Fifty-four patients (38 men, 16 women) who had been referred to Kagoshima University Hospital for treatment of CHF were prospectively randomized into Waon therapy and control groups. All patients of both groups had already been treated with medications for heart failure at admission of this study. In the Waon therapy group, 27 patients were treated with medication and Waon therapy. In the control group, 27 patients continued the conventional medications for CHF.

Inclusion criteria were New York Heart Association (NYHA) functional class II–IV and left ventricular ejection fraction (LVEF) < 50% on echocardiography. Exclusion criteria were the presence of severe aortic valve stenosis, hypertrophic cardiomyopathy with severe obstruction, CHF treated with catecholamines, and renal failure requiring hemodialysis. We also excluded patients with excessive artifacts in the HRV analysis such as atrial fibrillation, frequent atrial or ventricular premature contractions, marked repolarization abnormalities, and implantation of a pacemaker.

Informed consent was obtained from all of the patients prior to participation, and the protocol was approved by the Ethics Committee of the Faculty of Medicine, Kagoshima University.

Patients in the Waon therapy group received medications for heart failure and 20 sessions of Waon therapy (once a day, 5 days a week for 4 weeks). Patients in the control group received conventional treatment for heart failure including rest, oxygen administration, and medication for 4 weeks in the hospital. All examinations were performed at admission and 4 weeks after treatment.

Waon therapy [[18], [19], [20]], a form of thermal therapy, uses a far infrared-ray dry sauna at 60 °C and differs from traditional sauna. Waon therapy has an absence of hydration pressure, and was performed as previously reported [10]. The patients were placed in a 60 °C sauna system for 15 min; after leaving the sauna, they underwent bed rest with a blanket to keep them warm for an additional 30 min. All patients were weighed before and after the therapy, and oral hydration with water was used to compensate for weight loss due to perspiration.

Body weight, blood pressure and heart rate were measured at admission and 4 weeks after treatment. The cardiothoracic ratio (CTR) determined by chest radiography, and echocardiography was performed at admission and 4 weeks after treatment. Cardiac output (CO), LVEF, left ventricular end-diastolic volume (LVEDV), and left and right ventricular Tei index (LV-, RV-Tei index) [[21], [22], [23]] were evaluated by echocardiography. All Doppler and echocardiographic measurements were performed according to the guidelines of the American Society of Echocardiography specified in 2005 [24]. The LVEF and LVEDV were obtained by the modified biplane Simpson's method from the apical 2- and 4-chamber views. CO was calculated by the product of stroke volume and heart rate. Stroke volume was obtained by the LV outflow Doppler method as the product of area and the time–velocity integral of LV outflow track. The Tei index, the sum of isovolumic contraction and relaxation times divided by the ejection time, is a well-established good indicator of global cardiac function [[21], [22]]. It was obtained from Doppler recordings of LV and RV inflow and outflow.

A fasting plasma blood sample was taken in the morning to measure plasma concentrations of neurohormones, such as catecholamines and brain natriuretic peptide (BNP). Plasma noradrenaline concentration was measured with high-performance liquid chromatography (BML Co., Ltd., Tokyo, Japan), and plasma BNP concentration was measured with a chemiluminescent enzyme immunoassay using a commercially available kit (Pathfast, Mitsubishi Chemical Medience Co., Ltd., Tokyo, Japan), at admission and 4 weeks after treatment.

The indices of HRV can be divided into two major categories: time and frequency domain indices. We calculated the time domain index using the coefficient of variation of RR intervals (CVRR), which was determined by dividing the standard deviation of RR intervals (SD) by the mean RR interval (M) for a 5-min recording of the electrocardiogram at rest. Thus, CVRR, an index of parasympathetic nervous activity, was calculated as follows: CVRR (%) = (SD/M) × 100 [25]. In addition, we analyzed the frequency domain index to assess the magnitude of the individual components of the heart rate power spectrum. Three main spectral components are distinguished in a spectrum calculated from short-term recording of 2 to 5 min: very-low-frequency (VLF; 0.003–0.04 Hz), low-frequency (LF; 0.04–0.15 Hz), and high-frequency components (HF; 0.15–0.40 Hz) [[7], [26]]. We analyzed consecutive RR intervals in order to assess both LF and HF of the heart rate power spectrum using the MemCalc/Tonam^® system (Suwa Trust, Tokyo, Japan) [[27], [28], [29]]. Normalized units (nu) were calculated from the following equations: LF norm = LF/(LF + HF), and HF norm = HF/(LF + HF) [7]. The HF element and HF norm reflect only parasympathetic nervous activity, because the HF element is not reduced by sympathetic blockade with propranolol, but rather is abolished by vagal blockade with atropine [[30], [31], [32]]. In contrast, the LF/HF ratio and LF norm are generally used as indices of sympathetic nervous activity, because the LF element reflects both sympathetic and parasympathetic nervous activity [[29], [32]]. Time domain analysis and spectral analysis of HRV were performed for a consecutive 5-min period in this study. HRV has been shown to be influenced by various conditions such as circadian rhythm, room temperature, physical and mental stress, body position, eating, smoking, and sleeping. Therefore, we prohibited the subjects from intense exercise, smoking, and alcohol drinking during hospitalization, and prohibited them from eating for 3 h before the measurement. HRV was measured in a quiet and air-conditioned room. We also measured HRV after at least 15 min of rest in the supine position and at the same time each day to avoid the influence of circadian rhythm. In the Waon therapy group, HRV was measured at 6 h after Waon therapy.

The clinical characteristics of patients at admission are shown in Table 1. There were no significant differences in age, gender, NYHA functional class, etiology of heart failure, complications, or the use of medications between the two groups at admission. We used three beta-blockers such as carvedilol, atenolol, and metoprolol. The dosage of atenolol and metoprolol were converted into that of carvedilol, and there was no significant difference in dosage of beta-blockers at admission between the two groups (Waon therapy group: 4.5 ± 3.5 mg/day vs. control group: 3.4 ± 3.5 mg/day).

In addition, as shown in Table 2, there were no significant differences in body weight, systolic blood pressure, diastolic blood pressure, mean heart rate, plasma BNP, and noradrenaline levels, CTR, or echo-derived measures such as CO, LVEF, LVEDV, LV-Tei index, and RV-Tei index between the two groups at admission.

The changes in the clinical findings and variables after 4 weeks are summarized in Table 2. Body weight and systolic blood pressure significantly decreased at 4 weeks after treatment compared with admission in both groups. Diastolic blood pressure significantly decreased in the control group after 4 weeks compared with admission, but did not change in the Waon therapy group. Mean heart rate significantly decreased in the Waon therapy group after 4 weeks compared with admission, but did not change in the control group. There were no significant differences in these parameters between the two groups after 4 weeks.

Changes in chest radiography and echocardiography are also shown in Table 2. Chest radiography showed a significant decrease of the CTR at 4 weeks after treatment compared with admission in both groups. In addition, echocardiography demonstrated that CO, LVEF, LVEDV, and RV-Tei index significantly improved after 4 weeks in the Waon therapy group, but LV-Tei index did not change after Waon therapy. In the control group, only RV-Tei index significantly decreased after 4 weeks, but CO, LVEF, LVEDV, and LV-Tei index did not change after treatment. There were no significant differences in any of these indices between the two groups after 4 weeks.

As shown in Table 2, the plasma levels of BNP significantly decreased 4 weeks after treatment compared with admission in both groups. There was no significant difference in BNP levels between the two groups after 4 weeks. In the Waon therapy group, plasma noradrenaline levels significantly decreased 4 weeks after Waon therapy. In the control group, plasma noradrenaline levels tended to decrease after 4 weeks, but did not reach statistical significance. There was no significant difference in noradrenaline levels between the two groups after 4 weeks.