Anger recall mental stress decreases ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG) uptake and increases heterogeneity of cardiac sympathetic activity in the myocardium in patients with ischemic cardiomyopathy

Background: Acute psychological stressors such as anger can precipitate ventricular arrhythmias, but the mechanism is incompletely understood. Quantification of regional myocardial sympathetic activity with ¹²³I-metaiodobenzylguanidine (¹²³I-mIBG) SPECT imaging in conjunction with perfusion imaging during mental stress may identify a mismatch between perfusion and sympathetic activity that may exacerbate a mismatch between perfusion and sympathetic activity that could create a milieu of increased vulnerability to ventricular arrhythmia.

Methods: Five men with ischemic cardiomyopathy (ICM), and five age-matched healthy male controls underwent serial ¹²³I-mIBG and ^99mTc-Tetrofosmin SPECT/CT imaging during an anger recall mental stress task and dual isotope imaging was repeated approximately 1 week later during rest. Images were reconstructed using an iterative reconstruction algorithm with CT-based attenuation correction. The mismatch of left ventricular myocardial ¹²³I-mIBG and ^99mTc-Tetrofosmin was assessed along with radiotracer heterogeneity and the ¹²³I-mIBG heart-to-mediastinal ratios (HMR) were calculated using custom software developed at Yale.

Results: The hemodynamic response to mental stress was similar in both groups. The resting-HMR was greater in healthy control subjects (3.67 ± 0.95) than those with ICM (3.18 ± 0.68, P = .04). Anger recall significantly decreased the HMR in ICM patients (2.62 ± 0.3, P = .04), but not in normal subjects. The heterogeneity of ¹²³I-mIBG uptake in the myocardium was significantly increased in ICM patients during mental stress (26% ± 8.23% vs. rest: 19.62% ± 9.56%; P = .01), whereas the ^99mTc-Tetrofosmin uptake pattern was unchanged.

Conclusion: Mental stress decreased the ¹²³I-mIBG HMR, increased mismatch between sympathetic activity and myocardial perfusion, and increased the heterogeneity of ¹²³I-mIBG uptake in ICM patients, while there was no significant change in myocardial defect size or the heterogeneity of ^99mTc-Tetrofosmin perfusion. The changes observed in this proof-of-concept study may provide valuable information about the trigger-substrate interaction and the potential vulnerability for ventricular arrhythmias.