Online Appendix for the following JACC article
TITLE:
Anatomic Versus Physiologic Assessment of Coronary Artery Disease: Role of CFR,
FFR, and PET Imaging in Revascularization Decision-Making
AUTHORS:
K. Lance Gould, MD, Nils P. Johnson, MD, MS, Timothy M. Bateman, MD, Rob S.
Beanlands, MD, Frank M. Bengel, MD, Robert Bober, MD, Paolo G. Camici, MD, Manuel D.
Cerqueira, MD, Benjamin J. W. Chow, MD, Marcelo F. Di Carli, MD, Sharmila Dorbala, MD,
MPH, Henry Gewirtz, MD, Robert J. Gropler, MD, Philipp A. Kaufmann, MD, Paul Knaapen,
MD, PHD, Juhani Knuuti, MD, PHD, Michael E. Merhige, MD, K. Peter Rentrop, MD, Terrence
D. Ruddy, MD, Heinrich R. Schelbert, MD, PHD, Thomas H. Schindler, MD, Markus
Schwaiger, MD, Stefano Sdringola, MD, John Vitarello, MD, Kim A. Williams, MD, Sr, Donald
Gordon, MD, Vasken Dilsizian, MD, Jagat Narula, MD, PHD
APPENDIX
More Physiologic Insights
Pharmacologic versus exercise stress and severity of stress-induced abnormalities. Quantitative
PET perfusion imaging essentially requires pharmacologic stress in order to acquire the first-pass
arterial activity necessary for determining absolute flow. The motion of exercise basically
precludes this early first-pass acquisition for routine clinical imaging. Additionally, exercise, like
cold pressor stress and other non-anatomic factors, cause heterogeneous sympathetic and
endothelial-mediated epicardial coronary vasoconstriction (S70-S78). Consequently, perfusion
defects during exercise stress reflect both the fixed structural severity of the stenosis as well as
superimposed functional vasoconstriction. By this mechanism, exercise may cause worse
perfusion defects than pure vasodilation agents (S74,S75).
Therefore, perfusion defects with vasodilation stress agents reflect the fixed structural
disease that is appropriate for mechanical revascularization. The functional component of
1
exercise-induced vasoconstriction can almost always be best treated medically. In addition,
vasodilator stress imaging identifies myocardial steal for assessing collateral function that is not
possible with exercise. While exercise stress has value, its lack in quantitative PET is not a
significant limitation – and may even be an advantage – in view of these considerations.
Differences in ischemic thresholds. Differences among published ischemic, low-flow threshold
arise mostly from the definition of “ischemia”, although flow tracers and models play a role as
well. For this paper, its flow maps and case examples, ischemia is strictly defined as a new or
worse dipyridamole-induced perfusion defect with significant ECG changes and/or severe angina
during stress. The ischemic flow threshold would likely be higher if defined by prior abnormal
SPECT, ECG stress testing, or clinical symptoms remote from the PET scan. The FFR threshold
for ischemia was originally defined by prior non-invasive stress testing (usually treadmill or
SPECT) with rare or no angina or ECG changes at the time of adenosine hyperemia for FFR.
Defining “ischemia” or “balanced stenosis” by coronary anatomy is not appropriate due to the
poor correlation of function with anatomy.
Stress imaging immediately after treadmill exercise is a period of substantially different
physiology than imaging during actual peak vasodilator hyperemia due to exercise. While
dobutamine stress reproduces many aspects of exercise stress, it has complex effects that
ultimately only simulate exercise. Quantitative myocardial perfusion has only rarely been
reported with supine exercise that, however, also involves significantly different physiology than
upright stress of daily life.
Interestingly, dipyridamole more frequently causes angina than adenosine in patients with
severe stenosis or occluded collateralized coronary arteries. Dipyridamole has slower, more
prolonged effects than adenosine. Typically angina with dipyridamole begins at the end of a 4
2
minute infusion or in the next minute thereby suggesting that several minutes of flow at ischemic
thresholds are required to cause angina and ECG changes. The much shorter duration of
adenosine may cause less angina for the same low flow level due to its more brief duration.
Normalizing quantitative perfusion for pressure rate product (PRP). Normalizing flow to PRP is
appropriate for analyzing group statistics, like average resting, maximum flow, and CFR. Using
normalized values for an individual patient artificially normalizes that patient to an average
group behavior that precludes individual revascularization decisions. For an individual, the nonnormalized stress flow and CFR are the essential, observed values for a given patient.
Normalizing for PRP does not improve the area under the curve (AUC) for the prediction of
ischemia by maximum flow or CFR (17).
“Balanced stenosis”. While FFR is a pressure-derived relative CFR, they are not the same.
Pressure derived FFR is normalized to aortic pressure whereas flow derived relative CFR is
normalized to other “normal” maximal coronary artery flow. Therefore, another dichotomy
between CFR and FFR arises with “balanced” segmental stenosis (without diffuse disease)
whereby relative CFR maybe normal while absolute FFR and CFR are abnormal. However, true,
localized, severe, perfectly balanced, fluid dynamically equivalent stenosis without diffuse
disease with a normal perfusion image during adequate stress is “rare” in the first author’s
experience. Severe three vessel segmental stenosis or balanced left main and right coronary
artery stenosis are nearly always associated with diffuse disease that may reduce the relative
severity of stress defects but do not normalize the relative PET stress images. The important
point is that people with normal relative PET scans do not routinely need an angiogram out of
3
fear of missing “balanced CAD”. Severely reduced absolute CFR with corresponding symptoms
are nearly always a reliable guide for an angiogram in these circumstances.
Absolute stress perfusion alone? Absolute stress perfusion alone has been proposed as a sole
measure of severity without considering rest flow or CFR (32). While appropriate in some
patients, for individual certainty, additional determinations of rest flow and CFR are essential for
two types of patients commonly seen:
(i) Some patients may have low stress flow, even at ischemic threshold levels, but with
concomitant low resting flow, as those taking beta blockers with a CFR of 2.5 to 3.0, no ECG
changes, no angina, normal LV function at rest and stress, and clinically stability. Considering
them ischemic on the basis of peak flow alone would be incorrect and revascularization is
inappropriate due to adequate CFR and absence of ischemia. Patients with heart failure, after
bypass surgery with diffuse disease, or hypertrophic thick LV wall as in hypertrophic
cardiomyopathy or after valve replacement for aortic stenosis may have reduced blood pressure,
low wall stress, low resting perfusion, reduced stress flow and adequate CFR.
(ii) Regional defects on stress flow images alone without rest flow images do not resolve the
question of whether the defect is due to a non-transmural scar or stress induced ischemia. The
first clinical case example shown in Figure 9 of the published text demonstrates a severe stress
defect. In the absence of rest flow images or CFR, this severe stress defect could represent scar
for which revascularization is contraindicated or could represent ischemia for which
revascularization is essential. This example illustrates the potentially life threatening errors that
might occur by relaying on stress images alone. The absence of activity in such severe defects
precludes using contractile function on ECG gated images for identifying scar versus viable
ischemic myocardium, thereby requiring resting images.
4
Variability of quantitative myocardial perfusion. The variability of quantitative myocardial
perfusion is due primarily to biological variation associated with the range of coronary
pathophysiology from young healthy volunteers with no risk factors to severe clinically manifest
CAD. The test retest coefficient of variation indicating methodologic precision is shown in
Supplement Table 1 below for PET and other common measurements in cardiology and
summarized in Table 4 of the published text. The coefficient of variation for quantitative PET
perfusion of 14% is within the range for other common cardiac related measurements of 10% to
29% such as percent diameter stenosis by quantitative angiography, ejection fraction by
echocardiographic or gated SPECT imaging, SPECT summed stress scores, serum C-reactive
protein, or low-density lipoprotein levels.
Inappropriate Use Of Cardiac PET Perfusion Imaging
1. While cardiac PET has a rich prognostic literature (28,S51-S54,S71,S77), withholding risk
factor treatment or suboptimal risk factor treatment based on normal images or flow capacity has
no basis at this time since risk factors need treatment regardless of imaging tests.
2. Subclinical coronary atherosclerosis is widely prevalent and therefore quantitative myocardial
PET perfusion imaging will be mildly or moderately “abnormal” in most such people. Such PET
scans should not be used as an excuse for angiograms and procedures in these patients. Only
severe, large regional defects or quantitative ischemic flow threshold should prompt an invasive
procedure.
3. Restricting cardiac PET solely to obese patients is not appropriate since PET offers important
clinical benefits to patients of all body sizes.
5
Technical Requirements For Quantitative Myocardial Perfusion Imaging
Many different PET scanners and software analysis tools are available commercially. All are
suitable for cardiac PET with absolute flow quantification if they fulfill the following minimal
requirements.
1. Identification and correction of attenuation/emission mis-registration that can cause artifactual
abnormalities and degrade quantitative measurements sufficiently to be clinically meaningless or
misleading.
2. Linear count recovery up to 3 million counts per second seen on the first-pass bolus of Rb-82
or N-13 ammonia and 2D imaging to avoid scanner saturation that degrades the arterial input
function essential for flow quantification. For 3D imaging, the scanner must be linear up to 10 to
12 million counts per second and requires lower dose and/or slower rubidium infusion (see
below).
3. Regional two-dimensional flow display such as a topographic or polar map to facilitate
identification of coronary arterial distributions, although polar maps distorts the visual spatial
size from base-to-apex more than a topographic view.
4. Either list mode or serial dynamic frames for quantification of arterial input and subsequent
myocardial uptake for determining absolute perfusion.
5. Flow software that may be specific, developed, proven at each site, or used from other sites
along with their acquisition protocol but must provide quantitative myocardial perfusion in
absolute units, not expressed as percent of “normals” that lacks the essential critical threshold
ranges of absolute perfusion characterizing ischemia.
6. While 3D acquisition is commonly used for PET perfusion imaging, carefully done reports by
manufacturers’ physicists prove that for cardiac PET perfusion imaging – “2D mode can be
6
preferable from an noise equivalent counts [NEC] standpoint … In addition to large random
coincidence event rates, and count losses due to dead time, event mispositioning due to pulse
pileup can significantly degrade image quality at high activity. At higher activities, the random
event rate becomes prohibitive in 3D (thus degrading NEC rates), and 2D mode becomes
superior from an NEC point of view” (S92).
Almost all of the reported quantitative flows in the Supplement Table were done with 2D
PET. However, many modern scanners do not offer 2D imaging due to current manufacturing
trends and cost containment, focus on “hot spot” cancer imaging, dose reduction due to higher
counts with 3D acquisition and little visual difference between 2D and 3D images. However, the
much higher random coincidence counts and dead time loses that degrade quantitative count
recovery as reported above remain a major limitation of 3D PET for quantitative perfusion
imaging that requires the high first pass arterial input function. Accordingly, 3D is reported to
provide absolute, quantitative flows but only with a reduced tracer dose and/or slower infusion to
avoid scanner saturation during the first past arterial phase. While 3D PET can be made to work,
the 3D scanners are not ideally designed to meet the difficult requirements of cardiac PET
optimized for bolus dosing to obtain low noise, high quality arterial input images. In order to
encourage manufacturers and as information for users, writing NEMA-like standards specific to
cardiac PET imaging would be a useful step.
7. Similarly many cardiac PET centers use ordered subset expectation maximization (OSEM)
reconstruction rather than filtered back project (FBP). However, careful physics studies also
demonstrate better contrast recovery for “cold spot” imaging by FBP compared to OSEM that is
optimized for “hot spot” cancer imaging. “For all count and NEC levels, higher and more
consistent cold area contrast recovery was found with FBP reconstruction as compared to OSEM
7
… Therefore, FBP reconstruction methods should be considered in place of OSEM for cold
feature imaging in cardiac PET” (S93).
Controversies
Should every cardiovascular, heart, or imaging center do cardiac PET? Does the absence of
PET imply “inferior” practice? The answer is no to both questions. Cardiac PET cannot be done
casually. It requires specific interest, commitment, training, and experience, as outlined in the
COCATS requirements (S94). The PET physician must be able to provide accurate and reliable
myocardial perfusion and absolute flow, clinical integration of physiologic data, and a definitive
management decision for each individual patient. For caregivers with these characteristics, it is a
powerful and effective guide to patient management because it provides fundamental reliable
physiologic data not otherwise available.
Reimbursement incentives. While physiologic severity of stenosis by invasive FFR is done in the
United States, it raises a complex issue. In Europe where the randomized FFR trials originated,
stents and revascularization procedures are a cost that reduces remaining resources needed for
other uses. Therefore, FFR to reduce the number of stent procedures has an economic incentive
as well as better outcomes than procedures based on the angiogram.
In the United States, stents and revascularization procedures are a revenue source that
contributes to income for the hospital in which the procedures are performed. Therefore, in the
United States, measuring FFR increases cost with a reasonable probability that the measured
FFR does not indicate a stent or revascularization procedure, thereby reducing incoming revenue.
Consequently, there is a strong economic disincentive to rely on frequent FFR measurements to
guide revascularization decisions.
8
Noninvasive quantitative PET perfusion imaging identifies the minority of patients with
large, regional areas of ischemic flow capacity who are most likely to benefit from invasive
procedures, while directing the remaining majority of patients to medical treatment. PET thus
avoids the uncertainty of current stress tests where nearly three fourths of traditional nuclear
stress tests, including the overt positives, had no influence on medical or invasive treatment
(S83). Cardiac PET should be done for obtaining specific definitive answers needed for a clinical
management decision.
Availability, complexity and cost. Cardiac PET is considered complex, costly, and not widely
available. Complexity is largely a function of interest, since PET technology and its
interpretation are straightforward but require care and attention to technical and physiologic
details. Semi-automated software, physiologic displays, and well-developed technician and
physician training programs exist. The Rb-82 generator eliminates the requirement for a
cyclotron in immediate association with the PET scanner. Volume economics are reasonable
with reported lower overall costs of care compared to not using PET (39,S84).
Competitive interests such as for particular scanners or software or protocols are commonly
related to commercial interests that may obscure the fundamentals of cardiac PET as outlined
here. Any version for any given center should provide accurate flow measurements by meeting
the basic technical requirements listed above. The ranges of flows among PET centers may vary
slightly among different centers and software packages. Consequently, each center should make
its own reference data base of quantitative myocardial perfusion in healthy young volunteers for
the upper limits and in patients with definite stress-induced ischemia for the lower thresholds, or
use the limits from established protocols in the existing literature.
Tasks and Studies Needed
9
Compared to standard SPECT imaging, quantitative myocardial perfusion PET involves a
fundamentally different technology, physiologic understanding, interpretation and commitment
to definitive conclusions that determine revascularization procedures, rather than raising issues
that require a confirmatory angiogram. For definitive non-invasive quantitative imaging to
resolve the issue of excess invasive procedures while optimizing their use, several further steps
are needed as follows:
(i) A specific high-level committee within ACC focused on and dedicated to PET perfusion
imaging and clinical coronary physiology needs to be established with membership comprised of
those with a published record of commitment to the principles addressed here.
(ii) An official ACC policy statement confirming the value of PET that will serve all its
subspecialty sections by providing more physiologic assessment of coronary function and justify
more widespread use and reimbursement for PET thereby reducing overall costs as documented
in the literature.
(iii) Further scientific studies, particularly of low flow ischemic thresholds with different forms
of stress including exercise, dobutamine, dipyridamole, adenosine, and regadenoson due to the
substantial differences in physiology, duration of low flow and different balance of supply and
demand for each of these stress modalities as briefly indicated above.
(iv) A process for standardized quality control of quantitative myocardial perfusion that defines
the steps by which a facility doing PET perfusion imaging verifies its flow methodology,
acquires a true “normal” database from healthy volunteers, defines low-flow ischemic thresholds
in an appropriate clinical group of patients and documents clinical integration into reports to
guide patient management as the standard reference “gatekeeper” for invasive procedures.
10
(v) Write new NEMA-like standards for quantitative myocardial PET perfusion imaging since
the technical requirements are markedly different than current NEMA standards oriented to
cancer imaging with F-18 radionuclides.
(vi) Randomized trials of revascularization based on quantitative absolute maximum flow and
CFR as measured by cardiac PET.
11
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21
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24
Supplement Figure Legends
Supplement Figure 1. Case 2 shows a large mild stress abnormality but with coronary flow
capacity well above the ischemic threshold confirmed by an FFR of 0.85 at an angiogram by
protocol indicating that revascularization was not indicated.
Supplement Figure 2. Case 3 shows a moderate sized, moderately severe, stress abnormality due
to known occlusion of a collateralized Ramus Intermedius that considered in clinical context
indicated enhanced medical management without further invasive procedures.
Supplement Figure 3. Case 4 shows a small but moderately severe basal inferior stress induced
abnormality that has excellent coronary flow capacity for which angiogram was not indicated.
Supplement Figure 4. Case 5 shows minimal localized stress abnormality but severely diffusely
reduced stress flow in/cc/min/gm reflecting severe diffuse CAD without segmental stenosis for
which angiogram was not indicated despite severe diffuse CAD.
25
Supplement Figure 1. Case 2
26
Case 2
HISTORY: 57 year-old female with exertional dyspnea, traditional cardiac risk factors
(hypertension, dyslipidemia, diabetes for 15 years), and prior chest radiation for esophageal
cancer.
DESCRIPTION: Myocardial perfusion imaging was carried out by positron emission
tomography (PET) at resting conditions and during dipyridamole stress using rubidium-82.
PROCEDURE: There were no complications with the procedure. The patient had no angina and
no ST changes on EKG after dipyridamole. Baseline blood pressure was 126/69, heart rate 73.
FINDINGS:
Relative Myocardial Perfusion Images: The PET images show (figure 9, panel A) a medium
sized, mild severity, lateral and inferior stress-induced perfusion defect involving 20% of the left
ventricle in the distribution the Left Circumflex coronary artery (LCx).
Absolute Coronary Flow Reserve & Myocardial Perfusion: For the whole heart, absolute
myocardial perfusion (cc/min/gm) averaged 0.87 at resting conditions, 2.10 after dipyridamole
stress and coronary flow reserve (CFR) averaged 2.45 for the whole heart. Average stress
perfusion and CFR are mildly reduced diffusely through out the heart but adequate and above
ischemic thresholds.
In the mild lateral and inferior stress induced defect, absolute stress myocardial perfusion was
1.71 cc/min/gm and CFR was 1.93, both moderately reduced but well above the ischemic
threshold (no large blue or green areas in figure 9, panel B).
Other:
1) The CT scan done for attenuation of PET data shows moderate coronary calcification of all
coronary arteries.
2) Gated PET perfusion images showed normal left ventricular contraction with ejection fraction
over 70%.
CONCLUSIONS: Based on the PET scan with stress flow and coronary flow reserve well
above ischemic threshold, coronary angiography is not indicated. (However, coronary angiogram
on a research protocol was done confirming PET findings with an FFR of 0.85 and no indication
for revascularization).
27
Supplement Figure 2. Case 3
28
Case 3
HISTORY: 64 year-old male with known, severe CAD (s/p PCI of the LAD in 1990 then of the
ramus in 2000, with invasive angiogram in 2009 showing an occluded ramus and LCx with welldeveloped collaterals) with stable warm-up angina for 20 years. Recent return of mild angina
after suboptimal compliance with his treatment regimen.
DESCRIPTION: Myocardial perfusion imaging was carried out by positron emission
tomography (PET) at resting conditions and during dipyridamole stress using rubidium-82.
PROCEDURE: There were no complications with the procedure. The patient had no angina
with no ST changes on EKG after dipyridamole. Baseline resting blood pressure was 118/57 and
heart rate 40.
FINDINGS:
Relative Myocardial Perfusion Images: The PET images show (figure 10, panel A) a medium
sized, moderate severity, lateral stress-induced perfusion defect in a ramus-like distribution.
Absolute Coronary Flow Reserve & Myocardial Perfusion: For the whole heart, absolute
myocardial perfusion (cc/min/gm) averaged 0.45 at resting conditions, 1.43 after dipyridamole
stress and coronary flow reserve (CFR) averaged 3.18 for the whole heart. Average maximum
absolute perfusion is substantially reduced but absolute CFR is good and well above ischemic
threshold due to low resting flow from beta blockade.
In the lateral defect, minimum stress perfusion is 0.76 (figure 10, panel B) and coronary flow
reserve is 1.76 indicating that myocardial perfusion with stress increases via collaterals by 76%
over resting levels. While absolute stress perfusion is at ischemic threshold, rest flow is low and
therefore CFR adequate with no large area with flow capacity below ischemic threshold (no large
blue or green areas on the threshold coronary flow map in figure 10, panel C).
Other:
1) The CT scan done for attenuation of PET data shows coronary stents and/or dense coronary
calcification in all coronary arteries.
2) Gated PET perfusion images showed normal left ventricular contraction with an ejection
fraction of 64%.
CONCLUSIONS: Over the past 20 years, regular exercise and optimal lifestyle and medical
therapy have eliminated walk-through angina due to beneficial effects on collateral perfusion.
With departure from these guidelines, mild angina has recurred. Therefore, the patient must
return to optimal lifestyle and medical therapy without further invasive procedures now.
29
Supplement Figure 3. Case 4.
30
Case 4
HISTORY: 60 year-old male with exertional dyspnea and traditional cardiac risk factors
(dyslipidemia, 20 pack-year tobacco, family history of premature CAD).
DESCRIPTION: Myocardial perfusion imaging was carried out by positron emission
tomography (PET) at rest and during dobutamine stress using rubidium-82.
PROCEDURE: There were no complications with the procedure. Baseline ECG showed right
bundle branch block (RBBB). The patient had no angina with no additional ST changes after
dobutamine stress due to asthma. Baseline blood pressure was 111/63, heart rate 55. At
maximum stress, blood pressure was 112/63, heart rate 136, a normal response after dobutamine
stress.
FINDINGS:
Relative Myocardial Perfusion Images. The PET images show (figure 11, panel A) a small
sized, mild severity, basal inferior resting perfusion defect involving 1% of the left ventricle that
is larger and more severe during stress, involving 10% of the LV in the distribution of an A-V
nodal or LV Posterior extension branch of the Right Coronary Artery. In addition, there is a mild
basal anterior resting defect that is smaller with dipyridamole stress in the distribution of a small
obtuse marginal branch suggesting endothelial dysfunction.
Absolute Coronary Flow Reserve & Myocardial Perfusion: For the whole heart, absolute
myocardial perfusion (cc/min/gm) averaged 0.87 at resting conditions, 3.93 after stress and
coronary flow reserve (CFR) averaged 4.55 for the whole heart (figure 11, panel B). Average
maximum perfusion and CFR are excellent.
In the basal inferolateral stress-induced defect, absolute stress myocardial perfusion was 1.90
cc/min/gm and CFR was 2.83, both mildly reduced but well above low flow threshold causing
ischemia as shown by the coronary flow map (no large blue or green areas in figure 11, panel C).
Other: The CT scan done for attenuation of PET data shows no coronary calcification.
CONCLUSIONS: While the PET scan shows mild coronary artery disease, invasive procedures
are not indicated due to the small and mild relative perfusion defect with good coronary flow
capacity substantially above the low flow limits of ischemia.
31
Supplement Figure 4. Case 5.
32
Case 5
HISTORY: 69 year-old asymptomatic male for second opinion on recommended coronary
bypass surgery. Positive coronary calcium CT led to invasive angiogram, reported to show threevessel 90% stenoses.
DESCRIPTION: Myocardial perfusion imaging was carried out by positron emission
tomography (PET) at resting conditions and during dipyridamole stress using rubidium-82.
PROCEDURE: There were no complications with the procedure. The patient had no angina but
had 1 mm ST depression on EKG after dipyridamole stress, resolving after intravenous
aminophylline. Baseline blood pressure was 107/55 with heart rate 52.
FINDINGS:
Relative Myocardial Perfusion Images: The PET images show (figure 12, panel A) a small
size, mild severity, distal inferior stress-induced perfusion defect involving 1% of the left
ventricle in the distribution the distal Posterior Descending coronary artery or the distal LAD
wrapping around the apex.
Absolute Coronary Flow Reserve & Myocardial Perfusion: For the whole heart, absolute
myocardial perfusion (cc/min/gm) averaged 0.52 at resting conditions, 1.47 after dipyridamole
stress (figure 12, panel B) and coronary flow reserve (CFR) averaged 2.83 for the whole heart.
Average maximum perfusion and CFR are mildly reduced diffusely through out the heart but
adequate and well above ischemic thresholds.
In the small, mild, distal inferior stress induced defect, absolute coronary flow reserve is 2.02
that is moderately reduced in this small area but above the threshold causing ischemia (no large
blue or green areas in figure 12, panel C).
Other: The CT scan done for attenuation of PET data shows dense coronary calcification in the
LAD and Right coronary arteries.
CONCLUSIONS: While the PET scan shows mild diffuse CAD, revascularization is not
indicated due to absence of symptoms, absence of significant regional stress-induced perfusion
defects, and overall adequate coronary flow capacity above the low-flow limits of ischemia.
Follow-up: No clinical events over 3 years of follow-up, continued asymptomatic status, and
good coronary flow capacity by repeat PET without regional stress-induced perfusion
abnormalities.
33
Supplement Table 1. Test retest variability of common measurements in cardiology.
PET Flow variability
Sdringola et al. JACCi 2011;4:402-412 (S44), Table 5.
Flow in normal test-retest variability in 13 papers where Coefficient of Variance (CV) =
SD/mean)
Average CV = 14% for rest flow, stress flow, and CFR by PET (range 9% to 18%)
Angiogram %DS variability
Moer Int J CV Img 2003;19:457
White AJC 2001;87:40
Steigen Int J CV Img 2008;24:453
Ave SD for arbitrary mean 60%DS
Average CV = SD/mean = 11.3/60 = 17%
116
163
906
1185
#
SD method
9.3 two observers
11.5 repeat analysis
13.2 repeat analysis
11.3
LDL measurement variability
Controis JH et al. J Clin Lipidology 2011;5:264-272 (Table 4)
Eight papers, Average CV = 9.5%
EF ECHO variability
Otterstad JE, Froeland G, St John Sutton M, Holme I. Eur Heart J. 1997;18:507-13 (table 3).
Average CV = 15%
EF spect variability
Iftikar A et al JNM 2009;50:554-562 (Fig 4)
SD ± 10% EF units. For assumed EF of 60%
Average CV = 10/60 = 17%
Hedeer F et all BMC Medical Imaging 2010;10:10
SD = ±27% for average EF of 60%
Average CV = 27/60 = 45%
SPECT SSD (summed stress score) variability
Cerqueira et all JACC CV Imaging 2008;1:307-16 Figure 2 page 312
SD of test retest SSS = ± 3.5 for an estimated mean SSS of 12
SSS CV = 3.5/12 = 29%
CRP variability
Bower et al. Arch Intern Med 2012;22:1519
CV = 46%
34
Supplement Table 2. Literature review of adult, non-congenital cardiac PET with quantitative flow
First author
Krivokapich
Hutchins
Krivokapich
Camici
Czernin
Czernin
Sambuceti
Sambuceti
Mueller
Dayanikli
Beanlands
Czernin
Czernin
Neglia
Sambuceti
Czernin
Di Carli
Muzik
Weismueller
Posma
Yokoyama
Kofoed
Di Carli
Campisi
Pedrinelli
Yokoyama
Gimelli
Muzik
Country
Citation
Isotope
Normal volunteer or control subjects
USA
JACC 1989;80:1328
N-13
USA
JACC 1990;15:1032
N-13
USA
JACC 1991;18:512
N-13
Italy
JACC 1991;17:879
N-13
USA
Circulation 1993;88:62
N-13
USA
Circulation 1993;88:62
N-13
Italy
AJC 1993;72:538
N-13
Italy
Circulation 1994;90:1696
N-13
USA
AHJ 1994;128:52
N-13
USA
Circulation 1994;90:808
N-13
Canada
JACC 1995;26:1465
N-13
USA
Circulation 1995;92:197
N-13
USA
Circulation 1995;92:197
N-13
Italy
Circulation 1995;92:796
N-13
Italy
JACC 1995;26:615
N-13
USA
Circulation 1995;91:2891
N-13
USA
Circulation 1995;91:1944
N-13
USA
JACC 1996;28:757
N-13
USA
Am J Card Imaging 1996;10:154
N-13
Netherlands Heart 1996;76:358
N-13
Japan
Circulation 1996;94:3232
N-13
USA
Circulation 1997;95:600
N-13
USA
NEJM 1997;336:1209
N-13
USA
AJC 1997;80:27
N-13
Italy
J Hypertens 1997;15:667
N-13
Japan
JACC 1997;30:1472
N-13
Italy
JACC 1998;31:366
N-13
USA
JACC 1998;31:534
N-13
35
N
Rest
Stress
13
7
10
12
12
18
14
9
11
11
12
8
13
13
13
12
10
10
10
28
11
20
8
10
7
12
13
20
0.75 ± 0.43
0.88 ± 0.17
0.83 ± 0.46
1.04 ± 0.25
0.92 ± 0.25
0.76 ± 0.17
1.03 ± 0.25
0.92 ± 0.13
1.50 ± 0.74
4.17 ± 1.12
1.56 ± 0.71
2.99 ± 1.06
2.7 ± 0.6
3.0 ± 0.8
3.66 ± 0.92
3.59 ± 0.71
2.6 ± 0.4
2.64 ± 0.39
2.55 ± 0.53
2.10 ± 0.23
2.06 ± 0.35
3.78 ± 0.86
3.46 ± 0.78
2.31 ± 0.47
2.3 ± 0.5
3.40 ± 0.57
1.92 ± 0.31
0.66 ± 0.08
0.65 ± 0.13
0.71 ± 0.13
0.78 ± 0.18
1.08 ± 0.20
1.00 ± 0.20
0.62 ± 0.10
0.9 ± 0.2
0.77 ± 0.16
0.67 ± 0.17
1.06 ± 0.26
0.75 ± 0.35
0.68 ± 0.16
0.79 ± 0.06
0.68 ± 0.16
0.76 ± 0.25
0.73 ± 0.17
1.09 ± 0.2
0.67 ± 0.11
3.22 ± 1.74
2.30 ± 0.32
2.94 ± 0.12
2.04 ± 0.30
1.98 ± 0.62
2.62 ± 0.12
3.57 ± 1.0
2.85 ± 0.49
CFR
4.8 ± 1.3
2.2 ± 0.7
3.0 ± 0.70
4.1 ± 0.9
4.27 ± 0.52
3.92 ± 0.55
3.05 ± 0.61
2.82 ± 1.07
3.82 ± 0.71
2.6 ± 0.7
4.6 ± 0.9
3.02 ± 0.94
2.8 ± 1.0
4.22 ± 1.42
3.45 ± 1.03
3.86 ± 0.35
3.16 ± 0.85
3.8 ± 1.0
3.35 ± 1.03
4.28 ± 0.65
Stevens
van Veldhuisen
Bengel
Giorgetti
Buus
Shikama
van den Heuvel
Preumont
Fujiwara
Fujiwara
Yokoyama
van den Heuvel
Jenni
Yonekura
Ibrahim
Cecchi
Olsen
Joerg-Ciopor
Pop-Busui
Schindler
Graf
USA
Netherlands
Germany
Italy
Denmark
Japan
Netherlands
Belgium
Japan
Japan
Japan
Netherlands
Switzerland
Japan
Germany
Italy
Denmark
Switzerland
USA
USA
Austria
Schindler
Alexanderson
Fritz-Hansen
Gerber
USA
Mexico
Denmark
Belgium
Lebech
Alexanderson
Denmark
Mexico
Teragawa
Japan
JACC 1998;31:1575
J Cardiovasc Pharmacol 1998;32:S46
JACC 1998;32:1955
JNC 1999;6:11
AJC 1999;83:149
AJC 1999;84:434
JACC 2000;35:19
J Heart Lung Transplant 2000;19:538
EHJ 2001;22:479
EHJ 2001;22:479
JNC 2001;8:445
Int J Cardiovasc Imaging 2001;17:353
JACC 2002;39:450
JNC 2002;9:62
JACC 2002;39:864
NEJM 2003;349:1027
J Hum Hypertens 2004;18:445
J Thorac Cardiovasc Surg 2004;128:163
JACC 2004;44:2368
Eur J Nucl Med Mol Imaging
2006;33:1140
JNM 2007;48:175
Eur J Nucl Med Mol Imaging
2007;34:1178
JNC 2007;14:566
JMRI 2008;27:818
JNC 2008;15:363
Eur J Nucl Med Mol Imaging
2008;35:2049
Mol Imaging Biol 2009;11:1
Eur J Nucl Med Mol Imaging
2010;37:368
36
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
13
12
10
10
15
8
22
7
8
11
16
10
14
15
14
12
11
15
10
0.69 ± 0.08
2.73 ± 0.26
0.77 ± 0.06
1.03 ± 0.23
0.80 ± 0.03
0.66 ± 0.06
1.02 ± 0.16
0.72 ± 0.06
0.61 ± 0.06
0.75 ± 0.14
0.79 ± 0.30
3.40 ± 0.57
3.78 ± 0.64
2.31 ± 0.12
0.78 ± 0.25
3.18 ± 1.23
0.8 ± 0.2
1.00 ± 0.23
0.72 ± 0.15
0.72 ± 0.20
0.69 ± 0.09
2.9 ± 0.8
2.71 ± 0.94
2.3 ± 0.5
3.04 ± 1.00
2.75 ± 0.26
N-13
N-13
43
10
0.65 ± 0.14
0.81 ± 0.23
2.00 ± 0.64
3.41 ± 0.94
N-13
N-13
N-13
N-13
20
18
10
6
0.64 ± 0.15
1.85 ± 0.57
0.71 ± 0.16
0.71 ± 0.18
2.03 ± 0.67
N-13
N-13
14
17
0.75 ± 0.03
0.57 ± 0.15
2.3 ± 0.3
1.81 ± 0.36
3.0 ± 0.3
3.27 ± 0.72
N-13
14
0.86 ± 0.21
2.78 ± 0.65
3.38 ± 0.95
2.80 ± 1.04
2.66 ± 0.41
2.09 ± 0.23
1.89 ± 0.42
2.82 ± 1.48
2.7 ± 0.04
4.6 ± 0.9
2.93 ± 0.17
2.71 ± 0.10
3.49 ± 0.58
2.58 ± 0.71
3.54 ± 1.11
2.62 ± 0.5
4.21 ± 0.86
3.47 ± 1.25
3.9 ± 1.2
2.7 ± 0.9
3.2 ± 1.0
3.87 ± 0.92
4.43 ± 0.77
3.27 ± 0.72
Valenta
Vincenti
Alexanderson
Alexanderson
Scholtens
Ishida
Traub-Weidinger
Alexanderson
Iida
Bergmann
Geltman
Rechavia
Senneff
McFalls
Rosen
Uren
Radvan
Marinho
Annane
Pitkaenen
Pitkaenen
Bednarcyzk
Pitkaenen
Laine
Gnecchi-Ruscone
Gnecchi-Ruscone
Pagano
Iida
Laine
Kaufmann
Sakuma
Switzerland
Switzerland
Mexico
Mexico
Netherlands
Japan
Austria
Mexico
Japan
USA
USA
England
USA
USA
England
England
England
England
France
Finland
Finland
USA
Finland
Finland
England
England
England
Japan
Finland
England
Japan
JNC 2010;17:1023
Nuklearmedizin 2010;49:173
JNC 2010;17:1015
JNM 2010;51:1927
JNC 2011;18:238
Int J Cardiol 2012;155:442
Thyroid 2012;22:245
JNC 2012;19:979
Circulation 1988;78:104
JACC 1989;14:639
JACC 1990;16:586
JACC 1992;19:100
AJC 1993;71:333
EHJ 1993;14:336
Circulation 1994;90:50
NEJM 1994;330:1782
JASE 1995;8:864
Circulation 1996;93:737
Circulation 1996;94:973
JACC 1996;28:1705
AJC 1997;79:1690
J Cardiovasc Pharmacol 1997;30:731
Diabetes 1998;47:248
JACC 1998;32:147
Muscle Nerve 1999;22:1549
Muscle Nerve 1999;22:1549
Heart 2000;83:456
Eur J Nucl Med 2000;27:192
J Clin Endocrinol Metab 2000;85:1868
Circulation 2000;102:1233
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
26
10
17
16
13
6
8
21
7
11
16
12
26
8
20
21
18
25
6
20
10
4
12
19
7
12
21
53
16
8
0.71 ± 0.13
2.29 ± 0.51
2.28 ± 0.47
0.73 ± 0.27
0.70 ± 0.16
2.96 ± 1.18
1.85 ± 0.48
1.07 ± 0.31
0.83 ± 0.26
0.95 ± 0.09
0.90 ± 0.22
1.25 ± 0.28
0.85 ± 0.13
1.17 ± 0.33
0.86 ± 0.10
1.00 ± 0.22
1.13 ± 0.26
4.79 ± 1.16
3.34 ± 0.52
AJR 2000;175:1029
O-15
10
0.64 ± 0.19
37
3.55 ± 1.15
4.62 ± 1.58
3.40 ± 1.09
3.60 ± 1.41
3.58 ± 0.89
3.00 ± 1.00
3.37 ± 1.25
3.28 ± 0.70
3.24 ± 0.81
3.15 ± 0.48
2.91 ± 0.78
3.36 ± 0.78
4.66 ± 1.38
3.8 ± 1.1
3.97 ± 0.89
3.3 ± 1.5
3.06 ± 1.08
3.7 ± 1.2
1.02 ± 0.25
0.83 ± 0.13
0.78 ± 0.11
1.13 ± 0.14
0.88 ± 0.25
0.80 ± 0.22
0.80 ± 0.32
0.97 ± 0.33
1.02 ± 0.23
0.93 ± 0.34
0.76 ± 0.19
0.90 ± 0.22
4.49 ± 1.27
4.71 ± 1.21
4.45 ± 1.37
3.80 ± 1.44
3.66 ± 0.84
3.90 ± 0.77
3.1 ± 1.3
3.40 ± 1.73
3.38 ± 0.97
3.99 ± 0.82
1.61 ±
0.66
4.00 ± 0.67
5.4 ± 1.5
6.10 ± 1.64
5.31 ± 1.86
4.99 ± 2.5
4.67 ± 1.16
4.04 ± 0.62
3.2 ± 1.6
3.82 ± 2.12
4.6 ± 1.2
4.55 ± 0.84
2.52 ± 0.84
Tadamura
Pagano
Saraste
Koskenvuo
Chareonthaitawee
Raitakari
Iwado
Akinboboye
Kates
Soto
Soto
Stolen
Laine
Akinboboye
Sundell
Kaufmann
Kaufmann
Kaufmann
Kaufmann
Tansley
Wyss
Tsukamoto
Kalliokoski
Elliott
Namdar
Dijkmans
Paerkkae
Naya
Laaksonen
Japan
England
Finland
Finland
USA
Finland
JACC 2001;37:130
Heart 2001;85:208
Clin Physiol 2001;21:114
J Magn Reson Imaging 2001;13:361
Cardiovasc Res 2001;50:151
Atherosclerosis 2001;156:469
Eur J Nucl Med Mol Imaging
Japan
2002;29:984
USA
JACC 2002;40:703
USA
JACC 2003;41:293
USA
AJP Heart Circ Physiol 2003;285:H2158
USA
AJP Heart Circ Physiol 2003;285:H2158
Finland
AJC 2004;93:64
Finland
Heart 2004;90:270
USA
Am J Hypertens 2004;17:433
Finland
Diabetologia 2004;47:725
England
Circulation 2004;110:1431
England
Circulation 2004;110:1431
England
Circulation 2004;110:1431
England
Circulation 2004;110:1431
England
J Heart Lung Transplant 2004;23:1283
Eur J Nucl Med Mol Imaging
Switzerland 2005;32:84
Japan
Circ J 2005;69:188
Finland
J Inherit Metab Dis 2005;28:563
England
Heart 2006;92:357
Switzerland JACC 2006;47:405
Netherlands JASE 2006;19:285
Finland
Magn Reson Med 2006;55:772
Japan
Circ J 2007;71:348
AJP Integr Comp Physiol
Finland
2007;293:R837
38
O-15
O-15
O-15
O-15
O-15
O-15
20
21
10
12
169
55
0.67 ± 0.16
0.99 ± 0.21
0.67 ± 0.15
0.65 ± 0.20
0.99 ± 0.23
0.81 ± 0.17
4.33 ± 1.23
3.1 ± 1.3
1.66 ± 0.62
1.78 ± 0.72
3.54 ± 1.01
3.49 ± 1.42
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
12
8
17
14
16
13
12
10
12
8
9
12
13
11
0.92 ± 0.14
1 ± 0.2
1.0 ± 0.2
0.96 ± 0.28
1.05 ± 0.18
1.0 ± 0.21
3.69 ± 0.76
3.9 ± 1
1 ± 0.3
0.88 ± 0.25
0.81 ± 0.08
0.78 ± 0.12
0.89 ± 0.11
0.88 ± 0.13
1.09 ± 0.22
4 ± 0.8
4.5 ± 1.4
3.31 ± 0.87
3.42 ± 0.74
3.26 ± 0.62
3.40 ± 0.94
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
10
7
30
24
10
16
18
10
1.33 ± 0.42
4.52 ± 1.10
0.92 ± 0.26
0.83 ± 0.18
3.44 ± 0.78
2.51 ± 0.58
4.37 ± 0.84
3.76 ± 1.21
3.49 ± 0.71
O-15
7
0.79 ± 0.19
4.11 ± 2.08
1.17 ± 0.25
1.05 ± 0.36
2.09 ± 0.83
2.06 ± 0.49
3.01 ± 1.2
3.2 ± 1.5
2.52 ± 0.84
2.79 ± 0.97
3.75 ± 1.24
4.3 ± 1.6
4.03 ± 0.68
3.08 ± 1.35
4.25 ± 0.30
4 ± 0.4
5.3 ± 1.9
2.93 ± 0.79
2.91 ± 0.77
2.79 ± 0.76
2.65 ± 0.67
3.56 ± 1.42
3.82 ± 0.82
4.4 ± 1.6
3.03 ± 0.85
2.53 ± 0.69
4.32 ± 1.78
4.25 ± 0.69
Laaksonen
Ohba
Range
Range
Kaufmann
Kaehoenen
Kaehoenen
Kaehoenen
Ilveskoski
Ilveskoski
Ilveskoski
Ilveskoski
Range
Koivuviita
Namdar
Recio-Mayoral
Koepfli
Schaefer
Paul
Finland
Japan
Germany
Germany
England
Finland
Finland
Finland
Finland
Finland
Finland
Finland
Germany
Finland
Switzerland
England
Switzerland
Germany
Germany
Lortie
El Fakhri
Sdringola
Dunet
Canada
USA
USA
Switzerland
Prior
Johnson
Johnson
Johnson
Fukushima
Switzerland
USA
USA
USA
USA
AJP Integr Comp Physiol
2007;293:R837
Circ J 2007;71:884
EHJ 2007;28:2223
EHJ 2007;28:2223
AJP Heart Circ Physiol 2007;293:H2178
Scand J Clin Lab Invest 2007;67:596
Scand J Clin Lab Invest 2007;67:596
Scand J Clin Lab Invest 2007;67:596
Scand J Clin Lab Invest 2007;67:723
Scand J Clin Lab Invest 2007;67:723
Scand J Clin Lab Invest 2007;67:723
Scand J Clin Lab Invest 2007;67:723
JNM 2009;50:390
Nephrol Dial Transplant 2009;24:2773
PLoS One 2009;4:e5665
EHJ 2009;30:1837
EHJ 2009;30:2993
Anesthesiology 2011;114:1373
Eur J Nucl Med Mol Imaging
2012;39:416
Eur J Nucl Med Mol Imaging
2007;34:1765
JNM 2009;50:1062
JACC Cardiovasc Imaging 2011;4:402
Circ J 2012;76:160
Eur J Nucl Med Mol Imaging
2012;39:1037
JACC Cardiovasc Imaging 2012;5:430
JACC Cardiovasc Imaging 2012;5:430
JACC Cardiovasc Imaging 2012;5:430
JNM 2012;53:887
39
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
7
10
9
13
10
25
42
61
4
9
9
18
22
22
15
25
10
6
0.72 ± 0.20
0.79 ± 0.29
1.14 ± 0.18
1.14 ± 0.22
0.88 ± 0.13
0.86 ± 0.27
0.78 ± 0.17
0.82 ± 0.16
0.84 ± 0.18
0.94 ± 0.37
0.75 ± 0.13
0.83 ± 0.19
0.87 ± 0.16
0.87 ± 0.14
1.21 ± 0.32
1.15 ± 0.24
1.15 ± 0.23
1.03 ± 0.09
3.46 ± 1.31
3.70 ± 0.67
3.92 ± 0.93
3.33 ± 0.78
3.48 ± 0.99
4.67 ± 2.01
4.15 ± 1.77
4.07 ± 1.7
3.06 ± 0.45
3.53 ± 1.12
3.38 ± 0.83
3.20 ± 0.76
3.57 ± 0.88
2.47 ± 0.85
2.26 ± 0.56
4.11 ± 0.84
2.21 ± 0.65
O-15
20
1.12 ± 0.20
3.68 ± 0.84
3.39 ± 0.93
Rb-82
Rb-82
Rb-82
Rb-82
14
20
125
18
0.69 ± 0.14
0.83 ± 0.15
0.70 ± 0.15
0.88 ± 0.26
2.83 ± 0.81
1.72 ± 0.41
2.75 ± 0.58
2.57 ± 0.60
4.25 ± 1.37
2.00 ± 0.67
4.03 ± 0.84
3.0 ± 0.6
Rb-82
Rb-82
Rb-82
Rb-82
Rb-82
22
241
258
610
42
1.03 ± 0.42
0.70 ± 0.15
0.75 ± 0.24
0.72 ± 0.20
0.8 ± 0.2
3.82 ± 1.21
2.71 ± 0.58
2.78 ± 0.59
1.99 ± 0.34
2.3 ± 0.8
3.88 ± 0.91
4.02 ± 0.85
3.94 ± 0.77
2.91 ± 0.51
5.16 ± 1.64
3.51 ± 0.94
3.24 ± 1.03
4.00 ± 1.10
3.79 ± 1.28
4.04 ± 1.47
4.73 ± 1.88
4.02 ± 1.27
3.37 ± 0.97
2.93 ± 1.05
1.94 ± 0.61
3.81 ± 1.07
2.01 ± 0.72
Weighted average
Parodi
Dayanikli
Czernin
Yokoyama
Pedrinelli
Yokoyama
Gimelli
Stevens
Stevens
Campisi
Campisi
Baller
Masuda
Madsen
Madsen
Yokoyama
Masuda
Yonekura
Italy
USA
USA
Japan
Italy
Japan
Italy
USA
USA
USA
USA
Germany
Japan
Denmark
Denmark
Japan
Japan
Japan
Pirich
Olsen
Duvernoy
Pop-Busui
Pop-Busui
Mishra
Mishra
Germany
Denmark
USA
USA
USA
USA
USA
All
N-13
O-15
Rb-82
Patients with risk factors only
Drugs 1992;44 Suppl 1:48
N-13
Circulation 1994;90:808
N-13
Circulation 1995;91:2891
N-13
Circulation 1996;94:3232
N-13
J Hypertens 1997;15:667
N-13
JACC 1997;30:1472
N-13
JACC 1998;31:366
N-13
JACC 1998;31:1575
N-13
JACC 1998;31:1575
N-13
Circulation 1998;98:119
N-13
Circulation 1998;98:119
N-13
Circulation 1999;99:2871
N-13
Ann Nucl Med 2000;14:353
N-13
Cardiology 2000;94:91
N-13
Cardiology 2000;94:91
N-13
JNC 2001;8:445
N-13
EHJ 2001;22:1451
N-13
JNC 2002;9:62
N-13
Eur J Nucl Med Mol Imaging
2004;31:663
N-13
J Hum Hypertens 2004;18:445
N-13
J Clin Endocrinol Metab 2004;89:2783
N-13
JACC 2004;44:2368
N-13
JACC 2004;44:2368
N-13
JACC 2005;45:553
N-13
JACC 2005;45:553
N-13
40
3,484
849
1,285
1,350
0.82 ± 0.06
0.79 ± 0.06
0.94 ± 0.07
0.73 ± 0.04
2.86 ± 1.29
2.66 ± 0.90
3.54 ± 1.78
2.39 ± 0.44
27
16
12
11
25
25
50
7
7
16
17
23
12
15
15
16
11
13
0.97 ± 0.25
0.76 ± 0.18
0.70 ± 0.17
0.81 ± 0.31
0.81 ± 0.17
0.74 ± 0.24
0.89 ± 0.22
0.79 ± 0.23
1.09 ± 0.29
0.68 ± 0.13
0.68 ± 0.14
0.87 ± 0.20
2.35 ± 0.95
2.17 ± 0.56
2.23 ± 0.35
1.29 ± 0.19
2.06 ± 0.77
1.84 ± 0.99
2.18 ± 0.75
3.24 ± 1.35
2.04 ± 0.73
1.92 ± 0.38
2.04 ± 0.47
1.82 ± 0.36
0.87 ± 0.20
0.79 ± 0.11
0.78 ± 0.12
0.71 ± 0.26
2.23 ± 0.78
2.42 ± 0.65
1.78 ± 0.51
1.26 ± 0.65
21
21
15
12
16
109
111
0.71 ± 0.16
0.88 ± 0.12
1.1 ± 0.2
0.85 ± 0.20
0.91 ± 0.13
0.80 ± 0.23
0.80 ± 0.26
2.18 ± 0.54
1.57 ± 0.24
2.6 ± 0.9
2.67 ± 1.26
2.04 ± 0.42
1.98 ± 0.59
2.06 ± 0.67
3.55 ± 1.36
3.42 ± 1.02
3.77 ± 2.27
3.44 ± 0.80
2.93 ± 0.86
3.36 ± 0.83
1.59 ± 0.41
2.77 ± 0.85
2.51 ± 0.88
2.2 ± 0.6
1.70 ± 0.64
2.60 ± 0.97
3.15 ± 1.02
2.27 ± 0.63
1.75 ± 0.24
2.50 ± 0.91
3.20 ± 0.77
1.91 ± 0.35
2.62 ± 0.98
2.75 ± 1.02
Mishra
McMahon
Schindler
Schindler
Schindler
Wielepp
Duvernoy
Schindler
Alexanderson
Lebech
Lebech
Motivala
Motivala
Motivala
Alexanderson
Kjaer
Vaccarino
Vaccarino
Vaccarino
Teragawa
Valenta
Vincenti
Kristoffersen
Alexanderson
Charytan
Charytan
Charytan
USA
USA
USA
USA
USA
JACC 2005;45:553
Diabetes Care 2005;28:1145
JACC 2005;45:1505
JACC 2005;45:1505
JACC 2005;45:1505
Eur J Nucl Med Mol Imaging
Germany 2005;32:1371
USA
J Womens Health (Larchmt) 2006;15:45
Eur J Nucl Med Mol Imaging
USA
2006;33:1140
Mexico
JNC 2007;14:566
Eur J Nucl Med Mol Imaging
Denmark 2008;35:2049
Eur J Nucl Med Mol Imaging
Denmark 2008;35:2049
USA
JNC 2008;15:510
USA
JNC 2008;15:510
USA
JNC 2008;15:510
Mexico
Mol Imaging Biol 2009;11:1
Denmark Diabetes Res Clin Pract 2009;84:34
USA
Arch Intern Med 2009;169:1668
USA
Arch Intern Med 2009;169:1668
USA
Arch Intern Med 2009;169:1668
Eur J Nucl Med Mol Imaging
Japan
2010;37:368
Switzerland JNC 2010;17:1023
Switzerland Nuklearmedizin 2010;49:173
Denmark Nucl Med Commun 2010;31:874
Mexico
JNC 2010;17:1015
USA
Circ Cardiovasc Imaging 2010;3:663
USA
Circ Cardiovasc Imaging 2010;3:663
USA
Circ Cardiovasc Imaging 2010;3:663
41
N-13
N-13
N-13
N-13
N-13
128
8
18
22
32
0.76 ± 0.25
0.90 ± 0.30
0.84 ± 0.15
0.70 ± 0.18
0.71 ± 0.21
1.84 ± 0.62
2.02 ± 0.60
2.61 ± 0.91
2.17 ± 0.67
N-13
N-13
26
16
0.9 ± 0.3
1.04 ± 0.24
2.4 ± 0.8
2.70 ± 0.94
3.0 ± 1.1
2.81 ± 1.34
N-13
N-13
59
18
0.69 ± 0.14
1.72 ± 0.71
N-13
12
0.86 ± 0.04
2.8 ± 0.4
3.2 ± 0.3
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
13
18
21
21
22
14
53
53
366
0.80 ± 0.04
1.04 ± 0.22
0.86 ± 0.18
1.03 ± 0.34
0.53 ± 0.18
0.89 ± 0.05
0.63 ± 0.11
0.67 ± 0.13
0.68 ± 0.13
2.5 ± 0.4
2.49 ± 0.78
2.71 ± 0.65
2.69 ± 0.63
1.41 ± 0.52
2.01 ± 0.14
1.66 ± 0.53
1.54 ± 0.36
1.67 ± 0.54
3.2 ± 0.3
2.50 ± 0.94
3.25 ± 0.91
2.88 ± 1.17
2.80 ± 1.40
2.36 ± 0.24
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
13
26
16
12
14
53
158
224
0.95 ± 0.16
0.89 ± 0.21
1.97 ± 0.83
1.83 ± 0.49
1.34 ± 0.26
2.50 ± 0.25
2.72 ± 1.09
1.81 ± 0.61
1.95 ± 0.79
1.88 ± 0.66
2.13 ± 0.99
2.14 ± 0.73
1.48 ± 0.39
3.11 ± 0.32
2.79 ± 0.94
2.32 ± 0.88
2.82 ± 1.26
2.48 ± 0.94
2.76 ± 1.04
0.98 ± 0.26
0.81 ± 0.23
0.74 ± 0.24
0.80 ± 0.24
Alexanderson
Di Carli
Liga
Traub-Weidinger
Alexanderson
Annane
Pitkaenen
Choudhury
Pitkaenen
Pitkaenen
Pitkaenen
Laine
Kaufmann
Kaufmann
Kaufmann
Iwado
Akinboboye
Kates
Akinboboye
Sundell
Sundell
Wyss
Tsukamoto
Srinivasan
Srinivasan
Kaufmann
Fan
Schaefer
Naya
Range
Mexico
USA
Italy
Austria
Mexico
France
Finland
England
Finland
Finland
Finland
Finland
England
England
England
JNM 2010;51:1927
JNM 2011;52:1369
JNM 2011;52:1704
Thyroid 2012;22:245
JNC 2012;19:979
Circulation 1996;94:973
JACC 1996;28:1705
EHJ 1997;18:108
AJC 1997;79:1690
AJC 1997;79:1690
Diabetes 1998;47:248
JACC 1998;32:147
JACC 2000;36:103
JACC 2000;36:103
Circulation 2000;102:1233
Eur J Nucl Med Mol Imaging
Japan
2002;29:984
USA
JACC 2002;40:703
USA
JACC 2003;41:293
USA
Am J Hypertens 2004;17:433
Finland
Diabetologia 2004;47:725
Finland
Diabetologia 2004;47:725
Eur J Nucl Med Mol Imaging
Switzerland 2005;32:84
Japan
Circ J 2005;69:188
USA
JACC 2005;46:42
USA
JACC 2005;46:42
Switzerland JNM 2005;46:1272
Finland
Atherosclerosis 2006;188:391
Germany Int J Clin Pharmacol Ther 2006;44:319
Japan
Circ J 2007;71:348
Germany EHJ 2007;28:2223
42
N-13
N-13
N-13
N-13
N-13
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
16
462
63
10
19
10
15
16
7
14
12
16
19
61
11
0.71 ± 0.15
0.78 ± 0.25
2.34 ± 0.39
1.88 ± 0.68
1.09 ± 0.32
0.92 ± 0.19
2.87 ± 0.93
2.07 ± 0.71
0.92 ± 0.24
1.17 ± 0.40
0.88 ± 0.17
0.85 ± 0.11
0.84 ± 0.18
0.83 ± 0.21
0.84 ± 0.14
0.87 ± 0.14
0.90 ± 0.12
3.19 ± 1.59
2.27 ± 0.60
3.16 ± 2.02
4.20 ± 1.38
3.17 ± 1.57
2.85 ± 1.20
3.30 ± 0.86
3.63 ± 1.02
3.38 ± 0.33
2.39 ± 0.39
3.5 ± 1.6
2.06 ± 0.62
3.41 ± 1.64
4.91 ± 1.46
3.76 ± 1.69
3.46 ± 1.23
3.95 ± 0.93
4.23 ± 1.29
3.79 ± 0.60
O-15
O-15
O-15
O-15
O-15
O-15
18
14
19
7
9
12
0.86 ± 0.11
1.1 ± 0.4
1.1 ± 0.3
1 ± 0.3
0.82 ± 0.13
0.96 ± 0.23
3.20 ± 1.12
2.8 ± 0.9
3.78 ± 1.83
2.8 ± 0.8
3 ± 0.9
2.9 ± 0.9
4.0 ± 1.3
3 ± 0.3
3.6 ± 1.0
4.2 ± 1.4
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
9
22
10
10
10
23
24
30
25
1.46 ± 0.18
4.86 ± 1.18
1.19 ± 0.19
1.20 ± 0.24
1.59 ± 0.70
0.83 ± 0.15
0.92 ± 0.13
0.98 ± 0.19
0.95 ± 0.19
3.70 ± 0.48
3.05 ± 0.26
3.93 ± 1.87
4.14 ± 1.63
2.12 ± 0.92
3.14 ± 0.40
2.69 ± 0.41
2.58 ± 1.11
5.11 ± 2.23
2.77 ± 0.82
2.07 ± 0.80
2.95 ± 1.06
2.51 ± 1.04
2.6 ± 1.0
2.0 ± 0.5
2.6 ± 0.73
Naoumova
Naoumova
Koivuviita
Koivuviita
Koivuviita
Recio-Mayoral
Koepfli
Koepfli
Lubberink
Danad
Danad
El Fakhri
Naya
Fukushima
England
England
Finland
Finland
Finland
England
Switzerland
Switzerland
Netherlands
JACC 2007;50:2051
JACC 2007;50:2051
Nephrol Dial Transplant 2009;24:2773
Nephrol Dial Transplant 2009;24:2773
Nephrol Dial Transplant 2009;24:2773
EHJ 2009;30:1837
EHJ 2009;30:2993
EHJ 2009;30:2993
JNM 2010;51:575
Eur J Nucl Med Mol Imaging
Netherlands 2012;39:102
Netherlands JNC 2012;19:256
USA
JNM 2005;46:1264
USA
JACC 2011;58:1807
USA
JNM 2012;53:887
Weighted average
Vanoverschelde
Sambuceti
Vanoverschelde
Sambuceti
Gewirtz
Picano
Marzullo
Sambuceti
Di Carli
Hautvast
Skopicki
Belgium
Italy
Belgium
Italy
USA
Italy
Italy
Italy
USA
Netherlands
USA
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
12
14
5
6
11
25
10
10
25
1.05 ± 0.21
1.11 ± 0.20
1.18 ± 0.18
1.27 ± 0.19
1.25 ± 0.32
1.25 ± 0.27
1.82 ± 0.39
0.94 ± 0.16
1.00 ± 0.45
2.70 ± 1.03
2.57 ± 0.97
3.30 ± 1.28
2.61 ± 1.04
3.17 ± 1.21
2.94 ± 0.83
4.70 ± 1.15
3.40 ± 1.22
2.35 ± 0.95
2.66 ± 1.11
2.38 ± 1.05
3.21 ± 1.31
2.12 ± 0.82
2.67 ± 1.06
2.44 ± 0.78
2.63 ± 0.55
3.75 ± 1.36
2.56 ± 1.12
O-15
O-15
Rb-82
Rb-82
Rb-82
All
N-13
O-15
Rb-82
128
173
8
73
40
3,592
2,629
842
121
1.02 ± 0.32
1.05 ± 0.34
0.80 ± 0.18
1.01 ± 0.20
1.2 ± 0.6
0.85 ± 0.08
0.78 ± 0.05
1.02 ± 0.10
1.06 ± 0.16
3.44 ± 1.20
3.40 ± 1.19
1.48 ± 0.37
3.57 ± 1.37
3.45 ± 1.32
2.03 ± 0.31
2.33 ± 0.60
13
32
8
24
26
18
14
19
18
9
27
0.49 ± 0.11
0.76 ± 0.21
0.88 ± 0.17
0.68 ± 0.14
0.27 ± 0.17
0.73 ± 0.20
0.39 ± 0.27
0.61 ± 0.11
0.9 ± 0.2
1.15 ± 0.29
0.75 ± 0.34
Established coronary artery disease
Circulation 1992;85:9
N-13
AJC 1993;72:538
N-13
Circulation 1993;87:1513
N-13
Circulation 1994;90:1696
N-13
JACC 1994;23:851
N-13
Circulation 1994;89:753
N-13
JACC 1995;26:342
N-13
JACC 1995;26:615
N-13
Circulation 1995;91:1944
N-13
AJC 1996;77:462
N-13
Circulation 1996;94:643
N-13
43
2.3 ± 0.9
2.25 ± 1.07
1.92 ± 0.50
3.29 ± 1.52
2.16 ± 0.79
1.52 ± 0.65
1.12 ± 0.44
1.18 ± 0.34
1.43 ± 0.61
0.49 ± 0.18
0.93 ± 0.37
2.3 ± 0.6
1.58 ± 0.30
1.06 ± 0.72
2.80 ± 1.39
2.58 ± 0.99
3.36 ± 2.00
2.30 ± 0.34
1.4 ± 0.6
1.98 ± 0.71
1.3 ± 0.5
2.4 ± 0.4
1.46 ± 0.43
Krivokapich
Campisi
Neumann
Mellwig
Giorgetti
Giorgetti
Kitsiou
Zervos
Kosa
Gerber
Akinboboye
Akinboboye
Tamura
Fujiwara
Fujiwara
Mesotten
Yonekura
van den Heuvel
van den Heuvel
Sonoda
Tawakol
Tawakol
Graf
Geshi
Higuchi
Geshi
Gerber
Carpeggiani
Valenta
Scholtens
Amaya
USA
USA
Germany
Germany
Italy
Italy
USA
USA
Germany
Belgium
USA
USA
Japan
Japan
Japan
Belgium
Japan
Netherlands
Netherlands
Japan
USA
USA
Austria
Japan
Germany
Japan
Belgium
JACC 1996;28:565
AJC 1997;80:27
JACC 1997;30:1270
Atherosclerosis 1998;139:173
JNC 1999;6:11
JNC 1999;6:11
JACC 1999;33:678
Coron Artery Dis 1999;10:185
JACC 1999;34:1036
JACC 1999;34:1939
JACC 2001;37:109
JACC 2001;37:109
Jpn Circ J 2001;65:23
EHJ 2001;22:479
EHJ 2001;22:479
Eur J Nucl Med 2001;28:466
JNC 2002;9:62
Cardiovasc Res 2002;55:97
Cardiovasc Res 2002;55:97
Int J Cardiol 2004;93:131
JACC 2005;45:1580
Coron Artery Dis 2005;16:443
Nuklearmedizin 2006;45:248
Int J Cardiol 2008;126:366
Microcirculation 2007;14:805
Int J Cardiol 2008;126:366
JNC 2008;15:363
J Cardiovasc Med (Hagerstown)
Italy
2008;9:893
Switzerland JNC 2010;17:1023
Netherlands JNC 2011;18:238
Japan
Int J Cardiol 2012;159:144
44
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
15
15
19
9
7
7
26
14
14
14
8
10
21
5
6
19
18
11
12
23
14
14
12
17
12
17
22
0.93 ± 0.20
0.65 ± 0.14
2.16 ± 0.52
1.61 ± 0.33
0.93 ± 0.22
0.43 ± 0.13
0.51 ± 0.15
0.64 ± 0.24
0.91 ± 0.29
0.76 ± 0.19
0.85 ± 0.29
0.90 ± 0.18
0.87 ± 0.19
0.86 ± 0.24
0.82 ± 0.24
0.78 ± 0.17
0.75 ± 0.25
1.73 ± 0.63
0.88 ± 0.37
0.55 ± 0.17
2.54 ± 0.51
2.78 ± 1.63
1.91 ± 0.68
2.03 ± 0.40
1.14 ± 0.44
3.18 ± 0.85
2.06 ± 0.60
2.74 ± 0.64
0.68 ± 0.27
1.38 ± 0.16
1.17 ± 0.46
0.83 ± 0.21
1.14 ± 0.37
1.39 ± 0.49
1.07 ± 0.36
1.45 ± 0.34
1.07 ± 0.19
1.01 ± 0.18
0.97 ± 0.33
0.68 ± 0.24
0.76 ± 0.48
1.64 ± 0.22
1.72 ± 0.27
1.47 ± 0.54
1.18 ± 0.32
N-13
N-13
N-13
N-13
15
28
15
33
1.02 ± 0.34
0.99 ± 0.22
0.60 ± 0.16
0.62 ± 0.22
0.62 ± 0.25
0.67 ± 0.20
0.62 ± 0.25
0.70 ± 0.24
1.83 ± 0.61
1.5 ± 0.5
1.7 ± 0.5
1.60 ± 0.57
2.61 ± 0.93
1.19 ± 0.63
1.55 ± 0.39
1.19 ± 0.63
2.0 ± 1.3
3.00 ± 0.76
1.73 ± 0.40
2.34 ± 0.52
1.73 ± 0.40
1.58 ± 0.69
1.42 ± 0.38
1.13 ± 0.26
1.31 ± 0.59
1.54 ± 0.39
1.45 ± 0.30
1.99 ± 0.47
2.09 ± 0.57
Mannacio
Mannacio
Ishida
Ishida
Sarazawa
Sarazawa
Slart
Morton
Morton
Walsh
Rechavia
Merlet
Uren
McFalls
Uren
Severi
Miller
Marinho
Bednarcyzk
Fath-Ordoubadi
Schneider
Pagano
Rimoldi
Rimoldi
Spyrou
Pagano
Sakaguchi
Sakaguchi
Nowak
J Thorac Cardiovasc Surg
Italy
2012;143:1030
J Thorac Cardiovasc Surg
Italy
2012;143:1030
Japan
Int J Cardiol 2012;155:442
Japan
Int J Cardiol 2012;155:442
Japan
JNC 2012;19:507
Japan
JNC 2012;19:507
Eur J Nucl Med Mol Imaging
Netherlands 2012;39:1065
England
JACC 2012;60:1546
England
JACC 2012;60:1546
USA
JACC 1990;15:119
England
Eur J Nucl Med 1992;19:1044
France
JNM 1993;34:1899
England
JACC 1993;22:650
USA
EHJ 1993;14:336
England
NEJM 1994;330:1782
Italy
JACC 1995;26:1187
USA
Circulation 1996;94:2447
England
Circulation 1996;93:737
USA
J Cardiovasc Pharmacol 1997;30:731
England
Heart 1999;82:210
Germany JACC 1999;34:1005
England
Heart 2000;83:456
England
J Cardiovasc Pharmacol 2000;36:310
England
J Cardiovasc Pharmacol 2000;36:310
England
AJP Heart Circ Physiol 2000;279:H2634
England
Heart 2001;85:208
Japan
Ann Thorac Surg 2002;74:493
Japan
Ann Thorac Surg 2002;74:493
Germany JNC 2003;10:34
45
N-13
30
N-13
N-13
N-13
N-13
N-13
30
16
19
11
23
N-13
N-13
N-13
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
22
16
25
11
6
14
12
5
35
12
11
30
4
24
10
22
12
14
8
30
13
22
42
1.02 ± 0.2
0.96 ± 0.28
0.59 ± 0.22
0.57 ± 0.16
0.64 ± 0.22
0.51 ± 0.20
0.85 ± 0.26
0.77 ± 0.24
1.54 ± 0.54
0.82 ± 0.05
0.78 ± 0.27
0.96 ± 0.20
0.99 ± 0.10
1.14 ± 0.42
0.98 ± 0.26
1.3 ± 0.4
0.92 ± 0.25
1.13 ± 0.47
0.89 ± 0.24
1.02 ± 0.24
0.92 ± 0.20
1.05 ± 0.31
0.87 ± 0.12
0.92 ± 0.30
0.60 ± 0.02
2.34 ± 0.32
2.3 ± 0.2
2.01 ± 0.41
1.40 ± 0.51
1.07 ± 0.38
1.51 ± 0.54
0.86 ± 0.39
2.1 ± 0.3
2.34 ± 0.63
1.91 ± 0.43
2.39 ± 0.56
1.69 ± 0.37
1.07 ± 0.47
1.72 ± 0.66
1.24 ± 0.49
1.5 ± 0.6
2.06 ± 0.44
1.57 ± 0.31
0.98 ± 0.08
1.71 ± 0.78
1.73 ± 0.91
2.97 ± 0.94
2.10 ± 1.16
1.98 ± 0.87
2.7 ± 0.9
2.20 ± 0.52
1.80 ± 0.82
2.1 ± 0.8
2.07 ± 1.08
1.41 ± 0.17
1.26 ± 0.6
2.46 ± 0.98
1.99 ± 0.66
1.36 ± 0.28
1.31 ± 0.65
1.26 ± 0.7
1.59 ± 0.40
1.48 ± 0.66
1.90 ± 0.13
1.43 ± 0.07
Yoshinaga
Rajappan
Wyss
Pitt
Kageyama
Jagathesan
Marques
Kaufmann
Ohara
Ohara
Namdar
Gaemperli
Masi
Ling
Ling
Ling
El Fakhri
Lortie
Johnson
Prior
Japan
England
Switzerland
England
Japan
England
Netherlands
England
Japan
Japan
Switzerland
England
Italy
Canada
Canada
Canada
USA
JNC 2003;10:275
Circulation 2003;107:3170
Circulation 2003;108:1202
EHJ 2004;25:500
Eur J Nucl Med Mol Imaging 2006;33:6
J Cardiovasc Pharmacol 2006;48:110
EHJ 2007;28:2320
AJP Heart Circ Physiol 2007;293:H2178
Hypertens Res 2008;31:1307
Hypertens Res 2008;31:1307
PLoS One 2009;4:e5665
EHJ 2010;31:1722
Diabetologia 2012;55:2494
AHJ 2005;149:1137
AHJ 2005;149:1137
AHJ 2005;149:1137
JNM 2005;46:1264
Eur J Nucl Med Mol Imaging
Canada
2007;34:1765
USA
JACC Cardiovasc Imaging 2011;4:990
Eur J Nucl Med Mol Imaging
Switzerland 2012;39:1037
Weighted average
Neglia
Gerber
Weismueller
Torres
Italy
Belgium
USA
Italy
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
Rb-82
Rb-82
Rb-82
Rb-82
27
22
8
21
21
44
27
10
30
30
15
61
12
23
24
25
5
Rb-82
Rb-82
13
12
Rb-82
All
N-13
O-15
Rb-82
Subjects with cardiomyopathy
Circulation 1995;92:796
N-13
Circulation 1996;94:651
N-13
Am J Card Imaging 1996;10:154
N-13
JACC 1997;30:65
N-13
46
3.86 ± 1.24
2.02 ± 0.60
2.26 ± 0.35
1.90 ± 0.75
3.01 ± 1.38
1.65 ± 0.47
1.08 ± 0.27
2.17 ± 0.82
0.80 ± 0.22
0.93 ± 0.25
1.09 ± 0.27
0.72 ± 0.23
0.96 ± 0.36
0.90 ± 0.18
0.92 ± 0.17
0.94 ± 0.26
0.91 ± 0.19
1.57 ± 0.67
2.76 ± 1.29
1.79 ± 0.63
2.10 ± 0.92
1.86 ± 0.94
2.03 ± 0.32
1.91 ± 0.29
1.9 ± 0.41
2.26 ± 0.91
0.60 ± 0.05
2.70 ± 0.84
2.45 ± 0.78
2.44 ± 0.88
0.87 ± 0.11
2.06 ± 1.13
2.25 ± 0.20
2.08 ± 0.30
2.1 ± 0.53
2.47 ± 0.83
1.65 ± 0.27
2.09 ± 0.63
2.26 ± 1.07
2.14 ± 0.56
1.46 ± 0.06
0.91 ± 0.32
2.03 ± 0.85
0.98 ± 0.47
2.45 ± 1.29
1.77 ± 0.99
11
1,650
872
665
113
0.88 ± 0.21
0.83 ± 0.10
0.75 ± 0.09
0.94 ± 0.09
0.85 ± 0.07
2.53 ± 1.01
1.71 ± 0.71
1.46 ± 0.50
1.95 ± 0.76
2.23 ± 0.95
2.85 ± 0.86
2.02 ± 0.70
1.92 ± 0.51
2.10 ± 0.88
2.19 ± 0.82
22
39
10
17
0.80 ± 0.25
0.84 ± 0.27
0.69 ± 0.27
0.83 ± 0.22
1.91 ± 0.76
1.57 ± 0.39
1.87 ± 0.90
2.57 ± 1.15
van Veldhuisen
Shikama
Shikama
van den Heuvel
van den Heuvel
Jenni
Neglia
Neglia
Netherlands
Japan
Japan
Netherlands
Netherlands
Switzerland
Italy
Italy
Morales
van der Harst
van der Harst
Masci
Masci
Giannessi
Scholtens
Huang
Huang
Masi
Neglia
Italy
Netherlands
Netherlands
Italy
Italy
Italy
Netherlands
Taiwan
Taiwan
Italy
Italy
Bax
Stolen
Sundell
Tansley
Kalliokoski
Elliott
Ohba
Range
Range
Netherlands
Finland
Finland
England
Finland
England
Japan
Germany
Germany
Paul
Germany
J Cardiovasc Pharmacol 1998;32:S46
AJC 1999;84:434
AJC 1999;84:434
JACC 2000;35:19
Int J Cardiovasc Imaging 2001;17:353
JACC 2002;39:450
Heart 2007;93:808
Heart 2007;93:808
J Cardiovasc Med (Hagerstown)
2008;9:778
AJC 2010;105:517
AJC 2010;105:517
Circ Cardiovasc Imaging 2010;3:482
Circ Cardiovasc Imaging 2010;3:482
Metabolism 2011;60:227
JNC 2011;18:238
Ann Nucl Med 2011;25:462
Ann Nucl Med 2011;25:462
Diabetologia 2012;55:2494
JNC 2012 Aug 10 [Epub ahead of print]
Eur J Nucl Med Mol Imaging
2002;29:721
AJC 2004;93:64
JACC 2004;43:1027
J Heart Lung Transplant 2004;23:1283
J Inherit Metab Dis 2005;28:563
Heart 2006;92:357
Circ J 2007;71:884
JNM 2009;50:390
JNM 2009;50:390
Eur J Nucl Med Mol Imaging
2012;39:416
47
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
12
9
17
22
20
12
8
8
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
1.7 ± 0.08
0.58 ± 0.15
0.54 ± 0.13
1.02 ± 0.21
1.66 ± 0.36
0.86 ± 0.30
0.56 ± 0.20
0.65 ± 0.28
1.72 ± 0.75
1.16 ± 0.7
1.08 ± 0.49
26
8
8
7
11
55
16
3
8
12
81
0.69 ± 0.05
0.47 ± 0.12
0.50 ± 0.09
0.54 ± 0.12
0.50 ± 0.07
0.69 ± 0.13
0.50 ± 0.10
0.68 ± 0.15
0.77 ± 0.21
1.39 ± 0.15
0.72 ± 0.24
0.79 ± 0.43
0.87 ± 0.26
0.94 ± 0.20
1.46 ± 0.13
0.80 ± 0.37
1.81 ± 0.57
1.44 ± 0.53
0.59 ± 0.20
1.17 ± 0.62
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
O-15
34
20
10
11
15
10
23
12
18
0.86 ± 0.36
0.86 ± 0.17
0.7 ± 0.2
0.95 ± 0.29
1.73 ± 0.82
1.8 ± 1.1
0.99 ± 0.17
0.66 ± 0.20
0.82 ± 0.31
0.84 ± 0.27
1.37 ± 0.32
1.67 ± 0.73
1.32 ± 0.93
2.52 ± 1.29
2.01 ± 0.91
2.2 ± 1.4
1.49 ± 0.99
3.3 ± 1.2
1.41 ± 0.39
2.62 ± 1.08
1.68 ± 0.94
2.10 ± 1.01
O-15
10
1.19 ± 0.29
2.60 ± 0.96
2.41 ± 1.34
1.72 ± 0.21
1.71 ± 0.2
2.13 ± 0.83
2.05 ± 0.74
1.80 ± 0.84
2.12 ± 0.2
1.51 ± 0.18
1.64 ± 0.90
1.80 ± 0.63
1.83 ± 0.50
2.11 ± 0.14
1.72 ± 0.69
2.71 ± 0.73
1.96 ± 0.78
1.80 ± 0.18
2.00 ± 0.85
All
N-13
O-15
594
431
163
0.73 ± 0.07
0.69 ± 0.05
0.85 ± 0.09
1.47 ± 0.56
1.35 ± 0.36
1.86 ± 1.01
Hypertrophic cardiomyopathy
JACC 1991;17:879
N-13
AJC 1994;74:363
N-13
Heart 1996;76:358
N-13
EHJ 1997;18:1946
N-13
NEJM 2003;349:1027
N-13
J Thorac Cardiovasc Surg 2004;128:163
N-13
J Thorac Cardiovasc Surg 2004;128:163
N-13
JNM 2012;53:407
N-13
JNM 2012;53:407
N-13
JNM 2012;53:407
N-13
AJC 2012;110:1033
N-13
AJC 2012;110:1033
N-13
EHJ 1997;18:108
O-15
EHJ 1997;18:1946
O-15
Basic Res Cardiol 1999;94:49
O-15
Circ J 2007;71:884
O-15
AJP Heart Circ Physiol 2011;301:H129
O-15
All
Weighted average N-13
O-15
23
20
6
58
51
11
11
10
11
12
28
29
12
26
15
7
15
345
270
75
1.14 ± 0.43
0.81 ± 0.23
1.84 ± 0.31
0.85 ± 0.33
0.84 ± 0.32
0.67 ± 0.15
0.89 ± 0.21
0.89 ± 0.14
1.04 ± 0.33
0.9 ± 0.14
0.92 ± 0.22
0.89 ± 0.23
0.82 ± 0.23
0.82 ± 0.23
1.02 ± 0.28
0.49 ± 0.05
0.94 ± 0.23
0.90 ± 0.10
0.91 ± 0.11
0.85 ± 0.07
1.63 ± 0.58
1.42 ± 0.52
Weighted average
Camici
Gistri
Posma
Lorenzoni
Cecchi
Joerg-Ciopor
Joerg-Ciopor
Bravo
Bravo
Bravo
Bravo
Bravo
Choudhury
Lorenzoni
Choudhury
Ohba
Timmer
Khorsand
Rust
Chen
Schepis
Burkhard
Italy
Italy
Netherlands
Italy
Italy
Switzerland
Switzerland
USA
USA
USA
USA
USA
England
England
England
Japan
Netherlands
Mixed patients (risk factors and/or known coronary artery disease)
Austria
JNC 2005;12:410
N-13
77
0.98 ± 0.31
USA
Phys Med Biol 2006;51:5347
N-13
6
0.70 ± 0.36
USA
JNM 2007;48:1259
N-13
20
1.02 ± 0.39
Switzerland JNM 2007;48:1783
N-13
21
0.81 ± 0.28
Switzerland Eur J Nucl Med Mol Imaging
N-13
35
0.96 ± 0.21
48
2.02 ± 0.67
1.95 ± 0.40
2.21 ± 1.35
1.6 ± 0.4
1.50 ± 0.71
1.50 ± 0.69
1.55 ± 0.39
1.49 ± 0.47
1.97 ± 0.32
1.58 ± 0.49
1.72 ± 0.46
1.81 ± 0.44
1.82 ± 0.50
1.64 ± 0.44
1.52 ± 0.38
1.39 ± 0.31
0.73 ± 0.11
1.84 ± 0.67
2.31 ± 0.40
1.76 ± 0.58
2.27 ± 0.51
1.62 ± 0.57
1.90 ± 0.31
2.05 ± 0.61
1.45 ± 0.52
1.49 ± 0.31
1.57 ± 0.33
1.61 ± 0.35
1.42 ± 0.19
1.84 ± 0.36
1.89 ± 0.36
1.67 ± 0.34
2.79 ± 1.18
2.25 ± 1.70
2.61 ± 1.03
1.75 ± 0.32
1.70 ± 0.66
3.02 ± 1.31
2.71 ± 0.98
1.77 ± 0.59
Gnecchi-Ruscone
England
Curillova
El Fakhri
Fukushima
USA
USA
USA
Goudarzi
USA
Goudarzi
Ziadi
Ziadi
Murthy
Rischpler
Rischpler
Johnson
Johnson
Johnson
USA
Canada
Canada
USA
USA
USA
USA
USA
USA
2010;37:517
AJC 1998;81:1165
Eur J Nucl Med Mol Imaging
2009;36:1603
JNM 2009;50:1062
JNM 2011;52:726
Eur J Nucl Med Mol Imaging
2011;38:1908
Eur J Nucl Med Mol Imaging
2011;38:1908
JACC 2011;58:740
JACC 2011;58:740
Circulation 2011;124:2215
JNM 2012;53:723
JNM 2012;53:723
JACC Cardiovasc Imaging 2012;5:430
JACC Cardiovasc Imaging 2012;5:430
JACC Cardiovasc Imaging 2012;5:430
Weighted average
O-15
15
3.72 ± 1.05
2.71 ± 1.15
Rb-82
Rb-82
Rb-82
136
22
275
1.0 ± 0.2
1.13 ± 0.19
0.93 ± 0.36
1.7 ± 0.6
2.81 ± 1.02
1.97 ± 0.82
1.7 ± 0.5
2.51 ± 0.89
2.21 ± 0.95
Rb-82
52
0.80 ± 0.22
2.09 ± 0.57
2.75 ± 0.66
Rb-82
Rb-82
Rb-82
Rb-82
Rb-82
Rb-82
Rb-82
Rb-82
Rb-82
All
N-13
O-15
Rb-82
52
27
650
2783
19
184
108
120
163
4765
159
15
4591
0.79 ± 0.24
0.89 ± 0.38
1.04 ± 0.38
1.01 ± 0.28
1.0 ± 0.3
0.9 ± 0.3
0.69 ± 0.16
0.64 ± 0.18
0.62 ± 0.14
0.97 ± 0.10
0.95 ± 0.09
0.97 ± 0.10
2.19 ± 0.64
1.30 ± 0.85
2.28 ± 0.91
1.80 ± 0.65
1.6 ± 0.8
1.8 ± 0.7
1.51 ± 0.16
1.23 ± 0.37
1.18 ± 0.26
1.86 ± 0.58
2.37 ± 1.24
3.72 ± 1.05
1.84 ± 0.54
2.89 ± 0.76
1.46 ± 0.70
2.33 ± 0.90
1.73 ± 0.44
1.7 ± 0.6
2.1 ± 0.8
2.26 ± 0.30
1.97 ± 0.59
1.93 ± 0.40
1.93 ± 0.48
2.64 ± 1.51
2.71 ± 1.15
1.91 ± 0.43
N-13
N-13
N-13
N-13
N-13
N-13
N-13
N-13
45
10
13
16
34
8
10
58
1.04 ± 0.22
1.13 ± 0.25
1.01 ± 0.19
0.82 ± 0.04
2.52 ± 0.96
2.35 ± 0.66
3.46 ± 0.82
1.67 ± 0.13
0.81 ± 0.23
3.41 ± 0.94
Syndrome X
Camici
Camici
Picano
Buus
Marroquin
Jessurun
Graf
Graf
Italy
Italy
Italy
Denmark
USA
Netherlands
Austria
Austria
Circulation 1992;86:179
Cardiovasc Drugs Ther 1994;8:221
Circulation 1994;89:753
AJC 1999;83:149
AHJ 2003;145:628
Eur J Pain 2003;7:507
Eur J Clin Invest 2006;36:326
Eur J Clin Invest 2006;36:326
49
2.18 ± 0.56
3.49 ± 0.91
2.06 ± 0.14
2.85 ± 1.35
1.59 ± 0.15
4.43 ± 0.77
2.14 ± 0.88
Graf
Graf
Scholtens
Geltman
Merlet
Shelton
Rosen
Austria
Austria
Netherlands
USA
France
USA
England
JNM 2007;48:175
JNM 2007;48:175
JNC 2011;18:238
JACC 1990;16:586
JNM 1993;34:1899
JNM 1993;34:717
Circulation 1994;90:50
N-13
N-13
N-13
O-15
O-15
O-15
O-15
All
N-13
O-15
28
51
14
17
6
9
29
348
287
61
0.93 ± 0.29
1.25 ± 0.38
0.83 ± 0.25
1.38 ± 0.46
0.87 ± 0.10
1.22 ± 0.19
1.05 ± 0.25
1.06 ± 0.11
1.04 ± 0.10
1.15 ± 0.12
3.13 ± 0.84
2.15 ± 0.67
1.16 ± 0.41
3.68 ± 2.01
3.50 ± 0.82
4.16 ± 0.93
2.73 ± 0.81
2.65 ± 1.31
2.44 ± 0.96
3.28 ± 1.87
3.46 ± 0.73
1.77 ± 0.42
1.39 ± 0.31
3.0 ± 1.8
4.00 ± 0.67
3.5 ± 1.0
2.66 ± 0.76
2.54 ± 1.31
2.42 ± 1.20
3.01 ± 1.50
Prior cardiac transplantation
JACC 1991;18:512
N-13
Circulation 1994;90:204
N-13
AJC 1996;78:550
N-13
AJC 1996;78:550
N-13
Circulation 1997;95:600
N-13
NEJM 1997;336:1209
N-13
J Heart Lung Transplant 2005;24:2022
N-13
JNM 2010;51:906
N-13
JACC 1992;19:100
O-15
AJC 1993;71:333
O-15
Circulation 2004;110:1431
O-15
All
Weighted average N-13
O-15
12
10
10
14
32
14
10
27
14
35
6
184
129
55
1.05 ± 0.39
1.7 ± 0.3
0.74 ± 0.15
0.94 ± 0.12
0.94 ± 0.26
0.99 ± 0.07
0.98 ± 0.31
0.94 ± 0.18
1.16 ± 0.26
1.63 ± 0.51
1.31 ± 0.19
1.14 ± 0.18
1.00 ± 0.10
1.48 ± 0.23
1.70 ± 0.60
2.5 ± 0.9
1.84 ± 0.64
1.91 ± 0.53
1.69 ± 0.78
3.08 ± 0.19
1.95 ± 0.61
2.30 ± 0.56
2.73 ± 1.03
3.49 ± 1.70
3.08 ± 0.28
2.44 ± 1.34
2.09 ± 0.58
3.25 ± 2.19
1.6 ± 0.7
Weighted average
Krivokapich
Chan
Preumont
Preumont
Kofoed
Di Carli
Jaeger
Wu
Rechavia
Senneff
Kaufmann
USA
USA
Belgium
Belgium
USA
USA
Germany
Taiwan
England
USA
England
50
2.66 ± 0.57
2.08 ± 0.54
1.82 ± 0.55
3.31 ± 0.32
2.09 ± 0.68
2.54 ± 0.92
2.50 ± 1.13
2.3 ± 1.2
2.43 ± 0.56
2.29 ± 0.86
2.26 ± 0.68
2.37 ± 1.25