TCT imaging & physiology 2008 Wakayama Medical University · Wakayama Medical University Concept of...

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


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


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


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 )


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 )


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)


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


Difference between CFR & FFR

%DS Microvasculardisease


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


Concept of CFR, FFR & IMR

IMRIMR


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 ) ]


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).


CFR & FFR


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


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


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)


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


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


Transmural Extent of Infarction by delayed enhancement by MRI

Grade 1Grade 1 Grade 2Grade 2 Grade 3Grade 3 Grade 4Grade 4Every 25%Every 25%


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)


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.


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


ECG at the time of admission( 70 y.o., male )


CombowireCombowire BaselineBaseline

HyperemiaHyperemia

h-MVr = h-Pd / h-APV = 40 / 59= 0.68 (mmHg/cm・sec-1）



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


ECG at the time of admissionECG at the time of admission( 64 y.o., male )


Combowire BaselineBaseline

HyperemiaHyperemia




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




Transmural extent of hyperenhancement Grade 4, peak CK 7182 → transmural MI

Transmural extent of hyperenhancement Grade 4, peak CK 7182 → transmural MI


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)


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



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



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.


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.


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)


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


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


・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)


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


Combowire configuration


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)


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


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

TCT imaging & physiology 2008 Wakayama Medical University · Wakayama Medical University Concept of...

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