Continuing Education Activity

Coronary artery disease is the leading cause of death in men and women in the United States. The instantaneous wave-free ratio (iFR) can be used to determine whether or not coronary lesions that are visualized angiographically should undergo percutaneous intervention. This activity describes the instantaneous wave-free ratio and its use in the cardiac catheterization lab to determine the hemodynamic significance of coronary lesions and highlights the role of the interprofessional team in caring for percutaneous coronary intervention candidates.

Objectives:

• Assess the technical aspects of the instantaneous wave-free ratio (iFR).

• Determine how the instantaneous wave-free ratio is used in the management of coronary artery disease.

• Identify instantaneous wave-free ratio values at which coronary lesions are determined to be hemodynamically unstable and therefore should undergo percutaneous intervention.

• Communicate the importance of collaboration amongst the interprofessional team to ensure the appropriate selection of candidates for percutaneous intervention.

Introduction

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 evaluating CAD.[2] During catheterization, a sheath gets introduced to the arterial system via either the femoral or, increasingly more commonly, 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 percutaneous coronary intervention (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 to optimize medical therapy for treating 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]

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 flows through a specific lesion. The DEFER trial (2007) determined that the 5-year, event-free survival was not significantly different between patients 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 myocardial infarction (MI), and repeat revascularization at 1 year compared with standard PCI alone.[6] In FFR, the interventionist utilizes a specialized guidewire to measure flow velocities and pressure across a target lesion. Following administering 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 demonstrated no significant differences in the prediction of myocardial ischemia.[7] The MACE trial further justified using iFR, revealing that IiR-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 are non-inferior to the FFR cutoff of 0.8.[9][10] 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 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.

Anatomy and Physiology

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

Indications

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

Contraindications

There are no contraindications at this time for iFR. However, current recommendations for iFR do not include patients with ACS. 

Equipment

iFR requires a specialized guidewire with pressure and flow velocity sensing capabilities and computer software that accurately calculates iFR values. Additional equipment, including the vascular sheath, cardiac catheters, and imaging modalities, are unchanged from traditional cardiac catheterization.

Personnel

iFR should be performed only by board-certified cardiologists with formal training in interventional cardiac catheterization.

Preparation

Once the computer software for calculating iFR is installed and specialized catheters are available, minimal additional setup is required compared to standard cardiac catheterization.

Technique or Treatment

In iFR, the same pressure wires utilized in FFR are passed to a point distal to a stenotic lesion. During a period of diastole known as the “wave-free period,” IiR 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.

Complications

There are minimal complications associated directly with iFR; however, they are the same as those of a standard cardiac catheterization with angiography and PCI and include the following:

• Bleeding
• Access site hematoma and pseudoaneurysm
• Acute kidney injury caused by the contrast agent
• Anaphylaxis caused by the contrast agent
• Coronary artery dissection

Clinical Significance

Clinically, iFR may be utilized to assess indeterminate coronary artery stenosis further for lesions anywhere from 40% to 90%, but recommendations do not include patients with ACS. Patients with clinical symptoms or non-invasive testing consistent with ischemia and an iFR of 0.89 or less are candidates for PCI. While a patient with an iFR greater than 0.93 typically qualifies for optimization of medical therapy (OMT), those with a ratio of 0.90 to 0.93 should have a follow-up with FFR. In a patient with clinical symptoms not consistent with ischemia, PCI is recommended for iFR under 0.86. In those with an iFR ratio over 0.89, OMT is recommended. Patients with iFR ratios between 0.86 and 0.89 are recommended for FFR confirmation (see Image. iFR Flow Chart).[11]

Enhancing Healthcare Team Outcomes

In late 2018, the European Society of Cardiology (ESC) announced that it had incorporated iFR into its updated revascularization guidelines. The recommendations noted that iFR should be performed alongside FFR to objectively assess coronary lesions' hemodynamic relevance. The current AHA/ACC guidelines do not formally address using iFR during coronary revascularization. While an invasive cardiologist performs the procedure, the rest of the healthcare team should inform the patient about the importance of lifestyle changes in lowering the risk of coronary artery disease.