Although strategies based on the cl

Although strategies based on the classical pathophysiological concepts are useful for the management of a substantial proportion of patients with chronic stable angina and the majority of patients with ACS, the paradigm that obstructive CAD is synonymous with myocardial ischemia needs to be revised because it is not universally applicable to individuals presenting with chronic stable angina5 or to a proportion of patients with ACS.6 Indeed, functional mechanisms have been documented that can cause myocardial ischemia in the absence of obstructive CAD. Epicardial coronary artery spasm, as initially proposed by Prinzmetal et al7 and further documented and characterized by Maseri et al,8 are striking examples. Evidence gathered over the past 30 years has made it clear that functional and structural mechanisms affecting prearterioles, arterioles, and capillaries represent yet another major cause for myocardial ischemia (Figure 1) in the absence of obstructive CAD9–13 and can also trigger ischemia in patients with CAD.14