Pathophysiology and clinical presentation of ischemic chest pain

INTRODUCTION

Patients presenting with chest pain often undergo a thorough evaluation to assess the possible presence of anginal pain due to myocardial ischemia, which is the result of coronary artery disease or left ventricular hypertrophy. A careful history and physical examination is critical to accurately establish the diagnosis of angina pectoris and to exclude other causes of chest pain, such as musculoskeletal problems. (See "Differential diagnosis of chest pain in adults".)

A clinical diagnosis of angina pectoris has a 90 percent predictive accuracy for the presence of myocardial ischemia, which is most often the result of coronary disease. However, based upon Bayesian principles, the predictive accuracy varies with the prevalence of coronary disease in the population (eg, men versus women, young versus old) [1,2]. The predictive accuracy of angina is equal to or perhaps greater than the diagnostic accuracy of exercise testing [3,4]. (See "Stress testing for the diagnosis of coronary heart disease".)

The pathophysiology and clinical manifestations of ischemic chest pain will be reviewed here. The evaluation of the patient with suspected ischemic chest pain is discussed separately. (See "Management of suspected acute coronary syndrome in the emergency department" and "Diagnostic approach to chest pain in adults".)

MECHANISM OF ANGINA

The mechanisms responsible for the sensation of angina are complex and not clearly defined. An important feature is that ischemia reduces the formation of adenosine triphosphate (ATP), resulting in the development of acidosis, the loss of the normal ATP sodium-potassium pump, the loss of myocardial membrane integrity, and the release of chemical substances that stimulate chemosensitive and mechanoreceptive receptors innervated by unmyelinated nerve cells found within cardiac muscle fibers and around the coronary vessel [5]. The substances that are released include lactate, serotonin, bradykinin, histamine, reactive oxygen species, and adenosine [6-8]. In addition there are substances released from platelets, which often spontaneously aggregate in the area of a coronary artery stenosis, which may also be responsible for myocardial ischemia and angina. These include serotonin, thromboxane A2, and 5-hydroxytyrptamine [9,10].

There is substantial evidence that the primary mediator of angina is adenosine, via stimulation of the A1 adenosine receptor [11-14]. It is also possible that venodilation as a response to ischemia can activate these receptors. The nerve fibers travels along the sympathetic afferent pathways from the heart and enter the sympathetic ganglia in lower cervical and upper thoracic spinal cord (C7-T4). Impulses are then transmitted via the ascending spinothoracic pathways to the medial and lateral thalamus and ultimately activate several areas of the cerebral cortex [5].