ORIGINAL ARTICLE Takotsubo cardiomyopathy: FDG myocardial uptake pattern in fasting patients. Comparison of PET/CT, SPECT, and ECHO results Malgorzata Kobylecka, MD, PhD,a Monika Budnik, MD,b Janusz Kochanowski, MD, PhD,b Radoslaw Piatkowski, MD, PhD,b Marek Chojnowski, MD,a Katarzyna Fronczewska-Wieniawska, MD, PhD,a Tomasz Mazurek, MD, PhD,b Joanna Maczewska, MD,a Michał Peller, MD,b Grzegorz Opolski, MD, Prof,b and Leszek Krolicki, MD, Profa a b
Nuclear Medicine Department, Medical University of Warsaw, Warsaw, Poland 1st Department of Cardiology, Medical University of Warsaw, Warsaw, Poland
Received Aug 25, 2016; accepted Dec 14, 2016 doi:10.1007/s12350-016-0775-x
Background. The aim of this study was to assess the accumulation pattern of 18F-FDG in fasting patients with takotsubo cardiomyopathy (TTC) and to correlate the results with perfusion scintigraphy and echocardiography. Methods. 18 consecutive patients with TTC were identified by clinical symptoms, cardiac catheterization, and echocardiography. Coronary angiography (CA) and transthoracic echocardiography (TTE) were performed on the day of the onset of symptoms. An assessment of myocardial perfusion (99mTc-MIBI) and glucose metabolism (18F-FDG) was performed within 18 days. Results. SPECT showed no regional perfusion abnormalities in 10/18 patients, and a mild perfusion defect was found in 8/18 patients. Perfusion abnormalities were limited to apical and para-apical regions. In 8/18 cases, there was an increased selective apical 18F-FDG accumulation. In 10/18 cases, in spite of the fastened 18F-FDG protocol, slightly inhomogeneous 18FFDG uptake was present in the entire myocardium: with relatively reduced uptake of 18F-FDG in the apical region and LV mid-segments. Conclusion. This study demonstrated the heterogeneous nature of myocardial 18F-FDG accumulation in patients with TTC. Selective, preferential apical 18F-FDG uptake in almost half of the patients confirms an existing disorder of glucose metabolism, similar to that observed in stunned or hibernated myocardium. (J Nucl Cardiol 2017) Key Words: Takotsubo cardiomyopathy Æ molecular imaging viability Æ PET Æ SPECT apical ballooning nuclear imaging Æ radioisotopes
Reprint requests: Monika Budnik, MD, 1st Department of Cardiology, Medical University of Warsaw, Banacha 1a, 02-097 Warsaw, Poland;
[email protected] 1071-3581/$34.00 Copyright Ó 2017 American Society of Nuclear Cardiology.
Kobylecka et al Takotsubo cardiomyopathy
Abbreviations TTC Takotsubo cardiomyopathy 18F-FDG Fluorodeoxyglucose CA Coronary angiography TTE Transthoracic echocardiography MIBI Technetium (99mTc) sestamibi (Hexakis(2-methoxy-2-methylpropyl isonitrile) technetium (99mTc)) SPECT Single-photon emission computed tomography LV Left ventricle PET Positron emission tomography SUVmax Standard uptake value FFA Free fatty acids
BACKGROUND Myocardial 18F-FDG-PET study in patients with takotsubo cardiomyopathy (TTC) is usually performed after glucose load protocol.1–3 The healthy myocardium in postprandial state shows usually high and homogeneous 18F-FDG uptake. The ischemic myocardium can have preserved but relatively lower glucose uptake, due to delayed delivery and slower metabolism. Such decreased apical uptake of radiopharmaceutical is typical for TTC.1–3 Although this accumulation pattern is well established, there is still continuous discussion about its character. The expected image of normal myocardium in fasting condition shows the lack of or low and heterogeneous 18F-FDG uptake, because the free fatty acids (FFA) are the main source of energy production. High 18F-FDG uptake is typical for ischemic or hibernating myocardium in fasted stage due to its preferential anaerobic glucose utilization during hypoxia. This preferential uptake is usually clearly visible and delineated from the surrounding normal, low myocardial glucose utilization. We hypothesized that the assessment of fasting 18F-FDG myocardial uptake pattern could help evaluate the ischemic or post-ischemic character of the disturbances, showing high selective uptake in mechanism of ‘‘ischemic memory.’’4,5 To our knowledge, there is only one case report published in 2012 reporting this pattern of selective uptake in TTC patient.6 There is no literature describing this kind of 18F-FDG accumulation pattern in a larger group of fasting patients with TTC. The aim of this study was to assess the accumulation pattern of 18F-FDG in fasting patients with confirmed TTC and to correlate the results with perfusion scintigraphy and echocardiography.
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METHODS 18 consecutive patients (17 females and 1 male with a mean age of 74 (57–90 years)) with TTC hospitalized between 01/ 2010 and 11/2015 in the 1st Department of Cardiology, Medical University of Warsaw, were included in the study. Patients were diagnosed with TTC on the basis of the Mayo Clinic criteria7: transient hypokinesis, akinesis, or dyskinesis of the left ventricular mid-segments with or without apical involvement; the regional wall motion abnormalities extend beyond a single epicardial vascular distribution; a stressful trigger is often, but not always, present; absence of obstructive coronary disease or angiographic evidence of acute plaque rupture; new ECG abnormalities (either ST segment elevation and/or T-wave inversion) or modest elevation in cardiac troponin; and the absence of pheochromocytoma or myocarditis. All patients had coronary angiography performed. In case of possibility of myocarditis, MRI was performed. The clinical characteristics including age, gender, coronary disease risk factors, symptoms, and possible triggering factor were listed in Table 1. An 18F-FDG metabolic PET, 99mTc-MIBI perfusion SPECT, and echocardiography were performed in all the patients. The study was approved by an institutional review committee. All subjects gave informed consent.
Myocardial Perfusion Study All patients underwent rest 99mTc-MIBI SPECT study (single-photon emission computed tomography) during the
Table 1. Clinical characteristics of TTC patients Age (years) Female pts (%) BMI (kgm-2) Symptoms Chest pain at admission (%) Dyspnoea at admission (%) Emotional stress (%) Troponin I max (ngmL-1) CK MB mass max (ngmL-1) EF in the Echo at admission (%) Dominant changes in the ECG ST segment elevation (%) ST segment depression (%) T inversion (%) Risk factors Hypertension (%) Smoking (%) Hypercholesterolemia (%) Family history (%) Fasting time (h)
74 (57–90) 94.4 26 (20–34) 88.9 61.1 50 2.63 (0.4–12.55) 10.394 (2.2–26.1) 44 (35–64) 61.1 19.5 19.5 88.9 16.7 72.2 16.7 15 (12–16)
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acute phase. The myocardial SPECT study was performed after overnight fasting. The study was conducted between 1 and 17 days from the onset of symptoms in all 18 patients with the use of double-head VariCam (Elscint) and SYMBIA T6 (Siemens) gamma cameras with a parallel hole, LEHR (lowenergy high-resolution) collimators. A dose of 600 MBq of 99mTc-MIBI at rest was intravenously injected, and data acquisition started 60 min thereafter. A 128 9 128 matrix was used and 60 images were acquired over 180° with 20 s per view, reconstructed by the use of the filtered back projection technique (Butterworth filter, cut-off 0.40, order 5). Standard tomographic images reoriented along the vertical long, horizontal long, and short axes were created. Left ventricular ejection fraction and end systolic and end diastolic volumes were calculated. QPS Cedars Sinai and Corridor 4DM software were used for qualitative and semi-quantitative analysis. For the analysis of the SPECT images, the AHA-recommended 17segment model polar map was used. Segments with perfusion of 100%–70% were considered normal, 70 to 50 as mildly to moderately reduced, and 50% and less as severely reduced, corresponding to scar tissue or hibernated myocardium.
Kobylecka et al Takotsubo cardiomyopathy
Coronary Angiography Coronary angiography was performed on the day of episode, by the radial or femoral approach. Coronary artery disease was defined as [50% stenosis in the luminal diameter of the epicardial coronary artery. No significant angiographic coronary atherosclerosis was found.
Statistical Analysis Statistical analysis was performed using SASÒ software, version 9.4. Continuous variables were presented as median value and interquartile range. All continuous variables were assumed to be non-normally distributed. Categorical data were presented as absolute and relative frequencies. Statistical significance of difference between groups was assessed: for quantitative variables with U Mann-Whitney test and for qualitative variables with Fisher’s exact test. A value of p \ .05 was considered significant for all tests.
RESULTS
Myocardial Glucose Metabolism Study
Echocardiography (TTE)
The 18F-FDG-PET/CT study was performed 1–18 days after the onset of symptoms. PET/CT fused acquisition was performed on a BIOGRAPH 64 (Siemens) PET/CT scanner. All studies were conducted after overnight fast. The image acquisition began 60 min after 250 MBq of 18F-FDG injection: first, a CT scan of thorax was performed, followed directly by 10-min PET acquisition. The Ca score assessment on the basis of CT study was performed simultaneously. CT data were used for attenuation correction of PET images. PET data were reconstructed with CT-based attenuation correction by the use of filtered back projection (Gaussian 6-mm filter). PET images were realigned along the short, horizontal long, and vertical long axes and then qualitatively and semiquantitatively interpreted by the use of QPS Cedars Sinai software.
At admission (Table 2), TTE showed abnormal contractile pattern: preserved basal function and apical akinesia/ dyskinesia were found in all patients. No patient had focal abnormalities inside the left ventricle (clots, thrombus, soft tissue mass). The left ventricular ejection fraction at admission was significantly reduced with a mean value of 44 (35%–64%). The contractility disturbances included segments with hypokinesis (total 32 in 9 patients), akinesis (total 76 segments in 18 patients), and dyskinesis (total 9 in 6 patients). The detailed numbers of impaired segments on admission and at the day of SPECT study are given in Table 2. Myocardial Perfusion Study
SPECT and PET Comparison A semiquantitative and qualitative analysis of myocardial 18-F-FDG and 99mTc-MIBI uptake was performed. A standard 17-segment AHA polar map was used to compare the SPECT and PET data, as recommended.8 A normalized tracer accumulation [50% of maximum both for PET and SPECT was considered viable.
SPECT examination was performed in all 18 cases between 1 and 17 days from the onset of symptoms (mean 5.4, SD 4.1). The images showed no regional perfusion abnormalities in 10/18 patients, as expected in patients without significant CAD. A mild perfusion defect not exceeding 4 segments of 17-segment model was found in 8/18 patients. Perfusion abnormalities were limited to apical and para-apical regions.
Echocardiography The exam was performed within 12 hours after admission, on the 3rd and 5th days of hospitalization, on the day of SPECT examination, and on the day of discharge. Left ventricular ejection fraction (LVEF) was calculated with the use of Simpson’s method. A standard 17-segment model was used to compare TTE abnormalities with PET and SPECT results.
Myocardial Glucose Metabolism Study 18F-FDG-PET study was performed in all 18 cases following the fasting preparation protocol during 1– 18 days (mean 5.1, SD 4.6) after the onset of symptoms. All studies were conducted after overnight fast, the time of fasting declared by patients varied from 12 to 16
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Table 2. Number of impaired left ventricular segments and % of left ventricular area calculated for 17segment model
ECHO
PET
Number of Number of abnormal % segments at the day % segments (initial) LV of SPECT LV 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18
4 5 9 8 6 7 6 8 5 5 5 7 5 5 6 6 5 5
24 30 54 50 36 40 36 50 30 30 30 40 30 30 36 36 30 30
– 5 3 5 3 7 0 0 6 – 1 0 0 5 6 0 5 5
– 30 18 30 18 40 0 0 36 – 0 0 0 0 36 0 30 30
SPECT
Number of abnormal segments
% LV
Number of abnormal segments
% LV
6 1 6 5 2 4 5 5 4 4 13 10 12 12 10 11 12 12
36 6 36 30 12 24 30 30 24 24 78 60 72 72 60 66 72 72
3 0 0 4 2 4 4 1 4 0 0 0 0 0 0 0 4 0
18 0 0 24 12 24 24 6 24 0 0 0 0 0 0 0 24 0
Comparison of PET, SPECT, and ECHO
hours—the last meal was eaten at 8 p.m. or earlier. The range of fasting glucose level obtained prior to FDG injection was 84–128 mgdL-1 (median 106 mgdL-1). In 8/18 cases, selective apical 18F-FDG accumulation was seen. In 10/18 cases, 18F-FDG uptake was present in all 17 segments but the uptake was inhomogeneous with a relatively reduced 18F-FDG accumulation in apical segments in comparison to basal segments. SPECT, PET, and TTE Comparison The mean interval between SPECT and PET examinations was 3.6 days (1–15, SD 4.1). Table 2 shows the number of abnormal left ventricular segments and the percentage of left ventricular area calculated for 17-segment model assessed by PET, SPECT, and TTE. Comparison of myocardial perfusion and glucose metabolism revealed few different metabolic/perfusion uptake patterns. In the group with reduced apical 18FFDG uptake and high metabolic activity elsewhere in the myocardium, 7/10 patients had a corresponding apical perfusion defect by SPECT (Figure 1). In patients
Fig. 1. Perfusion and metabolic images in patient with c reduced apical FDG accumulation. Declared fasting time is 16 hours. A 18F-FDG-PET qualitative and semiquantitative (polar map presentation) assessment: high FDG myocardial uptake with reduced apical accumulation. B 99mTc-MIBI qualitative and semiquantitative (polar map presentation) assessment: mildly reduced apical perfusion.
with selective apical 18F-FDG uptake, 1/8 patients had an apical perfusion defect, whereas 7/8 patients had no perfusion abnormality (Figure 2). The comparison of metabolism and perfusion revealed the patterns listed in Table 3. The patients were divided into two groups depending on the 18F-FDG uptake pattern by PET: group 1— patients with reduced apical uptake (10 pts), and group 2—patients with selective high apical uptake.8 A univariate analysis was performed, and the results are listed in Table 4. Despite the small number of patients studied, there were statistically significant differences between the two patient groups involving the number of abnormally perfused segments on SPECT, percentage of left
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ventricle with reduced perfusion, number of segments with reduced 18F-FDG uptake, percentage of LV with reduced 18F-FDG uptake, SUVmax of the basal and middle segments of the left ventricle, the and presence of well-specified stress factor in anamnesis, which were better specified for the group with reduced apical 18FFDG uptake. Ca score was numerically higher for the group with selective apical 18F-FDG uptake but the difference was not statistically significant. In both groups, there were no statistically significant differences between such parameters as age, BMI, blood pressure and heart rate, left ventricular ejection fraction, number of abnormal segments at TTE, ECG changes, glucose level at the time of 18F-FDG administration, time from 18F-FDG injection to PET acquisition, time from the event to PET study, as well as laboratory parameters and cardiovascular risk factors. DISCUSSION The study results revealed heterogeneous myocardial perfusion/metabolic patterns. The reasons may be numerous, but primarily physiological myocardial metabolism is heterogeneous, influenced by the patient’s metabolic condition. Influence of Specific 18F-FDG-PET Protocol on the Cardiac Image There are two 18F-FDG-PET protocols commonly used: glucose load and fasting protocols. 18F-FDG-PET cardiac study is usually performed in patients with TTC with the use of glucose load protocol, where high 18FFDG myocardial uptake is forced by administration of glucose. The typical perfusion/metabolic pattern showed reduced apical 18F-FDG uptake and slightly reduced or normal perfusion.1–3 Although the fasting preparation protocol was used for our analysis, in 10/18 cases we found decreased 18F-FDG uptake in the apical myocardium along with intense accumulation elsewhere. How to explain such uptake pattern in fasting patients with TTC? This unexpected finding can be the result of preferential glucose uptake due to pathophysiologic changes. Aging and cardiomyopathy are conditions that cause favorable myocardial glucose utilization. The finding might also be related to metabolic disturbances in TTC, which possibly in some cases affect entire myocardium. One has to consider also violation of patient’s preparation protocol related to the acute nature of the disease, where the 12-hour period of complete fasting is hard to control. Normal myocardium in fasting stage is characterized by low 18F-FDG uptake. It is well known that ischemic episode switches the myocardial metabolism
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Fig. 2. Perfusion and metabolic images in patient with high c apical FDG accumulation. Declared fasting time is 15 hour 30 minutes. A Selective high apical 18F-FDG uptake. An 18FFDG-PET/CT fusion image shows selective apical FDG accumulation. An 18F-FDG-PET polar map presentation shows apical and para-apical segments with selective high myocardial uptake. B 99mTc-MIBI qualitative and semiquantitative (polar map presentation) assessment: normal perfusion.
from fatty acids (FFA) to much less efficient anaerobic glucose utilization, regardless of the patient’s metabolic condition. The selective high apical 18F-FDG uptake was found in 8/18 patients. This favored glucose accumulation, which is better visible in fasting stage. We decided to apply fasting 18F-FDG-PET protocol, assuming that the area of favored glucose accumulation with low ‘‘normal’’ myocardial background could allow for better delineation of diseased myocardial area, while glucose load protocol, in our opinion, can blur minor 18F-FDG accumulation defects. There is no literature describing 18F-FDG accumulation pattern in a larger group of fasting patients with TTC. A case report presented by Myiachi et al6 described focal high 18F-FDG accumulation in the LV apex in an 85-year-old female diagnosed with TTC, after prolonged fasting. They concluded that the disturbances are probably the result of inflammation. With respect to the presented results, the metabolic switch of glucose utilization is most likely related to stunned myocardium, being the result of ischemic microcirculatory dysfunction. Temporarily, the myocardium with microcirculatory disorders may participate in anaerobic metabolism, which is less efficient for ATP generation. There might be also other sources of high-energy phosphates in these patients, such as enhanced production of ATP by glycolysis. This source of ATP is important during ischemia.9 SPECT Perfusion The results of the studies carried out by other groups of scientists are different. Some authors confirmed the low coronary flow reserve (CFR) in the acute TTC phase,10–12 and some did not detect any significant abnormalities.13 Feola et al.14 described the decreased apical 18F-FDG uptake consistent with impairment in myocardial cell metabolism, with normal MBF (myocardial blood flow) at rest, as the common uptake pattern is present in TTC patients after glucose load protocol. We found in majority of our patients only mild apical perfusion defect or even normal perfusion. Moreover, abnormal myocardial perfusion was less prominent than PET metabolic disorders. According to the reports of Feola and Camici,12,15 the CFR
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Table 3. Comparison of metabolism and perfusion
No. of pts 7 3
7 1
Perfusion/metabolism uptake pattern Inhomogeneous FDG uptake in the entire myocardium with relatively reduced apical uptake and mild perfusion defect Inhomogeneous FDG uptake in the entire myocardium with relatively reduced apical uptake and no SPECT perfusion defect Selective high apical FDG uptake and no perfusion defect Selective high apical FDG uptake and mild apical perfusion defect
PET FDG uptake pattern typical for glucose load FDG-PET protocol FDG uptake pattern typical for glucose load FDG-PET protocol FDG uptake pattern related to ischemic memory FDG uptake pattern related to ischemic memory
Table 4. Characteristics of the study groups
Demographic and clinical data Age (year) BMI (kgm-2) HR (bpm) Systolic BP (mmHg) Diastolic BP (mmHg) Fasting time (h) LVEF at admission (%) LVEF (echocardiography) on the day of PET study LVEF (echocardiography) on the day of SPECT study Number of abnormal segments in echocardiography Number of abnormal segments in echocardiography on the day of SPECT study ST segment elevation in the ECG (%) Stress factor in anamnesis (%) Glucose serum level at 18F-FDG injection Grading of coronary artery disease (based on total calcium score) Ca score (Agatston score) Number of segments with reduced 18F-FDG uptake % of LV with reduced 18F-FDG uptake Number of abnormal segments in SPECT % of LV with reduced perfusion SUVmax of basal and middle segments SUVmax of the apex
Reduced apical glucose uptake (n 5 10)
Selective apical glucose uptake (n 5 8)
p value
74 (57–90) 27 (21–34) 80 (60–100) 123 (70–150) 78 (50–115) 14 (12–16) 41 (35–52) 38.1 (25–54)
74 (60–84) 25 (20–34) 88 (70–100) 131 (100–160) 74 (50–95) 15 (12–16) 47 (36–64) 36.4 (30–59)
.82 .15 .24 .5 .75 .49 .09 .37
50.75 (38–65)
58.4 (43–66)
.22
6.3 (4–9)
6.2 (5–10)
.75
3.63 (0–7)
2.29 (0–6)
.37
70 80 104 (94–125) 2 (1–3)
50 12.5 115 (84–154) 2 (1–4)
.63 .015 .33 .54
5 (0–15) 4.2 (1–6)
53 (0–162) 11.5 (10–13)
.13 .0003
24.6 (6–36) 2.2 (0–4) 14.67 (0–24) 7.3 (3.2–12.5) 3.2 (2.1–5.7)
69 (60–78) 0.5 (0–4) 3.43 (0–24) 2.5 (1–3.8) 5.4 (2.6–13.6)
.0003 .0337 .02 .0005 .11
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Table 4 continued
Reduced apical glucose uptake (n 5 10) SUVmax of mediastinal blood pool Laboratory parameters TnI at admission (ngmL-1) TnI max (ngmL-1) CK MB mass at admission (ngmL-1) CK MB mass max (ngmL-1) CRP at admission (mgL-1) Cardiovascular risk factors CAD (%) Hypertension (%) Diabetes mellitus (%) Dyslipidemia (%) Smoking (%) Family history (%)
Selective apical glucose uptake (n 5 8)
p value
2.2 (1.3–3.0)
2.3 (1.1–3.8)
.89
2.662 (0.37–10.87) 3.497 (0.85–12.55) 9.04 (1.6–23.8) 12.53 (2.2–26.1) 4.88 (1.5–10.3)
1.231 (0.06–3.69) 1.538 (0.396–3.69) 6.65 (0.5–18.2) 7.73 (2.2–18.2) 9.96 (0.2–35)
.33 .18 .69 .33 .60
10 90 30 70 20 20
25 87.5 37.5 75 12.5 12.5
.56 1.00 1.00 1.00 1.00 1.00
impairment that emerged in TTC patients occurred in the absence of obstructive CAD and structural myocardial diseases. This reversible CFR reduction not associated with structural vascular changes is similar to the one observed in asymptomatic smokers and asymptomatic patients with hypercholesterolemia and normal coronary arteries.16,17 Prior studies with myocardial perfusion scintigraphy have demonstrated the presence of perfusion defects in the first days of TTC, with rapid normalization of the perfusion pattern and subsequent restoration of LV function, according to the paradigm of myocardial stunning.18,19 Since microcirculatory dysfunction is a general phenomenon in TTC20 and it causes myocardial stunning, it is the reason of metabolic switch to favored glucose utilization. Comparison of TTE, SPECT, and PET Results We noticed that the area of high apical 18F-FDG accumulation corresponded with the hypo- or akinetic myocardium, assessed by TTE. Comparing the results of 18F-FDG-PET and SPECT, we found that in 7/8 patients there was no visible perfusion defect, and one patient had minor apical perfusion defect. This can be a result of ‘‘ischemic memory,’’ where, after acute ischemic episode and restored perfusion, impaired energy metabolism is still present. Christensen et al 21 noticed that in the group of TTC patients after glucose load protocol the reduction of myocardial 18F-FDG uptake with normal perfusion does not fulfill the criteria of stunning. On the contrary, our group of fasting patients with the selective
apical myocardial 18F-FDG uptake with normal perfusion does fulfill the presented criteria of stunning. In our subgroup of fasting patients with reduced apical 18F-FDG uptake and high metabolic activity elsewhere in the myocardium, perfusion SPECT showed only mild apical perfusion defect (7/10) or even normal perfusion (3/10). The association of impaired glucose metabolism and normal perfusion in the dysfunctional area called a ‘‘reversible inverse mismatch’’22 or an ‘‘inverse flow-metabolism mismatch’’ is consistent with the metabolic state of stunned myocardium.23 Semiquantitative Analysis of SPECT/PET Results As described in the literature, reduced 18F-FDG uptake in apical region was recognized in the visual and semiquantitative assessment after comparison with the relatively higher 18F-FDG accumulation in normal functioning middle and basal segments. Unfortunately, neither qualitative nor semiquantitative analysis allows for the judgment of which segment has normal glucose utilization: midventricular and basal with reduced apical or perhaps normal apical with hyperintense 18F-FDG accumulation elsewhere. The semiquantitative assessment of 18F-FDG accumulation and SPECT perfusion is relative and always normalized to the most active pixel of the myocardium. Christensen21 concluded that the apparent perfusion defect might be an artifact explained by relative hypoperfusion of apical segments in relation to basal hyperperfusion—which was normalized to
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100%. This remark over the technical nature of the apical perfusion and metabolic defect is not concordant with our observations. The presence of selective 18FFDG uptake restricted to abnormal perfused and hypokinetic segments in fasting patients confirms the existing metabolic disorder, not the artificial nature of the apical disturbances.
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our study not only during the first week but also during the second and even the third week from the onset of symptoms. Another limitation is the small number of patients studied. The findings should be confirmed in larger studies. CONCLUSIONS
Pathophysiologic Consideration According to the literature, more than four possible mechanisms play important roles in the complex TTC pathophysiology: epimyocardial vasospasm, disturbances in microcirculation, catecholamine-related injury of the myocytes, and obstruction of the left ventricle outflow tract. Feola14 confirmed the presence of microcirculation disturbance in apical segments, which in their opinion explains the transient decrease in glucose uptake and the contractile abnormalities as a mechanism of the disease. According to many authors, the catecholamine excess is connected with the reduction of glucose and 18F-FDG uptake.23,24 It is also known that catecholamines are associated with interstitial mononuclear inflammatory response. A contraction band necrosis characteristic for reperfused ischemic myocardium was also described in biopsy findings in the state of catecholamine excess in TTC patients.12 Limitations of Study One of the study limitations is the difference in the time of SPECT and PET studies. The reason of the time discrepancies originated from the nature of acute onset of TTC resulting in logistic problems in performing the PET study: 18F-FDG has to be ordered in advance. Complexity in radiotracer design and delivery and PET expense are well known, limiting access to the procedure. The 18F-FDG study has to be performed ‘‘as soon as possible’’ after the TTC diagnosis, due to its transient character. The use of proper patient’s preparation protocol needs cooperation with both the patients and clinical ward. Although the planned study was to be carried out after overnight fasting, without glucose load protocol, in 10 cases the glucose was accumulated in the entire myocardium, which might suggest the notfastened patient’s state, but also as mentioned beforecan be result of the pathophysiologic changes or even physiologic aging. Although the time from the onset of symptoms to the study varied, all studies were performed during the subacute phase of TTC. Both diminished and selective high apical 18F-FDG uptake patterns were acquired in
This study demonstrated the heterogeneous nature of myocardial 18F-FDG accumulation in patients with TTC. Selective, preferential apical 18F-FDG uptake in almost half of the patients confirms an existing disorder of glucose metabolism, similar to that observed in stunned or hibernated myocardium, and excludes the artificial nature of the apical defect. The most important difference between the two described 18F-FDG uptake patterns was SPECT perfusion defect, more often observed in the group with reduced apical 18F-FDG uptake. Heterogeneous 18F-FDG uptake pattern may be associated with different variants of physiological myocardial uptake as well as with possible complex nature of metabolic disorders in TTC. The results obtained in our study suggest the presence of two possible forms of perfusion/metabolic disorders related probably to the severity of the disease: 1. The high selective apical 18F-FDG uptake is related to the switch into anaerobic glucose utilization due to transient vasospasm with rapid recovery. SPECT perfusion is usually normal or slightly reduced. 2. Myocardial 18F-FDG uptake in all LV segments, despite the fasting condition, might be related to metabolic disturbances in TTC, which possibly in some cases affect the entire myocardium. The SPECT study is usually abnormal, with mildly to moderately reduced apical perfusion. The possible reason considered could be the vasospasm with longer recovery. 3. The proposed hypothesis of stunning with early versus delayed recovery to explain these contrary findings needs additional proof and study.
NEW KNOWLEDGE GAINED Intense apical 18F-FDG accumulation speaks for stunned myocardium, as the cause of the TTC contractility disorders. The opposing 18F-FDG uptake pattern—decreased apical and preserved 18F-FDG accumulation elsewhere—is baffling, but it does not exclude myocardial stunning. Stunned myocardium in patients without existing morphologic changes in coronary arteries is the result of microcirculatory transient disorder. Most of our findings suggest that the decreased
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apical 18F-FDG accumulation reported in patients with TTC after 18F-FDG load protocol may not be artifactual in nature but rather related to a switch in glucose metabolism. Disclosure The authors have indicated that they have no financial conflict of interest.
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