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.

Relaxation and excitation are components of the effects of music listening. The tempo of music is often considered a critical factor when determining these effects: listening to slow-tempo and fast-tempo music elicits relaxation and excitation, respectively. However, the chemical bases that underlie these relaxation and excitation effects remain unclear. Since parasympathetic and sympathetic nerve activities are facilitated by oxytocin and glucocorticoid, respectively, we hypothesized that listening to relaxing slow-tempo and exciting fast-tempo music is accompanied by increases in the oxytocin and cortisol levels, respectively. We evaluated the change in the salivary oxytocin and cortisol levels of participants listening to slow-tempo and fast-tempo music sequences. We measured the heart rate (HR) and calculated the heart rate variability (HRV) to evaluate the strength of autonomic nerve activity. After listening to a music sequence, the participants rated their arousal and valence levels. We found that both the salivary oxytocin concentration and the high frequency component of the HRV (HF) increased and the HR decreased when a slow-tempo music sequence was presented. The salivary cortisol level decreased and the low frequency of the HRV (LF) to HF ratio (LF/HF) increased when a fast-tempo music sequence was presented. The ratio of the change in the oxytocin level was correlated with the change in HF, LF/HF and HR, whereas that in the cortisol level did not show any correlation with indices of autonomic nerve activity. There was no correlation between the change in oxytocin level and self-reported emotions, while the change in cortisol level correlated with the arousal level. These findings suggest that listening to slow-tempo and fast-tempo music is accompanied by an increase in the oxytocin level and a decrease in the cortisol level, respectively, and imply that such music listening-related changes in oxytocin and cortisol are involved in physiological relaxation and emotional excitation, respectively.

Liver abnormalities have a strong impact on clinical outcomes in patients with heart failure (HF), and are known as cardio-hepatic syndrome. The non-alcoholic fatty liver disease (NAFLD) fibrosis score (NFS) has been developed to identify liver fibrosis in patients with NAFLD. It remains to be determined whether NFS is associated with cardiovascular prognosis in patients with chronic heart failure (CHF). We calculated NFS in 516 patients with CHF admitted to our hospital. The clinical endpoints were deaths due to progressive HF, myocardial infarction, stroke, and sudden cardiac death, and rehospitalization for worsening HF. There were 173 cardiovascular events noted during a median follow-up of 464 days. Patients with cardiovascular events showed a higher NFS as compared with those without. We divided the patients into four groups according to quartiles of NFS. The proportion of New York Heart Association functional class III/IV and serum brain natriuretic peptide levels were increased with increasing NFS. Kaplan-Meier analysis revealed that cardiovascular event rate was increased with increasing NFS in patients with CHF. In multivariate Cox proportional hazards analysis, NFS was independently associated with cardiovascular events after adjustment for confounding factors. Elevated NFS was associated with unfavorable outcomes in patients with CHF. Liver fibrosis assessed by NFS may provide valuable prognostic information in patients with CHF.

Background: Peripheral artery disease (PAD) is an athero-occlusive disease and a known risk factor for cardiovascular events. The controlling nutritional status (CONUT) score and geriatric nutritional risk index (GNRI) are objective tools for evaluating malnutrition and are reportedly associated with poor clinical outcomes in patients with fatal diseases. However, the effect of malnutrition on the clinical outcomes in patients with PAD remains unclear. Methods and Results:We enrolled 357 patients with PAD who underwent endovascular therapy. Malnutrition was diagnosed by CONUT score and GNRI as in previous reports. During a median follow-up period of 1,071 days, there were 67 major adverse cardiovascular and leg events (MACLEs). The CONUT score-and GNRI-based malnutrition statuses were identified in 56% and 46% of the patients, respectively. Proportion of malnutrition increased with advancing Fontaine class. The multivariate Cox proportional hazard regression analysis demonstrated that both the CONUT score-and GNRI-based malnutrition status was an independent predictor of MACLEs. The Kaplan-Meier analysis demonstrated that the MACLE ratio increased with deteriorating malnutrition. Finally, the addition of the CONUT score or GNRI to the known risk factors significantly improved the net reclassification index and integrated discrimination index. Conclusions:Malnutrition was common and closely associated with the clinical outcomes in patients with PAD, indicating that it is a novel therapeutic target in the management of these patients. Methods Study PopulationThis was a prospective study of 357 patients who were admitted to hospital for first PAD treatment. PAD was diagnosed in accordance with the ankle-brachial index (ABI) and computed tomographic angiography findings. EVT was performed by experienced cardiologists according sarcopenia in patients with PAD.The aim of the present study was to reveal the clinical significance of malnutrition in patients with PAD. To clarify this, we focused on the CONUT score and examined (1) the prevalence of malnutrition, (2) effect of malnutrition on the clinical outcome, and (3) association between malnutrition and sarcopenia in patients with PAD.