CARDIOLOGY GRAND ROUNDS

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1 CARDIOLOGY GRAND ROUNDS Title: Fractional flow reserve (FFR) Computed tomography (CT) Speaker: John R. Lesser, MD Senior Consulting Cardiologist, Medical Director CT/CMR Minneapolis Heart Institute at Abbott Northwestern Hospital Date: Monday, December 7, 2015, Time: 7:00 8:00 AM Location: ANW Education Building, Watson Room OBJECTIVES At the completion of this activity, the participants should be able to: 1. Review the meaning and importance of invasive FFR measurements. 2. Recall the basic process necessary to obtain an FFR CT and the clinical settings where it may be useful. 3. Review some of our cases that demonstrate the strengths and limitations of the technique. Physician: This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of Allina Health and Minneapolis Heart Institute Foundation. Allina Health is accredited by the ACCME to provide continuing medical education for physicians. Allina Health designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credit(s) TM. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Nurse: This activity has been designed to meet the Minnesota Board of Nursing continuing education requirements for 1.2 hours of credit. However, the nurse is responsible for determining whether this activity meets the requirements for acceptable continuing education. DISCLOSURE STATEMENTS Speaker Dr. Lesser has declared he does not have any conflicts of interest to disclose. Planning Committee Dr. Michael Miedema, and Jolene Bell Makowesky have declared that they do not have any conflicts of interest associated with the planning of this activity. Dr. Robert Schwartz declared the following relationships stockholder: Cardiomind, Interface Biologics, Aritech, DSI/Transoma, InstyMeds, Intervalve, Medtronic, Osprey Medical, Stout Medical, Tricardia LLC, CoAptus Inc, Augustine Biomedical; scientific advisory board: Abbott Laboratories, Boston Scientific, MEDRAD Inc, Thomas, McNerney & Partners, Cardiomind, Interface Biologics; options: BackBeat Medical, BioHeart, CHF Solutions; speakers bureau: Vital Images; consultant: Edwards LifeSciences. PLEASE SAVE A COPY OF THIS FLIER AS YOUR CERTIFICATE OF ATTENDANCE Signature: My signature verifies that I have attended the above stated number of hours of the CME activity. Allina Health - Learning & Development Chicago Ave - MR Minneapolis MN 55407

2 FFR-CT: Background and Application John R. Lesser, MD Minneapolis Heart Institute The Minneapolis Heart Institute The Minneapolis Heart Institute Foundation Presenter Disclosure Information John R. Lesser, M.D. DISCLOSURE INFORMATION: The following relationships exist related to this presentation: None 1

3 Animal Coronary Constrictor vs Human Epicardial Doppler and CA Animal model Human measurements Gould KL. JACC Cardiovascular imaging 2009;2: White CW, et al. N Engl J Med 1984;310: Current Status with CAD Dx ACC NCDR Registry No known prior CAD 663 hospitals, ~ 400,000 pts. 84% had non-invasive testing 38% obstructive disease 39% no CAD at all + Non-invasive test: 41 vs. 35% (no stress test) significant CAD Patel MR, et al. NEJM 2010;362:

4 Non-invasive Tests in ACC NCDR Registry Cury RC. JCCT 2014;8:480-2 Standard noninvasive approach for sorting patients with possible angina is inadequate and inefficient 3

5 Flow Reserve Adenosine (dilates arterioles) Pa Pd Abnormal FFR < 0.8 Physiologic Significance of CAD Stenoses: Relationship of % Stenosis to Invasive FFR, stenoses, n = 2986 QCA Toth G, et al. EHJ 2014;35:

6 FFR and MPI: Multivessel CAD by CA n=76 patients n=201 vessels 42% agreement in vessel territory 36% MPI underestimated 22% MPI overestimated Melikian N et al. JACC Intv 2010;3: Dobutamine Stress Echo and FFR Jung PH, et al. EHJ 2008;29:

7 What is the gold standard for diagnosis? Anatomic or physiologic assessment? Goal is for the diagnostic process to be most closely associated improved outcomes Courage Trial: Stable CAD Anatomic Assessment (no LM lesion) Anatomic (PCI) vs OMT PCI+OMT OMT Death 7.6% 8.3% MI 13.2% 12.3% ACS 12.4% 11.8% Total: 19.0% 18.5% 4.6 year follow-up Boden W et al. N Engl J Med 2007;356:1503 6

8 FAME 1 Trial Meta-analysis (DEFER; FAME 1) of FFR studies and outcomes 20% fewer adverse events (vs. anatomy, OMT) 10% better anginal relief (vs. OMT alone) FFR is the clinical standard Johnson N, et al. JACC 2014;64:

9 FAME 2 n=441 n=447 Stable angina, multi-vessel CAD FFR < 0.8 PCI + OMT vs OMT 2 year f/u Primary combined endpoint 8.1 vs 19.5% (p< 0.001) Targeted PCI improved outcome De Bruyne B et al. NEJM 2014;371: FAME 2 Trial: PCI FFR Guided vs Maximal Med Tx Absolute treatment and F/U costs Fearon WF, et al. Circulation 2013;128:

10 Cost-Effectiveness of PCI FFR-Guided Tx PCI FFR guided vs maximal medical tx (FAME 2 Trial) Less angina with CAC 2 or > 11.1% versus 28.9%, P< Greater patient utility QOL questionairre (EQ-5D survey) $50,000 per QOL year Fearon WF, et al. Circulation 2013;128: Stress imaging or anatomic (invasive or non-invasive) tests are designed to assess the importance of a stenosis. They serve as a surrogate for the gold standard of invasive FFR 9

11 FFR Versus QCA, QCT, CCA, and CTCA (FFR invasive physiologic standard) Meijboom, W. B. et al. J Am Coll Cardiol 2008;52: CCTA vs QCA Marwan et al. JCCT 2014 * CCTA is excellent to R/O Stenosis 10

12 Rationale for FFR-CT CCTA problems with specificity and PPV QCA and CCTA highly correlated Stenoses > 50% predict ischemia < ½ lesions MPI poorly identifies specific ischemic coronary territories DEFER, FAME 1, 2 lessen events with targeted PCI based on invasive FFR Better than angio guided PCI or best med tx De Bruyne B, et al. NEJM 2012;367: Pijls NH et al. JACC 2007;49: Tonino PA, et al. NEJM 2009;360:

13 Inlet and outlet boundaries Myocardial mass Coronary anatomy Form-function principles Millions of nonlinear differential equations (Nadler-Stokes) to determine pressure and flow Standard coronary CTA acquisition Post-processing No additional contrast or radiation No additional medications Form and Function relationships Mass of an object relates to shape, anatomy, and physiology Coronary flow proportional to myocardial mass (directly measured from CTA) Distal blood vessel size adapts to chronic change in flow in 4 to 6 weeks Vessel feeding territory that is repetitively ischemic will decrease in size Small coronary branches have higher resistance to flow Resistance to flow proportional to number and size of branches 12

14 Computational Fluid Dynamics Boundary conditions supplied by the anatomy from CTA including the aortic root, ascending aorta, and coronary lumen Millions of nonlinear differential equations solved simultaneously with a supercomputer Calculate basilar resistance from distal vessel diameter and branch points Assume a max hyperemic decrease in distal resistance (0.24 of resting resistance) Taylor CA, et al. JACC 2013;61: Basis of FFR-CT (Ao root) (Ascending ao, cors) Taylor CA, et al. JACC 2013;61:

15 Possible Limitations Extensive coronary calcification Coronary motion Slice misregistration Overestimate severity with presence of microvascular disease No clear information with stents or grafts yet Taylor CA, et al. JACC 2013;61:

16 FFR-CT NXT Patients (n=251, 484 vessels) with 30 to 70% stenoses FFR-CT More careful requirements for CT image quality Improved technical and physiologic modeling based on retrospective (machine) learning from prior trials Invasive FFR on all vessels Norgaard BL, et al. JACC 2014;63: Invasive FFR vs n=254 n=484 15

17 Norgaard BL, et al. JACC 2014;63:

18 CCTA and FFR-CT vs FFR Per Patient Per Vessel Norgaard BL, et al. JACC 2014;63: PLATFORM Trial Noninvasive Invasive Compare effectiveness of 2 strategies 11 centers and 6 EU countries Primary Endpoint: Patients with a planned ICA Are patients evaluated using a CTA/FFR CT guided strategy less likely to undergo ICAs that show no obstructive CAD? Douglas PS, et al. EHJ 2015;doi: /eurheartj/ehv444 17

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