99mTc-MIBI washout rate as a marker of myocardial mitochondrial dysfunction: A systematic review and meta-analysis

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Abstract

BACKGROUND: This review outlines the features of the pharmacokinetics of the perfusion radiopharmaceutical 99mTc-MIBI, which allows the assessment of myocardial mitochondrial dysfunction, and shows the main clinical applications of the phenomenon of increased 99mTc-MIBI washout rate.

AIM: To systematize the data of fundamental (experimental) and clinical studies evaluating and estimating mitochondrial dysfunction according to myocardial perfusion scintigraphy data and perform meta-analysis of clinical studies in this field.

MATERIALS AND METHODS: PubMed, Scopus, Google Scholar, and eLibrary databases were searched until mid-2023. The following keywords, their combinations, and Russian-language counterparts were used: mitochondrial dysfunction, 99mTc-MIBI, 99mTc-Tetrofosmin, myocardial perfusion scintigraphy, reverse redistribution, washout, and washout rate. In the meta-analysis, a random-effects model was used to calculate the mean difference estimate.

RESULTS: Forty articles were selected for systematic analysis: 13 were experimental, 24 were original clinical papers, 2 were clinical cases, and 1 was a review. Six studies using a case–control design were selected for the meta-analyses. The total number of patients in the systematic review and meta-analysis were 551 and 196, respectively. In the analysis of the literature, the severity of the reverse redistribution phenomenon and 99mTc-MIBI washout rate correlated with mitochondrial and myocardial microstructure, left ventricular contractility and hemodynamics, natriuretic peptide levels, exercise tolerance, coronary atherosclerosis severity, myocardial oxidative metabolism, and risk of cardiovascular events. The meta-analysis showed that the washout rate was statistically significantly accelerated in individuals with cardiac pathologies, relative to controls (mean difference score, 9.5771 [95%]; confidence interval, 6.6001–12.5540; z=6.3053, p <0.0001).

CONCLUSION: The assessment of mitochondrial function by 99mTc-MIBI washout evaluation may provide additional insights into the functional status of cardiac muscles.

About the authors

Marina O. Gulya

Cardiology Research Institute, Tomsk National Research Medical Center

Email: mgulyatomsk@mail.ru
ORCID iD: 0000-0001-5689-9754
SPIN-code: 3064-3773
Scopus Author ID: 56700201800
ResearcherId: M-1017-2016

MD, Cand. Sci. (Med.)

Russian Federation, Tomsk

Konstantin V. Zavadovsky

Cardiology Research Institute, Tomsk National Research Medical Center

Author for correspondence.
Email: konstzav@gmail.com
ORCID iD: 0000-0002-1513-8614
SPIN-code: 5081-3495
ResearcherId: F-9990-2014

MD, Dr. Sci. (Med.)

Russian Federation, Tomsk

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2. Fig. 1. Schematic depiction of the mechanism of the accumulation of various diagnostic agents in the cell and intercellular space. 201/199Tl: thallium-201 or thallium-199; its uptake is determined by membrane integrity and normal functioning of the Na+/K+ pump. 82Rb: rubidium-82; its uptake is also determined by the Na+/K+ pump. 99mTc-MIBI/TF-based tracers: lipophilic cations that freely pass through the mitochondrial membrane and are retained because of the transmembrane potential. Dobutamine stimulates β1 and β2 adrenergic receptors, increasing the intracellular calcium concentration and inotropic function of the heart. 18F-FDG: fluorodeoxyglucose accumulates in the cell via the glucose transporter protein. 13NH3: ammonium is accumulated via passive diffusion and active transport of the Na+/K+ pump. H215O: oxygen-15 labeled water readily diffuses into the cell, forming an equilibrium between the extracellular and intracellular pools. Gadolinium is an extracellular diagnostic agent that is retained in the intercellular space.

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3. Fig. 2. An example of the absence and presence of 99mTc-MIBI reverse redistribution. Patient 1: female, 56 years old, CAD (grade II stable angina) secondary to nonobstructive coronary atherosclerosis; CHF, NYHA class II; LV ejection fraction, 64%; end-systolic volume, 42 mL; end-diastolic volume, 117 mL. Delayed imaging (240 min) revealed no perfusion defects. Patient 2: male, 58 years old; CAD (grade II stable angina); anterior descending artery stenosis, 75%; right coronary artery stenosis, 70%; CHF, NYHA class II; LV ejection fraction, 65%; end-systolic volume, 39 mL; end-diastolic volume, 112 mL. Delayed imaging (240 min) revealed perfusion defects (arrows) that were not detected during early imaging (60 min). Images were obtained at the Research Institute of Cardiology, Tomsk National Research Medical Center.

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4. Fig. 3. Meta-analysis results (k=6 studies). Mean differences ranged from 5.3000 to 14.9900; most ratings were positive (100%). The mean difference estimate based on the random effects model was 9.5771 (95% confidence interval: 6.6001–12.5540); the mean score was significantly different from zero (z=6.3053; p<0.0001).

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