Instantaneous Wave-Free Ratio (IFR)

Article Author:
Michael Soos
Article Author:
Daniel Gonzalez-Morales
Article Editor:
David McComb
Updated:
5/5/2020 12:25:51 AM
PubMed Link:
Instantaneous Wave-Free Ratio (IFR)

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 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.

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

Contraindications

The are no contraindication 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 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.

Personnel

At this time IFR should be performed only by board-certified cardiologists who have had formal training in interventional cardiac catheterization.

Preparation

Once the computer software for calculation of IFR is installed, and specialized catheters are available, minimal additional set up is required when compared to standard cardiac catheterization.

Technique

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,” 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.

Complications

There are minimal complications associated directly with IFR; however, they are not different from that of a standard cardiac catheterization with angiography and PCI.

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. In patients with clinical symptoms or non-invasive testing consistent with ischemia and IFR of 0.89 or less is a candidate for PCI. While a patient with IFR greater than 0.93 typically qualifies for optimization of medical therapy (OMT), those with a ratio of 0.9 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 IFR ratio over 0.89, OMT is recommended. Patients with IFR ratios between 0.86 and 0.89 are recommended for FFR confirmation. This information appears in the attached 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 (Level of Evidence: Class I A). The recommendations noted that IFR should be performed alongside FFR for the objective assessment of the hemodynamic relevance of coronary lesions. At this time the current AHA/ACC guidelines do not formally address the use of IFR during coronary revascularization.

While an invasive cardiologist performs the procedure, the primary care provider, nurse practitioner and internist should give the patient information on the importance of lifestyle changes to lower the risk of coronary artery disease.



  • Used with Permission from Shlofmitz E, Jeremias A. FFR in 2017: Current Status in PCI Management. http://www.acc.org. May 25, 2017. Accessed [Insert Access Date]. http://www.acc.org/latest-in-cardiology/articles/2017/05/25/08/34/ffr-in-2017-current-status-in-pci-management
    (Move Mouse on Image to Enlarge)
    • Image 9910 Not availableImage 9910 Not available
      Used with Permission from Shlofmitz E, Jeremias A. FFR in 2017: Current Status in PCI Management. http://www.acc.org. May 25, 2017. Accessed [Insert Access Date]. http://www.acc.org/latest-in-cardiology/articles/2017/05/25/08/34/ffr-in-2017-current-status-in-pci-management

References

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[3] Zhang H,Mu L,Hu S,Nallamothu BK,Lansky AJ,Xu B,Bouras G,Cohen DJ,Spertus JA,Masoudi FA,Curtis JP,Gao R,Ge J,Yang Y,Li J,Li X,Zheng X,Li Y,Krumholz HM,Jiang L, Comparison of Physician Visual Assessment With Quantitative Coronary Angiography in Assessment of Stenosis Severity in China. JAMA internal medicine. 2018 Feb 1     [PubMed PMID: 29340571]
[4] Boden WE,O'Rourke RA,Teo KK,Hartigan PM,Maron DJ,Kostuk WJ,Knudtson M,Dada M,Casperson P,Harris CL,Chaitman BR,Shaw L,Gosselin G,Nawaz S,Title LM,Gau G,Blaustein AS,Booth DC,Bates ER,Spertus JA,Berman DS,Mancini GB,Weintraub WS, Optimal medical therapy with or without PCI for stable coronary disease. The New England journal of medicine. 2007 Apr 12     [PubMed PMID: 17387127]
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[9] Berry C,van 't Veer M,Witt N,Kala P,Bocek O,Pyxaras SA,McClure JD,Fearon WF,Barbato E,Tonino PA,De Bruyne B,Pijls NH,Oldroyd KG, VERIFY (VERification of Instantaneous Wave-Free Ratio and Fractional Flow Reserve for the Assessment of Coronary Artery Stenosis Severity in EverydaY Practice): a multicenter study in consecutive patients. Journal of the American College of Cardiology. 2013 Apr 2     [PubMed PMID: 23395076]
[10] Jeremias A,Maehara A,Généreux P,Asrress KN,Berry C,De Bruyne B,Davies JE,Escaned J,Fearon WF,Gould KL,Johnson NP,Kirtane AJ,Koo BK,Marques KM,Nijjer S,Oldroyd KG,Petraco R,Piek JJ,Pijls NH,Redwood S,Siebes M,Spaan JAE,van 't Veer M,Mintz GS,Stone GW, Multicenter core laboratory comparison of the instantaneous wave-free ratio and resting Pd/Pa with fractional flow reserve: the RESOLVE study. Journal of the American College of Cardiology. 2014 Apr 8     [PubMed PMID: 24211503]
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