G5 Artikkeliväitöskirja

Evolving diagnostics of myocardial infarction: Differentiating acute and chronic cTnT elevations with improved assay




TekijätAalto, Rami

  • KustantajaTurun yliopisto

KustannuspaikkaTurku

Julkaisuvuosi2026

Sarjan nimiTurun yliopiston julkaisuja - Annales Universitatis Turkuensis: Ser. F Technica - Informatica

Numero sarjassa82

ISBN978-952-02-0635-2

eISBN 978-952-02-0636-9

ISSN 2736-9390

eISSN 2736-9684

Julkaisun avoimuus kirjaamishetkelläAvoimesti saatavilla

Julkaisukanavan avoimuus Kokonaan avoin julkaisukanava

Verkko-osoitehttps://urn.fi/URN:ISBN:978-952-02-0636-9


Tiivistelmä

Cardiovascular diseases (CVD) are the most common cause of death and coronary artery disease is the most prevalent CVD. In addition to morbidity and death, atherosclerotic cardiovascular disease produces major economic burden in society which is a combination of treatment costs and productive years lost. Atherosclerotic cardiovascular disease may lead to myocardial infarction (MI) where occlusion of coronary blood flow leads to myocardial ischemia and necrosis. Electrocardiography (ECG) is commonly utilized to rapidly identify ST-elevation myocardial infarction (STEMI). During non-ST-elevation myocardial infarction (NSTEMI) ECG changes can be inconclusive and further biomarker tests are warranted. Nowadays, cardiac troponins (cTn) are the preferred biomarkers of myocardial damage. Unfortunately, both cardiac troponin I (cTnI) and cardiac troponin T (cTnT) assays currently utilized are unable to differentiate between cTn elevation induced by MI and non-MI conditions, such as end-stage renal disease (ESRD). Intact or almost intact forms of cTnT (long cTnT) show improved specificity for MI when differentiating between chronic and acute cTnT elevation. To measure long cTnT reliably, highly sensitive assay is needed. The assay sensitivity can be enhanced by improving the properties of the labels used in the immunoassay. In this thesis, the first immunoassay targeting long forms of cTnT was developed, evaluated for its performance and clinically evaluated with MI and ESRD patients treated at the Turku University Hospital. The assay was compared to the 5th gen Roche Elecsys hs-cTnT assay. In addition, the stability of the sample matrix was evaluated in the context of the novel assay. The thesis also includes synthesis and characterization of novel europium chelate labels for time-resolved fluorescence immunoassays. The long cTnT immunoassay was successfully developed and evaluated. For the first time ever, it was clinically demonstrated that an assay targeting intact or almost intact cardiac troponin T could differentiate between cTnT elevation in MI and ESRD. The novel method clinically outperformed Elecsys hs-cTnT in this regard, especially by utilizing long/total cTnT ratio in the early hours of MI. Additionally, three new europium labels were successfully synthesized and characterized.



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