Author + information
- Received December 29, 2015
- Accepted January 28, 2016
- Published online May 23, 2016.
- Shiv K. Agarwal, MDa,
- Srikanth Kasula, MDa,
- Yalcin Hacioglu, MDa,
- Zubair Ahmed, MDa,b,
- Barry F. Uretsky, MDa,b and
- Abdul Hakeem, MDa,b,∗ ()
- aDepartment of Cardiovascular Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas
- bCardiology Section, Central Arkansas Veteran Affairs Health System, Little Rock, Arkansas
- ↵∗Reprint requests and correspondence:
Dr. Abdul Hakeem, Division of Cardiovascular Medicine, Central Arkansas VA Medical Center & University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205.
Objectives This study sought to evaluate the impact of fractional flow reserve (FFR) after percutaneous coronary intervention (PCI) on subsequent in-lab interventional management vessels that had undergone pre-PCI FFR and its prognostic value in predicting long-term (>1 year) outcomes.
Background Post-PCI FFR has been shown to be a predictor of intermediate-term (6 months) adverse events. However, its impact on immediate post procedure clinical decision making and long-term outcomes is not known.
Methods Consecutive patients undergoing PCI who had pre- and post-PCI FFR evaluations were followed for major adverse cardiovascular events (MACE).
Results In the study 574 patients (664 lesions) were followed for 31 ± 16 months. PCI led to significant improvement in FFR from 0.65 ± 0.14 to 0.87 ± 0.08 (p < 0.0001). Despite satisfactory angiographic appearance, 143 lesions (21%) demonstrated post-PCI FFR in the ischemic range (FFR ≤0.81). After subsequent interventions, FFR in this subgroup increased from 0.78 ± 0.08 to 0.87 ± 0.06 (p < 0.0001). Final FFR cutoff of ≤0.86 had the best predictive accuracy for MACE and ≤0.85 for TVR. Patients who achieved final FFR >0.86 had significantly lower MACE compared to the final FFR ≤0.86 group (17% vs. 23%; log-rank p = 0.02). Final FFR ≤0.86 had incremental prognostic value over clinical and angiographic variables for MACE prediction.
Conclusions Post-PCI FFR reclassified 20% of angiographically satisfactory lesions, which required further intervention thereby providing an opportunity for complete functional optimization at the time of the index procedure. This is particularly important as FFR post-PCI FFR was a powerful independent predictor of long-term outcomes.
- fractional flow reserve
- functional optimization
- major adverse cardiovascular outcomes
- percutaneous coronary intervention
Fractional flow reserve (FFR) has become the gold standard for establishing ischemia in the angiographically intermediate lesion and the use of percutaneous coronary intervention (PCI). Pre-PCI FFR holds a Class IA indication in the European (1) and IIa in the American College of Cardiology/American Heart Association guidelines (2) in this clinical scenario. Even though FFR in addition to angiography has been shown to be a valuable tool in improving long-term outcomes, a significant proportion of FFR-guided PCI patients continue to experience significant major adverse cardiac events (MACE). In the FAME (Fractional Flow Reserve versus Angiography for Guiding PCI in Patients with Multivessel Coronary Artery Disease) trial, MACE at 1 year in the FFR group was 13.2% and 20% at 2 years (3,4).
While angiography is considered limited in its ability to assess the functional severity of coronary lesions, the adequacy of PCI results is still largely assessed based on angiographic appearance alone. Presumably, this approach has been adopted in view of data showing the greatest variation between FFR and angiography is in the intermediate lesion range, with much less variation in general between FFR and angiography in the severe and mild lesion categories (5). Thus, the use of angiography alone after PCI is an extrapolation of available pre-PCI FFR data without empiric supporting evidence. In fact, studies evaluating post-PCI FFR have shown a wide variation of FFR values in angiographically satisfactory PCI results, reinforcing the notion that angiography is limited in determining the ischemic burden of a lesion even after intervention. The level of the FFR value post-PCI has shown a direct relationship to long-term outcomes (6–13). Thus, attempts to “functionally optimize” PCI results while the patient is in the cath lab might lead to improvement in long-term outcomes.
Despite hints of the clinical value of post-PCI FFR, it is rarely performed and clinical guidelines and expert consensus documents are silent on the use of using post-PCI FFR (1,2). In this regard it should be emphasized that previous studies are limited by including relatively low-risk patient population, angiographically simple lesions, single-vessel disease, small sample size (10,11), short duration (6 months) of follow-up (7,8), or use of bare-metal stents (BMS) (7,8) or balloon angioplasty (10). No study has described the impact of post-PCI FFR results on clinical decision-making while the patient was still in the catheterization laboratory (6–17). Hence, our objectives were to evaluate the frequency of unacceptably low or ischemic FFR after angiographically successful PCI, subsequent treatment in the catheterization laboratory and the long-term (>1 year) prognostic utility of post-PCI FFR in predicting MACE in a contemporaneous, large, real-world complex patient population utilizing predominantly drug-eluting stents (DES).
Consecutive patients undergoing PCI who had pre- and post-PCI FFR measurements between January 2009 and September 2014 at the Central Arkansas VA Health systems were studied. The study was approved by the institutional review board.
Measurement of FFR
FFR was performed using either the Volcano [San Diego, California] or St. Jude Medical [St. Paul, Minnesota] pressure wire placed in the distal artery. FFR wire was balanced, pressures normalized, and advanced distal to the lesion, after therapeutic anticoagulation. After administration of intracoronary (IC) nitroglycerin, baseline pressure gradient was recorded. FFR was then measured under maximal hyperemic condition with either intravenous adenosine (140 μg/kg/min) or intracoronary adenosine (at least >60 μg). After obtaining angiographically satisfactory PCI result as determined by the operator, baseline pressure gradient and FFR were repeated. In the presence of a residual gradient, manual pullback was performed to localize the area of pressure drop.
In the presence of a persistently ischemic, or if not ischemic, “unsatisfactory” (as determined by the operator) post-PCI FFR, a “subsequent intervention” was performed in many cases which may have included additional post dilation, further stenting, intravascular ultrasound (IVUS), optical coherence tomography (OCT), or a combination depending on the operator’s discretion. Following the subsequent intervention, FFR was repeated (final FFR). All the pre- and post-PCI angiograms were evaluated by the operator to estimate percent diameter stenosis.
Primary endpoint was major adverse cardiac events (MACE) defined as a composite of death, myocardial infarction (MI) (not related to intervention) and target vessel revascularization (TVR). MI after index hospitalization was defined as a clinical syndrome of ischemic symptoms and a rise in serum troponin a >99th percentile of reference lab value with or without or new ischemic ST-segment and T-wave changes (18). TVR was defined as subsequent revascularization of the index vessel by either PCI (additional stent or angioplasty) or coronary artery bypass graft of the target vessel.
Patient groups were compared using unpaired Student t test for continuous variables and the chi-square test for categorical variables. Unadjusted annual event rates were calculated by first estimating overall event rates through calculation of Kaplan-Meier curves, then dividing the event rate by the mean follow-up time for each group.
Lesion characteristics including FFR, PCI, and functional optimization were analyzed using lesion bases analysis. In the presence of multiple coronary stenoses, angiographic and hemodynamic variables related to the first lesion intervened and were used for clinical outcome analyses.
Receiver-operating characteristic (ROC) curve analysis was performed to assess the optimal “cutoff” value of final FFR for predicting MACE. Univariate multivariate Cox proportional hazards regression was used to identify independent MACE predictors. Variables with p < 0.10 in the univariate model and potential predictors of adverse outcomes were included in the multivariate model. The number of covariates was restricted to maintain ≥10 events per degree of freedom. Sequential Cox models were performed to determine the incremental prognostic benefit of angiographic parameters over clinical data and subsequently of final FFR over both. A statistically significant increase in the global chi-square value of the model defined incremental prognostic value. The proportional hazards assumption was tested graphically with Cox-adjusted log [minus log (survival)] curves (parallel) and statistically using time interaction test in SPSS. All significant covariates met the proportionality assumption, except age, which was time dependent, as would be expected (hazard of death and MACE increases with age). The level of statistical significance was set at 0.05, and a 2-sided probability value used for the analyses. All statistical calculations were performed using MedCalc Statistical Software version 15.2.1 (MedCalc Software, Ostend, Belgium) and SPSS Statistics, version 13 (IBM, Armonk, New York).
A total of 574 consecutive patients with 664 lesions undergoing PCI with documented FFR pre- and post- PCI formed the final data set. Demographics, indications for PCI, and angiographic findings are shown in Tables 1 and 2⇓ and are typical for a coronary population (45% diabetics, 93% hypertensive, 18% chronic kidney disease [CKD]).
Baseline angiographic and hemodynamic characteristics
Pre-PCI percent diameter stenosis was 73 ± 15%. Pre-PCI trans-stenotic pressure gradient was 0.84 ± 0.16 and pre-PCI FFR 0.65 ± 0.14. A total of 96% of lesions had FFR ≤0.80, with 73% ≤0.75 and 38% <0.65. Of 4% of lesions (n = 27) with FFR >0.80, median FFR was 0.81. There was no difference in the FFR obtained by intravenous (52%) and intracoronary (48%) adenosine (0.66 vs. 0.65; p = 0.49). There was a negative correlation between percent diameter stenosis and baseline FFR (r = –0.59; p < 0.0001).
Percutaneous intervention and ischemia relief
PCI led to a decrease in diameter stenosis from 73 ± 15% to 1 ± 5% (p < 0.00001). Repeat FFR after PCI showed effective ischemia reduction (pre-PCI FFR 0.65 ± 0.14; post-PCI FFR 0.87 ± 0.08; ΔFFR 0.22 ± 0.16; p < 0.0001) (Figure 1). A total of 21% of lesions (n = 143) had post-PCI FFR of ≤0.81 despite angiographically satisfactory PCI results. The mean post-PCI FFR in this group was 0.75 ± 0.05.
Subsequent procedures after post-PCI FFR
A total of 137 (20%) lesions underwent a subsequent procedure based on a suboptimal post-PCI FFR. The mean FFR for these lesions was 0.78 ± 0.07. In 58 (42%) lesions, further post-dilation of the implanted stent was performed, 45 (33%) had another stent implanted, while 24 (18%) underwent additional stenting and post-stent balloon dilation. 13 (9%) vessels were interrogated with intravascular ultrasound (IVUS) or OCT (Figure 2A). Post-dilation of the stent was performed with a bigger balloon size (median balloon to stent diameter difference: +0.25 mm; interquartile range [IQR]: 0.25 to 0.5 mm; p = 0.02) and higher pressure and duration of inflation (median: 19 atm; IQR: 15 to 23 atm; +23 s; IQR: 15 to 34). Patients who underwent subsequent intervention based on post-PCI FFR had longer total case duration (75 min [IQR: 62 to 87 min] vs. 65 min [IQR: 52 to 82 min]; p = 0.001), fluoroscopy time (18 min [IQR: 12 to 23 min] vs. 16 min [IQR: 11 to 21 min]; p = 0.03) but no difference in total contrast volume (144 ml [IQR: 92 to 241 ml] vs. 135 ml [IQR: 90 to 210 ml]; p = 0.3).
Impact of post-PCI FFR on functional optimization
Subsequent interventions led to an FFR improvement from 0.78 ± 0.07 to 0.87 ± 0.05 (p < 0.0001) (Figure 2B). Post-PCI FFR prompting subsequent intervention led to an overall increase in FFR and decreased persistently ischemic lesions (≤0.81) from 21% to 9% and increased the lesions with FFR ≥0.86 from 60% to 74% (Figure 3A). Comprehensive pullback in persistently ischemic lesions after “functional optimization” showed that the mean hyperemic distal to proximal pressure gradient in the distal vessel and immediately distal to the stent FFR were 0.76 ± 0.05 and 0.85 ± 0.05 (p < 0.001), respectively, compatible with diffuse disease distal to the lesion, which could likely not be corrected by further interventions. The number of persistently ischemic lesions based on distal stent FFR was 5% compared to the 9% based on distal vessel FFR (Figure 3B).
Events at follow-up
During a follow-up of 31 ± 16 months (96% >6-month follow-up; 86% >12-month follow-up) 109 (19%) patients had 134 MACE. There were 62 all-cause deaths, 12 patients with MI and 60 patients with TVR. There were 21 patients with more than 1 event during the follow-up: MI and TVR in 9 patients, TVR and subsequent death in 3 patients, MI and subsequent death in 1 patient, and >1 TVR in 8 patients.
Patient characteristics and MACE
Patients who experienced MACE were more likely to be older, have CKD have acute coronary syndrome (NSTEMI and unstable angina) as initial presentation (Table 1), have multivessel disease, and have diffuse disease (defined as diseased segment at least >20 mm in length and diffuse distal vessel disease) compared to those without MACE (Table 2). DES use was associated with decreased MACE (Table 2).
Multivariate MACE predictors
On Cox proportional hazards regression analysis, age (hazard ratio [HR]: 1.04; 95% confidence interval [CI]: 1.02 to 1.07; p < 0.01), CKD (HR: 1.79; 95% CI: 1.14 to 2.81; p = 0.01), acute coronary syndrome as initial presentation (HR: 1.69; 95% CI: 1.13 to 2.53; p = 0.01), presence of diffuse disease (HR: 1.83; 95% CI: 1.21 to 2.77; p < 0.01), and final FFR ≤0.86 (HR: 1.70; 95% CI: 1.12 to 2.58; p = 0.01) were predictive of MACE. Use of DES (HR: 0.59; 95% CI: 0.38 to 0.92; p = 0.02) was associated with decreased MACE (Table 3).
Predictive value of final FFR
ROC curve analysis identified a final FFR cutoff of ≤0.86 as having the best predictive accuracy for MACE. 32% of the patient had final FFR ≤0.86. Patients who achieved final FFR values >0.86 had significantly lower adverse event rate compared to a final FFR ≤0.86 group (17% vs. 23%; p = 0.02) (Figure 4). Similarly, ROC curve analysis identified a final FFR cutoff of ≤0.87 as having the best predictive accuracy for death (13.5% vs. 9%; p = 0.03) (Figure 5A) and final FFR cutoff of ≤0.85 as having the best predictive accuracy for TVR (12% vs. 8%; log-rank p = 0.03) (Figure 5B). Achieving final FFR values >0.86 had significantly lower event rate compared to the final FFR ≤0.86 group among the various subgroups including diffuse disease (21.1% vs. 31.6%; p = 0.02) (Figure 6A) and multivessel disease (21.2% vs. 27.9%; p = 0.02) (Figure 6B). The group of patients who received DES and achieved final FFR >0.86 had lowest event rates (13.1%) followed by patients with BMS and final FFR >0.86 (18.3%), patients with DES and final FFR ≤0.86 (26.6%) and patients with BMS and final FFR ≤0.86 (34.8%) (p <0.01), respectively (Figure 7). After excluding patients with diabetes, CKD, and/or diffuse disease, achieving a final FFR >0.91 (FFR value based on ROC curve analysis in this group) was associated with lower adverse event rates compared to the final FFR group ≤0.91. (7.1% vs. 18.9%; p = 0.04) (Figure 8).
Incremental prognostic value of final FFR in outcome prediction
Significant increases in global chi-square value for the Cox proportional hazards models occurred after the addition of final FFR to the baseline clinical model and clinical angiographic variables model (all p < 0.05) demonstrating the incremental prognostic utility of final FFR in outcome prediction (Figure 9).
The major study findings are that: 1) use of FFR after PCI in patients undergoing pre-PCI FFR modified treatment in approximately 20% of lesions; and 2) final FFR after PCI is a powerful predictor of long-term adverse cardiac events. One in 5 lesions (20%) demonstrated persistent ischemia after intervention despite angiographically satisfactory PCI results. FFR obtained after PCI thus led to subsequent interventions that improved the overall functional outcome and likely reduced MACE. FFR post-PCI thereby provided an opportunity for further intervention leading to ischemia resolution and functional lesion optimization. This study is the largest real-world cohort with the longest follow-up with predominant use of DES that validates the independent prognostic utility of post-PCI FFR in a high-risk population. Furthermore, we demonstrated the incremental prognostic value of post-PCI FFR in outcome prediction, above and beyond clinical and angiographic predictors.
“Functional optimization” of PCI results
Current guidelines rely solely on angiography to determine the adequacy of PCI results in patients in whom FFR is used to determine the presence of ischemia pre-PCI. Our data strongly suggest that such reliance will inadequately treat 1 of 5 lesions and such reliance increases the risk of subsequent events by not adequately treating ischemia. Multiple factors that may produce inadequate stenting results including stent underexpansion and/or strut malapposition, geographic miss of the culprit lesion or placement in a diseased bed, and/or diffuse atherosclerosis not fully appreciated on angiography. In this context, the utility of FFR for assessing the “effectiveness of PCI” has emerged as an attractive strategy. In fact, the very first successful balloon angioplasty in man, by Grüntzig et al. (19), was based on demonstrating the resolution of a resting trans-stenosis gradient.
Balloon dilation after stenting at higher atmospheres and/or larger size balloons was frequently performed to improve FFR. Higher inflation pressure has been shown to produce progressive improvement in post-PCI FFR as demonstrated by the FROST (The French Randomized Optimal Stenting Trial) III investigators (14). Post-PCI FFR provided an opportunity for functional optimization with subsequent interventions leading to a significant improvement in the final FFR across all ranges and reducing the persistent ischemic lesions from 21% to <9%. On comprehensive FFR wire pullback, <9% (∼5%) of lesions demonstrated persistent residual ischemia likely related to downstream diffuse disease, which could not have been corrected by further stenting or angioplasty without intervening on the entire vessel.
OCT or IVUS recording was not performed routinely in all patients to elucidate the reasons for persistent ischemia (16,17,20,21). Reith et al. (20) showed that there is significant correlation between intra-stent percent area stenosis on OCT and post-stent FFR. Similarly Ito et al. (21) showed inverse correlations between post-stent FFR and residual percent plaque volume and residual plaque volume index in IVUS. However, they found no correlation between FFR and IVUS-derived minimal stent area and quantitative coronary angiography derived minimal lesion diameter (21). Additionally, long-term adverse outcomes after stenting may be due in part to “suboptimal stenting.” Data from FFR-, OCT-, and IVUS-based studies have shown that with angiography alone, a significant proportion of patients undergoing PCI and stenting have suboptimal results, which may increase the risk of long-term MACE (22–25). IVUS-guided stent optimization has been suggested in a meta-analysis to reduce MACE incidence (22). Similarly, abnormal OCT findings after angiographically successful PCI were found to be independently predictive of MACE in the recently published CLI-OPCI (Centro per la Lotta contro l'Infarto-Optimisation of Percutaneous Coronary Intervention) II study (26).
The value of post-PCI FFR in predicting adverse cardiac outcomes has been suggested in a few prior studies but the lack of information regarding the utility of post-PCI FFR in functional optimization of PCI results has been a major limitation (6–13). In the current study, we have shown in a contemporaneous, real-world, high-risk population the utility of post-PCI FFR in attaining functional optimization and its impact on MACE. While the residual post-PCI angiographic stenosis was negligible (1 ± 5%), 143 lesions (21%) had post-PCI FFR ≤0.81 and 36% post-PCI FFR ≤0.85. In a recent report comparing instantaneous wave-free ratio (iFR) and FFR post-intervention, residual ischemia (<0.80) after PCI was found in 13% of the FFR cohort (15). The somewhat larger percentage of patients with residual ischemia in our series may relate to disease complexity.
Post-PCI FFR and prognosis
The value of post-PCI FFR in predicting adverse cardiac outcomes was first studied by Bech et al. (10) in a small group of single-vessel balloon angioplasty patients (n = 60) followed for 2 years. They identified that the patient with both optimal anatomic (post-PCI stenosis <35%) and optimal functional (post-PCI FFR ≥0.90) had a higher event-free survival than patients in whom either angiographic or functional result or both were suboptimal (88 ± 6% vs. 59 ± 9%; p = 0.01). Pijls et al. (7) in a multicenter registry of 750 patients identified FFR immediately after stenting as a predictor of MACE at 6 months follow-up. The event rates in patients with FFR >0.95 (4.9%) was significantly lower than in patients with FFR <0.80 (29.5%). Samady et al. (8) reanalyzed these data from 586 patients in this study and reported MACE rate was significantly higher in patients with post-stent FFR <0.90 when compared to post stent FFR ≥0.90 (19.1% vs. 5.7%; p < 0.01). A major limitation of these studies reported from the same multicenter registry was the relatively short follow-up period of 6 months and exclusive BMS use. Our study differs from these studies in that DES (79%) was predominantly used, lesions were functionally optimized and the follow-up duration was much longer (2.5 ± 1.4 years). The patient population in our study also had higher cardiovascular disease burden with at least twice the percentage of diabetic, hypertensive, and older age patients compared with these studies (11–14).
FFR >0.9 after intervention has been considered an optimal functional endpoint of PCI and has been associated with favorable outcomes (6–13). In our study, 43% of lesions achieved FFR >0.90. Comparatively, in a European multicenter registry 68% achieved FFR >0.9 (7,8), while in a Korean registry 50% achieved FFR >0.9 after PCI (11). The difference may be related to the study population and lesion characteristics. Previous studies (6–13) included relatively simple lesions with an overall lower CAD burden than in the current study. The final FFR of ≤0.86 in our study was based on the ROC curve analysis of the study population with MACE as a classification variable. The lower FFR cutoff in our study might be due to high disease burden in the study patient population as discussed previously. We have shown that after excluding patients with diabetes, CKD and diffuse disease, the optimal post-PCI FFR cutoff for MACE prediction was 0.91 (Figure 7), as shown in previous studies. As demonstrated in the current and previous studies, the final FFR value negatively correlates with adverse events (6–13) as well as late angina status (14). Our findings are further supported by a recent meta-analysis, which showed post-PCI FFR as having an inverse relationship both in continuous (HR: 0.86; 95% CI: 0.80 to 0.93; p < 0.001) and tertile (log-rank p < 0.001) analysis in predicting adverse outcomes (13).
The incidence of MACE in our study was 19%, higher than reported by Nam et al. (11) of 7.5%, Pijls et al. (7) of 10.2%, and Samady et al. (8) of 9.4%. This higher incidence is likely due in part to the fact that the patients were older with a higher prevalence of co-morbidities and a much longer follow-up. TVR incidence in our study was 9.1% with DES. This incidence was similar to that reported by Pijls et al. (7) of 8.9%, Nam et al. (11) of 10% and Samady et al. (8) of 7.7% with BMS. This relatively high TVR incidence with DES is in keeping with the factors noted earlier, namely high incidence of d coronary risk factors implying a high atherosclerotic burden. This study also showed that achieving a final FFR ≥0.85 was associated with a lower TVR rate. Pijls et al. (11) also showed the TVR incidence decreased as the value of FFR increased. Similarly Samady et al. (7) and Nam et al. (11) reported that achieving a FFR of >0.90 was associated with reduced TVR rates of 4.9% (vs. 14.8%; p < 0.01) and 2.5% (vs. 12.5%; p< 0.01), respectively. However, Matsuo et al. (12) reported no significant difference in target lesion revascularization based on post-PCI FFR value, but the post-PCI FFR cutoff used was quite low at 0.79, which was attributed to increased prevalence of diabetic and smaller vessel size in their study population.
Another unique and important aspect of the present study is that it included patients with both DES and BMS. Patients who received DES and achieved post-PCI FFR >0.86 had the lowest event rate (13.1%) and patient who received BMS and achieved post-PCI FFR ≤0.86 had the highest event rate (34.8%). The importance of achieving an optimal post-PCI FFR is further emphasized by the fact that patient who received BMS and achieved post-PCI FFR >0.86 had a lower event rate compared to patients with DES and FFR ≤0.86 (18.3% vs. 26.6%) (Figure 6).
The results of our study strengthen the role of post-PCI FFR in identification of persistently ischemic lesions despite adequate angiographic results and its use in functionally optimizing PCI. We have demonstrated that post-PCI FFR identifies a significant proportion of lesions (∼20%), which have suboptimal post-PCI FFR despite optimal angiographic results. Post-PCI FFR provides a valuable opportunity for “functional optimization” of lesion leading to ischemia resolution during initial intervention. In our study the total number of ischemic lesions was reduced from 21% to 8% after “functional optimization.” Moreover, there was improvement demonstrated in the final FFR values across all FFR values. Additionally, final FFR after PCI FFR provided independent and incremental prognostic information in predicting MACE. Measurement of a post-PCI FFR is intuitively attractive to improve immediate functional PCI results as well as long-term clinical outcomes and a goal to evaluate in future studies.
A limitation of this study includes its retrospective single-center design. As a result selection bias may have been responsible in part for the incidence of post-PCI FFR. We included all consecutive patients to minimize selection bias. Second, in about one-half of the patients, IC adenosine was used and while we demonstrated no difference in the FFR values in patients receiving IC and IV adenosine, comprehensive pullback assessment of the index vessel could not be performed in all the vessels to elucidate the potential mechanisms for persistent residual ischemia. Third, decision making and subsequent interventions were based on the operator’s discretion without a “preset” threshold based on a prospectively derived algorithm. Finally, this study was performed primarily on male veterans; hence our results can only be extrapolated to females and general population. A well-designed randomized trial will be an important step to validate the clinical value of post-PCI FFR in achieving such an “optimal functional result” and its impact on long-term outcomes.
This study emphasizes the value of post-PCI FFR by demonstrating that there is a relatively large group of patients with persistently ischemic lesions despite angiographically optimal PCI results and is strongly predictive of long-term adverse cardiac outcomes. We suggest that FFR after PCI be routinely measured in patients who undergo FFR pre-PCI as it gives a valuable opportunity for “functional optimization” while the patient is still in the cath lab.
WHAT IS KNOWN? Post-PCI FFR values after stenting have shown a wide range of variation after angiographically satisfactory PCI results and have correlated with short to intermediate term major adverse cardiac events in some studies. The impact of post-PCI FFR on subsequent interventional clinical decision making and on long-term outcomes is not known.
WHAT IS NEW? This study demonstrates that post-PCI FFR identifies a significant proportion of lesions (∼20%), which have suboptimal FFR (FFR <0.81) despite optimal angiographic results thereby providing an opportunity for “functional optimization” of PCI results. In our study the total number of ischemic lesions was reduced from 21% to 8% after “functional optimization.” Moreover, there was improvement demonstrated in the final FFR values across all ranges. Furthermore, post-PCI FFR provided independent and incremental prognostic information in predicting MACE.
WHAT IS NEXT? Future studies are needed to better understand the role of post-PCI FFR and how best we can use this information to improve long-term cardiac outcomes.
All authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- Abbreviations and Acronyms
- bare-metal stent(s)
- confidence interval
- drug-eluting stent(s)
- fractional flow reserve
- hazard ratio
- intravascular ultrasound
- major adverse cardiovascular event(s)
- myocardial infarction
- optical coherence tomography
- percutaneous coronary intervention
- receiver-operating characteristic
- target vessel revascularization
- Received December 29, 2015.
- Accepted January 28, 2016.
- American College of Cardiology Foundation
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