Search

Diagnosis of non-ST-segment elevation acute coronary syndromes (NSTEACS) is based on 3 cornerstones: clinical presentation, 12-lead electrocardiogram, and cardiac troponin measurement. Advances in the development of high-sensitivity cardiac troponin (hs-cTn) assays have substantially improved the detection of cardiomyocyte injury in a shorter time period, and hs-cTn has consequently been established as the gold-standard biomarker for the assessment of patients with suspected NSTEACS. The implementation of these assays in clinical practice allows a faster "rule-out", especially among low-risk patients, as well as a safer and more rapid "rule-in", with its therapeutic consequences. Current guidelines for the diagnosis of NSTEACS recommend the use of hs-cTn applied in rapid diagnostic algorithms based on serial hs-cTn sampling within the first few hours. The current work provides an overview of the use of hs-cTn for the early detection of NSTEACS., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Beyond the influence of lifestyle-related risk factors for myocardial infarction (MI), the mechanisms of genetic predispositions for MI remain unclear. We sought to identify and characterize differentially expressed genes in early-onset MI in a translational approach. In an observational case−control study, transcriptomes from 112 early-onset MI individuals showed upregulated G protein-coupled receptor 15 (GPR15) expression in peripheral blood mononuclear cells compared to controls (fold change = 1.4, p = 1.87 × 10−7). GPR15 expression correlated with intima-media thickness (β = 0.8498, p = 0.111), C-reactive protein (β = 0.2238, p = 0.0052), ejection fraction (β = −0.9991, p = 0.0281) and smoking (β = 0.7259, p = 2.79 × 10−10). The relation between smoking and MI was diminished after the inclusion of GPR15 expression as mediator in mediation analysis (from 1.27 (p = 1.9 × 10−5) to 0.46 (p = 0.21)). The DNA methylation of two GPR15 sites was 1%/5% lower in early-onset MI individuals versus controls (p = 2.37 × 10−6/p = 0.0123), with site CpG3.98251219 significantly predicting risk for incident MI (hazard ratio = 0.992, p = 0.0177). The nucleotide polymorphism rs2230344 (C/T) within GPR15 was associated with early-onset MI (odds ratio = 3.61, p = 0.044). Experimental validation showed 6.3-fold increased Gpr15 expression in an ischemic mouse model (p < 0.05) and 4-fold increased Gpr15 expression in cardiomyocytes under ischemic stress (p < 0.001). After the induction of MI, Gpr15gfp/gfp mice showed lower survival (p = 0.042) and deregulated gene expression for response to hypoxia and signaling pathways. Using a translational approach, our data provide evidence that GPR15 is linked to cardiovascular diseases, mediating the adverse effects of smoking.

In humans and mice, L-arginine:glycine amidinotransferase (AGAT) and its metabolites homoarginine (hArg) and creatine have been linked to cardiovascular disease (CVD), specifically myocardial infarction (MI) and heart failure (HF). The underlying molecular and regulatory mechanisms, however, remain unclear. To identify potential pathways of cardiac AGAT metabolism, we sequenced microRNA (miRNA) in left ventricles of wild-type (wt) compared to AGAT-deficient (AGAT -/- ) mice. Using literature search and validation by qPCR, we identified eight significantly regulated miRNAs in AGAT -/- mice linked to atherosclerosis, MI and HF: miR-30b, miR-31, miR-130a, miR-135a, miR-148a, miR-204, miR-298, and let-7i. Analysis of Gene Expression Omnibus (GEO) data confirmed deregulation of these miRNAs in mouse models of MI and HF. Quantification of miRNA expression by qPCR in AGAT -/- mice supplemented with creatine or hArg revealed that miR-30b, miR-31, miR-130a, miR-148a, and miR-204 were regulated by creatine, while miR-135a and miR-298 showed a trend of regulation by hArg. Finally, bioinformatics-based target prediction showed that numerous AGAT-dependent genes previously linked to CVD are likely to be regulated by the identified miRNAs. Taken together, AGAT deficiency and hArg/creatine supplementation are associated with cardiac miRNA expression which may influence cardiac (dys)function and CVD., (© 2022. The Author(s).)

Aims: To directly compare the diagnostic accuracy of high-sensitivity cardiac troponin (hs-cTn) T vs. hs-cTnI in the early non-invasive differentiation of Type 1 myocardial infarction (T1MI) due to plaque rupture and atherothrombosis from Type 2 myocardial infarction (T2MI) due to supply-demand mismatch., Methods and Results: In a prospective multicentre diagnostic study, two independent cardiologists centrally adjudicated the final diagnosis of T1MI vs. T2MI according to the fourth universal definition of myocardial infarction (MI), using all available clinical information including cardiac imaging in patients presenting with acute chest pain. Diagnostic accuracy was quantified by the area under the receiver operating characteristics curve (AUC). The most extensively validated hs-cTnT-Elecsys and hs-cTnI-Architect assays were measured at presentation, 1 h, and 2 h. Among 5887 patients, 1106 (19%) had a final diagnosis of MI, including 860 (78%) T1MI and 246 (22%) T2MI. The AUC of hs-cTnT-Elecsys to differentiate T1MI from T2MI was moderate and comparable to that provided by hs-cTnI-Architect: hs-cTnT-Elecsys AUC-presentation 0.67 [95% confidence interval (CI) 0.64-0.71], AUC-1 h 0.70 (95% CI 0.66-0.74), and AUC-2 h 0.71 (95% CI 0.66-0.75) vs. hs-cTnI-Architect AUC-presentation 0.71 (95% CI 0.67-0.74), AUC-1 h 0.72 (95% CI 0.68-0.76), and AUC-2 h 0.74 (95% CI 0.69-0.78), all P = not significant (NS). Similarly, the AUC of absolute changes was moderate and comparable for hs-cTnT-Elecsys and hs-cTnI-Architect (all P = NS). Cut-off concentrations achieving at least 90% specificity for the differentiation of T1MI vs. T2MI were >114 ng/L for hs-cTnT-Elecsys [odds ratio (OR) 4.2, 95% CI 2.7-6.6] and >371 ng/L for hs-cTnI-Architect (OR 4.0, 95% CI 2.6-6.2)., Conclusion: hs-cTnT-Elecsys and hs-cTnI-Architect provided comparable, albeit only moderate, diagnostic accuracy for the early differentiation of T1MI vs. T2MI., Clinical Trial Registration: ClinicalTrials.gov number, NCT00470587, https://clinicaltrials.gov/ct2/show/NCT00470587., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

The chemokine CXCL12 plays a fundamental role in cardiovascular development, cell trafficking, and myocardial repair. Human genome-wide association studies even have identified novel loci downstream of the CXCL12 gene locus associated with coronary artery disease and myocardial infarction. Nevertheless, cell and tissue specific effects of CXCL12 are barely understood. Since we detected high expression of CXCL12 in smooth muscle (SM) cells, we generated a SM22-alpha-Cre driven mouse model to ablate CXCL12 (SM-CXCL12 -/- ). SM-CXCL12 -/- mice revealed high embryonic lethality (50%) with developmental defects, including aberrant topology of coronary arteries. Postnatally, SM-CXCL12 -/- mice developed severe cardiac hypertrophy associated with fibrosis, apoptotic cell death, impaired heart function, and severe coronary vascular defects characterized by thinned and dilated arteries. Transcriptome analyses showed specific upregulation of pathways associated with hypertrophic cardiomyopathy, collagen protein network, heart-related proteoglycans, and downregulation of the M2 macrophage modulators. CXCL12 mutants showed endothelial downregulation of the CXCL12 co-receptor CXCR7. Treatment of SM-CXCL12 -/- mice with the CXCR7 agonist TC14012 attenuated cardiac hypertrophy associated with increased pERK signaling. Our data suggest a critical role of smooth muscle-specific CXCL12 in arterial development, vessel maturation, and cardiac hypertrophy. Pharmacological stimulation of CXCR7 might be a promising target to attenuate adverse hypertrophic remodeling.

Purpose: The Fourth Universal Definition of Myocardial Infarction (MI) has highlighted the different pathophysiological mechanisms that may lead to ischaemic and non-ischaemic myocardial injury and has emphasised that the diagnosis of myocardial infarction requires the presence of acute myocardial ischaemia in the setting of acute myocardial injury. This case based review intends to illustrate basic principles on how to apply this new, revised definition in clinical practice. Methods and Results: The distinction between different types of MIs (type 1 or type 2) and the delineation of MI from acute non-ischaemic myocardial injury may be challenging in individual patients, which is illustrated by presenting and discussing real-life routine cases. Conclusions: Type 1 MI is a consequence of coronary plaque rupture or erosion with intracoronary thrombus formation that is usually apparent on coronary angiography. Plausible triggering mechanisms causing myocardial oxygen supply/demand mismatch must be identified for the diagnosis of type 2 MI and its treatment should focus initially on management of the underlying disease attributable to acute myocardial ischaemia.

Aims: Identifying factors associated with worse outcome following carotid endarterectomy (CEA) is important to improve prevention of major adverse cardiovascular and cerebrovascular events (MACCE), yet rarely used for registries. We intended to identify predictors of MACCE following CEA as recently analysed for stenting., Methods and Results: Patients undergoing CEA at 2 centers over 13 years were entered into a database. Baseline clinical characteristics, procedural factors and a panel of clinical and lesion-related high-risk features (SHR) and exclusion criteria (SE), empirically compiled for stratification in the SAPPHIRE trial, were differentially analysed using Cox regressions. The analysis included 748 operations; 262 (35%) asymptomatic, 208 (28%) with previous strokes, and 278 (37%) with transient ischemic attacks (TIA). The overall 30-day MACCE rate was 6.7%, 5.0% in asymptomatic and 7.6% in symptomatic patients. Previous MI (HR 2.045, p = 0.022), diabetes (HR 2.111, p = 0.011) and symptomatic patients (HR 2.045, p = 0.044) were independently associated with MACCE. SE patients (n = 81) had a MACCE rate of 13.6%; the MACCE rate of the remainder dropped to 5.8% (4.7% in asymptomatic and 6.5% in symptomatic patients). Hazard ratio for SHR patients was 2.069 (CI 1.087-3.941) and 2.389 for SE (CI 1.223-4.666), each compared to all patients with lower risk and adjusted for symptomatic status. Among SHR and SE criteria NYHA 3-4, contralateral occlusions and intraluminal thrombus were significant determinants and MI < 4 weeks before CEA showed a strong trend (p = 0.05)., Conclusion: Patients identified by SHR and SE criteria, prior MI and diabetes warrant increased attention to prevent MACCE following CEA.

L-arginine:glycine amidinotransferase (AGAT) and its metabolites creatine and homoarginine (HA) have been linked to cardiovascular pathologies in both human and murine studies, but the underlying molecular mechanisms are poorly understood. Here, we report the first analysis of heart transcriptome variation using microarrays in an AGAT-deficient (AGAT -/- ) mouse model to evaluate AGAT-, creatine- and HA-dependent gene regulation. Our data revealed significant differences of gene expression between AGAT -/- and wild-type (WT) mice, affecting cardiac energy metabolism (Fbp2, Ucp2), cardiac hypertrophy and fibrosis (Nppa, Ctgf), immune response (Fgl2), and the conduction system of the heart (Dsc2, Ehd4, Hcn2, Hcn4, Scn4a, Scn4b). All of these genes being expressed on WT level in creatine-supplemented mice. Using in silico analysis based on the GEO database we found that most of these candidate genes (Ctgf, Dsc2, Fbp2, Fgl2, Hcn2, Nppa)  revealed significant alterations in a WT mouse model of myocardial infarction underlining a pathophysiological relationship between AGAT metabolism and cardiovascular disease.

Aims: Inflammation is a key driver of atherosclerosis and myocardial infarction (MI), and beyond proteins and microRNAs (miRs), long noncoding RNAs (lncRNAs) have been implicated in inflammation control. To obtain further information on the possible role of lncRNAs in the context of atherosclerosis, we obtained comprehensive transcriptome maps of circulating immune cells (peripheral blood mononuclear cells, PBMCs) of early onset MI patients. One lncRNA significantly suppressed in post-MI patients was further investigated in a murine knockout model., Methods and Results: Individual RNA-sequencing (RNA-seq) was conducted on PBMCs from 28 post-MI patients with a history of MI at age ≤50 years and stable disease ≥3 months before study participation, and from 31 healthy individuals without manifest cardiovascular disease or family history of MI as controls. RNA-seq revealed deregulated protein-coding transcripts and lncRNAs in post-MI PBMCs, among which nuclear enriched abundant transcript (NEAT1) was the most highly expressed lncRNA, and the only one significantly suppressed in patients. Multivariate statistical analysis of validation cohorts of 106 post-MI patients and 85 controls indicated that the PBMC NEAT1 levels were influenced (P = 0.001) by post-MI status independent of statin intake, left ventricular ejection fraction, low-density lipoprotein or high-density lipoprotein cholesterol, or age. We investigated NEAT1-/- mice as a model of NEAT1 deficiency to evaluate if NEAT1 depletion may directly and causally alter immune regulation. RNA-seq of NEAT1-/- splenocytes identified disturbed expression and regulation of chemokines/receptors, innate immunity genes, tumour necrosis factor (TNF) and caspases, and increased production of reactive oxygen species (ROS) under baseline conditions. NEAT1-/- spleen displayed anomalous Treg and TH cell differentiation. NEAT1-/- bone marrow-derived macrophages (BMDMs) displayed altered transcriptomes with disturbed chemokine/chemokine receptor expression, increased baseline phagocytosis (P < 0.0001), and attenuated proliferation (P = 0.0013). NEAT1-/- BMDMs responded to LPS with increased (P < 0.0001) ROS production and disturbed phagocytic activity (P = 0.0318). Monocyte-macrophage differentiation was deregulated in NEAT1-/- bone marrow and blood. NEAT1-/- mice displayed aortic wall CD68+ cell infiltration, and there was evidence of myocardial inflammation which could lead to severe and potentially life-threatening structural damage in some of these animals., Conclusion: The study indicates distinctive alterations of lncRNA expression in post-MI patient PBMCs. Regarding the monocyte-enriched NEAT1 suppressed in post-MI patients, the data from NEAT1-/- mice identify NEAT1 as a novel lncRNA-type immunoregulator affecting monocyte-macrophage functions and T cell differentiation. NEAT1 is part of a molecular circuit also involving several chemokines and interleukins persistently deregulated post-MI. Individual profiling of this circuit may contribute to identify high-risk patients likely to benefit from immunomodulatory therapies. It also appears reasonable to look for new therapeutic targets within this circuit., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Biomarkers are noninvasive, inexpensive, highly reproducible tools that allow clinicians to quantify pathophysiological processes relevant to a specific disease. Although the concept of biomarker-guided precision medicine is still in its infancy once a specific cardiovascular diagnosis is established, biomarker guidance has become the standard of care in the early diagnosis of acute cardiovascular disease in patients presenting to the emergency department with common symptoms such as acute chest pain or acute dyspnoea. This review highlights recent advances and remaining uncertainties regarding the use of the most relevant cardiovascular biomarkers, namely high-sensitivity cardiac troponin and natriuretic peptides in established indications such as the early diagnosis of acute myocardial infarction and heart failure. In addition, we address emerging indications such as the screening for perioperative myocardial infarction.

The 2015 non-ST-segment elevation acute coronary syndromes guidelines of the European Society of Cardiology have been published 4 years after the previous edition. A new algorithm was presented for the diagnosis of acute myocardial infarction based on the measurement of high-sensitivity cardiac troponin levels at presentation and at 1 hour, including a guidance on the duration of cardiac rhythm monitoring. New recommendations address the management of antiplatelet therapy regarding duration of dual antiplatelet therapy, in patients requiring long-term anticoagulation or undergoing urgent coronary artery bypass surgery as well as of acute bleeding events related to antithrombotics. The guidelines give a clear recommendation in favor of the radial access over the femoral one for coronary angiography and percutaneous revascularization.

Cardiovascular complications, particularly perioperative myocardial infarction/injury, seem to be major contributors to mortality after noncardiac surgery. With surgical procedures being very frequent (900 000/year in Switzerland), perioperative myocardial injury is common in everyday clinical practice. Over 80% of patients experiencing perioperative myocardial injury do not report symptoms. Therefore perioperative myocardial injury remains undiagnosed and untreated. Moreover, its silent presentation results in limited awareness among both clinicians and the public. Despite being largely asymptomatic, perioperative myocardial injury increases 30-day mortality nearly 10-fold. This review aims to increase the awareness of perioperative myocardial injury/infarction and give an overview of the emerging evidence, including pathophysiology, clinical presentation, prevention, and potential future treatments.

Background: The release pattern of copeptin during the initial 36 h of spontaneous acute myocardial infarction (AMI) has received relatively little investigation but may provide important information on optimal timing of diagnostic measurements., Methods: We investigated the release pattern of copeptin and cardiac troponin T in patients with suspected acute coronary syndrome (ACS). Blood samples were collected in the ambulance, at admission, and after 2, 4, 6, and 12-36 h. Copeptin and high-sensitivity cardiac troponin T (hs-cTnT) were measured in heparin plasma samples., Results: Of 93 patients studied, 37 (39.8%) had ST-elevation myocardial infarction (STEMI), 20 (21.5%) non-STEMI, 20 (21.5%) unstable angina pectoris (UAP), and 16 (17.2%) non-ACS diagnoses. Peak copeptin concentrations were detected during ambulance transport for NSTEMI patients [median 94.0 pmol/L, interquartile range (IQR) 53.3-302.1 pmol/L] and at admission for patients with STEMI (70.0 pmol/L, 22.0-144.8 pmol/L). In patients with AMI, copeptin decreased significantly over time (P < 0.0001). This was true for patients with STEMI (P = 0.005) and non-STEMI (P = 0.021). The diagnostic performance during ambulance transport was similar for hs-cTnT (area under the ROC curve 0.75, 95% CI 0.62-0.88) and copeptin (0.81, 0.69-0.92). In early presenters (n = 52), no patient with AMI was initially (in ambulance or at admission) negative for copeptin, resulting in an area under the ROC curve of 0.963 for ambulance values and a negative predictive value of 100%. In late presenters, the negative predictive value of copeptin was 50% in ambulance and at admission., Conclusions: Our analysis is the first to show a consistent early increase in copeptin at first medical contact in the ambulance and a decrease to routine values within 12-36 h in patients presenting early with spontaneous AMI., (© 2015 American Association for Clinical Chemistry.)

In the Providing Regional Observations to Study Predictors of Events in the Coronary Tree (PROSPECT) study, plaque burden, plaque composition, and minimal luminal area were associated with an increased risk of adverse cardiovascular events arising from untreated atherosclerotic lesions (vulnerable plaques) in patients with acute coronary syndromes (ACS). We sought to evaluate the utility of biomarker profiling and clinical risk factors to predict 3-year all-cause and nonculprit lesion-related major adverse cardiac events (MACEs). Of 697 patients who underwent successful percutaneous coronary intervention (PCI) for ACS, an array of 28 baseline biomarkers was analyzed. Median follow-up was 3.4 years. Beta2-microglobulin displayed the strongest predictive power of all variables assessed for all-cause and nonculprit lesion-related MACE. In a classification and regression tree analysis, patients with beta2-microglobulin >1.92 mg/L had an estimated 28.7% 3-year incidence of all-cause MACE; C-peptide <1.32 ng/ml was associated with a further increase in MACE to 51.2%. In a classification and regression tree analysis for untreated nonculprit lesion-related MACE, beta2-microglobulin >1.92 mg/L identified a cohort with a 3-year rate of 18.5%, and C-peptide <2.22 ng/ml was associated with a further increase to 25.5%. By multivariable analysis, beta2-microglobulin was the strongest predictor of all-cause and nonculprit MACE during follow-up. High-density lipoprotein (HDL), transferrin, and history of angina pectoris were also independent predictors of all-cause MACE, and HDL was an independent predictor of nonculprit MACE. In conclusion, in the PROSPECT study, beta2-microglobulin strongly predicted all-cause and nonculprit lesion-related MACE within 3 years after PCI in ACS. C-peptide and HDL provided further risk stratification to identify angiographically mild nonculprit lesions prone to future MACE., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Combined testing of copeptin and troponin at presentation to the emergency department (ED) has been shown to possess a high negative predictive value (NPV) for ruling out acute myocardial infarction (AMI) in patients with suspected acute coronary syndrome., Purpose: The aim of this study was to evaluate the diagnostic performance of the combination of copeptin and troponin for the exclusion of AMI in emergency patients with acute cardiac chief complaints and to assess diagnoses and outcome in copeptin-positive patients., Methods: In this prospective study, 537 consecutive patients with cardiac chief complaints were recruited from the ED. Blood samples were collected at admission., Results: The overall incidence of AMI in the study sample was 14.2% (n=76). In troponin-negative patients, copeptin showed a sensitivity of 76.9% (95% confidence interval (CI) 46.2-95.0), a specificity of 64.2% (95% CI 59.2-69.0), a positive predictive value (PPV) of 6.9% (95% CI 3.3-12.2) and an NPV of 98.8% (95% CI 96.5-99.8). The highest copeptin values were observed in patients with chronic heart failure, followed by ST-elevation myocardial infarction (STEMI), acute heart failure (AHF), pneumonia and non-STEMI (NSTEMI). A copeptin-value of above 10 pmol/l increased the risk of death within three months significantly (hazard ratio (HR)=5.42 (1.81-16.21) p=0.003)., Conclusion: Copeptin seems to be a promising biomarker for the initial evaluation of emergency patients with cardiac chief complaints. The study adds to the evidence that a single copeptin and troponin test at admission achieves a high NPV for ruling-out NSTEMI early in low-to-intermediate risk patients and thus--in combination with the clinical evaluation--seems to be of considerable relevance in emergency medicine., (© The European Society of Cardiology 2014.)

Background: High-sensitivity cardiac troponin (hs-cTn) may allow an earlier diagnosis of acute myocardial infarction (AMI)., Methods: We prospectively enrolled 1148 (derivation cohort) and 517 (external validation cohort) unselected patients presenting with suspected AMI to the emergency department. Final diagnosis was adjudicated by 2 independent cardiologists. Hs-cTnT was measured at presentation and after 2 hours. A diagnostic algorithm incorporating hs-cTnT values at presentation and absolute changes within the first 2 hours was derived., Results: AMI was the final diagnosis in 16% of patients in the derivation and 9.1% in the validation cohort. The 2-hour algorithm developed in the derivation cohort classified 60% of patients as "rule-out," 16% as "rule-in," and 24% in the "observational-zone." Resulting sensitivity and negative predictive value (NPV) were 99.5% and 99.9%, respectively, for rule-out, and specificity and positive predictive value (PPV) were 96% and 78%, respectively, for rule-in. Applying the 2-hour triage algorithm in the external validation cohort, 78% of patients could be classified as "rule-out," 8% as "rule-in," and 14% in the "observational-zone." Resulting sensitivity and NPV were 96% and 99.5%, respectively, for rule-out, and specificity and PPV were 99% and 85%, respectively, for rule-in. Cumulative 30-day survival rates were 100%, 98.9%, and 95.2% (P < .001), and 100%, 100%, and 95% (P < .001) in patients classified as "rule-out," "observational-zone," and "rule-in" in the 2 cohorts, respectively., Conclusions: A simple algorithm incorporating hs-cTnT baseline values and absolute changes over 2 hours allowed a triage toward safe rule-out, or accurate rule-in, of AMI in the vast majority of patients, with only 20% requiring more prolonged monitoring and serial blood sampling., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Current guidelines recommend troponin as the preferred biomarker to diagnose acute myocardial infarction (AMI) irrespective of the patient's sex. Recent reports have shown that sex-specific cut-offs should be considered but studies investigating sex-differences in the diagnostic accuracy of cardiac troponins are sparse., Objective: To evaluate whether the diagnostic performance of cardiac troponin at admission (cTn) under routine conditions is influenced by patient's sex., Methods: Between 15th of February 2009 and 15th of February 2010, women (n=1648) and men (n=2305) who presented to the emergency department with chest pain (n=3954) were enrolled. The diagnostic performance of the routine, contemporary sensitive cTn assays (TnI; Stratus® CS, Siemens and TnT; Roche Diagnostics) at baseline for the diagnosis of non-ST-elevation myocardial infarction (NSTEMI) was analyzed., Results: NSTEMI was diagnosed in 7.3% (n=287) of all patients. Men were more likely to be diagnosed with NSTEMI (8.8%; n=202) as compared to women (5.2%; n=85; p<0.001). Sensitivity was 56.1% (95% CI: 44.7-67.0%) in women and 70.1% (95% CI: 63.1-76.4%) in men. Specificity was 96.8% (95% CI: 95.6-97.7%) in women and 94.5% (95% CI: 93.3-95.6%) in men. This resulted in a lower positive predictive value (PPV) for women (53.5%; 95% CI: 42.4-64.3) as compared to men (60.8%; 95% CI: 54.1-67.2) and a slightly higher negative predictive value (NPV) for women: 97.1% (95% CI: 96.0-97.9) vs. 96.3% (95% CI: 95.2-97.2) in men., Conclusions: The findings of this study underline that the performance of cTn for the diagnosis of NSTEMI depends on a patient's sex, with a lower sensitivity and NPV in women. The definition and implementation of sex-specific cut-off values for cTn into clinical routine seems to be highly recommendable., (Copyright © 2015. Published by Elsevier Ireland Ltd.)

Aims: Detailed data on patients admitted for acute myocardial infarction (AMI) on a European-wide basis are lacking. The Euro Heart Survey 2009 Snapshot was designed to assess characteristics, management, and hospital outcomes of AMI patients throughout European Society of Cardiology (ESC) member countries in a contemporary 'real-world' setting, using a methodology designed to improve the representativeness of the survey., Methods: Member countries of the ESC were invited to participate in a 1-week survey of all patients admitted for documented AMI in December 2009. Data on baseline characteristics, type of AMI, management, and complications were recorded using a dedicated electronic form. In addition, we used data collected during the same time period in national registries in Sweden, England, and Wales. Data were centralized at the European Heart House., Results: Overall, 4236 patients (mean age 66±13 years; 31% women) were included in the study in 47 countries. Sixty per cent of patients had ST-segment elevation myocardial infarction, with 50% having primary percutaneous coronary intervention and 21% fibrinolysis. Aspirin and thienopyridines were used in >90%. Unfractionated and low-molecular-weight heparins were the most commonly used anticoagulants. Statins, beta-blockers, and angiotensin-converting enzyme inhibitors were used in >80% of the patients. In-hospital mortality was 6.2%. Regional differences were observed, both in terms of population characteristics, management, and outcomes., Conclusions: In-hospital mortality of patients admitted for AMI in Europe is low. Although regional variations exist in their presentation and management, differences are limited and have only moderate impact on early outcomes.

Aims: The calcium sensitizer levosimendan may counteract stunning after reperfusion of ischaemic myocardium, but no randomized placebo-controlled trials exist regarding its use in PCI-treated ST-segment elevation infarction (STEMI). We evaluated the efficacy and safety of levosimendan in patients with a primary PCI-treated STEMI complicated by symptomatic heart failure (HF)., Methods and Results: A total of 61 patients developing clinical signs of HF within 48 h after a primary PCI-treated STEMI (including cardiogenic shock) were randomized double-blind to a 25 h infusion of levosimendan or placebo. The primary endpoint was change in wall motion score index (WMSI) from baseline to day 5 measured by echocardiography. There was a significantly larger improvement in WMSI from baseline to day 5 in the levosimendan group compared with placebo (from 1.94 ± 0.20 to 1.66 ± 0.31 vs. 1.99 ± 0.22 to 1.83 ± 0.26, respectively, P = 0.031). There were significantly more episodes of hypotension during study drug infusion in the levosimendan group (67% vs. 36%, P = 0.029), but no significant difference in blood pressure at the end of infusion or in use of vasopressors. No significant between-group differences in changes in NT-proBNP levels, clinical composite score, frequency of atrial fibrillation or ventricular arrhythmia, infarct size at 6 weeks, or new clinical events up to 6 months were found. One and four patients died in the levosimendan and placebo group, respectively., Conclusions: Levosimendan treatment improved contractility in post-ischaemic myocardium in patients with PCI-treated STEMI complicated by HF. The treatment was well tolerated, without any increase in arrhythmias.

Context: Acute myocardial infarction (AMI) related to percutaneous coronary intervention (PCI) (MI type 4a) occurs in up to 26% of elective patients., Objective: To evaluate if sFLT-1 helps to predict MI type 4a in troponin negative patients with elective PCI., Materials and Methods: We enrolled 135 patients, 106 had a PCI. sFLT-1 levels were assessed at five time points before and after PCI., Results: MI type 4a occurred in 22.1% of patients. sFLT-1 levels at admission above 251 pg/mL indicated a significant relative risk for MI type 4a of 2.83., Conclusion and Discussion: Increased sFLT-1 levels at baseline might indicate unstable atherosclerosis and risk for microembolization and thus be predictive of MI type 4a.

Background: Both Type 2 diabetes and cardiovascular disease have been associated with enhanced coagulation and suppressed fibrinolysis., Objectives: To investigate a possible relationship between selected hemostatic variables and abnormal glucose regulation (AGR) in patients with acute ST-elevation myocardial infarction (STEMI) without known diabetes and to study changes in selected hemostatic variables from baseline to follow-up in STEMI patients with or without AGR., Methods: Plasminogen activator inhibitor-1 (PAI-1) activity, tissue plasminogen activator (t-PA) antigen, prothrombin fragment 1+2 (F(1+2)) and von Willebrand factor (vWF) were measured in fasting blood samples from 199 STEMI patients 16.5 h (median time) after admission and 3 months later. All patients were classified into normal glucose regulation (NGR) or AGR based on an oral glucose tolerance test at follow-up, according to the WHO criteria., Results: High PAI-1 activity (≥ 75th percentile) measured in-hospital was associated with AGR (n = 49) with an adjusted odds ratio of 2.2 (95% confidence interval, 1.1, 4.4). In addition, high levels of t-PA antigen (≥ 75th percentile) were associated with AGR (adjusted odds ratio, 3.5; 95% confidence inteval, 1.5, 8.2), but only in men. Changes in the levels of F(1+2) were significantly more pronounced in patients with AGR compared with NGR (adjusted P = 0.04)., Conclusion: Elevated levels of PAI-1 activity and t-PA antigen measured in-hospital in STEMI patients were associated with AGR classified at 3-month follow-up. Additionally, changes in the levels of F(1+2) were more pronounced in patients with AGR compared with NGR. The data suggest an enhanced prothrombotic state after an acute STEMI in patients with AGR without known diabetes., (© 2011 International Society on Thrombosis and Haemostasis.)

The universal definition of myocardial infarction has proved how important the role of biomarkers in the assessment of acute coronary syndrome (ACS) has become. As a result, management of patients with ACS today is more specific and personalized than ever, but there is still a lot of room for improvement. Unmet needs for a faster and more specific rule-in and rule-out of myocardial infarction, for a pronounced risk assessment allowing for standardized guidelines on personalized therapy and for an effective monitoring of our therapeutic efforts to guarantee an optimal risk-benefit turnout still require intensive biomarker research and clinical validation. This review addresses a set of cardiovascular biomarkers with different pathophysiological backgrounds and discusses their diagnostic, prognostic and therapeutic value in the setting of ACS and percutaneous coronary intervention (PCI). The article provides a review of the current knowledge and literature on biomarkers in ACS and PCI, discussing currently used biomarkers like cardiac troponin (cTN), high sensitive cardiac troponin (hscTn), natriuretic peptides (NPs) as well as promising future biomarkers like copeptin, choline and lipoprotein-associated phospholipase A2 (LP-PLA2). The review concentrates on the clinical application of these markers, evaluating not only their diagnostic and prognostic value but also their integrability into routine practice. There are currently a number of new biomarkers and new biomarker assays under investigation which give hope for a much improved diagnostic and risk stratification process. Large diagnostic clinical trials are still needed to evaluate their impact on ACS patient management and subsequent PCI in clinical practice.

Cardiac troponin I and T (cTn) are structural proteins unique to the heart. Detection of cTn in peripheral blood indicates cardiomyocyte necrosis. As acute myocardial infarction (AMI) is the most important cause of cardiomyocyte necrosis, cTns have become an integral part in the diagnosis of AMI. In this indication, cTns are superior to all other biomarkers indicating cardiomyocyte necrosis such as CK-MB and myoglobin, and are therefore considered the preferred marker in the diagnosis of AMI. It is important to highlight that cTn indicates and quantifies cardiomyocyte necrosis irrespective of its cause? The major limitation of contemporary cTn assays is a sensitivity deficit in the first few hours of AMI due to a delayed increase of circulating levels. Recent advances in assay technology have lead to a refinement in cardiac troponin (cTn) assays that have had a profound impact on clinical practice. High-sensitive cTn assays have two differentiating features from contemporary cTn assays: 1) detection of cTn in healthy persons and 2) a precise definition of what is "normal" (= the 99th percentile). Recent multicentre studies have shown that high-sensitive cTn assays improve the early diagnosis of AMI. To achieve the best clinical use, cTn has to be interpreted as a quantitative variable. Rising and/or falling levels differentiate acute from chronic cardiomyocyte necrosis. The term "troponin-positive" should therefore be avoided. "Detectable" levels will become the norm and have to be clearly differentiated from "elevated" levels. The differential diagnosis of a small amount of cardiomyocyte necrosis and therefore mild elevation of cTn is broad and includes acute and chronic cardiac disorders. The differential diagnosis of a large amount of cardiomyocyte necrosis and therefore substantial elevation of cTn is much smaller and largely restricted to AMI, myocarditis and tako-tsubo cardiomyopathy.

Background: Increased serum osteoprotegerin has been shown to be associated with increased mortality and heart failure development in patients with acute coronary syndromes. The aim of the present study was to elucidate a possible association between serum osteoprotegerin measured acutely in patients with ST-elevation myocardial infarction (STEMI) and final infarct size. METHODS Serum osteoprotegerin was measured in fasting blood samples from 199 patients with acute STEMI, sampled at a median time of 16 h after primary percutaneous coronary intervention (PCI). After 3 months, final infarct size (in percentage of left ventricular mass; LVM) was assessed by single-photon emission CT. The outcome variable final infarct size was dichotomised using the 75th percentile as the cutoff value (large infarct size ≥ 29.0%). A multivariable analysis was performed adjusting for multiple clinical and biochemical covariates., Results: Median (IQR) osteoprotegerin concentration was 1.4 (1.0, 2.1) ng ml⁻¹ and patients with high osteoprotegerin level (> median) at baseline had larger infarct size at 3 months compared with patients with low osteoprotegerin levels (< median) (25 (8, 40) vs 6 (0, 19)% of LVM, respectively, p < 0.0001). A high osteoprotegerin level was also associated with an approximately sevenfold increase in the odds of developing a large myocardial infarct (OR 7.0; 3.2, 15.5, p < 0.001). After adjustment for potential confounders including peak troponin T, the adjusted OR was 5.2 (2.0, 13.1) p < 0.001., Conclusion: High levels of circulating osteoprotegerin measured the first morning after a PCI-treated acute STEMI were strongly associated with final infarct size.

Aims: Magnetic resonance imaging (MRI) is often considered to be the gold standard in measuring left ventricular function and volumes. The aim of this study was to assess the agreements between standard echocardiography (standard echo), contrast echocardiography (contrast echo), single-photon emission computed tomography (SPECT), and MRI in the determination of left ventricular ejection fraction (EF) and end-diastolic volumes (EDV) in patients treated for acute ST-elevation myocardial infarction (STEMI)., Methods and Results: Standard echo, contrast echo, SPECT and MRI were performed on the same day, 3 months after STEMI in 150 patients participating in the NORwegian Study on District Treatment of ST-Elevation Myocardial Infarction (NORDISTEMI). Bland-Altman analysis of EF measured by all four imaging modalities showed generally low mean differences but wide limits of agreement. The mean EDV difference, however, was consistently higher when MRI was compared with standard echo (54.9 mL), contrast echo (41.7 mL) and SPECT (54.6 mL), and the limits of agreement were wider. The mean EDV differences between contrast echo vs. standard echo, SPECT vs. standard echo and contrast echo vs. SPECT were small., Conclusion: Our data suggest that all four imaging modalities measured EF closely similar after STEMI as demonstrated by a very small bias. The limits of agreement were however wide. EDV measured by MRI was consistently higher when compared with the other methods which may be caused by different tracing-methods and imaging principles. As echocardiography is preferable from a cost-benefit point of view, further analysis would be needed to clarify the nature of such differences.

Background: Inflammation plays an important role in the pathophysiology of both atherosclerosis and type 2 diabetes and some inflammatory markers may also predict the risk of developing type 2 diabetes. The aims of the present study were to assess a potential association between circulating levels of inflammatory markers and hyperglycaemia measured during an acute ST-elevation myocardial infarction (STEMI) in patients without known diabetes, and to determine whether circulating levels of inflammatory markers measured early after an acute STEMI, were associated with the presence of abnormal glucose regulation classified by an oral glucose tolerance test (OGTT) at three-month follow-up in the same cohort., Methods: Inflammatory markers were measured in fasting blood samples from 201 stable patients at a median time of 16.5 hours after a primary percutaneous coronary intervention (PCI). Three months later the patients performed a standardised OGTT. The term abnormal glucose regulation was defined as the sum of the three pathological glucose categories classified according to the WHO criteria (patients with abnormal glucose regulation, n = 50)., Results: No association was found between inflammatory markers and hyperglycaemia measured during the acute STEMI. However, the levels of C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) measured in-hospital were higher in patients classified three months later as having abnormal compared to normal glucose regulation (p = 0.031 and p = 0.016, respectively). High levels of CRP (≥ 75 percentiles (33.13 mg/L)) and MCP-1 (≥ 25 percentiles (190 ug/mL)) were associated with abnormal glucose regulation with an adjusted OR of 3.2 (95% CI 1.5, 6.8) and 7.6 (95% CI 1.7, 34.2), respectively., Conclusion: Elevated levels of CRP and MCP-1 measured in patients early after an acute STEMI were associated with abnormal glucose regulation classified by an OGTT at three-month follow-up. No significant associations were observed between inflammatory markers and hyperglycaemia measured during the acute STEMI.

Background: Thrombolysis remains the treatment of choice in acute ST-segment elevation myocardial infarction (STEMI) when primary percutaneous coronary intervention (PCI) cannot be performed within 90 to 120 minutes. The optimal treatment after thrombolysis is still debated, but several studies have shown improved clinical outcomes with early transfer for PCI. The aim of this study was to investigate whether an early invasive strategy after thrombolysis preserved left ventricular function better than a late invasive strategy., Methods: This was a substudy of the NORwegian study on DIstrict treatment of ST-Elevation Myocardial Infarction. Patients with STEMI of <6 hours of duration and >90 minutes of expected transfer delays to PCI were treated with aspirin, tenecteplase, enoxaparin, and clopidogrel and randomized to early or late invasive strategy (N = 266). Left ventricular volumes and ejection fraction were assessed by single-photon emission computed tomography, echocardiography, and magnetic resonance imaging 3 months after the index infarction., Results: Noninvasive imaging was completed in 241 patients (91%). Median end-diastolic and end-systolic volumes after 3 months did not differ between groups. Median ejection fraction was well preserved and also without differences: 63% (interquartile range 51-70) in the early invasive versus 65% (interquartile range 55-71) in the late invasive group when assessed by single-photon emission computed tomography (P = .30), 55% versus 55% when assessed by echocardiography (P = .88), and 57% versus 57% when assessed by magnetic resonance imaging (P = .99)., Conclusion: In this group of STEMI patients treated with thrombolysis, no difference in left ventricular function after 3 months was found between patients treated with early versus late invasive strategy., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Background: Thrombin and plasmin play a central role in ongoing thrombosis and platelet activation in patients with acute ST-elevation myocardial infarction (STEMI). Data of thrombin and plasmin activity in the early course of STEMI and the relation to outcome are scarce., Methods: We included 68 consecutive patients (53 male, 59 +/- 11.4 years) with STEMI who underwent acute catheter-based reperfusion therapy within the first 12 h after onset of symptoms. Blood samples were taken at admission and after 4, 8, 12 and 24 h. Thrombin activity and generation was measured by changes in the thrombin/antithrombin-III complex (TAT) and prothrombin fragment (F1.2); plasmin was measured by changes in the plasmin-alpha(2)/antiplasmin complex (PAP). A follow-up with respect to the combined primary endpoint consisting of death, acute myocardial infarction or urgent need for revascularization up to 6 weeks post-discharge was carried out., Results: TAT values showed no significant change over time in patients with and without the primary endpoint but there was a borderline difference between these groups at 4 h after admission (event group 9.0 vs no event group 4.7 microg l(-1), p = 0.057). F1.2 values were different between groups only after 24 h (event group 1.5 vs no event group 0.9 nmol l(-1), p = 0.028) and did not differ in serial sampling of 24 h. PAP values were higher in patients with events after 4 and 8 h and declined over time in the group without events (p <0.001). Odds ratios (OR) with respect to the primary endpoint were highest for TAT >4.8 microg l(-1) at 0 h and TAT >8.4 microg l(-1) at 4 h (OR 7.1, 95% confidence interval (CI) 1.5-34, p = 0.015 and OR 5.5, 95% CI 1.5-20.0, p = 0.01, respectively). The predictive value of plasmin concentrations were equally high after 4 h (PAP >962 microg l(-1); OR 6.8, 95% CI 1.8-26.2, p = 0.005) and 8 h (PAP >495 microg l(-1), OR 6.7, 95% CI 1.4-32.9, p = 0.024). Values for F1.2 were only predictive after 24 h (F1.2 >0.85 nmol l(-1), OR 13, 95% CI 1.4-117.8, p = 0.023)., Conclusions: Markers of thrombin and plasmin activity in acute STEMI are related to outcome. The marker for thrombin generation F1.2 becomes a significant predictor of outcome at 24 h after admission, reflecting the potentially adverse effects of ongoing thrombin generation. This underlines the potential for direct thrombin inhibition and individualization of treatment by thrombin markers in STEMI.

Objectives: To assess if myocardial perfusion scintigraphy (MPS) at rest can be of value in elucidating myocardial perfusion, ischaemia and perioperative myocardial infarction (PMI) associated with coronary artery bypass graft (CABG) surgery., Design: This was a prospective randomized study of patients undergoing elective CABG. Forty-eight patients in the control group underwent serial ECG recordings and measurements of CK-MB and cTnT. Fifty-four patients in the study group were additionally examined with MPS preoperatively and 2-4 days and 6 weeks postoperatively., Results: The study showed a highly significant (p < 0.001) improvement in myocardial radionuclide uptake from preoperatively to 2-4 days postoperatively. Judged from ECG and enzymatic changes, two control patients and one study patient only had PMI and no additional cases of PMI were demonstrated by MPS., Conclusion: MPS at rest showed that CABG significantly improved myocardial perfusion, by demonstrating an increase in radionuclide uptake. In diagnosing PMI, we found that MPS provided no additional information beyond cardiac biochemical markers and ECG changes.

Background: Previous studies have shown improvement in left ventricular function after intracoronary injection of autologous cells derived from bone marrow (BMC) in the acute phase of myocardial infarction. We designed a randomized, controlled trial to further investigate the effects of this treatment., Methods: Patients with acute ST-elevation myocardial infarction of the anterior wall treated with percutaneous coronary intervention were randomly assigned to the group that underwent intracoronary injection of autologous mononuclear BMC or to the control group, in which neither aspiration nor sham injection was performed. Left ventricular function was assessed with the use of electrocardiogram-gated single-photon-emission computed tomography (SPECT) and echocardiography at baseline and magnetic resonance imaging (MRI) 2 to 3 weeks after the infarction. These procedures were repeated 6 months after the infarction. End points were changes in the left ventricular ejection fraction (LVEF), end-diastolic volume, and infarct size., Results: Of the 50 patients assigned to treatment with mononuclear BMC, 47 underwent intracoronary injection of the cells at a median of 6 days after myocardial infarction. There were 50 patients in the control group. The mean (+/-SD) change in LVEF, measured with the use of SPECT, between baseline and 6 months after infarction for all patients was 7.6+/-10.4 percentage points. The effect of BMC treatment on the change in LVEF was an increase of 0.6 percentage point (95% confidence interval [CI], -3.4 to 4.6; P=0.77) on SPECT, an increase of 0.6 percentage point (95% CI, -2.6 to 3.8; P=0.70) on echocardiography, and a decrease of 3.0 percentage points (95% CI, 0.1 to -6.1; P=0.054) on MRI. The two groups did not differ significantly in changes in left ventricular end-diastolic volume or infarct size and had similar rates of adverse events., Conclusions: With the methods used, we found no effects of intracoronary injection of autologous mononuclear BMC on global left ventricular function., (2006 Massachusetts Medical Society)

Objectives: To study myocardial perfusion in ST-elevation myocardial infarction (STEMI) treated successfully with primary angioplasty. Additionally, to evaluate the predictive value of perfusion on subsequent infarct size., Design: Fifty patients with acute STEMI and restoration of normal epicardial flow after primary angioplasty were included in the study. TIMI myocardial perfusion (TMP) grades were determined at the end of the procedure. Contrast enhanced magnetic resonance imaging (MRI) including first-pass perfusion and delayed enhancement imaging were performed within five days and after three months., Results: The patients were divided into two groups: A=TMP 0-1, B=TMP 2-3. The early MRI showed significantly reduced myocardial perfusion in the infarct zone compared to remote myocardium in both groups (p<0.001), but the reduction was more pronounced in group A. The infarct sizes were smaller (p=0.0017) and the ejection fractions higher (p=0.0001) in group B than in group A at follow-up., Conclusions: In STEMI, early impairments in myocardial perfusion were observed in spite of successful treatment with angioplasty. Marked early impairments in perfusion were associated with larger infarct sizes on MRI after three months.

Conflicting results of an association of the human platelet antigen 1b (HPA-1b/PlA2), localized on the beta-subunit of the integrin alpha(IIb)beta3, and the alpha(2)807TT genotype of the integrin alpha2beta1 with coronary atherosclerosis and myocardial infarction have been reported. Both platelet receptor polymorphisms were genotyped in 3261 patients who had undergone coronary angiography, including 1175 survivors of a myocardial infarction, 1211 individuals with coronary artery disease but no history of myocardial infarction, and 571 control patients without angiographic coronary artery disease, and in 793 blood donors. In a case-control design, the prevalence of HPA-1b and alpha(2)807TT genotypes did not differ significantly between the patient groups with coronary artery disease or myocardial infarction and patient controls or blood donors. By contrast, using a multivariate case-only design, it was found that the median age of onset of myocardial infarction was 5.2 years earlier (P = 0.006) in carriers of the HPA-1b allele and 6.3 years earlier (P = 0.006) in carriers of the alpha(2)807TT genotype in the 264 survivors of myocardial infarction of recent onset with one- or two-vessel coronary artery disease. A significant interaction with the conventional risk factors hypercholesterolemia, smoking, diabetes, hypertension, and hyperfibrinogenemia was excluded. Human platelet antigen 1b and alpha(2)807TT are associated with premature myocardial infarction but not with coronary artery disease, suggesting a role of distinct integrin genotypes for increased platelet thrombogenicity. This association requires confirmation in follow-up studies.

Background: Achieving reperfusion as soon as possible is essential in order to reduce myocardial infarction size and thus improve prognosis. An increasing number of patients with myocardial infarction are treated with primary percutaneous coronary intervention (PCI). Technetium 99m-tetrofosmin myocardial perfusion tomography (SPECT) is a valid test for assessing myocardium at risk and final infarct size expressed by a hypoperfusion index (HPI) of the left ventricular mass., Material and Methods: 20 patients with acute ST-elevation myocardial infarction were treated with primary percutaneous coronary intervention within six hours of onset of symptoms. Myocardium at risk and final infarct size were assessed by Technetium 99m-tetrofosmin immediately before and a few hours, one week and six weeks after., Results: The hypoperfusion index immediately before percutaneous coronary intervention was 31%, four to six hours after PCI 25%, one week later 16% and six weeks later 12%, i.e. a relative reduction of 60% (p < 0.01). Anterior wall infarctions had a higher level of myocardium at risk before primary PCI compared to inferior wall infarctions (36% vs. 24%), but anterior wall infarctions had a higher salvage index compared to inferior wall infarctions., Interpretation: This non-controlled study shows a marked reduction in final infarction size in patients with acute ST-elevation myocardial infarction treated with primary PCI.

Background: Cardiac troponins are part of the new definition of acute myocardial infarction (AMI) by the European Society of Cardiology and the American College of Cardiology (ESC/ACC). In the new guidelines, it was suggested to establish reference values for cardiac troponins to calculate the 0.99 quantile (Q99) as cutoff for AMI diagnosis., Patients and Methods: We run a prospective series of troponin measurements in unselected outpatients who had no suspicion of cardiac ischemia. The selection of patients as reference population is based on a "goal-oriented concept of health". One hundred and ninety-five patients agreed that 10-ml additional blood was drawn at the occasion of the venous puncture done routinely in the evaluation of their case. Cardiac troponin I was measured using a point of care (POCT) device (Stratus CS, DadeBehring, TNI-PO). Additionally, heparin-plasma was obtained and immediately deep-frozen to -80 degrees C for later batch measurement of cardiac troponin T (Elecsys 2010, Roche Diagnostics, TnT) and troponin I (Centaur, Bayer, TnI-CL)., Results: The Q99 values were 0.14 microg/l for TnI-PO, 0.023 microg/l for TnT and 0.07 microg/l for TnI-CL in patients with creatinine levels below 1.5 mg/dl. These values lay above those obtained from people at good health for reference study purposes. On the level of our cutoffs, CVs were 7.5%, 6.4% and 23.7% for TnI-PO, TnT and TnI-CL, respectively., Conclusions: Only the TnI-PO and TnT tests fulfilled the imprecision criteria in our study. TnI-PO values between 0.10 and 0.14 microg/l and TnT values between 0.01 and 0.03 microg/l have to be interpreted carefully. Patients presenting with chest pain will be possibly true positives, but patients without chest pain and nondiagnostic ECGs should be subjected to repetitive troponin measurements and further noninvasive investigation and maybe not directly sent to the cardiac catheter laboratory.

Troponins I and T represent the current biomarker standard for diagnosis of myocardial infarction. Even small increases of cardiac troponins have prognostic implications, but not all patients at risk are correctly classified, particularly at admission. We identified elevated whole-blood choline as a promising marker and performed a prospective study of 327 patients with a suspected acute coronary syndrome that focused on the analysis of troponin-negative patients. Diagnostic classification of patients and the definition of troponin cutoffs were performed according to the new European Society of Cardiology/American College of Cardiology criteria. Blood was sampled serially and choline was measured using high-performance liquid chromatography mass spectrometry in whole blood. Patients were followed for 30 days. In patients with negative troponin I test results at admission (n = 250), choline was a predictor of cardiac death and nonfatal cardiac arrest (hazard ratio 6.0, p = 0.003), life-threatening arrhythmias (hazard ratio 3.75, p = 0.004), heart failure (hazard ratio 2.87, p = 0.002), and coronary angioplasty (hazard ratio 2.57, p = 0.001). In multivariate analysis of troponin-negative patients, choline was the strongest predictor of cardiac death or arrest (odds ratio 6.05, p = 0.01). Choline was not a marker for myocardial necrosis but indicated high-risk unstable angina in patients without acute myocardial infarction (sensitivity 86.4%, specificity 86.2%). Thus, an increased concentration of choline at hospital admission is a predictor of adverse cardiac events in patients with suspected acute coronary syndromes. Whole blood choline may be useful for early risk stratification of these patients, particularly if troponin results are negative on admission.

Background: There is little information available on long-term changes in left ventricular function and infarct size after acute myocardial infarction treated with primary angioplasty., Material and Methods: From 1996 to 1998, 100 consecutive patients were treated with primary angioplasty for acute ST-elevation myocardial infarction. Left ventricular ejection fraction was determined by radionuclide ventriculography before discharge, after six weeks and after a mean follow-up time of 20 months (range 11-37). Infarct size was assessed by technetium 99m-tetrofosmin myocardial perfusion tomography (SPECT) at rest, performed at the same time intervals., Results: Mean ejection fraction was 56% at discharge, 55% after six weeks and 57% after 20 months of follow-up. A mean perfusion defect of 19% was measured by SPECT after one week. After six weeks and 20 months of follow-up, the mean perfusion defects were reduced to 14% (p < 0.001) and 15%, respectively., Interpretation: Left ventricular function was well preserved and infarct sizes small to moderate 20 months (range 11-37) after primary angioplasty for acute myocardial infarction, demonstrating that the initial successful effect of the treatment was maintained.

Objective: To study changes in left ventricular function and infarct size during long-term follow-up after acute myocardial infarction treated with primary angioplasty., Design: From 1996 to 1998, 100 consecutive patients were treated with primary angioplasty for acute ST-elevation myocardial infarction. Angioplasty was successful in 95% of the patients. Global left ventricular ejection fraction (LVEF) was determined by radionuclide ventriculography before discharge, after 6 weeks and after a mean follow-up time of 20 months. Infarct size was assessed by technetium 99m-tetrofosmin myocardial perfusion tomography (SPECT) at rest, performed at the same time intervals., Results: Mean LVEF was 56% at discharge, 55% after 6 weeks and 57% after 20 months of follow-up. No significant improvement in LVEF was observed. Only 8% of the patients at follow-up had LVEF lower than 40%. After 1 week, a mean perfusion defect of 19% was measured by SPECT. After 6 weeks and 20 months of follow-up, the mean perfusion defects were reduced to 14% (p < 0.001) and 15%, respectively., Conclusion: Left ventricular function was well preserved with a mean LVEF of 57% 20 months after primary angioplasty for acute myocardial infarction. No significant change in LVEF was observed from 1 week after angioplasty to follow-up. Infarct sizes as assessed by SPECT imaging with tetrofosmin were reduced from 1 to 6 weeks, but did not change further during long-term follow-up. The reduction in the perfusion defects over time was probably due to gradual relief of stunning.

Background: There is little information available on long-term follow up of patients treated with primary angioplasty for acute myocardial infarction., Material and Methods: 100 consecutive patients with acute ST-elevation myocardial infarction and symptoms of less than six hours' duration were treated with primary angioplasty. Clinical examination was performed in 97 patients and exercise stress test in 74 patients 11-37 months (mean 20 months) later. Patients were observed for survival up to 48 months., Results: 24 patients had been rehospitalized, 16 because of chest pain. 77 patients were treated with beta blocker, 83 with statins, and 95 with antithrombotic medication. 84 patients were in NYHA (New York's Heart Association's classification's) class I at follow-up examination. Three patients died. 11 patients had a serious event, reinfarction (n = 3) or need for revascularization (n = 8) during the first 13 months. Total cumulative mortality rates after one and three years were 3% (95% CI 1-8) and 11% (95% CI 6-19)., Interpretation: The good initial results in primary angioplasty are maintained in long-term follow-up. This is in accordance with reports from centres abroad.

In this analysis of ischemic and hemorrhagic strokes after acute myocardial infarction (AMI) in 21,330 consecutively included patients with AMI, we found an incidence of stroke after AMI of 1.2% and a very poor prognosis. Previous stroke, atrial fibrillation, and older age were the strongest predictors of stroke after AMI; thrombolysis was a borderline risk factor and early therapy with aspirin was associated with a reduction in stroke after AMI.

Background: Much attention has lately been focused on primary angioplasty in the treatment of acute myocardial infarction. This report describe our results in 100 patients., Material and Methods: 100 consecutive patients with acute ST elevation myocardial infarction and a history of less than six hours were treated with primary angioplasty. The mean time from start of symptoms until establishment of reperfusion of the infarct related artery was 224 minutes; "the door-to-balloon" time was 69 minutes., Results: Angioplasty was successful in 95% of all patients. Mean ejection fraction measured before discharge in 71 patients was 56%. Hospital and 30-days' mortality was 1%. New revascularization was needed in 6%. Average observation period in the coronary care unit was 1.8 days; no patient needed treatment for ventricular arrhythmias after angioplasty. The first 24 hours 24% had symptomatic congestive heart failure, reduced to 11% at hospital discharge on day 6. Acute rehospitalization within the first 30 days was necessary in 7%, but only in 2% for chest pain., Interpretation: Our results are comparable to those of other high volume centres and show well preserved ventricular function and low hospital and 30-days' morbidity and mortality.

Background: International guidelines have been established for the use of cardiac markers in the early diagnosis and risk assessment of patients with acute coronary syndromes., Methods: A single center, prospective observational study was conducted in a tertiary care university hospital on 200 consecutive patients with suspected acute myocardial infarction (AMI). Blood was drawn on admission and after 2, 4, 8, 12 and 24 h for the measurement of CK-MB/CK activity, myoglobin, CK-MB mass and troponin I. A 6-week follow-up was undertaken for the combined end point of acute coronary syndrome and death., Results: Myoglobin showed an early diagnostic sensitivity of 0.65 on admission, 0.90 after 2 h and 0.92 after 4 h compared with 0.46, 0.74 and 0.88 for CK-MB/CK activity. The combination of myoglobin and cTnI increased the diagnostic value compared with myoglobin alone on admission, 2 and 4 h later. In multivariate analysis, cTnI and CK-MB/CK mass, but not myoglobin and CK-MB/CK activity, were shown to be independent predictors on the 6-week follow-up., Conclusions: Repetitive myoglobin measurements within 4 h of admission, combined with at least one early troponin test, was shown to be the strategy of choice in early AMI diagnosis and prognosis assessment.

Background: It has been suggested that inflammatory processes play a role in the pathogenesis of acute coronary syndromes (ACS). C-reactive protein (CRP) is a classic acute phase protein. It is yet unclear whether, in addition to established markers as troponin T (TnT), determination of CRP in patients admitted for ACS contributes significantly to the diagnosis and prognosis of ACS., Patients and Methods: We investigated 50 patients with ACS (59.4 SD 13.9 years) in the first hour after admission and 4-24 h later with respect to TnT (Elecsys, Roche Diagnostics) and CRP (biokit, modified Quantex CRP plus, analytical sensitivity 0.02 mg/dL). Fifty percent of the patients were classified as having unstable angina retrospectively. All patients were followed in the 6 weeks post discharge regarding death and recurrent ACS., Results: The cumulative event rate at 6 weeks after discharge was 62.5% for patients being CRP and TnT positive compared to 35.3% in TnT positive and CRP negative patients. In TnT negative patients a positive CRP test predicted 33.3% of events and 28.8% of patients negative for CRP and TnT had events at 42 days post discharge. Logistic regression analysis regarding the primary endpoint including TnT and CRP (4-24 h values), age, gender and diagnosis resulted in independent prediction of ACS or death by TnT (cutoff 0.1 microgram/L, p = 0.048, odds ratio = 7.5) and CRP (cutoff 0.862 mg/dL, p = 0.026, odds ratio = 5.3). Sensitivity/specificity for AMI diagnosis were 69.6%/75% for TnT and 12%/72% for CRP in the first hour and 91.3%/68.2% for TnT and 68%/72% for CRP 4-24 h later., Conclusions: Besides TnT, high sensitivity CRP determination has no additional value for early AMI diagnosis. The prognosis of these patients during the first 24 hours is significantly and independently predicted by CRP measurements in addition to troponin T.

Early onset of cardiopulmonary resuscitation (CPR) and defibrillation are the most important factors for improving outcome after cardiac arrest. Many patients do not receive thrombolytic therapy after prolonged CPR, as there is a fear of serious bleeding complications. Ten patients with cardiac arrest and acute myocardial infarction were treated with primary angioplasty after prolonged CPR. Angioplasty was successful in nine of the patients, and left ventricular function was well preserved after six weeks. Primary angioplasty is highly effective and safe in establishing reperfusion in selected patients with acute myocardial infarction and cardiac arrest.

20 patients with acute myocardial infarction and a medical history of less than six hours were treated with immediate percutaneous transluminal coronary angioplasty. The median time from start of symptoms until establishment of reperfusion of the infarct related artery was 190 minutes, and the time from admission to insertion of the balloon was 52 minutes. Angioplasty was successful in all patients, with no serious complications. All patients experienced pain relief immediately after angioplasty. No patients died or had further infarctions. None needed hospitalization during the first three months of follow up. Eight patients had an exercise test between five and seven days after angioplasty and the other 12 at their six-week check up; there were no signs of ischemia or anginal pain. Measurement of global ejection fraction one week and six weeks after treatment showed median normal values and no significant changes (58% versus 57%). Myocardial perfusion imaging was carried out in eight patients both before hospital discharge and six weeks later. Normalization and improvement was seen in six patients using this method, whereas the perfusion was found unaltered in two patients. Hibernation or stunning, or both are suggested as possible explanations for this. We found the method highly effective and safe in selected patients.

Experimental hibernating-model investigations of animals have shown that myocardial necrosis can be induced by longer-term intracoronary dobutamine infusion. This study was designed to determine whether myocardial infarction could be ascertained in patients with chronic regional wall motion abnormalities and greater than 75% stenosis in the supplying coronary artery through dobutamine stress echocardiography. Twenty patients with coronary artery disease and regional resting wall motion abnormalities were examined with a standard dobutamine protocol (5 to 50 microg/kg/min). Exclusion criteria were an acute coronary syndrome, severe heart failure, and severe hypertension. Creatine kinase (CK, CKMB), myoglobin, and troponine-I were measured before and at each of the first 7 hours after beginning of infusion. Fourteen of these 20 patients exhibited viable myocardium. The serum markers CK, CKMB, myoglobin, and troponin-I demonstrated no increase beyond the reference range, suggesting that with this protocol, no myocardial necrosis was induced.

The aim of this retrospective study involving 471 patients was to investigate the percentage of patients who returned to work after acute myocardial infarction. In the group of 350 patients who did not undergo subsequent aortocoronary bypass operation 70% returned to work, whereby half of these patients started work again within 6 months after infarction. A significantly higher number of patients who were enrolled in a cardiac rehabilitation programme returned to work as compared with patients not participating in such a programme (72% vs. 59%, respectively; p less than 0.04). There was, however, no difference between these 2 groups with respect to either the time point of resumption of work after myocardial infarction or the duration of employment between infarction and eventual retirement. Of the 121 patients who underwent an aortocoronary bypass operation, only 38% returned to work (p less than 0.001 vs. patients without bypass surgery).