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. .

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.

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.

Biomarkers of coagulation and fibrinolysis in acute myocardial infarction: a joint position paper of the Association for Acute CardioVascular Care and the European Society of Cardiology Working Group on Thrombosis.

The formation of a thrombus in an epicardial artery may result in an acute myocardial infarction (AMI). Despite major advances in acute treatment using network approaches to allocate patients to timely reperfusion and optimal antithrombotic treatment, patients remain at high risk for thrombotic complications. Ongoing activation of the coagulation system as well as thrombin-mediated platelet activation may both play a crucial role in this context. Whether measurement of circulating biomarkers of coagulation and fibrinolysis could be useful for risk stratification in secondary prevention is currently not fully understood. In addition, measurement of such biomarkers could be helpful to identify thrombus formation as the leading mechanism for AMI. The introduction of biomarkers of myocardial injury such as high-sensitivity cardiac troponins made rule-out of AMI even more precise. However, elevated markers of myocardial injury cannot provide proof of a type 1 AMI, let alone thrombus formation. The combined measurement of markers of myocardial injury with biomarkers reflecting ongoing thrombus formation might be helpful for the fast and correct diagnosis of an atherothrombotic type 1 AMI. This position paper gives an overview of the current knowledge and possible role of biomarkers of coagulation and fibrinolysis for the diagnosis of AMI, risk stratification, and individualized treatment strategies in patients with AMI.

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.

A case report on the successful interventional treatment of a rare cause of left heart failure in a 69-year-old woman.

BACKGROUND: Dyspnoea is very common in elderly patients and can be caused by a variety of different diseases. However, the initial diagnosis of patent ductus arteriosus (PDA) as a cause of left heart failure is very rare in this patient population. CASE SUMMARY: A 69-year-old physically active woman with known hypertension presented with worsening exertional dyspnoea. Echocardiography showed a dilated left ventricle with moderately reduced left ventricular ejection fraction, and evidence for PDA. The PDA was confirmed by computed tomography angiography and successfully closed by implantation of an Amplatzer PDA occluder II 06-06 mm. As a result, the heart failure symptoms receded completely. DISCUSSION: Congenital heart diseases should be considered as heart failure causes even in older adults. In addition to the standard medical therapy, there may be effective interventional treatment options to reverse the symptoms of heart failure in such patients.

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.

Analytical performance of a single epitope B-type natriuretic peptide sandwich immunoassay on the Minicare platform for point-of-care diagnostics.

Point-of-care B-type natriuretic peptide (BNP) testing with adequate analytical performance has the potential to improve patient flow and provide primary care givers with easy-to-use advanced diagnostic tools in the management of heart failure. We present the analytical evaluation of the Minicare BNP immunoassay under development on the Minicare I-20 platform for point-of-care testing. Analytical performance was evaluated using EDTA venous whole blood, EDTA plasma and capillary whole blood. Method comparison with a lab-testing system was performed using samples from 187 patients. Normal values were determined based on 160 healthy adults, aging from 19 to 70 years. Limit of blank (LoB), limit of detection (LoD) were determined to be 3.3 ng/L, 5.8 ng/L. Limit of quantitation (LoQ) in whole blood at 20% and 10% coefficient of variation (CV) was found < 9 ng/L and <30 ng/L respectively without significant differences between EDTA whole blood and EDTA plasma. Total CV was found to be from 6.7% to 9.7% for BNP concentrations between 92.6 and 3984 ng/L. The sample type comparison study demonstrated correlation coefficients between 0.97 and 0.99 with slopes between 1.03 and 1.09 between the different samples. Method comparison between Minicare BNP and Siemens ADVIA Centaur BNP demonstrated a correlation coefficient of 0.92 with a slope of 1.06. The 97.5% URL of a healthy population was calculated to be 72.6 ng/L. The Minicare BNP assay is a robust, easy-to-use and sensitive test for rapid determination of BNP concentrations that can be used in a near-patient setting.

Thyroid-stimulating hormone and adverse left ventricular remodeling following ST-segment elevation myocardial infarction.

BACKGROUND: Adverse left ventricular remodeling is one of the major determinants of heart failure and mortality in patients surviving ST-segment elevation myocardial infarction (STEMI). The hypothalamic-pituitary-thyroid axis is a key cardiovascular regulator; however, the relationship between hypothalamic-pituitary-thyroid status and post-STEMI left ventricular remodeling is unclear. We aimed to investigate the association between thyroid-stimulating hormone concentrations and the development of left ventricular remodeling following reperfused STEMI. METHODS: In this prospective observational study of 102 consecutive STEMI patients, thyroid-stimulating hormone levels were measured at the first day after infarction and 4 months thereafter. Cardiac magnetic resonance scans were performed within the first week as well as at 4 months follow-up to determine infarct characteristics, myocardial function and as primary endpoint left ventricular remodeling, defined as a 20% or greater increase in left ventricular end-diastolic volume. RESULTS: Patients with left ventricular remodeling (n=15, 15%) showed significantly lower concentrations of baseline (1.20 [0.92-1.91] vs. 1.73 [1.30-2.60] mU/l; P=0.02) and follow-up (1.11 [0.86-1.28] vs. 1.51 [1.15-2.02] mU/l; P=0.002) thyroid-stimulating hormone. The association between baseline thyroid-stimulating hormone and left ventricular remodeling remained significant after adjustment for major clinical (peak high-sensitivity cardiac troponin T and C-reactive protein, heart rate; odds ratio (OR) 5.33, 95% confidence interval (CI) 1.52-18.63; P=0.01) and cardiac magnetic resonance predictors of left ventricular remodeling (infarct size, microvascular obstruction, ejection fraction; OR 4.59, 95% CI 1.36-15.55; P=0.01). Furthermore, chronic thyroid-stimulating hormone was related to left ventricular remodeling independently of chronic left ventricular remodeling correlates (infarct size, ejection fraction, left ventricular end-diastolic volume, left ventricular end-systolic volume; OR 9.22, 95% CI 1.69-50.22; P=0.01). CONCLUSIONS: Baseline and chronic thyroid-stimulating hormone concentrations following STEMI were independently associated with left ventricular remodeling, proposing a novel pathophysiological axis in the development of post-STEMI left ventricular remodeling.

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.

Elevated Cardiac Troponin T in Patients With Skeletal Myopathies.

BACKGROUND: Cardiac troponins are often elevated in patients with skeletal muscle disease who have no evidence of cardiac disease. OBJECTIVES: The goal of this study was to characterize cardiac troponin concentrations in patients with myopathies and derive insights regarding the source of elevated troponin T measurements. METHODS: Cardiac troponin T (cTnT) and cardiac troponin I (cTnI) concentrations were determined by using high sensitivity assays in 74 patients with hereditary and acquired skeletal myopathies. Patients underwent comprehensive cardiac evaluation, including 12-lead electrocardiogram, 24-h electrocardiogram, cardiac magnetic resonance imaging, and coronary artery computed tomography. cTnT and cTnI protein expression was determined in skeletal muscle samples of 9 patients and in control tissues derived from autopsy using antibodies that are used in commercial assays. Relevant Western blot bands were subjected to liquid chromatography tandem mass spectrometry for protein identification. RESULTS: Levels of cTnT (median: 24 ng/l; interquartile range: 11 to 54 ng/l) were elevated (>14 ng/l) in 68.9% of patients; cTnI was elevated (>26 ng/l) in 4.1% of patients. Serum cTnT levels significantly correlated with creatine kinase and myoglobin (r = 0.679 and 0.786, respectively; both p < 0.001). Based on cTnT serial testing, 30.1% would have fulfilled current rule-in criteria for myocardial infarction. Noncoronary cardiac disease was present in 23%. Using cTnT antibodies, positive bands were found in both diseased and healthy skeletal muscle at molecular weights approximately 5 kDa below cTnT. Liquid chromatography tandem mass spectrometry identified the presence of skeletal troponin T isoforms in these bands. CONCLUSIONS: Measured cTnT concentrations were chronically elevated in the majority of patients with skeletal myopathies, whereas cTnI elevation was rare. Our data indicate that cross-reaction of the cTnT immunoassay with skeletal muscle troponin isoforms was the likely cause.

What to do when you question cardiac troponin values.

High-sensitivity cardiac troponin assays enable cardiac troponin measurement with a high degree of analytical sensitivity and a low level of analytical imprecision at the low measuring range. One of the most important advantages of these new assays is that they allow novel, more rapid approaches for ruling in or ruling out acute myocardial infarctions. The increase in the early diagnostic sensitivity of high-sensitivity cardiac troponin assays comes at the cost of a reduced acute myocardial infarction specificity of the biomarker, because more patients with other causes of acute or chronic myocardial injury without overt myocardial ischaemia are detected than with previous cardiac troponin assays. Increased troponin concentrations that do not fit with the clinical presentation are seen in the daily routine, mainly as a result of a variety of pathologies, and if tested in the same sample, even discrepancies between high-sensitivity cardiac troponin I and troponin T test results may sometimes be found as well. In addition, analytically false-positive test results occasionally may occur since no assay is perfect. In this review, we summarise the biochemical, pathophysiological and analytical background of the work-up for such a clinical setting.

How is cardiac troponin released from injured myocardium?

Cardiac troponin I and cardiac troponin T are nowadays the criterion biomarkers for the laboratory diagnosis of acute myocardial infarction due to their very high sensitivities and specificities for myocardial injury. However, still many aspects of their degradation, tissue release and elimination from the human circulation are incompletely understood. Myocardial injury may be caused by a variety of different mechanisms, for example, myocardial ischaemia, inflammatory and immunological processes, trauma, drugs and toxins, and myocardial necrosis is preceded by a substantial reversible prelethal phase. Recent experimental data in a pig model of myocardial ischaemia demonstrated cardiac troponin release into the circulation from apoptotic cardiomyocytes as an alternative explanation for clinical situations with increased cardiac troponin without any other evidence for myocardial necrosis. However, the comparably lower sensitivities of all currently available imaging modalities, including cardiac magnetic resonance imaging for the detection of particularly non-focal myocardial necrosis in patients, has to be considered for cardiac troponin test result interpretation in clinical settings without any other evidence for myocardial necrosis apart from increased cardiac troponin concentrations as well.