Fractional Flow Reserve
Measurements in
Acute Coronary Syndromes
Khôi Minh Lê, MD
Co-Director, Cardiac Catheterization Laboratory
Eisenhower Desert Cardiology Center
Rancho Mirage, CA
USA


FFR Major Trials
Trial

FFR cutoff

Finding

DEFER

0.75

In stable patients with 1-v CAD, stenting nonsignificant lesions does not improve clinical
outcomes compared to optimal medical therapy
(OMT)

FAME

0.80

In patients with multi-vessel disease, FFR
guidance improves clinical outcomes as compared

to angiographic guidance

FAME 2

0.80

In stable patients with a significant stenosis by
FFR, PCI + OMT is superior to OMT alone. In the
absence of a significant stenosis by FFR, OMT
alone is associated with a benign clinical outcome


FFR Background
• Coronary pressure is linearly related to flow only
if the coronary microcirculatory resistance is
constant and minimal
• FFR is calculated during adenosine-induced
hyperemia which achieves the necessary
resistance condition
• Without maximal hyperemia, the functional
severity of the coronary stenosis may be
underestimated (falsely elevated FFR
measurement)


Possible physiologic confounders for
FFR measurements in ACS patients
• Duration and intensity of ischemia
• Embolization of the downstream microvasculature
• Acutely elevated left ventricular filling pressures

• Altered ventricular wall stress
• Altered myocardial contractility
• Changes in local and systemic vasoconstrictors
• Recent caffeine, theophylline consumption
NB: In general, low FFR (<0.75) is a reliable indicator of a
functionally significant narrowing but a normal FFR
(>0.80) may not be reliable


FFR to assess STEMI culprit vessel
• Unreliable in the acute setting due to
uncertain reduction in maximal achievable
flow resulting in falsely elevated FFR
• How soon after a STEMI can we obtain a
reliable culprit vessel FFR measurement?

STEMI

Samady et al.
JACC 2006:47;2187-2193

De Bruyne et al.
Circ 2001:104;157-162

3 days

6 days


Multivessel disease in

Acute Coronary Syndromes
• Problems
• Problems
• Problems


In ACS patients, incomplete
revascularization (ICR) is associated
with poor clinical outcomes

These adverse outcomes were seen in
ACS patients with residual lesions of
≥50% in vessels ≥2mm
“…regardless of the %DS threshold
used to define ICR, the presence of
angiographic ICR is a strong
independent predictor of 1-year
MACE…”


Benefit of treating borderline nonculprit
vessel lesions in STEMI patients
PRAMI (NEJM 2013)
• 465 STEMI patients
• ≥50% nonculprit vessel
– Immediate multivessel PCI
– IRA PCI and optimal medical
therapy

• 1° endpoint composite

cardiac death, MI, or
refractory angina
Study stopped early due to
highly significant benefit
favoring multivessel PCI

CvLPRIT (ESC 2014)
• STEMI patients
• ≥50% nonculprit vessel
– Multivessel PCI during initial
hospitalization
– IRA PCI and optimal medical
therapy

• 1° endpoint 12 month MACE
(death, MI, heart failure,
revascularization)
Significant reduction in MACE
(10.0 vs 21.2%, p=0.009)
favoring multivessel PCI


Benefit of an early invasive approach in
ACS is well established

Fox, K. A. A. et al. J Am Coll Cardiol 2010;55:2435-2445

Mehta SR et al. N Engl J Med 2009;360:2165-2175



ACC/AHA 2014 NonSTEMI ACS
Guidelines
• Class IIb
• “A strategy of multivessel PCI, in contrast to
culprit lesion-only PCI, may be reasonable in
patients undergoing coronary
revascularization as part of treatment for
NSTE-ACS.”
• Level of Evidence: B


Difficulties with the treatment strategy
for multivessel disease
• Multivessel disease is common among ACS patients
• While the culprit lesion is usually identifiable (based on
the clinical history, the ECG, and the coronary
angiogram) there often is no pre-angiogram functional
study to guide treatment of nonculprit disease.
• Untreated nonculprit vessel disease (incomplete
revascularization) is associated with poor clinical
outcomes
• Post-ACS stress testing is more difficult, less reliable,
and less predictive than in stable CAD
• Is there a role for FFR to guide immediate (in cath lab)
decision-making in ACS?


Questions about FFR in ACS
• Is it safe?
• Are the measurements reliable

(reproducible)?
• Are the results useful?
• Can/should FFR be done routinely?


In unstable angina/NSTEMI patients,
is FFR of the culprit vessel safe?


FFR to assess the NSTEMI culprit vessel
Comparison to Stress Perfusion Scintigraphy (SPS)

• 70 patients with UA/NSTEMI, single vessel
disease with an intermediate lesion (stenosis
of 40-70%)
• Randomized to FFR (35 pts) vs SPS (35 pts)
– PCI if FFR <0.75 or positive SPS
– Medical therapy if FFR ≥0.75 or negative SPS

• FFR safely reduced duration and cost of
hospitalization compared to SPS
Leesar et al, J Am Coll Cardiol.
2003;41(7):1115-1121


Lower costs with FFR than SPS

Clinical equivalence

• Study limited to clinically stable patients with 1-vessel disease

• Small study, underpowered for clinical endpoints
• However, FFR shown to be safe in ACS
Leesar et al, J Am Coll Cardiol.
2003;41(7):1115-1121


In patients with AMI, are non-culprit
vessel FFR measurements reliable?


Nonculprit vessel FFR measurements taken during primary
PCI are reliable

101 patients with AMI
FFR of 112 nonculprit lesions done
at the time of the primary PCI and
repeated 1 month later showed no
significant difference
In only 2 lesions was the FFR acutely
>0.80 and <0.75 at follow-up.
Ntalianis et al. JACC Cardiov Intv
2010;3:1274-81


In unstable angina/NSTEMI patients,
can the FFR be used to guide
management?


Is using FFR to guide PCI as valid in unstable angina and

NSTEMI as it is in stable CAD?
Sels et al. JACC Cardiovasc
Interv.2011;4:1183–1189.


Baseline Characteristics of FAME Patients

Unstable Angina

36%

Tonino PA et al. N Engl J Med
2009;360:213-224.

29%


FAME: Benefit of FFR over angiography is similar
between stable CAD and ACS

FFR performed to both culprit and non-culprit vessels
Sels et al. JACC Cardiovasc
Interv.2011;4:1183–1189.


• Six UK centres, 350 NSTEMI patients referred for invasive
management
• Randomized to angiography-guided or FFR-guided
strategy
• Primary endpoint difference in proportion of patients

assigned to medical therapy
• Not powered to assess difference in clinical outcomes
Layland et al. Eur Heart J
2014:doi:10.1093/eurheartj/ehu338


Layland et al. Eur Heart J
2014:doi:10.1093/eurheartj/ehu338


FAMOUS-NSTEMI
Treatment decisions

38/176 (22%) patients had their treatment
decision changed based on FFR
Layland et al. Eur Heart J
2014:doi:10.1093/eurheartj/ehu338


FAMOUS-NSTEMI
Angiographically
significant
stenosis with
FFR>0.80
Insignificant
stenosis with
FFR≤0.80

Relationship between angiographic stenosis severity
and fractional flow reserve (FFR)

Layland et al. Eur Heart J
2014:doi:10.1093/eurheartj/ehu338