Citations

Abstract 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.

Background There are limited contemporary data prevalence and outcomes of acute ischemic stroke (AIS) complicating acute myocardial infarction (AMI). Methods and Results Adult (>18 years) AMI admissions using the National Inpatient Sample database (2000–2017) were evaluated for in‐hospital AIS. Outcomes of interest included in‐hospital mortality, hospitalization costs, length of stay, discharge disposition, and use of tracheostomy and percutaneous endoscopic gastrostomy. The discharge destination was used to classify survivors into good and poor outcomes. Of a total 11 622 528 AMI admissions, 183 896 (1.6%) had concomitant AIS. As compared with 2000, in 2017, AIS rates increased slightly among ST‐segment–elevation AMI (adjusted odds ratio, 1.10 [95% CI, 1.04–1.15]) and decreased in non–ST‐segment–elevation AMI (adjusted odds ratio, 0.47 [95% CI, 0.46–0.49]) admissions ( P <0.001). Compared with those without, the AIS cohort was on average older, female, of non‐White race, with greater comorbidities, and higher rates of arrhythmias. The AMI‐AIS admissions received less frequent coronary angiography (46.9% versus 63.8%) and percutaneous coronary intervention (22.7% versus 41.8%) ( P <0.001). The AIS cohort had higher in‐hospital mortality (16.4% versus 6.0%; adjusted odds ratio, 1.75 [95% CI, 1.72–1.78]; P <0.001), longer hospital length of stay, higher hospitalization costs, greater use of tracheostomy and percutaneous endoscopic gastrostomy, and less frequent discharges to home (all P <0.001). Among AMI‐AIS survivors (N=153 318), 57.3% had a poor functional outcome at discharge with relatively stable temporal trends. Conclusions AIS is associated with significantly higher in‐hospital mortality and poor functional outcomes in AMI admissions.

Abstract 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.

Abstract Background The prognostic implications of cardiac procedural myocardial injury and infarction (MI) in chronic coronary syndrome patients undergoing elective percutaneous coronary intervention (PCI) is still debated. Objective To determine the optimal cardiac troponin threshold for identifying prognostically important events. Methods Using a pooled dataset of nine registries and one randomized trial, we analysed individual data of 14,433 patients undergoing elective PCI with a normal or moderately elevated baseline pre-PCI cardiac troponin (cTn). A multivariate model was performed to evaluate the associations between post-PCI cTn elevation and 1-year mortality after PCI, including thresholds used by existing procedural myocardial injury definitions (Fourth Universal Definition of MI [UDMI] and Academic Research Consortium 2 [ARC-2] / Society for Cardiovascular Angiography and Interventions (SCAI)). The association between type 4a MI and 1-year mortality was also evaluated. Results Procedural myocardial injury defined by the Fourth UDMI occurred in 52.5% of patients and was not associated with 1-year mortality (adjOR 1.27, 95% CI [0.90–1.81] p=0.18). The association between post-PCI cTn elevation and 1-year mortality was significant above a 3-fold increase above the upper reference limit, and was optimal for a 5.2-fold increase which corresponded to an 18.3% rate of event, and an adjOR of 2.03 (95% CI [1.31–3.14], p=0.002) (figure). Procedural myocardial injury defined by the ARC-2/SCAI definition occurred in 1.3% of the patients, had a strong association with 1-year mortality (adjOR 4.15, 95% CI [1.62–10.64], p&lt;0.01) but lacked sensitivity (5.2% sensitivity). Type 4a MI occurred in 12.7% of patients, was strongly associated with 1-year mortality (adjOR 3.18, 95% CI [1.47–6.90], p=0.002), but could only be evaluated in a subset of patients (n=3 084) with available data on new myocardial ischaemia post-PCI. Conclusions We have demonstrated that a post-PCI cTn elevation ≥5x the 99th percentile URL in CCS patients with normal baseline cTn, represents the optimal threshold for defining prognostically important or “Major” procedural myocardial injury in the absence of evidence for new myocardial ischaemia. Major procedure related myocardial injury and type 4a MI should be considered as a quality metric and endpoints in clinical trials. Adjusted OR of mortality at 1 year Funding Acknowledgement Type of funding source: None

Abstract Background and introduction Cardioversion is commonly used to terminate cardiac arrhythmias. Some previous reports have suggested that cardioversion results in myocardial injury as evidenced by increased levels of cardiac troponin. However, many of these studies were done years ago with less sensitive troponin assays and monophasic waveform defibrillators. Purpose To determine if external direct current (DC) cardioversion with biphasic rectilinear waveform shocks results in myocardial injury as assessed by high sensitivity cardiac troponin T (hs-cTnT) and I (hs-cTnI). Methods Patients scheduled for elective DC cardioversion for atrial fibrillation or atrial flutter were recruited. Plasma samples for measurement of hs-cTnT and hs-cTnI were obtained pre-cardioversion and as late as feasible but at least 6 hours post-cardioversion [median of 9 (7–11) hours]. Results A total of 96 patients were recruited. One patient was excluded because the pre-cardioversion sample was hemolysed. Median (25th–75th interquartile range) cumulative energy delivered was 121.6J (62.4–277.4J) and median highest energy individual shock was 121.0J (62.1–146.2J). A total of 39 (41.1%) patients received more than 1 shock, 23 (24.2%) patients received a cumulative energy of 300J or higher and 5 (5.3%) patients received a cumulative energy of 1,000J or more. The median pre-cardioversion hs-cTnT value was 11.48 (7.19–18.38) ng/L and the median hs-cTnI value was 5.1 (2.0–9.4) ng/L. Median post-cardioversion hs-cTnT value were 12.46 (7.98–20.28) ng/L and hs-cTnI value were 6.3 (3.5–10.0) ng/L. Wilcoxon-Signed ranks test showed a statistically significant change between the pre-and-post cardioversion hs-cTnT values (Z=−4.237, p&lt;0.001) and hs-cTnI values (Z=−4.822, p&lt;0.001). In only 5 (hs-cTnT) and 4 patients (hs-cTnI) was there an increase of &gt;5 ng/L. There were 5 cases where the post-cardioversion values of both hs-cTnT and hs-cTnI were above the 50% reference change value. There was no relation between the change in hs-cTn values and sex, number of shocks, total energy delivered (even in those who received more than 1,000J), highest energy per shock, total current delivered, highest current delivered per shock or transthoracic impedance. Conclusion(s) There is a statistically significant but very small change in median hs-cTnT and hs-cTnI values (1 ng/L and 1.2 ng/L respectively) after DC cardioversion. The results were similar even in patients where high energy shocks were delivered and did not vary based on the pre cardioversion baseline value. Patients who have marked troponin elevations after cardioversion should be assessed for other causes of myocardial injury. It should not be assumed that they have myocardial injury from the cardioversion alone. Figure 1 Funding Acknowledgement Type of funding source: Other. Main funding source(s): Dr. Allan Jaffe has substantial research funds from both grants and private industry. Funds were used to pay for blood sample collection and analysis of high sensitivity cardiac troponin T at Mayo Clinic. Abbott Laboratories donated reagents for the high sensitivity cardiac troponin I analysis.

Background: Myocardial injury results in release of cardiac troponin (cTn) into the bloodstream, readily detected by high-sensitivity cTn (hs-cTn) assays. A noninvasive, rapid, home-based test to exclude acute myocardial injury at the time of the test and for the next 7 hours would help manage patients with suspected myocardial infarction. Since myocyte injury is associated with ECG changes, we hypothesized an artificial intelligence ECG (AI-ECG) could identify absence of injury. Objective: To train and test an AI-ECG convolutional neural network (CNN) to identify patients using a single ECG who are suspected of myocardial infarction who are low risk, with hs-cTn levels below the 99 th percentile at test time and for the subsequent 7 hours. Methods: A CNN tuned to identify the absence of a hs-cTnT (5 th Gen cTnT Roche Diagnostics) >15ng/L for men and >10ng/L for women was developed. All ECGs were recorded within one hour of the hs-cTnT assay. We used 73,012 ECGs and hs-cTnT pairs from 47,542 unique patients to train the network, 9031 ECGs from 5,811 patients for internal validation to optimize hyperparameters, and 11,904 ECGs with 21,191 hs-cTnT measurements up to 7 hours after the ECG, from 11,904 different patients as a holdout test set. Results: The mean age was 63.9±17.5 years, and 30,348 of the 59,446 patients (51%) were male. 5,852 patients (49.1%) had no elevation of hs-cTnT and 6,052 (50.9%) had an hs-cTnT above the 99 th percentile at baseline or within 7 hours of the test. Of the 11,904 patients in the test set, using a sensitive threshold, the 12 lead AI ECG identified 1037 patients (8.7%) likely to have a low risk for subsequent hs-cTnT increases > 99 th % (AUC 0.86), and the single lead ECG identified 685 patients. Of the 1037 low risk pts, 59 had an hs-cTnT > 99 th percentile within 7 hours. The mean maximum hs-cTnT among the 59 low-risk patients was 53 ng/L ± 92 vs 184 ng/L ± 1474 in the others. None of these low risk patients died within 14 days of the test. Conclusion: Use of the AI ECG to identify patients without cardiac injury at the time of the test and for 7 subsequent hours is feasible. This may permit rapid, point of care, home-based, bloodless, painless testing to exclude cardiac injury, facilitating care and management of patients with suspected ischemia.

Background: High-sensitivity cardiac troponin (hs-cTn) assays quantify cTn in patients at very low concentrations. Myocyte injury due to ischemia or other pathologies cause blood levels to increase, which is prognostic. A noninvasive, rapid, broadly available, home-based test to detect hs-cTn increases would facilitate risk-stratification. Since myocyte injury is associated with ECG changes, we hypothesized an artificial intelligence ECG (AI-ECG) could non-invasively predict current or impending hs-cTnT elevations. Objective: To develop an AI-ECG convolutional neural network (CNN) to detect an abnormal hs-cTnT (5 th Gen cTnT, Roche Diagnostics) concentration using a 12-lead ECG, and a single lead ECG (lead I), which would enable smartphone, home-based detection. Methods: We developed single lead and 12-lead ECG CNNs to detect a) hs-cTnT concentrations that were at or above the 6ng/L limit that can be reported b) above the 99 th percentile upper limits of >15ng/L for men and >10ng/L for women. All ECGs were recorded within one hour of the hs-cTnT measurements. We used 73,012 ECG and hs-cTnT pairs from 47,542 unique patients to train the network, 9031 ECGs from 5,811 patients for internal validation to optimize hyperparameters, and 18,276 ECG and hs-cTnT pairs from 11,904 different patients as a holdout test set to determine the area under the receiver-operator curve (AUC). Results: The mean age was 63.9±17.5 years, and 30,348 of the 59,446 patients (51%) were male. Of the 91,288 hs-cTnT pairs 73,271 (80.2%) were above 6ng/L and 50,799 (55.6%) are above the 99 th percentile. In the test set, the AUC for the detection of a hs-cTnT level higher than 6ng/L was 0.88 using the 12 lead ECG and 0.834 with the single lead. For the detection of hs-cTnT level above of 99 th percentile, the 12 lead ECG AUC was 0.853 and the single lead was 0.806. Conclusion: The AI-ECG permits detection of levels of hs-cTnT consistent with myocardial injury. This may allow a home-based, non-invasive test that would be massively scalable and could further enhance rapid-risk stratification and patient triage with potentially significant cost reductions and enable novel triage strategies at sites without hs-cTn assays.