Evidence for pre- to postsynaptic mismatch of the cardiac sympathetic nervous system in ischemic congestive heart failure

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.