FFR-guided Complete vs. Culprit Only Revascularization in AMI Patients Ki Hong Choi, MD On Behalf of FRAME-AMI Investigators

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FFR-guided Complete vs. Culprit Only Revascularization in AMI Patients Ki Hong Choi, MD On Behalf of FRAME-AMI Investigators Heart Vascular Stroke Institute, Samsung Medical Center, Seoul, Republic of Korea

Multivessel Disease in AMI 30-40% in the setting of STEMI Muller DW, et al Multivessel coronary artery disease: a key predictor of short-term prognosis after reperfusion therapy for acute myocardial infarction. Thrombolysis and Angioplasty in Myocardial Infarction (TAMI) Study Group. Am Heart J 1991;121:1042-9 Toma M,, et al. Non-culprit coronary artery percutaneous coronary intervention during acute ST-segment elevation myocardial infarction: insights from the APEX-AMI trial. European Heart Journal 2010;31:1701-7 44-60% in the setting of NSTEMI Effects of tissue plasminogen activator and a comparison of early invasive and conservative strategies in unstable angina and non-q-wave myocardial infarction. Results of the TIMI IIIB Trial. Thrombolysis in Myocardial Ischemia. Circulation 1994;89:1545 1556. Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators. Lancet 1999;354:708 715. AMI with multi-vessel disease was associated with poorer outcomes Park DW et al. Extent, location, and clinical significance of non-infarct-related coronary artery disease among patients with ST-elevation myocardial infarction. JAMA. 2014 Nov 19;312(19):2019-27.

Context PART 1 Reliability of fractional flow reserve (FFR) to evaluate the functional significance of non-culprit stenosis in patients with acute myocardial infarction (AMI) and multivessel disease. PART 2 Comparison of clinical outcomes between FFR-guided complete revascularization versus culprit only percutaneous coronary intervention (PCI) in patients with AMI and multi-vessel disease. PART 3 Optimal treatment strategy for patients with AMI and multi-vessel disease (focused on treatment criteria for non-culprit stenosis)

Context PART 1 Reliability of fractional flow reserve (FFR) to evaluate the functional significance of non-culprit stenosis in patients with acute myocardial infarction (AMI) and multivessel disease. PART 2 Comparison of clinical outcomes between FFR-guided complete revascularization versus culprit only percutaneous coronary intervention (PCI) in patients with AMI and multi-vessel disease. PART 3 Optimal treatment strategy for patients with AMI and multi-vessel disease (focused on treatment criteria for non-culprit stenosis)

Debates for Reliability of FFR in AMI patient - Potential Concerns of Blunted Hyperemic Response - 40 STEMI patients, PS matched with 40 Stable Angina without obstructive lesion A. CFR (Doppler) B. Resting Flow Velocity C. Hyperemic Flow Velocity They claimed blunted hyperemic response in STEMI setting Unreliability of non-culprit vessel FFR De Waard et al. JACC: Cardiovascular Intervention, 2016

Debates for Reliability of FFR in AMI patient - Reliability of Acute phase Non-culprit vessel FFR - Non-culprit vessel of AMI Patient Acute Phase (n=101) 1 Month Follow-Up (n=101) P Value LVEF (%) 59 ± 15 61 ± 14 NS LVEDP (mmhg) 18 ± 7 17 ± 7 NS FFR nonculprit 0.77 ± 0.13 0.77 ± 0.13 NS IMR nonculprit (IU) 20 ± 3 24 ± 6 NS DS nonculprit (%) 56 ± 14 55 ± 14 NS TIMI flow nonculprit 2.93 ± 0.30 2.97 ± 0.20 NS ctfc nonculprit 15 ± 6 15 ± 6 NS In patients with acute MI (including STEMI and NSTEMI), non-culprit FFR did not show significant change. Ntalianis, et al. JACC: Cardiovascular Intervention, 2010

Reliability of Acute phase Non-culprit vessel FFR - Validation using Animal Experiments - FFR and IMR Changes in Non-Culprit Vessel - Porcine Microvascular Damage Model - LAD (Microsphere) LCX (No Microsphere) P<0.001 P=0.286 P<0.001 P=0.105 Local microvascular damage in culprit vessel was not extended to non-culprit vessel territory, and non-culprit vessel FFR and IMR were not changed at all. Lee JM, Kim HK, Choi KH Koo BK et al. JACC: Cardiovascular Intervention, 2018

Reliability of Acute phase Non-culprit vessel FFR - Validation using Clinical Data - In STEMI non-culprit vessel CFR is depressed as with culprit vessel IMR is elevated only in culprit vessel In STEMI non-culprit vessel Resting coronary flow is increased Depressed CFR in non-culprit vessels of STEMI patients is mainly due to increased resting coronary flow not mainly due to depressed hyperemic coronary flow or increased microvascular resistance In STEMI non-culprit vessel Hyperemic coronary flow is not changed Choi KH, Lee JM Koo BK et al. JACC: Cardiovascular Intervention, 2018

Our Previous Research - Validation using Clinical Data - Interaction P (SIHD vs. AMI) = 0.371 Diameter Stenosis Even in the acute stage of MI, non-culprit FFR reliably reflect lesion severity. Choi KH, Lee JM Koo BK et al. JACC: Cardiovascular Intervention, 2018

Context PART 1 Reliability of fractional flow reserve (FFR) to evaluate the functional significance of non-culprit stenosis in patients with acute myocardial infarction (AMI) and multivessel disease. PART 2 Comparison of clinical outcomes between FFR-guided complete revascularization versus culprit only percutaneous coronary intervention (PCI) in patients with AMI and multi-vessel disease. PART 3 Optimal treatment strategy for patients with AMI and multi-vessel disease (focused on treatment criteria for non-culprit stenosis)

Non-culprit Lesion PCI after Primary PCI in STEMI - Angio-guided Complete Revascularization vs. Culprit-Only PCI - Preventive PCI for non-culprit lesion >50% DS Preventive PCI for non-culprit lesion > 70% DS or > 50% DS in 2 views Recent RCTs presented angiography-guided complete revascularization showed significant benefit in patient s outcome than culprit-only PCI PRAMI NEJM 2013;369:1115-23 CvLPRIT JACC 2015;65:963-72 In terms of hard endpoint (Death, MI PRAMI) or In terms of soft endpoint (MACE but not death/mi CvPRIT)

Non-culprit Lesion PCI after Primary PCI in STEMI - FFR-guided Staged CR vs. Culprit-Only PCI - DANAMI-3-PREMULTI Trial Staged non-culprit FFR median 2 days (2-4) FFR-guided staged complete revascularization showed significant benefit in terms of composite endpoints (Any death, MI, ischemia driven revascularization) DANAMI-3-PRIMULTI Lancet. 2015 Aug 15;386(9994):665-71.

Non-culprit Lesion PCI after Primary PCI in STEMI - FFR-guided Immediate CR vs. Culprit-Only PCI - MACCE event free Survival (%) COMPARE ACUTE Trial 100 7.8% 80 20.5% 60 40 HR 0.35 (95% CI 0.22-0.55), log-rank p<0.001 65% Risk Reduction 20 0 83% of patients received Immediate FFR-guidance for non-culprit vessel stenosis No. at Risk 0 3 6 9 12 Months FFR-CR 295 286 281 264 215 Culprit-Only 590 512 492 457 371 FFR-guided immediate complete revascularization showed significantly lower risk of MACCE than culprit-only PCI COMPARE-ACUTE N Engl J Med 2017; 376:1234-1244

Context PART 1 Reliability of fractional flow reserve (FFR) to evaluate the functional significance of non-culprit stenosis in patients with acute myocardial infarction (AMI) and multivessel disease. PART 2 Comparison of clinical outcomes between FFR-guided complete revascularization versus culprit only percutaneous coronary intervention (PCI) in patients with AMI and multi-vessel disease. PART 3 Optimal treatment strategy for patients with AMI and multi-vessel disease (focused on treatment criteria for non-culprit stenosis)

Non-culprit PCI in STEMI multivessel Updated ESC 2017 Guideline For Non-culprit vessel stenosis: The optimal timing of revascularization (immediate vs. staged) and optimal treatment criteria (%DS, FFR, or vulnerability) has not been clarified. Ibanez B et al. Eur Heart J. 2018 Jan 7;39(2):119-177.

Non-culprit PCI in STEMI multivessel Current Evidences and Future Perspectives

Future Perspectives - FFR-guided CR vs. Angiography-guided CR in AMI -

Summary In AMI Patients with Non-culprit Stenosis For the Non-Culprit Lesion of STEMI and NSTEMI (multivessel), FFR-guided strategy is reasonable and reliable, even in the acute stage of AMI. In STEMI with multivessel disease, FFR-guided strategy for non-culprit stenosis already proved its prognostic benefit than culprit-only PCI (DANAMI-3-PRIMULTI, COMPARE-ACUTE). In STEMI/NSTEMI with multivessel disease, More evidence is needed to compare FFR-guided CR vs. Angio-guided CR. FRAME-AMI Trial will clarify this issue.

Thank You For Your Attention! Ki Hong Choi, MD Clinical Fellow, Heart Vascular Stroke Institute, Samsung Medical Center, Seoul, Republic of Korea