New light on a forgotten disease: vasospastic angina

Six decades ago Prinzmetal et al. (1) described a particular form of angina that occurred at rest, in the absence of any increase of myocardial oxygen demand, and was associated with ST-segment elevation on electrocardiography rather than with the usual ST-segment depression observed during effort angina. The investigators suggested that this variant form of angina was caused by a primary reduction of coronary blood flow consequent to an increased tonus of stenotic coronary arteries (1). Some years later, coronary angiographic studies showed that variant angina was indeed caused by coronary artery spasm (CAS) (2). Accordingly, it is now often referred as vasospastic angina (VSA). CAS is defined as a sudden, intense, reversible vasoconstriction of a coronary artery branch resulting in subtotal or total occlusion. It can occur in stenotic or angiographically normal coronary segments, can be focal or diffuse, and can involve 1 or multiple epicardial coronary arteries. VSA occurs frequently at night or in the early morning, but in some patients it prevails in the afternoon. Angina episodes may be sporadic or present in clusters and may spontaneously subside and then recur after a variable period of time. Triggers of CAS also differ among patients, with exercise, for example, inducing CAS in about 25% of patients with VSA. Importantly, CAS can cause life-threatening arrhythmias and sudden death, and prolonged CAS is a cause of acute myocardial infarction (3). Accordingly, a prompt diagnosis is mandatory to prevent these serious complications; yet, the diagnosis of VSA is often missed for months after symptom onset (4). Of note, progress in this area has been limited, for 2 main reasons. First, the prevalence of VSA is low (1% to 1.5% of admissions for angina in Caucasian populations) (4), thus making the enrollment of large numbers of patients difficult. Second, calcium-channel blockers (CCBs) prevent CAS in the majority of patients, thus limiting the need for new forms of treatment. Yet, 10% to 20% of patients with VSA are refractory or develop poorly tolerated side effects to CCBs. Thus, elucidating the mechanisms of CAS might be important, as it might lead to development of new forms of treatment. --------------------------------------------------------------------------------