Digital DiagnosticsDigital DiagnosticsDigital DiagnosticsDigital Diagnostics2712-84902712-8962Eco-Vector56866810.17816/DD568668Systematic reviewsСистематические обзоры系统评价Review Article99mTc-MIBI washout rate as a marker of myocardial mitochondrial dysfunction: A systematic review and meta-analysisСкорость вымывания 99mTc-метокси-изобутил-изонитрила как маркёр митохондриальной дисфункции миокарда: систематический обзор и метаанализ99m锝-甲氧基异丁基异腈（99mTc-MIBI）洗脱率作为心肌线粒体功能障碍的标志物；系统综述和荟萃分析https://orcid.org/0000-0001-5689-975456700201800M-1017-20163064-3773GulyaMarina O.ГуляМарина ОлеговнаGulyaMarina O.
Russian Federation

MD, Cand. Sci. (Med.)

канд. мед. наук

MD, Cand. Sci. (Med.)

mgulyatomsk@mail.ruhttps://orcid.org/0000-0002-1513-8614F-9990-20145081-3495ZavadovskyKonstantin V.ЗавадовскийКонстантин ВалерьевичZavadovskyKonstantin V.
Russian Federation

MD, Dr. Sci. (Med.)

д-р мед. наук

MD, Dr. Sci. (Med.)

konstzav@gmail.comCardiology Research Institute, Tomsk National Research Medical CenterНаучно-исследовательский институт кардиологии, Томский национальный исследовательский медицинский центрCardiology Research Institute, Tomsk National Research Medical Center1010202315122023445095282208202311092023Copyright ©; 2023, Eco-VectorCopyright ©; 2023, Эко-векторCopyright ©; 2023, Eco-Vector2023Eco-VectorЭко-векторEco-Vectorhttps://creativecommons.org/licenses/by-nc-nd/4.0https://jdigitaldiagnostics.com/DD/article/view/568668

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.

Обоснование. В обзоре изложены особенности фармакокинетики перфузионного радиофармпрепарата 99mTc-MIBI, которые позволяют оценить митохондриальную дисфункцию миокарда, а также показаны основные клинические точки приложения феномена ускоренного вымывания данного индикатора.

Цель. Систематизация данных фундаментальных (экспериментальных) и клинических исследований в области изучения и оценки митохондриальной дисфункции по результатам перфузионной сцинтиграфии миокарда; проведение метаанализа клинических исследований в данной области.

Материалы и методы. Поиск проводился в базах данных Pubmed, Scopus, Google Scholar и eLibrary до середины 2023. Были использованы ключевые слова, их комбинации и англоязычные аналоги: митохондриальная дисфункция, 99mTc-МИБИ, 99mTc-Тетрофосмин, перфузионная сцинтиграфия миокарда, обратное перераспределение, вымывание, скорость вымывания. При выполнении метаанализа для расчёта средней оценки разницы была использована модель случайных эффектов.

Результаты. Для систематического анализа было отобрано 40 статей: 13 — экспериментальные, 24 — оригинальные клинические работы, 2 — клинические случаи, 1 обзор. Для выполнения метаанализа было отобрано 6 исследований по дизайну «случай–контроль». Общее число пациентов, составивших основу систематического обзора, — 551; число пациентов, составивших основу метаанализа — 196. Анализ литературы показал, что выраженность феномена обратного перераспределения и скорость вымывания 99mTc-MIBI взаимосвязаны с микроструктурой митохондрий и миокарда, сократимостью и гемодинамикой левого желудочка, уровнем натрийуретических пептидов, толерантностью к физическим нагрузкам, тяжестью коронарного атеросклероза, окислительным метаболизмом миокарда, уровнем риска сердечно-сосудистых событий. Метаанализ показал, что скорость вымывания статистически значимо повышена у лиц с патологией сердца, по отношению к контролю (средняя оценка разницы 9,5771 (95% доверительный интервал: от 6,6001 до 12,5540; z=6,3053; p <0,0001).

Заключение. Оценка функции митохондрий по данным оценки вымывания 99mTc-MIBI может предоставить дополнительные сведения о функциональном состоянии сердечной мышцы.

论证。本综述概述了灌注放射性药物99mTc-MIBI的药代动力学特征。这些特征可被用于评估心肌线粒体功能障碍。综述还说明了该指标加速洗脱现象的临床应用要点。

该研究的目的是系统整理关于通过心肌灌注闪烁成像研究和评估线粒体功能障碍领域的基 础（实验）和临床研究数据；对该领域的临床研究进行荟萃分析。

材料与方法。检索是在Pubmed、Scopus、Google Scholar和eLibrary数据库中进行的，检索期截至2023年年中。使用的关键词及其组合和英文对应词包括：线粒体功能障碍、99mTc-MIBI、 99m锝-替曲膦、心肌灌注闪烁成像、反向再分布、洗脱、洗脱率。在进行荟萃分析时，采用了随机效应模型来计算平均差异估计值。

结果。我们一共选中了40篇文章，以进行系统分析：其中13篇为实验性文章，24篇为临床医学论文，2篇为临床病例，1篇为综述。我们一共选中了6项研究，以进行病例对照模型的荟萃分析。系统综述中的患者总人数为551人；荟萃分析中的患者人数为196人。文献分析显示了，反向再分布现象的严重程度和99mTc-MIBI洗脱率与线粒体和心肌微结构、左室收缩力和血流动力、利尿钠肽水平、运动耐量、冠状动脉粥样硬化严重程度、心肌氧化代谢和心血管事件风险水平相关。荟萃分析表明了，与对照组相比，心脏病变受试者的洗脱率在统计学上显著较高。平均差异估计值为9.5771（95%置信区间：6.6001至12.5540；z=6.3053；p<0.0001）。

结论。通过99mTc-MIBI洗脱评估对线粒体功能进行评估，可为了解心肌功能状态提供更多信息。

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