Synergistic Adaptations to Exercise in the Systemic and Coronary Circulations That Underlie the Warm-Up Angina Phenomenon

Background-The mechanisms of reduced angina on second exertion in patients with coronary arterial disease, also known as the warm-up angina phenomenon, are poorly understood. Adaptations within the coronary and systemic circulations have been suggested but never demonstrated in vivo. In this study we measured central and coronary hemodynamics during serial exercise. Methods and Results-Sixteen patients (15 male, 61 +/- 4.3 years) with a positive exercise ECG and exertional angina completed the protocol. During cardiac catheterization via radial access, they performed 2 consecutive exertions (Ex1, Ex2) using a supine cycle ergometer. Throughout exertions, distal coronary pressure and flow velocity were recorded in the culprit vessel using a dual sensor wire while central aortic pressure was recorded using a second wire. Patients achieved a similar workload in Ex2 but with less ischemia than in Ex1 (P < 0.01). A 33% decline in aortic pressure augmentation in Ex2 (P < 0.0001) coincided with a reduction in tension time index, a major determinant of left ventricular afterload (P < 0.001). Coronary stenosis resistance was unchanged. A sustained reduction in coronary microvascular resistance resulted in augmented coronary flow velocity on second exertion (both P < 0.001). These changes were accompanied by a 21% increase in the energy of the early diastolic coronary backward-traveling expansion, or suction, wave on second exercise (P < 0.05), indicating improved microvascular conductance and enhanced left ventricular relaxation. Conclusions-On repeat exercise in patients with effort angina, synergistic changes in the systemic and coronary circulations combine to improve vascular-ventricular coupling and enhance myocardial perfusion, thereby potentially contributing to the warm-up angina phenomenon. (Circulation. 2012;126:2565-2574.)