Coronary autoregulation and assessment of stenosis severity without pharmacological vasodilation

For identification of myocardial ischaemia by non-invasive imaging or invasive physiological assessment, administration of a vasodilating or positive inotropic agent is often considered indispensable to exhaust the cardiac compensation mechanisms. Indeed, microcirculatory dilatation is needed for assessment of myocardial perfusion or coronary blood flow. However, three different modalities exist that quantify myocardial ischaemia without recourse to pharmacological stress agents, using either myocardial contrast echocardiography, imaging of myocardial blood volume or invasive coronary pressure measurement with the instantaneous wave-free ratio (iFR). The theoretical framework of these vasodilator-free modalities revolves around the two innate mechanisms that protect the myocardium from ischaemia at rest: coronary autoregulation and arteriogenesis. Coronary autoregulation and metabolic dilatation form the putative processes that regulate microvascular tone and constitute of a complex interplay between metabolic factors, myogenic control, and endothelium-based control that each interact with coronary arterioles of a different size. Arteriogenesis describes the development of large calibre collateral arteries from a pre-existing network, triggered by occlusive coronary artery disease. Following these descriptions, the fundamental principles and the existing evidence of these three diagnostic modalities are reviewed. Emphasis is placed on iFR, which is clinically best applicable. Instantaneous wave-free ratio has proven to be an effective method to determine the haemodynamic significance of coronary stenoses in two recent large randomized clinical trials, together enrolling over 4500 patients. Ultimately, this review aims to clarify the theoretical rationale and to describe the clinical implications of functional stenosis assessment under resting conditions.