Coronary artery disease (CAD) is a common pathologic process affecting more than 15 million Americans every year.[1] Currently, it is listed as the most common cause of death in both men and women, accounting for 24.2% and 22.0% of all deaths respectively in 2016. CAD is characterized by a narrowing or blockage within the coronary arteries often related to atherosclerosis. CAD, when significant, often results in reduced and inadequate blood flow to the myocardium leading to myocardial injury related to diminished oxygen and nutrient supply. Myocardial injury related to CAD often presents clinically as an acute coronary syndrome (ACS), including unstable angina (UA), non-ST segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI). ACS is a group of conditions characterized by angina or anginal equivalents that require emergency medical evaluation and treatment.

Cardiac catheterization with angiography is a minimally invasive diagnostic procedure and imaging modality that has become a mainstay in the evaluation of CAD.[2] During catheterization, a sheath gets introduced to the arterial system via either the femoral or, increasingly more common, the radial artery. A catheter is then advanced through the arterial system under fluoroscopy to the aortic root. Iodinated contrast is then utilized to visualize the aortic valve cusps and gain access to the right and left coronary arteries. After gaining access to individual coronary arteries utilizing a variety of guidewires, angiography is performed utilizing contrast to identify significant stenosis, atherosclerotic lesions or blockages within individual arteries. Historically, the significance of these lesions has been determined by visual approximation and estimation performed by a Cardiologist trained in either diagnostic or interventional cardiac catheterization. A study published in February 2018 evaluated coronary artery lesions treated with PCI in China confirmed that physician visual assessment (PVA) of stenosis resulted in higher readings of stenosis severity when compared with quantitative coronary angiography (QCA). Additionally, the study revealed significant variations across hospitals and physicians confirming the utility of additional diagnostic studies.[3]

Significant lesions, those with greater than 70% luminal narrowing, via visual estimation qualify for intervention utilizing techniques such as balloon angioplasty or percutaneous intervention with coronary artery stent placement. Lesions displaying less than 40% stenosis are determined non-significant and the recommendation in these cases is for optimization of medical therapy for the treatment of CAD. Interventions in patients with indeterminate lesions, between 40% and 70% stenosis, previously were subject to debate. In the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE, 2007), revascularization with PCI in stable CAD with high-grade stenosis failed to display benefit over optimal medical therapy.[4]

To better characterize these lesions and identify those that would benefit from intervention, additional diagnostic modalities have been developed including fractional flow reserve (FFR) and instantaneous wave-free ratio (IFR). FFR is described in depth within its own review article; however, in brief, FFR is a guidewire-based technique that measures blood pressure and flows through a specific lesion. In the DEFER trial (2007) it was determined that the five-year event-free survival was not significantly different between a patient who performed and deferred PCI on intermediate coronary stenosis with an FFR greater than 0.75.[5] In the study, fractional flow reserve versus angiography for guiding percutaneous coronary intervention (FAME), FFR guided PCI reduced composites of death, nonfatal MI, and repeat revascularization at one year when compared with standard PCI alone.[6] In FFR, the interventionist utilizes a specialized guidewire capable of measuring flow velocities and pressure across a target lesion. Following the administration of a hyperemic agent, typically adenosine, the FFR value is calculated. Studies have suggested that lesions with FFR value of less than approximately 0.75 are suspicious for inducible ischemia and would, therefore, benefit from PCI, while those with values greater than 0.75 are candidates for treatment with optimum medical therapy. 

IFR is a newer physiologic measurement that utilizes similar principles to FFR but does not require the use of a hyperemic agent. In a 2017 JACC study, IFR and FFR demonstrated no significant differences in the prediction of myocardial ischemia.[7] The MACE trial further justified the use of IFR revealing that IFR-guided revascularization was non-inferior to FFR-guided revascularization for major adverse cardiac events at 1-year follow-up.[8] In IFR, the same pressure wires utilized in FFR get passed to a point distal to a stenotic lesion. During a period of diastole known as the “wave-free period,” IFR then calculates the ratio of the distal coronary artery pressure (Pd) to the pressure within the aortic outflow tract (Pa). During this timeframe completing blood flow complicating these measurements is negligible. Lesions found to have a Pd/Pa ratio less than 0.89, are determined to be significant and has been shown to be non-inferior to the FFR cutoff of 0.8.[9][10] Coronary artery lesions determined to have IFR ratios less than 0.89 and FFR ratios less than 0.8 currently are recommended to undergo further treatment with PCI. As it is still a newer technology, some providers consider an IFR ratio of 0.86 to 0.93 an area of uncertainty and recommend a hybrid approach utilizing evaluation with FFR.

Relevant anatomy utilized during IFR is relatively limited, but detailed knowledge of the coronary vasculature is recommended and is reviewed elsewhere.

Indications for IFR is in patients with stable CAD and indeterminate lesions, between 40% and 70% stenosis.

The are no contraindication at this time for IFR. However, current recommendations for IFR do not include patients with ACS. 

IFR requires a specialized guidewire with pressure and flow velocity sensing capabilities in addition to computer software that allows for accurate calculation of IFR values. Additional equipment, including the vascular sheath, cardiac catheters, and imaging modalities are unchanged from traditional cardiac catheterization.