Citations

Abstract Objectives Understanding whether the novel long-T ITC complex might assist in interpreting clinical prognostic utility compared to established cardiac biomarkers is needed. We determined long term major adverse cardiac events (MACE) and all-cause mortality (ACM) predicated on novel long-T ITC complex and high sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) assays in the emergency department (ED). Methods cTn assays were measured on the Mindray CL-1200i platform at presentation in consecutive patients enrolled in ‘Mindray hs-cTnI Assay Analytical and Clinical Evaluation for the Diagnosis and RIsk Assessment of Myocardial InfarctIon’ (MERITnI) (NCT05853042) trial with suspected ischemia. Sex specific 99th percentiles upper reference limits (URLs) were: hs-cTnI female 14 ng/L, male 15 ng/L; hs-cTnT female 10 ng/L, male 19 ng/L; long-T ITC complex 0.9 ng/L, same for female and male. Results Of 1,070 patients, 59.4 % were male, 43.4 % White, 45.5 % Black, and 39.5 % ≥65 years. Independent of biomarkers, a continuum of risk over 1 year showed MACE increased to 16.1 % and ACM to 16.5 %. Long-T ITC complex did not show a continuum change, increasing only 0.1 % (HR: 1.001 (1.0–1.001) per ng/L. However, hs-cTnI increased 1.8 % (HR: 1.018 [1.009–1.027] for each ng/L (p<0.0001) and hs-cTnT increased 0.3 % per ng/L (HR: 1.003 [1.001–1.006]) (p=0.0028). Between subjects ≤URLs and >URLs, MACE and ACM all biomarkers showed significant (p<0.0001) differences over 1 year. For MACE in those >URL long-T ITC complex increased 11.2–25.2 %, hs-cTnI 18.0–35.0 % and hs-cTnT 8.9–24.2 %. For ACM in those >URL long-T ITC complex increased 4.5–23.3 %, hs-cTnI 5.0–26.2 %, and hs-cTnT 3.6–24.1 %. Conclusions Novel long-T ITC complex did not provide new prognostic value to either hs-cTnI or hs-cTnT. Patients with increased hs-cTnI and hs-cTnT concentrations had marked increases in MACE and ACM risk at 1-year.

Abstract Background We determined whether circulating cardiac troponin I–cardiac troponin T–troponin C (ITC) complex containing long-form cardiac troponin T (long-T ITC) complex and ratios of high-sensitivity cardiac troponin I (hs-cTnI) and high-sensitivity cardiac troponin T (hs-cTnT) could differentiate myocardial infarction (MI) from chronic and acute non-MI myocardial injuries in patients with suspected acute coronary syndrome. Methods We measured long-T ITC complex, hs-cTnI, and hs-cTnT (Mindray) at 0- and 2-h in consecutive patients enrolled in the Mindray hs-cTnI Assay Analytical and Clinical Evaluation for the Diagnosis and RIsk Assessment of Myocardial InfarctIon (MERITnI) trial. Results Among the 882 subjects studied (median 3.0 h presentation), 47 had acute MI (5.3%), 116 had acute non-MI myocardial injury, and 90 had chronic myocardial injury. At 0 and 2 h, areas under the curve (AUC) significantly differentiated acute MI from chronic myocardial injury for long-T ITC complex (0.72 and 0.81, respectively; P = 0.0082) but not acute non-MI myocardial injury (AUC, 0.65 and 0.69, respectively; P = 0.23). 0 and 2 h AUCs for long-T ITC complex/hs-cTnT and hs-cTnI/hs-cTnT ratios also significantly differentiated acute MI from chronic myocardial injury (AUC, 0.79 and 0.86, respectively) and acute non-MI myocardial injury (AUC, 0.68 and 0.71, respectively). There was no biomarker concentration or ratio value discrimination between type 1 and type 2 MIs. Conclusions Long-T ITC concentrations and long-T ITC complex/hs-cTnT and hs-cTnI/hs-cTnT ratios may clinically assist in differentiating acute MI from non-MI myocardial injuries when evaluating patients with suspected acute coronary syndrome. ClinicalTrials.gov Registration Number: NCT05853042.

Abstract Background/Introduction The use of a single low high-sensitivity cardiac troponin measurement to rule out myocardial infarction (MI) at presentation is advocated by international guidelines. Studies have not systematically compared high-sensitivity cardiac troponin (hs-cTn) I and T assays to determine which values should be used to rule out MI in patients with suspected acute coronary syndrome. Methods In a pooled analysis from three prospective observational cohort studies the lowest cTn concentration was determined that gave a negative predictive value (NPV) of ≥99.5% for MI or death at 30 days on presentation to the emergency department. EDTA or lithium heparin plasma or serum samples collected at presentation were measured using five hs-cTnI assays (Abbott ARCHITECT i2000, Beckman Coulter Access 2, Siemens Atellica IM, Ortho-Clinical Diagnostics VITROS 5600, LSI Medience PATHFAST) and one hs-cTnT assay (Roche Cobas e411). The diagnostic outcome of MI or death at 30 days was adjudicated according to the Fourth Universal Definition of MI. Optimal thresholds were determined to identify the highest proportion of patients that could be considered for discharge for a NPV of ≥99.5% for each assay. Results Among 941 patients, MI or death at 30 days occurred in 113 (12%). Optimized thresholds varied between assays ranging from &lt;2 to &lt;7 ng/L (Table) that identified between 22% and 60% of patients as low risk (0-1%) for MI or death at 30 days. Conclusions Our data identify differences in the effectiveness of thresholds between hs-cTnI and hs-cTnT assays for the same safety performance to rule out MI on presentation using a single measurement. In some cases, these thresholds differ from those used in clinical practice. Due to lack of assay standardization, optimal decision thresholds should be defined and validated for each high sensitivity cTn assay.

Abstract Background How to select healthy reference subjects in deriving 99th percentiles for cardiac troponin assays still needs to be clarified. To assist with global implementation of high sensitivity (hs)-cardiac troponin (cTn) I and hs-cTnT assays in clinical practice, we determined overall and sex-specific 99th percentiles in 9 hs-cTnI and 3 hs-cTnT assays using a universal sample bank (USB). Methods The Universal Sample Bank (USB) comprised healthy subjects, 426 men and 417 women, screened using a health questionnaire. Hemoglobin A1c (&gt;URL 6.5%), NT-proBNP (&gt;URL 125 ng/L) and eGFR (&lt;60 mL/min), were used as surrogate biomarker exclusion criteria along with statin use. 99th percentiles were determined by nonparametric, Harrell--Davis bootstrap, and robust methods. Results Subjects were ages 19 to 91 years, Caucasian 58%, African American 27%, Pacific Islander/Asian 11%, other 4%, Hispanic 8%, and non-Hispanic 92%. The overall and sex-specific 99th percentiles for all assays, before and after exclusions (n = 694), were influenced by the statistical method used, with substantial differences noted between and within both hs-cTnI and hs-cTnT assays. Men had higher 99th percentiles (ng/L) than women. The Roche cTnT and Beckman and Abbott cTnI assays (after exclusions) did not measure cTn values at ≥ the limit of detection in ≥50% women. Conclusions Our findings have important clinical implications in that sex-specific 99th percentiles varied according to the statistical method and hs-cTn assay used, not all assays provided a high enough percentage of measurable concentrations in women to qualify as a hs-assay, and the surrogate exclusion criteria used to define normality tended to lower the 99th percentiles.

Abstract Background The incidence and impact of acute infection among patients with type 1 (T1MI) and 2 myocardial infarction (T2MI) is not well known. Inflammation and increased procoagulant activity can lead to T1MI, whereas cytokine release can cause hemodynamic alterations affecting myocardial oxygen consumption and contribute to T2MI. Purpose Determine the incidence and prognostic impact of acute infection among patients with T1MI and T2MI. Methods Post-hoc analysis of UTROPIA (NCT02060760), a prospective, observational cohort study involving 1,640 consecutive emergency department patients with serial cardiac troponin (cTn) I measurements obtained on clinical indication. The incidence of acute infection, antibiotic use, and/or laboratory evidence of infection were examined among patients with T1MI and T2MI. 5-year cumulative survival curves were plotted using the Kaplan-Meier method, frequencies were compared via Chi-Square, and a multivariate cox-proportional hazards model was used to assess the impact of infection on mortality. Results Among 217 patients with acute MI (T1MI, n=77 and T2MI, n=140), acute infection occurred in 63 (29%) of patients. Acute infection was more common in patients with T2MI than T1MI (35% vs. 18%, p=0.009). The predominant source of infection was pneumonia (59%), followed by urinary tract infections (11%). Patients with T2MI were also more likely than T1MI to have sepsis (11% vs. 1%, p=0.012), bacteremia (30% vs. 18%, p=0.057), and antibiotic use (35% vs. 17%, p=0.005). At 5-years, patients with acute MI and acute infection had a higher mortality rate than patients without infection (49% vs. 25%, p=0.0006) (Figure). Among the 31 deaths in MI patients with acute infection, most deaths were non-cardiac (65%) and occurred in those with T2MI (77%). Following adjustment for age, sex, and comorbidities in a Cox proportional hazards model, acute infection was an independent predictor of death (hazard ratio: 2.2, 95% CI: 1.3–3.5, p=0.0016). Conclusion Acute infection occurs in almost a third of patients that are diagnosed with acute MI during the index hospitalization. Most infections are due to pneumonia and occur most often in patients classified as having T2MI. Acute infection is an independent risk factor for 5-year mortality, with nearly half of all patients with acute MI in whom concomitant acute infection is present during the index hospitalization dead at 5-years. Most deaths are non-cardiac and the vast majority occur in patients with T2MI. Acknowledgement/Funding Abbott Diagnostics and Hennepin Healthcare Research Institute (formerly MMRF)e

Abstract Background Few studies address long-term outcomes among patients with type 2 myocardial infarction (T2MI). It has been suggested that patients with T2MI with concomitant stable ischemic heart disease are at higher-risk. Purpose Our goals were two-fold. First, to examine 5-year mortality rates and mode of death among patients with type 1 (T1MI) and T2MI. Second, to evaluate the prognostic impact of coronary artery disease (CAD) on long-term outcomes among patients with T2MI. Methods Post-hoc analysis of UTROPIA (NCT02060760), a prospective, observational cohort study involving 1,640 consecutive emergency department patients with serial cardiac troponin (cTn) I measurements obtained on clinical indication. 5-year death rates, including mode of death, were examined among patients with T1MI and T2MI. CAD was defined as the presence of any of the following: history of CAD, prior MI, prior coronary artery bypass graft surgery, prior percutaneous coronary intervention, prior coronary stenting, or documented CAD (≥50%) on index admission angiography. Results Among 1640 patients, acute MI was diagnosed in 217 patients, including 77 (4.7%) classified as T1MI and 140 (8.5%) as T2MI. At 5-years, 23% (n=18) of patients with T1MI had died, with 61% (n=11) categorized as cardiac deaths. For T2MI, 37% (n=52) had died at 5-years, with 36% (n=19) categorized as cardiac deaths. Patients with T2MI had a higher 5-year mortality than T1MI (37% vs 23%, p=0.038) (Figure, Panel A), with T2MI more likely than T1MI to die from non-cardiac causes (64% vs. 39%, p=0.04). CAD was present in 22% (n=31) of patients with T2MI and associated with worse outcomes (p=0.0496) (Figure, Panel B). Conclusion T2MI has worse long term outcomes than T1MI. The predominant mode of death among patients with T2MI is non-cardiac. However, approximately 40% of deaths are cardiac. Further, we confirm the presence of CAD identifies a subset of patients with T2MI at high-risk. Acknowledgement/Funding Abbott Diagnostics and Hennepin Healthcare Research Institute (formerly MMRF)