Citations

Background: With demographic trends transitioning towards older adults, dementia and cognitive impairment are predicted to increase dramatically. We aim to elucidate the relationship between subclinical myocardial injury, as indicated by asymptomatic increased levels of high-sensitivity cardiac Troponin (hs-cTnT), and cognitive performance. Methods: We studied MESA participants from Exam 1 (2000-02) to Exam 6 (2016-18), categorizing them based on baseline hs-cTnT at Exam 1. Cognitive decline was defined as a decrease of ≥5 units in CASI between Exam 5&6. We used Pearson correlation and linear regression to analyze the association of hs-cTnT levels with CASI scores, and logistic regression to examine the association with cognitive decline. We also explored the relationship between different hs-cTnT categories and cognitive measures. Models were adjusted for demographics, lifestyle, APOE status, comorbidities, and medication use ( Figure ). Results: 4445 participants had both baseline hs-cTnT and valid Exam 5 CASI scores while only 1776 participants had valid Exam 6 CASI scores. Cohort was predominantly female (53%), mean age of 60 years, and 27% had at least one APOE e4 allele. Median hs-cTnT was 6.32 ng/L, and median CASI scores were 89 at Exam 5 and 91.5 at Exam 6. We found a negative correlation between the log-hs-cTnT at Exam 1 and Exam 5 with CASI scores at Exam 5. An increase of one unit in log-hs-cTnT level was associated with a decrease of 0.67 (CI -1.17, -0.17) in CASI and corresponded to higher odds (OR: 1.44; CI 1.05-1.95) of cognitive decline, after adjusting for covariates. When comparing various categories of hs-cTnT with category 1, we observe that the odd of cognitive decline increases as the category increases. However, this trend does not hold for category 5 with significantly lower sample size ( Figure ). Conclusion: Our findings indicate an inverse relationship between hs-cTnT and cognitive function years later, which is significantly attenuated by known risk factors for cognitive decline. Further research is needed to determine hs-cTnT as a predictor of future global cognitive functions.

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 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.

Background: High-sensitivity (hs) cardiac troponin (cTn) assays quantifies cTn in most healthy men and women. Whether quantifiable cTn concentrations below the 99 th percentile upper-reference limit have short term prognostic implications in emergency department (ED) patients remains uncertain. Methods: Multicenter (n=22) United States (US) cohort of ED patients undergoing at least one hs-cTnT measurement (CV Data Mart Biomarker cohort). For this assay, the lowest reportable concentration is <6 ng/L. Sex-specific 99 th percentiles of 10 ng/L for women and 15 ng/L for men were used. The primary outcome was index hospitalization mortality. Results: A total of 85610 patients were examined, including 43043 women and 42567 men. A total of 775 index hospitalization deaths (0.91%) occurred, including 361 (0.84%) in women and 414 (0.97%) in men. Among women, baseline hs-cTnT concentrations were non-quantifiable (<LoQ) in 37.5%, quantifiable (LoQ-99 th ) in 21.6%, and increased >99 th percentile in 40.9%. Among men, baseline hs-cTnT concentrations were non-quantifiable (<LoQ) in 20.0%, quantifiable (LoQ-99 th ) in 37.4%, and increased >99 th percentile in 42.6%. Patients with higher concentrations were more likely to be older and had more comorbidities. Continuous baseline hs-cTnT (log) were associated with a higher odds of index hospitalization mortality (OR 1.26, 95% CI 1.24-1.28). Following multivariable analyses, quantifiable hs-cTnT (LoQ-99 th ) also were associated with index hospitalization mortality in all patients (OR 2.07, 95% 1.22-3.53), and in both women (OR 3.13, 95% CI 1.51-6.50) and men (OR 2.17, 95% 1.28-3.69) (Figure). Conclusions: Hs-cTnT concentrations within the reference range are more common in men than in women. Quantifiable hs-cTnT concentrations within the sex-specific reference range are associated with a higher risk of index hospitalization mortality, with a larger prognostic effect in women than in men.

Background: The 2021 ACC/AHA chest pain guidelines recommend risk scores such as HEAR (History, Electrocardiogram, Age, Risk Factors) for short term risk-stratification yet limited data exists integrating them with high-sensitivity cardiac troponin T (hs-cTnT). Methods: Retrospective, multicenter (n=2), observational, U.S. cohort study of consecutive ED patients without ST-elevation myocardial infarction (MI) who had at least one hs-cTnT (limit of quantitation, LoQ, <6 ng/L, and sex-specific 99 th percentiles of 10 ng/L for women and 15 ng/L for men) measurement on clinical indication in whom HEAR scores (0-8) were calculated. The composite major adverse cardiovascular (MACE) outcome was 30-day MI and death. Results: Among 1,979 ED patients undergoing hs-cTnT measurement, 1045 (53%) were classified as low-risk (0-3), 914 (46%) as intermediate-risk (4-6), and 20 (1%) as high-risk (7-8) based on HEAR scores. HEAR scores were not associated with an increased risk of 30-day MACE after adjusted analyses. Outcomes according to risk-strata based on HEAR scores and baseline hs-cTnT are shown in Table 1. Patients with quantifiable hs-cTnT (LoQ-99 th ) had an increased risk for 30-day MACE (3.4%) despite being estimated to be low-risk (0-3) per HEAR scores. Conversely, those with serial hs-cTnT<99 th percentile remained at low-risk (range 0% to 1.2%) for 30-day MACE across HEAR score strata. Conclusions: HEAR scores are of limited value in those with baseline hs-cTnT<LoQ or hs-cTnT>99 th percentile where hs-cTnT identifies very low and high-risk patients irrespective of HEAR scores. In those with baseline quantifiable hs-cTnT within the reference range (<99 th percentile), a higher risk (>1%) for 30-day MACE exists even in those with low HEAR scores. With serial hs-cTnT measurements, HEAR scores overestimate risk when hs-cTnT remains <99 th percentile.

Introduction: Differentiating type 2 myocardial infarction (T2MI) from myocardial injury can be difficult. The presence of objective evidence of acute myocardial ischemia may facilitate the identification of high-risk T2MI patients. Methods: Retrospective, observational cohort post-hoc analysis of adult emergency department patients undergoing hs-cTnT measurement. Patients with ≥1 hs-cTnT>99th percentile were adjudicated following the Fourth Universal Definition of MI. Patients were categorized as “subjective T2MI” when ischemic symptoms were the lone criteria supporting T2MI, or “objective T2MI” when there was ≥1 objective clinical feature (electrocardiography, imaging, angiography) of acute myocardial ischemia. The primary outcome was mortality. Results: A total of 857 patients were included, amongst which 55 (6.4%) were classified as subjective T2MI, 36 (4.2%) as objective T2MI, and 702 (82%) as myocardial injury. Among objective T2MIs, the most common criteria were ischemic electrocardiographic changes (n=29). Median (IQR) maximum hs-cTnT were 24 (18, 43) ng/L in myocardial injury, 34 (19, 80) in subjective T2MI, and 74 (35, 237) in objective T2MI. Those with objective T2MI had a higher risk of mortality during the index presentation (17% vs. 1.7%, p<0.0001; HR 11.1 95% CI 3.7-33.4) and at 2-year follow-up (47% vs. 31%, p=0.04; HR 1.92, 95% CI 1.17-3.14) than those with myocardial injury (Figure). Objective T2MI had a higher mortality than subjective T2MI at index presentation (17% vs. 2.0%, p=0.01) and at 1- (25% vs. 9.1%, p=0.04) and 3-months (31% vs. 13%, p=0.04) follow-up. There were no mortality differences between subjective T2MI and myocardial injury. Conclusions: In patients diagnosed with T2MI, those with objective evidence of myocardial ischemia have significantly worse outcomes compared to those with myocardial injury and subjective T2MI. A more rigorous definition of T2MI might be a more effective way to define this important entity.