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Il tribunale del cardiologo:Il tribunale del cardiologo:Processo allo studio della riserva coronaricaProcesso allo studio della riserva coronarica
Avvocato difensoreAvvocato difensore
Lauro Cortigiani Lauro Cortigiani
U.O. Malattie CardiovascolariU.O. Malattie Cardiovascolari
Ospedale “Campo di Marte”, LuccaOspedale “Campo di Marte”, Lucca
““CARDIOLOGIA E’ PROGRESSO”CARDIOLOGIA E’ PROGRESSO”
II° Congresso Tosco-Umbro della FICII° Congresso Tosco-Umbro della FIC
Montecatini terme, 14-15 novembre 2007 Montecatini terme, 14-15 novembre 2007
CardioLuccaCardioLucca
Co
ron
ary
blo
od
flo
w
Coronary stenosis % 0
0
1
2
3
4
20 40 60 80 100
Basal flowBasal flow
Maximal flowMaximal flow
Effects of coronary stenosis on CFREffects of coronary stenosis on CFR
Gould. Am J Cardiol 1974;34:48CardioLuccaCardioLucca
CFR>2 CFR>2 (86%)(86%)
CFRCFR<<22 (30%)(30%)
Subjects at risk
CFR>2CFR>2 39 21 12 5
CFRCFR<<22 47 22 6 2
0 12 24 360
20
40
60
80
100
Time (months)Sp
on
tan
eo
us
ev
en
t-fr
ee
su
rviv
al
(%)
n = 86n = 86p = 0.0001p = 0.0001
Prognostic effect of CFR in patients with Prognostic effect of CFR in patients with 51% to 75% stenosis of the LAD 51% to 75% stenosis of the LAD
Rigo, for the EPIC-FR. Am J Cardiol 2007;100:1527CardioLuccaCardioLucca
Infa
rcti
on
-fre
e s
urv
iva
l %
Correlation between CFR and LAD stenosisCorrelation between CFR and LAD stenosis
EPIC-FR 2007CardioLuccaCardioLucca
n = 1,243n = 1,243r = 0.53r = 0.53p < 0.0001p < 0.0001
0 10 20 30 40 50 60 70 80 90 1000
1
2
3
4
5
6r = 0.53p < 0.0001
LAD stenosis %
CF
R
n = 1,243n = 1,243 r = - 0.53r = - 0.53 p < 0.0001 p < 0.0001
Factors affecting the functional significance Factors affecting the functional significance of coronary artery stenosisof coronary artery stenosis
Percent diameter stenosisPercent diameter stenosis Geometry and lenght of the lesionGeometry and lenght of the lesion Minimum diameter and cross-sectional area of the lesionMinimum diameter and cross-sectional area of the lesion Size of the vessel proximal and distal to the lesionSize of the vessel proximal and distal to the lesion Vasoactivity of the lesionVasoactivity of the lesion Viable or necrotic state of myocardiumViable or necrotic state of myocardium Degree of distal collateral supportDegree of distal collateral support Left ventricular hypertrophyLeft ventricular hypertrophy Microvascular diseaseMicrovascular disease
Folland. Circulation 1994;89:2005(modified)CardioLuccaCardioLucca
Sekiya. Am J Hypertens 2000;13:789
Relation between LV mass and CFR Relation between LV mass and CFR
Rigo, Cortigiani. Eur Heart J 2006;27(abs)
Intracoronary DopplerIntracoronary Doppler Transthoracic DopplerTransthoracic Doppler
0 20 40 60 80 100 120 140 160 1800
1
2
3
4
5r = 0.57p < 0.0001
LV mass index (g/m2)
CF
R o
n L
AD
r = 0.85p < 0.01
% i
ncr
eas
e o
f C
BF
wit
h A
Ch
LV mass index (g/m2)
40 60 80 100 120 140 160 18050
100
150
200
250
300
350
400
CardioLuccaCardioLucca
LV mass index (g/m2)
CF
R o
n L
AD
r = - 0.85r = - 0.85p < 0.01p < 0.01
r = - 0.57r = - 0.57p < 0.0001p < 0.0001
Transthoracic Doppler of mid-distal LADTransthoracic Doppler of mid-distal LAD
Modified apical 3-chambersModified apical 3-chambers
CardioLuccaCardioLucca
Techniques of assessing CFRTechniques of assessing CFR
MesaurementMesaurement
of flowof flow
Radiation Radiation exposureexposure CostCost AvailabilityAvailability AccuracyAccuracy
PETPET AbsoluteAbsolute ++++++ Very highVery high -- ++++++
Intracoronary Intracoronary DopplerDoppler RelativeRelative ++++++ HighHigh ++ ++++++
Magnetic Magnetic resonanceresonance RelativeRelative -- HighHigh ++ ++++++
Transesophageal Transesophageal DopplerDoppler RelativeRelative -- LowLow ++++ ++++
Transthoracic Transthoracic DopplerDoppler RelativeRelative -- Very lowVery low ++++++ ++++
Picano. Stress Echocardiography. 4th ed, 2003CardioLuccaCardioLucca
Comparison of CFR on LAD by transthoracic Comparison of CFR on LAD by transthoracic Doppler and intracoronary Doppler flow wireDoppler and intracoronary Doppler flow wire
Caiati. Circulation 1999;99:771CardioLuccaCardioLucca
Mean + 2SDMean + 2SDMean + 2SDMean + 2SD
Mean - 2SDMean - 2SD
MeanMean
R = 0.88 R = 0.88
CFR profile with transthoracic DopplerCFR profile with transthoracic Doppler
Hyperemic Hyperemic
Resting diastolic velocityResting diastolic velocity
SystoleSystole DiastoleDiastole
VelocityVelocity(cm/sec)(cm/sec)
VelocityVelocity(cm/sec)(cm/sec) RestingResting
HyperemicHyperemic
CardioLuccaCardioLucca
CFRCFR ==
CFRCFR == 68 68
3232 == 2.13 2.13
RestingResting HyperemicHyperemic
CardioLuccaCardioLucca
78
88
96 9792 94 94
0
20
40
60
80
100
HozumiJACC1998
CaiatiJACC1999
PizzutoAJC2003
NohtomiJASE2003
RuscazioJACC2003
RigoAJC2003
Cortigiani JACC 2007
Feasibility of transthoracic Doppler of LADFeasibility of transthoracic Doppler of LAD
CardioLuccaCardioLucca
%
n=1544n=1544n=230n=230n=110n=110n=53n=53n=45n=45n=138n=138n=18n=18
94
88
97
78
94
81
91
100
76
91 93
65
84
78
0
20
40
60
80
100
HozumiJACC1998
CaiatiJACC1999
PizzutoAJC2003
NohtomiJASE2003
RuscazioJACC2003
RigoAJC2003
EPIC-FR2007
%
n=1243n=1243n=230n=230n=110n=110n=53n=53n=45n=45n=138n=138n=18n=18
Diagnostic value of CFR for LAD diseaseDiagnostic value of CFR for LAD disease
SensitivitySensitivity SpecificitySpecificity
CardioLuccaCardioLucca
89
77 79
92
7176
0
20
40
60
80
100
%
SensitivitySensitivity SpecificitySpecificity AccuracyAccuracy
NormotensivesNormotensives(n = 396)
Hypertensives(n = 847)
p = 0.06p = 0.06p = 0.40p = 0.40 p = 0.28p = 0.28
Accuracy of CFR Accuracy of CFR <<2.0 to assess 2.0 to assess >>70% LAD 70% LAD stenosis in normotensives and hypertensivesstenosis in normotensives and hypertensives
CardioLuccaCardioLuccaEPIC-FR 2007
Better value of CFR to assess Better value of CFR to assess >>70% LAD stenosis70% LAD stenosis
2.002.001.92
EPIC-FR 2007CardioLuccaCardioLucca
0 20 40 60 80 100
100-Specificity
100
80
60
40
20
0
Sen
siti
vity
0 20 40 60 80 100
100-Specificity
100
80
60
40
20
0
Sen
siti
vity
1.921.921.971.97
AUC = 0.90 (0.88-0.92)AUC = 0.90 (0.88-0.92)Sensitivity = 89%Sensitivity = 89%Specificity = 82%Specificity = 82%
AUC = 0.89 (0.85-0.91)AUC = 0.89 (0.85-0.91)Sensitivity = 88%Sensitivity = 88%Specificity = 79%Specificity = 79%
396 Normotensives396 Normotensives 847 Hypertensives847 Hypertensives
26
31
0
10
20
30
40
%
1-2 vessel1-2 vessel(n = 248)
Frequency of reduced CFR on LAD in pts with Frequency of reduced CFR on LAD in pts with RCA or LCx disease and <70% LAD stenosisRCA or LCx disease and <70% LAD stenosis
0-vessel0-vessel(n = 720)
n = 968
p = 0.15p = 0.15
EPIC-FR 2007CardioLuccaCardioLucca
CardioLuccaCardioLucca
Transthoracic Doppler of RCATransthoracic Doppler of RCA
Modified apical 2-chambersModified apical 2-chambers
89 91 8996
75 72
0
20
40
60
80
100
RigoCU
2005
TakeuchiJASE2004
VociAJC2002
%
n=151n=151 n=446n=446n=81n=81
Feasibility and diagnostic value Feasibility and diagnostic value of CFR for RCA disease of CFR for RCA disease
SensitivitySensitivity SpecificitySpecificity
54
83
68
0
20
40
60
80
100
RigoCU
2005
TakeuchiJASE2004
VociAJC2002
%
n=151n=151 n=446n=446n=81n=81
FeasibilityFeasibility
CardioLuccaCardioLucca
Limitations of CFR as “stand-alone” Limitations of CFR as “stand-alone” diagnostic criteriondiagnostic criterion
CardioLuccaCardioLucca
Only LAD is sampledOnly LAD is sampled
Inability to distinguish between Inability to distinguish between macrovascular and microvascular CADmacrovascular and microvascular CAD
Only LAD is sampledOnly LAD is sampled
Inability to distinguish between Inability to distinguish between macrovascular and microvascular CADmacrovascular and microvascular CAD
67
93
79
9086 89
Dip 2D + CFRDip 2D + CFR
CFR on LAD adds diagnostic value over wall CFR on LAD adds diagnostic value over wall motion analysis during dipyridamole stress echo motion analysis during dipyridamole stress echo
CardioLuccaCardioLucca
5 studies 5 studies 741 pts741 pts
SensitivitySensitivity SpecificitySpecificity AccuracyAccuracy
%%
Dip 2DDip 2D
Rigo. J Cardiovasc Med 2006;7:472
CardioLucca
Mestre Mestre Rigo RigoCesenaCesena Gherardi GherardiPisa Pisa Sicari, Picano Sicari, PicanoLuccaLucca Cortigiani CortigianiNapoliNapoli Galderisi GalderisiEmpoli Empoli Gianfaldoni GianfaldoniBelgradeBelgrade Djordjevic-DikicDjordjevic-Dikic
EPIC-FR: Recruiting Centers 2007 EPIC-FR: Recruiting Centers 2007
CardioLuccaCardioLucca
00 66 1010 minmin
DipyridamoleDipyridamole 0.84 mg/kg in 6’0.84 mg/kg in 6’
TIMELINETIMELINE
1 lead ECG1 lead ECG
12 lead ECG12 lead ECG
BP recordingBP recording
Drugs infusionDrugs infusionAminophylline Aminophylline
120 mg in 1’ (up to 240 mg in 2’)120 mg in 1’ (up to 240 mg in 2’)
CFR-PWCFR-PW
2D echo2D echoContinuous Continuous
monitoring and monitoring and
Pulsed recordingPulsed recording
Continuous Continuous
monitoring and monitoring and
Pulsed recordingPulsed recording
On the echo-monitorOn the echo-monitor
Dipyridamole stress echo with CFR assessmentDipyridamole stress echo with CFR assessment
CardioLuccaCardioLucca
0 12 240
20
40
60
80
100
Months
Eve
nt-
free
su
rviv
al (
%)
6 18
CFR >2 / DET – CFR >2 / DET –
CFR CFR <<2 / DET –2 / DET –CFR >2 / DET + CFR >2 / DET +
CFR CFR <<2 / DET +2 / DET +
n = 1,145n = 1,145p < 0.0001p < 0.0001
CardioLuccaCardioLucca
Incremental prognostic value of CFR Incremental prognostic value of CFR over wall motion analysis over wall motion analysis
Rigo, for the EPIC-FR. Eur Heart J 2008;(in press)
2,2
4,7
0
2
4
6
8
10
A
nn
ual
har
d e
ven
t ra
te (
%)
Suspected CADSuspected CAD Known CADKnown CAD
6.0
8.5
4.7
2.2
NondiabeticsNondiabetics DiabeticsDiabetics
Annual hard event rate in diabetics and nondiabeticsAnnual hard event rate in diabetics and nondiabetics
5,456 pts
Cortigiani. JACC 2006;47:605 CardioLuccaCardioLucca
0 365 730 1095 1460 182550
60
70
80
90
100
20 1 3
log-rank for trend = 160.6p < 0.0001
184311321732
1562 826 815
1359 647 660
725 271 344
4 5
1153 496 542
944379437
94
8178
Nondiabetics
Years
Prognostic value of stress echo resultPrognostic value of stress echo result
0 365 730 1095 1460 182550
60
70
80
90
100
Ischemia Scar
20 1 3
log-rank for trend = 15.3p < 0.0001
212229308
156150119
124108 88
53 43 36
Subjects at risk
Normal
4 5
937562
695847
84
60
67
Diabetics
Years
Ha
rd e
ven
t-fr
ee
su
rviv
al (
%)
n = 749 p < 0.0001
n = 4,707 p < 0.0001
Cortigiani. JACC 2006;47:605 CardioLuccaCardioLucca
DiabeticsDiabetics NondiabeticsNondiabetics
n = 4,707n = 4,707p < 0.0001p < 0.0001
n = 749n = 749p < 0.0001p < 0.0001
Prognostic value of CFR in diabetics and Prognostic value of CFR in diabetics and nondiabetics with no inducible ischemia nondiabetics with no inducible ischemia
0 365 730 10950
10
20
30
40
50
60
CFR > 2CFR < 2
n = 207p < 0.0001
2
66141
Subjects at risk
37 85
14 34
2 31
7 19
16
58
Follow-up (years)
Sp
on
tan
eo
us
ev
en
ts %
0 365 730 10950
10
20
30
40
50
60
n = 923p < 0.0001
2
243680
124 434
65 228
2 31
29 96
8
32
Follow-up (years)
Sp
on
tan
eo
us
ev
en
ts %
DiabeticsDiabetics NondiabeticsNondiabetics
CardioLuccaCardioLuccaCortigiani, for the EPIC-FR. JACC 2007;50:1354
Anti-ischemic therapy negatively affects Anti-ischemic therapy negatively affects the prognostic value of stress echo the prognostic value of stress echo
SE- / On therapySE- / On therapy(88%)(88%)
SE+ / Off therapySE+ / Off therapy(84%)(84%)
SE+ / On therapySE+ / On therapy(81%)(81%)
SE- / Off therapySE- / Off therapy(95%)(95%)
Time (months)Time (months)
To
tal
mo
rta
lity
(%
)T
ota
l m
ort
ali
ty (
%)
CardioLuccaCardioLuccaSicari, Cortigiani, Picano. Circulation 2004;109:2428
n = 7,333n = 7,333
0 12 24 36 48 0
20
40
60
80
100
n = 1,506n = 1,506p < 0.0001p < 0.0001
Time (months)
Infa
rcti
on
-fre
e s
urv
iva
l (%
)
CFR CFR <<2 - On Therapy (74%)2 - On Therapy (74%)CFR CFR <<2 - Off Therapy (79%)2 - Off Therapy (79%)
CFR >2 - Off Therapy (93%)CFR >2 - Off Therapy (93%)CFR >2 - On Therapy (91%)CFR >2 - On Therapy (91%)
CFR>2 - On TherapyCFR>2 - On Therapy 369 260 135 54 10 CFRCFR<<2 - Off Therapy2 - Off Therapy 262 108 57 24 7
CFR>2 - Off TherapyCFR>2 - Off Therapy 586 369 186 87 27
CFRCFR<<2 - On Therapy2 - On Therapy 289 105 40 16 2
Subjects at risk
0 12 24 36 48
Sicari, for the EPIC-FR. SubmittedCardioLuccaCardioLucca
Anti-ischemic therapy does not affect Anti-ischemic therapy does not affect the prognostic value of CFRthe prognostic value of CFR
Characteristics of 1.243 patientsCharacteristics of 1.243 patientsCFR > 2CFR > 2(n = 725)(n = 725)
CFR CFR << 2 2(n = 514)(n = 514)
p valuep value
AgeAge 62±1162±11 65±1065±10 <0.0001<0.0001
MenMen 63%63% 63%63% 0.850.85
Prior infarctionPrior infarction 34%34% 39%39% 0.060.06
Prior PCIPrior PCI 35%35% 30%30% 0.060.06
Family history of CADFamily history of CAD 24%24% 26%26% 0.390.39
DiabetesDiabetes 20%20% 26%26% 0.020.02
HypercholesterolemiaHypercholesterolemia 62%62% 71%71% 0.00060.0006
HypertensionHypertension 65%65% 73%73% 0.0030.003
Smoking habitSmoking habit 35%35% 37%37% 0.490.49
Resting LVEFResting LVEF 55±755±7 52±952±9 <0.0001<0.0001
Ischemia on SEIschemia on SE 19%19% 53%53% <0.0001<0.0001
CFRCFR 2.63±0.542.63±0.54 1.70±0.251.70±0.25 <0.0001<0.0001
2-3 vessel2-3 vessel 6%6% 31%31% <0.0001<0.0001
1 vessel1 vessel 21%21% 33%33% <0.0001<0.0001
0 vessel0 vessel 73%73% 36%36% <0.0001<0.0001
EPIC-FR 2007 CardioLuccaCardioLucca
Multivariable prognostic indicatorsMultivariable prognostic indicators(death, STEMI, NSTEMI)(death, STEMI, NSTEMI)
HR (95% CI)HR (95% CI) p valuep value
Ischemia at stress echoIschemia at stress echo 3.37 (2.43-4.68)3.37 (2.43-4.68) < 0.0001< 0.0001
CFR CFR <<2.02.0 2.82 (2.12-4.57) 2.82 (2.12-4.57) < 0.0001< 0.0001
CAD at angiographyCAD at angiography 2.34 (1.68-3.26)2.34 (1.68-3.26) < 0.0001< 0.0001
HypertensionHypertension 1.64 (1.21-2.40)1.64 (1.21-2.40) 0.0020.002
CardioLuccaCardioLuccaEPIC-FR 2007
0
50
100
150
200
250
300
350
400
450
500
Glo
ba
l ch
i-s
qu
are
ClinicalClinical ClinicalClinicalLVEFLVEF
ClinicalClinicalLVEFLVEFAngioAngio
ClinicalClinicalLVEFLVEFAngioAngio
SESE
ClinicalClinicalLVEFLVEFAngioAngio
SESECFRCFR
+ 14%+ 14%
+ 279%+ 279%
+ 46%+ 46%
+ 13%+ 13%
Incremental prognostic value of CFR Incremental prognostic value of CFR
EPIC-FR 2007 CardioLuccaCardioLucca
0
50
100
150
200
250
300
350
400
450
500
Glo
ba
l ch
i-s
qu
are
ClinicalClinical ClinicalClinicalLVEFLVEF
ClinicalClinicalLVEFLVEF
SESE
ClinicalClinicalLVEFLVEF
SESECFRCFR
ClinicalClinicalLVEFLVEF
SESECFRCFR
AngioAngio
+ 14%+ 14%
+ 394%+ 394%
+ 25%+ 25% + 2%+ 2%
Incremental prognostic value of CFR Incremental prognostic value of CFR
EPIC-FR 2007 CardioLuccaCardioLucca
0 365 730 10950
25
50
75
100
CFR < 2 CFR > 2
325196
Subjects at risk
76 83
29 41
11 10
n = 524p = 0.0007
2-3 vessel CAD
Days
Ev
en
ts %
Prognostic value of CFR in pts with and Prognostic value of CFR in pts with and without significant (without significant (>>70% stenosis) CAD70% stenosis) CAD
0 365 730 10950
25
50
75
100
187533
135 447
73 264
31 120
n = 720p < 0.0001
1 vessel CAD
Days
Ev
en
ts %
EPIC-FR 2007 CardioLuccaCardioLucca
No significant CADNo significant CADSignificant CADSignificant CAD
n = 523p = 0.0007
n = 720p < 0.0001
327
0 365 730 10950
10
20
30
40
50
60
LAD (-) RCA (-)LAD (+) RCA (-)
p < 0.0001
2
58
1
271 95 69 116
Subjects at risk
1
LAD (-) RCA (+)LAD (+) RCA (+)
54
41
2 3
234 22 29 54
154 7 16 34
67 4 6 11
Follow-up (years)
Ev
en
ts %
CardioLuccaCardioLuccaEPIC-FR 2007
Prognostic implication of CFR Prognostic implication of CFR assessed on LAD and RCA assessed on LAD and RCA
n = 553p < 0.0001
7
70 68
51
0
20
40
60
80
LAD (-)LAD (-)RCA (-)RCA (-)
LAD (+)LAD (+)RCA (-)RCA (-)
LAD (-)LAD (-)RCA (+)RCA (+)
LAD (+)LAD (+)RCA (+)RCA (+)
Frequency of significant CAD according Frequency of significant CAD according to CFR assessed on LAD and RCA to CFR assessed on LAD and RCA
CardioLuccaCardioLuccaEPIC-FR 2007
553 pts553 ptsSig
nif
i ca n
t C
AD
%S
ign
i fic
a nt
CA
D %
Prognostic value of CFR in Prognostic value of CFR in dilated cardiomyopathydilated cardiomyopathy
Rigo, for the EPIC-FR. Eur Heart J 2006;27:1319
CFRCFR<<22 (22%)(22%)
CFR>2CFR>2 (70%)(70%)
CFR>2CFR>2
CFRCFR<<22
CardioLuccaCardioLucca
n=129n=129p=0.0001p=0.0001
CFR>2CFR>2
CFRCFR<<22
Subjects at risk
Prognostic value of PET derived CFR in HCMPrognostic value of PET derived CFR in HCM
Cecchi. NEJM 2003;349:1027CardioLuccaCardioLucca
Doppler echocardiographic derived CFR in HCMDoppler echocardiographic derived CFR in HCM
68 HCM patients (5868 HCM patients (5812 yy; 59% men)12 yy; 59% men)
NYHA class I-II NYHA class I-II
Angiographically normal coronary Angiographically normal coronary arteries (n=37) or negativity of stress arteries (n=37) or negativity of stress test and likelihood of CAD <5% (n=31)test and likelihood of CAD <5% (n=31)
High-dose dipyridamole (0.84 mg High-dose dipyridamole (0.84 mg over 6’) with CFR assessmentover 6’) with CFR assessment of LAD of LAD
Follow-up: Follow-up: 222213 months13 months
CardioLuccaCardioLuccaCortigiani, for the EPIC-FR. Submitted
Follow-up eventsFollow-up events
1 sudden death1 sudden death1 AMI1 AMI4 ICD4 ICD6 hospitalizations for heart failure6 hospitalizations for heart failure (4 of whom for pulmonary edema)(4 of whom for pulmonary edema)5 unstable anginas5 unstable anginas8 atrial fibrillations8 atrial fibrillations2 syncope2 syncope
27 events27 events
CardioLuccaCardioLuccaCortigiani, for the EPIC-FR. Submitted
Univariate Univariate analysis analysis
(HR, 95% CI)(HR, 95% CI) p valuep value
Multivariate Multivariate analysis analysis
(HR, 95% CI)(HR, 95% CI) p valuep value
AgeAge 1.00 (0.99-1.03)1.00 (0.99-1.03) 0.810.81
MenMen 1.25 (0.57-2.75)1.25 (0.57-2.75) 0.570.57
AnginaAngina 3.50 (1.62-7.58)3.50 (1.62-7.58) 0.0010.001 2.53 (1.11-5.74)2.53 (1.11-5.74) 0.030.03
NYHA IINYHA II 4.86 (2.25-10.48)4.86 (2.25-10.48) <0.0001<0.0001
SyncopeSyncope 3.54 (1.51-8.30)3.54 (1.51-8.30) 0.0040.004
Paroxysmal or chronic AFParoxysmal or chronic AF 2.24 (1.00-5.01)2.24 (1.00-5.01) 0.050.05
NSVTNSVT 2.11 (0.92-4.84)2.11 (0.92-4.84) 0.080.08
LBBB on ECGLBBB on ECG 1.16 (0.49-2.75)1.16 (0.49-2.75) 0.730.73
Left atrial dimensionLeft atrial dimension 1.18 (1.04-1.33)1.18 (1.04-1.33) 0.0080.008
LV end-diastolic dimensionLV end-diastolic dimension 1.00 (0.93-1.07)1.00 (0.93-1.07) 0.95 0.95
EF%EF% 0.94 (0.87-1.02)0.94 (0.87-1.02) 0.140.14
Maximal LV thicknessMaximal LV thickness 1.19 (1.08-1.30)1.19 (1.08-1.30) <0.0001 <0.0001
Rest LV obstruction (Rest LV obstruction (>>30 mmHg) 30 mmHg) 6.52 (2.93-14.51)6.52 (2.93-14.51) <0.0001<0.0001 2.70 (1.14-6.39)2.70 (1.14-6.39) 0.020.02
Moderate to severe mitral regurg.Moderate to severe mitral regurg. 2.96 (1.23-7.12)2.96 (1.23-7.12) 0.010.01
CFR CFR <<22 7.61 (2.61-22.16)7.61 (2.61-22.16) <0.0001<0.0001 4.30 (1.34-13.78)4.30 (1.34-13.78) 0.010.01
ECG changesECG changes 2.38 (0.93-6.08)2.38 (0.93-6.08) 0.070.07
Cox analysisCox analysis
Cortigiani, for the EPIC-FR. Submitted
0 365 730 10950
25
50
75
100
CFR <2.0CFR >2.0
p < 0.0001
2
79
17
3137
Subjects at risk
2330
12 18
2 31
5 8
Follow-up (years)
Ev
en
ts %
Event-rates according to CFREvent-rates according to CFR
CardioLuccaCardioLucca
CFR >2CFR >2
(79%)(79%)
CFR CFR <<2 2 (17%)(17%)
CFR CFR <<2 2 CFR >2 CFR >2
n = 68n = 68p < 0.0001p < 0.0001
Cortigiani, for the EPIC-FR. Submitted
Functional aspects of coronary circulation Functional aspects of coronary circulation
Ischemia Ischemia
CFRCFR
CardioLuccaCardioLucca
ConclusionsConclusions
CFR evaluation of LAD by transthoracic Doppler:CFR evaluation of LAD by transthoracic Doppler:
is highly feasible (>90%);is highly feasible (>90%);
increases the sensitivity of dipyridamole stress increases the sensitivity of dipyridamole stress echo with only modest loss in specificity;echo with only modest loss in specificity;
provides strong and independent prognostic provides strong and independent prognostic information in patients with known or suspected information in patients with known or suspected
CAD (including diabetics), additional to that of CAD (including diabetics), additional to that of wall motion analysis and angiographic findings;wall motion analysis and angiographic findings;
if effective to risk stratify patients with dilated if effective to risk stratify patients with dilated and hypertrophic cardiomyopathy.and hypertrophic cardiomyopathy.
MicrovascularMicrovasculardiseasediseaseNormalNormal
Moderate- Moderate- to-severe to-severe
CADCAD
Wall motionWall motion
Mild-to-Mild-to-Moderate Moderate
CADCAD
CFRCFR
ST
RE
SS
ST
RE
SS
CoronaryCoronaryangiographyangiography
Prognostic Prognostic impactimpact ±±-- ++ ++++
Coronary anatomic and prognostic CFR conditions Coronary anatomic and prognostic CFR conditions
CardioLuccaCardioLuccaCortigiani, for the EPIC-FR. JACC 2007;50:1354
Diagnostic value of CFR for LAD diseaseDiagnostic value of CFR for LAD disease
N° ptsN° pts FeasibilityFeasibility SensitivitySensitivity SpecificitySpecificity AccuracyAccuracy
HozumiHozumiJACC 1998JACC 1998 1818 78%78% 94%94% 100%100% 98%98%
CaiatiCaiatiJACC 1999JACC 1999 138138 88%88% 88%88% 76%76% 87%87%
Pizzuto Pizzuto Am J Cardiol 2003Am J Cardiol 2003 4545 96%96% 97%97% 91%91% 93%93%
Ruscazio Ruscazio JACC 2003JACC 2003 5353 97%97% 78%78% 93%93% 80%80%
Nohotomi Nohotomi JASE 2003JASE 2003 110110 92%92% 94%94% 65%65% 81%81%
RigoRigoAm J Cardiol 2003Am J Cardiol 2003 230230 94%94% 81%81% 84%84% 83%83%
EPIC-FR 2007EPIC-FR 2007 1,2431,243 92%92% 91%91% 73%73% 77%77%
CardioLuccaCardioLucca
N° ptsN° pts FeasibilityFeasibility SensitivitySensitivity SpecificitySpecificity AccuracyAccuracy
VociVociAm J Cardiol 2002Am J Cardiol 2002
8181 54%54% 89%89% 96%96% --
TakeuchiTakeuchiJASE 2004JASE 2004 151151 83%83% 91%91% 75%75% 83%83%
Rigo Rigo Cardiovasc Ultras 2005Cardiovasc Ultras 2005
446446 68%68% 89%89% 72%72% 81%81%
CardioLuccaCardioLucca
Diagnostic value of CFR for RCA diseaseDiagnostic value of CFR for RCA disease
0
1
2
3
4
5
RESTREST EXEEXE DOBUDOBU ADOADO DIPYDIPY
CFR and stressesCFR and stresses
Iskandrian. J Nucl Cardiol 1994:1;94
X
X
X
X
X
CF
RC
FR
CardioLuccaCardioLucca
CFR with vasodilator agentsCFR with vasodilator agents
AdenosineAdenosine DipyridamoleDipyridamole
Patient tolerancePatient tolerance LowerLower HigherHigher
Drug costDrug cost 100 Euros100 Euros 1 Euro1 Euro
HyperventilationHyperventilation HigherHigher LowerLower
Vasodilator effect onsetVasodilator effect onset Seconds (30)Seconds (30) Minutes (2-3)Minutes (2-3)
Combined wall motion and CFRCombined wall motion and CFR DifficultDifficult PossiblePossible
Multiple coronary imagingMultiple coronary imaging DifficultDifficult PossiblePossible
Picano. Stress Echocardiography. 4th ed, 2003CardioLuccaCardioLucca
PatientsPatients CFR > 2CFR > 2(n=37)(n=37)
CFR CFR << 2 2(n=31)(n=31) p valuep value
AgeAge 59±1259±12 57±1157±11 0.590.59
MenMen 65%65% 52%52% 0.270.27
AnginaAngina 14%14% 45%45% 0.0040.004
NYHA classNYHA class 1.3±0.41.3±0.4 1.4±0.51.4±0.5 0.220.22
SyncopeSyncope 3%3% 29%29% 0.020.02
Paroxysmal or chronic AFParoxysmal or chronic AF 14%14% 35%35% 0.030.03
NSVTNSVT 13%13% 23%23% 0.190.19
LBBB on ECGLBBB on ECG 24%24% 26%26% 0.890.89
Left atrial dimension (mm)Left atrial dimension (mm) 42±442±4 45±445±4 0.020.02
LV end-diastolic dimension (mm)LV end-diastolic dimension (mm) 50±550±5 50±550±5 0.920.92
LV end-sistolic dimension (mm)LV end-sistolic dimension (mm) 30±530±5 31±631±6 0.570.57
EF%EF% 58±558±5 59±659±6 0.300.30
Maximal LV thickness (mm)Maximal LV thickness (mm) 17±317±3 20±420±4 <0.0001<0.0001
Rest LV obstruction (Rest LV obstruction (>>30 mmHg) 30 mmHg) 5%5% 55%55% <0.0001<0.0001
Moderate to severe mitral regurg.Moderate to severe mitral regurg. 8%8% 23%23% 0.090.09
CFR on LADCFR on LAD 2.2±0.42.2±0.4 1.8±0.11.8±0.1 <0.0001<0.0001
ECG changesECG changes 30%30% 42%42% 0.290.29
CardioLuccaCardioLuccaCortigiani, for the EPIC-FR. Submitted
Causes of reduced CFR in Causes of reduced CFR in dilated cardiomyopathydilated cardiomyopathy
LV hypertrophy LV hypertrophy Increased LV end-diastolic pressureIncreased LV end-diastolic pressure
Coronary small vessel diseaseCoronary small vessel disease
LV hypertrophy LV hypertrophy Increased LV end-diastolic pressureIncreased LV end-diastolic pressure
Coronary small vessel diseaseCoronary small vessel disease
CardioLuccaCardioLucca