ORIGINAL PAPER

Low-carbohydrate diet versus euglycemic hyperinsulinemicclamp for the assessment of myocardial viabilitywith 18F-fluorodeoxyglucose-PET: a pilot study

Jose Soares Jr. • Filadelfo Rodrigues Filho • Marisa Izaki •

Maria Clementina P. Giorgi • Rosa M. A. Catapirra •

Rubens Abe • Carmen G. C. M. Vinagre • Giovanni G. Cerri •

Jose Claudio Meneghetti

Received: 24 July 2013 / Accepted: 29 October 2013 / Published online: 20 November 2013

� Springer Science+Business Media Dordrecht 2013

Abstract Positron emission tomography with 18F-fluoro-

deoxyglucose (FDG-PET) is considered the gold standard for

myocardial viability. A pilot study was undertaken to compare

FDG-PET using euglycemic hyperinsulinemic clamp before18F-fluorodeoxyglucose (18F-FDG) administration (PET-

CLAMP) with a new proposed technique consisting of a 24-h

low-carbohydrate diet before 18F-FDG injection (PET-DIET),

for the assessment of hypoperfused but viable myocardium

(hibernating myocardium). Thirty patients with previous

myocardial infarction were subjected to rest 99mTc-sestamibi-

SPECT and two 18F-FDG studies (PET-CLAMP and PET-

DIET). Myocardial tracer uptake was visually scored using a

5-point scale in a 17-segment model. Hibernating myocar-

dium was defined as normal or mildly reduced metabolism

(18F-FDG uptake) in areas with reduced perfusion (99mTc-

sestamibi uptake) since 18F-FDG uptake was higher than the

degree of hypoperfusion–perfusion/metabolism mismatch

indicating a larger flow defect. PET-DIET identified 79 seg-

ments and PET-CLAMP 71 as hibernating myocardium.

Both methods agreed in 61 segments (agreement = 94.5 %,

j = 0.78). PET-DIET identified 230 segments and PET-

CLAMP 238 as nonviable. None of the patients had hypo-

glycemia after DIET, while 20 % had it during CLAMP. PET-

DIET compared with PET-CLAMP had a good correlation for

the assessment of hibernating myocardium. To our knowl-

edge, these data provide the first evidence of the possibility of

myocardial viability assessment with this technique.

Keywords Cardiology � Positron emission

tomography � 18F-fluordeoxyglucose � Myocardial

viability � Carbohydrate-restricted diet

Introduction

In patients with chronic coronary artery disease, left ventric-

ular dysfunction may result either from regions with fibrosis or

with ischemic but viable myocardium; the identification of

these areas has important clinical implications [1–3]. In recent

decades, several imaging techniques have been used for this

purpose [4]. Positron emission tomography using 18F-fluoro-

deoxyglucose (FDG-PET) is considered the reference stan-

dard for the detection of myocardial viability, given the

extensive clinical experience, the considerable research data

and its relatively high accuracy for predicting functional

recovery following revascularization [3, 5, 6]. Traditional18FDG-PET myocardial viability assessment requires inte-

gration of rest perfusion imaging (assessed by SPECT or PET)

with myocardial glucose metabolism imaging to assess the

perfusion (reduced)/metabolism (preserved) mismatch pat-

tern—hallmark of myocardial hibernation [7]. It uniquely

detects dysfunctional/hypoperfused but viable myocardium

(hibernating myocardium), in contrast to the total extent of

viability (normal plus dysfunctional/hypoperfused myocar-

dium) [8].

J. Soares Jr. � F. Rodrigues Filho � M. Izaki �M. C. P. Giorgi � R. M. A. Catapirra � R. Abe �G. G. Cerri � J. C. Meneghetti

Nuclear Medicine Department, Heart Institute (InCor),

University of Sao Paulo Medical School, Av. Dr. Eneas de

Carvalho Aguiar, 44, Sao Paulo, SP CEP: 05403-000, Brazil

F. Rodrigues Filho (&)

Rua Carlos Vasconcelos, 977, Fortaleza CEP 60115-171, Brazil

e-mail: filadelfo@yahoo.com

C. G. C. M. Vinagre

Lipid Metabolism Laboratory, Heart Institute (InCor), University

of Sao Paulo Medical School, Av. Dr. Eneas de Carvalho Aguiar,

44, Sao Paulo, SP CEP: 05403-000, Brazil

123

Int J Cardiovasc Imaging (2014) 30:415–423

DOI 10.1007/s10554-013-0324-5

However, specificity values for FDG-PET vary a lot in

the literature, according to the study populations, image

analysis criteria, and metabolic condition at the time of

scanning [9, 10]. Standardization of the metabolic condi-

tion may be done with oral glucose load, use of a nicotinic

acid derivative or, preferably, by using a hyperinsulinemic

euglycemic clamp (CLAMP), which stimulates the uptake

of both glucose and 18F-FDG in the myocardium, including

areas of hibernating myocardium [7, 11–13]. The CLAMP

provides excellent image quality, usually demonstrates

uniform tracer uptake and enables PET studies to be per-

formed under steady and standardized metabolic conditions

[7]. This technique, however, is very laborious and time

consuming, in addition to requiring careful monitoring to

prevent hypoglycemia [11, 14, 15].

Carbohydrate restriction leads to a decrease of plasma

insulin levels and, under such conditions, the normal myo-

cardium consumes preferably free fatty acids (FFA) [9, 16].

However, even in these situations, the hibernated/ischemic

areas compensate their loss of oxidative potential by shifting

toward greater utilization of glucose as the main substrate

(through the glycolytic pathway) [3, 17, 18]. In this setting, a

FDG-PET scan will show reduced uptake in normal myo-

cardial areas but not in hibernated areas [19]. In the present

study we compared impaired perfusion myocardial regions,

assessed with 99mTc-sestamibi myocardial perfusion scin-

tigraphy (MIBI), with glucose metabolism by FDG-PET

imaging after a 24-h low-carbohydrate diet, on the day prior

to the exam (DIET), and after euglycemic hyperinsulinemic

clamping before 18F-FDG injection (CLAMP).

Methods

Patients

Thirty patients with a history of previous myocardial

infarction underwent viability scanning between October

2005 and March 2007. Their clinical characteristics are

summarized in Table 1. The mean time from the last episode

of infarction and the study enrollment was 20 months (range,

4–72 months). In the coronary angiography, occlusions

[70 % were described for the left anterior descending artery

in 23 (77 %) patients, circumflex artery in 8 (27 %), and right

coronary artery in 11 (37 %). Obstruction affected 1, 2, or 3

arteries in 57, 23, and 20 % of the patients, respectively. All

patients gave informed consent as a part of a protocol

approved by the ethics committee of our institution.

Study design

All the patients underwent rest myocardial perfusion scin-

tigraphy with 99mTc-sestamibi (MIBI) and two FDG-PET

studies, one with CLAMP and the other with DIET, at a

maximum interval of 2 weeks. Additionally, blood samples

were drawn for measurements of glucose (GLU), insulin

(INS), and free fat acids (FFA) before the start of CLAMP

(T1), before injection of 18F-FDG during the CLAMP (T2),

and before administration of 18F-FDG, in the PET-DIET

(T3). A subgroup analysis was performed considering non-

diabetic (NDM, n = 22) and diabetic patients (DM, n = 8).

Rest myocardial perfusion scintigraphy (MIBI)

The images were obtained with an ADAC Cardio MD

(Phillips, The Netherlands) gamma camera, equipped with a

low-energy, high-resolution collimator, with 64 projections

of 30 s each in an orbit of 180�, synchronized to the elec-

trocardiogram, 60 min after an intravenous administration

of 740 MBq (20 mCi) of 99mTc-sestamibi. The images were

processed using the iterative method and pre-reconstruction

Butterworth filter. End-diastolic volume (EDV), end-sys-

tolic volume (ESV), and left ventricular ejection fraction

(LVEF) were obtained using QGS software (Quantitative

Gated SPECT—Cedars-Sinai, Los Angeles, CA, US).

FDG-PET with hyperinsulinemic euglycemic clamp

(PET-CLAMP)

Patients assigned to PET-CLAMP started fasting at

10:00 P.M. the night before. Medication, if any, was

maintained, even among diabetic patients. The CLAMP

for diabetic and non-diabetic patients was performed

Table 1 Summary of patients’ clinical characteristics

Characteristics na

Male 22 (73 %)

Mean age (years) 56.8 ± 12

High blood pressure 19 (63 %)

Diabetes mellitus (type II) 8 (27 %)

Dyslipidemia 23 (77 %)

Current smoking habit 5 (17 %)

BMI

Normal (18.5–24.9) 10 (33 %)

Pre-obese (25.0–29.9) 16 (53 %)

Class I obesity (30.0–34.9) 3 (10 %)

Class II obesity (35.0–39.9) 1 (3 %)

Functional class

I 19 (63 %)

II 9 (30 %)

III 2 (7 %)

IV 0

Previous revascularization 5 (17 %)

a Number of patients

416 Int J Cardiovasc Imaging (2014) 30:415–423

123

according to the guidelines of the America Society of

Nuclear Cardiology (sample protocol A) [20]. After 20 min

of CLAMP, if capillary glucose (CG) was below 160 mg/

dL (8.88 mmol/L), an administering of 370 MBq (10 mCi)

of 18F-FDG was accomplished. If not, small IV boluses of

insulin were administered and CG measured every 10 min,

until it decreased below 160 mg/dL or stabilized. Mea-

surements of CG were obtained during the CLAMP and at

the beginning and end of image acquisition for detection of

possible hypoglycemia (CG \60 mg/dL/3.33 mmol/L).

Approximately 60 min after an injection of 18F-FDG, the

patient was positioned in the equipment (GE Advance NXi

PET Imaging System, Milwaukee, US). Initially, a trans-

mission image was acquired for heart alignment and

attenuation correction, and afterwards the 18F-FDG emis-

sion images were obtained for a 15-minutes period.

Image processing was carried out with an iterative recon-

struction process (OSEM—ordered subset expectation

maximization).

FDG-PET with carbohydrate-restricted diet

(PET-DIET)

Patients were kept on a carbohydrate-restricted diet (aver-

age: 15–20 g carbohydrate) during the 24 h preceding the

examination, and started fasting at 10:00 P.M. the night

before. They were given written guidelines on how to

perform the diet. Bread, sugar, rice, pasta, cereals, potatoes,

grains, flour, fruits, corn, beets, carrots and any other root

vegetables were not allowed. The foods allowed included

4–6 meals with green salads, vegetables and meats, poultry,

fish, fowl, and eggs. The patients were asked to discontinue

the administration of insulin and oral hypoglycemic drugs

after 12:00 A.M. on the previous day to avoid hypoglyce-

mia. Upon arrival at the department, 370 MBq (10 mCi) of18F-FDG was administered intravenously. Again, approxi-

mately 60 min after an injection of 18F-FDG, the patient

was positioned in the equipment (GE Advance NXi PET

Imaging System, Milwaukee, US) and images were

acquired. Measurements of CG were performed at the

beginning and end of image acquisition. Image acquisition

and processing of PET-DIET were carried out in the same

manner as described for PET-CLAMP.

Image interpretation

Perfusion and 18F-FDG images were visually interpreted

by 2 experienced observers, in a masked manner. The

differences were resolved by consensus. Perfusion and

FDG-PET images (CLAMP and DIET) were scored using a

17-segment model recommended by the American Heart

Association [21]. Perfusion and PET-CLAMP were scored

on a 0–4 scale (0—normal uptake; 1—mild reduction in

uptake; 2—moderate reduction in uptake; 3—severe

reduction in uptake; and 4—no uptake). In MIBI, the

scores were added to determine the summed rest score

(SRS) and the percentage of hypoperfused myocardium.

In PET-DIET, the following score classification was

used: 0-intense 18F-FDG uptake; 1-mild 18F-FDG uptake

but clearly above to the left ventricle blood pool; 2-mild18F-FDG uptake similar to the left ventricle blood pool; 3

and 4-faint or no discernible 18F-FDG uptake. Score 0

represents an 18F-FDG uptake clearly higher than the left

ventricle blood pool, while score 1 represents uptake

slightly but unequivocally higher than blood pool. In PET-

DIET evaluation the distinction between scores 3 and 4

was difficult to carry out because of the absence of glucose

uptake in normal myocardial regions at this metabolic

condition. Therefore, both of them were considered nega-

tive for mismatch, irrespective of the perfusional score.

Perfusion/metabolism mismatch was defined as a seg-

ment with decreased perfusion by MIBI (scores 1–4) and

present glucose metabolism by PET-CLAMP (scores 0–3,

with score PET-CLAMP \ MIBI) or by PET-DIET (scores

0–2, with score PET-DIET \ MIBI). Myocardial segments

with perfusion/metabolism mismatch were considered

hibernating myocardium (positive for viability). Compar-

ative analysis was also performed by myocardial regions

(anterior/lateral/septal/inferior/apical), vascular territories

(left anterior descending/circumflex/right coronary) and

patients. The presence of mismatch in at least 2 segments

of the same region (or the same vascular territory or the

same patient) was considered a positive result for myo-

cardial viability.

Table 2 summarizes the findings of contractility, per-

fusion and 18F-FDG uptake with PET-CLAMP and PET-

DIET in the normal myocardium, hibernating myocardium

and fibrosis.

Statistical analysis

The Student t test was used to compare the means of 2

groups. Laboratory findings were analyzed with Friedman’s

test and Dunn’s pair-wise comparison test. Agreement

between the 2 methods was analyzed with the kappa index

(j) and weighted kappa (jw), varying between 0 (absence of

agreement) and 1 (perfect agreement) [22]. An alpha error

\0.05 was considered as the level of significance.

Results

Rest myocardial perfusion scintigraphy

Mean LVEF was (29 ± 10) %, and SRS showed a mean

perfusional defect of (40 ± 12) % (Table 3). Of the 510

Int J Cardiovasc Imaging (2014) 30:415–423 417

123

segments evaluated, only 201 (39.4 %) had preserved

perfusion (Table 4).

Preparation analysis: PET

In PET-CLAMP, six (20 %) patients had hypoglycemia

just after clamping was completed, with symptoms (sudo-

resis and visual blurring) in 4 of them. The mean duration

of CLAMP was (57.4 ± 16.0) minutes, and it took longer

in patients that had hypoglycemia (72 min 9 51 min;

p = 0.01) and in diabetic patients (71 min 9 53 min;

p = 0.01). The DIET was well accepted by the patients,

and the exam was carried out without any abnormality; no

episodes of hypoglycemia occurred before or after the scan.

Analysis of mismatch areas

The analysis of PET-CLAMP showed mismatch in 71

(13.9 %) segments while the analysis of PET-DIET showed

it in 79 (15.5 %). Including all segments (well perfused and

hypoperfused), the agreement between methods was 94.5 %,

with a kappa index (j) of 0.78 (CI 95 % 0.70–0.86;

p \ 0.01), which means a substantial agreement (Table 5)

[22]. Even when we evaluate the agreement only in the

segments with hypoperfusion on MIBI, the agreement was

90.9 %, with j = 0.75 (CI 95 % 0.70–0.81; p \ 0.01),

Table 6 shows the agreement according to the region, vas-

cular territory and patient. Figures 1 and 2 show examples of

images.

These analyses were also carried out with weighted

kappa (jw), considering the number of positive segments

in each region and vascular territory, reaching even higher

indexes, considered as an almost perfect agreement

(Tables 7, 8) [22].

For patient subgroups (NDM and DM), agreement by

segments was also calculated (Table 9). The kappa index

was lower for diabetic patients (j = 0.70), but still remains

substantial agreement.

Laboratory findings

Following PET-DIET (T3), the mean glycemia was

82.8 mg/dL (4.60 mmol/L) and blood insulin was

32.6 pmol/L, both lower than T1—after fasting (98.4 mg/

dL–5.46 mmol/L and 40.28 pmol/L) and T2—after

CLAMP (100.3 mg/dL–5.57 mmol/L and 3,296.1 pmol/L)

values (p \ 0.01). The mean FFA values after the diet

(0.97 mmol/L) were higher than those obtained in T1

(0.80 mmol/L) and T2 (0.52 mmol/L) (p \ 0.05).

Discussion

These data show a good correlation between PET-DIET

and PET-CLAMP for the assessment of hibernating myo-

cardium (perfusion/metabolism mismatch) in this popula-

tion. Our patients represented a high-risk population, with

previous myocardial infarction and ischemic cardiomyop-

athy. Mean LVEF was (29 ± 10) %, and mean SRS (27.2)

corresponds to approximately 40 % of LV perfusion

abnormality. The group studied was similar in terms of

clinical severity to patients in the majority of studies of

viability detection [3, 8, 15, 23–28].

Table 2 Summary of MIBI, PET-CLAMP and PET-DIET findings

Contraction

(MIBI-gated

SPECT)

Perfusion

(MIBI)

18F-FDG

uptake

(PET-

CLAMP)

18F-FDG

uptake

(PET-

DIET)

Normal

myocardium

Normal Normal Normal Reduced

Hibernating

myocardium

Reduced Reduced Normal or

increased

Normal or

increased

Fibrosis Reduced Reduced Reduced Reduced

Table 3 Summary of MIBI scintigraphy findings

Parameter

SRS 27.2 ± 7.9

LVEF (%) 29 ± 10

ESV (mL) 146.1 ± 60.1

EDV (mL) 197.9 ± 58.6

Table 4 Distribution of segments and MIBI perfusion scores

Scores

0 201 (39.4 %)

1 39 (7.6 %)

2 96 (18.8 %)

3 127 (24.9 %)

4 47 (9.2 %)

Table 5 Distribution of myocardial segments for the presence of

mismatch in both methods

DIET CLAMP

? -

? 61 18

- 10 421

A = 94.5 %; j = 0.78

A agreement; j kappa index

418 Int J Cardiovasc Imaging (2014) 30:415–423

123

Table 6 Distribution of the areas for the presence of mismatch according to both methods

Area n PET-DIET/PET-CLAMP

?/? ?/- -/? -/- Aa jb CIc 95 % p

Region 150 42 7 6 95 91 % 0.80 0.73–0.87 \0.01

Arterial territory 90 31 5 4 50 90 % 0.79 0.66–0.92 \0.01

Patient 30 17 1 2 10 90 % 0.79 0.56–1.00 \0.01

a Agreementb Kappa indexc Confidence interval 95 %

Fig. 1 Rest 99mTc-sestamibi

and 18F-FDG images on short-

axis and horizontal long-axis.

MIBI showed perfusion

abnormality in anterior, septal,

apical and inferior wall, which

match with PET-CLAMP and

PET-DIET images. Note that

PET-CLAMP demonstrated the

same pattern of perfusion while

PET-DIET showed no

discernible 18F-FDG uptake in

all myocardium

Fig. 2 Example of mismatch in

LV inferolateral wall

demonstrated by PET-CLAMP

and PET-DIET. Rest 99mTc-

sestamibi and 18F-FDG images

on short-axis and horizontal

long-axis. MIBI showed severe

reduction in uptake in

inferolateral wall. PET-CLAMP

demonstrated mild reduction in

uptake in inferolateral wall and

normal uptake in the other LV

regions. PET-DIET

demonstrated marked 18F-FDG

uptake in inferolateral wall

(arrow). It is important to note

that in PET-DIET, 18F-FDG

uptake occurred only in

inferolateral wall, with no

uptake in normal perfused

myocardial, indicating the

pattern of hibernation in that

region

Int J Cardiovasc Imaging (2014) 30:415–423 419

123

After fasting, myocardial 18F-FDG regional distribution

may be heterogeneous [29]. It is recommended that18F-FDG viability scans should be performed under glucose

loaded conditions, usually an oral load of 25–100 g [18].

However, an unsatisfactory image quality may be found in

20–25 % of these patients [9]. Many of them are diabetics or

insulin resistant, and the amount of insulin released will not

induce the maximal stimulation of glucose uptake [30, 31].

Therefore, the comparison of PET-DIET with PET after oral

glucose load or fasting would certainly result in many lim-

itations. The CLAMP effectively results in a standardization

of the metabolic conditions in all patients and provides

excellent image quality [9, 18, 30, 31]. Its routine use

improves the discrimination between viable and non-viable

myocardium, increasing the accuracy [15]. However,

increased glucose consumption by healthy myocardium

results in increased 18F-FDG uptake in normal regions with

a relative decreased uptake in ischemic myocardium, and as

a consequence the extent of tissue viability may be under-

estimated [3].

Furthermore, during or after the CLAMP, in our study,

20 % of patients had hypoglycemia. This requires moni-

toring blood glucose even after its end, at least for 15 min.

Other studies have also documented this risk of hypogly-

cemia [14, 32]. Another problem is the logistics. Some-

times, it takes almost 1 h until the moment of 18F-FDG

injection, and this delay is very complicated not only

because of the short half-life of F-18, but also because in a

busy PET department, patient timing is critical.

The diet tested in this study may be considered quite

restrictive, with less than 20 g of carbohydrates and, even

if a patient had been less careful, this intake would prob-

ably not exceed 40–50 g, which is still considered a

restricted diet [16, 33]. After DIET, GLU and INS levels

were lower and FFA values were higher than the post-

fasting levels on the CLAMP day. In fact, serum glucose

and insulin levels were expected to reach a minimum after

24 h with low intake of carbohydrates, resulting in an

increase in circulating levels of FFA, as lipolysis is not

inhibited by insulin, and increase of FFA uptake by myo-

cardial cells [34–36]. In hibernating myocardium, as the

aerobic beta-oxidation of FFAs falls off in the setting of

reduced oxygen supply, the only substract that may be used

is glucose by anaerobic catabolism [36, 37].

The PET-DIET technique was not associated with

hypoglycemia. 18F-FDG can be injected upon the patient’s

arrival without delay. This method for patient preparation

has the advantages of simplicity, logistics and economy.

On the other hand, after DIET extensive necrosis with a

small amount of hibernating tissue may show 18F-FDG

uptake, leading to a possible overestimation of the viable

tissue [3].

Despite PET perfusion imaging being preferable to

SPECT for comparison with 18F-FDG images, in current

Table 7 Distribution of myocardial regions for the number of mis-

match segments according to both methods

DIET CLAMP Total

0 1 2 3

0 162 4 5 0 171

1 3 4 5 2 14

2 3 0 14 2 19

3 0 0 1 5 6

Total 168 8 25 9 210

A = 88 %; jw = 0.75; CI 95 % 0.70–0.85; p \ 0.01

A agreement, jw weighted kappa index, CI confidence interval 95 %

Table 8 Distribution of vascular territories for the number of mis-

match segments according to both methods

DIET CLAMP Total

0 1 2 3 4 5

0 50 1 3 0 0 0 54

1 3 9 0 0 0 0 12

2 1 3 9 0 1 0 14

3 1 1 1 1 1 0 5

4 0 0 0 0 1 0 1

5 0 0 0 2 0 2 4

Total 55 14 13 3 3 2 90

A = 80 %; jw = 0.83; CI 95 % 0.73–0.83; p \ 0.01

A agreement, jw weighted kappa index, CI confidence interval 95 %

Table 9 Distribution of the segments for the presence of mismatch according to both methods, in the subgroups of patients NDM and DM

Subgroup n PET-DIET/PET-CLAMP

?/? ?/- -/? -/- Aa (%) jb CIc 95 % p

NDM 22 56 17 7 294 93.5 0.78 0.70–0.87 \0.01

DM 8 5 1 3 127 97 0.70 0.42–0.98 \0.01

a Agreementb Kappa indexc Confidence interval 95 %

420 Int J Cardiovasc Imaging (2014) 30:415–423

123

clinical practice FDG-PET images are often read in com-

bination with SPECT perfusion images [8, 18]. For over-

coming possible limitations, gated SPECT images were

analyzed, and scores were corrected in apparent perfusion

defects with normal regional wall motion and thickening.

The visual analysis of perfusion and metabolism used in

our study is a well accepted technique and it enables a

more appropriate pairing between the segments [9].

One of the initial difficulties was the development of a

scoring system for PET-DIET, as a new technique. How-

ever, as long as objective classification parameters were

defined based on the left ventricle blood pool uptake, the

procedure was easy to analyze. Care should be taken in

the interpretation of PET-CLAMP and PET-DIET images

as they represent different metabolic conditions. In both,

the higher score represents a lesser uptake of 18F-FDG, 0

(zero) being the preserved uptake and 4 (four) being

the absence of uptake. In PET-CLAMP, normal myocar-

dial regions have preserved glucose uptake, and in PET-

DIET, normal myocardial regions have low or no dis-

cernible 18F-FDG uptake, and areas with glucose uptake

will characterize hibernating myocardium (Table 2).

PET-CLAMP revealed mismatch (viability) in 23 % of

the hypoperfused segments in 99mTc-sestamibi, or 13.9 %

of the total, and PET-DIET in 25.5 %, or 15.5 % of the

total. The prevalence of myocardial viability in this study

was similar [38, 39] or even slightly lower than the prev-

alence reported in the literature [1, 2, 40]. This may be

because most studies consider not only the segments with

mismatch but also the segments with normal perfusion as

myocardium viability [2, 28, 38, 40, 41]. The comparison

between PET-CLAMP and PET-DIET indicates substantial

agreement for mismatch areas (94.5 %, j = 0.78), even

when we carry out the analysis only in the hypoperfused

segments (90.9 %/0.75) or according to the LV region

(91 %/0.80), vascular territory (90 %/0.79), and patient

(90 %/0.79). These results show very good correlation

between the methods, which is similar or even superior to

levels reported in the literature for this kind of comparison.

Comparing 18F-FDG-SPECT with 18F-FDG-PET in

patients with the same metabolic status, Burt et al. [39]

found an agreement of 91.8 %, with j = 0.76 and Srini-

vasan et al. [2] found j = 0.59. Tamaki et al. [42] reported

an agreement of 86.6 % comparing 201Tl reinjection with18F-FDG-PET (with fasting) in hypoperfused segments.

When patients were analyzed by subgroup, the kappa

index remained high for NDM (j = 0.78) and DM

(j = 0.70) patients, with a substantial agreement. This

finding is important because PET-DIET may become an

acceptable alternative in DM patients. As they have limited

ability to produce endogenous insulin and their cells are

less able to respond to insulin stimulation, they do not show

a good response to oral glucose stimulation [13, 18, 43].

Therefore, one of the few options available for performing

FDG-PET in these patients is with the clamping procedure

[13, 43]. With DIET, hibernating myocardium, even in

diabetic patients, takes up glucose/18F-FDG, because it

may not use FFA by aerobic beta-oxidation [36, 37], and

consequently it may be detected in FDG-PET.

Patient follow-up after myocardial revascularization was

not performed. FDG-PET has a relatively high accuracy for

predicting functional recovery following revascularization

[6, 8], and several clinical trials have already demonstrated its

value in regard to functional recovery, mentioning positive

results with PET as myocardial viability without post-revas-

cularization confirmation [13, 40, 42, 44]. Indeed, this

improvement should not be considered as the only criterion for

the presence of myocardial viability [10, 31]. In our study, the

purpose was to compare techniques of assessment of hiber-

nating myocardium areas considering that one of them is

currently a well-accepted method [8, 30, 31]. Likewise, sev-

eral other studies designed for this purpose have dispensed

post-revascularization follow-up [1, 2, 13, 38–41, 45], but

more studies with this analysis for PET-DIET are needed.

Our pilot study provides preliminary data suggesting

that the evaluation of myocardial viability (hibernating

myocardium) with FDG-PET 24-h low-carbohydrate diet

has a good agreement and is comparable in accuracy to

FDG-PET using the hyperinsulinemic euglycemic clamp, a

well-established method. We believe that this method is

a feasible method and can be done in any Nuclear Medi-

cine laboratory. Some additional benefits are simplicity,

safety, logistics and a reduction in clamp material costs.

Although in our study the correlation was good with

the PET-CLAMP technique, further studies are needed to

determine its value.

Acknowledgments This research was supported by financial

assistance of FAPESP—The State of Sao Paulo Research Founda-

tion—process 04/13824-2.

Conflict of interest None.

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