Browsing by Subject "Troponin I"

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    Ideal high sensitivity troponin baseline cutoff for patients with renal dysfunction.
    (The American journal of emergency medicine, 2022-06) Limkakeng, Alexander T; Hertz, Julian; Lerebours, Reginald; Kuchibhatla, Maragatha; McCord, James; Singer, Adam J; Apple, Fred S; Peacock, William F; Christenson, Robert H; Nowak, Richard M
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    Meta-analysis of cardiomyopathy-associated variants in troponin genes identifies loci and intragenic hot spots that are associated with worse clinical outcomes.
    (Journal of molecular and cellular cardiology, 2020-05) Tadros, Hanna J; Life, Chelsea S; Garcia, Gustavo; Pirozzi, Elisa; Jones, Edward G; Datta, Susmita; Parvatiyar, Michelle S; Chase, P Bryant; Allen, Hugh D; Kim, Jeffrey J; Pinto, Jose R; Landstrom, Andrew P
    INTRODUCTION:Troponin (TNN)-encoded cardiac troponins (Tn) are critical for sensing calcium and triggering myofilament contraction. TNN variants are associated with development of cardiomyopathy; however, recent advances in genetic analysis have identified rare population variants. It is unclear how certain variants are associated with disease while others are tolerated. OBJECTIVE:To compare probands with TNNT2, TNNI3, and TNNC1 variants and utilize high-resolution variant comparison mapping of pathologic and rare population variants to identify loci associated with disease pathogenesis. METHODS:Cardiomyopathy-associated TNN variants were identified in the literature and topology mapping conducted. Clinical features were compiled and compared. Rare population variants were obtained from the gnomAD database. Signal-to-noise (S:N) normalized pathologic variant frequency against population variant frequency. Abstract review of clinical phenotypes was applied to "significant" hot spots. RESULTS:Probands were compiled (N = 70 studies, 224 probands) as were rare variants (N = 125,748 exomes; 15,708 genomes, MAF <0.001). TNNC1-positive probands demonstrated the youngest age of presentation (20.0 years; P = .016 vs TNNT2; P = .004 vs TNNI3) and the highest death, transplant, or ventricular fibrillation events (P = .093 vs TNNT2; P = .024 vs TNNI3; Kaplan Meir: P = .025). S:N analysis yielded hot spots of diagnostic significance within the tropomyosin-binding domains, α-helix 1, and the N-Terminus in TNNT2 with increased sudden cardiac death and ventricular fibrillation (P = .004). The inhibitory region and C-terminal region in TNNI3 exhibited increased restrictive cardiomyopathy (P =.008). HCM and RCM models tended to have increased calcium sensitivity and DCM decreased sensitivity (P < .001). DCM and HCM studies typically showed no differences in Hill coefficient which was decreased in RCM models (P < .001). CM models typically demonstrated no changes to Fmax (P = .239). CONCLUSION:TNNC1-positive probands had younger ages of diagnosis and poorer clinical outcomes. Mapping of TNN variants identified locations in TNNT2 and TNNI3 associated with heightened pathogenicity, RCM diagnosis, and increased risk of sudden death.
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    Outpatient versus observation/inpatient management of emergency department patients rapidly ruled-out for acute myocardial infarction: Findings from the HIGH-US study.
    (American heart journal, 2021-01) Nowak, Richard M; Jacobsen, Gordon; Limkakeng, Alexander; Peacock, William F; Christenson, Robert H; McCord, James; Apple, Fred S; Singer, Adam J; deFilippi, Christopher R

    Background

    The actual Emergency Department (ED) dispositions of patients enrolled in observational studies and meeting criteria for rapid acute myocardial infarction (AMI) rule-out are unknown. Additionally, their presenting clinical profiles, cardiac testing/treatments received, and outcomes have not been reported.

    Methods

    Patients in the HIGH-US study (29 sites) that ruled-out for AMI using a high-sensitivity cardiac troponin I 0/1-hour algorithm were evaluated. Clinical characteristics of patients having ED discharge were compared to patients placed in observation or hospital admitted (OBS/ADM). Reports of any OBS/ADM cardiac stress test (CST), cardiac catheterization (Cath) and coronary revascularization were reviewed. One year AMI/death and major adverse cardiovascular event rates were determined.

    Results

    Of the 1,020 ruled-out AMI patients 584 (57.3%) had ED discharge. The remaining 436 (42.7%) were placed in OBS/ADM. Patients with risk factors for AMI, including personal or family history of coronary artery disease, hypertension, previous stroke or abnormal ECG were more often placed in OBS/ADM. 175 (40.1%) had a CST. Of these 32 (18.3%) were abnormal and 143 (81.7%) normal. Cath was done in 11 (34.3%) of those with abnormal and 13 (9.1%) with normal CST. Of those without an initial CST 85 (32.6%) had Cath. Overall, revascularizations were performed in 26 (6.0%) patients. One-year AMI/death rates were low/similar (P = .553) for the groups studied.

    Conclusions

    Rapidly ruled-out for AMI ED patients having a higher clinician perceived risk for new or worsening coronary artery disease and placed in OBS/ADM underwent many diagnostic tests, were infrequently revascularized and had excellent outcomes. Alternate efficient strategies for these patients are needed.
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    Performance of Novel High-Sensitivity Cardiac Troponin I Assays for 0/1-Hour and 0/2- to 3-Hour Evaluations for Acute Myocardial Infarction: Results From the HIGH-US Study.
    (Annals of emergency medicine, 2020-07) Nowak, Richard M; Christenson, Robert H; Jacobsen, Gordon; McCord, James; Apple, Fred S; Singer, Adam J; Limkakeng, Alexander; Peacock, William F; deFilippi, Christopher R
    STUDY OBJECTIVE:We determine the accuracy of high-sensitivity cardiac troponin I (hs-cTnI), European-derived, rapid, acute myocardial infarction, rule-out/rule-in algorithms applied to a US emergency department (ED) population. METHODS:Adults presenting to the ED with suspected acute myocardial infarction were included. Plasma samples collected at baseline and between 40 and 90 minutes and 2 and 3 hours later were analyzed in core laboratories using the Siemens Healthineers hs-cTnI assays. Acute myocardial infarction diagnosis was independently adjudicated. The sensitivity, specificity, and negative and positive predictive values for rapid acute myocardial infarction rule-out/rule-in using European algorithms and 30-day outcomes are reported. RESULTS:From 29 US medical centers, 2,113 subjects had complete data for the 0/1-hour algorithm analyses. With the Siemens Atellica Immunoassay hs-cTnI values, 1,065 patients (50.4%) were ruled out, with a negative predictive value of 99.7% and sensitivity of 98.7% (95% confidence interval 99.2% to 99.9% and 96.3% to 99.6%, respectively), whereas 265 patients (12.6%) were ruled in, having a positive predictive value of 69.4% and specificity of 95.7% (95% confidence interval 63.6% to 74.7% and 94.7% to 96.5%, respectively). The remaining 783 patients (37.1%) were classified as having continued evaluations, with an acute myocardial infarction incidence of 5.6% (95% confidence interval 4.2% to 7.5%). The overall 30-day risk of death or postdischarge acute myocardial infarction was very low in the ruled-out patients but was incrementally increased in the other groups (rule-out 0.2%; continued evaluations 2.1%; rule-in 4.8%). Equivalent results were observed in the 0/2- to 3-hour analyses and when both algorithms were applied to the hs-cTnI ADVIA Centaur measurements. CONCLUSION:The European rapid rule-out/rule-in acute myocardial infarction algorithm hs-cTnI cut points can be harmonized with a demographically and risk-factor diverse US ED population.