Is FFR a Substitute For Sound Clinical Judgement ? Jeffrey W. Moses, MD Columbia University Medical...
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Transcript of Is FFR a Substitute For Sound Clinical Judgement ? Jeffrey W. Moses, MD Columbia University Medical...
Is FFR a Substitute For Sound Clinical Judgement ?
Jeffrey W. Moses, MDColumbia University Medical Center/
NY-Presbyterian Hospital
Conflicts of Interest
• Consultant /SAB: BSC,Abbott
74 y/o woman with effort and rest angina ETT ; ex time 3’ with ST changes.
Anterior reversible perfusion defect
FFR of LAD 0.9 ......... Med Rx
Continued Sx on Med Rx
MLA=2.7mm2
PB=72%Vessel size=3.5mm
Repeat FFR 0.91
Complete symptomatic relief !
POST STENTMLA=5.9 mm2
Correllation Slide
• If FFR is validated by MPI…
• …how can it overrule an unequivocal MPI?
15 Studies:FFR and MPI (0.75 Cutoff)
n=996
Christou et al. Am. J Cardiol 2007;99:450
TP FN FP TN
331 100 143 422
FFR and the “Grey Zone”
De Bruyne, et al. Circulation 2001;104:157-62
FFR
Specificity
100
80
60
40
20
00.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
Sensitivity
FFR=0.75 0.80Specificity
Sensitivity
FFR=0.75 0.80
“Grey Zone”
FFR Test Retest Reproducibility
Petraco et al., J Am Coll Cardiol Intv 2013;6:222-5
What is Our Basis for Deferral?
DEFER: Patients with Intermediate Lesions with Equivocal or Negative Stress Tests: No Data With
Unequivocal Ischemia
Bech et al, Circ 2001;103:2928-34
Ste
nosi
s S
ever
ity (
%)
DeferGroup
PerformGroup
ReferenceGroup
FFR >0.75 FFR <0.75
20
30
40
50
3060
70
80
90
100
N=90N=91
N=144
3.3
7.9
15.7
0
5
10
15
20
%
P=0.20
P< 0.003
P< 0.005
DEFER PERFORM REFERENCE
FFR ≥ 0.75 FFR < 0.75
5 Year Cardiac Death and MI rate in DEFER Trial
Safety of Deferring PCI Based on FFR
Pijls, et al. J Am Coll Cardiol 2007;49:2105-11
Primary Endpoint: Death, MI, Urgent Revascularization at 2 years
FAME 2 : Trial DesignStable patients with 1, 2, or 3 vessel CAD evaluated for PCI with DES
n=1220
FFR in all target lesions
At least 1 stenosis with FFR ≤ 0.80 (n=888)
Randomization 1:1
PCI + MT MT
Randomized Trial
All FFR > 0.80(n=322)
MT
Registry
50% randomly assigned to follow-up
0
5
10
15
20
25
30
Cum
ulat
ive
inci
denc
e (%
)
166 156 145 133 117 106 93 74 64 52 41 25 13Registry447 414 388 351 308 277 243 212 175 155 117 92 53PCI+MT441 414 370 322 283 253 220 192 162 127 100 70 37MT
No. at risk
0 1 2 3 4 5 6 7 8 9 10 11 12
FAME 2: Primary Outcomes
MT vs. Registry: HR 4.32 (1.75-10.7); p<0.001
PCI+MT vs. Registry: HR 1.29 (0.49-3.39); p=0.61
PCI+MT vs. MT: HR 0.32 (0.19-0.53); p<0.001
Months after randomization
De Bruyne B et al. NEJM 2012:on-line
What a Difference a Decade Makes: 1 Year Outcomes
Deferral Perform
Non ischemic Ischemic
DEFER2001
20%
DEFER2001
8%
FAME II2011
3.0
FAME II2011
4.3
Circ 2012;201:2928
Possible Problems with FRR
• The flow impediment specific to the interrogated stenosis is underestimated as an opposite stenosis becomes more severe because maximal hyperemic flow is not achieved Branches between serial stenoses may inhibit
maximal hyperemia because of “branch steal.” Left ventricular hypertrophy causes inadequate
flow reserve because of a mismatch between the vasculature and myocardial mass
Exercise induced vasoconstriction not accounted for
Old Myocardial Infarction
Irreversible Microvascular Damage
Maximum Achievable Flow is Less
Smaller Gradient and Higher FFR across Any Given Stenosis
Chronic Microvascular Damage and FFR
Systemic Adenosine Infusion and Maximum Hyperemia: Variable Responses
• Routine set up for FFR measurement in my lab: venous sheath in the groin for adenosine infusion 140 μg/kg/min :FFR .98
• Repeat assessment by bolus injection of 100μg into RCA: short total AV block, then FFR 0.78 repeated with 50μg without AV block, then FFR 0.80
• Some patients may metabolize adenosine faster than others -> use a multipurpose catheter to deliver adenosine into the right atrium
FFR Gets Complex in Serial Stenosis
Pijls et al. Circulation. 2000;102:2371-2377
FFR in MI/ACS
• NOT in acute INFARCT or ACS lesion These lesions ALL need treatment
• May use in chronic infarct lesion Does not predict viability Does correlate with residual ischemia
• May use in non-culprit ACS lesions Avoid “over-treatment” Avoid need for subsequent stress testing
PCI in ACS : Angiographically Driven PCI Saves Lives
Fox et al, JACC 2010;55:435-45
Selective invasiveRoutine Invasive
High
Follow-up time (years)
Intermediate
LowCu
mu
lati
ve d
eath
an
d M
I
0 1 2 3 4 5
0%
5%
10%
15%
20%
25%
30%
35%
50%
45%
40%
Primary endpoint: Cardiac death, MI or refractory angina
Wald DS et al. NEJM 2013:on-line
91%
77%
Fre
edo
m f
rom
Pri
mar
y O
utc
om
e (%
)
Months
HR 0.35 (95%CI 0.21-0.58)P<0.001
No. at RiskPreventive PCINo Preventive PCI
0
231
6
234
12 18 24 30 36
168196
144166
122146
96118
7489
5067
0
20
40
60
80
100
PRAMI: “Preventative” PCI of Non-culprit Lsns after Culprit Lesion Primary PCI in STEMI
465 non-shock pts at 5 UK sites with MVD; after successful primary PCI randomized to NCL PCI of non-LM DS 50-99% stenoses vs. conservative care600 pts planned; DSMB stopped trial early after 465 pts enrolled (2008-2013)
Complete revasc
Culprit PCI only
Complete revasc
(N=234)
Culprit PCI only
(N=231)HR
(95%CI) P value
Pre-specified outcomes
Cardiac death, MI, or refractory angina 21 53 0.35 (0.21-0.58) <0.001
Cardiac death or MI 11 27 0.36 (0.18-0.73) 0.004
Cardiac death 4 10 0.34 (0.11-1.08) 0.07
Nonfatal MI 7 20 0.32 (0.13-0.75) 0.009
Refractory angina w/o CD or MI 12 30 0.35 (0.18-0.69) 0.002
Secondary outcomes
Noncardiac death 8 6 1.10 (0.38-3.18) 0.86
Repeat revascularization 16 46 0.30 (0.17-0.56) <0.001
Median FU 2.3 Years
Wald DS et al. NEJM 2013:on-line
PRAMI: “Preventative” PCI of Non-culprit Lsns after Culprit Lesion Primary PCI in STEMI
465 non-shock pts at 5 UK sites with MVD; after successful primary PCI randomized to NCL PCI of non-LM DS 50-99% stenoses vs. conservative care600 pts planned; DSMB stopped trial early after 465 pts enrolled (2008-2013)
How Do Patients End up on the Cath Table?
• ACS• Symptoms• Significant ischemia• Left ventricle dysfunction• Atypical symptoms and equivocal
non-invasives• Anatomically driven (ie abnormal CTA)
How Do Patients End up on the Cath Table?
• ACS• Symptoms• Significant ischemia• Left ventricle dysfunction• Atypical symptoms and equivocal
non-invasives• Anatomically driven (ie abnormal CTA)
VD 4.8x5.0 VA 19.5 mm2
LD 1.4x2.3LA 2.6 mm2
Recurrent Angina 9 Months Post Stent
FFR = 0.83
Are you going to Defer?
102
83
Recurrent Symptoms Post BMS
How Do Patients End up on the Cath Table?
• ACS• Symptoms• Significant ischemia• Left ventricle dysfunction• Atypical symptoms and equivocal
non-invasives• Anatomically driven (ie abnormal CTA)
Cardiac Mortality in Medically Treated Patients According to Ischemic Risk – CSMC Database
Hachamovitch et al Circulation. 2003;107:2900-07
% Total Myocardial Ischemia
0% 1- 5% 5-10% 11-20% >20%
Car
dia
c D
eath
Rat
e (%
)(1
.9 y
r F
U)
N=7110 N=1331 N=718 N=545 N=252
N=9,956 pts
0.0%
15.6%
22.3%
39.3%
0%
10%
20%
30%
40%
Dea
th o
r M
I R
ate
(%)
Rates of Death or MI by ResidualIschemia on 6-18m MPS
p=0.002
0%(n=23)
p=0.023
p=0.063
1%-4.9% (n=141)
5%-9.9%(n=88)
>10%(n=62)
Shaw LA et al. Circulation 2008;117:1283-91
How to Treat
ACS
“Classic” Symptoms
Significant ischemia
Left ventricle dysfunction
Atypical symptoms
+/- equivocal NI
Anatomic (culprit)
Anatomic
Anatomic
Anatomic +/- viability FFR
Location + severity+ / - FFR
FFR for ILMultivessel disease
Anatomically driven
Conclusions
• FFR needs to be put into the context of our overall understanding of coronary physiology , the prognosis of CAD and the influence of revascularization in various clinical and anatomic situations
• It has been validated in limited clinical trials and extending it to areas where other modalities (e.g., MPI , angiography ,viability studies) have demonstrated improvement of outcomes is simply not “evidence based”