Prognostic Value of Stress Dynamic Computed Tomography Perfusion With Computed Tomography Delayed Enhancement

JACC: CARDIOVASCULAR IMAGING

VOL.

-, NO. -, 2020

ª 2020 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION PUBLISHED BY ELSEVIER

ORIGINAL RESEARCH

Prognostic Value of Stress Dynamic Computed Tomography Perfusion With Computed Tomography Delayed Enhancement Satoshi Nakamura, MD,a Kakuya Kitagawa, MD,b Yoshitaka Goto, MD,a Masafumi Takafuji, MD,a Shiro Nakamori, MD,c Tairo Kurita, MD,c Kaoru Dohi, MD,c Hajime Sakuma, MDa

ABSTRACT OBJECTIVES This study sought to evaluate the prognostic value of stress dynamic computed tomography (CT) perfusion (CTP) with CT delayed enhancement (CTDE) in patients with suspected or known coronary artery disease (CAD) and in subgroups of patients with stent, heavy calcification, or stenosis. BACKGROUND The prognostic value of stress dynamic CTP with CTDE is unknown. METHODS Participants were 540 patients with suspected or known CAD. Major adverse cardiac events (MACEs) consisted of cardiac death, nonfatal myocardial infarction, unstable angina, or hospitalization for congestive heart failure. Ischemic score was calculated by scoring the reduction of normalized myocardial blood flow in 16 segments excluding areas of myocardial scarring. Ischemic perfusion defect (IPD) was defined as Ischemic score $4. Scar score was also calculated by scoring the transmural extent of scarring in each segment on CTDE. RESULTS During a median follow-up of 2.9 years, 43 MACEs occurred. By adding IPD to obstructive CAD ($50% stenosis) on coronary CT angiography, the concordance index for predicting MACEs increased from 0.73 to 0.82 in patients with suspected CAD (p ¼ 0.028) and from 0.61 to 0.73 in patients with known CAD (p ¼ 0.004). IPD and scar score of $4 were independent predictors when adjusted for each other in patients with suspected (adjusted hazard ratios: 7.5 [p < 0.001] and 3.0 [p ¼ 0.034], respectively) or known CAD (adjusted hazard ratios: 4.4 [p ¼ 0.001] and 3.2 [p ¼ 0.024], respectively). Patients with IPD had a higher annualized event rate than those without IPD in subgroups of those with stent (11.5% vs. 2.6%; p < 0.001), heavy calcification (13.3% vs. 3.1%; p < 0.001), 50% to 69% stenosis (8.8% vs. 1.0%; p < 0.001), or $70% stenosis (12.4% vs. 3.6%; p < 0.001). CONCLUSIONS Stress dynamic CTP with CTDE had incremental prognostic value over CT angiography in each group with suspected or known CAD and was prognostically useful in subgroups of patients with stent, heavy calcification, or obstructive CAD. IPD and myocardial scarring may play complementary roles in prognostic stratification. (J Am Coll Cardiol Img 2020;-:-–-) © 2020 by the American College of Cardiology Foundation.

From the aDepartment of Radiology, Mie University Graduate School of Medicine, Tsu, Mie, Japan; bDepartment of Advanced Diagnostic Imaging, Mie University Graduate School of Medicine, Tsu, Japan; and the

c

Department of Cardiology and

Nephrology, Mie University Graduate School of Medicine, Tsu, Mie, Japan. This study was partly supported by research grants from Siemens Japan. Dr. Dohi has received financial support from Otsuka and Takeda. Dr. Sakuma has received research grants from Daiichi Sankyo, Fuji Pharma, Fujifilm RI Pharma, and Eisai. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. Manuscript received July 3, 2019; revised manuscript received December 12, 2019, accepted December 20, 2019.

ISSN 1936-878X/$36.00

https://doi.org/10.1016/j.jcmg.2019.12.017

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Prognostic Value of Stress Dynamic CTP With CTDE

ABBREVIATIONS AND ACRONYMS ATP = adenosine triphosphate CABG = coronary artery bypass grafting

CAD = coronary artery disease CCS = coronary calcium score CI = confidence interval CMR = cardiac magnetic resonance

CT = computed tomography CT-FFR = computed tomography–derived fractional

C

oronary computed tomography (CT)

motion or breathing (n ¼ 15). Thus, 55 patients who

angiography (CTA) is an established

met the criteria were excluded, and we enrolled 563

imaging technique for the diagnosis

patients, who had follow-up after the cardiac CT was

and exclusion of coronary artery disease

performed.

(CAD) (1). However, CTA provides poor pre-

follow-up; therefore, the final study population CAD. Known CAD was defined as having a history of myocardial infarction (MI), percutaneous coronary

myocardial perfusion, could complement

intervention or coronary artery bypass grafting

the limited capability of CTA to assess the he-

(CABG).

modynamic significance of coronary stenosis (3,4).

Nonetheless,

abnormal

perfusion

detected by CTP can be induced not only by enhancement (CTDE) is a feasible and reliable imaging technique for detecting myocar-

CTDE = computed tomography

dial scarring. CTDE has been reported to offer

delayed enhancement

high diagnostic performance for detecting

CTP = computed tomography

infarcted areas determined by cardiac magnetic resonance (CMR) (5–7). Therefore, combined CTP and CTDE has the potential to

FFR = fractional flow reserve

differentiate

HR = hazard ratio

infarction. Previous studies showed that

IPD = ischemic perfusion defect

myocardial ischemia detected with perfusion

LAD = left anterior descending

imaging and delayed enhancement imaging

artery

by MRI was a strong predictor of cardiac

MACE = major adverse cardiac

events (8,9). Similarly, the detection of

myocardial

ischemia

from

myocardial ischemia by CTP with CTDE might improve risk stratification.

MI = myocardial infarction

We sought to evaluate the prognostic

ROC = receiver-operating

value of stress dynamic CTP with CTDE in

characteristic curve

to

imaging method with CT for evaluating

angiography

MBF = myocardial blood flow

lost

comprised 540 patients with suspected or known

ischemia but also by infarction. CT delayed

event

were

diction of hemodynamically significant ste-

flow reserve

ECG = electrocardiogram

patients

nosis (2). CT perfusion (CTP) imaging, an

CTA = computed tomography

perfusion

Twenty-three

patients with suspected or known CAD and in subgroups of patients with stent, heavy calcification, or stenosis.

IMAGE ACQUISITION. All CT data were acquired with

a second-generation (SOMATOM Definition Flash, Siemens Healthineers, Forchheim, Germany) or thirdgeneration dual-source CT scanner (SOMATOM Force; Siemens Healthineers). Patients were asked to avoid drinks containing caffeine for at least 24 h before undergoing stress testing. Unenhanced images for Agatston calcium scoring were acquired with electrocardiogram

(ECG)-triggered

high-pitch

spiral

scanning with 120-kV tube voltage before stress dynamic CTP (10). During the administration of 20 mg of adenosine triphosphate (ATP) at 160 m g/kg/min for >3 min (11), scan acquisition of dynamic CTP was initiated by injecting 40 ml of contrast medium with an iodine concentration of 370 mg/ml at a flow rate of 5 ml/s. Dynamic datasets were acquired for 30 s via ECGtriggered axial scan mode repeated at 2 alternating table positions to obtain a z-axis coverage of 73 mm or 105 mm for the second- or third-generation scanner, respectively. Tube voltage was set at 80 kV or 70 kV for the second- or third-generation scanner, respectively, and tube current was determined by using an automatic exposure control system with the quality

METHODS

reference of 350 mA/rotation at 120 kV (12). After completing data acquisition, ATP administration was

STUDY POPULATION. This study was designed as a

stopped. ECG images, blood pressure, and arterial

single-center, retrospective study. Medical records

oxygen saturation were monitored and recorded

were reviewed for 618 consecutive patients who

throughout the procedure.

completed a comprehensive cardiac CT examination

After dynamic stress CTP, standard prospective CTA

for evaluation of ischemic heart disease at our hos-

was performed at rest with the following scan param-

pital

2017

eters: 2  100-kV tube voltage or 80-kV and 0.28-s

(Figure 1). The cardiac CT examinations included

gantry rotation time, with injection of 0.84 ml/kg of

calcium scoring, CTA, stress dynamic CTP, and CTDE.

contrast medium with an iodine concentration of

The acquisition and analysis of the cardiac CT images

370 mg/ml over 12 s. Tube current was determined

were approved by the institutional review board, and

with the angular modulation technique.

between

March

2012

and

February

written informed consent was obtained from all pa-

CTDE images were acquired 7 min after CTA

tients at the time of cardiac CT. Exclusion criteria for

without additional contrast administration and were

this study were as follows: 1) age of <45 or >85 years

reconstructed by using targeted special frequency

(n ¼ 25); 2) no written informed consent for follow-

filtration and half-scan reconstruction (3). Tube

up, which was approved by the institutional review

voltage was 80 kV and tube current was 370 mA for a

board (n ¼ 15); and 3) severe artifacts on CTP due to

second-generation scanner and were automatically

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Nakamura et al.

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determined by the automatic exposure-control system with the quality reference of 580 mA/rotation at 80 kV for a third-generation scanner. IMAGE ANALYSIS. Analysis of dynamic CTP images

Prognostic Value of Stress Dynamic CTP With CTDE

F I G U R E 1 Flow Chart of Patient Selection

Patients who completed the cardiac CT n = 618

was performed with commercially available perfusion Exclusion criteria for the study, n = 55 - Age <45 or >85, n = 25 - No written informed consent for follow up, n = 15 - Severe artifacts, n = 15

software (Syngo Volume Perfusion CT Body, Siemens Healthineers). Myocardial blood flow (MBF) was estimated by using a dedicated parametric deconvolution technique, based on a 2-compartment model of the intravascular and extravascular spaces. The

Enrolled patients n = 563

maximum slope of time-attenuation curves fitted for every voxel was used to generate an MBF map of 3-

Follow-up loss n = 23

mm thickness and 1-mm increments. Polygonal regions of interest measuring 1 to 2 cm 2

Final study population n = 540

were placed within each of the 16 American Heart Association myocardial segments (excluding an apical segment) in the short-axis view on the MBF map, at a minimum distance of 1 mm from the endocardial and

A flow chart of the patient selection in this study. Medical records were reviewed for 618 consecutive patients who completed a comprehensive

epicardial borders to avoid contamination. When any

cardiac CT examination. Of them, 55 patients who met the exclusion criteria

myocardial scarring was identified on CTDE, we did

were excluded, and we therefore enrolled 563 patients in the study.

not include areas matching the myocardial scarring

Twenty-three patients were lost to follow-up; therefore, the final study

within regions of interest on the MBF map. A normalized MBF value was calculated as an MBF

population comprised 540 patients with suspected or known coronary artery disease. CT ¼ computed tomography.

value in each segment divided by the highest MBF value within the 16 segments on the MBF map. Ischemic score was calculated by adding the scores of

scale: 0: 0%; 1: 1% to 49%; 2: 50% to 69%; 3: 70% to

all segments using a 5-point scale based on normal-

99%; and 4: 100%.

ized MBF values: 0 ¼ normal (>0.75), 1 ¼ mildly

CTDE images were visually evaluated to determine

abnormal (#0.75, >0.675), 2 ¼ moderately abnormal

the presence or absence of hyperenhancement sug-

(#0.675, >0.60), 3 ¼ severely abnormal (#0.6), and

gestive of myocardial scarring within each of the 16

4 ¼ absent (11). Ischemic perfusion defect (IPD) was

segments by the consensus decision of 2 observers.

defined as ischemic score $4. When myocardial

Examples of perfusion defect and myocardial scarring

scarring covered an entire segment, the score for that

are shown in Figure 2. The transmural extent of

segment was counted as 0.

scarring was scored in each segment on CTDE images

Calcium score images were analyzed with a

using a 5-point scale: 0: 0%; 1: 1% to 24%; 2: 25% to

commercially available software package (Ziosta-

49%; 3: 50% to 74%; and 4: 75% to 100%. Scar score

tion2, Ziosoft Inc., Tokyo, Japan) using the Agatston

was calculated by summing up the scores in all

score with a cutoff of 130 Hounsfield units. The

segments.

analysis for calcium score was performed only for

FOLLOW-UP. Follow-up information was collected

patients with suspected CAD, because most of the

through a review of hospital records or telephone

patients with known CAD had stents or bypass grafts

interviews blinded to CT results. Patients who un-

(13). CTA images were visually evaluated in a joint

derwent early (#60 days after CT) revascularization

reading by 2 observers, including a radiologist with 10

were censored from follow-up thereafter. Major

years of experience in CTA. Coronary segments with a

adverse cardiac events consisted of cardiac death,

reference diameter of $1.5 mm were assessed for the

nonfatal MI, unstable angina, and hospitalization for

detection of stenosis. Obstructive CAD, severe ste-

congestive heart failure. Hard events included cardiac

nosis, multivessel disease, and proximal left anterior

death and nonfatal MI. Cardiac death was defined as

descending artery (LAD) stenosis on CTA was defined

death caused by acute MI, ventricular arrhythmias, or

as $50% stenosis in $1 vessel, $70% stenosis in $1

congestive heart failure. Nonfatal MI was defined as

vessel, $50% stenosis in $2 vessels, and $50% ste-

prolonged angina accompanied by new ECG abnor-

nosis in the left main or proximal LAD, respectively.

malities and increased cardiac biomarkers. Unstable

Stenosis score was calculated by summing up points

angina was defined as new-onset, worsening, or rest

for stenosis in each vessel according to a 5-point

angina requiring hospital admission. Congestive

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Prognostic Value of Stress Dynamic CTP With CTDE

F I G U R E 2 Examples of Perfusion Defect and Myocardial Scarring

A

B

C

D

Representative myocardial blood flow map (left) and CT delayed enhancement (right) showing (A) perfusion defect larger than myocardial scarring, (B) perfusion defect with matching myocardial scarring, (C) perfusion defect without myocardial scarring, and (D) no perfusion defect or myocardial scarring. White and black arrows represent perfusion defect and myocardial scarring, respectively.

heart failure was defined as the development of

predictor was evaluated by calculating the global chi-

appropriate symptoms, such as cough, shortness of

square test and receiver-operating characteristic

breath, dyspnea on exertion, paroxysmal nocturnal

(ROC) curves analysis. ROC curves were built based

dyspnea, and reduced exercise tolerance, associated

on a logistic regression model, and the Delong test

with either new radiologic findings consistent with

was used to compare the concordance index. Kaplan-

congestive heart failure or new physical signs

Meier curves were used to estimate cumulative event

including pulmonary rales, S 3 gallop sound, and

rates of MACEs. Differences between time-to-event

weight gain.

curves were compared by using the log-rank test.

STATISTICAL ANALYSIS. Continuous variables are

Annualized event rates were calculated by dividing 3-

presented as the mean  SD and were evaluated with

year Kaplan-Meier event rates by 3. A 2-sided p

the Mann-Whitney U test. Categorical variables are

value <0.05 was considered statistically significant.

expressed

were

All analyses were performed by using the SPSS sta-

compared by using the Fisher exact test. The influ-

tistical package, version 23.0 (IBM, Armonk, New

ence of predictors on MACEs was determined by us-

York) and the R statistical package, version 3.4.4 (R

ing Cox proportional hazards regression analysis, and

Foundation

the results are reported as hazard ratios (HRs) with

Austria).

as

frequency

(proportion)

and

for

Statistical

Computing,

Vienna,

95% confidence intervals (CIs). Univariate Cox proportional hazards regression analysis was performed

RESULTS

to identify potential predictors of MACEs. Multivariate Cox proportional hazards regression analysis was

PATIENT

performed by using stepwise forward selection for

AND

CHARACTERISTICS,

variables with p < 0.05 in the univariate analysis to

STRESS. Table 1 shows baseline patient characteris-

determine independent predictors of MACEs. The

tics in all patients and those with suspected or

incremental value of a predictor over another

known CAD.

HEMODYNAMIC

RADIATION

RESPONSE

DURING

DOSE, ATP

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Prognostic Value of Stress Dynamic CTP With CTDE

T A B L E 1 Baseline Patient Characteristics

T A B L E 2 Imaging Results

All Patients (N ¼ 540)

Suspected CAD (n ¼ 332)

Male

350 (65)

221 (67)

129 (62)

Age, yrs

68  9.1

67  10

69  8.9

Body mass index, kg/m2

Known CAD (n ¼ 208)

24.0  3.7 24.0  3.7 23.9  3.6

Coronary risk factors

All Patients (N ¼ 540)

Suspected CAD (n ¼ 332)

Known CAD (n ¼ 208)

Coronary calcium score 0

—

92 (28)

—

1–99

—

88 (27)

—

100–399

—

68 (20)

—

$400

—

84 (25)

—

Hypertension

374 (69)

225 (68)

149 (72)

Dyslipidemia

334 (62)

162 (49)

172 (83)

Diabetes

179 (33)

98 (30)

81 (39)

Obstructive CAD

244 (45)

118 (36)

126 (61)

Current smoker

80 (15)

48 (14)

32 (15)

Severe stenosis

142 (26)

68 (20)

74 (36)

Family history of CAD

101 (19)

52 (16)

49 (24)

Multivessel disease

144 (27)

70 (21)

74 (36)

Body mass index >25 kg/m2

177 (33)

112 (34)

65 (31)

Proximal LAD stenosis

117 (22)

44 (13)

73 (35)

Stenosis score $6

155 (29)

55 (17)

100 (48)

169 (31)

88 (26)

81 (39)

38 (11)

41 (20) 154 (74)

Echocardiography

Coronary CT angiography

LVEF <50%

64 (12)

20 (6)

44 (21)

Dynamic CT perfusion

Wall motion abnormality

168 (31)

50 (15)

118 (57)

Ischemic score $4* Ischemic score $8

Symptom Typical

62 (11)

34 (10)

Atypical

28 (13)

79 (14)

CT delayed enhancement

107 (20)

76 (23)

31 (15)

Myocardial scar

196 (36)

42 (13)

Nonanginal

81 (15)

57 (17)

24 (12)

$2 segments with scarring

150 (28)

26 (8)

124 (60)

Dyspnea

62 (11)

37 (11)

25 (12)

Scar score $4

126 (23)

20 (6)

106 (51)

Scar score $8

73 (14)

8 (2)

65 (31)

148 (27)

0 (0)

148 (71)

Stent

137 (25)

0 (0)

137 (66)

Values are n (%). *Ischemic perfusion defect was defined as ischemic score $4.

Stent without CABG

124 (23)

0 (0)

124 (60)

CAD ¼ coronary artery disease; CT ¼ computed tomography; LAD ¼ left anterior descending artery.

42 (8)

0 (0)

42 (20)

108 (20)

0 (0)

108 (52)

History of CAD PCI

CABG Old myocardial infarction Values are n (%) or mean  SD.

CABG ¼ coronary artery bypass grafting; CAD ¼ coronary artery disease; LVEF ¼ left ventricular ejection fraction; PCI ¼ percutaneous coronary intervention.

n ¼ 24) experienced a MACE: cardiac death: n ¼ 3, nonfatal MI: n ¼ 7, unstable angina: n ¼ 23, and hospitalizations for congestive heart failure: n ¼ 10. Noncardiac death was observed in 16 patients. Fortyfive patients who underwent early revascularization (percutaneous coronary intervention: n ¼ 44, CABG:

The dose-length products for CTA, CTP, and CTDE were 191  117, 315  109, and 117  35 mGy$cm, respectively, and the effective doses for each imaging modality were 2.67  1.64, 4.42  1.53, and 1.64  0.48 mSv, respectively, using a conversion coefficient of 0.014. The effective dose for calcium scoring was <0.5 mSv for all patients. Heart rate increased significantly from 64  11 beats/min at baseline to 76  12 beats/min under stress (p < 0.001). Systolic blood pressure decreased significantly from 131  20 mm Hg at baseline to 116  20 mm Hg during stress (p < 0.001), whereas diastolic blood pressure declined significantly from 67  10 mm Hg to 57  10 mm Hg (p < 0.001). In our population, no patients had any major complications related to stress agent. At CTA acquisition, the mean heart rate was 67  10 beats/min.

n ¼ 1) were censored at the time of revascularization. UNIVARIATE

COX

PROPORTIONAL

HAZARDS

REGRESSION ANALYSIS. Univariate predictors for

MACEs are listed in Table 3. Sex, age, and clinical predictors were not statistically significant. Ischemic score $4 was the strongest predictor in all patients (HR: 7.5; 95% CI: 3.9 to 14.6; p < 0.001) and those with suspected CAD (HR: 9.9; 95% CI: 3.6 to 27.6; p < 0.001), and ischemic score $8 was the strongest predictor in patients with known CAD (HR: 6.8; 95% CI: 3.0 to 15.6; p < 0.001). All predictors of CTA (obstructive CAD, severe stenosis, multivessel disease, proximal LAD stenosis, and stenosis score $6) were significant predictors for all patients and those with suspected or known CAD. Univariate predictors for hard events are listed in Supplemental Table 1. Significant predictors of hard

IMAGING RESULTS. Results for coronary calcium

events in all patients were current smoker, wall motion

score (CCS), CTA, CTP, and CTDE are presented in

abnormality, CTA findings (obstructive CAD, severe

Table 2.

stenosis, multivessel disease, and proximal LAD ste-

OUTCOMES. During a median follow-up of 2.9 years,

nosis), ischemic score of $4 and $8, and CTDE findings

43 patients (suspected CAD, n ¼ 19; known CAD,

($2 segments with scarring and scar score $ 4).

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Prognostic Value of Stress Dynamic CTP With CTDE

T A B L E 3 Univariate Predictors of MACEs

All Patients

Suspected CAD

Known CAD

HR (95% CI)

p Value

HR (95% CI)

p Value

HR (95% CI)

Male

0.9 (0.5–1.7)

0.727

0.6 (0.3–1.5)

0.310

0.9 (0.4–2.4)

p Value

0.897

Age >70 yrs

1.5 (0.8–2.7)

0.195

2.0 (0.8–5.1)

0.123

1.1 (0.5–2.5)

0.826

Hypertension

1.1 (0.6–2.1)

0.796

1.3 (0.5–3.5)

0.654

0.9 (0.4–2.1)

0.748

Dyslipidemia

1.5 (0.8–2.8)

0.235

0.9 (0.4–2.2)

0.840

1.7 (0.5–5.7)

0.386

Diabetes

1.8 (0.9–3.3)

0.057

1.9 (0.8–4.8)

0.158

1.4 (0.6–3.2)

0.376

Current smoker

0.9 (0.4–2.1)

0.747

1.1 (0.3–3.9)

0.826

0.6 (0.2–2.2)

0.482

Coronary risk factors

Family history of CAD

1.3 (0.6–2.6)

0.510

0.3 (0.0–2.0)

0.207

2.2 (0.9–4.9)

0.069

Body mass index >25 kg/m2

0.9 (0.5–1.7)

0.659

0.3 (0.1–1.2)

0.086

1.8 (0.8–3.9)

0.176

2.0 (0.9–4.5)

0.093

3.6 (1.0–12.4)

0.044

1.2 (0.4–3.5)

0.754

2.1 (1.1–3.8)

0.019

1.6 (0.5–5.0)

0.379

1.6 (0.7–3.8)

0.272

Echocardiography LVEF <50% Wall motion abnormality Coronary calcium score $100

—

—

3.7 (1.3–10.3)

0.012

—

—

$400

—

—

6.5 (2.6–16.8)

<0.001

—

—

Coronary CT angiography Obstructive CAD

5.1 (2.5–10.3)

<0.001

6.6 (2.4–18.3)

<0.001

2.9 (1.1–7.8)

0.033

Severe stenosis

5.6 (3.1–10.4)

<0.001

8.0 (3.2–19.9)

<0.001

3.2 (1.3–7.4)

0.005

Multivessel disease

4.3 (2.4–7.9)

<0.001

5.6 (2.3–13.8)

<0.001

3.3 (1.4–7.4)

0.005

Proximal LAD stenosis

6.2 (3.4–11.3)

<0.001

11.0 (4.4–27.3)

<0.001

3.1 (1.4–7.1)

0.006

Stenosis score $6

4.8 (2.6–8.8)

<0.001

6.8 (2.8–16.9)

<0.001

3.0 (1.3–7.2)

0.012

Dynamic CT perfusion Ischemic score $4*

7.5 (3.9–14.6)

<0.001

9.9 (3.6–27.6)

<0.001

5.3 (2.2–12.9)

<0.001

Ischemic score $8

6.9 (3.7–12.5)

<0.001

7.5 (3.0–18.6)

<0.001

6.8 (3.0–15.6)

<0.001 0.064

CT delayed enhancement Myocardial scarring

3.7 (2.0–6.8)

<0.001

4.0 (1.5–10.4)

0.005

3.1 (0.9–10.5)

$2 segments with scarring

3.2 (1.7–5.8)

<0.001

5.0 (1.8–13.8)

0.002

1.8 (0.7–4.3)

0.197

Scar score $4

5.3 (2.9–9.7)

<0.001

7.7 (2.9–20.4)

<0.001

4.1 (1.5–11.0)

0.005

*Ischemic perfusion defect was defined as ischemic score $4. CI ¼ confidence interval; HR ¼ hazard ratio; MACE ¼ major adverse cardiac event; other abbreviations as in Tables 1 and 2.

Ischemic score $4 was the strongest predictor of hard

predictor when adjusted for obstructive CAD, severe

events (HR: 25.8; 95% CI: 3.3 to 204; p ¼ 0.002).

stenosis, proximal LAD stenosis, multivessel disease,

MULTIVARIATE

and scar score $4. In these models, multivessel dis-

COX

PROPORTIONAL

HAZARDS

for multivariate

ease and scar score $4 were independent predictors

analysis were created to evaluate whether IPD

against IPD, whereas obstructive CAD, severe steno-

(ischemic score $4) was an independent predictor

sis, and proximal LAD stenosis were not.

REGRESSION

ANALYSIS. Models

when adjusted for each of the predictors (Table 4). In

Multivariate analysis of predictors for hard events

all patients, IPD was an independent predictor when

are listed in Supplemental Table 2. IPD remained an

adjusted for obstructive CAD, severe stenosis, prox-

independent predictor of hard events in all patients

imal LAD stenosis, scar score $4, and wall motion

when adjusted for current smoker, wall motion ab-

abnormality. In these models, obstructive CAD, se-

normality, severe stenosis, and scar score $4. In

vere stenosis, proximal LAD stenosis, and myocardial

these analysis, current smoker was an independent

scarring were also independent predictors against

predictor against IPD, whereas wall motion abnor-

IPD, but wall motion abnormality was not. In patients

mality, severe stenosis, and scar score $4 were not.

with suspected CAD, IPD remained an independent

RISK STRATIFICATION BY IPD IN ALL PATIENTS AND

predictor when adjusted for obstructive CAD, severe

THOSE

stenosis, proximal LAD stenosis, scar score $4, and

Kaplan-Meier curves by IPD (Figure 3) showed that

WITH

SUSPECTED

OR

KNOWN

CAD.

CCS $400. In these models, obstructive CAD, severe

annualized event rates for MACEs were significantly

stenosis, proximal LAD stenosis, scar score $4, and

different between patients with and without IPD

CCS $400 were independent predictors against IPD.

among all patients (8.4% vs. 1.1%; p < 0.001) (Figure 3A)

In patients with known CAD, IPD was an independent

and those with suspected (7.8% vs. 0.8%; p < 0.001)

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calculated (Figure 4). Figure 4A shows that, by adding

T A B L E 4 Multivariate Analysis

IPD to obstructive CAD, global chi-square scores

Predictors

HR (95% CI)

p Value

IPD

5.5 (2.8–10.9)

<0.001

Versus obstructive CAD

3.2 (1.5–6.7)

IPD

5.0 (2.4–10.2)

All patients 0.002 <0.001 0.001

increased significantly from 25.1 to 59.5 in all patients (p < 0.001), from 17.5 to 37.9 in patients with suspected CAD (p < 0.001), and from 5.0 to 18.6 in patients with known CAD (p ¼ 0.001). ROC curve analysis for prediction of MACEs

Versus severe stenosis

3.1 (1.6–6.0)

IPD

5.1 (2.6–10.3)

<0.001

Versus proximal LAD stenosis

3.7 (2.0–7.1)

<0.001

adding IPD to obstructive CAD was significantly

IPD

5.4 (2.7–10.8)

<0.001

higher than that in obstructive CAD alone in all pa-

(Figure 4B) showed that the concordance index after

Versus scar score $4

3.2 (1.7–6.0)

<0.001

tients and in those with suspected and known CAD.

IPD

6.7 (3.4–13.3)

<0.001

By adding IPD to obstructive CAD, the concordance

Versus wall motion abnormality

1.5 (0.8–2.7)

0.256

index increased from 0.68 to 0.78 in all patients

Patients with suspected CAD IPD

6.8 (2.4–19.5)

<0.001

(p < 0.001), from 0.73 to 0.82 in patients with suspected CAD (p ¼ 0.028), and from 0.61 to 0.73 in pa-

Versus obstructive CAD

3.9 (1.4–11.3)

0.012

IPD

6.0 (2.0–18.2)

0.001

Versus severe stenosis

3.6 (1.4–9.8)

0.007

Supplemental Figure 2 shows the incremental

IPD

6.0 (2.0–17.5)

0.001

prognostic value of IPD over subcategories of CTA-

tients with known CAD (p ¼ 0.004).

Versus proximal LAD stenosis

6.1 (2.3–15.9)

<0.001

detected stenosis (severe stenosis, multivessel dis-

IPD

7.5 (2.5–22.2)

<0.001

Versus scar score $ 4

ease, and proximal LAD stenosis) in all patients and in

3.0 (1.1–8.5)

IPD

7.0 (2.4–20.1)

<0.001

Versus coronary calcium score $400

4.0 (1.5–10.6)

0.004

IPD

4.5 (1.8–11.2)

0.001

Versus obstructive CAD

1.9 (0.7–5.3)

0.204

those with suspected and known CAD (p < 0.05 for each

IPD

3.8 (1.5–9.7)

0.002

group) (Supplemental Figure 3). The best cutoffs of

Versus severe stenosis

2.1 (0.9–4.9)

0.100

stenosis score and ischemic score for prediction of

IPD

4.4 (1.8–10.9)

0.001

MACEs in all patients were 6 and 4, respectively.

Versus multivessel disease

2.3 (1.0–5.5)

0.049

IPD

4.3 (1.7–10.8)

0.002

Versus proximal LAD stenosis

2.1 (0.9–4.9)

0.091

IPD

4.4 (1.8–10.8)

0.001

difference in annualized event rates for MACEs be-

Versus scar score $4

3.2 (1.2–8.7)

0.023

tween patients without obstructive CAD and without

0.034

Patients with known CAD

those with suspected and known CAD by global chisquare tests (p < 0.05 for each test). Furthermore, we performed ROC curve analysis for stenosis score versus stenosis score plus ischemic score in all patients and in

We compared Kaplan-Meier curves by CTA and CTP (Supplemental Figure 4). There was no significant

IPD (p ¼ 0.959) and between patients with obstructive IPD ¼ ischemic perfusion defect; other abbreviations as in Tables 1 and 2.

CAD and with IPD (p ¼ 0.139). RISK STRATIFICATION BY IPD IN THE SETTING OF

(Figure 3C) or known (9.2% vs. 1.9%; p < 0.001)

STENT OR HEAVY CALCIFICATION. Figure 5A shows

(Figure 3E) CAD. For prediction of hard events, patients

that, among patients with stents who had no CABG, a

with IPD displayed higher event rates than those

significant difference in annualized event rates was

without IPD among all patients (2.6% vs. 0.2%;

apparent between patients with and without IPD

p < 0.001) (Figure 3B) and among those with suspected

(11.5% vs. 2.6%; p < 0.001).

(3.1% vs. 0%; p < 0.001) (Figure 3D) or known (2.1% vs.

In patients with heavy calcification, among those with suspected CAD, IPD had a significant association

0.6%; p ¼ 0.021) (Figure 3F) CAD. Annualized event rates for MACEs in patients with

with poor prognosis. Annualized event rates for

ischemic scores of #3, 4 to 7, and $8 were 1.1%, 6.3%

MACEs were significantly higher in patients with IPD

and 11.3% respectively, in all patients (p < 0.001);

than in those without among patients with a calcium

0.8%, 5.8%, and 11.1% in patients with suspected CAD

score 400 (13.3% vs. 3.1%; p < 0.001) (Figure 5B).

respectively, (p < 0.001); and 1.9%, 6.7%, and 11.0%

RISK

in patients with known CAD, respectively (p < 0.001)

STRATIFICATION

BY

IPD ACCORDING

TO

DEGREE OF STENOSIS. Kaplan-Meier curves by IPD

(Supplemental Figure 1).

according to CTA results (Figure 6) showed that pa-

INCREMENTAL PROGNOSTIC VALUE OF IPD OVER

tients with IPD had a worse prognosis than those

OBSTRUCTIVE CAD. To evaluate the incremental

without IPD among those with moderate (50% to

prognostic value of IPD over obstructive CAD, global

69%) stenosis but no severe ($70%) stenosis (annu-

chi-square

alized event rate: 8.8% vs. 1.0%; p < 0.001)

scores

and

concordance

index

were

7

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F I G U R E 3 Kaplan-Meier Curves by IPD in All Patients and Those With Suspected or Known CAD

All Patients

A

B

Prediction of MACEs 1.0

Prediction of Hard Events 1.0

IPD (-)

IPD (-)

0.8

Event-Free Survival

Event-Free Survival

IPD (+) IPD (+) 0.6 0.4 0.2 log-rank, p < 0.001

0.0 0

1

2

3

0.8 0.6 0.4 0.2 log-rank, p < 0.001

0.0 0

4

Follow-Up Time (Years)

1

2

3

4

Follow-Up Time (Years)

Patients at risk

Patients at risk

IPD (-)

371

326

259

170

102

IPD (-)

371

326

259

170

102

IPD (+)

169

117

90

54

29

IPD (+)

169

117

90

54

29

Patients with Suspected CAD

C

D

Prediction of MACEs

Prediction of Hard Events

IPD (-)

0.8 IPD (+) 0.6 0.4 0.2 log-rank, p < 0.001

0.0 0

1

2

3

IPD (-) IPD (+)

1.0 Event-Free Survival

Event-Free Survival

1.0

0.8 0.6 0.4 0.2 log-rank, p < 0.001

0.0 0

4

Follow-Up Time (Years)

1

2

3

4

Follow-Up Time (Years) Patients at risk

Patients at risk IPD (-)

244

217

179

118

75

IPD (-)

244

217

179

118

75

IPD (+)

88

60

46

29

18

IPD (+)

88

60

46

29

18

Patients with Known CAD

E

F

Prediction of MACEs

Prediction of Hard Events 1.0

1.0

IPD (-)

0.8 IPD (+)

0.6 0.4 0.2 log-rank, p < 0.001

0.0 0

1

2

3

Event-Free Survival

IPD (-) Event-Free Survival

8

IPD (+)

0.8 0.6 0.4 0.2 log-rank, p = 0.021

0.0 0

4

Follow-Up Time (Years)

1

2

3

4

Follow-Up Time (Years)

Patients at risk

Patients at risk

IPD (-)

127

109

80

52

27

IPD (-)

127

109

80

52

27

IPD (+)

81

57

44

25

11

IPD (+)

81

57

44

25

11

Kaplan-Meier curves by IPD for prediction of MACEs in (A) all patients, (C) those with suspected CAD, and (E) those with known CAD and Kaplan-Meier curves by IPD for prediction of hard events in (B) all patients, (D) those with suspected CAD, and (F) those with known CAD. CAD ¼ coronary artery disease; IPD ¼ ischemic perfusion defect; MACE ¼ major adverse cardiac event.

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F I G U R E 4 Incremental Prognostic Value of IPD Over Obstructive CAD

A

B

Global Chi-Square Test All Patients

Suspected CAD

ROC Curve Analysis All Patients

Known CAD

Suspected CAD

p < 0.001

p = 0.001

p < 0.001

Known CAD

p = 0.028

p < 0.001

p = 0.004

1

59.5

0.82

0.78

0.73

0.68 0.61

C-Index

Global Chi-Square

0.73

37.9

25.1 18.6

17.5

5.0

0 Obstructive Obstructive CAD CAD + IPD

Obstructive Obstructive CAD CAD + IPD

Obstructive Obstructive CAD CAD + IPD

Obstructive Obstructive CAD CAD + IPD

Obstructive Obstructive CAD CAD + IPD

Obstructive Obstructive CAD CAD + IPD

(A) Global chi-square tests and (B) receiver-operating characteristic (ROC) curve analysis to evaluate the incremental prognostic value of IPD over obstructive CAD. C-index ¼ concordance index; other abbreviations as in Figure 3.

(Figure 6A), with severe ($70%) stenosis (12.4% vs.

RISK STRATIFICATION BY COMBINATION OF IPD

3.6%; p < 0.001) (Figure 6B), with 1-vessel ($50%

AND SCAR SCORE. Kaplan-Meier curves by combi-

stenosis in 1 vessel) disease (7.4% vs. 0.6%; p ¼ 0.001)

nation of CTP and CTDE (Figure 7A) showed that,

(Figure 6C), and with multivessel ($50% stenosis

among patient groups stratified by the presence or

in $2 vessels) disease (13.3% vs. 3.8%; p ¼ 0.002)

absence of IPD and scar score $4, annualized event

(Figure 6D).

rates for MACEs were 12.1%, 5.7%, 2.5%, and 0.9%

F I G U R E 5 Kaplan-Meier Curves by IPD in the Setting of Stent or Heavy Calcification

A

B

Stent

Calcium Score ≥400 1.0

1.0

IPD (-)

IPD (-) 0.8

0.6

Event-Free Survival

Event-Free Survival

0.8

IPD (+)

0.4

IPD (+)

0.6 0.4 0.2

0.2 log-rank, p < 0.001

0.0 0

1

2

3

log-rank, p < 0.001

0.0 0

4

Follow-Up Time (Years)

1

2

3

4

Follow-Up Time (Years)

Patients at risk

Patients at risk

IPD (-)

87

77

58

38

20

IPD (-)

45

34

29

19

12

IPD (+)

37

26

20

12

8

IPD (+)

39

24

15

11

5

Kaplan-Meier curves by IPD for the prediction of MACEs in patients with (A) stent or (B) coronary calcium score of $400. For patients with stent, those who had undergone bypass grafting were excluded. Abbreviations as in Figure 3.

9

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F I G U R E 6 Kaplan-Meier Curves by IPD According to Degree of Stenosis

A

B

50-69% Stenosis

≥70% Stenosis

1.0

1.0

IPD (-)

IPD (-) IPD (+)

Event-Free Survival

Event-Free Survival

0.8 0.6 0.4 0.2

0.8 0.6

IPD (+)

0.4 0.2

log-rank, p < 0.001

0.0 0

1

2

3

log-rank, p < 0.001

0.0 0

4

Follow-Up Time (Years)

1

2

3

4

Follow-Up Time (Years)

Patients at risk

Patients at risk

IPD (-)

69

62

49

31

16

IPD (-)

56

41

31

24

15

IPD (+)

33

27

17

6

2

IPD (+)

86

52

39

24

12

C

D

One-Vessel Disease 1.0

Multi-Vessel Disease

IPD (-)

1.0

Event-Free Survival

0.8 Event-Free Survival

10

IPD (+) 0.6 0.4 0.2 log-rank, p = 0.001

0.0 0

1

2

3

IPD (-)

0.8 0.6

IPD (+)

0.4 0.2 log-rank, p = 0.002

0.0 0

4

Follow-Up Time (Years)

1

2

3

4

Follow-Up Time (Years)

Patients at risk

Patients at risk

IPD (-)

59

52

41

32

20

IPD (-)

66

51

39

24

11

IPD (+)

42

29

23

13

7

IPD (+)

78

51

34

18

8

Kaplan-Meier curves by IPD for prediction of MACEs in patients (A) with moderate (50% to 69%) stenosis, (B) severe ($70%) stenosis, (C) 1-vessel ($50% stenosis in 1 vessel) disease, and (D) multivessel ($50% stenosis in $2 vessels) disease on CTA. Abbreviations as in Figure 3.

in patients with IPD (þ) and scar score $4, with IPD (þ)

and

scar

score

<4,

with

IPD(–)

and

scar

score $4, and with IPD(–) and scar score <4, respectively (p < 0.001). In Figure 7B, global chi-

Supplemental Figure 5 shows annualized event rates for MACEs in patients with and without scar score of $4 or IPD. Kaplan-Meier

curves

in

patients

with

sub-

square tests showed that IPD and scar score $4

endocardial (having segments with scar score 1 to 2

had incremental prognostic value over each other

and not having segments with scar score $3) or

(p < 0.001).

transmural (having segments with scar score $3)

Figure 8 and the Central Illustration showed annu-

scarring are shown in Supplemental Figure 6. Annu-

alized event rates for MACEs by combination of

alized event rates were 3.6% and 9.5% in patients

obstructive CAD, scar score $ 4, and IPD in all pa-

with subendocardial or transmural scar, respectively

tients and those with suspected or known CAD.

(p ¼ 0.002).

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F I G U R E 7 Complementary Prognostic Value of IPD and Scar Score

B

Kaplan-Meier Curves by Combination of IPD and Scar

Event-Free Survival

1.0 0.8

IPD (-) + Scar Score <4 IPD (-) + Scar Score ≥4 IPD (+) + Scar Score <4

0.6

IPD (+) + Scar Score ≥4

0.4

Global Chi-Square Test p < 0.001

p < 0.001

67.3

Global Chi-Square

A

67.3

48.6 36.0

0.2 log-rank, p < 0.001

0.0 0

1

2

3

IPD

4

Follow-Up Time (Years)

IPD +Scar Score ≥4

Scar Score ≥4 Scar Score ≥4 +IPD

Patients at risk IPD (-) + Scar Score <4 311

279

222

147

IPD (-) + Scar Score ≥4 60

47

37

23

89 13

IPD (+) + Scar Score <4 103

67

52

32

21

IPD (+) + Scar Score ≥4 66

50

38

22

8

(A) Kaplan-Meier curves by combination of IPD and scar score in all patients. (B) Global chi-square test shows incremental prognostic value of IPD and scar score of $4 over each other. IPD ¼ ischemic perfusion defect.

Details of events in patients with IPD or scarring

emission CT among 379 patients with suspected or

are given in Supplemental Table 3. There was no

known CAD. However, in that study, no analysis for

significant difference in the number of each event

each patient group with suspected or known CAD was

between IPD and scar score $4.

performed. The present study demonstrates the

DISCUSSION The main findings of the present study were that: 1)

F I G U R E 8 Annualized Event Rates for Maces by Combination of Stenosis, Scar, or IPD

stress dynamic CTP with CTDE had incremental 15.6

prognostic value over CTA in each patient group with unfavorable prognosis in subgroups of patients with stent, heavy calcification, or obstructive CAD; and 3) IPD and myocardial scarring were independent predictors when adjusted for each other, with incremental prognostic value over each other. Compared with the prior study (11), we emphasized use of CTDE, distinction between ischemia and scarring, analysis in patients with known CAD, and role of IPD in the subcategories of patients with stent, heavy calcification, or moderate stenosis. RISK STRATIFICATION WITH CTP IN PATIENTS WITH

11.8

12.9

11.3 10.2

9.1

8.7

6.3 6.1 6.5

1.1 0.8

1.9

Obstructive CAD (-)

Obstructive CAD (+)

SUSPECTED OR KNOWN CAD. Several studies have

evaluated the prognostic value of CTP in patients

13.5

13

Annualized Event Rate (%)

suspected or known CAD; 2) IPD was associated with

All Patients

Obstructive Obstructive Obstructive CAD (+) CAD (+) CAD (+) + Scar Score ≥4 + IPD (+) + Scar Score ≥4 + IPD (+) Suspected CAD

Known CAD

with suspected or known CAD (14–16). Chen et al. (14) reported that the combination of CTA and static CTP

Annualized event rates for MACEs by combination of obstructive CAD, scar score, and

yielded a prediction of 2-year event-free survival

IPD. Abbreviations as in Figure 3.

similar to that obtained by ICA and single-photon

Nakamura et al.

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C E NT R AL IL L U STR AT IO N Prognostic Value of Stress Dynamic Computed Tomography Perfusion With Computed Tomography Delayed Enhancement

A

B

Ischemic Perfusion Defect (IPD)

15.6

CT Delayed Enhancement Annualized Event Rate (%)

Stress Dynamic CT Perfusion

Risk Stratification by Stenosis, Scar, and IPD

8.7

6.3 6.1 6.5

1.9

Obstructive CAD (-)

Obstructive CAD (+)

All Patients

Obstructive Obstructive Obstructive CAD (+) CAD (+) CAD (+) + Scar Score ≥4 + IPD (+) + Scar Score ≥4 + IPD (+) Suspected CAD

Known CAD

Risk Stratification by IPD According to Coronary Status Heavy Calcification

Stents Event-Free Survival

12.9

11.3 10.2

9.1

1.1 0.8

C

13.5

13 11.8

Obstructive CAD

1.0

1.0

1.0

1.0

0.8

0.8

0.8

0.8

0.6

0.6

0.6

0.6

0.4

0.4

0.4

0.2

0.2 p < 0.001

0.0 0

1

2

3

4

0.4

0.2 p < 0.001

0.0 0

(Year)

1

2

3

50%-69% stenosis

0.2

p < 0.001

0.0

0.0

4

1

0

2

3

4

≥70% stenosis p < 0.001 0

1

(Year)

(Year) IPD (+)

2

3

4

(Year)

IPD (–)

Nakamura, S. et al. J Am Coll Cardiol Img. 2020;-(-):-–-.

(A) Images derived from dynamic CT perfusion with CT delayed enhancement for a patient with IPD. (B) Annualized event rates for MACEs by combination of stenosis, IPD, and scar score in all patients and those with suspected or known CAD. (C) Kaplan-Meier curves in patients stratified by the presence or absence of IPD according to coronary status (stent, heavy calcification, moderate stenosis, and severe stenosis). CT ¼ computed tomography; CTA ¼ computed tomography angiography; CAD ¼ coronary artery disease; IPD ¼ ischemic perfusion defect; MACE ¼ major adverse cardiac event.

prognostic value of CTP in each patient group with or

invasive angiography. The present study shows that,

without a history of CAD.

in the setting of moderate stenosis on CTA, the

RISK STRATIFICATION BY IPD IN PATIENTS WITH

presence of IPD was associated with adverse out-

OBSTRUCTIVE CAD ON CTA. One study showed that

comes, whereas patients without IPD had good

CTP improved risk stratification among patients

prognosis, implying the utility of IPD for the selective

with $50% stenosis with $70% stenosis on CTA (11).

use of invasive angiography in patients with moder-

However, evaluating the prognostic value of CTP in

ate stenosis.

patients with moderate (50% to 69%) stenosis and no

COMPARISON OF CTP WITH CT-DERIVED FRACTIONAL

severe stenosis on CTA is of interest because this is

FLOW

the population in which functional assessment may

computation from coronary CTA datasets (CT-FFR)

be important for the selection of patients undergoing

has emerged as a promising noninvasive tool for

RESERVE. Fractional

flow

reserve

(FFR)

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assessing the hemodynamic severity of epicardial

the present study used IPD from CTP and CTDE,

coronary stenosis. A recent study showed that dy-

whereas

namic CTP and CT-FFR both identify functionally

perfusion by CTP alone. Fifth, in our study, there

significant CAD with comparable accuracy, and by

were many comparisons using the alpha criterion of

combining the 2 techniques, diagnostic performance

0.05; the results might include type 1 errors. Finally,

can be improved (3). However, CT-FFR may not be

we performed not vessel territory–based but patient-

suitable for patients with known CAD after stenting or

based analysis to show the prognostic importance of

heavy calcification (17). A prior study showed the

IPD and scarring in a patient level. Further studies are

clinical potential of CTP to improve the diagnostic

needed to evaluate the prognostic value of IPD and

accuracy of CTA for detecting in-stent stenosis (18). In

scarring involving sites with stents or calcification.

the present study, CTP was useful for risk stratification of patients with stent or heavy calcification, implying that CTP may be a preferred method for predicting prognosis in such patients. In this study, ischemic score was obtained by scoring the reduction of normalized MBF values in each myocardial segment, thereby enabling dynamic CTP to quantify the severity of the ischemic burden. The poorer prognosis associated with larger ischemic burden demonstrated in our study suggests the importance of assessment of the severity of myocardial

perfusion

defect

for

risk

stratification.

In

contrast, CT-FFR provides information only on lesions in epicardial coronary arteries and cannot provide direct measurement of microvascular disease or diffuse atherosclerotic burden in the left ventricular myocardium level. STUDY LIMITATIONS. First, this study was a single-

center, retrospective study. A prospective, multicenter study should be performed to confirm the results of this study. Second, although the total radiation dose in this study was relatively small (mean effective dose: 8.7 mSv), adding CTP and CTDE to CTA increased the radiation dose compared with CTA alone. Third, all images in this study were obtained using dual-source CT. Further investigation is needed to clarify whether the same results as in our study could be obtained by using other types of CT scanners. Fourth, although the population in this

the

previous

study

adopted

abnormal

CONCLUSIONS Stress dynamic CTP with CTDE had incremental prognostic value over CTA in each group with suspected or known CAD and was prognostically useful in subgroups of patients with stent, heavy calcification, or obstructive CAD. IPD and myocardial scarring may

play

complementary

roles

in

prognostic

stratification. ADDRESS

FOR

CORRESPONDENCE:

Dr.

Kakuya

Kitagawa, Department of Radiology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan. E-mail: [email protected]. mie-u.ac.jp. PERSPECTIVES COMPETENCY IN MEDICAL KNOWLEDGE: Stress dynamic CTP with CTDE provided incremental prognostic value over CTA not only in patients with suspected CAD but also in those with known CAD and may be recommended for prediction of prognosis in patients with stent, heavy calcification, or obstructive CAD. IPD and myocardial scarring may play complementary roles in prognostic stratification. TRANSLATIONAL OUTLOOK: Additional studies are needed to validate these findings in a prospective, multicenter setting.

study included patients from our previous study (11),

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KEY WORDS CT delayed enhancement, dynamic CT perfusion, prognostic value

A PPE NDI X For supplemental figures and tables, please see the online version of this paper.