Bifurcation FFR - Helpful or Wasteful? Allen Jeremias, MD, MSc Director, Interventional Cardiology Research Assoc. Director, Cardiac Catheterization St. Francis Hospital, Roslyn, NY Director, Physiology Core Laboratory Cardiovascular Research Foundation, NY, NY

Disclosure Statement of Financial Interest Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the organization(s) listed below. Affiliation/Financial Relationship Company Consulting Fees/Honoraria Astra Zeneca Volcano/Philips Abbott Vascular Medtronic St. Jude Medical

Why “Physiologic Evaluation” in Bifurcation Lesion? Uniqueness of side branch lesions Various size, various amount of supplying myocardium Side branch ostial lesion is unique Underlying plaque  Eccentric plaque Remodeling  Negative remodeling Mechanisms of ostial narrowing after main branch stenting Carina shift, plaque shift, stent struts, thrombus….. Koo and De Bruyne. Eurointervention 2010;6:J94-J98.

Anatomical and Functional Mismatch Diagonal branch: Minimal lumen diameter: 1.7mm Lumen area: 2.7mm2 Vessel area: 5.0mm2 LAD FFR LAD: Minimal lumen diameter: 1.8mm Lumen area: 2.8mm2 Vessel area: 9.0mm2 Diagonal FFR Courtesy Bon-Kwon Koo, MD, PhD 5

Poor Correlation btw Diameter Stenosis and FFR in Jailed Side Branches Fractional Flow Reserve SNUH SB-FFR registry Park SH & Koo BK, J Ger Cardiol 2012 Ahn JM, et al. JACC intv 2012 Fractional Flow Reserve Kumsars I, et al. Eurointervention 2011 Bellenger, et al. Heart 2007

Physiologic Assessment of Jailed Side Branch Lesions 97 lesions in 92 patients All had >50% angio stenosis and TIMI 3 flow after being jailed by stent All > 2mm in diameter FFR successful in all but 3 lesions No TVR (f/u 10 months) for FFR > 0.75 BK Koo, et al. JACC 2005; 46:633

Reason for Mismatch: Carina Shift Carina shift accentuates lumen eccentricity and results in more angiographic diameter loss than lumen area loss Koo BK, et al. Circ Cardiovasc Interv 2010;3:113

Which side branch is clinically important? Focus more on “myocardial mass at risk” than angiographic parameters ~10% How much % of myocardium is at risk? Hachamovitch, Circulation 2003

What is the ischemic burden of the myocardium?

Shiono Y et al., Catheter Cardiovasc Interv 2014;1;84(3):406-13. Impact of myocardial supply area on transstenotic hemodynamics as determined by FFR Representative cases with mismatch between QCA and FFR. A: Intermediate stenosis (percent diameter stenosis = 53%) was seen in a proximal LAD which had a large‐sized diagonal branch. Because the myocardial area supplied by the coronary artery distal to the stenosis was large (modified APPROACH score = 47.75%), the FFR value was below the ischemic threshold (FFR = 0.58). B: Severe stenosis (percent diameter stenosis = 80%) was found in mid RCA with small myocardial supply area (modified APPROACH score = 9.25%). Then, the FFR value was above the ischemic threshold (FFR = 0.91). APPROACH score, Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease score; FFR, fractional flow reserve; LAD, left anterior descending artery; QCA, quantitative coronary angiography; RCA, right coronary artery. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] IF THIS IMAGE HAS BEEN PROVIDED BY OR IS OWNED BY A THIRD PARTY, AS INDICATED IN THE CAPTION LINE, THEN FURTHER PERMISSION MAY BE NEEDED BEFORE ANY FURTHER USE. PLEASE CONTACT WILEY'S PERMISSIONS DEPARTMENT ON PERMISSIONS@WILEY.COM OR USE THE RIGHTSLINK SERVICE BY CLICKING ON THE 'REQUEST PERMISSIONS' LINK ACCOMPANYING THIS ARTICLE. WILEY OR AUTHOR OWNED IMAGES MAY BE USED FOR NON-COMMERCIAL PURPOSES, SUBJECT TO PROPER CITATION OF THE ARTICLE, AUTHOR, AND PUBLISHER. Shiono Y et al., Catheter Cardiovasc Interv 2014;1;84(3):406-13.  

Shiono Y et al., Catheter Cardiovasc Interv 2014;1;84(3):406-13. Impact of Myocardial Supply Area on Transstenotic Hemodyamics as Determined by FFR Percent Diameter Stenosis Myocardial Supply Area Shiono Y et al., Catheter Cardiovasc Interv 2014;1;84(3):406-13.  

Clinical Significance: Main vs. Side Branch - Responses to 1-minute balloon occlusion -   LAD Diagonal P value Chest pain (VAS score) 5 2 <0.0001 ST elevation ≥ 1mm 92.3% 35.4% 0.001 QTc interval, msec 454.0±45.4 440.4±35.7 0.07 QTc dispersion, msec 83.8±39.2 70.7±28.5 Side branches have much less clinical relevance in terms of symptoms, ischemia and arrhythmic potential Koo BK, et al., JACC Cardiovasc Intervent 2012

Collateral Supply Higher in Branch Vessels assessed by coronary wedge pressure (Pw) Diagonal Pw 39mmHg, Pw/Pa 0.36 LAD Pw 23mmHg, Pw/Pa 0.26 Koo BK, et al., JACC Cardiovasc Intervent 2012

Difference in Collateral Recruitability - LAD vs. Diagonals -   LAD Diagonal P value Pre-intervention FFR 0.67±0.10 0.71±0.11 0.02 Pw, mmHg 21.0±6.5 26.7±9.4 <0.0001 Pw/Pa 0.22±0.07 0.27±0.08 0.001 Pw: coronary wedge pressure, Pa: aortic pressure Diagonal branch has higher Pw and Pw/Pa than LAD and may have higher collateral recruitability and more protection from ischemia Koo BK, et al., JACC Cardiovasc Intervent 2012

Collateral Supply Independent Predictor of Mortality 739 pts with chronic stable angina followed over 10 years Coronary pressure derived ‘collateral flow index’ (CFI) determined during a 1-minute coronary balloon occlusion Independent predictors of 10-year mortality: Age Low CFI Smoking Meier P, et al., Circulation 2007

61 year old woman atypical Chest pain, no ischemia testing How would you treat this bifurcation? Zaiee A, et al. AJC, 2004;93:1404-07

61 year old woman atypical Chest pain, no ischemia testing How would you treat this bifurcation? FFR=0.94 Zaiee A, et al. AJC, 2004;93:1404-07

FFR of “jailed” Circumflex Pre Stent Post Stent FU @ 8 mo Nam CW, et al. Korean Circ J 2011;41:304-7.

FFR of “jailed” Circumflex FFR of “jailed” circumflex in 43 patients after LM cross-over PCI During median 12.5 month follow-up only one adverse event (non-cardiac death) in 37 patients with deferred ostial LCx treatment Kang SJ, et al. Catheter Cardiovasc Intervent 2014;83:545-52.

Kumsars, et al. Eurointervention 2012;7:1155-61. Kissing Balloon Inflation for Jailed Side Branches FFR in 75 “Jailed” side branches from Nordic-Baltic Bifurcation III study (42 with final kissing, 32 without) Final Kissing No Immediately Post PCI 8 Month Follow-Up FFR No difference in clinical outcomes Kumsars, et al. Eurointervention 2012;7:1155-61.

Percent Diameter Stenosis vs. Functional Significance Before PCI After MB stenting After kissing balloon

DKCRUSH-VI Randomized Bifurcation Trial • Chinese Multi-Center Study • 320 Patients • SB at least 2.5mm • Medina 1,1,1/0,1,1 • 9% distal LMCA Chen SL, et al, JACC Cardiovasc Interv 2015

One-year clinical outcomes DKCRUSH-VI Study Design One-year clinical outcomes Angio group (n=160) FFR group (n=160) p Cardiac death, n(%) 1 (0.6) 2 (1.3) 0.56 MI, n(%) 22 (13.8) 19 (11.9) 0.74 TLR, n(%) 8 (5.0) 5 (3.1) 0.57 CABG, n(%) ----- TVR, n(%) 11 (6.9) 9 (5.6) 0.82 MACE, n(%) 29 (18.1) 1.00 ST-def/prob, n(%) • Less SB intervention with FFR (56% vs 63%, p=0.07) • Fewer stents with FFR (26% vs 38%, p=0.01) Chen SL, et al, JACC Cardiovasc Interv 2015

Consensus: FFR in Bifurcations Lassen JF, et al. EuroIntervention 2016;12(1):38‐46

Consensus: FFR in Bifurcations Sawaya FJ, et al. JACC Cardiovasc Interv. 2016;9(18):1861‐78