Il tribunale del cardiologo: Processo allo studio della riserva coronarica Avvocato difensore Lauro...

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


40 60 80 100 120 140 160 18050

100

150

200

250

300

350

400



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


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


CFRCFR ==

CFRCFR == 68 68

3232 == 2.13 2.13

RestingResting HyperemicHyperemic


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


%

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


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


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



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


Limitations of CFR as “stand-alone” Limitations of CFR as “stand-alone” diagnostic criteriondiagnostic criterion


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


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


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


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


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


0

50

100

150

200

250

300

350

400

450

500

Glo

ba

l ch

i-s

qu

are

ClinicalClinical ClinicalClinicalLVEFLVEF

ClinicalClinicalLVEFLVEFAngioAngio


SESE


SESECFRCFR

+ 14%+ 14%

+ 279%+ 279%

+ 46%+ 46%

+ 13%+ 13%

Incremental prognostic value of CFR Incremental prognostic value of CFR


0

50

100

150

200

250

300

350

400

450

500

Glo

ba

l ch

i-s

qu

are

ClinicalClinical ClinicalClinicalLVEFLVEF

ClinicalClinicalLVEFLVEF

SESE


SESECFRCFR


SESECFRCFR

AngioAngio

+ 14%+ 14%

+ 394%+ 394%

+ 25%+ 25% + 2%+ 2%

Incremental prognostic value of CFR Incremental prognostic value of CFR


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 %


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 %


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


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


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


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


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


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%


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%


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


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


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


Il tribunale del cardiologo: Processo allo studio della riserva coronarica Avvocato difensore Lauro...

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