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Background: Pregnancy-associated plasma protein A (PAPP-A) has been suggested as a candidate marker for the identification of unstable plaques in coronary arteries. We assessed the value of PAPP-A for predicting short-term cardiovascular events in a large cohort of patients presenting with cardiac chest pain. Methods: We included consecutive patients who presented to a teaching hospital in Germany with chest pain of cardiac origin confirmed by coronary angiography. We analyzed PAPP-A levels from serum samples drawn within 30 minutes after arrival in the emergency department or in the catheterization laboratory. Patients were followed for 90 days or until death for major adverse cardiovascular events, defined as the combined outcome of stent thrombosis, myocardial (re)infarction, ischemic stroke or cardiovascular-related death. Results: A total of 2568 patients (mean age [± standard deviation (SD)] 68 ±11 years; 74% male) presented with cardiac chest pain: 55% had stable angina and 45% had acute coronary syndrome. The PAPP-A levels ranged from 4 to 2154 mIU/L (median 14.0 mIU/L, interquartile range 9.3-25.2 mIU/L). Major adverse cardiovascular events occurred in 203 patients (7.9%). The mean PAPP-A level was higher among patients who had an event than among those who did not (62 ± 156 v. 21 ± 23 mIU/L, p < 0.001). In a multivariable analysis, PAPP-A remained a significant independent predictor of the primary outcome within 90 days (hazard ratio per 1 SD increase in PAPP-A level 1.96, 95% confidence interval 1.74-2.21). The optimal prognostic cutoff value was a PAPP-A level of 34.6 mIU/L. Interpretation: Higher levels of serum PAPP-A were independently associated with an increased short-term risk of cardiovascular events in patients presenting with cardiac chest pain. Further studies are required to validate the use of PAPP-A in routine clinical practice to predict future cardiovascular events., Coronary artery disease is the leading single cause of death in the Western world. (1) Patients with coronary artery disease cycle between asymptomatic phases, episodes of progressive angina and acute [...]

Atrial function provided incremental prognostic value for major adverse cardiovascular event prediction beyond established clinical and cardiac MRI parameters, including ventricular function and infarct size.

Recently, a novel left atrioventricular coupling index (LACI) has been introduced providing prognostic value to predict cardiovascular events beyond common risk factors in patients without cardiovascular disease. Since data on cardiovascular magnetic resonance (CMR)-derived LACI in patients following acute myocardial infarction (AMI) are scarce, we aimed to assess the diagnostic and prognostic implications of LACI in a large AMI patient cohort.

Zusammenfassung.Die Sarkoidose ist eine systemische Erkrankung des Bindegewebes mit Granulombildung. Die Mehrzahl der Patienten weist eine pulmonale Beteiligung auf. Eine kardiale Beteiligung ist in bis zu 25 % der Fälle zu beobachten, wobei die Erkrankung häufig auch asymptomatisch verläuft. Klinisch manifestiert sich die kardiale Sarkoidose in der Regel als (dilatative) Kardiomyopathie oder durch Herzrhythmusstörungen. Eine klare Diagnose mit histologischem Nachweis der Epitheloidzellgranulome im Herzen gelingt durch eine Endomyokardbiopsie, wobei diese invasive Untersuchung eine begrenzte Sensitivität aufweist. Neben der Elektrokardiographie und der Echokardiographie spielen insbesondere die kardiale Magnetresonanztomographie und die FDG-Positronenemissionstomographie (PET) eine zunehmende Rolle bei der Diagnose sowie Verlaufsbeurteilung der kardialen Sarkoidose. Die first line Therapie der kardialen Sarkoidose erfolgt in der Regel mittels Kortikosteroiden, im Einzelfall kann als second line Therapie oder bei Steroid-Nebenwirkungen eine Behandlung mittels Disease Modifying Antirheumatic Drugs (insbesondere Methotrexat) erwogen werden, bei schweren therapierefraktären Verläufen als third line auch eine Biologika Therapie (TNF-α Antikörper). Dieser Artikel gibt einen Überblick über aktuelle Empfehlungen und den Stellenwert neuerer diagnostischer und therapeutischer Verfahren.

Introduction:Recently a novel left atrioventricular coupling index (LACI) has been introduced providing prognostic value to predict cardiovascular events beyond common risk factors in patients without cardiovascular disease. Since data on cardiovascular magnetic resonance (CMR)-derived LACI in patients following acute myocardial infarction (AMI) are scare we aimed to assess and validate the diagnostic and prognostic implications of LACI in a large AMI patient cohort.Methods:1044 patients following AMI were included. After primary percutaneous coronary intervention CMR imaging and subsequent functional analyses were performed in median 3 days after AMI. LACI was defined by the ratio of the left atrial end-diastolic volume divided by the left ventricular end-diastolic volume. Major adverse cardiac events (MACE) including death, reinfarction or congestive heart failure within 12 months after the index event were defined as primary clinical endpoint.Results:LACI was significantly higher in patients with MACE compared to those without MACE (p < 0.001). Youden Index identified an optimal LACI cut-off of 34.7% to classify patients at high-risk (p < 0.001 on log-rank testing). Greater LACI was independently associated with MACE on univariate regression modeling (HR 8.1, 95% CI 3.4% - 14.9 %, p < 0.001) and maintained independence after adjusting for baseline confounders and left ventricular ejection fraction (LVEF) on multivariate regression analyses (HR 3.1 95% CI 1.0 - 9., p = 0.049). Furthermore, LACI assessment enabled further risk stratification in high-risk patients according to traditionally utilized reduced LVEF ≤ 35 % (p < 0.001 on log-rank testing).Conclusions:Atrial-ventricular interaction using CMR-derived LACI is a superior measure of outcome beyond sole LA or LV volume analyses and EF especially in high-risk patients following AMI.

Introduction:Feasibility of automated volume-derived cardiac functional evaluation has successfully been demonstrated using cardiovascular magnetic resonance (CMR) imaging. Notwithstanding, strain assessment has proven incremental value for cardiovascular risk stratification. Since introduction of deformation imaging to clinical practice has been complicated by time-consuming post-processing, we sought to investigate automation respectively.Methods:CMR data (n=1095 patients) from two prospectively recruited acute myocardial infarction (AMI) populations with ST-elevation (STEMI) (AIDA STEMI n=759) and non-STEMI (TATORT-NSTEMI n=336) were analysed fully automated and manually on conventional cine sequences. LV function assessment included global longitudinal, circumferential, and radial strains (GLS/GCS/GRS). Agreements were assessed between automated and manual strain assessments. The former were assessed for major adverse cardiac event (MACE) prediction within 12 months following AMI.Results:Manual and automated derived GLS showed the best and excellent agreement with an intraclass correlation coefficient (ICC) of 0.81. Agreement was good for GCS and poor for GRS. Amongst automated analyses, GLS (HR 1.12, 95% CI 1.08-1.16, p<0.001) and GCS (HR 1.07, 95% CI 1.05-1.10, p<0.001) best predicted MACE with similar diagnostic accuracy compared to manual analyses; area under the curve (AUC) for GLS (auto 0.691 vs. manual 0.693, p=0.801) and GCS (auto 0.668 vs. manual 0.686, p=0.425). Amongst automated functional analyses, GLS was the only independent predictor of MACE in multivariate analyses (HR 1.10, 95% CI 1.04-1.15, p<0.001).Conclusions:Considering high agreement of automated GLS and equally high accuracy for risk prediction compared to the reference standard of manual analyses, automation may improve efficiency and aid in clinical routine CMR examinations.

Plaque erosion leads to exposure of subendothelial collagen, which may be targeted by glycoprotein VI (GPVI). We aimed to detect plaque erosion using 64Cu-labeled GPVI-Fc (fragment crystallized).

Coronary artery disease remains a major hazard within the western world despite early revascularisation and advanced medical therapy strategies. One of its major substrates is platelet activation and thrombus formation, triggering acute events such as myocardial infarction and ischemic strokes. There are a variety of non-invasive imaging strategies being translated from bench to bedside into clinical practice that tackle specific aspects of the pathophysiology of thrombus formation. Some of those techniques are able to visualize native contrast differences between thrombus and surrounding tissue, others focus on the use of specific contrast agents targeting thrombotic components such as fibrin or activated platelets. Some of those techniques are still in the pre-clinical stage; others have already entered the clinical arena. The current review article will introduce different techniques and their stage of development on their way from bench to bedside with a specific focus on cardiac magnetic resonance imaging, that has evolved over the last years providing high quality information on anatomy, perfusion and myocardial tissue characteristics such as scarring in clinical practice. Finally, we will give an outlook on how this exciting field might evolve in the future.

Platelets and their activation have a pivotal role in the development of atherosclerotic diseases such as acute myocardial infarction (AMI), stroke and peripheral arterial occlusion. Biomarkers of platelet activation are making inroads into clinical studies and may serve as promising agents upstream to established downstream markers of myocardial necrosis such as troponin and creatin kinase. Targeting the degree of platelet activation assessed by the key collagen receptor of platelet activation, glycoprotein VI (GPVI), may have diagnostic and prognostic value for the assessement of high-risk groups of patients with symptomatic coronary artery disease and ischemic stroke and may be worthwhile to help to facilitate clinical decision-making and to rapidly initiate adequate therapy. The concert of platelet count, platelet activation, platelet aggregation and subsequent inflammation has had a significant impact on the clinical outcome in patients with atherosclerotic diseases. For a therapeutical approach to ameliorate prognosis, the use of antiplatelet treatment in particular in AMI patients with low response to clopidogrel has partly been overcome by novel second antiplatelet drugs on top of aspirin such as prasugrel and ticagrelor. Antiplatelet therapy may be adapted according to a GPVI-based platelet activity monitoring along with aggregometry of residual platelet aggregation. Other approaches using protease-activated receptor- 1 antagonists vorapaxar or atopaxar, which inhibit the platelet thrombin receptor, soluble GPVI called Revacept©, which blocks the collagen binding sites at the vascular lesion and anopheline saliva protein derived from the malaria vector mosquito, a platelet adhesion inhibitor independent of a GPVI mechanism, still wait for their breakthrough.

One of the key receptors involved in the prothrombotic stage of an acute coronary syndrome (ACS) is platelet glycoprotein VI (GPVI). This constitutively expressed collagen receptor is platelet-specific and has shown to be a useful biomarker tool for the early detection of atheroslerotic diseases such as ACS and ischemic stroke. In a multimarker panel of several biomarkers, platelet GPVI may contribute to risk stratification and prediction of clinical outcome in patients with symptomatic atherosclerotic diseases. Moreover, the soluble receptor of GPVI may also be an interesting and prospective target for molecular imaging to identify sites of vulnerable plaques as the results of preclinical studies suggest. Apart from the diagnostic use of platelet as well as soluble, plasmatic GPVI, therapeutical implications may be the blockade of collagen binding sides of GPVI, as platelet GPVI is not able to bind to collagen where the binding sides were already saturated with soluble GPVI. This therapeutic aspect could serve as a promising strategy for antithrombotic and antiatherosclerotic therapy in future.

Cytokines have an important role in both the initiation and perpetuation of viral myocarditis. Because a causative therapy of myocarditis is not yet well established and immunomodulation is a promising approach, the influence of interleukin (IL)-15, a proinflammatory cytokine, on the course of experimental myocarditis in Coxsackievirus B3 (CVB3)-infected mice was examined.

Cardiovascular risk factors are associated with coronary artery disease (CAD) and with cognitive dysfunction. However, the precise pathogenic mechanisms responsible for this association remain elusive. In the present study, CAD patients with cognitive impairment showed significantly higher platelet activation compared with CAD patients without cognitive impairment. In addition, we identified platelet activity to be a significant independent predictor for the severity of cognitive impairment in these patients. We discuss the link between platelet hyperactivity and dementia (including Alzheimer`s disease) based on the literature and our findings. We also discuss the potential mechanisms involved. This link may become a therapeutic option.

A 67-year-old woman who presented with acute chest pain is reported. Three days before admission, she suffered from a flu-like infection. Coronary angiography showed no coronary stenosis. Ventriculography showed moderately reduced left ventricular function characterized by the so-called ‘apical ballooning’. Endomyocardial biopsies and polymerase chain reaction analysis of the plasma revealed an acute infection with human herpesvirus 6 subtype A. Histological and immunohistochemical analyses revealed myocarditis with areas of interstitial macrophages and fibrosis. The present case report links, for the first time, myocarditis with a human herpesvirus 6 subtype A infection and the appearance of apical ballooning.

Background:Right ventricular (RV) function is a known predictor of adverse events in heart failure and following acute myocardial infarction (AMI). While right atrial (RA) involvement is well characterized in pulmonary arterial hypertension, its relative contributions to adverse events following AMI especially in patients with heart failure and congestion needs further evaluation.Methods:1235 MI patients underwent CMR after primary percutaneous coronary intervention (PCI) in 15 centers across Germany (n=795 with ST-elevation MI and 440 with non ST-elevation MI). Right atrial (RA) performance was evaluated using cardiac magnetic resonance myocardial feature tracking (CMR-FT) for the assessment of RA reservoir (total strain ?s), conduit (passive strain ?e), booster pump function (active strain ?a) and associated strain rates (SR) in a blinded core-laboratory. The primary clinical endpoint was the occurrence of major adverse cardiac events (MACE) 12 months post MI.Results:RA reservoir (?sp=0.061, SRs p=0.049) and conduit functions (?ep=0.006, SRe p=0.030) were impaired in patients with MACE as opposed to RA booster pump (?ap=0.579, SRa p=0.118) and RA volume index (p=0.866). RA conduit function was associated with clinical onset of heart failure and MACE independently of RV systolic function (multi-variable analysis HR 0.95, 95% CI 0.91-0.99, p=0.006) while RV systolic function was no independent prognosticator (HR 0.98, 95% CI 0.96-1.00, p=0.055). Furthermore, RA conduit strain identified low- and high-risk groups within patients with relatively preserved and reduced RV and LV systolic functions (p<0.019 on log rank testing).Conclusions:Right atrial impairment is a distinct feature and independent risk factor in patients following AMI and can be easily assessed using CMR-FT derived quantification of RA strain.

Background:Prognosis in acute myocardial infarction (AMI) depends on the amount of infarct related artery (IRA) subtended myocardium and associated damage but has not been described in great detail. Consequently, we sought to describe IRA associated pathophysiological consequences using cardiac magnetic resonance (CMR).Methods:1235 AMI patients (n=795 ST-elevation (STEMI) and 440 non-STEMI) underwent CMR following percutaneous coronary intervention. Blinded core-laboratory data were compared according to left anterior descending (LAD), left circumflex (LCx) and right coronary artery (RCA) regarding major adverse clinical events (MACE) within 12 months. Left ventricular (LV) global longitudinal/circumferential/radial (GLS/GCS/GRS) as well as left atrial (LA) total (?s), passive (?e) and active (?a) strains were determined using CMR-feature tracking. Tissue characterisation included infarct size (IS) and microvascular obstruction.Results:LAD and LCx were associated with higher mortality compared to RCA lesions (4.6% and 4.4% vs 1.6%). LAD lesions showed largest IS (16.8%), largest ventricular (LV ejection fraction (EF) 47.4%, GLS -13.2%, GCS -20.8%) and atrial (?s 20.2%) impairment. There was less impairment in LCx (IS 11.8%, LVEF 50.8%, GLS -17.4%, GCS -25.0%, ?s 20.7%) followed by RCA lesions (IS 11.3%, LVEF 50.8%, GLS -19.1%, GCS -26.6%, ?s 21.7%). In AUC analyses ?s (LAD, RCA) and GLS (LCx) best predicted MACE (AUC>0.69). Multivariate analyses identified ?s (p=0.017) in LAD and GLS (p=0.034) in LCx infarcts as independent predictors of MACE.Conclusions:CMR allows IRA specific phenotyping and characterisation of morphologic and functional changes. These alterations carry infarct specific prognostic implications and may represent novel diagnostic and therapeutic targets following AMI.