Cardiac syndrome X and myocardial ischemia: Pathogenesis

Abstract

Cardiac syndrome X (CSX) is characterized by: (1) angina chest pain triggered by effort; (2) ST-segment depression on exercise stress electrocardiogram or other findings compatible with myocardial ischemia; (3) normal coronary arteries at angiography, in absence of any specific cardiac or systemic disease. Myocardial ischemia related to abnormalities in coronary microcirculation is in most cases responsible for the angina symptoms (microvascular angina, MVA). Metabolic evidence of myocardial ischemia has been found in a sizeable, although variable proportion of patients, whereas left ventricular contractile abnormalities during stress tests have been detected in only a minority of patients. A plausible explanation for the typical lack of left ventricular dysfunction and metabolic abnormalities can reside in the fact that the coronary microvascular dysfunction is patchily distributed across the myocardial wall, rather than being confluent in large areas. The mechanisms responsible for coronary microvascular dysfunction (CMVD) include both reduced coronary microvascular dilation and enhanced coronary microvascular -constriction. Moreover, the impaired microvascular dilator function may involve both endothelium-independent and endothelium-dependent mechanisms. The causes responsible for CMVD in CSX are also heterogeneous. Traditional cardiovascular risk factors, including hypertension, dyslipidaemia, blood glucose disorders and smoking might play some role. Some conditions frequently found associated with CSX, however, include abnormal adrenergic nerve function, insulin resistance, inflammation and (in women) estrogen deficiency. CMVD can be responsible for angina in other groups of patients presenting with a different clinical picture than CSX. In particular, in some patients MVA can present as an acute/unstable form of angina, simulating non ST elevation acute coronary syndrome. The mechanisms responsible for CMVD in these patients have not been adequately investigated; however, intense vasoconstriction of prearteriolar and/or arteriolar coronary vessels is expected to represent the major mechanism of ischemia.