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Abstract Background Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as these patients often have elevated baseline high-sensitivity cardiac troponin T (hs-cTnT) concentrations. Methods Observational U.S. cohort study of emergency department (ED) patients undergoing hs-cTnT measurement. Cases with >1 hs-cTnT increase >99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2- and 6-hour hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (eGFR <60 ml/min/1.73m2). Results The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 701 (82%) patients with myocardial injury, 64 (7.5%) with type 1, and 91 (11%) with type 2 MI. In CKD patients with baseline hs-cTnT thresholds of >52, >100, >200 or >300 ng/L, PPVs for acute MI were 37% [95% CI 28-46], 53% (95% CI 39-67), 73% (95% CI 50-89) and 80% (95% CI 44-98), and in those without CKD, 64% (95% CI 50-77), 69% (95% CI 49-85), 59% (95% CI 33-82) and 54% (95% CI 25-81). In CKD patients with a 2-hour hs-cTnT delta of >10, >20 or >30 ng/L, the corresponding PPVs were 65% (95% CI 50-78), 86% (95% CI 68-96) and 88% (95% CI 68-97), and in those without CKD, 65% (95% CI 51-78), 73% (95% CI 57-86) and 75% (95% CI 58-88) (Figure). Conclusion Diagnostic performance of standard baseline and serial 2-hour hs-cTnT thresholds to rule-in MI is suboptimal in patients with CKD. It significantly improves when using higher baseline thresholds and delta values.

Abstract Aims Diagnosing myocardial infarction (MI) in patients with chronic kidney disease (CKD) is difficult as they often have increased high-sensitivity cardiac troponin T (hs-cTnT) concentrations. Methods and results Observational US cohort study of emergency department patients undergoing hs-cTnT measurement. Cases with ≥1 hs-cTnT increase > 99th percentile were adjudicated following the Fourth Universal Definition of MI. Diagnostic performance of baseline and serial 2 h hs-cTnT thresholds for ruling-in acute MI was compared between those without and with CKD (estimated glomerular filtration rate < 60 mL/min/1.73 m2). The study cohort included 1992 patients, amongst whom 501 (25%) had CKD. There were 75 (15%) and 350 (70%) patients with CKD and 80 (5%) and 351 (24%) without CKD who had acute MI and myocardial injury. In CKD patients with baseline hs-cTnT thresholds of ≥52, >100, >200, or >300 ng/L, positive predictive values (PPVs) for MI were 36% (95% CI 28–45), 53% (95% CI 39–67), 73% (95% CI 50–89), and 80% (95% CI 44–98), and in those without CKD, 61% (95% CI 47–73), 69% (95% CI 49–85), 59% (95% CI 33–82), and 54% (95% CI 25–81). In CKD patients with a 2 h hs-cTnT delta of ≥10, >20, or >30 ng/L, PPVs were 66% (95% CI 51–79), 86% (95% CI 68–96), and 88% (95% CI 68–97), and in those without CKD, 64% (95% CI 50–76), 73% (95% CI 57–86), and 75% (95% CI 58–88). Conclusion Diagnostic performance of standard baseline and serial 2 h hs-cTnT thresholds to rule-in MI is suboptimal in CKD patients. It significantly improves when using higher baseline thresholds and delta values.

Abstract Background There are no robust data addressing the United States (US) experience with the 0/2 hours (h) European Society of Cardiology (ESC) algorithm using high-sensitivity cardiac troponin T (hs-cTnT). Purpose To evaluate the diagnostic performance of the 0/2h ESC-recommended absolute deltas in a US population. Methods Observational US cohort study of ED patients undergoing 0 and 2 h hs-cTnT measurements. The 99th percentiles upper reference limits (URL) used were 10 ng/L for women and 15 ng/L for men. Diagnostic outcomes were the adjudicated diagnoses of acute myocardial infarction (MI, type 1 or 2). Results A total of 1084 patients met inclusion criteria, amongst which 49% were women. Chest discomfort was reported in 521 (48%) patients. Among patients with a baseline hs-cTnT≤99th URL (n=434), 4 MIs occurred. To rule-out MI, an absolute 0-2h delta change <4 ng/L resulted in a sensitivity of 100% (95% CI: 39.8, 100) and a negative predictive value (NPV) of 100% (95% CI: 99.1, 100). To rule-in MI, an absolute 0-2h delta ≥10 ng/L had a specificity of 99.8 % (95% CI: 98.7, 99.9) and positive predictive value (PPV) of 75% (95% CI: 19.4, 99.4). Among patients with a baseline hs-cTnT >99th URL (n=650), 110 MIs occurred. In these patients, both rule-out (sensitivity 65%, NPV 91%) and rule-in (specificity 7.2%, PPV 11%) were poor using the ESC-recommended absolute deltas. Among patients with modest hs-cTnT increases (99th URL to 100 ng/L) neither the ESC-recommended absolute nor the Fourth Universal Definition of MI (UDMI)-recommended relative deltas provided acceptable performance. Among patients with marked hs-cTnT increases at presentation (>100 ng/L), a relative delta change >20% as recommended by the UDMI resulted in a superior rule-in performance, with a specificity of 92.0% (95% CI 74.0, 99.0) and PPV of 84.6% (57.4, 95.7). Conclusions In our unselected US-cohort of patients undergoing hs-cTnT, the 0/2h ESC algorithm had a good diagnostic performance in patients without myocardial injury at presentation. Conversely, in patients with myocardial injury at baseline, the ESC-recommended absolute deltas performed poorly to determine who had MI. In patients with marked hs-cTnT increases >100 ng/L at presentation, the UDMI recommended 20% relative change showed good rule-in performance.

Abstract Background Artificial intelligence-augmented electrocardiogram (AI-ECG) algorithms have been developed from the standard 12-lead ECG and validated for the recognition of left ventricular systolic dysfunction (LVSD), defined as LV ejection fraction (LVEF)≤35%. Whether AI-ECG facilitates identification of LVSD and is associated with adverse outcomes in emergency department (ED) patients undergoing high-sensitivity cardiac troponin (hs-cTnT) testing is uncertain. Purpose To investigate the diagnostic and prognostic performance of AI-ECG in ED patients undergoing hs-cTnT measurement. Methods Observational US cohort study of ED patients undergoing hs-cTnT measurement. Cases with hs-cTnT increases >sex-specific 99th percentiles were adjudicated following the Fourth Universal Definition of Myocardial Infarction (MI). Post-discharge major adverse cardiac events (MACE) included death, MI, heart failure (HF) hospitalization, stroke or transient ischemic attack, and new onset atrial fibrillation/flutter during 2-years follow-up. The AI-ECG network output, which is a continuous number between 0–1, that provides a probability of LVSD, was obtained for each patient from the first ECG during the index presentation. An AI-ECG threshold of ≥0.256 indicates a positive screen that correlates with a high probability of LVSD. Results Among 1977 patients, 1729 (87%) had a negative AI-ECG screen, while 248 (13%) had a positive AI-ECG screen. Patients with a positive AI-ECG screen were older and had more comorbidities. As compared to patients with hs-cTnT≤99th percentile in whom AI-ECG was positive in 5.8%, those with hs-cTnT>99th percentile had a positive AI-ECG in 22% of cases (p<0.0001). Based on adjudicated diagnoses, the frequency of a positive AI-ECG was 20% in myocardial injury, 38% in type 1 MI, and 20% in type 2 MI. At 2-years follow-up, as compared to patients with a negative AI-ECG, those with a positive AI-ECG had a higher risk for MACE (48% vs. 21%, p<0.0001, adjusted HR 1.39, 95% CI 1.11–1.75) (Figure 1), mainly because of more deaths (43% vs. 30%, p=0.004) and HF hospitalizations (36% vs. 13%, p<0.0001). A positive AI-ECG was associated with a higher risk for MACE (60% vs. 41%, p<0.0001, adjusted HR 1.30, 95% CI 1.02–1.64) in those with hs-cTnT increases >99th percentile, but not in those without hs-cTnT increases. Among patients with an echocardiogram during index presentation or within 30-days (n=452), the diagnostic accuracy of AI-ECG for LVEF ≤35% was 81.4% (95% CI 77.5, 84.9) with a negative predictive value of 96.5% (95% CI 94.0, 98.2). A normal LVEF (>50%) was observed in 87% of those with a negative AI ECG, whereas in those with a positive AI-ECG LVEF was reduced (<50%) in 60%. Conclusions Among ED patients evaluated with hs-cTnT, a positive AI-ECG screen for LVSD identifies patients at high risk of MACE. These findings are largely because of more deaths and HF hospitalizations in those with hs-cTnT increases >sex-specific 99th percentiles. Funding Acknowledgement Type of funding sources: None.

Abstract Aims Limited US outcome data exist among patients with myocardial injury and types 1 and 2 myocardial infarction (MI) evaluated with high-sensitivity cardiac troponin (hs-cTn). Methods and results This is an observational US cohort study of emergency department (ED) patients undergoing hs-cTnT measurement. Cases with ≥1 hs-cTnT increase >99th percentile were adjudicated following the Fourth Universal Definition of MI. Post-discharge major adverse cardiovascular events (MACE) included death, MI, heart failure (HF) hospitalization, stroke or transient ischaemic attack, and new-onset atrial fibrillation or flutter during 2 years follow-up. Among 2002 patients, 857 (43%) had ≥1 hs-cTnT >99th percentile. Among these, 702 (81.9%) had myocardial injury, 64 (7.5%) had type 1 MI, and 91 (10.6%) had type 2 MI. Compared with patients without myocardial injury, type 2 MI [8.4 vs. 50%; adjusted hazard ratio (HR) 2.31, 95% confidence interval (CI) 1.49–3.58] and myocardial injury (8.4 vs. 47%; adjusted HR 3.13, 95% CI 2.39–4.09) had a higher risk of MACE, in large part because of death and HF hospitalizations. Compared with patients with type 1 MI, type 2 MI (23 vs. 50%; adjusted HR 2.24; 95% CI 1.23–4.10) and myocardial injury (23 vs. 47%; adjusted HR 2.02; 95% CI 1.20–3.40) also have a higher risk of MACE. Conclusion Among unselected US ED patients undergoing hs-cTnT measurement, most increases are due to myocardial injury, and type 2 MI is more frequent than type 1 MI. Patients with myocardial injury and type 2 MI have morbid outcomes, in large part due to death and HF.

Background: There are good data to support using a single high-sensitivity cardiac troponin T (hs-cTnT) below the limit of detection of 5 ng/L to exclude acute myocardial infarction. Per the US Food and Drug Administration, hs-cTnT can only report to the limit of quantitation of 6 ng/L, a threshold for which there are limited data. Our goal was to determine whether a single hs-cTnT below the limit of quantitation of 6 ng/L is a safe strategy to identify patients at low risk for acute myocardial injury and infarction. Methods: The efficacy (proportion identified as low risk based on baseline hs-cTnT<6 ng/L) of identifying low-risk patients was examined in a multicenter (n=22 sites) US cohort study of emergency department patients undergoing at least 1 hs-cTnT (CV Data Mart Biomarker cohort). We then determined the performance of a single hs-cTnT<6 ng/L (biomarker alone) to exclude acute myocardial injury (subsequent hs-cTnT >99th percentile in those with an initial hs-cTnT<6 ng/L). The clinically intended rule-out strategy combining a nonischemic ECG with a baseline hs-cTnT<6 ng/L was subsequently tested in an adjudicated cohort in which the diagnostic performance for ruling out acute myocardial infarction and safety (myocardial infarction or death at 30 days) were evaluated. Results: A total of 85 610 patients were evaluated in the CV Data Mart Biomarker cohort, among which 24 646 (29%) had a baseline hs-cTnT<6 ng/L. Women were more likely than men to have hs-cTnT<6 ng/L (38% versus 20%, P <0.0001). Among 11 962 patients with baseline hs-cTnT<6 ng/L and serial measurements, only 1.2% developed acute myocardial injury, resulting in a negative predictive value of 98.8% (95% CI, 98.6–99.0) and sensitivity of 99.6% (95% CI, 99.5–99.6). In the adjudicated cohort, a nonischemic ECG with hs-cTnT<6 ng/L identified 33% of patients (610/1849) as low risk and resulted in a negative predictive value and sensitivity of 100% and a 30-day rate of 0.2% for myocardial infarction or death. Conclusions: A single hs-cTnT below the limit of quantitation of 6 ng/L is a safe and rapid method to identify a substantial number of patients at very low risk for acute myocardial injury and infarction.

AbstractDespite the widespread adoption of primary percutaneous intervention and modern antithrombotic therapy, ST-segment elevation myocardial infarction (STEMI) remains the leading cause of death in the United States and remains one of the most important causes of morbidity and mortality worldwide. Certain high-risk patients present a challenge for diagnosis and treatment. The widespread adoption of primary percutaneous intervention in addition to modern antithrombotic therapy has resulted in substantial improvement in the short- and long-term prognosis following STEMI. In this review, we aim to provide a brief analysis of the state-of-the-art treatment for patients presenting with STEMI, focusing on cardiogenic shock, current treatment and controversies, cardiac arrest, and diagnosis and treatment of mechanical complications, as well as multivessel and left main-related STEMI.