Abnormalities of Neurohormonal and Cardiac Autonomic Nervous Activities Relate Poorly to Functional Status in Fontan Patients

Abstract

Background— Impaired cardiac autonomic nervous activities and increased neurohumoral activities (CANA, NHA) characterize Fontan patients. However, the clinical significance of these changes is not clearly understood. Our purpose was to clarify the clinical significance of the CANA and NHA in stable Fontan patients. Methods and Results— We divided 22 atriopulmonary connection (APC) and 75 total cavopulmonary connection (TCPC) patients into 4 subgroups according to New York Heart Association (NYHA) class (1.8±0.6) and measured various CANA and NHA indices. All NHA indices were elevated in the symptomatic patients ( P <0.001). Natriuretic peptides were higher in the APC than in the TCPC patients, and the hemodynamics showed no correlation with brain natriuretic peptide in the APC patients. Low arterial oxygen saturation and impaired hemodynamics greatly influenced all elevated NHA indices ( P <0.01), except for plasma renin activity, in the TCPC patients. Impaired CANA indices did not relate to NYHA class, although surgeries were associated with lower heart rate variability. In addition to poor correlation between NHA and CANA, age and ventricular morphology had no impact on all CANA and NHA indices, except for high norepinephrine in right ventricular Fontan patients. Conclusions— Although symptomatic Fontan patients exhibit higher NHA, CANA is not related to either NYHA class or NHA. APC itself is responsible for higher natriuretic peptides, and arterial oxygen desaturation has a great impact on elevated NHA in the TCPC patients. These characteristics of the NHA and CANA differ from those of heart failure patients with biventricular physiology.

Aortopulmonary Collateral Flow is Related to Pulmonary Artery Size and Affects Ventricular Dimensions in Patients After the Fontan Procedure

“…The mean BNP values of 28 pg/ml in our study population match with previous studies that found BNP values of asymptomatic Fontan patients were comparable to those of healthy age-matched controls [22][23][24]. Regarding the utility of BNP in single-ventricle patients these studies showed somewhat inconsistent results.…”

“…Regarding the utility of BNP in single-ventricle patients these studies showed somewhat inconsistent results. While in some studies higher BNP-levels were associated with type of TCPC-connection, degree of atrioventricular valve regurgitation, ventricular morphology, diastolic function, and clinical status [22][23][24][25][26], the use of BNP as an early marker of ventricular dysfunction, a surveillance tool or as an endpoint in clinical studies remains questionable [22,27].…”

Evaluation of Exercise Capacity with Cardiopulmonary Exercise Testing and Type B Natriuretic Peptide Concentrations in Adult Patients with Patent Atrial Septal Defect

“…Even though the considerable majority of studied patients did not present the signs and symptoms of heart failure, their plasma BNP levels were significantly higher than in the control group. Elevated BNP levels in patients with congenital heart disease (mainly in children) were also observed by other investigators [18,23,24,25,26,27,28]. Bolger et al [18] showed in 56 adult patients with congenital heart disease that increased BNP levels were not directly related to abnormal heart anatomy, but only to NYHA functional class.…”

“…Few studies have shown increased BNP levels in right ventricular failure [23, 24]. The analyses of BNP levels in patients with congenital heart diseases are also sparse [18,23,24,25,26,27,28]. We are not aware of any reports on serum BNP levels in adults with patent ASD.…”

Clinical Profiles of Adult Patients With Single Ventricular Physiology

“…29 Our results are consistent with theirs, although the post-Fontan follow-up period was 15.2±6.7 years at the time of entry in our data. In addition to the palliative nature of Fontan circulation, elevated neurohorumonal factors, 30 cytokines, 31 and imbalanced cardiac autonomic nervous activity 30 may have an adverse effect on the long-term outcomes and may contribute to the timedependent increase in these cardiovascular events. In cyanotic congenital heart disease, endothelial dysfunction may result in local thrombosis.…”