium.

Photoaffinity labeling of integrin alpha IIb beta 3 (glycoprotein IIb-IIIa) on intact platelets with 8-azido-[gamma-32P]ATP.

The fibrinogen receptor GPIIb-IIIa plays a crucial role in platelet aggregation. Here we show that the adenine nucleotide, 8-azido-ATP, inhibits ADP-induced conformational change of the platelet fibrinogen receptor GPIIb-IIIa (integrin alpha IIb beta 3). Photoaffinity labeling of intact platelets with 8-azido-[gamma-32P]ATP exclusively modifies two plasma-membrane glycoproteins which are identical with both subunits of GPIIb-IIIa. The presence of adenine-nucleotide-binding sites on GPIIb-IIIa implies that the platelet fibrinogen receptor is directly regulated by extracellular adenine nucleotides.