Focus on Acute Coronary Syndromes

Focus on Acute Coronary Syndromes Emanuele Barbato, MD, PhD, FESC Cardiovascular Center Aalst, Belgium

Potential conflicts of interest Consulting fees and honoraria on my behalf go to the Cardiovascular Research Center Aalst Contracted Research between the Cardiovascular Research Center Aalst and the following pharmaceutical and device companies: Ablynx, Astra Zeneca, BMS, Eli Lilly, GSK, Therabel, Abbott Vascular, Biotronik, Boston Scientific, Cordis J&J, Edwards, Medtronic, Orbus Neich, St Jude, Terumo Ownership Interest: Cardiovascular Research Center Aalst is cofounder of Cardio³BioSciences, a start-up company focusing on cellbased regenerative cardiovascular therapies

Acute Coronary Syndromes Culprit Vessel Acute Phase STEMI UA / NSTEMI Non-culprit vessel Chronic or Stabilized Phase

Post-PCI

Acute Coronary Syndromes Culprit Vessel Acute Phase STEMI UA / NSTEMI Non-culprit vessel Chronic or Stabilized Phase

FFR is mandatory for the treatment of MVD FFF = ratio of maximal myocardial flow in the stenotic territory to normal maximal myocardial flow Maximal hyperemia or minimal microvascular resistance is crucial for FFR Failure to achieve minimal microvascular resistance results into an underestimation of the functional severity of the coronary stenosis

Acute phase Residual epicardial obstruction: - stenosis not completely releaved - thrombi in the epicardial compartment Microvascular impairment: - cell death - arteriolar dysfunction - no reflow, intercellular edema - micro-embolization - stunning

Vasodilator Response FFR is mandatory for the treatment of MVD Impaired Coronary Vasodilator Response in STEMI (post-strk, n=13, PET) p<0.01 p=0.05 1 week 6 months Infarcted Region Controls Uren NG et al NEJM 1994

Sub-Acute and Chronic phase residual (or recurrent) epicardial stenosis permanent microvascular damage decreased perfusion territory ( physiologic ) : only viable myocardium needs to be perfused and myocardial blood flow should be studied in relation to the perfusion area.

Chronic Microvascular Damage and FFR FFR=0.50 DS=75% Normal Myocardium Myocardial Infarction FFR=0.84 DS=75% Scar Normal Myocardium

FFR in the Culprit Lesion Is FFR < 0.80 a valid cut-off value to exclude / confirm the presence of reversible myocardial ischemia in patients with prior (chronic) MI?

FFR in Chronic MI (Culprit Vessel) Comparison of FFR in 57 patients with an MI 6 days old to SPECT imaging before and after PCI De Bruyne et al. Circulation 2001

FFR in Chronic MI (Culprit Vessel) Best FFR cutoff value < 0.80 in the setting of old MI De Bruyne et al. Circulation 2001

FFR in Chronic MI (Culprit Vessel) Relationship between FFR and mass of myocardium at risk De Bruyne et al. Circulation 2001

FFR after Recent MI (Culprit Vessel) FFR and SPECT performed in 48 patients 3.7 days after MI ( 3 days after STEMI: 73%; 2 days after NSTEMI) 23 patients also had myocardial contrast echo Follow-up SPECT was performed 11 weeks later to identify true positive and negatives Samady et al., J Am Coll Cardiol 2006

FFR after Recent MI (Culprit Vessel) Concordance 91%; Best FFR Cutoff is 0.78 Samady et al., J Am Coll Cardiol 2006

Acute Coronary Syndromes Culprit Vessel Acute Phase STEMI UA / NSTEMI Non-culprit vessel Chronic or Stabilized Phase

Open question How long do you have to wait for microvascular stunning to resolve and before you can get a reproducible FFR? Time to recovery of the microvasculature is variable (from days to weeks?), depending on the size of the infarct.

Acute Coronary Syndromes Culprit Vessel Acute Phase STEMI UA / NSTEMI Non-culprit vessel Chronic or Stabilized Phase

Vasodilator Response FFR is mandatory for the treatment of MVD Impaired Coronary Vasodilator Response in STEMI (post-strk, n=13, PET) p<0.01 p<0.01 p=0.05 1 week 6 months Infarcted Region 1 week 6 months Remote Region Controls Uren NG et al NEJM 1994

FFR in Non-Culprit Stenoses During the Acute Phase of a Myocardial Infarction 1.00 0.95 0.90 0.85 0.80 0.75 104 patients with acute MI 112 non-culprit stenoses FFR - acute phase and - 1 month later 0.70 0.65 0.60 0.55 0.50 0.45 0.40 In 2/112 stenoses, the FFR value was >0.80 at the acute phase but <0.75 at follow-up 0.35 0.30 0.25 0.20 ACUTE FOLLOW-UP p=ns Ntalianis A et al JACC interv 2010

IMR measured in 14 patients acutely and at follow-up Index of Microcirculatory resistance IU 80 n=14 70 60 50 40 30 20 10 p=ns 0 ACUTE FOLLOW UP Ntalianis A et al JACC interv 2010

FFR = 0.87

Acute Coronary Syndromes Culprit Vessel Acute Phase STEMI UA / NSTEMI Non-culprit vessel Chronic or Stabilized Phase

70 patients with UA/NSTEMI, SVD and intermediate lesion randomized to FFR or stress perfusion scan Leesar et al. J Am Coll Cardiol 2003

Cost-Effectiveness and Hospital Stay Leesar et al. JACC 2003

Clinical Events at 1 Year Follow-Up Leesar et al. J Am Coll Cardiol 2003

FFR is mandatory for the treatment of MVD 201 patients with 50% stenosis (2/3 ACS) in which intervention was deferred based on FFR Potvin et al. Am J Cardiol 2006

FFR NSTE ACS (Culprit + Non Culprit Vessel) Fractional Flow Reserve versus Angiography for Multivessel Evaluation Tonino et al. New Engl J Med 2009

Baseline Characteristics Angio- Guided n = 496 FFR- Guided n = 509 P Value Age, mean ±SD 64±10 65±10 0.47 Male, % 73 75 0.30 Diabetes, % 25 24 0.65 Hypertension, % 66 61 0.10 Current smoker, % 32 27 0.12 Hyperlipidemia, % 73 72 0.62 Previous MI, % 36 37 0.84 NSTE ACS, % 36 29 0.11 Previous PCI, % 26 29 0.34 LVEF, mean ±SD 57±12 57±11 0.92 LVEF < 50%, % 27 29 0.47

Comparison of MACE in FAME patients with and without ACS Tonino et al. J Am Coll Cardiol 2011 (submitted)

Conclusions In the acute phase of STEMI, FFR of the culprit vessel is useless/unreliable, but can be accurately measured in the non-culprit vessel In the subacute or chronic phase of STEMI, once microvascular stunning has decreased, FFR is reliable to evaluate the residual ischemic potential of an open Infarct-related artery (IRA) FFR appears accurate and safe in the setting of UA/NSTE-ACS for both culprit and non-culprit vessels