Atypical Presentation in Patients with Acute Coronary Syndrome

Chest pain has been reported as a cardinal clinical feature among the patients with acute coronary syndrome (ACS). However, several patients exhibit the atypical or no symptom on initial evaluation. Atypical symptom was defined as the absence of chest pain before or during admission, and may have included gastrointestinal or respiratory symptoms such as dyspnea, nausea, vomiting, and abdominal discomfort. Patients who present without chest pain are frequently misdiagnosed, and less likely to receive optimal treatment for ACS. Consequently, greater in-hospital morbidity, and mortality are noted. Therefore, understanding the factor associated with atypical presentations may help in the earlier detection and treatments in patients with ACS. Prior to discussing the risk factor, clarifying the concept of symptom in patients with ACS is needed to figure out this theme. In this manuscript, atypical presentation is used interchangeably 1 or 1+2 in figure 1 according to each reference (Fig.1).


Risk factors of atypical presentation
In NRMI-2 registry, Variables such as older age, gender, race, and co-morbidities (diabetes, stroke, heart failure) were considered as a risk factor for atypical symptom (Table.1), and many studies have described the association of aging, gender, and diabetes mellitus.

Women
Atypical presentation in ACS was observed more commonly in women than men in large cohort studies (Table 2). Women with coronary heart disease are older by 10 years and have mor e ri s k fact or s than men. It m ig ht be due t o lack o f ear ly recog n it ion a nd management.
There are several differences between men and women in presentation. Women were less likely to have typical angina, rated their pain as more intense, used different words to describe it (more burning, sharp), and reported more non-pain-related symptoms than men. They experienced pain and other sensations in the neck area more frequently.
Another feature of chest pain in women is that angina being induced by rest, sleep, mental stress instead of or addition to physical exertion. Psychosocial factors might also affect symptom presentation and diagnostic approach in women. For example, a history of anxiety disorders is associated with a lower probability of significant angiographic disease among women with chest pain symptoms. As women underestimate their own risk of coronary artery disease, diagnostic approach by physician could be altered less aggressively than men. Compared with men, women are less likely to perform cardiac monitoring, cardiac enzyme measurement, electrocardiogram, cardiac consultation, admission to a coronary care unit, undergo less coronary angiography, angioplasty, and bypass surgery.

Diabetes mellitus
Some patients with diabetes mellitus (DM) have a blunted perception of ischemic chest pain, which could result in atypical presentation. The suggested mechanisms of this phenomenon are as follows; 1) autonomic neuropathy, 2) prolongation of the anginal perceptual threshold. Sympathetic denervation diabetic patients have evidence of a significant reduction in MIBG uptake, most likely on the basis of autonomic dysfunction. Furthermore, diabetic patients with silent myocardial ischemia have evidence of a diffuse abnormality in metaiodobenzylguanidine (MIBG) uptake, suggesting that abnormalities in pain perception may be linked to sympathetic denervation. Similar finding has also been observed with positron emission tomography. Moreover, regional heterogeneity in sympathetic denervation could result in potentially life-threatening myocardial electrical instability that may lead to life-threatening arrhythmias. Another mechanism of abnormal perception is prolongation of the angina perceptual threshold during exercise. Anginal perceptual threshold (the time from onset of 0.1 mV of ST segment depression to onset of angina during treadmill exercise) is prolonged in diabetic patients with coronary artery disease. The permissive effect of a prolonged anginal perceptual threshold on exercise capacity is undesirable as reflected by its correlation with ischemia at peak exercise (r = 0.6, p less than 0.001): the longer the threshold, the greater the exercise capacity and the more severe the ischemia.

Age and atypical presentation
Advanced age is an important predictor of atypical presentation and poor prognosis. Recent study in Korea examined and compared the risk factor associated with atypical presentation according to the age parameter. In this study, diabetes and hyperlipidemia significantly predicted atypical symptom in relatively young (<70 years) age group. Otherwise, comorbid conditions such as stroke or chronic obstructive pulmonary disease were the positive predictors in relatively old age group (>70 years) (

Conclusions
ACS patients with atypical presentation are under-diagnosed and under-treated high risk group. Several clinical risk factors could be helpful in prediction of ACS in this group.