Petr Jarolim1, Purvish P Patel2, Michael J Conrad3, Lei Chang2, Vojtech Melenovsky4, David H Wilson5. 1. Brigham and Women's Hospital and Harvard Medical School, Boston, MA; 2. Quanterix Corporation, Lexington, MA; 3. Brigham and Women's Hospital and. 4. Institute for Clinical and Experimental Medicine, Prague, Czech Republic. 5. Quanterix Corporation, Lexington, MA; dwilson@quanterix.com.
Abstract
BACKGROUND: The association between increases in cardiac troponin and adverse cardiac outcomes is well established. There is a growing interest in exploring routine cardiac troponin monitoring as a potential early indicator of adverse heart health trends. Prognostic use of cardiac troponin measurements requires an assay with very high sensitivity and outstanding analytical performance. We report development and preliminary validation of an investigational assay meeting these requirements and demonstrate its applicability to cohorts of healthy individuals and patients with heart failure. METHODS: On the basis of single molecule array technology, we developed a 45-min immunoassay for cardiac troponin I (cTnI) for use on a novel, fully automated digital analyzer. We characterized its analytical performance and measured cTnI in healthy individuals and heart failure patients in a preliminary study of assay analytical efficacy. RESULTS: The assay exhibited a limit of detection of 0.01 ng/L, a limit of quantification of 0.08 ng/L, and a total CV of 10% at 2.0 ng/L. cTnI concentrations were well above the assay limit of detection for all samples tested, including samples from healthy individuals. cTnI was significantly higher in heart failure patients, and exhibited increasing median and interquartile concentrations with increasing New York Heart Association classification of heart failure severity. CONCLUSIONS: The robust 2-log increase in sensitivity relative to contemporary high-sensitivity cardiac troponin immunoassays, combined with full automation, make this assay suitable for exploring cTnI concentrations in cohorts of healthy individuals and for the potential prognostic application of serial cardiac troponin measurements in both apparently healthy and diseased individuals.
BACKGROUND: The association between increases in cardiac troponin and adverse cardiac outcomes is well established. There is a growing interest in exploring routine cardiac troponin monitoring as a potential early indicator of adverse heart health trends. Prognostic use of cardiac troponin measurements requires an assay with very high sensitivity and outstanding analytical performance. We report development and preliminary validation of an investigational assay meeting these requirements and demonstrate its applicability to cohorts of healthy individuals and patients with heart failure. METHODS: On the basis of single molecule array technology, we developed a 45-min immunoassay for cardiac troponin I (cTnI) for use on a novel, fully automated digital analyzer. We characterized its analytical performance and measured cTnI in healthy individuals and heart failurepatients in a preliminary study of assay analytical efficacy. RESULTS: The assay exhibited a limit of detection of 0.01 ng/L, a limit of quantification of 0.08 ng/L, and a total CV of 10% at 2.0 ng/L. cTnI concentrations were well above the assay limit of detection for all samples tested, including samples from healthy individuals. cTnI was significantly higher in heart failurepatients, and exhibited increasing median and interquartile concentrations with increasing New York Heart Association classification of heart failure severity. CONCLUSIONS: The robust 2-log increase in sensitivity relative to contemporary high-sensitivity cardiac troponin immunoassays, combined with full automation, make this assay suitable for exploring cTnI concentrations in cohorts of healthy individuals and for the potential prognostic application of serial cardiac troponin measurements in both apparently healthy and diseased individuals.
Authors: Odayme Quesada; Omeed Elboudwarej; Michael D Nelson; Ahmed Al-Badri; Mitra Mastali; Janet Wei; Bijan Zarrabi; Nissi Suppogu; Haider Aldiwani; Puja Mehta; Chrisandra Shufelt; Galen Cook-Wiens; Daniel S Berman; Louise E J Thomson; Eileen Handberg; Carl J Pepine; Jennifer E Van Eyk; C Noel Bairey Merz Journal: Am Heart J Plus Date: 2022-03-03
Authors: Chrisandra Shufelt; Eldin Dzubur; Sandy Joung; Garth Fuller; Kelly N Mouapi; Irene Van Den Broek; Mayra Lopez; Shivani Dhawan; Corey W Arnold; William Speier; Mitra Mastali; Qin Fu; Jennifer E Van Eyk; Brennan Spiegel; C Noel Bairey Merz Journal: NPJ Digit Med Date: 2019-09-03
Authors: Chrisandra L Shufelt; Andy Kim; Sandy Joung; Lili Barsky; Corey Arnold; Susan Cheng; Shivani Dhawan; Garth Fuller; William Speier; Mayra Lopez; Mitra Mastali; Kelly Mouapi; Irene van den Broek; Janet Wei; Brennan Spiegel; Jennifer E Van Eyk; C Noel Bairey-Merz Journal: J Am Heart Assoc Date: 2020-09-08 Impact factor: 6.106