Instantaneous Wave-Free Ratio

Excerpt

Coronary artery disease (CAD) is a common pathologic process affecting more than 15 million Americans every year. 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 narrowing or blockage of the coronary arteries, often due 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 evaluating CAD. During catheterization, a sheath is introduced into the arterial system via either the femoral or, increasingly, the radial artery. A catheter is then advanced through the arterial system under fluoroscopy to the aortic root. Iodinated contrast is then used to visualize the aortic valve cusps and to access 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 percutaneous coronary intervention (PCI) in China and confirmed that physician visual assessment (PVA) of stenosis severity yielded higher readings than quantitative coronary angiography (QCA). Additionally, the study revealed significant variations across hospitals and physicians, confirming the utility of additional diagnostic studies.

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 with less than 40% stenosis are considered non-significant, and the recommendation in these cases is to optimize medical therapy to treat CAD. Interventions in patients with indeterminate lesions and between 40% and 70% stenosis were previously debated. In the Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation (COURAGE, 2007), PCI for stable CAD with high-grade stenosis did not confer benefit over optimal medical therapy.

Additional diagnostic modalities have been developed to characterize these lesions better and identify those that would benefit from intervention, including fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR). FFR is described in depth within its review article; however, FFR is a guidewire-based technique that measures blood pressure and flow through a specific lesion. The DEFER trial (2007) found that 5-year event-free survival did not differ significantly between patients who underwent PCI and those who deferred PCI for intermediate coronary stenosis with an FFR greater than 0.75. In the study, FAME (Fractional Flow Reserve versus Angiography for Guiding Percutaneous Coronary Intervention), FFR-guided PCI reduced the composite of death, nonfatal myocardial infarction (MI), and repeat revascularization at 1 year compared with standard PCI alone. In FFR, the interventionist utilizes a specialized guidewire to measure flow velocities and pressure across a target lesion. Following administration of a hyperemic agent, typically adenosine, the FFR value is calculated. Studies have suggested that lesions with an FFR value of less than 0.75 are suspicious for inducible ischemia and would benefit from PCI. In contrast, those with values greater than 0.75 are candidates for treatment with optimum medical therapy.

iFR is a newer physiologic measurement that utilizes principles similar to FFR but does not require a hyperemic agent. In a 2017 JACC study, iFR and FFR showed no significant differences in predicting myocardial ischemia. The MACE trial further supported the use of iFR, showing that IiR-guided revascularization was non-inferior to FFR-guided revascularization for major adverse cardiac events at 1-year follow-up. In iFR, the same pressure wires used in FFR are advanced to a point distal to the stenotic lesion.

During diastole, known as the “wave-free period,” iFR calculates the ratio of distal coronary artery pressure (Pd) to aortic outflow tract pressure (Pa). During this timeframe, blood flow complicating these measurements is negligible. Lesions with a Pd/Pa ratio of less than 0.89 are considered significant and non-inferior to the FFR cutoff of 0.8. Coronary artery lesions with iFR ratios less than 0.89 and FFR ratios less than 0.8 are recommended for further treatment with PCI. As it is still a relatively new technology, some providers consider an iFR ratio of 0.86 to 0.93 to be an area of uncertainty and recommend a hybrid approach that incorporates FFR evaluation.