Author + information
- Kai M. Eggers, MD, PhD∗ (, )
- Tomas Jernberg, MD, PhD,
- Lars Lindhagen, PhD and
- Bertil Lindahl, MD, PhD
- ↵∗Department of Medical Sciences, Cardiology, Uppsala University, S-751 85 Uppsala, Sweden
Cardiac troponin (cTn) levels are commonly used as a clue whether or not to initiate beneficial treatments in patients with non–ST-segment elevation acute coronary syndrome (NSTE-ACS). The current view is that patients with cTn elevation should undergo invasive assessment aiming at coronary revascularization. This notion, however, is based on data from older studies using less sensitive cTn assays and partly high cutoffs (1,2).
Newer high-sensitivity (hs) cTn assays allow for the measurement of minute amounts of circulating cTn and are increasingly used in clinical practice. It is currently not clear whether there might be a hs-cTn threshold indicating benefit from invasive assessment in NSTE-ACS. A randomized study to answer this question is hardly feasible, given the notion on this management strategy in the guidelines (3). In order to further investigate this issue, we conducted a retrospective, registry-based cohort study.
We investigated a cohort of NSTE-ACS patients from the SWEDEHEART (Swedish Web-system for enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies) registry, part of the TOTAL-AMI (Tailoring Of Treatment in All comers with Acute Myocardial Infarction) project. TOTAL-AMI, SWEDEHEART, and the study cohort have been described elsewhere (4). In short, patients with first-time admissions between 2009 and 2013 to hospitals using the high-sensitivity cardiac troponin T (hs-cTnT) assay (Roche Diagnostics, Basel, Switzerland) with the 99th percentile of 14 ng/l as diagnostic cutoff were selected. We did not consider patients with hs-cTnT ≤14 ng/l (because explorative analyses indicated that the interrelations between invasive assessment, hs-cTnT levels, and outcome were affected by a considerable degree of residual confounding) and with hs-cTnT >1,000 ng/l (because management decisions usually are straightforward in these cases). Notably, the SWEDEHEART registry documents only the highest cTn level recorded during the hospitalization. The composite of death and myocardial infarction within 1 year was considered as outcome, as reported from national registries and without central adjudication (4). The study had been conducted according to the principles of the Declaration of Helsinki and was approved by the Regional Ethical Review Board in Stockholm.
The study population consisted of 18,062 NSTE-ACS patients (median age 72 [64 to 80] years; 62.5% male). Coronary angiography was performed in 13,953 (77.3%) patients and showed normal or nonobstructive (<50% stenosis) arteries, 1- to 2-vessel disease, or 3-vessel disease/left main stenosis in 1,764 (12.7%), 7,838 (56.5%), and 4,266 (30.8%) patients, respectively, with available and evaluable angiographic results. In total, 10,532 (58.3%) patients underwent a coronary revascularization procedure. Within 1 year from admission, 2,590 patients (14.3%) reached the composite endpoint. The multivariable adjusted hazard ratio of an invasive assessment (n = 16,998) was 0.48 (95% confidence interval: 0.43 to 0.53) with a significant interaction of hs-cTnT (ln) levels (pinteraction = 0.001). Multivariable adjusted spline plots indicated that risk reduction started at hs-cTnT levels exceeding 30 ng/l (Figure 1A). A sensitivity analysis using 1:1 propensity score matching of patients who were or were not assessed invasively (n = 9,482) supported this association of hs-cTnT levels with risk (Figure 1B). Similar findings emerged when men and women were assessed separately (data not shown).
In summary, invasive assessment seems beneficial regarding hard cardiovascular endpoints in NSTE-ACS patients with hs-cTnT levels >30 ng/l. The impact of invasive assessment on these outcomes appears to be limited in patients with hs-cTnT levels <30 ng/l but might be considered as a symptom-limiting option or if features of coronary instability are present, for example, recurrent angina or ischemic electrocardiographic changes. Despite the size of our cohort, we lacked statistical power to investigate specific subgroups, for example, younger patients or those with specific comorbidities. There is, thus, a need to better define management recommendations in these patients and those with non-elevated or marginally elevated hs-cTnT levels.
Please note: The TOTAL-AMI project has received funding from the Swedish Foundation of Strategic Research, Stockholm, Sweden. This organization had no role in the design of study, the collection and interpretation of the data, the preparation of the manuscript, and the decision to submit it for publication. Dr. Eggers has received honoraria for lectures from Abbott Laboratories; and has served as a consultant for Abbott Laboratories and Fiomi Diagnostics. Dr. Lindahl has served as a consultant for Roche Diagnostics, Thermo Fisher Scientific, bioMérieux Clinical Diagnostics, Philips Healthcare, and Fiomi Diagnostics; and has received research grants from bioMérieux Clinical Diagnostics and Fiomi Diagnostics. Drs. Jernberg and Lindhagen have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
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