Capabilities of gated myocardial perfusion imaging in detecting decreased myocardial blood flow reserve in patients with non-obstructive coronary artery disease

Introduction: In patients with non-obstructive coronary artery disease, decreased myocardial blood flow reserve (MBFR) is a key pathophysiologic link. Noninvasive assessment of microcirculatory status is available to a very limited number of institutions, in contrast to routine gated myocardial perfusion imaging (gMPI). Mechanical dyssynchrony (MD) is one of the promising additional index of gMPI, but nowadays there are very few data on its comparison with MFR by SPECT.

Aim: To evaluate the potential of MD according to gMPI in identifying patients with decreased MBFR according to dynamic SPECT.

Material and Methods. The study included 62 patients with non-significant (<50%) coronary artery stenosis according to multislice computed tomography (MSCT) coronary angiography. All patients underwent dynamic SPECT and routine gMPI with 99mTc-technetril. Myocardial blood flow indices at rest and stress, as well as MBFR were evaluated according to dynamic SPECT data. Perfusion indices (SSS, SRS, SDS) and MD indices HBW (phase histogram width, grad.) and PSD (phase histogram standard deviation, grad.) were assessed according to gMPI. Patients were then divided into 2 groups depending on myocardial blood flow reserve indices with a threshold value 2.0.

Results. 30 patients were included in the group with reduced MBFR (MBFR<2.0) and 32 patients in the group with preserved MBFR (MFR ≥ 2.0). There was no difference in the main clinical and demographic parameters between the groups. The groups differed in all MD parameters: HBWrest, 64.8 (55.8; 86;4) and 50.4 (42.2; 57.6), p = 0.004; HBWstress, 64.8 (50.4; 93;6) and

50.4 (50.4;63.0), р = 0.03; PSDrest, 17.2 (13.5;22.4) and 12.9 (9.9;14.0), р = 0.01; PSDstress, 15.8 (13.7;23.0) and 12.9 (11.6;15.0), р = 0.01. The only independent predictor of decreased MBFR <2.0 was HBW at rest > 57.6o; OR 1.07; CI (1.01; 1.12); р < 0.001; AUC = 0.810.

Conclusion. Mechanical dyssynchrony assessed by gMPI correlates with myocardial blood flow reserve according to dynamic SPECT in patients with non-obstructive coronary artery disease. The most pronounced association with MBFR has phase histogram bandwidth at rest. In patients with non-obstructive coronary artery disease, if HBW at rest is > 57.6o according to ECG-PCM, a reduced myocardial blood flow reserve can be suspected.

1. Del Buono M.G., Montone R.A., Camilli M., Carbone S., Narula J., Lavie C.J. et al. Coronary microvascular dysfunction across the spectrum of cardiovascular diseases: JACC State-of-the-Art Review. J. Am. Coll. Cardiol. 2021;78(13):1352–1371. https://doi.org/10.1016/j.jacc.2021.07.042

2. Agostini D., Roule V., Nganoa C., Roth N., Baavour R., Parienti J.J. et al. First validation of myocardial flow reserve assessed by dynamic 99mTc-sestamibi CZT-SPECT camera: head to head comparison with 15O-water PET and fractional flow reserve in patients with suspected coronary artery disease. The WATERDAY study. Eur. J. Nucl. Med. Mol. Imaging. 2018;45(7):1079–1090. https://doi.org/10.1007/s00259-0183958-7

3. Zavadovsky K.V., Mochula A.V., Boshchenko A.A., Vrublevsky A.V., Baev A.E., Krylov A.L. et al. Absolute myocardial blood flows derived by dynamic CZT scan vs invasive fractional flow reserve: Correlation and accuracy. J. Nucl. Cardiol. 2021;28(1):249–259. https://doi.org/10.1007/s12350-019-01678-z

4. Zavadovsky K.V., Vesnina Zh.V., Anashbaev Zh.Zh., Mochula A.V., Sazonova S.I., Ilyushenkova Yu.N. et al. Current status of nuclear cardiology in the Russian Federation. Russian Journal of Cardiology. 2022;27(12):105–114. https://doi.org/10.15829/1560-4071-2022-5134

5. Lee K., Han S., Ryu J., Cho S.-G., Moon D.H. Prognostic value of left ventricular mechanical dyssynchrony indices derived from gated myocardial perfusion SPECT in coronary artery disease: a systematic review and meta-analysis. Annals of nuclear medicine. 2024;38(6):441– 449. https://doi.org/10.1007/s12149-024-01915-7

6. Fan L., Namani R., Choy J.S., Kassab G.S., Lee L.C. Effects of mechanical dyssynchrony on coronary flow: insights from a computational model of coupled coronary perfusion with systemic circulation. Front. Physiol. 2020;11:915. https://doi.org/10.3389/fphys.2020.00915

7. Fan L., Namani R., Choy J.S., Awakeem Y., Kassab G.S., Lee L.C. Role of coronary flow regulation and cardiac-coronary coupling in mechanical dyssynchrony associated with right ventricular pacing. Am. J. Physiol. Heart Circ. Physiol. 2021;320(3):H1037–H1054. https://doi.org/10.1152/ajpheart.00549.2020

8. Van Tosh A., Votaw J.R., Cooke C.D., Reichek N., Palestro C.J., Nichols K.J. Relationships between left ventricular asynchrony and myocardial blood flow. J. Nucl. Cardio. 2017;24(1):43–52. https://doi.org/10.1007/s12350-015-0270-9

9. Van Tosh A., Votaw J.R., Cooke C.D., Cao J.J., Palestro C.J., Nichols K.J. Early onset of left ventricular regional asynchrony in arteries with sub-clinical stenosis. J. Nucl. Cardio. 2021;28(3):1040–1050. https://doi.org/10.1007/s12350-020-02251-9

10. Sciagrà R., Lubberink M., Hyafil F., Saraste A., Slart R.H.J.A., Agostini D. et al.; Cardiovascular Committee of the European Association of Nuclear Medicine (EANM). EANM procedural guidelines for PET/CT quantitative myocardial perfusion imaging. Eur. J. Nucl. Med. Mol. Imaging. 2021;48(4):1040–1069. https://doi.org/10.1007/s00259-020-05046-9

11. AlJaroudi W., Jaber W.A., Cerqueira M.D. Effect of tracer dose on left ventricular mechanical dyssynchrony indices by phase analysis of gated single photon emission computed tomography myocardial perfusion imaging. J. Nucl. Cardiol. 2012;19(1):63–72. https://doi.org/10.1007/s12350-011-9463-z

12. Shipulin V.V., Gonchikova E.V., Polikarpov S.A., Mochula A.V. Association of cardiac mechanical dyssynchrony indices with data of dynamic singlephoton emission computed tomography of the myocardium: the role of the time interval between the stress test and recording. Siberian Journal of Clinical and Experimental Medicine. 2024;39(2):149–159. https://doi.org/10.29001/2073-8552-2022-756

13. Askew J.W., Miller T.D., Ruter R.L., Jordan L.G., Hodge D.O., Gibbons R.J. et al. Early image acquisition using a solid-state cardiac camera for fast myocardial perfusion imaging. J. Nucl. Cardiol. 2011;18(5):840–846. https://doi.org/10.1007/s12350-011-9423-7

14. Peix A., Padrón K., Cabrera L.O., Pardo L., Sánchez J. Left ventricular mechanical dyssynchrony in patients with chest pain and normal epicardial coronary arteries. J. Nucl. Cardiol. 2021;28(3):1055–1063. https://doi.org/10.1007/s12350-019-01804-x

15. Pazhenkottil A.P., Buechel R.R., Husmann L., Nkoulou R.N., Wolfrum M., Ghadri J.R. et al. Long-term prognostic value of left ventricular dyssynchrony assessment by phase analysis from myocardial perfusion imaging. Heart. 2011;97(1):33–37. https://doi.org/10.1136/hrt.2010.201566

16. Zhang H., Shi K., Fei M., Fan X., Liu L., Xu C. et al. A left ventricular mechanical dyssynchrony-based nomogram for predicting major adverse cardiac events risk in patients with ischemia and no obstructive coronary artery disease. Front. Cardiovasc. Med. 2022;9:827231. https://doi.org/10.3389/fcvm.2022.827231

17. Okuda K., Nakajima K., Matsuo S., Kashiwaya S., Yoneyama H., Shibutani T. et al. Comparison of diagnostic performance of four software packages for phase dyssynchrony analysis in gated myocardial perfusion SPECT. EJNMMI Res. 2017;7(1):1–9. https://doi.org/10.1186/s13550-017-0274-3

18. Schindler T.H., Fearon W.F., Pelletier-Galarneau M., Ambrosio G., Sechtem U., Ruddy T.D. et al. Myocardial perfusion PET for the detection and reporting of coronary microvascular dysfunction: A JACC: Cardiovascular Imaging Expert Panel Statement. JACC Cardiovasc. Imaging. 2023;16(4):536–548. https://doi.org/10.1016/j.jcmg.2022.12.015

19. Schindler TH, Nitzsche EU, Olschewski M., Brink I., Mix M., Prior J. et al. PET-measured responses of MBF to cold pressor testing correlate with indices of coronary vasomotion on quantitative coronary angiography. J. Nucl. Med. 2004;45(3):419–428. https://doi.org/10.1097/00006231200404000-00092x

20. van de Hoef T.P., Siebes M., Spaan J.A., Piek J.J. Fundamentals in clinical coronary physiology: why coronary flow is more important than coronary pressure. Eur. Heart J. 2015;36(47):3312–3319. https://doi.org/10.1093/eurheartj/ehv235