Negative chronotropic response to low-dose atropine is associated with parasympathetic nerve-mediated cardiovascular response in postoperative patients with congenital heart disease

Objectives To investigate the negative chronotropic response (NCR) to low-dose atropine in postoperative patients with congenital heart disease (CHD). Background Low-dose atropine causes a NCR through the central nervous system muscarinic receptor and is attenuated in adult heart failure patients. It has never been evaluated in CHD patients. Methods NCR corrected for basal heart rate (HR) (minimal HR/basal HR=cNCR) was determined after low-dose atropine (3 μg/kg) administration in 124 postoperative CHD patients (97 biventricular repair and 27 Fontan patients) and 11 controls and was compared with the cardiac autonomic nervous and functional status. Results The cNCR in simple CHD (post atrial or ventricular septal defect closure), complex biventricular CHD, and Fontan patients were 0.92±0.04, 0.94±0.04 and 0.96±0.04, respectively, and higher than in controls (0.87±0.03, p<0.001). In the complex CHD patients, higher cNCR was mainly associated with the lower pharmacologically determined cardiac parasympathetic nervous tone (PST), HR variability, high atrial natriuretic peptide, and lower right ventricular ejection fraction (p<0.0001). In Fontan patients, the lower β sensitivity of the sinus node and the PST mainly determined the higher cNCR (p<0.01) and the cNCR did not correlate with either hemodynamics or exercise capacity. Conclusions NCR is attenuated in proportion to the impaired cardiac parasympathetic nervous system and hemodynamics in postoperative complex biventricular CHD patients. In addition to PST, β sensitivity of the sinus node significantly influences the NCR in Fontan patients.