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

¹ Division of Cardiology, Department of Medicine, University of Washington, Seattle, Washington; ² Department of Radiology, University of Washington, Seattle, Washington; and ³ Division of Cardiology, Department of Medicine, VA Medical Center and University of Washington, Seattle, Washington

Correspondence: For correspondence or reprints contact: James H. Caldwell, MD, Nuclear Medicine, Box 356113, University of Washington, Seattle, WA 98195. E-mail: jcald{at}u.washington.edu

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. Methods: In 13 patients with ischemic CHF and 25 aged-matched healthy volunteers, presynaptic function was measured by PET of ¹¹C-meta-hydroxyephedrine (¹¹C-mHED), a norepinephrine (NE) analog. Postsynaptic function, β-adrenergic receptor (BAR) density (B'_max), was measured by imaging ¹¹C-CGP12177. Myocardial blood flow (MBF) was measured by imaging ¹⁵O-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. Results: 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. Conclusion: 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.

Key Words: imaging heart failure • sudden death • sympathetic nervous system

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.

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