Original Contribution

Prospective Evaluation of the Impact of Side-Holes and Guide-Catheter Disengagement From the Coronary Ostium on Fractional Flow Reserve Measurements

Krishna S. Patel, BS;  Georgios E. Christakopoulos, MD;  Aris Karatasakis, MD;  Barbara Anna Danek, MD;  Phuong-Khanh J. Nguyen-Trong, MD;  Suwetha Amsavelu, BS;  Jeffrey F. Stetler, BS;  Bavana V. Rangan, BDS, MPH;  Michele Roesle, RN, BSN;  Shuaib Abdullah, MD;  Tayo Addo, MD;  Subhash Banerjee, MD;  Emmanouil S. Brilakis, MD, PhD

Krishna S. Patel, BS;  Georgios E. Christakopoulos, MD;  Aris Karatasakis, MD;  Barbara Anna Danek, MD;  Phuong-Khanh J. Nguyen-Trong, MD;  Suwetha Amsavelu, BS;  Jeffrey F. Stetler, BS;  Bavana V. Rangan, BDS, MPH;  Michele Roesle, RN, BSN;  Shuaib Abdullah, MD;  Tayo Addo, MD;  Subhash Banerjee, MD;  Emmanouil S. Brilakis, MD, PhD

Abstract: Background. We prospectively examined the impact of side-holes and guide-catheter disengagement on fractional flow reserve (FFR) measurements. Methods. Twenty-five patients undergoing clinically indicated FFR measurement for intermediate coronary artery stenosis were enrolled. Four FFR measurements were made in random order during intravenous adenosine infusion with: (a) an engaged side-hole guide catheter; (b) a disengaged side-hole guide catheter; (c) an engaged non-side-hole guide catheter; and (d) disengaged non-side-hole guide catheter. Results. Mean patient age was 65 ± 9 years and 100% were men. The mean distal poststenotic pressure/proximal aortic pressure (Pd/Pa) at baseline was 0.93 ± 0.05 mm Hg. Using intravenous adenosine infusion, the mean FFR measured with engaged vs disengaged non-side-hole guide catheters was 0.87 ± 0.09 vs 0.83 ± 0.10, respectively (mean difference, 0.039 ± 0.04; P<.001). The mean FFR with engaged vs disengaged side-hole guide catheters was 0.85 ± 0.10 vs 0.83 ± 0.10 (mean difference, 0.020 ± 0.02; P<.001). The mean difference in FFR measurements was 0.024 ± 0.03 (P<.001) among engaged guide catheters and 0.005 ± 0.03 (P=.47) among disengaged guide catheters. Conclusions. When FFR measurements are performed with engaged guide catheters, side-hole catheters provide lower measurements. When FFR measurements are obtained with disengaged guide catheters, they are even lower and similar between guide catheter types.

J INVASIVE CARDIOL 2016;28(8):306-310. Epub 2016 April 15.

Key words: fractional flow reserve, side-hole guide catheter, non-side-hole guide catheter

Fractional flow reserve (FFR) is currently the gold standard for invasively assessing the physiologic significance of coronary artery stenoses.1,2 Low FFR measurements are associated with ischemia, as assessed by non-invasive testing.3 Use of FFR improves the outcomes of multivessel percutaneous coronary intervention (PCI) as compared with angiography-guided PCI.4,5 Moreover, FFR-guided PCI has been shown to be superior to medical therapy alone among stable patients with multivessel coronary artery disease.6,7

Given the implications of FFR measurements on subsequent clinical care, accuracy of the measurements is of utmost importance, yet FFR measurements are subject to many potential sources of error. One source of error is guide pressure dampening during guide-catheter engagement that decreases the proximal pressure, leading to erroneous overestimation of the FFR.8-10 Disengagement of the guide catheter eliminates pressure dampening, allowing more accurate FFR measurements.11 An alternative technique to prevent pressure dampening is use of side-hole guide catheters, which are not commonly used in everyday practice as they may mask pressure dampening even when coronary flow is decreased.12,13 Side-hole guide catheters could, however, obviate the need for guide-catheter disengagement during FFR measurements. We performed a prospective study to examine the impact of guide-catheter engagement and presence of side-holes on FFR measurements.


Study population. The study population consisted of 25 patients, all of whom were over the age of 18 years and all of whom provided written informed consent prior to the procedure. Patients were included in this study if they were scheduled to undergo clinically indicated coronary catheterization that could require FFR of an intermediate coronary artery lesion with 30%-70% stenosis based on visual estimation. Patients were excluded if significant difficulty was met advancing the pressure guidewire into the coronary artery or if severe ostial disease was present (≥70% diameter stenosis within 5 mm from the coronary artery ostium).

Study procedures. All enrolled patients underwent clinically indicated coronary catheterization for diagnostic purposes via femoral approach (right femoral artery in 23 patients and left femoral artery in 2 patients). Six Fr guide catheters were used in 23 patients and 8 Fr in 2 patients. Anticoagulation was achieved with unfractionated heparin in all patients. One patient had 2 intermediate coronary lesions and underwent two sets of FFR measurements. The guide catheters used for the study included AL 2.0, EBU 3.75, JL 3.5, JL 4.0, JR 4.0, XB 3.0, and XB 3.5. 

FFR measurements. Four FFR measurements were performed for each of the 26 lesions. First, proximal aortic pressure (Pa) and distal poststenotic pressure (Pd) were measured to determine Pd/Pa at baseline. Adenosine was then infused through a central vein to induce hyperemia. FFR measurements were performed after 3 minutes of infusion with both a side-hole and a non-side-hole guide catheter, both while they were engaged and disengaged, in random order. A pressure wire pullback was performed after each measurement in all patients and in cases of drift (>0.02, that occurred in 9 of 26 lesions) FFR measurements were repeated until no drift was present.

Statistical analysis. Sample size calculation: Assuming that the difference between FFR measured with an engaged non-side-hole guide catheter and FFR measured with an engaged side-hole guide catheter would be 0.03 ± 0.04 (which is a conservative estimate considering that the observed difference in a prior study by Aminian et al was 0.05 ± 0.04),11 the number of patients needed to have 90% power with a=0.05 was 21, which was increased to 25 to account for potential incomplete measurements in some patients.  

The four FFR measurements as well as baseline Pd/Pa were presented as mean ± standard deviation and were compared using one-sided paired t-tests. The four pairs of t-tests included engaged non-side-hole vs engaged side-hole, disengaged non-side-hole vs disengaged non-side-hole, engaged side-hole vs disengaged side-hole, and engaged non-side-hole vs disengaged non-side-hole guide catheters. A one-sided P-value of <.05 was considered statistically significant. The normality assumption for the paired t-test was checked using Q-Q plots and normality tests (Kolmogorov-Smirnov and Shapiro-Wilk). Both tests showed a P-value >.05, suggesting a normal distribution. Statistical analyses were performed using JMP version 11.0 (SAS Institute). 


During June and July 2015, a total of 25 patients were enrolled in the study and underwent FFR measurement of 26 vessels with intermediate coronary lesions. The mean age was 65 ± 9 years and all patients were men. The patient demographics and procedural characteristics are summarized in Table 1 and Table 2, respectively. Four patients with FFR ≤0.80 subsequently underwent PCI of the FFR target lesion. 

FFR measurements. The hemodynamic measurements are summarized in Table 3. The mean baseline Pd/Pa was 0.93 ± 0.05 mm Hg. During intravenous adenosine infusion, the mean FFR for an engaged non-side-hole guide catheter was 0.87 ± 0.09 and decreased to a mean of 0.83 ± 0.10 with the catheter disengaged (mean difference, 0.039 ± 0.04; P<.001) (Figure 1). The mean FFR for an engaged side-hole guide catheter was 0.85 ± 0.10 and decreased to 0.83 ± 0.10 with the catheter disengaged (mean difference, 0.02 ± 0.02; P<.001). The higher FFR with disengaged guide catheters was due to an increase in Pa as shown in Figures 2 and 3.

The mean difference in FFR for an engaged non-side-hole guide catheter vs an engaged side-hole guide catheter was 0.024 ± 0.03 (P<.001). No significant difference was observed between disengaged non-side-hole guide catheters and disengaged side-hole guide catheters (mean difference, 0.005 ± 0.03; P=.47). Overall, 6 lesions had FFR ≤0.80 with both an engaged non-side-hole catheter and an engaged side-hole catheter (Figure 4); however, after disengagement 6 more lesions had FFR ≤0.80.

Subgroup analyses stratifying patients by minimum FFR and by target vessel are shown in Figure 5 and Figure 6, respectively.


The main findings of our study are that: (1) when FFR measurements are performed with engaged guide catheters, side-hole guide catheters provide lower FFR measurements than non-side-hole guide catheters; and (2) guide catheter disengagement is associated with the lowest FFR measurements (with either side-hole or non-side-hole guide catheters).

To the best of our knowledge, our study is the first to examine the impact of side-hole guide catheters on FFR measurements. As anticipated, when the guide catheter is engaged in the coronary ostium, use of side-hole guide catheters provided lower FFR measurements as compared with non-side-hole guide catheters. This is due to less guide-catheter pressure dampening (higher Pa), avoiding an artifactual increase in FFR (which is calculated as Pd/Pa at maximum hyperemia). Although the absolute difference was relatively small (0.02 ± 0.02), it could be clinically significant, especially in cases with FFR measurements close to 0.80 (although it did not actually make a difference in classification in our study, as shown in Figure 4). However, FFR measurements further decreased (by another 0.02) when even the non-side-hole guide catheters were disengaged, suggesting that use of side-hole guide catheters still has limitations in obtaining the lowest possible FFR measurement.    

Aminian et al performed FFR measurements in 21 patients with isolated intermediate lesions of the proximal left anterior descending (LAD) artery with the guide catheter engaged in the coronary ostium and after at least 30 seconds of guide catheter disengagement.11 FFR with engaged guide catheters was 0.81 ± 0.07, which decreased to 0.77 ± 0.08 after 38 ± 6 seconds of guide-catheter disengagement (mean difference, 0.05 ± 0.04). This resulted in reclassification of 28% of patients who had FFR >0.80 with engaged guide catheter but <0.80 with disengaged guide catheters. Our findings are similar to those of Aminian et al, showing a decrease of 0.039 ± 0.04 with guide-catheter disengagement, with a reclassification to hemodynamically significant in 30% of the initially FFR negative lesions. In addition, our study extends Aminian’s findings to non-LAD lesions and within the target vessel. 

Study limitations. Both use of side-holes and guide disengagement have limitations. Disengaging the guide catheter may be a technically difficult maneuver, resulting in lesion uncrossing, especially in right coronary artery lesions. Use of side-hole guides can result in a false sense of security by masking a decrease in antegrade vessel perfusion until hemodynamic changes become apparent. Additional limitations of our study include the single-center design and the relatively small number of patients included, although it was large enough to detect significant differences between the compared groups. As is typical of veteran populations, all study patients were men, limiting extrapolation to women. Lastly, the study did not follow the clinical outcomes of the patients after the FFR measurements were completed.


In summary, use of side-hole guide catheters provides lower FFR measurements as compared with regular guide catheters when the catheters are engaged in the coronary ostia. However, guide-catheter disengagement results in even lower measurements (regardless of guide-catheter type), suggesting this as the preferred technique for optimal FFR measurement.  


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From the VA North Texas Healthcare System and University of Texas Southwestern Medical Center, Dallas, Texas.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Addo reports personal fees from AstraZeneca, Merck, The Medicines Company, and Medicure. Dr Banerjee reports research grants from Gilead and the Medicines Company; consultant/speaker honoraria from Covidien and Medtronic; ownership in MDCare Global (spouse); intellectual property in HygeiaTel. Dr Brilakis reports consulting/speaker honoraria from Abbott Vascular, Asahi Intecc, Boston Scientific, Elsevier, GE Healthcare, Somahlution, St. Jude Medical, and Terumo; research support from Boston Scientific and InfraRedx; spouse is an employee of Medtronic. The remaining authors report no conflicts of interest regarding the content herein.

Manuscript submitted January 7, 2016 and accepted January 11, 2016.

Address for correspondence: Emmanouil S. Brilakis, MD, PhD, Dallas VA Medical Center (111A), 4500 South Lancaster Road, Dallas, TX 75216. Email: esbrilakis@gmail.com