Incorporating iFR in the Cath Lab

Disclosure: Dr. Buch reports he is a member of the advisory board for Volcano and AstraZeneca, and has received research grants from Volcano and Gilead Sciences. 

Dr. Ashesh N. Buch can be contacted at bucha@ecu.edu.

For many years, the East Carolina Heart Institute (ECHI) at East Carolina University has used coronary physiology in the form of fractional flow reserve (FFR) to help more accurately determine the physiologic significance of an epicardial coronary lesion. It is limitation of blood flow, rather than pressure, that results in ischemia. Coronary flow is, however, more difficult to measure than pressure. Based on the early pioneering work of Drs. Bruyne and Pijls, FFR is defined as the ratio of flow in a stenosed artery to the flow in the same artery if the stenosis was hypothetically not present. This is based on the concept that if resistance is minimal and stable (during maximal hyperemia), pressure can be used as a surrogate for flow (Ohm’s Law). In a normal artery, aortic pressure (Pa) and distal coronary pressure (Pd) are equal. FFR is calculated as ratio of Pd/Pa during maximal hyperemia, with a normal value of 1.0, and is measured by passing an angioplasty wire that has a distal pressure sensor down a vessel. ECHI has embraced this more accurate physiologic assessment vs the more prevalent visual assessment of the angiogram, and incorporated it into a heart team approach, where the cardiologist and heart surgeon jointly assess the best course of treatment for managing patients with coronary artery disease. ECHI was an early adopter and proponent of the heart team approach to treating coronary disease and later, heart valve disorders.  

iFR — a natural evolution

For the faculty team at ECHI, the introduction of instant wave-free-ratio (the iFR Modality, Volcano Corporation) was a natural evolution of FFR. iFR is an adenosine-free, pressure only, coronary physiologic index for assessing physiologic severity of an epicardial coronary stenosis. Used within the boundaries of current published data, its use obviates the need for a vasodilator in approximately 65% of cases (as ongoing studies complete, this number should rise). The physiology behind iFR is relatively simple. Coronary microvascular resistance varies over the cardiac cycle; it is highest in systole and lowest in diastole, when the majority of flow through the coronary vessels occurs. There is a specific period in diastole, when resistance is particularly low and stable. The ratio of distal coronary pressure to aortic pressure during that specific period of diastole thus far appears to be equivalent to FFR in a wide range of patients and intermediate coronary lesions. 

As long-standing users of FFR, ECHI is comfortable and proficient with physiological assessment, so integration of iFR was fairly easy. Nonetheless, we have taken an evidence-based, conservative approach, whereby the risks are low for the patients and the benefits substantial. Based on the data and the ADVISE II study¹, we have implemented a combination of FFR and iFR known as the hybrid approach, as recommended by the Imperial College group². In this approach, we first use iFR. If iFR measurements are greater than 0.93, a deferral of percutaneous coronary intervention (PCI) is warranted; measurements less than 0.86 are treated by revascularization.  However, if iFR measurements fall within this quite generous and currently deliberately conservative “grey” zone (between 0.86 and 0.93), we give adenosine and conduct an FFR assessment.  

Incorporating iFR into the cath lab

iFR integration into the cath lab was easy. It involved a simple software upgrade on the Volcano tower and in-service training for staff before we started using iFR. An important success factor was to educate the staff early on regarding the prerequisites for a successful iFR assessment; namely, the importance of getting a good electrocardiogram (ECG) signal with a dominant R wave and a clear pressure signal. In the first few weeks, wrinkles in workflow were ironed out, largely relating to what the technologists needed to do to get a decent ECG signal on the tower and thus, a valid iFR measurement. Initially, we used each case to review the differences in using the console for iFR and FFR, and how to switch between these modalities during a procedure. We used every opportunity to talk the staff through the procedure, highlighting the differences between iFR and FFR, including how to change the console screen and the steps involved. We have not looked back.      

Bringing the surgeons on board

Our surgeons were already on board with physiologic assessment, so that was also an easy transition. We merely sent out an email to all our colleagues explaining the differences between iFR and FFR, and giving them the figures for the hybrid approach.  As long as we made it clear in the charts what the values mean in terms of whether they were physiologically significant or not, our surgeons have been very comfortable with it. They just want to hear our interpretation of the data. 

Challenges

The primary challenge to adoption among interventional cardiologists is a hesitancy to eliminate adenosine. This is understandable and it is what practitioners are used to. 

It is fair to say some of our private practice doctors at ECHI were hesitant to use iFR. They are not sure about the science behind it. They are cognizant of the competing arguments over the iFR modality in the academic press, thus leading to a more conservative view that I can understand and fully respect. Our opinion, however, is that the ADVISE II protocol is extremely conservative already, relying on minimizing error in the grey zone. When iFR is high, in all probability, the FFR will also be high and conversely when the iFR is very low, the FFR is also very likely to be low. Both modalities have a coefficient of variation. At the conservative ADVISE II-based iFR cut-offs (iFR values <0.86 or >0.93), the intra-patient variability with repeated testing would not affect the validity of the treat/don’t treat decision with reference to their corresponding FFR values. Thus, for iFRs <0.86 and >0.93, we avoid the use of adenosine, spare the patient its side effects, save the hospital time and money, and as a healthcare provider, based on the current clinical data, we are confident in the diagnosis. Adenosine is administered in the grey zone to obtain an FFR value pending further clinical trial data for iFR values in this zone.

By definition, FFR and iFR are continuous variables. Yet, as interventional cardiologists, we are expected to assess physiological severity in a purely dichotomous manner. Furthermore, values of iFR and FFR cannot ever be the same — they are different tests, analogous to Fahrenheit and Celsius for temperature. The purpose of the ongoing non-inferiority DEFINE-FLAIR trial, the largest clinical coronary physiology study to date, is to answer this question:  Are the differences in iFR compared to FFR values in the current ADVISE II iFR grey zone (where both modalities will have a coefficient of variation that can result in treat/don’t treat decision being altered) clinically relevant? The majority of our private practice colleagues are taking a more conservative approach with occasional use of iFR with the hybrid approach pending this trial data. 

Trust the clinical data

When we started using iFR, we didn’t perform internal validations or collect proprietary data. Some institutions and practitioners have done that, but to a certain extent it is inherently flawed. You will only reproduce the published study results if you use exactly the same patient subsets as in the study with at least the same number of patients, which is unlikely, because patient populations differ. If one were to attempt to replicate the study in your own institution, you will get slightly different results, since each practitioner uses FFR in different clinical circumstances and angiographic interpretation of disease varies widely. Therefore, we decided not to attempt to replicate the published studies, were persuaded of their scientific rigor, and use the ADVISE hybrid algorithm. 

Impact of iFR

Since implementing iFR in our institution, amongst those who use an iFR-guided approach, we have seen a 65% reduction in adenosine use, similar to that predicted by ADVISE II, and with resulting cost savings. Even more important are the notable clinical benefits over FFR.

Post PCI assessment

We are required to document the presence of ischemia before treatment, but few document ischemia resolution post-treatment. I find iFR to be a rapid and accurate method to assess functional gain after PCI. One can do the same with FFR, but it necessitates repeated adenosine infusions or injections, all of which add time, costs and increased discomfort for the patient (compared to obviously no symptoms when iFR is used). Thus, after performing PCI, we merely reattach the wire to the connector and get an iFR value post PCI that hopefully demonstrates a higher value compared to the initial value. As we move to a system of reimbursement based on demonstrating quality of care, documenting a satisfactory physiologic result is compelling. 

Assessment of tandem lesions

Another area where I think iFR is proving to be superior to FFR is in assessing tandem lesions. I cannot stress how useful iFR has been in this frequent clinical scenario. For a vessel with sequential stenosis, the operator first wants to determine whether in aggregate, the stenoses are physiologically significant. If so, then the operator ascertains where the greatest pressure drop lies in order to guide placement of a stent. This can be achieved with FFR, which relies on there being a stable FFR value after maximal hyperemia is achieved. Not infrequently, however, and more common than described in the published literature, the FFR value rises after reaching its nadir during continuous adenosine infusion. In this case, an iFR pullback is much easier and more reliable than a pullback during continuous hyperemia with adenosine where not infrequently, one is chasing a moving value.      

We use iFR pullback a lot, when the iFR value is positive. If the value lies in the grey zone, you have to do FFR with adenosine.   

Long-term adoption of iFR

According to the International Survey on Interventional Strategy published in Circulation in October 2014³, 71 percent of cardiologists who participated in the survey used visual assessment only to assess intermediate stenosis. Even when resources were not an obstacle to using FFR, and not doing so was contrary to guidelines, most did not use physiological assessment. Of those, only 53 percent of purely visual decisions were concordant with FFR. The evidence is clear — we must continue to promote and support transition from angiographic-based decisions to physiology-based decisions with FFR and iFR.

My belief is that once clinicians are introduced to iFR, understand its scientific basis, and experience it hands-on in the lab, more will transition to the physiologic approach. Furthermore, combined with the time and cost savings, and vastly improved patient outcomes, I think this makes iFR an extremely compelling package to adopt. Of course, there will always be doctors who will remain cautious, wait for additional studies and the new guidelines that result, but at the very least, all should be using FFR right now.   

Physiologic assessment with iFR alone

If doctors wish to use iFR alone and not the hybrid approach, they can. If they want to use a single iFR cutoff of 0.89 to 0.90, equating to an FFR of 0.8, there is no bar. In fact, the FDA-cleared labeling indicates that a dichotomous iFR cut point of 0.89 can provide an 82.5% match with FFR. Though not strictly within the confines of current study and data, there are circumstances when for sound clinical reasons, doctors would not want to give adenosine and rigidly following the current protocol may not always be in the patient’s best interests. 

Conclusion

iFR is an easy-to-implement means to adopt a physiology-based approach to evaluating coronary stenoses and thus improve patient care. Patient experience is enhanced by the ability to minimize the number of instances patients have to receive adenosine. I find iFR to be more efficient and convenient than FFR, and it enables practitioners to improve procedures through simplified post-PCI assessments and diagnosis of tandem lesions. For our team at ECHI, there is no better option. 

References

1. Escaned J, Echavarría-Pinto M, Garcia-Garcia HM, van de Hoef TP, de Vries T, Kaul P, et al.; ADVISE II Study Group. Prospective Assessment of the Diagnostic Accuracy of Instantaneous Wave-Free Ratio to Assess Coronary Stenosis Relevance: Results of ADVISE II International, Multicenter Study (ADenosine Vasodilator Independent Stenosis Evaluation II). JACC Cardiovasc Interv. 2015 May;8(6): 824-833. doi: 10.1016/j.jcin.2015.01.029.
2. Petraco R, Park JJ, Sen S, Nijjer SS, Malik IS, Echavarría-Pinto M, et al. Hybrid iFR-FFR decision-making strategy: implications for enhancing universal adoption of physiology-guided coronary revascularisation. EuroIntervention. 2013 Feb 22; 8(10): 1157-1165. doi: 10.4244/EIJV8I10A179.
3. Toth GG, Toth B, Johnson NP, De Vroey F, Di Serafino L, Pyxaras S, et al. Revascularization decisions in patients with stable angina and intermediate lesions: results of the international survey on interventional strategy. Circ Cardiovasc Interv. 2014 Dec; 7(6): 751-759. doi: 10.1161/CIRCINTERVENTIONS.114.001608.