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Wakayama Medical UniversityWakayama Medical University
Takashi Akasaka, MD, PhDDepartment of Cardiovascular Medicine
Wakayama Medical University, Japan
Takashi Akasaka, MD, PhDDepartment of Cardiovascular Medicine
Wakayama Medical University, Japan
Evaluation of Microvascular DysfunctionEvaluation of Microvascular Dysfunction
TCT imaging & physiology 2008TCT imaging & physiology 2008
Wakayama Medical UniversityWakayama Medical University
Evaluation of Microvascular Dysfunction
• Many indexes have been proposed as the predictors demonstrating microvascular condition.
• Many indexes have been proposed as the predictors demonstrating microvascular condition.
• Many reports have been focused on the relation between LV function recovery and microvasculardysfunction in AMI.
• Many reports have been focused on the relation between LV function recovery and microvasculardysfunction in AMI.
Coronary flow velocity pattern CFR (cornary flow reserve)Pzf (Zero flow pressure)Qc/Qn, CWPMVRI, h-MVr
Coronary flow velocity pattern CFR (cornary flow reserve)Pzf (Zero flow pressure)Qc/Qn, CWPMVRI, h-MVr
Wakayama Medical UniversityWakayama Medical University
ASV & DcT vs LVWMSIASV & DcT vs LVWMSI
ASV(cm/s)ASV(cm/s)
0
20
-201.0 2.0 3.0
1M WMSI1M WMSI
r = - 0.54p < 0.01
ASV(cm/s)ASV(cm/s)
0
20
-201.0 2.0 3.0
1M WMSI1M WMSI
r = - 0.54p < 0.01
(Kawamoto T, Yoshida K, Akasaka T, et al. Circulation 1999;100: 339-345)(Kawamoto T, Yoshida K, Akasaka T, et al. Circulation 1999;100: 339-345)
DcT(ms)DcT(ms)
1.0 2.0 3.01M WMSI1M WMSI
2000
1000
0
r = - 0.62p < 0.01
DcT(ms)DcT(ms)
1.0 2.0 3.01M WMSI1M WMSI
2000
1000
0
r = - 0.62p < 0.01
DDT > 600
DDTDDT
DDTDDT
DDT > 600DDT≦600DDT≦ 600
Wakayama Medical UniversityWakayama Medical University
LV volumes and ejection fractionLV volumes and ejection fraction
nsns p < 0.001p < 0.001
LVEDVILVEDVI LVESVILVESVI LVEFLVEF
8080 8080
160160
00LVEDVILVEDVI LVESVILVESVI LVEFLVEF
nsnsnsns
160160
00
acuteacute latelate
DDT > 600DDT > 600 DDT ≦ 600DDT ≦ 600
p < 0.001p < 0.001p < 0.05p < 0.05
( Yamamuro A,AkasakaT,et al.Circulation 100;144,1999 )( Yamamuro A,AkasakaT,et al.Circulation 100;144,1999 )
Wakayama Medical UniversityWakayama Medical University
Correlation of Doppler variables of coronary flow with changes of LVEDVI
Correlation of Doppler variables of coronary flow with changes of LVEDVI
60
0
Change in LVEDVI over 6 months
DcT(ms)100 1100600
y= - 0.06x + 49; r = - 0.71
-60
y= - 1.0x + 1 1.7;r = - 0.62
60
0
SAPV(cm/sec)-40 500
-60
( Yamamuro A,AkasakaT,et al.Circulation 100;144,1999 )( Yamamuro A,AkasakaT,et al.Circulation 100;144,1999 )
Wakayama Medical UniversityWakayama Medical University
Relationship between Qc / Qn & LVWM recovery
(Lee CW, et al. J Am Coll Cardiol 2000;35:949-955)(Lee CW, et al. J Am Coll Cardiol 2000;35:949-955)
Wakayama Medical UniversityWakayama Medical University
FFR & acute myocardial infarction
Normal Myocardium
Normal Myocardium
InfarctedInfarctedMyocardiumMyocardium
FFR=0.60
FFR=0.80
DS=70%DS=70%
DS=70%DS=70%
Myocardial Infarction
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Difference between CFR & FFR
%DS Microvasculardisease
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Relationship between FFR & CFR
( Meuwissen M, et al. Circulation 103:184 -187, 2001)( Meuwissen M, et al. Circulation 103:184 -187, 2001)
Stenosis (+)Viability (+)
Stenosis (-)Viability (+)
Stenosis (±)Viability (-)
???
FFR
CFR
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Concept of CFR, FFR & IMR
IMRIMR
Wakayama Medical UniversityWakayama Medical University
Concept of hyperemic microvascular resistanceConcept of hyperemic microvascular resistance
APV : time-averaged peak velocityAPV : time-averaged peak velocity
AoAo
PaPa
RmvRmv
PvPvPdPd RARARsRs
h-Rmv : hyperemic microvascular resistance = ( Pd – Pv ) HE / Qs HEh-Rmv : hyperemic microvascular resistance = ( Pd – Pv ) HE / Qs HE
h-MRv : hyperemic microvascular resistance index = ( Pd – Pv ) HE / APV HEh-MRv : hyperemic microvascular resistance index = ( Pd – Pv ) HE / APV HE
APVAPVQsQs
Qs: coronary flow through the stenosisQs: coronary flow through the stenosis
IMR : index of microcirculatory resistance = Pa・Tmn・[ (Pd– Pw ) / (Pa– Pw ) ]IMR : index of microcirculatory resistance = Pa・Tmn・[ (Pd– Pw ) / (Pa– Pw ) ]
Wakayama Medical UniversityWakayama Medical University
Volcano ComboWire®
Doppler Velocity
Transducer
Doppler Velocity
Transducer
Pressure Sensor
Pressure Sensor
A dual-sensor (pressure and Doppler velocity) guidewire has an ability to estimate coronary microvascularresistance (MVR).
A dual-sensor (pressure and Doppler velocity) guidewire has an ability to estimate coronary microvascularresistance (MVR).
Wakayama Medical UniversityWakayama Medical University
CFR & FFR
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Pressure-flow loop during hyperemia
Coronary pressure (mmHg)Coronary pressure (mmHg)
Cor
onar
y flo
w v
eloc
ity (c
m/s
ec)
Cor
onar
y flo
w v
eloc
ity (c
m/s
ec)
PzfPzf
Wakayama Medical UniversityWakayama Medical University
Simultaneous assessment of FFR & CFR Operation PrincipleOperation Principle
Catheter
Syringe
CORONARY ARTERYBlood Flow Sensor element
Transit mean time; Tmn
CFR= Tmn restTmn hyp
Dilution graph
Tmn rest
Tmn hyp
1.Bolus injection during rest
2.Bolus injection during hyp
IMR = Pa・Tmn・[ (Pd– Pw ) / (Pa– Pw ) ]≒Pd・TmnIMR = Pa・Tmn・[ (Pd– Pw ) / (Pa– Pw ) ]≒Pd・Tmn
Wakayama Medical UniversityWakayama Medical University
CFR measurements by thermodilution method
CFR 1.83
THERMO
( De Bruyne B, et al. Circulation 104:2003-2006, 2001) ( De Bruyne B, et al. Circulation 104:2003-2006, 2001) ( Pijls NHJ, et al. Circulation 105:2482-2486, 2002) ( Pijls NHJ, et al. Circulation 105:2482-2486, 2002)
Wakayama Medical UniversityWakayama Medical University
Peak CK with low and high IMR
( Fearon WF, et al. J Am Coll Cardiol 51:560-565, 2008) ( Fearon WF, et al. J Am Coll Cardiol 51:560-565, 2008)
Peak
CK
(ng/
ml)
Peak
CK
(ng/
ml)
1000 1000
2000 2000
3000 3000
4000 4000
00IMR≦32IMR≦32 IMR>32IMR>32
1201±9111201±911
3128±16343128±1634
P=0.002P=0.002
Wakayama Medical UniversityWakayama Medical University
Three-month wall motion score with low and high IMR
( Fearon WF, et al. J Am Coll Cardiol 51:560-565, 2008) ( Fearon WF, et al. J Am Coll Cardiol 51:560-565, 2008)
Wal
l Mot
ion
Scor
e at
3 m
onth
s W
all M
otio
n Sc
ore
at 3
mon
ths
1010
2020
3030
00IMR≦32IMR≦32 IMR>32IMR>32
20±420±4
28±728±7P=0.001P=0.001
55
1515
2525
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Transmural Extent of Infarction by delayed enhancement by MRI
Grade 1Grade 1 Grade 2Grade 2 Grade 3Grade 3 Grade 4Grade 4Every 25%Every 25%
Wakayama Medical UniversityWakayama Medical University
0
20
40
60
80
100
0 1-25 26-50 51-75 76-100
%Se
gmen
t tha
t im
prov
ed%
Segm
ent t
hat i
mpr
oved
Transmural extent of infarction (%) Transmural extent of infarction (%)
All dysfunctional segments
Transmural Extent of Acute Myocardial Infarction Predicts Long-Term Improvement in Contractile Function
(Kim RJ, et al; N Eng J Med 2000; 343: 1445-53)(Kim RJ, et al; N Eng J Med 2000; 343: 1445-53)
Wakayama Medical UniversityWakayama Medical University
Objective
The aim of this study was to assess the relationship between MVR and the transmural extent of infarction (TEI) after primary percutaneous coronary intervention (PCI) in AMI.
The aim of this study was to assess the relationship between MVR and the transmural extent of infarction (TEI) after primary percutaneous coronary intervention (PCI) in AMI.
Wakayama Medical UniversityWakayama Medical University
Age, years Male sex n, (%)Non-insulin dependent-diabetes mellitus n, (%)Hypertension n, (%)Dyslipidemia n, (%)Current smoking n, (%)Family history of coronary aretry disease n, (%)Culprit vesselLAD
Time to the evaluation of coronary microcirculation (hour)
Age, years Male sex n, (%)Non-insulin dependent-diabetes mellitus n, (%)Hypertension n, (%)Dyslipidemia n, (%)Current smoking n, (%)Family history of coronary aretry disease n, (%)Culprit vesselLAD
Time to the evaluation of coronary microcirculation (hour)
65 ± 11 17 (81) 7 (29) 14 (58) 9 (38) 9 (38)12 (57)
24 (100)4.96 ±2.1
65 ± 11 17 (81) 7 (29) 14 (58) 9 (38) 9 (38)12 (57)
24 (100)4.96 ±2.1
n=24n=24
Patient characteristics
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ECG at the time of admission( 70 y.o., male )
Wakayama Medical UniversityWakayama Medical University
CombowireCombowire BaselineBaseline
HyperemiaHyperemia
h-MVr = h-Pd / h-APV = 40 / 59= 0.68 (mmHg/cm・sec-1)
h-MVr = h-Pd / h-APV = 40 / 59= 0.68 (mmHg/cm・sec-1)
Wakayama Medical UniversityWakayama Medical University
Contrast-enhanced MRI(two weeks after primary PCI)
Contrast-enhanced MRI(two weeks after primary PCI)
Transmural extent of hyperenhancement Grade 0, peak CK 185 → avoted MI
Transmural extent of hyperenhancement Grade 0, peak CK 185 → avoted MI
Wakayama Medical UniversityWakayama Medical University
ECG at the time of admissionECG at the time of admission( 64 y.o., male )
Wakayama Medical UniversityWakayama Medical University
Combowire BaselineBaseline
HyperemiaHyperemia
h-MVr = h-Pd / h-APV = 73 / 24= 3.04 (mmHg/cm・sec-1)
h-MVr = h-Pd / h-APV = 73 / 24= 3.04 (mmHg/cm・sec-1)
Wakayama Medical UniversityWakayama Medical University
Coronary microvascular resistance estimated by a novel dual-sensor (pressure and Doppler velocity) guidewire reflects myocardial viability after myocardial infarction
Coronary microvascular resistance estimated by a novel dual-sensor (pressure and Doppler velocity) guidewire reflects myocardial viability after myocardial infarction
Pressure-flow loop
Zfp=64mmHgZfp=64mmHg
Wakayama Medical UniversityWakayama Medical University
Contrast-enhanced MRI(two weeks after primary PCI)
Contrast-enhanced MRI(two weeks after primary PCI)
Transmural extent of hyperenhancement Grade 4, peak CK 7182 → transmural MI
Transmural extent of hyperenhancement Grade 4, peak CK 7182 → transmural MI
Wakayama Medical UniversityWakayama Medical University
y = 0.0005x + 0.831
0
1
2
3
4
5
6
7
100 2100 4100 6100 8100 10100 12100
peakCK
h-M
Rv
r=0.892, p<0.0001
Relationship between hyperemic microvascularresistance index and peak CK
Relationship between hyperemic microvascularresistance index and peak CK
(Kitabata H, et al; J Am Coll Cardiol Imag. 2009, 2: in press)(Kitabata H, et al; J Am Coll Cardiol Imag. 2009, 2: in press)
Wakayama Medical UniversityWakayama Medical University
Relationship between hyperemic microvascularresistance and transmural extent of MI by de-MRIRelationship between hyperemic microvascular
resistance and transmural extent of MI by de-MRI
00
11
22
33
44
55
66
MVR
I (m
mH
g・cm
-1・s
)M
VRI (
mm
Hg・
cm-1・s
)
Grade 1Grade 1 Grade 2Grade 2 Grade 3Grade 3 Grade 4Grade 4
Transmural Extent of InfarctionTransmural Extent of Infarction
P<0.0001P<0.0001
(Kitabata H, et al; J Am Coll Cardiol Imag. 2009, 2: in press)(Kitabata H, et al; J Am Coll Cardiol Imag. 2009, 2: in press)
Wakayama Medical UniversityWakayama Medical University
00
0.20.2
0.40.4
0.60.6
0.80.8
1.01.0
00 0.20.2 0.40.4 0.60.6 0.80.8 1.01.0
1-Specificity1-Specificity
Sens
itivi
tySe
nsiti
vity
MVRIMVRIPzfPzfDDTDDTCFRCFR
ROC curve in each indexROC curve in each index
(Kitabata H, et al; J Am Coll Cardiol Imag. 2009, 2: in press)(Kitabata H, et al; J Am Coll Cardiol Imag. 2009, 2: in press)
Wakayama Medical UniversityWakayama Medical University
SummarySummary1. The condition of coronary microcirculation is an
important determinant of myocardial viability and clinical outcomes in AMI.
1. The condition of coronary microcirculation is an important determinant of myocardial viability and clinical outcomes in AMI.
2. There would be some indexes to speculate micro-circulation condition such as CFR, DDT, Pzf andmicrovascular resistance index.
2. There would be some indexes to speculate micro-circulation condition such as CFR, DDT, Pzf andmicrovascular resistance index.
3. A 0.014-inch dual-sensor (pressure and Doppler velocity) guidewire (CombowireTM ) and pressureguidewire with thermodilution may allow us to estimate these indexes at the same time.
3. A 0.014-inch dual-sensor (pressure and Doppler velocity) guidewire (CombowireTM ) and pressureguidewire with thermodilution may allow us to estimate these indexes at the same time.
Wakayama Medical UniversityWakayama Medical University
ConclusionConclusion
Within the indexes to speculate micro-circulation condition such as CFR, DDT, Pzf and microvascularresistance index (MVRI & h-MVr), MVRI & h-MVrmight be the best predictor of the LV functional recovery.
Within the indexes to speculate micro-circulation condition such as CFR, DDT, Pzf and microvascularresistance index (MVRI & h-MVr), MVRI & h-MVrmight be the best predictor of the LV functional recovery.
Wakayama Medical UniversityWakayama Medical University
Methods(1)Methods(1)Study population・24 patients who underwent primary PCI for the first anterior
AMIwithin 12 hours from the onset of symptoms
Exclusion criteria・Left main trunk lesion ・History of prior MI ・Cardiogenic shock・Renal insufficiency (serum creatinine >1.5mg/dl) ・Insulin-dependent diabetes mellitus ・Contraindications to MRI (pacemaker, atrial fibrillation,
claustrophobia and so on)
Study population・24 patients who underwent primary PCI for the first anterior
AMIwithin 12 hours from the onset of symptoms
Exclusion criteria・Left main trunk lesion ・History of prior MI ・Cardiogenic shock・Renal insufficiency (serum creatinine >1.5mg/dl) ・Insulin-dependent diabetes mellitus ・Contraindications to MRI (pacemaker, atrial fibrillation,
claustrophobia and so on)
Wakayama Medical UniversityWakayama Medical University
Methods(2)Methods(2)Primary percutaneous coronary intervention・Thrombectomy ・Bare metal stent
Hemodynamic measurements and data analysis・Immediately after PCI, a 0.014-inch dual-sensor guidewire was placed distal to the culprit lesion to take per-beat averages of pressure and
flow velocity simultaneously. ・Microvascular resistance index (MVRI) during maximal hyperemia; [Mean distal pressure] / [Average peak flow velocity] (mmHg・cm-1・
s)
・ Hyperemic agent; intravenous infusion of adenosine (150 µg / kg / min)Creatine kinase (CK) and CK-MB fraction measurements・Before and immediately after primary PCI, and every 3 hours for the
Primary percutaneous coronary intervention・Thrombectomy ・Bare metal stent
Hemodynamic measurements and data analysis・Immediately after PCI, a 0.014-inch dual-sensor guidewire was placed distal to the culprit lesion to take per-beat averages of pressure and
flow velocity simultaneously. ・Microvascular resistance index (MVRI) during maximal hyperemia; [Mean distal pressure] / [Average peak flow velocity] (mmHg・cm-1・
s)
・ Hyperemic agent; intravenous infusion of adenosine (150 µg / kg / min)Creatine kinase (CK) and CK-MB fraction measurements・Before and immediately after primary PCI, and every 3 hours for the
Wakayama Medical UniversityWakayama Medical University
Delayed contrast-enhanced MRI and data analysis・Two weeks after the onset of AMI・ Gadolinium-diethlenetriamine pentaacetic acid (0.1mmol/kg) ・1.5-T MR scanner (Gyroscan Intera CV, Philips, the Netherlands) ・Transmural extent of infarction (TEI) by delayed contrast-enhanced
MRI;grade 1= 0 to 25% of hyperenhanced extent of left ventricular wall, grade 2= 26 to 50%, grade 3 = 51 to 75% and grade 4 =76 to 100%
Delayed contrast-enhanced MRI and data analysis・Two weeks after the onset of AMI・ Gadolinium-diethlenetriamine pentaacetic acid (0.1mmol/kg) ・1.5-T MR scanner (Gyroscan Intera CV, Philips, the Netherlands) ・Transmural extent of infarction (TEI) by delayed contrast-enhanced
MRI;grade 1= 0 to 25% of hyperenhanced extent of left ventricular wall, grade 2= 26 to 50%, grade 3 = 51 to 75% and grade 4 =76 to 100%
Methods(3)Methods(3)
grade 2grade 2 grade 4grade 4grade 3grade 3grade 1grade 1
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・Infarct size by delayed ce-MRI (%LV);
[Sum of the volume of DE regions for all slices] / [Sum of the LVmyocardial cross-sectional volumes] ×100
Methods(4)
Wakayama Medical UniversityWakayama Medical University
0
1
2
3
4
5
6
7
0 1 2 3 4 5
transmural extent of infarction
h-M
Rv (
mm
Hg・
cm
-1・s)
Relationship between hyperemic microvascularresistance and transmural extent of MI by de-MRIRelationship between hyperemic microvascular
resistance and transmural extent of MI by de-MRI
Wakayama Medical UniversityWakayama Medical University
Combowire configuration
Wakayama Medical UniversityWakayama Medical University
0
20
40
60
80
100
0grade0
1-25grade1
26-50grade2
51-75grade3
76-100grade4
Impr
oved
Con
tract
ility
(%)
Transmural Extent of Hyperenhancement (%) (contrast-enhanced MRI)
All Dysfunctional Segments
Relation between the Transmural Extent of Hyperenhancement before Revasculaization and the Likelihood of Increased Contractility after
Revascularization
(Kim RJ, et al; N Eng J Med 2000; 343: 1445-53)
Wakayama Medical UniversityWakayama Medical University
Main complaint) chest painCoronary risk factor) current smoking
family history of coronary artery diseaseP. I.) Feb. 8, 2007 Admission to our hospital with
continuous chest pain lasted > 30 minutes at rest.ECG: ST segment elavation in aVL, V1-5 leadsEchocardiogaraphy: akinesis in the LAD territoryEmergency CAG:
#6: 99% (collateral flow from RCA), #13: 100% (CTO)Labo. data (emergency room):
WBC 11500, CRP 0.10mg/dl, CK 43IU/l, CK-MB 13IU/l, GOT 15IU/l, GPT 16IU/l, LDH 215IU/l, TroponinT(-)
Main complaint) chest painCoronary risk factor) current smoking
family history of coronary artery diseaseP. I.) Feb. 8, 2007 Admission to our hospital with
continuous chest pain lasted > 30 minutes at rest.ECG: ST segment elavation in aVL, V1-5 leadsEchocardiogaraphy: akinesis in the LAD territoryEmergency CAG:
#6: 99% (collateral flow from RCA), #13: 100% (CTO)Labo. data (emergency room):
WBC 11500, CRP 0.10mg/dl, CK 43IU/l, CK-MB 13IU/l, GOT 15IU/l, GPT 16IU/l, LDH 215IU/l, TroponinT(-)
Case 1: 70 y.o., maleCase 1: 70 y.o., male
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Main Complaint) chest painCoronary risk factor) current smokingP.I.) March 11, 2007 Admission to our hospital with aggravating
chest pain at restECG: QS pattern in V1-4 leads, abnomal Q in aVL
ST segment elavation in I, aVL, V1-5 leadsEchocardiogaraphy: akinesis in the LAD territoryEmergency CAG:
#6: 100% (collateral flow ; none)Labo. data (emergency room):
WBC 9400, CRP0.60mg/dl, CK 1535IU/l, CK-MB 113IU/l, GOT 155IU/l, GPT 38IU/l, LDH 493IU/l, TroponinT(+)
Main Complaint) chest painCoronary risk factor) current smokingP.I.) March 11, 2007 Admission to our hospital with aggravating
chest pain at restECG: QS pattern in V1-4 leads, abnomal Q in aVL
ST segment elavation in I, aVL, V1-5 leadsEchocardiogaraphy: akinesis in the LAD territoryEmergency CAG:
#6: 100% (collateral flow ; none)Labo. data (emergency room):
WBC 9400, CRP0.60mg/dl, CK 1535IU/l, CK-MB 113IU/l, GOT 155IU/l, GPT 38IU/l, LDH 493IU/l, TroponinT(+)
Case 2 :64 y.o., maleCase 2 :64 y.o., male