Journal of Invasive Cardiology

Abstract: Background. Randomized trials using measurement of fractional flow reserve (FFR) to guide percutaneous coronary intervention (PCI) have demonstrated both safety and efficacy with regard to cardiac events. Real-world, long-term outcomes using an FFR-based revascularization strategy are unknown. Methods. Prospective clinical data were collected on consecutive patients referred for coronary angiography and found to have lesions of intermediate severity where the operators were unable to make a decision regarding revascularization based on angiographic, clinical, and stress testing parameters. FFR was measured on intermediate lesions, and revascularization was deferred on those lesions with a measurement >0.8. Clinical outcomes of interest included death, myocardial infarction, and late revascularization status. Results. A total of 151 patients were included in this study. Fifty-seven patients (37.7%) underwent revascularization based on their FFR measurement. The mean length of follow-up was 6.1 years (range, 5-10 years). Follow-up was completed in 97.0%. At the end of the follow-up period, 107 patients (70.9%) were alive. Late revascularization had been performed in 18 patients (11.9%). Comparing the initial revascularization group with the group in which revascularization was deferred, 64.9% and 74.5% were alive, respectively (P=.29). Of the initial revascularization group, 12.3% had undergone late revascularization of the lesion on which FFR was originally performed, compared with 11.7% in the deferred group (P=.99). Conclusions. FFR is a useful adjunct to coronary angiography in selecting patients with lesions of intermediate angiographic severity in whom coronary revascularization may be safely deferred.

J INVASIVE CARDIOL 2012;24(7):309-315

Key words: fractional flow reserve, pressure wire, percutaneous coronary intervention

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Coronary artery revascularization is appropriate and indicated for many patients with coronary artery disease (CAD).^1-3 Selection of patients for revascularization based on visual assessment of coronary stenosis by angiography alone is difficult in some cases since angiography provides limited insight into the physiologic significance of intermediate coronary lesions.^4-6 Additional concerns regarding the association between drug-eluting stents and late complications, continued exposure to dual anti-platelet therapy, and increased costs make appropriate use of these devices critical.⁷

Measurement of fractional flow reserve (FFR) can be used to quantify the flow limitation caused by a coronary stenosis at the time of angiography. When compared to traditional angiography-guided PCI, a strategy of FFR-guided PCI has been shown to be safe and effective in randomized controlled trials.^8,9 The Fractional Flow Reserve versus Angiography for Multivessel Evaluation (FAME) study demonstrated that an FFR-based revascularization strategy significantly reduced the combined rate of death, non-fatal myocardial infarction, and repeat revascularization over 1 year, while reducing overall costs.^8,10 Long-term, real-world outcomes using this strategy, however, are largely unknown.

We report our experience using a strategy of FFR-guided revascularization in patients with long-term clinical follow-up of up to 10 years. The objective of this analysis was to compare long-term clinical outcomes in patients with intermediate coronary lesions in whom an FFR measurement led to initial coronary revascularization with those whose FFR measurement led to the deferral of revascularization.

Methods

All patients who underwent coronary angiography in our cardiac catheterization laboratory were included in this analysis if an FFR-guided decision regarding revascularization was used during their procedure. All procedures were performed by 2 experienced interventional operators (JDL and SPS) at the Manhattan Campus of the VA New York Harbor Healthcare System in New York, NY, from January 1, 2000 to December 31, 2005.

Coronary angiography was performed using standard techniques and views. The severity of all coronary lesions was initially graded by the operator’s qualitative assessment. The decision to pursue FFR measurement as an adjunct to angiography was made by the operator only in cases when additional information was required after review of angiographic, clinical, and stress testing data to make a decision regarding coronary revascularization. Most commonly, this was needed when stress testing had not been performed or when the results of stress testing appeared discordant from the angiographic data.

For each stenosis included in our analysis, FFR was measured during maximum hyperemia using a coronary pressure guidewire (Radi Medical Systems). Maximum hyperemia was induced using an intracoronary bolus of adenosine (20-40 µg), and the FFR was calculated from the ratio of the mean hyperemic distal coronary pressure and the mean hyperemic proximal coronary pressure.^11,12 Often, multiple FFR measurements of the lesion were made, and the lowest measurement was used as the final assessment.

The decision to proceed with or defer coronary revascularization was left to the discretion of the operator. In general, lesions with FFR measurements of <0.75 were considered for revascularization; medical therapy was recommended for lesions with measurements of >0.8. Lesions with measurements in the range of 0.75-0.8 were considered intermediate, and decisions regarding revascularization were made according to the operator’s judgment. The method by which revascularization was performed was also left to the operator and included balloon angioplasty, coronary artery stenting with either bare-metal or drug-eluting stents, and referral for coronary artery bypass grafting (CABG).

Baseline and follow-up clinical assessments were made by review of the patient’s electronic medical record available through the Veterans Administration. All available records were assessed through July 1, 2010. All follow-up clinical encounters, decisions regarding medical management, and referral for additional testing or revascularization procedures were scheduled or performed according to routine clinical practice at the discretion of the patient’s healthcare providers.

Clinical outcomes of interest included vital status, subsequent myocardial infarction, clinical angina status, and late revascularization of the index lesion. Classification of patient’s mode of presentation, medical co-morbidities, follow-up clinical status, and presence of myocardial infarction were adjudicated by two independent clinicians blinded to coronary catheterization procedural data and index revascularization status. Myocardial infarction (MI) was defined as a rise and fall of cardiac biomarkers above the 99th percentile of the upper reference limit in the setting of symptoms consistent with ischemia or electrocardiographic changes including ST-segment deviation, new left bundle branch block, or new pathologic Q-waves.¹³ Periprocedural MI was excluded from the analysis.

Stress tests results performed prior to the patient’s referral for angiography were also examined and assessed for concordance and discordance with the subsequent FFR results. FFR results were considered concordant with stress test results if the FFR measurement was <0.8 and there was evidence of ischemia in the corresponding coronary distribution on SPECT imaging, or the FFR measurement was >0.8 and there was no evidence of ischemia in the corresponding coronary distribution on SPECT imaging. The extent of ischemia noted on SPECT imaging was classified according to number of coronary territories affected by ischemia. Patients that underwent exercise stress testing without imaging were excluded from this part of the analysis.

Categorical variables are expressed as proportions and compared using the chi-square test or Fisher’s exact test. Normally distributed continuous variables are presented using means and standard deviations, and comparisons were performed using an unpaired two-sided t-test. Non-normally distributed continuous variables are expressed as medians and interquartile ranges, and comparisons were performed using a Wilcoxon test. Clinically relevant patient-level baseline measures were entered into a multivariate logistic regression analysis to investigate relationships with the outcomes of interest. Time-to-death data are presented as a Kaplan-Meier estimate and compared with the log-rank test. A two-sided P<.05 was considered to indicate a statistically significant result. All statistical analyses were performed using SPSS for Windows, version 17.0 (SPSS Inc).

Results

From January 1, 2000, through December 31, 2005, a total of 151 patients underwent FFR measurement to assess the significance of 171 coronary lesions. Of these patients, 57 (37.7%) had immediate coronary revascularization or referral for CABG, and 94 (62.3%) had revascularization deferred. The mean length of follow-up was 6.1 years.

Baseline characteristics were comparable in both groups (Table 1). The mean age was 65.2 years, and the majority of the patients were male. Approximately one-half of the patients had diabetes, and one-third had prior MI, prior PCI, or abnormal left ventricular function. Over 90% of the patients were considered to have moderate or severe medical co-morbidities. The modes of presentation were similar in both groups, with over one-third of the patients presenting with an acute coronary syndrome. The majority of patients had preceding stress tests, and over 85% of these tests were considered abnormal. Approximately one-quarter of the stress test results included SPECT imaging consistent with multi-vessel ischemia. On angiography, the number of diseased vessels was not significantly different, with more than one-half of patients presenting with multi-vessel coronary disease. 

With regard to FFR measurement and revascularization, the LAD was the most frequently assessed coronary artery, and it was more often assessed in patients in the initial revascularization group (81.0%) than in the deferred group (65.7%; P=.04). In patients with a preceding stress test, FFR results were concordant with the nuclear findings in 67.2% of those in the initial revascularization group and 59.0% in the deferred group (P=.38). By design, the FFR measurement was significantly lower in the initial revascularization group (0.71) compared to that of the deferred group (0.83; P<.001). There was a trend toward more revascularization of additional lesions in the initial revascularization group (33.3%) than the deferred group (22.3%; P=.14). In patients who underwent initial revascularization of the index lesion, 78% underwent PCI while the remaining patients underwent CABG.