Ola, Oluwabukola Mary

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 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 Guidelines suggest that the diagnosis of acute myocardial infarction (MI) is likely when high concentrations of high-sensitivity cardiac troponin (hs-cTn) are present in the initial sample. These concentration thresholds are much higher than the 99th percentile and are said to provide a high positive predictive value (PPV) for acute MI1. Purpose Evaluate the PPV of recommended baseline hs-cTnT thresholds (>52 and >100 ng/L) for the diagnosis of acute MI from our multi-center United States (US) experience. Methods Retrospective, multicenter (n=22), observational biomarker study involving consecutive, adult patients presenting to the emergency department (ED) in whom at least 1 hs-cTnT measurement was obtained within 12 hours of presentation (CV DataMart Biomarker cohort). The primary endpoint was also evaluated in an adjudicated cohort of consecutive patients presenting to the ED with at least 1 hs-cTnT >99th percentile (ACTION cohort). These cases were adjudicated based on the Fourth Universal Definition of MI by trained physicians. The primary efficacy endpoint was the PPV of acute MI (type 1 or 2), type 1 MI and type 2 MI during index hospitalization using baseline hs-cTnT thresholds of >52 ng/L and >100 ng/L. Results The CV DataMart Biomarker cohort consisted of 143,709 patients, amongst whom 3,003 (2.1%) were diagnosed with acute MI using ICD codes. In the CV DataMart Biomarker cohort, baseline hs-cTnT concentrations of >52 ng/L and >100 ng/L resulted in PPVs of 12% (95% CI: 11, 12) and 17% (95% CI: 17, 19) for acute MI, respectively. In patients with chest pain and baseline hs-cTnT concentrations >52 ng/L, PPV for acute MI was 17% (95% CI: 15, 18), and in those with hs-cTnT concentrations >100 ng/L, PPV was 22% (95% CI: 19, 25). The adjudicated ACTION cohort consisted of 2,107 patients, amongst whom 155 (7.4%) were diagnosed with acute MI including 64 (41%) with type 1 MI and 91 (59%) with type 2 MI. In the ACTION cohort, baseline hs-cTnT concentrations of >52 ng/L and >100 ng/L resulted in PPVs of 46% (95% CI: 40, 53) and 62% (95% CI: 53, 70) for acute MI, respectively. In patients with chest pain and baseline hs-cTnT concentrations >52 ng/L, PPV was 67% (95% CI: 57, 76) for acute MI, 52% (95% CI: 41, 62) for type 1 MI and 15% (95% CI: 8.4, 24) for type 2 MI. In those with chest pain and baseline hs-cTnT concentrations >100 ng/L, PPV was 77% (95% CI: 65, 87) for acute MI, 64% (95% CI: 51, 75) for type 1 MI and 14% (95% CI 6.4, 24) for type 2 MI (Figure). Conclusion Using previously recommended high-risk hs-cTnT thresholds of 52 and 100 ng/L in US patients provides reasonable performance to rule-in acute MI when used in patients with chest pain. When used more broadly across all-comers, the diagnostic performance is poor.

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 Background Several high-sensitivity cardiac troponin (cTn) assays have been cleared by the United States (US) Food and Drug Administration (FDA) for clinical use. Although some of them have been used outside the US for some time, there is limited experience thus far across US sites. Following FDA clearance of the Roche 5th Gen cTnT assay in January 2017, a multicenter US regional healthcare system introduced this more sensitive cTnT assay into clinical practice in September 2018. Purpose To examine cTn testing patterns, incidence of acute myocardial infarction (MI), and resource utilization before and after implementation of the 5th Gen cTnT assay across a large US healthcare system. Methods Using electronic-health records reporting software (Cogito SlicerDicer, EPIC), administrative data was examined to evaluate the transition (4-months before and after implementation) from the 4th to 5th Gen cTnT assays across 16 hospitals but not the major hub hospital of the system that transitioned at a separate time. Adult patient visits (emergency and hospital encounters), cTnT testing, incidence of chest discomfort and acute MI, and resource utilization, including hospital admissions, were examined during the transition period. Results 98,558 adult ED patient visits occurred during an 8-month period across 16 hospitals, including 50,485 and 48,073 patient visits before (5/12/18 – 9/11/18) and after (9/12/18 – 1/11/19) implementation of the 5th Gen cTnT assay respectively. cTnT testing occurred in 20% (range 8.9–34.8%) of all ED visits, with testing performed in the absence of chest pain in 54% (range 37–67%) of cases. Acute MI was diagnosed in 5.6% (n=561) of cases using the 4th Gen cTnT assay as compared to 6.6% (n=608) of cases using the 5th Gen cTnT assay (absolute difference 1.0%, 95% CI: 0.32–1.68, p=0.004). Much of the increase in MI diagnoses were in women (2.2% vs. 2.8%, p=0.008). The proportion of ED patients requiring hospital admission did not differ between pre- and post-implementation periods (24.1% vs. 23.6%, p=0.4); however, among the subset of patients with chest pain, fewer admissions occurred post-implementation (17.9% vs. 15.8%, p=0.006). There was no increase in echocardiography (9.3% vs. 8.4%), coronary angiography (2.9% vs. 3.1%), or cardiac consultations (7.3% vs. 7.3%) utilization post-implementation. Conclusions Cardiac troponin testing occurs in nearly 20% of ED visits in a large multicenter regional healthcare system. About half of all tests are ordered in the absence of chest pain, with a low MI rate observed among the patients undergoing testing. Following implementation of the 5th Gen cTnT assay, testing rates/patterns remained unchanged, with a small but significant increase in MI diagnoses, primarily due to more women being diagnosed with MI. Fewer ED patients with chest pain required admission. Despite using a more sensitive cTn assay, hospital admissions and resource utilization did not increase post-implementation.