The interpretation of cardiac troponin elevation in sepsis remains one of the most persistent diagnostic dilemmas in intensive care medicine. The study published in this issue attempts to address this challenge by examining coronary angiography results in septic patients with elevated troponin levels scheduled for the procedure [1].
Determining the exact etiology of elevated troponin levels constitutes a complex clinical problem, primarily because troponin release can be a consequence of a variety of mechanisms beyond thrombotic coronary occlusion, including supply–demand mismatch, direct cytokine-mediated myocardial toxicity, microvascular dysfunction, or impaired renal clearance. Troponin elevation may be present in up to 60% of patients with sepsis or septic shock, making it one of the most frequent consult questions in the intensive care unit [2]. Because troponin elevation is so prevalent in this population, assuming an ischemic cardiac origin by default, risks unnecessary diagnostic testing and potentially harmful interventions. Consequently, troponin interpretation in high-risk septic patients should be firmly grounded in the overall clinical context rather than numerical values alone. Although a rise in troponin is alarming, it often reflects the severity of critical illness rather than an important coronary event. Indeed, positive troponin results are attributable to new-onset coronary artery disease in only approximately 4.5–6% of septic patients [3]. The vast majority of elevations represent myocardial injury driven by the hemodynamic and metabolic stress in sepsis. Importantly, assay characteristics (troponin I versus troponin T, analytical sensitivity, and baseline chronic elevation) further complicate interpretation and should be explicitly considered. Reliance on a single peak value is particularly problematic; serial measurements demonstrating a significant rise and/or fall provide greater specificity for acute myocardial infarction (AMI) and are more informative in clinical practice. The clinically relevant question at the bedside is therefore not whether troponin is elevated, but whether the probability of an acute occlusive coronary event is sufficiently high to justify invasive diagnostics in a critically ill patient. Electrocardiographic changes, bedside echocardiography with assessment of regional wall motion abnormalities, and careful evaluation of symptoms or ischemic equivalents must remain integral components of decision-making.
Timely diagnosis of AMI remains critical, as missing a thrombotic event can be fatal. In this context, machine learning approaches are beginning to assist clinicians by integrating complex, multidimensional datasets that exceed human cognitive capacity. A 2024 study by Fang et al. employed a prediction model incorporating ten clinical parameters to distinguish septic myocardial injury from AMI [4]. Although troponin emerged as the most influential variable within the model, it was insufficient on its own to improve diagnostic specificity. These findings reinforce the necessity of a multimodal diagnostic strategy.
Beyond the acute phase of critical illness, troponin elevation during sepsis carries prognostic significance that extends well beyond hospital discharge. Several studies have demonstrated an association between septic troponin elevation and an increased risk of major adverse cardiovascular events within the subsequent year, suggesting that sepsis may induce lasting myocardial or endothelial injury [5, 6]. Accordingly, a history of troponin elevation during sepsis should be considered an independent factor in post-discharge cardiovascular risk stratification and follow-up care.
The study by Jannello et al. provides valuable angiographic data in a population in which invasive coronary evaluation is rarely performed, and this should be acknowledged as a strength [1]. The authors retrospectively analyzed septic patients who underwent coronary angiography and found that the presence of an acute culprit lesion (plaque rupture or intracoronary thrombus) was statistically associated with higher troponin concentrations. However, such lesions were identified in only about 10% of patients, indicating that the overwhelming majority of septic individuals with elevated troponin did not have an occlusive coronary event requiring intervention. Given the relatively small sample size, it is not surprising that no significant differences in mortality were detected between patients who underwent percutaneous coronary intervention and those who did not.
These interesting and potentially important study findings must nonetheless be interpreted with caution due to several important limitations. Most importantly, the decision to perform coronary angiography was left entirely to the discretion of the treating physician, without predefined or standardized referral criteria, thereby introducing substantial selection bias. Additionally, the study cohort was heavily skewed toward patients with established coronary artery disease, which was present in approximately 50% of participants – far exceeding the prevalence expected in an unselected septic population. It remains unclear whether known pre-existing coronary artery disease independently influenced the decision to pursue angiography, further confounding the observed associations between sepsis, troponin elevation, and coronary findings. An additional and important limitation is the lack of data on troponin kinetics; only peak troponin values were reported. In everyday clinical practice, dynamic changes in troponin levels are often more discriminative for AMI than isolated peak measurements, which may reflect chronic myocardial injury or reduced renal clearance. One should remember that a rash, uncritical attribution of troponin elevation in sepsis to acute coronary occlusion may expose patients to unnecessary antiplatelet therapy, contrast-induced nephropathy, bleeding complications, and procedural risks associated with invasive coronary angiography. In critically ill patients, these harms may outweigh the potential benefits when pre-test probability for type 1 MI is low. The authors aimed to stratify septic patients with elevated troponin levels to identify clinically relevant coronary artery disease. While troponin is an attractive biomarker due to its availability and sensitivity, it is unlikely that even large randomized trials will define a specific troponin cut-off that reliably identifies septic patients who require coronary intervention. The biological and clinical overlap between septic myocardial injury and ischemic heart disease is simply too great for a single biomarker to resolve.
Future research should prioritize standardized criteria for angiography referral, systematic assessment of troponin kinetics, and integrated risk stratification models combining clinical judgment, ECG, echocardiography, and biomarkers. For now, in the context of sepsis, troponin release should be regarded as a marker of myocardial stress rather than a diagnosis – and treating it as the latter risks doing more harm than good.
