The Use of iFR Measurements to Simplify Decision Making for PCI

Disclosure: Dr. Vincent J. Pompili reports no conflicts of interest regarding the content herein.

Dr. Vincent Pompili can be contacted at vincent.pompili@osumc.edu.

The Ohio State University’s (OSU) Richard Ross Heart Hospital is a high-volume, academic interventional cardiovascular practice. There are nine full-time interventional cardiologists and three interventional cardiology fellows utilizing five cath labs and five exercise testing labs. We treat about 300 ST-elevation myocardial infarctions (STEMIs) and perform an additional 1,800 percutaneous coronary interventions (PCIs) each year.

At OSU, we have utilized fractional flow reserve (FFR) for many years. In this era of appropriate use criteria (AUC) and the mandate to report the level of appropriateness for each PCI performed, we believed it was critical to transition early on to a physiologic assessment or risk not meeting these guidelines. Data have conclusively shown that physiologic assessment of intermediate lesions is more reliable in guiding intervention and leads to better outcomes than angiographic assessment alone. Both the FAME and the DEFER trials showed an improvement in treatment and economic outcomes when FFR was used to guide PCI decisions. FAME II also showed significant improvement in economic outcomes using physiologic-guided PCI. Physiologic assessment is now the gold standard. In fact, recognizing this diagnostic shift, the 2012 AUC update provides guidance on the use of FFR to determine PCI appropriateness.

Even with substantial clinical data and appropriate use guidelines urging interventional cardiologists to adopt physiologic assessment over the static angiogram, a significant percentage are still reluctant to do so.¹ Would an easier, more cost-effective solution nudge this recalcitrance into a willingness to transition to physiologic assessment? What if interventional cardiologists were able to obtain greater accuracy when evaluating complex disease such as elongated and/or multiple lesions? And finally, what interventional cardiologist would not relish a physiological solution that provides virtually immediate assessment and feedback that their intervention was appropriate, comprehensive, and complete? 

Leveraging physiologic assessment for Appropriate Use Criteria

At OSU, we analyzed our data from the American College of Cardiology National Cardiovascular Data Registry (ACC-NCDR) database. It was clear that we were having some issues in regard to patients who presented with stable angina and were referred for catherization, but who didn’t have a direct correlation on the stress test for the ischemic area that was focused on during the cath. We estimated that approximately 15 percent of our PCIs were “inappropriate”; and although within the normal range, this was certainly below our desired goal. 

All interventional cath labs across the country submit to the ACC-NCDR database and the level of appropriateness of each PCI is documented. To date, a cath lab’s score has not affected reimbursement; however, the goal for our lab is to maintain data within the top 90th percentile of activities across the spectrum within the NCDR. Every quarter, the data is presented to our cardiovascular quality committee. If there is an outlier in the data, we present a strategy to improve those data elements to the extent possible. 

The use of FFR in our cath labs, especially in patients who cannot tolerate stress testing, is a key diagnostic tool that aids evidence-based decision-making within AUC guidelines. However, the use of FFR adds a level of complexity, time, and cost that many labs are unwilling to accept and accordingly, limits the use of physiologic assessment in cases where its use is clearly warranted. I strongly believe that the introduction of a simpler diagnostic method will prompt cath labs to embrace the benefits of physiologic data, enabling them to more appropriately treat lesions that require treatment and defer those that do not require treatment. 

A simpler means to physiologic assessment

Cleared by the FDA in March 2014, instant wave-free ratio (the iFR modality) (Volcano Corporation) is an easier method to achieve physiologic assessment than fractional flow reserve measurement. iFR assesses whether a stenosis is causing a limitation of blood flow in coronary arteries with subsequent ischemia without the requirement of running adenosine. iFR is performed using the same high-fidelity pressure wires used in FFR, passed distal to the coronary stenosis. iFR measures the ratio of distal coronary pressure (Pd) to the aortic pressure (Pa) during an isolated period during diastole, called the “wave-free period.” During this “quiet” period, competing forces (waves) that affect coronary flow are inactive, creating a linear relationship between pressure and flow. Accordingly, pressure readings accurately represent blood flow at this instant in the cardiac cycle. As well, there exists a very high degree of correlation between an iFR cutoff value of 0.9 and an FFR cutoff value of 0.8.^2,3 

From a physiological data perspective, FFR and iFR provide comparable value. However, the similarities end there. iFR is much easier to use, less costly in terms of time and outlays, obviates the need for often uncomfortable and at times deleterious impacts from adenosine, fosters improved diagnosis of complex disease, and provides for almost immediate feedback of the interventionalist’s work if they choose to incorporate post-PCI iFR measurements for validation. 

Still a nascent technology, iFR data is being collected by early adopters in a variety of hospitals and clinics, as well as through recruiting outcome studies such as DEFINE FLAIR and iFR Swedeheart, which seek to establish a dichotomous, outcomes-based cut point from more than 4,000 patients. Like its FFR predecessor, iFR requires additional data to validate cut points. In the interim, we employ a hybrid approach to ensure that we are appropriately treating lesions and mitigating risk of inappropriate procedures.⁴ In this approach, an iFR measurement is taken and a reading of greater than .93 supports a deferral, while readings of less than .86 should be treated by revascularization. An iFR reading between .86 and .93 falls in the “grey zone” and requires adenosine administration and an FFR assessment to guide therapy. The hybrid approach raises the sensitivity and specificity above 90 percent, which assuages physician concerns of the reliability of the data until ongoing iFR studies are reported.

However, it is the ease of use with iFR that promotes the utilization of the physiologic approach. As in many cath labs, our team is paying attention to appropriate use; however, on busy days, it can be challenging to urge staff to commit the extra time and steps in their procedure to obtain a physiologic assessment with FFR. In contrast, dropping the wire down and getting an iFR measurement offers a much more rapid ability to obtain a physiologic assessment, unencumbered by the need to administer adenosine. I would say more than half the time we are able to use iFR alone to assess whether or not to proceed with an intervention, making it an extremely effective and efficient physiologic tool. 

Reducing steps and time

iFR was launched in early fall 2014. Our Volcano labs are fully integrated with the cath lab system, so integration of iFR was plug-and-play for our five labs. All nine of the interventional cardiologists at OSU have become strong proponents of iFR, as they were with FFR. When iFR came on board, we saw the added value, the simplification of the process of obtaining physiologic measurements, and cost savings. It was an easy transition.

An average PCI takes approximately 30 minutes if physiologic data is not required. An FFR measurement adds another 15 minutes. The adenosine must be prepared (our pharmacy mixes the drug), infuse the drug, and analyze the resulting data. Using iFR, however, adds only five minutes. We save at least 10 minutes over a typical FFR procedure. In a lab such as ours, where we might do ten interventions in a day, iFR can save a significant amount of time overall — sometimes over one and a half hours each day, in addition to simplifying workflow and increasing throughput. 

Reduction of adenosine use

In approximately 70 percent of our cases requiring physiologic measurement, we no longer have to prep our patients for an infusion of IV adenosine in order to obtain physiologic data. In terms of cost savings, ease of use, and reduced time in the cath lab, iFR has given us the data that we require without the expense and the time required to administer IV adenosine. 

In cases where we have used iFR, fully 60 percent of our patients had appropriate results with iFR alone, allowing us to either defer or proceed with PCI. The remaining 40 percent of patients were in the grey zone with protocol dictating the hybrid approach described previously. 

We have also seen an improvement in overall patient experience with iFR. When we infuse adenosine in our patients for those two to three minutes, many develop flushing, discomfort, and agitation, and some patients can experience chest pain or shortness of breath. Substituting iFR means no adenosine is used, so those symptoms are not a concern, resulting in an improved experience for the patient. 

Improving PCI

In addition to its simplicity, time and money savings, and improved patient experience, I am equally excited about the added capabilities offered by iFR. 

Pullbacks. One of the things I learned in Europe during my iFR training was the concept of the wire pullback. When presented with complex disease, a long lesion or multiple long lesions in a vessel, careful evaluation of those areas is necessary in order to treat only those areas that actually require treatment. In a minimalist approach to stenting, iFR enables greater focus and customization of the ischemic area. The iFR pullback process to customize PCI is starting to be used extensively in my practice. With iFR, the process is much simpler than with FFR; the wire is placed down the artery and a slow, controlled pullback is performed, tracking along the coronary artery to localize precisely where the intervention is needed. 

Post PCI evaluation. As a final step to determine results, we can readily and accurately measure iFR post PCI. Without reinfusing adenosine, we just reconnect the wire and it takes a mere five seconds for this secondary measurement. 

I believe that a post PCI iFR can provide additional peace of mind to the operator, validating that the most likely source of ischemia in the artery has been addressed. Post PCI iFR measurement may also lead directly to improved patient outcomes, though this has not yet been verified through studies or testing due to iFR approval by the FDA merely a year ago. If the iFR is abnormal after PCI, it would make it probable that a flow-limiting lesion is still present. Is the lesion proximal or distal? That has to be addressed. What I can say, conclusively, is that if there is an abnormal iFR post intervention, we add another level of scrutiny to our intervention by looking for a proximal or distal lesion, and evaluating any need for further treatment. 

iFR — The here and now

FFR and iFR are similar physiological tools. Of the two, iFR is clearly simpler to use. The same confidence that we had with FFR, we now have with iFR. I am confident that ongoing iFR studies will confirm all iFR measurements to be as accurate as FFR. For me, at this point, it is all about time and efficiency, getting good data, and not spending time on adenosine except in grey zone cases. 

For a hospital not utilizing a physiologic approach, I strongly recommend that they start. Data from FAME, FAME I, and FAME II consistently demonstrate that physiologic-guided intervention in intermediate lesions is a proven and effective standard of care. 

The simplicity of iFR will drive physicians to adopt the physiologic approach. Interventional cardiologists are not precluded from doing FFR by using iFR; it is just a matter of switching the functionality of the same wire and hanging adenosine.

It is important that we all incorporate appropriate use documentation for PCI. That mandate is coming from external bodies and internal reporting, and the physiologic measurement approach is probably one of the simplest ways to comply.

References

1. Hannawi B, Lam WW, Wang S, Younis GA. Current use of fractional flow reserve: a nationwide survey. Texas Heart Institute Journal. 2014; 41(6): 579-584. doi:10.14503/THIJ-13-3917.
2. Berry C, van ‘t Veer M, Witt N, Kala P, Bocek O, Pyxaras SA, et al. 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. J Am Coll Cardiol. 2013 Apr 2; 61(13): 1421-1427. doi: 10.1016/j.jacc.2012.09.065. 
3. Jeremias A, Maehara A, Généreux P, Asrress KN, Berry C, De Bruyne B, et al. Multicenter core laboratory comparison of the instantaneous wave-free ratio and resting Pd/Pa with fractional flow reserve: the RESOLVE study. J Am Coll Cardiol. 2014 Apr 8; 63(13): 1253-1261. doi: 10.1016/j.jacc.2013.09.060.
4. Sen S, Escaned J, Malik IS, Mikhail GW, Foale RA, Mila R, et al. Development and validation of a new adenosine-independent index of stenosis severity from coronary wave-intensity analysis: results of the ADVISE (ADenosine Vasodilator Independent Stenosis Evaluation) study. J Am Coll Cardiol. 2012 Apr 10; 59(15): 1392-1402. doi: 10.1016/j.jacc.2011.11.003.

Further reading on iFR from Cath Lab Digest

    Samuels BA. Clinical and Economic Advantages of the iFR modality for physiologic assessment. Cath Lab Digest. 2014 Dec; 22(12). Available online at https://www.cathlabdigest.com/article/Clinical-Economic-Advantages-iFR-Modality-Physiologic-Assessment. Accessed April 17, 2015.