Cardiac Resynchronization Therapy Upregulates Cardiac Autonomic Control


  • This study received funding from Scientist Development Grant from AHA Greater Midwest Affiliate AHA 0435347Z and Award for Research in Cardiology Grant from the Mayo Clinic and Foundation.

  • Dr. Shen is the PI of an investigator initiated, multicenter research trial funded by Medtronic; Dr. Miyazaki has received research grants from Guidant, St. Jude Medical, and Medtronic; Dr. Hayes serves on the medical advisory boards of Boston Scientific, Sorin, and St. Jude Medical.

  • Manuscript received 5 December 2007; Revised manuscript received 6 March 2008; Accepted for publication 10 March 2008.

Address for correspondence: Yong-Mei Cha, M.D., Mary Brigh building 4-523, 200 First Street, SW, Rochester, MN 55905, USA. Fax: 507-266-0228; E-mail:


Objective: To determine the effect of cardiac resynchronization therapy (CRT) on sympathetic nervous function in heart failure (HF).

Background: Neurohormonal dysregulation and cardiac autonomic dysfunction are associated with HF and contribute to HF progression and its poor prognosis. We hypothesized that mechanical resynchronization improves cardiac sympathetic function in HF.

Methods: Sixteen consecutive patients receiving CRT for advanced cardiomyopathy and 10 controls were included in this prospective study. NYHA class, 6-minute walk distance, echocardiographic parameters, plasma norepinephrine (NE) were assessed at baseline, 3-month and 6-month follow-up. Cardiac sympathetic function was determined by 123iodine metaiodobenzylguanidine (123I-MIBG) scintigraphy and 24-hour ambulatory electrocardiography.

Results: Along with improvement in NYHA class (3.1 ± 0.3 to 2.1 ± 0.4, P < 0.001) and LVEF (23 ± 6% to 33 ± 12%, P < 0.001), delayed heart/mediastinum (H/M) 123I-MIBG ratio increased significantly (1.8 ± 0.7 to 2.1 ± 0.6, P = 0.04) while the H/M 123I-MIBG washout rate decreased significantly (54 ± 25% to 34 ± 24%, P = 0.01) from baseline to 6-month follow-up. The heart rate variability (HRV) measured in SD of normal-to-normal intervals also increased significantly from baseline (82 ± 30 ms) to follow-up (111 ± 32 ms, P = 0.04). The improvement in NYHA after CRT was significantly associated with baseline 123I-MIBG H/M washout rate (r = 0.65, P = 0.03). The improvement in LVESV index was associated with baseline 123I-MIBG delayed H/M ratio (r =−0.67, P = 0.02) and H/M washout rate (r = 0.65, P = 0.03).

Conclusion: After CRT, improvements in cardiac symptoms and LV function were accompanied by rebalanced cardiac autonomic control as measured by 123I-MIBG and HRV.