Int J Cardiovasc Imaging (2014) 30:415–423 DOI 10.1007/s10554-013-0324-5
ORIGINAL PAPER
Low-carbohydrate diet versus euglycemic hyperinsulinemic clamp for the assessment of myocardial viability with 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´ Cla´udio Meneghetti
•
Received: 24 July 2013 / Accepted: 29 October 2013 / Published online: 20 November 2013 Ó Springer Science+Business Media Dordrecht 2013
Abstract Positron emission tomography with 18F-fluorodeoxyglucose (FDG-PET) is considered the gold standard for myocardial viability. A pilot study was undertaken to compare FDG-PET using euglycemic hyperinsulinemic clamp before 18 F-fluorodeoxyglucose (18F-FDG) administration (PETCLAMP) 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-sestamibiSPECT and two 18F-FDG studies (PET-CLAMP and PETDIET). Myocardial tracer uptake was visually scored using a 5-point scale in a 17-segment model. Hibernating myocardium was defined as normal or mildly reduced metabolism (18F-FDG uptake) in areas with reduced perfusion (99mTcsestamibi uptake) since 18F-FDG uptake was higher than the degree of hypoperfusion–perfusion/metabolism mismatch indicating a larger flow defect. PET-DIET identified 79 segments and PET-CLAMP 71 as hibernating myocardium. Both methods agreed in 61 segments (agreement = 94.5 %,
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. Ene´as de Carvalho Aguiar, 44, Sa˜o Paulo, SP CEP: 05403-000, Brazil F. Rodrigues Filho (&) Rua Carlos Vasconcelos, 977, Fortaleza CEP 60115-171, Brazil e-mail:
[email protected] C. G. C. M. Vinagre Lipid Metabolism Laboratory, Heart Institute (InCor), University of Sao Paulo Medical School, Av. Dr. Ene´as de Carvalho Aguiar, 44, Sa˜o Paulo, SP CEP: 05403-000, Brazil
j = 0.78). PET-DIET identified 230 segments and PETCLAMP 238 as nonviable. None of the patients had hypoglycemia after DIET, while 20 % had it during CLAMP. PETDIET compared with PET-CLAMP had a good correlation for the assessment of hibernating myocardium. To our knowledge, 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 ventricular 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-fluorodeoxyglucose (FDG-PET) is considered the reference standard 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]. Traditional 18 FDG-PET myocardial viability assessment requires integration of rest perfusion imaging (assessed by SPECT or PET) with myocardial glucose metabolism imaging to assess the perfusion (reduced)/metabolism (preserved) mismatch pattern—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 myocardium) [8].
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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 condition 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 performed 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 myocardium 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 myocardial areas but not in hibernated areas [19]. In the present study we compared impaired perfusion myocardial regions, assessed with 99mTc-sestamibi myocardial perfusion scintigraphy (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).
Int J Cardiovasc Imaging (2014) 30:415–423 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) Functional class
1 (3 %)
I
19 (63 %)
II
9 (30 %)
III
2 (7 %)
IV Previous revascularization a
0 5 (17 %)
Number of patients
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 nondiabetic (NDM, n = 22) and diabetic patients (DM, n = 8).
Methods
Rest myocardial perfusion scintigraphy (MIBI)
Patients
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 electrocardiogram, 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-systolic volume (ESV), and left ventricular ejection fraction (LVEF) were obtained using QGS software (Quantitative Gated SPECT—Cedars-Sinai, Los Angeles, CA, US).
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 scintigraphy with 99mTc-sestamibi (MIBI) and two FDG-PET
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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
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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. Measurements 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 transmission image was acquired for heart alignment and attenuation correction, and afterwards the 18F-FDG emission images were obtained for a 15-minutes period. Image processing was carried out with an iterative reconstruction process (OSEM—ordered subset expectation maximization). FDG-PET with carbohydrate-restricted diet (PET-DIET) Patients were kept on a carbohydrate-restricted diet (average: 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 hypoglycemia. Upon arrival at the department, 370 MBq (10 mCi) of 18 F-FDG was administered intravenously. Again, approximately 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
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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-mild 18 F-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 PETDIET 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 negative for mismatch, irrespective of the perfusional score. Perfusion/metabolism mismatch was defined as a segment 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). Comparative 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 myocardial viability. Table 2 summarizes the findings of contractility, perfusion and 18F-FDG uptake with PET-CLAMP and PETDIET 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
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Table 2 Summary of MIBI, PET-CLAMP and PET-DIET findings Contraction (MIBI-gated SPECT)
Perfusion (MIBI)
Normal myocardium
Normal
Normal
Hibernating myocardium
Reduced
Fibrosis
Reduced
Reduced Reduced
18
F-FDG uptake (PETCLAMP)
18
Normal
Reduced
F-FDG uptake (PETDIET)
Normal or increased
Normal or increased
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 %)
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 (sudoresis 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 %,
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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
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, vascular 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 myocardium (perfusion/metabolism mismatch) in this population. Our patients represented a high-risk population, with previous myocardial infarction and ischemic cardiomyopathy. 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].
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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
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
Region
a
Agreement
b
Kappa index
c
Confidence interval 95 %
Fig. 1 Rest 99mTc-sestamibi and 18F-FDG images on shortaxis 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 99mTcsestamibi 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
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Table 7 Distribution of myocardial regions for the number of mismatch segments according to both methods DIET
CLAMP 0
Total 1
2
3
0
162
4
5
0
1
3
4
5
2
14
2 3
3 0
0 0
14 1
2 5
19 6
168
8
25
9
210
Total
171
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 mismatch segments according to both methods DIET
CLAMP 0
Total 1
2
3
4
5
0 1
50 3
1 9
3 0
0 0
0 0
0 0
54 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
55
14
13
3
3
2
90
Total
A = 80 %; jw = 0.83; CI 95 % 0.73–0.83; p \ 0.01 A agreement, jw weighted kappa index, CI confidence interval 95 %
After fasting, myocardial 18F-FDG regional distribution may be heterogeneous [29]. It is recommended that 18 F-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 limitations. 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 underestimated [3]. Furthermore, during or after the CLAMP, in our study, 20 % of patients had hypoglycemia. This requires monitoring blood glucose even after its end, at least for 15 min. Other studies have also documented this risk of hypoglycemia [14, 32]. Another problem is the logistics. Sometimes, 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 probably 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 postfasting 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 myocardial 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 9 Distribution of the segments for the presence of mismatch according to both methods, in the subgroups of patients NDM and DM Subgroup
NDM DM a b c
n
PET-DIET/PET-CLAMP ?/?
?/-
-/?
-/-
Aa (%)
jb
CIc 95 %
p
22
56
17
7
294
93.5
0.78
0.70–0.87
\0.01
8
5
1
3
127
97
0.70
0.42–0.98
\0.01
Agreement Kappa index Confidence interval 95 %
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clinical practice FDG-PET images are often read in combination with SPECT perfusion images [8, 18]. For overcoming 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. However, 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 myocardial regions have preserved glucose uptake, and in PETDIET, normal myocardial regions have low or no discernible 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 prevalence 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 Srinivasan et al. [2] found j = 0.59. Tamaki et al. [42] reported an agreement of 86.6 % comparing 201Tl reinjection with 18 F-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].
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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-revascularization 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 hibernating myocardium areas considering that one of them is currently a well-accepted method [8, 30, 31]. Likewise, several 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 Medicine 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 Sa˜o Paulo Research Foundation—process 04/13824-2. Conflict of interest
None.
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