Tc-99m sestamibi single photon emission computed tomography for guiding percutaneous coronary intervention in patients with multivessel disease: a comparison with quantitative coronary

ORIGINAL PAPER

Tc-99m sestamibi single photon emission computedtomography for guiding percutaneous coronary interventionin patients with multivessel disease: a comparisonwith quantitative coronary angiographyand fractional flow reserve

Stefan Forster Æ Johannes Rieber Æ Christopher Ubleis ÆMayo Weiss Æ Peter Bartenstein Æ Paul Cumming ÆVolker Klauss Æ Marcus Hacker

Received: 14 April 2009 / Accepted: 1 September 2009 / Published online: 16 September 2009

� Springer Science+Business Media, B.V. 2009

Abstract To evaluate the accuracy of myocardial

perfusion SPECT (MPI) in the detection and allocation

of vessel specific perfusion defects (PD) using standard

distribution territories in a routine clinical procedure of

patients with multivessel disease (MVD). Combined

quantitative coronary angiography and fractional flow

reserve (QCA/FFR) measurements were used as inva-

sive reference standard. 216 vessels in 72 MVD

patients (67 ± 10 years, 28 female) were investigated

using MPI and QCA. FFR of 93 vessels with interme-

diate stenoses was determined. MPI detected signifi-

cant stenoses according to QCA/FFR findings with a

sensitivity of 85%. However, vessel-based evaluation

using standard myocardial distribution territories

delivered a sensitivity of only 62% (28 MPI? out of

45 (QCA/FFR)? findings), with specificity, PPV and

NPV of 90, 62 and 90%. 7/17 false positive and 7/17

false negative findings (41%) could be attributed to

incorrect allocation of reversible PD to their respective

coronary arteries. 6/17 (35%) perfusion territories

were classified as false negative when additional fixed

PD were present. MPI had reasonable sensitivity for

the detection of significant coronary artery disease in

patients with multivessel disease. However, sensitivity

decreased markedly, when the significance of each

individual stenosis was evaluated using standard

myocardial supplying territories. In this setting, 41%

of false negative and false positive MPI findings

resulted from incorrect allocation of reversible perfu-

sion defects to their determining supplying vessel.

Keywords Myocardial perfusion SPECT �Fractional flow reserve � Multivessel disease �Percutaneous coronary intervention �Coronary angiography

Introduction

Based on an extensive body of data, myocardial

perfusion single photon emission tomography (MPI)

is widely used for risk stratification and assessment of

both ischemia and viability in patients with coronary

artery disease (CAD) [4]. However, given that MPI is

an imaging technique measuring flow enhancement in

S. Forster � C. Ubleis � M. Weiss � P. Bartenstein �P. Cumming � M. Hacker

Department of Nuclear Medicine, University of Munich,

Munich, Germany

J. Rieber � V. Klauss

Department of Cardiology, Medizinische Poliklinik-

Innenstadt, University of Munich, Munich, Germany

M. Hacker (&)

Klinik und Poliklinik fur Nuklearmedizin der LMU,

Marchioninistr. 15, 81377 Munchen, Germany

e-mail: [email protected]

123

Int J Cardiovasc Imaging (2010) 26:203–213

DOI 10.1007/s10554-009-9510-x

diverse myocardial beds based on changes in relative

radiotracer uptake [26], there arise distinct limitations

in its use in the evaluation of patients with multivessel

disease (MVD) [7, 10]. In particular, the allocation of

perfusion defects to their determining coronary arter-

ies or specific coronary lesions—a precondition for

performing appropriate percutaneous coronary inter-

vention (PCI) [15, 16, 36]—is frequently hampered

when morphological correlation is not available [7,

10, 35, 41, 23, 40]. Additionally, the detection of

ischemic myocardial regions might be compromised

in patients with fixed perfusion defects due to the

presence of myocardial scaring or chronic hypo

perfusion, as has been shown in a recent study [32].

In a clinical cardiology setting, two-dimensional

quantitative coronary angiography (QCA), although

often underestimating or overestimating a lesion‘s

functional severity, is still the standard technique for

guiding PCI in patients with multivessel CAD [14, 39].

Initial results from the Fractional Flow Reserve

versus Angiography for Multivessel Evaluation

(FAME) study, however, reported in 1,005 patients

with multivessel CAD a significant reduction of the

composite end point of death, non-fatal myocardial

infarction (MI), and repeated revascularization during

a 1 year follow-up, when additional measurements of

fractional flow reserve (FFR) were performed [38].

FFR is defined as the ratio of maximum achievable

coronary blood flow in a stenotic coronary artery

relative to the maximal blood flow in the same vessel

in the absence of all epicardial obstructions [11].

Initial studies compared FFR with MPI as a reference

standard in patients both with single-vessel and

multivessel disease [5, 7, 8, 12, 21, 25, 29, 43]. On

the basis of various clinical studies, an FFR cut-off

value\0.75 was established for the detection of flow-

limiting or functionally significant coronary artery

stenoses. Recent publications confirmed the validity

of the cut-off value of 0.75 also in comparison to

H215O positron emission tomography blood flow

measurements in patients with chronic MI [24], as

well as after revascularization therapy and during

long-term follow up [3, 31].

The aim of the present study was to evaluate MPI

for the detection and allocation of flow-limiting

stenoses in patients with multivessel disease, com-

pared to an invasive reference standard of QCA/FFR.

We hypothesized that the accuracy of MPI is limited

for vessel-based evaluation using standard myocardial

distribution territories due to the uncertainty of

allocating perfusion defects to particular coronary

arteries without knowledge of individual coronary

vascular anatomy.

Methods

Patient Selection

Patients were included in the study if they had

multivessel coronary artery disease, which was

defined as coronary artery stenoses of at least 50%

of the vessel diameter in at least two of the three

major epicardial coronary arteries. Patients who had

had a myocardial infarction were included if the

infarction had occurred at least 10 days before study

inclusion. Patients who had undergone previous PCI

were also included in the study. Patients who had

angiographically significant left main coronary artery

disease, previous coronary-artery bypass surgery, or

patients who were pregnant were excluded.

QCA with FFR measurements and MPI were

performed in all patients.

The study was approved by the local ethics

committee and written informed consent was obtained

from all patients.

Quantitative Coronary Angiography (QCA) and

FFR measurements

All patients were instructed to abstain from caffeine

and chocolate for 12 h prior to catheterization. At

least two orthogonal views were obtained, and the

projection showing the most severe narrowing was

used for quantitative coronary measurements (Philips

DCI, The Netherlands). Using the guiding catheter as

a scaling device, measurements of the minimal lumen

diameter as well as proximal and distal reference

diameters were made [36].

FFR was measured in all vessels with intermediate

stenoses, i.e. in the range C50 and B75%. Vessels with

severe ([75%) or low-grade stenoses (\50%) were not

investigated for pressure measurements. After crossing

the target lesion with a dedicated sensor-tipped 0.014-

inch angioplasty guidewire (WaveWireWaveMap,

Volcano Therapeutics, Rancho Cordova, CA, USA;

or PressureWire, Radi Medical Uppsala, Sweden)

while under angiographic guidance, the pressure

204 Int J Cardiovasc Imaging (2010) 26:203–213

123

sensor was positioned beyond the stenosis in the distal

portion of the artery. Phasic and mean aortic pressure

as well as phasic and mean coronary pressure distal to

the stenoses were then measured under maximum

coronary hyperemia, which was induced by intrave-

nous administration of 140 lg/kg min-1 of adenosine

(Adrecar, Sanofi, Munich, Germany). FFR was defined

as the ratio of mean poststenotic pressure and mean

aortic pressure measured during maximum hyperemia.

Significance of a stenosis was classified by dicho-

tomous criteria (significant or non-significant), accord-

ing to the composite of the QCA and FFR findings. A

lesion was classified as significant if severe stenosis

was detected in QCA, or if FFR measurement yielded a

value of\0.75. Occluded vessels or those who could

not be assessed by FFR due to subtotal occlusions were

also rated as significant. A lesion was classified as non-

significant if QCA showed no abnormality, stenosis

\50%, or if FFR was C0.75.

Myocardial Perfusion SPECT (MPI)

When appropriate, physical or pharmacological stress/

rest MPI was performed according to a one-day

protocol with Tc-99m sestamibi, as follows; before

the termination of the stress test, a dose of 4 MBq/kg of

Tc-99m sestamibi (at least 300 MBq) was adminis-

tered intravenously. For the subsequent resting study, a

dose of 10 MBq/kg of Tc-99m sestamibi (at least

700 MBq) was injected. If systolic blood pressure was

greater than 120 mm Hg, 0.8 mg nitroglycerine was

sublingually administered to the patients before injec-

tion of the radiopharmaceutical for the rest image.

Image acquisition was performed with a triple-

headed camera system (Philips [formerly Picker]

Prism 3000 XP, Cleveland, Ohio). Possible attenuation

artefacts were corrected by applying an attenuation

correction based on a simultaneous transmission

measurement with 153Gd (STEP�), with 360� rotation

in continuous mode, or alternately by performing gated

SPECT acquisition for wall motion analyses, as

described previously [19]. Images were reconstructed

over 360� with 20 slices along the short axis, the long

axis, and the four-chamber view for each study. A

standardized filter (Low Pass 4th power, cut-off-

frequency 0.26) was used. Quantitative analysis of

MPI perfusion studies was carried out using QPS

processing software (Cedars-Sinai Medical Center,

Los Angeles, California).

Image analysis was performed by agreement of two

experienced observers (M.H. and S.F.) blinded to the

results of QCA/FFR, the coronary distribution type, or

the presence of coronary normal variants such as

ramus intermedius, or the location of stenoses. A

commonly used 20 segment model was employed for

division of the left ventricular myocardium images

[6]. Each of the 20 segments was scored according to

the guideline for semiquantitative analysis (‘‘Semi-

quantitative Scoring System: The Fivepoint Model’’:

0 = normal; 1 = mildly reduced—not definitely

abnormal; 2 = moderate reduced—definitely abnor-

mal; 3 = severely reduced; 4 = absent radiotracer

distribution) [1]. Segmental scores were summed for

the three main coronary arteries (LAD, RCA, LCx)

according to standard myocardial perfusion territo-

ries, as described elsewhere [8], resulting in regional

perfusion scores under stress (SSSr, regional Summed

Stress Score) and rest (SRSr, regional Summed Rest

Score) conditions. The difference of SSSr and SRSr

was defined as the regional Summed Difference Score

(SDSr). On the basis of previously published results,

stenoses and their respective supplying territories with

an SDSr C 1 were considered significant, while

stenoses and their respective supplying territories

with an SDSr = 0 were considered as non-significant

[18]. SRSr C 1 was defined as fixed perfusion defect.

Evaluation of the allocation process

In addition to the above territorial mapping, allocation

of ischemic myocardial regions to appropriate target

vessels was evaluated. Wrong allocation was assumed

for the following combinations of disagreement:

(1) MPI suggested ischemia of a target vessel with

non-significant stenosis (\50% or an FFR C

0.75); and at the same time significant stenosis

(between 50 and 75% with an FFR \ 0.75 or

stenosis [ 75%) was present in another vessel,

which (according to standard distribution terri-

tories) did not show ischemia on MPI ((MPI)?/

(QCA/FFR)-).

(2) MPI did not suggest ischemia, but significant

stenosis was nonetheless present in the respec-

tive distribution territory, and at the same time

MPI detected ischemia in another vessel with

non-significant stenosis ((MPI)-/(QCA/

FFR)?)).

Int J Cardiovasc Imaging (2010) 26:203–213 205

123

Statistical analysis

Descriptive analysis for categorical and continuous

parameters was performed using SPSS version 13.0

(SPSS, Chicago, IL, USA). Results are presented as

mean ± standard deviation (SD) and range, unless

stated otherwise. Paired and unpaired t-tests were

used when appropriate. Statistical significance was

tested on the 5% level.

Results

Seventy two consecutive patients (28 female, mean

age 67 ± 10 years) with multivessel disease (32

patients with two- and 40 patients with three-vessel

disease) were eligible for the study.

QCA with FFR measurements and MPI were

performed in each patient within an interval of

13 ± 43 days. QCA/FFR was performed before MPI

in 13 and after MPI in 59 patients.

Ergometric stress was performed in 17 patients,

whereas pharmacological stress or a combined stress

protocol was applied in 55 patients. Patient charac-

teristics are summarized in Table 1.

Quantitative coronary angiography and FFR

measurements

About 216 vessels in 72 patients were investigated

with QCA, morphological characteristics are sum-

marized in Table 2. FFR measurements were per-

formed in 93 vessels with intermediate stenoses, i.e.

C50 and B75%. Here, the FFR values ranged from

0.42 to 1.0, with a mean FFR of 0.78 ± 0.10. There

was a significant difference detected between mean

diameter stenosis of significant lesions compared to

non-significant lesions (71.2 ± 11.5% vs. 34.8 ±

28.7%, P \ 0.001). No correlation was found

between FFR values and degree of angiographic

stenoses (n = 93) ranging between 50 and 75%.

According to QCA, 14 vessels showed severe

stenoses ([75%) and were rated as significant. Ten of

these coronary arteries showed total occlusions, six in

the proximal and four in the distal part of the artery.

However, at least partial collateral filling (Rentrop

grade 2 or higher) was present in seven (70%) of the

occluded vessels. 31 of the 93 intermediate stenoses

showed FFR \0.75, such that overall 45/216 lesions

were rated as significant by definition.

MPI in the detection of significant coronary artery

lesions using standard myocardial distribution

territories

Vessel based evaluation

A total of 216 perfusion territories were analyzed for

MPI (3 territories per patient). 64 territories were

identified as showing abnormal perfusion (any PD),

45 with reversible perfusion defects (SDSr C 1) and

Table 1 Clinical characteristics of study cohort (n = 72)

Clinical parameters

Sex (m/f) 44/28

Age years ± SD 67 ± 8.5

Diabetes mellitus (%) 26 (36)

Hypertension (%) 53 (74)

Hypercholesterolemia (%) 47 (65)

Current smoker (%) 34 (47)

Family predisposition (%) 22 (31)

First-pass LVEFrest % 53 ± 10

2-vessel disease (%) 32 (44)

3-vessel disease (%) 40 (56)

Table 2 Procedural characteristics of significant versus non-

significant lesions as defined by QCA/FFR

Significant

n = 45

Non-significant

n = 171

Morphological characteristics

QCA diameter stenosis % 71.2 ± 11.5** 34.8 ± 28.7

QCA widthprox (mm) 2.8 ± 1.6** 1.8 ± 1.6

QCA widthdist (mm) 2.7 ± 1.3** 1.7 ± 1.5

Functional characteristics

FFR (n = 93) 0.63 ± 0.1** 0.85 ± 0.1

SSSr 4.8 ± 6.6** 1.5 ± 4.0

SRSr 3.1 ± 6.2** 1.0 ± 3.4

SDSr 1.7 ± 2.5** 0.4 ± 1.5

QCA Quantitative coronary angiography, FFR fractional flow

reserve, SSSr (regional) summed stress score, SRSr (regional)

summed rest score, SDSr (regional) summed difference score.

Values are mean ± SD

** P \ 0.001


123

19 with fixed perfusion defect (PD) (SRS C 1). 15

perfusion territories showed a combination of both,

reversible and fixed perfusion defects.

Considering only reversible perfusion defects on

MPI, 28 of 45 perfusion territories were rated

significant by QCA/FFR, while 17 of the 45 territo-

ries were classified as non-significant by QCA/FFR.

On the other hand, 17 of 45 coronary lesions rated as

significant by QCA/FFR showed no reversible per-

fusion defects on MPI. 154 of all 216 vessels showed

no perfusion defects in MPI and were non-significant

in QCA/FFR (‘‘true’’ negatives; see Table 3). In the

detection and allocation of myocardial ischemia by

MPI, sensitivity was 62%, specificity was 90%, ppV

was 62%, npV was 90% and accuracy was 84%.

When the presence of any perfusion defect was

taken into account, 33 of 64 myocardial supplying

territories were rated significant by QCA/FFR and 12

of 45 significant lesions showed neither reversible nor

fixed perfusion defects on MPI (Table 3). This

indicates sensitivity of 73%, specificity of 82%,

ppV of 52%, npV of 92%, and an accuracy of 80%.

Considering only the 93 vessels with intermediate

stenoses (C50 and B75%) with all individually

available FFR measurements, sensitivity was 77%,

specificity was 82%, ppV was 69%, npV was 88%

and accuracy was 81% when reversible perfusion

defects in MPI were evaluated (data not shown in

detail).

Patient based evaluation

For all patients, sensitivity was 79%, specificity was

74%, ppV was 72%, npV was 81% and accuracy was

76%, when only reversible perfusion defects were

considered and sensitivity increased to 85%, while

specificity was 54%, ppV was 61%, npV was 81%

and accuracy was 68%, when any perfusion defect

was rated as pathological (Table 4).

For the subgroup of diabetes mellitus patients,

sensitivity was 70%, specificity was 81%, ppV was

70%, npV was 81% and accuracy was 77%, when

only reversible perfusion defects were considered and

sensitivity increased to 77%, while specificity was

54%, ppV was 63%, npV was 70% and accuracy was

65%, when any perfusion defect was rated as

pathological (Table 5).

Table 3 Vessel-based evaluation

QCA/FFR MPI

PD present No PD

present

Reversible PD

Significant 28 17

Non-significant 17 154

Any PD

Significant 33 12


Reversible PD Any PD

Sensitivity 0.62 0.73

Specificity 0.90 0.82

Positive predictive value 0.62 0.52

Negative predictive value 0.90 0.92

Accuracy 0.84 0.80

Accuracy of MPI in the detection of significant stenoses using

standard myocardial distribution territories compared to the

defined reference standard (QCA/FFR) in patients with

multivessel disease (n = 216)

PD perfusion defect

Table 4 Patient-based evaluation

QCA/FFR MPI

PD present No PD

present

Reversible PD

Significant 26 7


Any PD

Significant 28 5







Accuracy 0.76 0.68

Accuracy of MPI in the detection of significant stenoses

compared to the defined reference standard (QCA/FFR) in

patients with multivessel disease (n = 72)

PD perfusion defect


123

MPI and allocation of reversible perfusion defects

Seven of the 17 patients (41%) without reversible

perfusion defects on MPI, but exhibiting significant

stenosis in QCA/FFR, showed reversible perfusion

defects in an adjacent territory with non-significant

stenosis in the respective supplying vessel ((MPI)-/

(QCA/FFR)? disagreement, Figs. 1, 2). Addition-

ally, six (MPI)-/(QCA/FFR)? findings showed fixed

perfusion defects in the respective myocardial sup-

plying territory and the remaining four (MPI)-/

(QCA/FFR)? were ‘‘true’’ false negatives without

any perfusion defect on MPI. Seven of 17 patients

(29%) with non-significant stenosis in QCA/FFR, but

with reversible perfusion defects on MPI had signif-

icant stenosis in another coronary artery ((MPI)?/

(QCA/FFR)- disagreement). The remaining 10

(MPI)?/(QCA/FFR)- were ‘‘true’’ false positives.

Overall, 14 of 34 (MPI)?/(QCA/FFR)- or (MPI)-/

(QCA/FFR)? findings (41%) occurred due to wrong

allocation of MPI reversible perfusion defects to their

determining and supplying vessel, according to stan-

dard myocardial distribution territories.

Discussion

Numerous studies have shown high overall sensitiv-

ity, up to 90%, for MPI to identify patients with two-

or three vessel disease [9, 28, 30, 42]. Particularly in

these patients, the detection of functionally signifi-

cant coronary artery stenoses is an important

precondition for adequate treatment and improved

outcome. However, as compared to intracoronary

pressure measurements, which are performed directly

in the target vessels, MPI alone has limited capacity

to detect functionally significant stenoses, and to

allocate correctly the perfusion defects to specific

vessels or even coronary lesions in patients with

MVD, as shown in the present study.

The most important result for planning and

guiding individual therapies is the limited utility of

MPI alone for allocating correctly reversible and

fixed perfusion defects to their respective coronary

artery, or even to their determining coronary artery

lesion. Indeed, 41% of our disagreements (41% of

(MPI)-/(QCA/FFR)? and 41% of (MPI)?/(QCA/

FFR)-) resulted from just such allocation problems.

These limitations of MPI are well known and

previously documented in comparison studies

between MPI and invasive coronary angiography

[2] and can be explained by previously published post

mortem analysis, reporting only 50–60% accordance

between standard myocardial perfusion territories and

supplying areas of the three main coronary arteries, a

discrepancy arising from the extensive inter-individ-

ual variability of the coronary tree [20].

However, the diagnostic accuracy of MPI was

rarely investigated using a combined morphological

and functional reference standard, which was recently

shown superior to QCA alone in patients with MVD

[38]. To ensure an objective comparison in the

present study, MPI perfusion defects were systemat-

ically assigned to one of the three main coronary

arteries (RCA, LAD and LCX).

As such, our procedure does not necessarily reflect

clinical routine diagnostics in patients with MVD.

One possible clinical scenario is to determine

whether a demonstrated anatomical abnormality is

causing flow limitation requiring intervention in the

setting of an intermediate or no diagnostic finding on

QCA, especially when revascularization may not be

straightforward for the interventionist like in the

presence of long segment of disease, nearby branches

Table 5 Patient-based evaluation

QCA/FFR MPI

PD present No PD

present

Reversible PD

Significant 7 3


Any PD

Significant 10 3

Non-significant 6 7






Accuracy 0.77 0.65

Accuracy of MPI in the detection of significant stenoses

compared to the defined reference standard (QCA/FFR) in a

subgroup of patients with multivessel disease and diabetes

mellitus (n = 26)

PD perfusion defect


123

or in the presence of poor visualization on QCA, in-

or peri-stent restenosis.

Indeed, specific limitations of the MPI method

without knowledge of patient‘s coronary anatomy

were evident in the present study, even if early

studies have demonstrated how well this method can

demonstrate a culprit lesion or draw attention to one

which may have been initially overlooked at QCA.

In a recent study of 36 patients (88 vessels) suffering

from MVD, Ragosta et al. [32] reported that 36% of all

vascular zones lacking fixed or reversible perfusion

abnormalities on MPI showed either pathological FFR

(\0.75), or total occlusions in QCA. From this

observation, it was concluded that numerous hemody-

namically significant stenoses would be overlooked if

clinical judgment were based only upon MPI. In their

interpretation, most cases of discordance between MPI

and FFR measurements were primarily due to perfu-

sion imaging correctly identifying the most severe

stenosis, but not identifying other zones subtended by

lesser, but still significant, lesions. In seven of 22

patients (32%), MPI was completely normal in all

perfusion territories, despite the occurrence of patho-

logically FFR in one or more territories.

The observed high rate of improper classification

of an individual vascular territory based on MPI using

standard myocardial distribution territories would

lead to errors in management that are clinically

unacceptable. This well known limitation has led to

the proposed use of 3-D image fusion of the coronary

arteries visualized by coronary angiography, with

myocardial perfusion maps [13], an elegant approach

that has not yet found widespread use in routine

diagnostic practice. It has to be emphasized, that

Fig. 1 Example of a (MPI)-/(QCA/FFR)? finding (according to SDSRCA = 0) in a 60 years old male patient with fixed perfusion

defect in the RCA-territory and a significant 65% RCA stenosis with corresponding pathological FFR of 0.73


123

decisions regarding revascularization of specific

arteries in patients with MVD cannot be based on

MPI alone and that there is a need of proper

anatomical information (i.e. one should better rely

on incorporation of the angiogram with adjunctive

use of FFR as appropriate). Certainly, non-invasive

methods combining morphological and functional

imaging strategies using SPECT-CT or PET-CT

hybrid scanners will improve MPI as a tool for the

selection of vessel regions that are candidates for

intervention. There are already promising studies

using hybrid imaging technology [17, 27], which

were able to show improved allocation of perfusion

defects to specific coronary artery lesions and, thus,

potentially will improve therapy planning.

Assessing the diagnostic performance of MPI was

a further aspect in the present study, we found that

4/17 patients with significant stenosis in QCA/FFR

(24%) had no perfusion defect in MPI, reflecting

‘‘true’’ false negative ((MPI)-/(QCA/FFR)?) results.

This reflects a well-known limitation for MPI, which

can be attributed to the occurrence of balanced

ischemia in the absence of valid myocardial reference

areas [22, 41]. A further reason for discrepant results

in which MPI was negative while QCA/FFR positive

in the present study (6/17 patients, 35%), was the

Fig. 2 49 years old male patient with (MPI)?/(QCA/FFR)?

finding (according to SDSLAD = 4) with partially reversible

perfusion defect in the LAD-territory and corresponding 55%

LAD stenosis with pathological FFR of 0.69, (MPI)-/(QCA/

FFR)? finding (according to SDSRCX = 0) without perfusion

defect in the RCX-territory, but 70% RCX-stenosis and

pathological FFR of 0.72 and (MPI)?/(QCA/FFR)- finding

(according to SDSRCA = 4) with reversible perfusion defect in

the RCA territory, but normal appearing RCA in the

arteriogram. Bull‘s eyes quantitative display indicating two

perfusion defects, one in the septum and one in the apical

region. The partially reversible perfusion defect in the septum

was allocated to the LAD region, as major reversibility was

located in the LAD standard distribution territory. Respec-

tively, the apical perfusion defect was allocated to the RCA


123

occasional presence of fixed perfusion defects mask-

ing ischemia, which is also a well-known limitation

of MPI arising from an underestimation of the true

extent of myocardial viability in the standard resting

images [34]; see example Fig. 1. Some of the fixed

perfusion defects might have reflected not MI, but

rather stunned or hibernating myocardium, particu-

larly in this selective patient group with more

advanced stages of disease. For this reason, we

applied nitroglycerin before the tracer injection at

rest, so as to enhance tracer uptake in the ischemic

myocardium compared with that seen in the nonvi-

able and nonischemic myocardium. This approach

has earlier been shown to improve MPI viability

detection [37].

Study limitations

Our study has several limitations. First, FFR mea-

surement was not performed in all three coronary

arteries; therefore, the reference standard consists of a

combination of angiographic diameter stenosis mea-

surements with and without corresponding FFR

values, reflecting an approach already published by

our group [33]. A separate comparison of MPI with

FFR in intermediate stenoses delivered a sensitivity

of 77%, which was in line with previous studies,

confirming that these assumptions were appropriate.

In general, it is at present difficult to control for the

effects of perfusion derived from collateral vessels,

competitive flow, differential ischemia and other

factors [26]. Additionally, functionally relevant ste-

noses \50% as well as intramyocardial vessel

affections and peripheral stenoses, which both are

inaccessible for FFR measurements, could have lead

to false positive MPI findings. However, analysis in

the subgroup of patients with diabetes mellitus (and

therefore higher possibility of microvascular disease)

revealed similar ability for MPI in the detection of

significant stenoses when compared to the whole

patient cohort, such that the rate of microvasculature

related false positives in the current study is deemed

to be low.

Another limitation is presented by the lack of

gated SPECT in all patients, such that regional wall

motion and thickening patterns have not been imple-

mented for optimal validation of MPI for the

identification of significant stenoses.

Conclusion

Myocardial perfusion SPECT had reasonable sensi-

tivity for the detection of significant coronary artery

disease in patients with multivessel disease relative to

quantitative coronary angiography with/without addi-

tional FFR measurements. However, sensitivity

decreased markedly, when the significance of each

individual stenosis was evaluated using standard

myocardial supplying territories. In this setting,

41% of false negative and false positive MPI findings

resulted from incorrect allocation of reversible per-

fusion defects to their determining supplying vessel.

Acknowledgments We are grateful for the support and

superb technical assistance of the staff in the departments of

Nuclear Medicine and Cardiology at the University of Munich.

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Tc-99m sestamibi single photon emission computed tomography for guiding percutaneous coronary intervention in patients with multivessel disease: a comparison with quantitative coronary

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