The ischaemic constellation: an alternative to the ischaemic cascade—implications for the validation of new ischaemic tests

The ischaemic cascade is the concept that progressive myocardial oxygen supply–demand mismatch causes a consistent sequence of events, starting with metabolic alterations and followed sequentially by myocardial perfusion abnormalities, wall motion abnormalities, ECG changes, and angina. This concept would suggest that investigations that detect expressions of ischaemia earlier in the cascade should be more sensitive tests of ischaemia than those that detect expressions appearing later in the cascade. However, careful review of the studies on which the ischaemic cascade is based suggests that the ischaemic cascade concept may be less well supported by the literature than assumed. In this review we explore this, discuss an alternative method for conceptualising ischaemia, and discuss the potential implications of this new approach to clinical studies and clinical practice.