[Digitalization and clinical decision tools]. / Digitalisierung und Clinical Decision Tools.

Digitalization in cardiovascular emergencies is rapidly evolving, analogous to the development in medicine, driven by the increasingly broader availability of digital structures and improved networks, electronic health records and the interconnectivity of systems. The potential use of digital health in patients with acute chest pain starts even in the prehospital phase with the transmission of a digital electrocardiogram (ECG) as well as telemedical support and digital emergency management, which facilitate optimization of the rescue pathways and reduce critical time intervals. The increasing dissemination and acceptance of guideline apps and clinical decision support tools as well as integrated calculators and electronic scores are anticipated to improve guideline adherence, translating into a better quality of treatment and improved outcomes. Implementation of artificial intelligence to support image analysis and also the prediction of coronary artery stenosis requiring interventional treatment or impending cardiovascular events, such as heart attacks or death, have an enormous potential especially as conventional instruments frequently yield suboptimal results; however, there are barriers to the rapid dissemination of corresponding decision aids, such as the regulatory rules related to approval as a medical product, data protection issues and other legal liability aspects, which must be considered.

Characteristics and outcomes in patients with a prior myocardial infarction treated with extended dual antiplatelet therapy with ticagrelor 60 mg: findings from ALETHEIA, a multi-country observational study.

BACKGROUND: Guidelines recommend extended dual antiplatelet therapy, including ticagrelor 60 mg twice daily, in high-risk post-myocardial infarction (MI) patients who have tolerated 12 months and are not at high bleeding risk. The real-world utilization and bleeding and ischaemic outcomes associated with long-term ticagrelor 60 mg in routine clinical practice have not been well described. METHODS: Register and claims data from the USA (Optum Clinformatics, IBM MarketScan, and Medicare) and Europe (Sweden, Italy, UK, and Germany) were extracted. Patients initiating ticagrelor 60 mg ≥12 months after MI, meeting eligibility criteria for the PEGASUS-TIMI (Prevention of Cardiovascular Events in Patients with Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin - Thrombolysis in Myocardial Infarction 45) 54 trial, were included. The cumulative incidence of the composite of MI, stroke, or all-cause mortality and that of bleeding requiring hospitalization were calculated. Meta-analyses were performed to combine estimates from each source. RESULTS: A total of 7035 patients treated with ticagrelor 60 mg met eligibility criteria. Median age was 67 years and 29% were females; 12% had a history of multiple MIs. The majority (95%) had been treated with ticagrelor 90 mg prior to initiating ticagrelor 60 mg. At 12 months from initiation of ticagrelor 60 mg, the cumulative incidence [95% confidence interval (CI)] of MI, stroke, or mortality was 3.33% (2.73-4.04) and was approximately three-fold the risk of bleeding (0.96%; 0.69-1.33). CONCLUSIONS: This study provides insights into the use of ticagrelor 60 mg in patients with prior MI in clinical practice. Observed event rates for ischaemic events and bleeding generally align with those in the pivotal trials, support the established safety profile of ticagrelor, and highlight the significant residual ischaemic risk in this population.Clinical Trials.gov Registration NCT04568083.

The German CPU registry: Comparison of smokers and nonsmokers.

BACKGROUND: Chest pain is a major reason for admission to an internal emergency department, and smoking is a well-known risk factor for coronary artery disease (CAD) and acute coronary syndrome (ACS). The aim of this analysis is to illustrate the differences between smokers and nonsmokers presenting to German chest pain units (CPU) in regard to patient characteristics, CAD manifestation, treatment strategy, and prognosis. METHODS: From December 2008 to March 2014, 13,902 patients who had a complete 3­month follow-up were enrolled in the German CPU registry. The analysis comprised 5796 patients with ACS and documented smoking status. RESULTS: Of all the patients in the CPU registry, 35.2% were smokers. Compared with nonsmokers, they were 13.5 years younger (58.2 vs. 71.7 years, p < 0.001), predominantly men (77.1% vs. 65.2%, p < 0.001), and were more frequently diagnosed with single-vessel disease (32.1% vs. 25.2%) as well as ST-elevation myocardial infarction (STEMI; 23.8% vs. 15.5%, p < 0.001). Although the Global Registry of Acute Coronary Events (GRACE) Risk Score for hospital mortality was lower in the group of smokers (106.1 vs. 123.3, p < 0.001), we did not observe any differences in CPU death (0.4% vs. 0.4%, p = 0.69) and CPU major adverse cardiac event (MACE) rates (3.8% vs 2.9%, p = 0.073) between the groups. In the 3­month follow-up, we documented higher mortality rates in the nonsmoker group (1.9% vs. 2.9%, p = 0.035) in correlation with the GRACE Risk Score (80.3 vs. 105.2, p < 0.001). MACE rates were similar during the follow-up (3.1% vs. 4.1%, p = 0.065). CONCLUSION: Observations from the German CPU registry demonstrate that smoking is a strong predictor of acute CAD manifestation early in life, especially STEMI. In spite of a lower GRACE Risk Score and fewer comorbidities, smokers had a rate of hospital mortality similar to the older group of nonsmokers.

[Perioperative cardiovasular morbidity and mortality in noncardiac surgical interventions : Measures for optimal anesthesiological care]. / Perioperative kardiovaskuläre Morbidität und Letalität bei nichtherzchirurgischen Eingriffen : Maßnahmen der optimalen anästhesiologischen Betreuung.

Because of new surgical techniques, advanced monitoring modalities and improvements in perioperative care, perioperative mortality and morbidity have been significantly reduced in the last decades; however, patients still suffer from high perioperative mortality and morbidity, especially those with pre-existing cardiovascular diseases. Not only perioperative myocardial infarction but also myocardial injury after non-cardiac surgery, which presents without clinical symptoms, is associated with an adverse outcome. Patients at risk require particular interdisciplinary attention throughout the perioperative phase. The premedication visit is of particular importance. In addition to a thorough patient medical history and physical assessment, the perioperative handling of the patient's pre-existing medication and possible necessity for further preoperative tests should be verified. If necessary and where possible, optimization of the patient's state of health can be planned together with other disciplines. It is the anesthesiologist's responsibility to optimally guide and support patients with pre-existing cardiovascular diseases through the entire surgical procedure. This review summarizes perioperative interventions that have an influence on patient mortality and morbidity and evaluates the underlying evidence. This covers the perioperative handling of cardioprotective medication, choice of the anesthetic regimen, blood pressure management and transfusion regimens. Furthermore, this review highlights recent findings, e.g. perioperative reloading with statins and short-term preoperative initiation of beta blockers. The pros and cons of thoracic epidural anesthesia in patients with an elevated cardiovascular risk are discussed. Not only intraoperative hypotension should be of concern to anesthesiologists but also postoperative hypotension can have a deleterious impact on the outcome. This is relevant in the time period when a significant proportion of patients have already left the monitoring ward. The recently published recommendations by the World Health Organization concerning perioperative hyperoxia might not be beneficial for patients with an elevated cardiovascular risk. Finally, the treatment options for perioperative cardiovascular events are explained and an algorithm for handling of patients with perioperative myocardial injury without clinical ischemic symptoms is suggested (myocardial injury after non-cardiac surgery).

[Cardiac troponins and beyond in acute coronary syndrome]. / Kardiales Troponin und mehr beim akuten Koronarsyndrom.

Cardiac biomarkers are an integral component of the diagnostic work-up of patients with suspected acute coronary syndrome (ACS). Cardiac troponin (cTn) is the most sensitive diagnostic biomarker for patients with ACS and enables the differentiation of acute non-ST-elevation myocardial infarction (NSTEMI) from unstable angina. All cardiac and non-cardiac differential diagnoses must be taken into consideration. The use of cTn has a prognostic value in a multitude of acute and chronic diseases apart from ACS. Highly sensitive cTn (hsTn) assays should be preferentially used. Point-of-care (POC) troponin assays can be used for rule-in of acute MI but are generally not useful for rule-out of MI due to their lack of sensitivity compared to hsTn assays. This, however, may change with recent developments of newer and improved POC troponin assays. For exclusion of MI using hsTn assays, there are various protocols available, such as the instant rule-out with undetectable hsTn levels at admission or normal hsTn/cTn levels combined with normal copeptin levels or rule-out with serial controls of hsTn after 1, 2 or 3 h. This article provides an overview of guideline-recommended rule-out protocols for patients with suspected ACS and discusses recent advances in POC troponin assays.

[Diagnosis of myocardial infarction in critically ill, ventilated patients]. / Infarktdiagnostik beim kritisch kranken, beatmeten Patienten.

Elevated cardiac troponin values are frequently observed in critically ill patients. These are often not due to myocardial infarction (MI) but caused by various other etiologies of myocardial injury. Understanding the etiology of any troponin elevation is of enormous importance for management and therapy. According to the fourth version of the Universal Definition of MI, myocardial injury is present if at least one troponin value is above the 99th percentile upper reference limit and considered acute, when a rise and/or fall occurs. Patients with acute MI are a subgroup of patients with acute myocardial injury, who present in an ischemic clinical context. Variables defining the clinical criteria of MI include symptoms of ischemia, presumably new electrocardiographic (ECG) changes or imaging evidence of new loss of viable myocardium or regional wall motion abnormalities, or detection of an intracoronary thrombus. In critically ill or mechanically ventilated patients, the diagnosis of MI is challenging due to limitations in history taking, co-existence of comorbidities, overlapping symptoms and equivocal or unspecific ECG changes. This article presents the diagnostic criteria of the Universal MI definition, discusses subtypes of MI and focuses on various differential diagnoses. Furthermore, implications of diagnosis of MI in critically ill patients, especially regarding the use of ECG and troponin assays, are discussed.

Biomarker in cardiology : DGK welcomes ESC Munich 2018.

Biomarkers have become essential tools for diagnosis and risk stratification in cardiology. This update provides an overview on the development and clinical application of selected biomarkers with a focus on cardiac troponins (cTn). We will specifically indicate the contribution of members of the German Cardiac Society to the field both in test development and evaluation as well as application in clinical care settings. Furthermore, we briefly touch on the development of novel biomarkers and expanded applications in personalized medicine and as companion diagnostics.

[Essential cardiac biomarkers in the differential diagnosis of acute chest pain : An update]. / Essenzielle kardiale Biomarker in der Differenzialdiagnose des akuten Thoraxschmerzes : Ein Update.

Cardiac biomarkers are an integral part of the diagnostic work-up and risk stratification of patients with chest pain. Cardiac troponins are highly sensitive diagnostic biomarkers in patients with acute coronary syndrome and have prognostic value in a multitude of acute and chronic diseases. In patients with suspected pulmonary embolism (PE) D­dimer can be used together with the Wells score for exclusion of PE. In patients with confirmed PE, B­type natriuretic peptide (BNP), N­terminal pro-BNP (NT-proBNP) and heart-type fatty acid binding protein (h-FABP) can be used for risk stratification. Although normal D­dimer levels largely decrease the possibility of acute aortic dissection, clinicians should not rely on D­dimer alone to exclude the diagnosis of acute aortic syndrome. This continuing medical education article provides an overview of the most important biomarkers recommended in current guidelines for differential diagnoses of patients with chest pain with a focus on cardiac troponins in acute coronary syndrome.

NT-proBNP during and after primary PCI for improved scheduling of early hospital discharge.

BACKGROUND: The Zwolle Risk Score (ZRS) identifies primary percutaneous coronary intervention (PPCI) patients at low mortality risk, eligible for early discharge. Recently, this score was improved by adding baseline NT-proBNP. However, the optimal timepoint for NT-proBNP measurement is unknown. METHODS: PPCI patients in the On-Time 2 study were candidates. The ZRS and NT-proBNP levels on admission, at 18-24 h, at 72-96 h, and the change in NT-proBNP from baseline to 18-24 h (delta NT-proBNP) were determined. We investigated whether addition of the different NT-proBNP measurements to the ZRS improves the prediction of 30-day mortality. Based on cut-off values reflecting zero mortality at 30 d, patients who potentially could be discharged early were identified and occurrence of major adverse cardiac events (MACE) and major bleeding until 10 d was registered. RESULTS: 845 patients were included. On multivariate analyses, NT-proBNP at baseline (HR 2.09, 95% CI 1.59-2.74, p < 0.001), at 18-24 h (HR 6.83, 95% CI 2.94-15.84), and at 72-96 h (HR 3.32, 95% CI 1.22-9.06) independently predicted death at 30 d. Addition of NT-proBNP to the ZRS improved prediction of mortality, particularly at 18-24 h (net reclassification index 29%, p < 0.0001, integrated discrimination improvement 17%, p < 0.0001). Based on ZRS (<2) or NT-proBNP at 18-24 h (<2500 pg/ml) 75% of patients could be targeted for early discharge at 48 h, with expected re-admission rates of 1.2% due to MACE and/or major bleeding. CONCLUSIONS: NT-proBNP at different timepoints improves prognostication of the ZRS. Particularly at 18-24 h post PPCI, the largest group of patients that potentially could be discharged early was identified.

[Bleeding in patients receiving dual antiplatelet therapy after acute coronary syndrome - significance, prevention and interdisciplinary management]. / Interdisziplinäres Management von Blutungen unter dualer antithrombozytärer Therapie nach akutem Koronarsyndrom.

For secondary prevention of acute coronary syndrome, guidelines recommend dual antiplatelet therapy with acetylsalicylic acid and a P2Y12 receptor antagonist such as clopidogrel, prasugrel or ticagrelor for a period of 12 months. Premature discontinuation of dual antiplatelet therapy is associated with an increased risk of ischaemic events. However, antiplatelet therapy is also associated with an increased risk of bleeding that should not be under- or overestimated. To ensure an optimal care of patients receiving dual antiplatelet therapy after an acute coronary syndrome, an interdisciplinary group of experienced experts in the fields of cardiology, cardiac surgery, gastroenterology, anaesthesiology, intensive care and haemostaseology gathered bleeding-related information and developed recommendations relevant to daily clinical practice. These include the significance of bleeding events in the course of treatment, measures for bleeding prevention and the adequate care of patients with bleedings.

Admission heart rate in relation to presentation and prognosis in patients with acute myocardial infarction. Treatment regimens in German chest pain units.

BACKGROUND: Higher heart rates on admission have been associated with poor outcomes in patients with an acute coronary syndrome in previous cohorts. Whether such a linear relationship still exists in contemporary high-level care is unclear. METHODS: Prospectively collected data from patients presenting with myocardial infarction (MI) in centers participating in the Chest Pain Unit (CPU) Registry between December 2008 and July 2014 were analyzed. Patients were classified according to their initial heart rate (I: < 50; II: 50-69; III: 70-89; IV: ≥ 90 bpm). A total of 6,168 patients out of 30,339 patients presenting to 38 centers were included in the study. RESULTS: Patients in group IV had more comorbidities, while patients in group I more often had a history of MI. Patients in the lowest heart rate group presented significantly earlier to the hospital (4 h 31 min vs. 7 h 37 min; p < 0.05) and had the highest rate of interventions. The overall survival after 3 months was significantly worse in group IV after adjusting for baseline variables. In the subgroup analysis, heart rate was a prognostic factor in the non-ST-segment elevation MI group but not in the ST-segment elevation MI group. The correlation between heart rate and major adverse cardiac events followed a J-shaped curve with worst outcomes in the lowest and highest heart rate groups. CONCLUSION: Patients admitted to a dedicated CPU with the diagnosis of MI and a heart rate > 90 bpm experience reduced survival at 3 months despite optimal treatment. Patients with bradycardia also seem to be at increased risk for cardiovascular events despite much earlier presentation and treatment.

Troponins in heart failure.

The signs and symptoms of heart failure are frequently unspecific and correlate poorly with objective indices of cardiac function. Objective assessment of cardiac function by echocardiography or other imaging modalities also correlate poorly with symptomatic status and functional capacity. Accordingly, there is a need for circulating biomarkers that can provide incremental diagnostic and prognostic information to the existing armamentarium of tests. The introduction of more sensitive assays that allow determination of very low circulating concentrations of the myofibrillar proteins cardiac troponin I and T has not only resulted in improved diagnostic accuracy in the setting of acute coronary syndromes. The high sensitivity assays have also shown that cardiac troponins are frequently found chronically circulating in a variety of acute and chronic, cardiac and non-cardiac disease conditions, including acute heart failure and chronic symptomatic and asymptomatic left ventricular dysfunction. Cardiac troponin I and T provide may provide clinically useful prognostic information both concerning the future risk of developing heart failure in asymptomatic subjects and the risk of fatal events and hospital admissions in those with already established heart failure This review summarizes current literature on the clinical performance and utility of cardiac troponin measurements as diagnostic and prognostic tools in patients with symptomatic heart failure, as well as in those with asymptomatic left ventricular dysfunction, and clinical phenotypes at high risk for developing heart failure, including stable coronary artery disease, left ventricular hypertrophy, and aortic stenosis.

Comprehensive bio-imaging using myocardial perfusion reserve index during cardiac magnetic resonance imaging and high-sensitive troponin T for the prediction of outcomes in heart transplant recipients.

We sought to determine the ability of quantitative myocardial perfusion reserve index (MPRI) by cardiac magnetic resonance (CMR) and high-sensitive troponin T (hsTnT) for the prediction of cardiac allograft vasculopathy (CAV) and cardiac outcomes in heart transplant (HT) recipients. In 108 consecutive HT recipients (organ age 4.1±4.7 years, 25 [23%] with diabetes mellitus) who underwent cardiac catheterization, CAV grade by International Society for Heart & Lung Transplantation (ISHLT) criteria, MPRI, late gadolinium enhancement (LGE) and hsTnT values were obtained. Outcome data including cardiac death and urgent revascularization ("hard cardiac events") and revascularization procedures were prospectively collected. During a follow-up duration of 4.2±1.4 years, seven patients experienced hard cardiac events and 11 patients underwent elective revascularization procedures. By multivariable analysis, hsTnT and MPRI both independently predicted cardiac events, surpassing the value of LGE and CAV by ISHLT criteria. Furthermore, hsTnT and MPRI provided complementary value. Thus, patients with high hsTnT and low MPRI showed the highest rates of cardiac events (annual event rate=14.5%), while those with low hsTnT and high MPRI exhibited excellent outcomes (annual event rate=0%). In conclusion, comprehensive "bio-imaging" using hsTnT, as a marker of myocardial microinjury, and CMR, as a marker of microvascular integrity and myocardial damage by LGE, may aid personalized risk-stratification in HT recipients.

[Essential cardiac biomarkers in myocardial infarction and heart failure]. / Essenzielle kardiale Biomarker bei Myokardinfarkt und Herzinsuffizienz.

With the discovery of novel biomarkers in cardiovascular diseases, over the past decades considerable improvements in diagnosis, risk stratification and patient care could be achieved; however, despite extensive research, only few biomarkers have met the requirements of significantly improving diagnostic or prognostic approaches. Among the most established markers are cardiac troponins and natriuretic peptides, which are recommended in current guidelines for myocardial infarction or heart failure and are routinely used in clinical practice. Cardiac troponins T and I are the preferred biomarkers of choice for definition of myocardial infarction and proved to be prognostically relevant not only in acute coronary syndrome but also in non-cardiac diseases. The natriuretic peptides B-type natriuretic peptide (BNP) and amino-terminal pro-B-type natriuretic peptide (NT-proBNP) aid in diagnosis, risk stratification and monitoring of heart failure. In recent years several new promising markers have been proposed which might add incremental clinical information, most notably copeptin and growth differentiation factor (GDF) 15; however, larger studies are still required before recommendations for routine clinical use can be made.

Long-term outcome after heart transplantation predicted by quantitative myocardial blush grade in coronary angiography.

The purpose of our study was to investigate whether the quantification of myocardial blush grade (MBG) during surveillance coronary angiography can predict long-term outcome after heart transplantation (HT). In 105 HT recipients who underwent cardiac catheterization, cardiac allograft vasculopathy (CAV) was assessed visually using the ISHLT grading scale (prospective cohort study). MBG was quantified by dividing the plateau of contrast agent gray-level intensity (G(max)) by the time-to-peak intensity (T(max)). In a subgroup (n = 72), myocardial perfusion index by cardiac magnetic resonance imaging (CMR) was assessed. During a mean follow-up duration of 2.7 (standard deviation [SD] 1.0) years, 26 patients experienced cardiac events, including 7 with cardiac death and 19 who underwent coronary revascularization. G(max)/T(max) was related to CAV by ISHLT criteria and to subsequent cardiac events. By univariate analysis, patient age, organ age, CAV, MBG and myocardial perfusion index by CMR were all predictive for cardiac events. Multivariable analysis demonstrated that G(max)/T(max) provided the most robust prediction of cardiac death (hazard ratio [HR] = 0.2, 95% confidence interval [CI] = 0.06-0.64, p < 0.01) and cardiac events (HR = 0.52, 95% CI = 0.32-0.84, p < 0.01), beyond clinical parameters and the presence of CAV. G(max)/T(max) is a valuable surrogate parameter of microvascular integrity, which is associated with cardiac death and revascularization procedures after HT.

Prevalence, kinetic changes and possible reasons of elevated cardiac troponin T in patients with AV nodal re-entrant tachycardia.

BACKGROUND: Elevated cardiac troponin (cTn) has been reported to occur with AVNRT. Little is known about prevalence, kinetic changes, and possible reasons of increased cTn. METHODS: We evaluated 139 consecutive patients presenting with AVNRT to the emergency department between 2006 and 2010. Cardiac troponin T (cTnT) was measured serially at baseline, after three and six hours. Patients were evaluated for the presence of structural heart disease or CAD. Troponin was defined as elevated if a value exceeded the lower limit of detection (10 ng/l) using the fourth generation cTnT, or if the value > 99 th percentile (14 ng/l) using the new highly sensitive cTn assay. RESULTS: A cTnT > LLD (n = 29) or > 99 th percentile (n = 16) was found in 45 patients (32.4%) within the initial six hours after hospitalization. All patients were symptomatic with palpitations, chest discomfort or dyspnea. A complete cardiac evaluation was carried out, including coronary angiography in 32 patients demonstrating an underlying structural heart disease or CAD in 18 cases (56%). Significant CAD was detected in 16 cases. 8 cases required PCI during hospitalization. Elevated cTnT was seen in patients with and without structural heart disease. CONCLUSIONS: AVNRT is a possible reason for elevated cTnT, even in the absence of relevant structural heart disease or CAD.

Antiplatelet therapy - ticagrelor.

UNLABELLED: Ticagrelor, a cyclopentyltriazolopyrimidine (CPTP), is the representative of a new chemical class of P2Y(12) receptor inhibitors that differ from thienopyridines (ticlopidin, clopidogrel, prasugrel) as ticagrelor is not a prodrug requiring active biotransformation by cytochromes in the liver and thus is characterized by a more rapid, more effective and more consistent platelet inhibition than ticlopidin or clopidogrel. An extensive study program for dose finding and safety for AZD6140 (DISPERSE studies) and a large-scaled phase III trial (PLATO) were undertaken on more than 18,000 patients for validation of efficacy and safety. In the PLATO trial, patients presenting with the broad spectrum of ACS, i.e. unstable angina, non-STEMI or STEMI, were randomized to ticagrelor (Brilique, Brilinta) or clopidogrel within 24 hours after onset of symptoms, regardless whether they were allocated to a planned invasive or conservative treatment. Compared to clopidogrel, ticagrelor reduced rates of the primary endpoint consisting of cardiovascular death, non-fatal MI, or stroke, without an excess of the primary safety endpoint that was PLATO-defined major bleedings. Results from the pre-specified confirmatory subgroup of patients undergoing planned invasive treatment was consistent with PLATO main trial. In addition, the primary endpoint, as well as CV death and all cause death were consistently reduced with ticagrelor in numerous exploratory subgroups including STEMI patients, those planned for non-invasive treatment, patients undergoing CABG, patients with renal failure, and those with diabetes mellitus, although patients were pretreated before coronary angiography and patients with clopidogrel pretreatment were not excluded. CONCLUSIONS: The pharmacological properties and convincing study results of the PLATO trial have stimulated a paradigm change for dual antiplatelet therapy. The new ESC guidelines on the management of ACS without ST segment elevation recommend the use of clopidogrel only when a new antiplatelet drug, e.g. ticagrelor or prasugrel is not available or contraindicated.

Diagnostic and prognostic performance of a novel high-sensitivity cardiac troponin T assay compared to a contemporary sensitive cardiac troponin I assay in patients with acute coronary syndrome.

OBJECTIVE: The study sought to compare the clinical performance of two more sensitive cardiac troponin (cTn) assays, a novel high-sensitivity (hs) troponin T assay and a contemporary cTnI assay. METHODS: We measured hs-cTnT (Roche TnThs) and cTnI (Siemens Centaur Ultra) on presentation in 1,384 patients with suspected acute coronary syndrome (ACS) who underwent early invasive strategy within 24 h after presentation. Kaplan-Meier, Cox proportional hazards, and receiver-operating characteristic (ROC) analysis was used to compare their prognostic performance for the prediction of all-cause death and death/MI (myocardial infarction) after a median of 271 days. We also compared the diagnostic performance of these assays on presentation for early diagnosis of non-STEMI. RESULTS: Both hs-cTnT and cTnI were independently predictive of long-term death (OR 3.51 vs. 2.19) and the composite of death/MI (OR 9.24 vs. 3.61), across the spectrum of ACS and in patients without ACS. When used as a continuous variable, ROC analysis demonstrated significantly higher areas under the curve (AUC) for hs-cTnT as compared to cTnI for the prediction of death/MI (0.721 vs. 0.672, P = 0.024), a trend to better prediction of all-cause death (0.721 vs. 0.672, P = 0.093) and significantly higher AUC for early diagnosis of non-STEMI (0.965 vs. 0.901, P < 0.001). CONCLUSION: Using the 99th percentile cutoff for hs-cTnT and cTnI, both assays enable prediction of adverse long-term outcomes and earlier diagnosis of non-STEMI. Used as a continuous variable, the hs-cTnT assay showed superior performance compared to the cTnI assay, especially in regard to prognosis.

Cardiac troponin T concentrations above the 99th percentile value as measured by a new high-sensitivity assay predict long-term prognosis in patients with acute coronary syndromes undergoing routine early invasive strategy.

OBJECTIVE: A recently developed immunoassay for high-sensitivity measurement of cardiac troponin T (hsTnT) allows measurement at the 99th percentile for a normal population with an assay imprecision <10%. It is unclear whether such a low cutpoint (14 ng/L) is helpful for long-term risk stratification of patients with an acute coronary syndrome (ACS) undergoing routine early invasive strategy. PATIENTS AND MAIN OUTCOME MEASURES: Consecutive patients with ACS admitted to a chest pain unit were studied. The usefulness of hsTnT for early diagnosis of myocardial infarction (MI) and prediction of all-cause death or death/MI over a median of 271 days following presentation was compared against the fourth generation cTnT at the 99th percentile cutpoint. RESULTS: Of 1,384 patients with ACS enrolled, 47.8% had non-ST-segment elevation MI (NSTEMI), 26.4% unstable angina, 21.8% STEMI and 4% had non-ACS. Adjusted risk for all-cause death [adjusted HR 8.26 (95%CI: 1.13-66.33), p = 0.038] and death/MI [adjusted HR 2.71 (95% CI: 1.15-6.38), p = 0.023] were significantly higher with hsTnT above the 99th percentile. In particular, among patients with a standard fourth generation cTnT result below the 99th percentile cutoff (0.01 ng/mL), hsTnT improved risk assessment. Mortality risk associated with an elevated hsTnT was present across the spectrum of ACS, as well as in conditions with hsTnT elevations not related to ACS. CONCLUSION: hsTnT at the 99th percentile cutoff is useful for the diagnostic evaluation of patients with ACS, and provides strong and independent predictive power for adverse long-term outcomes even after early invasive strategy.

HMGB1 as a predictor of infarct transmurality and functional recovery in patients with myocardial infarction.

OBJECTIVES: High-mobility group box 1 (HMGB1) protein is an innate danger signal for the initiation of host defence and tissue repair. The aim of this study was to analyse serum HMGB1 concentration and its correlation with infarct transmurality and functional recovery in patients with ST-elevation (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). DESIGN: We prospectively examined patients with first-time STEMI (n = 46) or NSTEMI (n = 49), treated according to current guidelines. Contrast-enhanced cardiac magnetic resonance imaging was performed 2-4 days after infarction for the estimation of infarct transmurality and was repeated after 6 months for the estimation of residual left ventricular function. HMGB1 was measured 2-4 days after infarction. RESULTS: High-mobility group box 1 concentration was related to infarct size and to residual ejection fraction in patients with STEMI (r(2) = 0.81 and r(2) =0.40, respectively, P < 0.001 for both) and NSTEMI (r(2) = 0.74 and r(2) = 0.25, respectively, P < 0.001 for both). Receiver operating characteristic (ROC) curve-derived cut-off values of 6.2 and 5.9 ng mL(-1) for patients with STEMI and NSTEMI, respectively, were predictive of infarct transmurality greater than 75% (STEMI: area under the curve (AUC) = 0.93, standard error (SE) = 0.04, 95% confidence interval (CI) = 0.81-0.98; NSTEMI: AUC = 0.96, SE = 0.04, 95% CI = 0.86-0.99). HMGB1 cut-off values of 7.2 and 6.4 ng mL(-1) for patients with STEMI and NSTEMI, respectively, were predictive of residual ejection fraction 6 months after myocardial infarction (MI) (STEMI: AUC = 0.81, SE = 0.07, 95% CI = 0.66-0.91; NSTEMI: AUC = 0.81, SE = 0.09, 95% CI = 0.68-0.91). CONCLUSION: High-mobility group box 1 serum levels represent a highly valuable surrogate marker for infarct transmurality and for the prediction of residual left ventricular function after MI.