Key result
Up to ~8% of confirmed NSTE-ACS patients present with normal initial ECGs, necessitating multimodal diagnostics.
Why the study?
A clinically relevant subgroup of NSTE-ACS patients presents with typical ischemic symptoms despite a normal initial 12-lead ECG, creating substantial diagnostic difficulty.
A normal initial ECG does not exclude NSTE-ACS, necessitating the integration of rapid high-sensitivity troponin algorithms and multimodality imaging to prevent underdiagnosis and adverse outcomes.
Emphasizes diagnostic vigilance for symptomatic NSTE-ACS despite normal ECG; extends guidelines with synthesized evaluation strategies.
Non-ST-segment elevation acute coronary syndrome (NSTE-ACS) represents a major subtype of acute coronary syndrome (ACS). A clinically relevant but often overlooked subgroup of patients presents with typical ischemic symptoms despite a normal initial 12-lead electrocardiogram (ECG), creating real diagnostic difficulty. This narrative review synthesizes current evidence across several domains: epidemiology, pathophysiology, clinical presentation, diagnostic evaluation, and management of NSTE-ACS patients with normal ECGs. A structured literature search of PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) databases, with emphasis on prospective cohort studies, registries, systematic reviews, meta-analyses, and current European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) guideline recommendations. Depending on the definition of “normal ECG” and study population, approximately 1%–8% of confirmed NSTE-ACS patients present with a normal initial ECG. These patients frequently exhibit single-vessel disease, non-obstructive coronary artery disease, or alternative mechanisms such as coronary vasospasm and microvascular dysfunction. High-sensitivity cardiac troponin (hs-cTn) assays using rapid 0/1-h or 0/2-h algorithms constitute the diagnostic cornerstone, while coronary computed tomography angiography (CCTA) provides valuable anatomical assessment, particularly in low-to-intermediate-risk patients. This review presents an integrated diagnostic algorithm, critically evaluates the complementary roles of multimodality imaging techniques, and discusses future directions including artificial intelligence-assisted ECG interpretation and wearable monitoring technologies.
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Zhang et al. (2026) conducted a review in Non-ST-segment elevation acute coronary syndrome (NSTE-ACS) with normal electrocardiogram. Approximately 1% to 8% of confirmed NSTE-ACS patients present with a normal initial ECG, necessitating a multimodal diagnostic approach utilizing high-sensitivity cardiac troponin and advanced imaging.
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