Fractional Flow Reserve Measurements in Acute Coronary Syndromes Khôi Minh Lê, MD Co-Director, Cardiac Catheterization Laboratory Eisenhower Desert Cardiology Center Rancho Mirage, CA USA FFR Major Trials Trial FFR cutoff Finding DEFER 0.75 In stable patients with 1-v CAD, stenting nonsignificant lesions does not improve clinical outcomes compared to optimal medical therapy (OMT) FAME 0.80 In patients with multi-vessel disease, FFR guidance improves clinical outcomes as compared to angiographic guidance FAME 0.80 In stable patients with a significant stenosis by FFR, PCI + OMT is superior to OMT alone In the absence of a significant stenosis by FFR, OMT alone is associated with a benign clinical outcome FFR Background • Coronary pressure is linearly related to flow only if the coronary microcirculatory resistance is constant and minimal • FFR is calculated during adenosine-induced hyperemia which achieves the necessary resistance condition • Without maximal hyperemia, the functional severity of the coronary stenosis may be underestimated (falsely elevated FFR measurement) Possible physiologic confounders for FFR measurements in ACS patients • Duration and intensity of ischemia • Embolization of the downstream microvasculature • Acutely elevated left ventricular filling pressures • Altered ventricular wall stress • Altered myocardial contractility • Changes in local and systemic vasoconstrictors • Recent caffeine, theophylline consumption NB: In general, low FFR (0.80) may not be reliable FFR to assess STEMI culprit vessel • Unreliable in the acute setting due to uncertain reduction in maximal achievable flow resulting in falsely elevated FFR • How soon after a STEMI can we obtain a reliable culprit vessel FFR measurement? STEMI Samady et al JACC 2006:47;2187-2193 De Bruyne et al Circ 2001:104;157-162 days days Multivessel disease in Acute Coronary Syndromes • Problems • Problems • Problems In ACS patients, incomplete revascularization (ICR) is associated with poor clinical outcomes These adverse outcomes were seen in ACS patients with residual lesions of ≥50% in vessels ≥2mm “…regardless of the %DS threshold used to define ICR, the presence of angiographic ICR is a strong independent predictor of 1-year MACE…” Benefit of treating borderline nonculprit vessel lesions in STEMI patients PRAMI (NEJM 2013) • 465 STEMI patients • ≥50% nonculprit vessel – Immediate multivessel PCI – IRA PCI and optimal medical therapy • 1° endpoint composite cardiac death, MI, or refractory angina Study stopped early due to highly significant benefit favoring multivessel PCI CvLPRIT (ESC 2014) • STEMI patients • ≥50% nonculprit vessel – Multivessel PCI during initial hospitalization – IRA PCI and optimal medical therapy • 1° endpoint 12 month MACE (death, MI, heart failure, revascularization) Significant reduction in MACE (10.0 vs 21.2%, p=0.009) favoring multivessel PCI Benefit of an early invasive approach in ACS is well established Fox, K A A et al J Am Coll Cardiol 2010;55:2435-2445 Mehta SR et al N Engl J Med 2009;360:2165-2175 ACC/AHA 2014 NonSTEMI ACS Guidelines • Class IIb • “A strategy of multivessel PCI, in contrast to culprit lesion-only PCI, may be reasonable in patients undergoing coronary revascularization as part of treatment for NSTE-ACS.” • Level of Evidence: B In unstable angina/NSTEMI patients, can the FFR be used to guide management? Is using FFR to guide PCI as valid in unstable angina and NSTEMI as it is in stable CAD? Sels et al JACC Cardiovasc Interv.2011;4:1183–1189 Baseline Characteristics of FAME Patients Unstable Angina 36% Tonino PA et al N Engl J Med 2009;360:213-224 29% FAME: Benefit of FFR over angiography is similar between stable CAD and ACS FFR performed to both culprit and non-culprit vessels Sels et al JACC Cardiovasc Interv.2011;4:1183–1189 • Six UK centres, 350 NSTEMI patients referred for invasive management • Randomized to angiography-guided or FFR-guided strategy • Primary endpoint difference in proportion of patients assigned to medical therapy • Not powered to assess difference in clinical outcomes Layland et al Eur Heart J 2014:doi:10.1093/eurheartj/ehu338 Layland et al Eur Heart J 2014:doi:10.1093/eurheartj/ehu338 FAMOUS-NSTEMI Treatment decisions 38/176 (22%) patients had their treatment decision changed based on FFR Layland et al Eur Heart J 2014:doi:10.1093/eurheartj/ehu338 FAMOUS-NSTEMI Angiographically significant stenosis with FFR>0.80 Insignificant stenosis with FFR≤0.80 Relationship between angiographic stenosis severity and fractional flow reserve (FFR) Layland et al Eur Heart J 2014:doi:10.1093/eurheartj/ehu338 Other MACE Angio (2.9%) FFR 10 (5.7%) MI related to PCI or CABG Angio 11 (6.3%) FFR (2.8%) of the 10 patients with late MACE in the FFR group had been reassigned from PCI to medical therapy based on FFR >0.80 Layland et al Eur Heart J 2014:doi:10.1093/eurheartj/ehu338 FAMOUS-STEMI Conclusions • In NSTEMI patients, an FFR-guidance strategy is feasible, commonly changes management, and reduces revascularization • A larger trial is needed to assess clinical outcomes and cost-effectiveness Can FFR be measured reliably? Culprit Acute Nonculprit NO STEMI YES After 3-6 days YES NONSTEMI YES YES Regardless of setting, a low FFR is a reliable indicator of a functionally significant narrowing but a normal FFR may not be definitive Benefit of treating borderline nonculprit vessel lesions in STEMI patients PRAMI (NEJM 2013) • 465 STEMI patients • ≥50% nonculprit vessel – Immediate multivessel PCI – IRA PCI and optimal medical therapy • 1° endpoint composite cardiac death, MI, or refractory angina Study stopped early due to highly significant benefit favoring multivessel PCI CvLPRIT (ESC 2014) • STEMI patients • ≥50% nonculprit vessel – Multivessel PCI during initial hospitalization – IRA PCI and optimal medical therapy • 1° endpoint 12 month MACE (death, MI, heart failure, revascularization) Significant reduction in MACE (10.0 vs 21.2%, p=0.009) favoring multivessel PCI Unanswered questions • Although FFR may reliably predict the hemodynamic significance of a stenosis, is the ability of FFR to guide treatment as relevant in ACS as it is in stable CAD? • Particularly, does an FFR > 0.80 predict the same benign clinical course for an unstable lesion as for a stable one? • In ACS are nonculprit lesions stable? Acute coronary syndromes are distinguished by systemic inflammation, with altered coagulation and impaired endothelial function As a result, other coronary plaques may be destabilized explaining the higher risk of MACE in the early post infarct period 32