Chest pain and discomfort are essential symptoms in the diagnosis of acute coronary syndrome (ACS). Early detection of the signs and symptoms of ACS may help in the identification of acute myocardial infarction (MI) and is crucial for optimal medical care, timely reperfusion therapy, and prevention of cardiac events. However, 33% of patients with ACS present without chest pain or discomfort, which can influence their receipt of timely lifesaving therapy [1].

Atypical symptoms are defined as the absence of chest pain before or during admission and can include gastrointestinal or respiratory symptoms such as dyspnea, nausea, vomiting, and abdominal discomfort. According to recent recommendations in the European guidelines [2], an immediate invasive strategy should be performed in the case of very-high-risk criteria in patients with non-ST-segment elevation MI (NSTEMI). However, an atypical presentation of symptoms in patients with NSTEMI can delay timely reperfusion and thrombolytic therapy. In a study based on the National Registry of MI 2 (NRMI-2), the absence of chest pain and the absence of discomfort at hospital presentation were the most significant factors predicting a lower use of reperfusion therapy [3,4].

Whether traditional risk factors such as age, gender, and diabetes can affect the presentation of symptoms in NSTEMI patients is not well known. Only a few studies have highlighted this under-investigated subject. In comprehensive studies, atypical symptoms were noted more commonly in patients with diabetes, women, and elderly patients with ACS [1,5]. In a large prospective observational study, Culic et al. [5] reported that diabetes was an independent predictor of an atypical presentation of acute MI in men and women.

However, the data from two registries showed no differences in the incidence of pre-infarction angina between diabetic and nondiabetic groups. In that analysis, patients with diabetes were older and were more often female than those without diabetes [6]. Therefore, selection bias resulting from traditional risk factors may have been present. To address this issue, in this study we sought to use propensity score analysis to investigate the association between symptom presentation and 12-month mortality in patients with NSTEMI.

We analyzed the impact of presentation with atypical symptoms on timely revascularization and clinical outcomes in NSTEMI patients undergoing primary PCI. Before matching, 23% of the study population presented with non-chest pain complaints (44.8% female). Previous studies have reported associations between atypical symptoms and advancing age, female gender, history of diabetes mellitus, chronic renal disease, and dementia. Therefore, such patients are at increased risk for delays in proper treatment and in-hospital mortality [1,7,8]. Canto et al. [9] analyzed 1.1 million patients enrolled in the National Registry of Myocardial Infarction between 1994 and 2004 and investigated sex differences in MI symptom presentation and subsequent hospital mortality after adjustment for age. However, other studies reported no statistically significant differences in the frequency of typical symptoms among women and men [10,11]. Several studies have reported that patients with diabetes experience less pain than do patients without diabetes, whereas other studies found no difference [8,12-15]. A review of other observational studies showed inconclusive results in terms of the association of traditional risk factors such as older age, female gender, race, and diabetes with atypical symptoms. Such inconclusive results might be explained by the heterogeneity of the population. Therefore, to reduce the effect of confounding factors on atypical complaints in the present study, we performed propensity score matching.

In the propensity-matched cohort, atypical symptoms independently predicted 1-year mortality in patients with NSTEMI (HR, 2.820; 95% CI, 1.058 to 7.515; p = 0.038). However, age, diabetes, hypertension, hs-CRP, and smoking were not associated with 1-year mortality in the matched cohort.

The timely provision of optimal medical therapy or revascularization therapy is crucial in the clinical assessment of MI patients. Unfortunately, MI patients presenting without chest pain at the hospital often remain misdiagnosed. In the 2015 European Society of Cardiology guidelines for the management of ACS in patients presenting without persistent ST-segment elevation, an immediate invasive strategy (< 2 hours) was recommended for very high-risk NSTEMI patients, an early invasive strategy (< 24 hours) for high-risk patients, and a maximal delay of 72 hours for angiography in patients with at least one intermediate risk criterion, recurrent symptoms, or known ischemia on noninvasive testing [2]. Several randomized controlled trials have reported data showing that an early invasive strategy is safe and associated with a lower risk of refractory ischemia and a shorter hospital stay [16,17]. However, atypical clinical manifestations may further delay effective reperfusion therapy. In the NRMI-2 report, patients with atypical symptom presentation had a longer delay before seeking a hospital (mean, 7.9 hours vs. 5.3 hours) [3]. Our study demonstrated that NSTEMI patients presenting with non-chest pain complaints also showed delays in the symptoms-to-balloon time, the contact-to-device time, and the door-to-balloon time. These delays may be explained by difficulties in identifying appropriate symptoms in these patients, resulting in delays in performing electrocardiograms in the emergency department.

Length of stay in the coronary care unit was longer in the group with atypical symptoms than in the typical symptoms group. This can be explained by delayed diagnosis and appropriate treatment in this group of patients.