The clinical approach to diagnosing peri-procedural myocardial infarction after percutaneous coronary interventions according to the fourth universal definition of myocardial infarction - from the study group on biomarkers of the European Society of Cardiology (ESC) Association for Acute CardioVascular Care (ACVC).

PURPOSE: This review intends to illustrate basic principles on how to apply the Fourth Universal Definition of Myocardial Infarction (UDMI) for the diagnosis of peri-procedural myocardial infarction (MI) after percutaneous coronary interventions (PCI) in clinical practice. METHODS AND RESULTS: Review of routine case-based events. Increases in cardiac troponin (cTn) concentrations are common after elective PCI in patients with chronic coronary syndrome (CCS). Peri-procedural PCI-related MI (type 4a MI) in CCS patients should be diagnosed in cases of major peri-procedural acute myocardial injury indicated by an increase in cTn concentrations of >5-times the 99th percentile upper reference limit (URL) together with evidence of new peri-procedural myocardial ischaemia as demonstrated by electrocardiography (ECG), imaging, or flow-limiting peri-procedural complications in coronary angiography. Measurement of cTn baseline concentrations before elective PCI is useful. In patients presenting with acute MI undergoing PCI, peri-procedural increases in cTn concentrations are usually due to their index presentation and not PCI-related, apart from obvious major peri-procedural complications, such as persistent occlusion of a large side branch or no-reflow after stent implantation. CONCLUSION: The distinction between type 4a MI, PCI-related acute myocardial injury, and chronic myocardial injury can be challenging in individuals undergoing PCI. Careful integration of all available clinical data is essential for correct classification.

Exposing the High Heterogeneity of Circulating Pro B-Type Natriuretic Peptide Fragments in Healthy Individuals and Heart Failure Patients.

BACKGROUND: The high molecular complexity of variably O-glycosylated and degraded pro B-type natriuretic peptide (proBNP) derived molecular forms challenges current immunoassays. Antibodies used show pronounced differences in cross-reactivities with these circulating fragments, which still need to be better characterized on a molecular level. To pave the way for advanced quantitative assays in the future, it is critical to fully understand these circulating forms. METHODS: Plasma samples were collected from 8 heart failure (HF) patients and 2 healthy controls. NT-proBNP and proBNP were purified by immunoprecipitation and analyzed by nano-flow liquid chromatography coupled to high-resolution mass spectrometry. Fragments formed during proteolysis in solution digestion were distinguished from naturally occurring peptides by using an 18O stable isotope labeling strategy. RESULTS: We detected 16 previously unknown circulating fragments of proBNP peptides (9 of which are located in the N-terminal and 7 in the C-terminal region), revealing a more advanced state of degradation than previously known. Two of these fragments are indicative of either unidentified processing modes or a far-reaching C-terminal degradation (or a combination thereof) of the precursor proBNP. CONCLUSIONS: Our results further restrict ideal target epitopes for immunoassay antibodies and expand the current thinking of diversity, degradation, and processing of proBNP, as well as the distribution of circulating forms.

Application of the fourth universal definition of myocardial infarction in clinical practice.

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.

Clinical evaluation of capillary B-type natriuretic peptide testing.

Background Capillary B-type natriuretic peptide (BNP) testing is attractive in outpatient and emergency settings. The aim of this study was to perform an evaluation of the clinical performances of capillary BNP testing as compared with venous whole blood and plasma point-of-care (POC) BNP as well as plasma N-terminal (NT) proBNP central laboratory testing. Methods BNP was measured with a novel single epitope POC assay (Minicare® BV, Eindhoven, The Netherlands) and NT-proBNP with a central laboratory assay (Roche Diagnostics®, Vienna, Austria). Results BNP and NT-proBNP were measured in 269 patients of a Department of Cardiology (mean age 67.9 ± 13 years, 26.4% females). Capillary BNP very closely correlated with whole blood venous BNP (r = 0.99, p < 0.001). There was also a close correlation of plasma BNP and NT-proBNP concentrations (r = 0.79, p < 0.001). The diagnostic performances of capillary BNP, whole blood venous BNP, plasma BNP and plasma NT-proBNP for acute heart failure (areas under receiver operating characteristic curves [AUC ROC]: 0.73-0.77) or systolic left ventricular dysfunction in the whole study population (AUC ROC: 0.72-0.76) did not differ significantly. All were significant independent predictors of cardiovascular death during follow-up of the whole study population. Conclusions Our study for the first time demonstrated a very close correlation of capillary and venous whole blood or plasma BNP concentrations using the same BNP assay in a large patient cohort. The diagnostic performances of different BNP specimens did not differ significantly, and no significant differences between BNP and NT-proBNP were found either.

Possible mechanisms behind cardiac troponin elevations.

Cardiac-specific troponins are elevated in blood following cardiac injury and are the preferred diagnostic biomarkers when acute myocardial infarction is suspected clinically. Cardiac troponin (cTn) elevations are also observed in clinical conditions without obvious connection to cardiac injury. Irrespective of the underlying condition, cTn elevation is linked to a poor prognosis, even if the elevation is stable over time. Here, we explore mechanisms that may lead to cTn elevations, including necrosis, apoptosis, necroptosis, cell wounds and decreased clearance. The aim is to broaden the perspective of how we interpret unexpected cTn elevations in patients. The cTn elevations may not be able to serve as direct proof of myocardial necrosis especially in the absence of a clear-cut reason for its release. Abbreviations: AMI: acute myocardial infarction; cTn: cardiac troponin; cTnI: cardiac troponin I; cTnT: cardiac troponin T; MLKL: mixed lineage kinase domain-like; TUNEL: terminal deoxynucleotidyl transferase nick end labeling.

Clinical performance of a new point-of-care cardiac troponin I test.

BACKGROUND: We evaluated the clinical performance of the Minicare cardiac troponin-I (cTnI), a new point-of-care (POC) cTnI test for the diagnosis of acute myocardial infarction (AMI) in a prospective, multicentre study (ISRCTN77371338). METHODS: Of 474 patients (≥18 years) admitted to an emergency department (ED) or chest pain unit (CPU) with symptoms suggestive of acute coronary syndrome (ACS; ≤12 h from symptom onset), 465 were eligible. Minicare cTnI was tested immediately, 3 h and 6 h after presentation. AMI diagnoses were adjudicated independently based on current guidelines. RESULTS: The diagnostic performance of the Minicare cTnI test at 3 h was similar for whole blood and in plasma: sensitivity 0.92 vs. 0.90; specificity 0.91 vs. 0.90; positive predictive value (PPV) 0.68 vs. 0.66; negative predictive value (NPV) 0.98 vs. 0.98; positive likelihood ratio (LR+) 10.18 vs. 9.41; negative likelihood ratio (LR-) 0.09 vs. 0.11. The optimal diagnostic performance was obtained at 3 h using cut-offs cTnI >43 ng/L plus cTnI change from admission ≥18.5 ng/L: sensitivity 0.90, specificity 0.96, PPV 0.81, NPV 0.98, and LR+ 21.54. The area under the receiver operating characteristics (ROC) curve for cTnI whole blood baseline value and absolute change after 3 h curve was 0.93. CONCLUSIONS: These data support the clinical usefulness of Minicare cTnI within a 0 h/3 h-blood sampling protocol supported by current guidelines for the evaluation of suspected ACS.

Open surgical retrieval of an embolized PFO occluder system.

Device migration after intervention for persistent foramen ovale occlusion is a rare complication. In case of failure of endovascular device retrieval, open surgical removal is indicated, safe, and reliable.

Novel biomarkers predicting cardiac function after acute myocardial infarction.

BACKGROUND: Measurement of biomarkers provides a cost-effective and widely available method to estimate cardiac dysfunction and clinical outcome of patients with acute myocardial infarction (AMI). SOURCES OF DATA: PubMed entries with terms 'myocardial infarction' and the respective biomarker. AREAS OF AGREEMENT: Cardiac troponins and natriuretic peptides are closely related to left ventricular dysfunction and the occurrence of adverse clinical events following AMI. AREAS OF CONTENTION: The incremental value of novel biomarkers is controversial. FUTURE DIRECTIONS: The combination of traditional and novel biomarkers might further improve risk stratification of patients with AMI. SEARCH STRATEGY: We searched all entries on the PubMed database with the MeSH terms 'myocardial infarction' and 'cardiac troponins', 'natriuretic peptides', 'copeptin', galectin-3', 'corin', 'fetuin-A', 'adiponectin' and 'microRNA'.

Cardiac index after acute ST-segment elevation myocardial infarction measured with phase-contrast cardiac magnetic resonance imaging.

OBJECTIVES: Phase-contrast CMR (PC-CMR) might provide a fast and robust non-invasive determination of left ventricular function in patients after ST-segment elevation myocardial infarction (STEMI). METHODS: Cine sequences in the left-ventricular (LV) short-axis and free-breathing, retrospectively gated PC-CMR were performed in 90 patients with first acute STEMI and 15 healthy volunteers. Inter- and intra-observer agreement was determined. The correlations of clinical variables (age, gender, ejection fraction, NT pro-brain natriuretic peptide [NT-proBNP] with cardiac index (CI) were calculated. RESULTS: For CI, there was a strong agreement of cine CMR with PC-CMR in healthy volunteers (r: 0.82, mean difference: -0.14 l/min/m(2), error ± 23 %). Agreement was lower in STEMI patients (r: 0.61, mean difference: -0.17 l/min/m(2), error ± 32 %). In STEMI patients, CI measured with PC-CMR showed lower intra-observer (1 % vs. 9 %) and similar inter-observer variability (9 % vs. 12 %) compared to cine CMR. CI was significantly correlated with age, ejection fraction and NT-proBNP values in STEMI patients. DISCUSSION: The agreement of PC-CMR and cine CMR for the determination of CI is lower in STEMI patients than in healthy volunteers. After acute STEMI, CI measured with PC-CMR decreases with age, LV ejection fraction and higher NT-proBNP. KEY POINTS: • Cine CMR and PC-CMR correlate well in healthy volunteers. • Agreement is lower in STEMI patients. • Cardiac Output should be measured with one method longitudinally. • Cardiac output decreases with age after myocardial infarction.

Multimarker approach for the prediction of microvascular obstruction after acute ST-segment elevation myocardial infarction: a prospective, observational study.

BACKGROUND: Presence of microvascular obstruction (MVO) derived from cardiac magnetic resonance (CMR) imaging is among the strongest outcome predictors after ST-segment elevation myocardial infarction (STEMI). We aimed to investigate the comparative predictive values of different biomarkers for the occurrence of MVO in a large cohort of reperfused STEMI patients. METHODS: This study included 128 STEMI patients. CMR imaging was performed within the first week after infarction to assess infarct characteristics, including MVO. Admission and peak concentrations of high-sensitivity cardiac troponin T (hs-cTnT), creatine kinase (CK), N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (hs-CRP), lactate dehydrogenase (LDH), aspartate transaminase (AST) and alanine transaminase (ALT) were measured. RESULTS: MVO was detected in 69 patients (54%). hs-cTnT, CK, hs-CRP, LDH, AST and ALT peak concentrations showed similar prognostic value for the prediction of MVO (area under the curve (AUC) = 0.77, 0.77, 0.68, 0.79, 0.78 and 0.73, all p > 0.05), whereas the prognostic utility of NT-proBNP was weakly lower (AUC = 0.64, p < 0.05). Combination of these biomarkers did not increase predictive utility compared to hs-cTnT alone (p = 0.349). CONCLUSIONS: hs-cTnT, CK, hs-CRP, LDH, AST and ALT peak concentrations provided similar prognostic value for the prediction of MVO. The prognostic utility of NT-proBNP was lower. Combining these biomarkers could not further improve predictive utility compared to hs-cTnT alone.

Comparison of conventional and high-sensitivity troponin in patients with chest pain: a collaborative meta-analysis.

BACKGROUND: Multiple studies have evaluated the diagnostic and prognostic performance of conventional troponin (cTn) and high-sensitivity troponin (hs-cTn). We performed a collaborative meta-analysis comparing cTn and hs-cTn for diagnosis of acute myocardial infarction (AMI) and assessment of prognosis in patients with chest pain. METHODS: MEDLINE/PubMed, Cochrane CENTRAL, and EMBASE were searched for studies assessing both cTn and hs-cTn in patients with chest pain. Study authors were contacted and many provided previously unpublished data. RESULTS: From 17 included studies, there were 8,644 patients. Compared with baseline cTn, baseline hs-cTn had significantly greater sensitivity (0.884 vs 0.749, P < .001) and negative predictive value (NPV; 0.964 vs 0.935, P < .001), whereas specificity (0.816 vs 0.938, P < .001) and positive predictive value (0.558 vs 0.759, P < .001) were significantly reduced. Based on summary receiver operating characteristic curves, test performance for the diagnosis of AMI was not significantly different between baseline cTn and hs-cTn (0.90 [95% CI 0.85-0.95] vs 0.92 [95% CI 0.90-0.94]). In a subanalysis of 6 studies that alternatively defined AMI based on hs-cTn, cTn had lower sensitivity (0.666, P < .001) and NPV (0.906, P < .001). Elevation of baseline hs-cTn, but negative baseline cTn, was associated with increased risk of death or nonfatal myocardial infarction during follow-up (P < .001) compared with both negative. CONCLUSION: High-sensitivity troponin has significantly greater early sensitivity and NPV for the diagnosis of AMI at the cost of specificity and positive predictive value, which may enable early rule in/out of AMI in patients with chest pain. Baseline hs-cTn elevation in the setting of negative cTn is also associated with increased nonfatal myocardial infarction or death during follow-up.

Measurement of natriuretic peptides at the point of care in the emergency and ambulatory setting: current status and future perspectives.

The measurement of natriuretic peptides (NPs), B-type NP or N-terminal pro-B-type NP, can be an important tool in the diagnosis of acute heart failure in patients presenting to an Emergency Department (ED) with acute dyspnea, according to international guidelines. Studies and subsequent meta-analyses are mixed on the absolute value of routine NP assessment of ED patients. However, levels of NPs are likely to be used also to guide treatment and to assess risk of adverse outcomes in other patients at risk of developing heart failure, including those with pulmonary embolism or diabetes, or receiving chemotherapy. Natriuretic peptide levels, like other biomarkers, can now be measured at the point of care (POC). We have reviewed the current status of NP measurement together with the potential contribution of POC measurement of NPs to clinical care delivery in the emergency and other settings. Several POC systems for measuring NP levels are now available: these produce test results within 15 minutes and appear sufficiently sensitive and robust to be used routinely in diagnostic evaluations. Point-of-care systems could be used to assess NP levels in the ED and community outpatient settings to monitor the risk of acute heart failure. Furthermore, the use of protocol-driven POC testing of NP within the time frame of a patient consultation in the ED may facilitate and accelerate the throughput and disposition of at-risk patients. Appropriately designed clinical trials will be needed to confirm these potential benefits. It is also important that processes of care delivery are redesigned to take full advantage of the faster turnaround times provided by POC technology.

The high-sensitivity cardiac troponin T assay is superior to its previous assay generation for prediction of 90-day clinical outcome in ischemic stroke.

BACKGROUND: Cardiac troponin T (cTnT) has been reported to be a predictor of stroke outcome. We hypothesized that the high-sensitivity cTnT (hs-cTnT) assay is superior to its previous assay generation for stroke outcome prediction. METHODS: cTnT was measured on emergency department admission in 60 consecutive patients (35 males, age 69.4 ± 13.9 years) with ischemic stroke. Adverse 90-day clinical outcome was defined as death or dependence (modified Rankin scale ≥ 3 or Barthel index < 75). RESULTS: Stroke aetiology was microangiopathy in three, macroangiopathy in 17, cardiac embolism in 26, dissection in one and unknown in 13 patients. At 90-day follow-up 16 (27%) patients had an adverse outcome. Receiver operating characteristics (ROC) curve analysis yielded a significantly better performance of hs-cTnT vs. cTnT (area under ROC curve: 0.80 [95% CI 0.68-0.89] vs. 0.70 [95% CI 0.57-0.82], p = 0.017). The optimal discriminator values according to ROC analysis were 5.1 ng/L (hs-cTnT assay) and 11 ng/L (4th generation cTnT assay) with: sensitivities 94% vs. 56%, specificities 57% vs. 84%, positive predictive values 44% vs. 56%, and negative predictive values 96% vs. 84%. CONCLUSIONS: Improvements in cTnT assay sensitivity and precision at the low measuring range resulted in a more accurate prediction of ischemic stroke outcome, particularly for ruling out worse outcome.

Cardiac troponin: a critical review of the case for point-of-care testing in the ED.

The measurement of cardiac troponin concentrations in the blood is a key element in the evaluation of patients with suspected acute coronary syndromes, according to current guidelines, and contributes importantly to the ruling in or ruling out of acute myocardial infarction. The introduction of point-of-care testing for cardiac troponin has the potential to reduce turnaround time for assay results, compared with central laboratory testing, optimizing resource use. Although, in general, many point-of-care cardiac troponin tests are less sensitive than cardiac troponin tests developed for central laboratory-automated analyzers, point-of-care systems have been used successfully within accelerated protocols for the reliable ruling out of acute coronary syndromes, without increasing subsequent readmission rates for this condition. The impact of shortened assay turnaround times with point-of-care technology on length of stay in the emergency department has been limited to date, with most randomized evaluations of this technology having demonstrated little or no reduction in this outcome parameter. Accordingly, the point-of-care approach has not been shown to be cost-effective relative to central laboratory testing. Modeling studies suggest, however, that reengineering overall procedures within the emergency department setting, to take full advantage of reduced therapeutic turnaround time, has the potential to improve the flow of patients through the emergency department, to shorten discharge times, and to reduce cost. To properly evaluate the potential contribution of point-of-care technology in the emergency department, including its cost-effectiveness, future evaluations of point-of-care platforms will need to be embedded completely within a local decision-making structure designed for its use.

Ultrasound-assisted catheter-directed thrombolysis for successful rescue treatment of acute pulmonary embolism in decompensated Fontan palliation.

A 22-year-old woman with complete Fontan palliation for tricuspid valve hypoplasia and chronic anemia presented to a local hospital for swelling of her left arm. Initially, the patient was hemodynamically stable without dyspnea or chest pain. Admission hemoglobin was 53 g/L and D-dimer 0.51 mg/L. Sonography showed signs of venous congestion of the left arm, but no definitive signs of venous thrombosis. Subsequently she developed dyspnea with a decrease in transcutaneous oxygen saturation to 85%. Computed tomography angiography revealed bilateral pulmonary embolism with occlusion of the right pulmonary artery. The patient was transferred to a tertiary care center. Gastroscopy detected only small stomach ulcers, and because of ongoing hemodynamic instability, the decision was to initiate rescue ultrasound-assisted catheter-directed local thrombolysis. This treatment was effective with rapid hemodynamic stabilization without bleeding complications and without residual emboli in a long-term follow-up cardiac catheterization. .

Cardiac troponin T and creatine kinase predict mid-term infarct size and left ventricular function after acute myocardial infarction: a cardiac MR study.

PURPOSE: To assess the relation of cardiac troponin T (cTnT) and creatine kinase (CK) release with infarct size and left ventricular function evaluated during the subacute phase as well as four months after acute myocardial infarction (AMI) by contrast-enhanced MRI (CE-MRI). MATERIALS AND METHODS: CMR of 80 patients (68 male, mean age 54.2 ± 11.7 years) was performed within 8 days and 4 months after first acute ST-elevation AMI with successful primary angioplasty. CK and cTnT concentrations were determined serially from admission to day 4 after symptom onset. RESULTS: All single time-points, estimated average release and peak concentrations of CK and cTnT markers correlated significantly with acute and mid-term infarct size (r = 0.43 to 0.79, all P < 0.001), ejection fraction (EF%) (r = -0.42 to -0.58, all P < 0.002) as well as with end-systolic volume (ESV) (r = 0.32 to 0.57, all P < 0.002) at all times of assessment. Patients with cTnT concentrations below the cutoff value of 3.26 µg/L measured 48 h after AMI-related symptom onset had a significant improvement in global (EF: P < 0.0001) myocardial function during the study period, whereas in those with cTnT ≥ 3.26 µg/L, functional recovery did not occur (P = 0.09). CONCLUSION: All single, mean and maximum concentrations of cTnT and CK measured within the first 4 days after AMI permit an accurate prediction of infarct size and left ventricular function as determined in the acute phase as well as four months after AMI by CE-MRI.

Recommendations for the use of cardiac troponin measurement in acute cardiac care.

The release of cardiomyocyte components, i.e. biomarkers, into the bloodstream in higher than usual quantities indicates an ongoing pathological process. Thus, detection of elevated concentrations of cardiac biomarkers in blood is a sign of cardiac injury which could be due to supply-demand imbalance, toxic effects, or haemodynamic stress. It is up to the clinician to determine the most probable aetiology, the proper therapeutic measures, and the subsequent risk implied by the process. For this reason, the measurement of biomarkers always must be applied in relation to the clinical context and never in isolation. There are a large number of cardiac biomarkers, but they can be subdivided into four broad categories, those related to necrosis, inflammation, haemodynamic stress, and/or thrombosis. Their usefulness is dependent on the accuracy and reproducibility of the measurements, the discriminatory limits separating pathology from physiology, and their sensitivity and specificity for specific organ damage and/or disease processes. In recent years, cardiac biomarkers have become important adjuncts to the delivery of acute cardiac care. Therefore, the Working Group on Acute Cardiac Care of the European Society of Cardiology established a committee to deal with ongoing and newly developing issues related to cardiac biomarkers. The intention of the group is to outline the principles for the application of various biomarkers by clinicians in the setting of acute cardiac care in a series of expert consensus documents. The first of these will focus on cardiac troponin, a pivotal marker of cardiac injury/necrosis.

Cardiovascular biomarkers in patients with COVID-19.

The coronavirus disease 2019 (COVID-19) pandemic has increased awareness that severe acute respiratory distress syndrome coronavirus-2 (SARS-CoV-2) may have profound effects on the cardiovascular system. COVID-19 often affects patients with pre-existing cardiac disease, and may trigger acute respiratory distress syndrome (ARDS), venous thromboembolism (VTE), acute myocardial infarction (AMI), and acute heart failure (AHF). However, as COVID-19 is primarily a respiratory infectious disease, there remain substantial uncertainty and controversy whether and how cardiovascular biomarkers should be used in patients with suspected COVID-19. To help clinicians understand the possible value as well as the most appropriate interpretation of cardiovascular biomarkers in COVID-19, it is important to highlight that recent findings regarding the prognostic role of cardiovascular biomarkers in patients hospitalized with COVID-19 are similar to those obtained in studies for pneumonia and ARDS in general. Cardiovascular biomarkers reflecting pathophysiological processes involved in COVID-19/pneumonia and its complications have a role evaluating disease severity, cardiac involvement, and risk of death in COVID-19 as well as in pneumonias caused by other pathogens. First, cardiomyocyte injury, as quantified by cardiac troponin concentrations, and haemodynamic cardiac stress, as quantified by natriuretic peptide concentrations, may occur in COVID-19 as in other pneumonias. The level of those biomarkers correlates with disease severity and mortality. Interpretation of cardiac troponin and natriuretic peptide concentrations as quantitative variables may aid in risk stratification in COVID-19/pneumonia and also will ensure that these biomarkers maintain high diagnostic accuracy for AMI and AHF. Second, activated coagulation as quantified by D-dimers seems more prominent in COVID-19 as in other pneumonias. Due to the central role of endothelitis and VTE in COVID-19, serial measurements of D-dimers may help physicians in the selection of patients for VTE imaging and the intensification of the level of anticoagulation from prophylactic to slightly higher or even therapeutic doses.