Evidence for Pre- to Postsynaptic Mismatch of the Cardiac Sympathetic Nervous System in Ischemic Congestive Heart Failure

• Published in: Journal of Nuclear Medicine Vol. 49; no. 2; pp. 234 - 241
• Main Authors: Caldwell, James H, Link, Jeanne M, Levy, Wayne C, Poole, Jeanne E, Stratton, John R
• Format: Journal Article
• Language: English
• Published: United States Soc Nuclear Med 01.02.2008; Society of Nuclear Medicine
• Subjects: Aged; Autonomic Nervous System Diseases - diagnostic imaging; Autonomic Nervous System Diseases - etiology; Cardiovascular disease; Conflicts of interest; Data collection; Evidence-Based Medicine; Female; Heart attacks; Heart Failure - diagnostic imaging; Heart Failure - etiology; Heart Ventricles - diagnostic imaging; Heart Ventricles - innervation; Hormone replacement therapy; Human subjects; Humans; Male; Mass spectrometry; Myocardial Ischemia - complications; Myocardial Ischemia - diagnostic imaging; Radionuclide Imaging; Radiopharmaceuticals; Synapses - diagnostic imaging; Ventricular Dysfunction, Left - diagnostic imaging; Ventricular Dysfunction, Left - etiology
• ISSN: 0161-5505; 1535-5667; 2159-662X
• DOI: 10.2967/jnumed.107.044339

Pre- and postsynaptic cardiac sympathetic function is altered in ischemic congestive heart failure (CHF). Whether there is a presynaptic-to-postsynaptic mismatch or whether mismatch is related to adverse cardiac events is unknown. In 13 patients with ischemic CHF and 25 aged-matched healthy volunteers, presynaptic function was measured by PET of (11)C-meta-hydroxyephedrine ((11)C-mHED), a norepinephrine (NE) analog. Postsynaptic function, beta-adrenergic receptor (BAR) density (B'(max)), was measured by imaging (11)C-CGP12177. Myocardial blood flow (MBF) was measured by imaging (15)O-water. Each heart was analyzed both globally and regionally, excluding infarcted regions, and a mismatch score, defined as the ratio of B'(max) to NE uptake (PS(nt))(,) was used to indicate mismatch of post- and presynaptic function. Global and regional MBF was not different between CHF and healthy subjects. The global measure of PS(nt) was lower in CHF (0.32 +/- 0.34) than that in healthy subjects (0.81 +/- 0.33, P < 0.0001) and in all 12 regions. Global B'(max) tended to be lower in CHF than that in healthy subjects (10.0 +/- 6.4 pmol/mL vs. 13.4 +/- 4.2, P = 0.056) and in all 12 regions. The global mismatch score (B'(max):PS(nt)) in CHF patients was significantly greater than that in healthy subjects (50.3 +/- 50.7 vs. 19.3 +/- 9.7, P = 0.005) and also greater in 11 of 12 regions. After 1.5 y of follow-up, 4 individuals had an adverse outcome (CHF death, new or recurrent sudden death, or progressive CHF leading to transplantation). Three of the 4 had mismatch scores > 3 times that of the healthy subjects or the CHF patients without an adverse outcome. Mismatch between pre- and postsynaptic left ventricular sympathetic function is present in patients with severe CHF and may be more marked in those with adverse outcomes.