Elsevier

Journal of Nuclear Cardiology

Volume 30, Issue 6, December 2023, Pages 2454-2463
Journal of Nuclear Cardiology

Original Article
Meta-analysis of the effectiveness of heparin in suppressing physiological myocardial FDG uptake in PET/CT

https://doi.org/10.1007/s12350-023-03296-2Get rights and content

Abstract

Background

The present meta-analysis aims to investigate the effectiveness of heparin administration in suppressing physiological myocardial 18F-fluorodeoxyglucose (FDG) uptake on positron emission tomography (PET)/computed tomography (CT), as its role in this regard has not been well investigated.

Methods

PRISMA guidelines were used to interrogate the PubMed, Embase, Cochrane library, Web of Knowledge, and www.clinicaltrail.gov databases from the earliest records to March 2023. The final analysis included five randomized controlled trials (RCTs). Meta-analysis was conducted to compare the effectiveness of unfractionated heparin (UFH) administration versus non-UFH administration, and subgroup analysis based on fixed and variable fasting durations was conducted. Effect sizes were pooled using a random-effects model, and the pooled odds ratios (ORs) were calculated.

Results

Five eligible RCTs with a total of 910 patients (550 with heparin, 360 without heparin) were included. The forest plot analysis initially indicated no significant difference in the suppression of myocardial FDG uptake between the UFH and non-UFH groups (OR 2.279, 95% CI 0.593 to 8.755, p = 0.23), with a high degree of statistical heterogeneity (I2 = 91.16%). Further subgroup analysis showed that the fixed fasting duration group with UFH administration had statistically significant suppression of myocardial FDG uptake (OR 4.452, 95% CI 1.221 to 16.233, p = 0.024), while the varying fasting duration group did not show a significant effect.

Conclusions

According to the findings of our meta-analysis, we suggest that intravenous administration of UFH can be considered as a supplementary approach to suppress myocardial FDG uptake.

Introduction

The suppression of physiological myocardial 18F-fluorodeoxyglucose (FDG) uptake in positron emission tomography (PET)/computed tomography (CT) scans is mainly achieved through three main methods: prolonged fasting, high-fat low-carbohydrate diet (HFLCD), and intravenous unfractionated heparin (UFH). Prolonged fasting causes the myocardium to switch to lipids as its primary energy source. Multiple authors have suggested the implementation of 12 to 18 hours fasting as a means to decrease physiological myocardial FDG uptake.1,2 HFLCD reduces insulin release and increases systemic lipolysis.3 Heparin has been utilized as a pharmacological approach to manipulate myocardial metabolism. The most recommended protocol involves a single 50 IU/kg dose of heparin administered approximately 15 minutes before FDG administration.4 This approach has been suggested as a supplementary method to prolonged fasting or HFLCD to suppress glucose metabolism in the myocardium.

Several authors reported that combining HFLCD, prolonged fasting, and UFH are more effective in suppressing cardiac glucose metabolism than HFLCD or prolonged fasting alone.5, 6, 7 Larson et al. found that combining these three methods resulted in adequate suppression of myocardial FDG uptake in 95% of patients.8 However, studies by Christopoulos et al.9 and Huang et al.3 using only HFLCD and prolonged fasting without UFH still showed that 91% to 93% of patients achieved good suppression. The use of UFH remains inconclusive due to the efficacy of myocardial suppression and the risk of heparin-induced thrombocytopenia and requires further research to establish an appropriate protocol.2

A meta-analysis by Tang et al.10 found that different patient preparation methods can affect the sensitivity and specificity of FDG PET in diagnosing cardiac sarcoidosis and prolonged fasting had a greater impact than heparin infusion. The meta-analysis did not provide conclusions on the effect of heparin infusion alone on diagnostic accuracy. The study also observed heterogeneity in the effect of intravenous heparin infusion alone across various studies. The aim of the present meta-analysis is to gather and quantify results from relevant randomized controlled trials (RCTs) and compare the efficacy of administering UFH in suppressing myocardial FDG uptake in PET/CT scans.

Section snippets

General guidelines

This meta-analysis was registered in INPLASY under the registration number INPLASY202330015 and was conducted following the guidelines outlined in the latest version of the PRISMA 2020.11 Ethics review board approval and participant informed consent were not required. The primary objective of this study was to evaluate the efficacy of administering heparin in suppressing physiological myocardial FDG uptake.

Literature search

A comprehensive literature search was conducted using PubMed as the primary source and

Included studies

The PRISMA flowchart for the literature search is illustrated in Figure 1. A total of 39 articles were initially identified through title and abstract screening, of which 23 were excluded due to non-compliance with inclusion criteria. The remaining 16 articles underwent full-text review, and 11 were ultimately excluded for various reasons such as being a case report (n = 2), review paper (n = 4), animal study (n = 2), lacking a placebo control (n = 2), or lacking suppression score data (n = 1).

Efficacy of UFH in suppressing myocardial FDG uptake

Three approaches have been proposed to reduce myocardial FDG uptake. Prolonged fasting induces a metabolic shift in the myocardium towards lipid utilization. HFLCD suppresses insulin secretion and enhances lipolysis. The combination of prolonged fasting and HFLCD is more effective in decreasing GLUT-4 expression and reducing myocardial glucose uptake. In addition, heparin administration has been shown to activate serum lipoprotein lipase and increase circulating free fatty acid (FFA) levels.

Limitations

The present meta-analysis is subject to several limitations that must be taken into account. First, the number of studies included in the analysis is limited, with only five RCTs meeting the criteria as outlined in the PRISMA flowchart. Studies with small sample sizes are often associated with increased sampling errors. Second, the high degree of statistical heterogeneity among the RCTs makes subgrouping challenging for subgroup analysis. Despite the presence of a statistically significant

Conclusion

The present meta-analysis suggests a higher overall suppression of physiological myocardial FDG uptake when UFH is used in combination with other patient preparation protocols, highlighting the significant role of UFH as an adjunctive factor. Therefore, the use of intravenous UFH can be considered as a supplementary method for patients who are unable to prolong fasting or fully comply with the prescribed diet before undergoing FDG PET/CT. After proper clinical assessment of the risk–benefit

New Knowledge Gained

The use of intravenous UFH in combination with other patient preparation protocols, such as prolonged fasting and HFLCD, leads to a more pronounced suppression of physiological myocardial FDG uptake, highlighting that UFH serves as a significant adjunctive factor in this regard.

Acknowledgements

We thank Dr. I-Chen Tsai for his valuable suggestions on the meta-analysis method.

Disclosures

The authors have no relationships to disclose.

References (18)

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Shan-Ho Chan and Cheng-Kai Huang have contributed equally to this work.

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