Impact of Measuring Fractional Flow Reserve on Decision-Making in the Cath Lab in a Cohort of Patients (FULL TITLE BELOW)

FULL TITLE: Impact of Measuring Fractional Flow Reserve on Decision-Making in the Cath Lab in a Cohort of Patients Being Considered for Coronary Revascularization

ABSTRACT: Background. Fractional flow reserve (FFR) is an accepted standard to detect the functional significance of coronary stenoses. Recent trials suggest that revascularization of moderate coronary stenoses can be safely deferred if the FFR is ≥ 0.75 and FFR can be used to guide therapy in multivessel disease. Aim. In a cohort of patients with moderate angiographic coronary disease, we sought to examine the influence of FFR on lesion revascularization and the impact of multivessel FFR assessment on revascularization strategy. Methods and Results. Patients with FFR measurements taken between April 2005 to October 2007 were included. Out of 300 cases performed in this time, 264 patients were included. Patients were 62 ± 11 years and 1.3 ± 0.54 vessels were examined per case. 92.7% of lesions with a FFR

J INVASIVE CARDIOL 2010;22:413–416

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Many patients are referred for percutaneous coronary intervention (PCI) on the basis of the coronary angiogram alone with no separate functional assessment of ischemia. Coronary angiography is notoriously poor in identifying hemodynamically significant lesions,¹ and many people may undergo unnecessary revascularization procedures. Myocardial fractional flow reserve (FFR) has been shown to be highly accurate in the determination of functionally significant coronary lesions.² FFR is derived from pressure measurements made in the distal coronary artery, beyond the epicardial stenosis, under conditions of hyperemia and presumed minimal microvascular resistance.³ Data are now available showing that revascularization of a moderate coronary stenosis can be safely deferred if the FFR is ≥ 0.75.⁴ In addition, FFR can be used to guide therapy in cases of multivessel disease.⁵ Carefully selected trial patients, however, are often rarely representative of the real world, which leaves the generalizability of these results open to interpretation. The purpose of this study was to investigate the use of the pressure wire in a large unselected cohort of patients with moderate coronary stenoses being considered for PCI. We sought to examine the use of FFR measurements on how they influenced decision-making in the catheterization laboratory and how the use of the pressure wire in patients with multivessel disease resulted in the reclassification of disease severity in such cases.

Methods

Between April 2005 and October 2007, consecutive patients who were undergoing a clinically indicated pressure-wire assessment in a vessel with moderate coronary stenosis (with a visual angiographic diameter of 50–75%) that was being considered for percutaneous revascularization were selected. The population included those with both single and multivessel disease. Patients who had been recruited into clinical trials that mandated invasive coronary physiological measurements as part of their protocol were excluded. One milligram of intracoronary isosorbide dinitrite was administered prior to coronary angiography. The FFR was recorded as previously described using a 0.014" pressure wire (RADI Systems, St. Jude Medical, St. Paul, Minnesota) under conditions of hyperemia induced by an infusion of adenosine at 140 µg/kg/min through a central vein.⁶ FFR was calculated as (Pd - Pv)/(Pa - Pv) where Pa, Pv and Pd are simultaneous aortic, right atrial and distal coronary pressures, respectively. Right atrial pressure was measured in all cases.⁷ The number of vessels examined was recorded, as was the choice of treatment for that vessel. A full demographic dataset was obtained for all patients. All patients were preloaded with aspirin and clopidogrel and received 5,000 IU of periprocedural intravenous unfractionated heparin. Data were expressed as mean ± standard deviation and qualitative variables as percentages. The student’s t-test was used to compare mean values for quantitative variables and chi-square tests were used to compare qualitative variables. A p-value of Results During the observation period, 5,609 PCI procedures were carried out in our institution. Of these, 300 patients (5.3%) underwent a pressure-wire assessment. There was a mixture of elective and urgent cases. Out of these, 264 were included in the analysis. Reasons for exclusion from the analysis were as follows: 14 patients who had been recruited into clinical trials that mandated pressure-wire measurements were excluded; in 9 patients FFR measurement was unsuccessful (4 unable to wire vessel, 3 adenosine-induced heart block, 2 adenosine-induced bronchospasm); in 6 patients FFR was no longer indicated due to vessel closure, etc; and in 7 cases FFR was not recorded. Patient age was 61.8 ± 11 years. Full demographic data are shown in Table 1. Patients in the defer group were in general older, with a higher proportion of females, but otherwise the groups were well matched in terms of cardiac risk factors and the incidence of single-, double- and triple-vessel coronary disease. The incidence of patients with isolated left main stem (LMS) disease was also similar. Patients in the revascularization group were more likely to be discharged on clopidogrel (p = 0.03), but otherwise there were no differences between the groups, with both being well treated with aspirin, beta-blockers, ACE inhibitors and statins. A total of 334 vessels were examined with a pressure wire in this study population. The majority of patients had an FFR measurement in a single vessel, but 23% underwent multivessel examination, and overall, 1.3 ± 0.54 vessels were examined per patient. Of these vessels, 75 (22%) were revascularized and 259 (77%) were left alone. Thus, in this cohort of patients with moderate angiographic coronary disease being considered for revascularization, 191 (75%) patients avoided the revascularization of at least one vessel as a result of the FFR being measured. These results are summarized in Figure 1 (Table 2). Fifty-two out of 56 (92.8%) lesions with a FFR 0.8 underwent revascularization. Of the overall patients revascularized, 9 (12%) underwent coronary artery bypass grafting (CABG) and 64 (88%) underwent PCI. In vessels that were revascularized, the FFR was 0.71 ± 0.07, and in those deferred, the FFR was 0.86 ± 0.06 (p Discussion This study suggests that in a large, heterogeneous “real-world” population of patients being considered for percutaneous revascularization, the measurement of FFR has a significant impact on decision-making in the catheterization laboratory. FFR measurement is associated with high procedural success rates (98%) and low complication rates (1.5%), and in the vast majority of cases, directly influenced patient care. In patients with multivessel disease apparent from coronary angiography, FFR can be used to reclassify the severity of these lesions, with the majority of patients benefiting from at least one vessel “spared” from revascularization. The measurement of FFR in a vessel with a moderate coronary stenosis has been advocated by the latest clinical guidelines.^8,9 Coronary angiography alone is notoriously poor at discriminating functionally significant coronary lesions from those that are not.¹⁰ It has been shown that patients without demonstrable ischemia do not benefit from revascularization, with little evidence suggesting improvement of symptoms or prognosis.¹¹ Indeed, unnecessary revascularization procedures may expose the patient to additional risk, as well as increase the burden of healthcare expenses.¹² In patients with moderate coronary stenoses, FFR has been shown to have a strong correlation with noninvasive tests of myocardial ischemia and is robust and highly reproducible over a range of hemodynamic conditions.² The concept of a lesion being “functionally” significant as opposed to being “angiographically” significant is important to consider, as in many cases, lesions continue to be treated on their angiographic appearance alone. The current study shows that in a nonselected cohort of patients being considered for coronary revascularization, FFR is being used appropriately as a clinically useful tool with subsequent treatment being directly influenced by the measurements obtained. In this sample 93% of patients with an FFR 0.8 had intervention deferred. All of the lesions examined were of at least moderate severity angiographically and were being considered for revascularization. A significant proportion of the patients in the present study involved multivessel FFR measurements. In this situation, coronary angiography alone has been shown to be inaccurate, with potentially important consequences. Multivessel PCI is associated with increased risk, increased exposure to radiation, more contrast dye and greater use of anticoagulants during the procedure, as well as an increased risk of stent-related complications further down the line.¹³ On the other hand, hemodynamically significant three-vessel disease carries adverse prognosis and must not be missed. The recent FAME5 study examined whether routine measurement of FFR, in addition to angiography, improved outcomes. A total of 1,005 patients with multivessel coronary artery disease were randomized to undergo PCI with implantation of drug-eluting stents guided by angiography alone or guided by FFR measurements in addition to angiography. Before randomization, lesions requiring PCI were identified on the basis of their angiographic appearance. Patients assigned to angiography-guided PCI underwent stenting of all indicated lesions, whereas those assigned to FFR-guided PCI underwent stenting of indicated lesions only if the FFR was ≤ 0.80. The primary endpoint was the rate of death, nonfatal myocardial infarction and repeat revascularization at 1 year. Although the number of indicated lesions was the same in each group, the number of stents used per patient was significantly less in the FFR group (2.7 ± 1.2 and 1.9 ± 1.3, respectively; p 14 In the present study population, the influence of physiologic assessment was even greater, as three-quarters of patients being considered for multivessel PCI based on their angiogram avoided the need for revascularization of at least one vessel based on the FFR measurements. Study limitations. The main purpose of this study was to examine the impact of FFR measurements on clinical decision-making in a real-world population of patients undergoing PCI at a large center. This was a retrospective, observational study and was not powered to compare clinical endpoints.

Conclusion

The measurement of FFR in a heterogeneous population with moderate coronary stenoses being considered for coronary revascularization has a significant impact on clinical decision-making. FFR can be used to reclassify disease severity in patients with multivessel stenoses, reducing the need for vessel revascularization in the majority of cases.

References

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From The Rayne Institute, St Thomas' Hospital, KCL, London, United Kingdom. Disclosure: Dr. Lockie is supported by the British Heart Foundation. None of the other authors have any financial relationships or conflicts of interest regarding the content herein. Manuscript submitted April 29, 2010, provisional acceptance given May 20, 2010, final version accepted June 23, 2010. Address for correspondence: Tim Lockie, MBChB, The Rayne Institute, 3rd Floor Lambeth Wing, St Thomas' Hospital, KCL, London, SE1 7EH, United Kingdom. E-mail: tim.lockie@gstt.nhs.uk