CFR and Coronary Capacity for Prognosis Carlo Di Mario, MD, FESC, FACC, FRCP Careggi University Hospital, Florence

Carlo Di Mario, MD, PhD, FESC, FACC, FSCAI, FRCP  Disclosure: I received institutional research grants both at the Royal Brompton Hospital, London -UK and Careggi University Hospital, Florence -IT from Medtronic, Edwards, Abbott, Shockwave, Philips-Volcano, Amgen

The use of coronary pressure to estimate coronary flow impairment is based on the assumption that pressure is proportional linear to flow when coronary resistance is minimal and constant HYPEREMIC FLOW VELOCITIES CFVR: BASELINE European Heart Journal (2015)36, 3312–3319

CFR-Coronary Flow Reserve CFR represents the vasodilator capacity of the coronary vascular bed during hyperaemia CRF ASSESSMENT INVASIVE TECHNIQUES NON INVASIVE TECHNICQUES PET SPECT MR Contrast Echocardiography Thermodiluition Invasive doppler based technique (CFVR- coronary flow velocity reserve)

Echavarria-Pinto M, Van de Hoef TP,Serruys PW,Piek JJ, Escaned J, Curr Opin Cardiol 2014, 29:564–570

Discordance between FFR and CFR Berry, Radcliffe Cardiology 2014 Van de Hoef et al Eur Heart J (2015)36, 3312–3319

67 years old female patient with typical anginal symptoms, diabetes mellitus, hypertension (uncontrolled, LVH), obesity, no pre-catheterisation non-invasive provocative test Tip of Combowire flipped backwards EuroIntervention 2015

Caffeine attenuates intravenous adenosine-induced hyperemia in FFR measurement. Even increased adenosine doses up to 210 μg/kg/min cannot fully surmount the antagonism. patients n 47 J Invasive Cardiol 2014;26(11):580-585

After 2.5 x 13 mm DES; patient asymptomatic EuroIntervention 2015

ILIAS Trial, JACC 2002 No PTCA N= 124 No PTCA N= 37 No PTCA N= 21 9 (24 %) 1 (5%) 1 (11%) 8 (6%)

DEBATE STUDY (Doppler Endpoints Balloon angioplasty Trial Europe) 297 Patients with Doppler Measurements after PCI Group I, n=44, DS ≤35% and CFR >2.5; Groups II+III+IV, n=158, DS >35% or CFR ≤2.5; Group II, n=60, DS >35% and CFR >2.5; group III, n=42, DS ≤35% and CFR ≤2.5; Group IV, n=56, DS >35% and CFR ≤2.5 Percent incidence of recurrence of symptoms and/or ischemia (AI), TLR, and angiographic restenosis (Rest) in the four groups identified by predefined residual diameter stenosis and distal coronary flow reserve after PTCA. Values are percentages.. The percentage of events (1 month AI, 6 month AI, TLR, and rest, respectively), in patients with DS ≤35% or CFR >2.5 (combination of groups I, II, and III) is 15%, 39%, 26%, and 34%. Percent incidence of recurrence of symptoms and/or ischemia, TLR, and angiographic restenosis in the four groups Serruys P, Di Mario C et al. Circulation 1997 Confirmed by the larger DEBATE II and DESTINI trials

Long term outcome between FFR and CFVR of intermediate coronary stenoses 157 consecutive patients with intermediate coronary stenoses by Fractional Flow Reserve and Coronary Flow Velocity Reserve CFVR assessed with an intracoronary guidewire Van de Hoef, Piek et al Circ Cardiovasc Interv. 2014;7:301-311

313 patients and 663 lesions were assessed with FFR, CFR, IMR Intermediate lesions: 40-70% by angiographic view Exclusion criteria:haemodinamic instability, MI, left ventricle dysfunction Cut off: FFr 0.80, CFR 2.0, IMR 23 (greater than 75% population studied, reported after correction using the Yong formula since Pv was not measured) Median follow up 658 days Lee, Yang et al J Am Coll Cardiolc V O L . 6 7 , N O . 1 0 , 2 0 1 6

Lee, Yang et al J Am Coll Cardiolc V O L . 6 7 , N O . 1 0 , 2 0 1 6

DEFINE FLOW trial-ongoing Title: Distal Evaluation of Functional Performance With Intravascular Sensors to Assess the Narrowing Effect - Combined Pressure and Doppler FLOW Velocity Measurements (NCT02328820) Simultaneous assessment with a combined pressure and flow sensor to assess FFR and CFR - FFR>0.80, CFR >2  optimal medical therapy - FFR<0.80, CFR>2  optimal medical therapy - FFR<0.80, CFR<2  PCI Primary outcome: MACE 24 months Secondary outcome: angina 24 months Start date: October 2014 2/3 patients enrolled Europe, USA, Korea and Japan Final data collection: December 2018

CFR-Coronary Flow Reserve with thermodiluition

IMR-Index of Microvascular Resistance IMR is mainly determined by the microcirculation Pressure and temperature are measured simultaneously since the pressure- sensor and thermistor are located at the same point on the coronary guidewire (3 cm from the distal end) IMR is a coronary guidewire-based measure of coronary microvascular function IMR provides information on microvascular dysfunction that could be informative both in stable patients and also in patients with acute or recent MI Amier RP,et al. Heart2013;100:13–20

1,096 patients with 1,452 coronary arteries From 8 centers in 5 countries South Korea, United Kingdom, Spain, USA and Australia Patients who underwent elective measurement of both FFR and IMR Patients with myocardial infaction were excluded Mean FFR was 0.84 and median IMR corr was 16.6 U Lee JM , Koo BK et al. Circ Intervention 2015

IMR did not show any correlation with angiographic stenosis FFR showed significant correlation with angiographic stenosis IMR did not show any correlation with angiographic stenosis Lee JM , Koo BK et al. Circ Intervention 2015

Prognostic value of IMR after primary PCI IMR was measured in 253 patients after primary PCI in hospital Primary endpoint: rate of death or heart failure hospedalization Fearon, Low et al Circulation 2013;127:2436-41

IMR as a predictor of EF recovery in STEMI patients Faustino, Bravo Batista, J Interven Cardiol 2016;29:137–145

CFC-Coronary Flow Capacity integrates both CFR and maximal hyperemic flow to depict myocardial blood flow impairment due to a combination of obstructive, diffuse, and microcirculatory involvement of the coronary vasculature Willerson and Holmes Coronary artery desease Textbook

Coronay flow capacity map Willerson and Holmes Coronary artery desease Textbook

>2.8 CFR > 49 cm/s HAPV 2.1-2.7 CFR 33-49 cm/s HAPV 1.7-2.1 CFR Van de Hoef,, Escaned, Piek et al J Am Coll Cardiol Cardiov Intv vol 8, n°13, 2015

40.5% 33.1% 10.0% 16.4% 299 vessels in 228 patients studied between 1997 and 2006 with deferred treatment in 154 patients Van de Hoef,, Escaned, Piek et al J Am Coll Cardiol Cardiov Intv vol 8, n°13, 2015

Van de Hoef,, Escaned, Piek et al J Am Coll Cardiol Cardiov Intv vol 8, n°13, 2015

Van de Hoef,, Escaned, Piek et al J Am Coll Cardiol Cardiov Intv vol 8, n°13, 2015

CFR and Coronary Capacity Multiparametric assessment for Prognosis CFR Multiparametric assessment FFR/iFR IMR Conclusions CFC Prognosis is influenced by many more parameters than physiological stenosis severity alone (ie FFR/iFR) CFR, reflecting multiple factors contributing to flow impairment, may have better prognostic value while FFR may overestimate the prognostic importance of a lesion when flow is well preserved Coronary capacity corrects CFR for absolute hyperaemic flow and may avoid the black-and-white characterisation of conventional indices