Cardiac resynchronization therapy upregulates cardiac autonomic control

Abstract

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 (123)iodine metaiodobenzylguanidine ((123)I-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) (123)I-MIBG ratio increased significantly (1.8 +/- 0.7 to 2.1 +/- 0.6, P = 0.04) while the H/M (123)I-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 (123)I-MIBG H/M washout rate (r = 0.65, P = 0.03). The improvement in LVESV index was associated with baseline (123)I-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 (123)I-MIBG and HRV.

Figure 1

Shown are the changes in NYHA class after CRT in each individual patient. One patient did not survive at 6-month follow-up.

Figure 2

Figure depicts the delta changes of NYHA function class, distance of 6-minute walk, LV end-diastolic volume (LVEDV) index, LV end-systolic volume (LVESV) index, LV ejection fraction (LVEF), the degree of mitral regurgitation (MR), interventricular conduction delay by tissue Doppler, and intraventricular conduction delay by strain rate in 3-month and 6-month follow-up after CRT.*P < 0.05;**P < 0.01 compared with baseline.

Figure 3

The figure shows the standard deviation of all normal to normal intervals (SDNN), the SD of the averages NN intervals in all 5-minute segments (SDANN) expressed as Mean ± SD at baseline, 3-month and 6-month follow-up after CRT. *P < 0.05 compared with baseline; #P < 0.05 compared with control baseline.

Figure 4

The histogram shows the effect of CRT on ¹²³I-MIBG imaging after CRT. The initial and delayed H/M ratios were lower and H/M washout rate was higher in patients with HF compared with controls at baseline. The delayed H/M ratio and H/M washout rate were significantly improved in 6-month after CRT. *P < 0.05; ** P < 0.01 compared to baseline; ##P < 0.01 compared with control baseline.

Figure 5

The figure shows significant correlation of change in NYHA class after CRT with baseline ¹²³I-MIBG H/M washout (A), and correlations of change in LV end-systolic volume (LVESV) index after CRT with baseline intraventricular dyssynchrony (the standard deviation of differences in timing intervals from QRS onset to peak negative strain of 12 basal and mid LV segments) (B), baseline ¹²³I-MIBG delayed H/M ratio (C), and H/M washout rate (D).