Relationship between left ventricular mechanical dyssynchrony and accelerated 99mTc-MIBI clearance in patients with heart failure

Aim. To evaluate ^99mTc-methoxy-isobutyl-isonitrile (^99mTc-MIBI) washout rate and its relationship with contractility and left ventricular (LV) mechanical dyssynchrony in patients with heart failure (HF) of non-ischemic origin.

Material and methods. The study included 20 patients with HF of non-ischemic origin with indications for cardiac resynchronization therapy (CRT). Ten patients without HF were included in the comparison group. All patients underwent ^99mTc-MIBI myocardial perfusion scintigraphy (MPS). We assessed the ^99mTc-MIBI washout rate, as well as LV perfusion, contractility, and mechanical dyssynchrony using phase analysis data (phase standard deviation, histogram bandwidth (HBW), asymmetry, and gradient). Six months after CRT, all patients with HF underwent MPS to assess the changes of studied parameters.

Results. According to MPS, patients with HF had a higher ^99mTc-MIBI washout rate from the LV myocardium compared with the comparison group (10,9 (8,49-13,8) vs 3,98 (0,9-9,8)%, p=0,0001), as well as severe LV mechanical dyssynchrony (standard deviation: 66 (55,11-73,24) vs 13,1 (10,1-19,6), p<0,0001; HBW: 207 (165-246) vs 40 (33-66), p<0,0001). The ^99mTc-MIBI washout rate was positively correlated with LV end-diastolic (r=0,46, p<0,001) and LV end-systolic volumes (r=0,44, p<0,001) and negatively correlated with LV ejection fraction (r=0,41, p<0,001). A moderate correlation was found between the ^99mTc-MIBI washout rate and following LV mechanical dyssynchrony and contractility parameters: HBW (r=0,412, p<0,001), asymmetry (r=-0,41, p<0,001), gradient (r=-0,44, p<0,001), wall motion (r=-0,45, p=0,001), wall thickening (r=-0,54, p<0,001). Six months after CRT, all patients showed a significant decrease in the ^99mTc-MIBI washout rate from 12,4 (10,3-14,9) to 8,14 (3,37-8,88)%, p=0,0006.

Conclusion. In patients with HF of non-ischemic origin, an increase in the ^99mTc-MIBI washout rate from the LV myocardium is associated with the severity of impaired cardiac contractility and mechanical dyssynchrony.

1. Garganeeva AA, Bauer VA, Borel KN. The pandemic of the XXI century: chronic heart failure is the burden of the modern society. Epidemiology (literature review). The Siberian Journal of Clinical and Experimental Medicine. 2014;29(3):8-12. (In Russ.) doi:10.29001/2073-8552-2014-29-3-8-12.

2. Gulya MO, Zavadovsky KV. 99mTc- MIBI washout rate as a marker of myocardial mitochondrial dysfunction: A systematic review and meta-analysis. Digital Diagnostics. 2023;4(4):509-28. (In Russ.) doi:10.17816/DD568668.

3. S hibayama J, Yuzyuk TN, Cox J, et al. Metabolic remodeling in moderate synchronous versus dyssynchronous pacing- induced heart failure: integrated metabolomics and proteomics study. PLoS One. 2015;10(3):e0118974. doi:10.1371/journal.pone.0118974.

4. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Russian Journal of Cardiology. 2023;28(1):5168. (In Russ.) 2021 doi:10.15829/1560-4071-2023-5168.

5. Stiles MK, Fauchier L, Morillo CA, et al. 2019 HRS/EHRA/APHRS/LAHRS focused up date to 2015 expert consensus statement on optimal implantable cardioverter- defibrillator programming and testing. Heart Rhythm. 2020;17:e220-e228. doi:10.1016/j.hrthm.2019.02.034.

6. Matsuo S, Nakae I, Tsutamoto T, et al. A novel clinical indicator using Tc-99m sestamibi for evaluating cardiac mitochondrial function in patients with cardiomyopathies. J Nucl Cardiol. 2007;14(2):215-20. doi:10.1016/j.nuclcard.2006.10.022.

7. Kirk JA, Kass DA. Cellular and Molecular Aspects of Dyssynchrony and Resynchronization. Card Electrophysiol Clin. 2015;7(4):585-97. doi:10.1016/j.ccep.2015.08.011.

8. Lobanova OA, Golovanova NE, Gaikovaya LB. The role of mitochondrial dysfunction and disorders of energy metabolism in the pathogenesis of chronic heart failure. Russian journal of physiology. 2017;103(6):606-16. (In Russ.)

9. Torrealba N, Aranguiz P, Alonso C, et al. Mitochondria in Structural and Functional Cardiac Remodeling. Adv Exp Med Biol. 2017;982:277-306. doi:10.1007/978-3-319-55330-6_15.

10. Matsuo S, Nakajima K, Kinuya S. Evaluation of Cardiac Mitochondrial Function by a Nuclear Imaging Technique using Technetium-99m- MIBI Uptake Kinetics. Asia Ocean J Nucl Med Biol. 2013;1(1):39-43. doi:10.7508/aojnmb.2013.01.008.

11. Yamanaka M, Takao S, Otsuka H, et al. The Utility of a Combination of 99mTc- MIBI Washout Imaging and Cardiac Magnetic Resonance Imaging in the Evaluation of Cardiomyopathy. Annals of Nuclear Cardiology. 2021;7(1):8-16. doi:10.17996/anc.21-00124.

12. Liu Z, Johnson G 3rd, Beju D, et al. Detection of myocardial viability in ischemic- reperfused rat hearts by Tc-99m sestamibi kinetics. J Nucl Cardiol. 2001;8(6):677-86. doi:10.1067/mnc.2001.117687.

13. Kawamoto A, Kato T, Shioi T, et al. Measurement of technetium-99m sestamibi signals in rats administered a mitochondrial uncoupler and in a rat model of heart failure. PLoS One. 2015;10(1):e0117091. doi:10.1371/journal.pone.0117091.

14. Kato T. Analysis of Cardiac Metabolic Remodeling in Heart Failure Using Nuclear Medicine and Its Application: Japanese Society of Nuclear Cardiology Award. Ann Nucl Cardiol. 2020;6(1):91-4. doi:10.17996/anc.20-00112.

15. Masuda A, Yoshinaga K, Naya M, et al. Accelerated (99m)Tc-sestamibi clearance associated with mitochondrial dysfunction and regional left ventricular dysfunction in reperfused myocardium in patients with acute coronary syndrome. EJNMMI Res. 2016;6(1):41. doi:10.1186/s13550-016-0196-5.