Comparative study of therapeutic effects of short- and long-acting loop diuretics in outpatients with chronic heart failure (COLD-CHF).

BACKGROUND: Loop diuretics have two different classes with different duration of activity: short-acting such as furosemide (duration of activity, 6h) and long-acting such as azosemide (duration of activity, 10-12h). We conducted a multicenter, randomized, controlled trial in order to compare the therapeutic effects of azosemide, a long-acting loop diuretic, and furosemide, a short-acting one, on neurohumoral factors and cardiac function in outpatients with chronic heart failure (CHF). METHODS: We enrolled 98 patients with CHF who were receiving furosemide and an angiotensin-converting enzyme inhibitor, and they were randomly divided into furosemide (n=49) and azosemide (n=49) groups. The furosemide group continued furosemide at the same dosage, and the azosemide group switched from furosemide to azosemide. At baseline and after 3 months, we measured body weight, and levels of brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), norepinephrine, active renin, creatinine, blood urea nitrogen, sodium, potassium, and hematocrit. Chest X-ray and echocardiography were also performed. RESULTS: Body weight and plasma levels of BNP and ANP significantly decreased after 3 months in the azosemide group compared to the furosemide group. There were no significant differences in changes of levels of creatinine, blood urea nitrogen, sodium, potassium, hematocrit, norepinephrine, and active renin after 3 months between the furosemide and azosemide groups. Echocardiography and chest X-ray did not demonstrate significant differences between the two groups. CONCLUSIONS: Long-acting azosemide is suggested to be useful for the improvement of neurohumoral factors compared with short-acting furosemide in patients with CHF.

Highly sensitive cardiac troponin T in heart failure: comparison with echocardiographic parameters and natriuretic peptides.

BACKGROUND: Circulating cardiac troponin T is a marker of cardiomyocyte injury, and predicts adverse outcomes in patients with chronic heart failure. However, the significance of highly sensitive cardiac troponin T (hs-TnT) in cardiac dysfunction remains uncertain. The purpose of this study is to evaluate the correlation between hs-TnT and echocardiographic parameters or natriuretic peptides in patients with heart failure. METHODS AND RESULTS: We analyzed 283 consecutive out- or in-patients who had B-type natriuretic peptide (BNP) ≥20 pg/mL and were examined by echocardiography (mean age 66.5±13.9 years old; 159 males). Hs-TnT, BNP, N-terminal pro-BNP (NT-proBNP), and creatinine levels were measured simultaneously. LVEDD (left ventricular end-diastolic dimension), LVEF (left ventricular ejection fraction), E', E/E', left ventricular (LV) Tei index, and right ventricular (RV) Tei index were determined with echocardiography. The linear regression analyses demonstrated that loghs-TnT correlated with LVEDD (R=0.242, p<0.0001), LVEF (R=-0.369, p<0.0001), E' (R=-0.447, p<0.0001), E/E' (R=0.364, p<0.0001), LV Tei index (R=0.303, p<0.0001), RV Tei index (R=0.443, p<0.0001), and estimated glomerular filtration rate (eGFR) (R=-0.489, p<0.0001). Using multiple variable regression analysis, loghs-TnT independently correlated with LVEF, E/E', RV Tei index, and eGFR. Furthermore, loghs-TnT significantly correlated with logBNP (R=0.567, p<0.0001) or logNT-proBNP (R=0.647, p<0.0001). Multiple variable regression analysis demonstrated that loghs-TnT independently correlated with logBNP, age, and eGFR, or with logNT-proBNP, age, sex, and eGFR. CONCLUSIONS: The hs-TnT correlated with cardiac dysfunction evaluated by echocardiography and natriuretic peptides in patients with heart failure. The elevation of hs-TnT levels in heart failure may represent cardiac dysfunction due to minor and ongoing myocardial injury.

Relationship between bilirubin concentration, coronary endothelial function, and inflammatory stress in overweight patients.

AIM: Bilirubin has antioxidant properties and may protect against atherosclerosis and coronary heart disease (CHD). Further, in patients with metabolic syndrome, hyperbilirubinemia is associated with attenuation of insulin resistance. The aim of the present study was to determine the relationship between serum bilirubin concentration and coronary endothelial function in overweight patients. METHODS: The study population consisted of 107 patients without CHD who underwent coronary flow studies. Vascular reactivity was examined by intra-coronary administration of papaverine and nitroglycerin. Coronary endothelial function was evaluated by assessing the change in coronary artery diameter to papaverine [percent change in flow-mediated dilatation (%FMD)] and nitroglycerin (%NTG). Serum total bilirubin, high-sensitivity C-reactive protein (hs-CRP), high density lipoprotein-cholesterol (HDL-C), fasting plasma glucose and immunoreactive insulin levels were also measured, and the homeostasis model assessment insulin resistance (HOMA-IR) index was calculated. Patients were divided into two groups according to body mass index (BMI): an overweight group (BMI ≥ 25; n = 36) and a normal weight group (BMI < 25; n = 71). RESULTS: In the overweight group, univariate analysis revealed that log-transformed total bilirubin was positively correlated with %FMD and HDL-C (r = 0.38, p< 0.05; r = 0.30, p < 0.05, respectively) and was inversely correlated with log-transformed hs-CRP and HOMA-IR (r = -0.45, p < 0.01; r = -0.45, p< 0.05, respectively). Multivariate analysis revealed that log-transformed hs-CRP was the only independent predictor of log-transformed total bilirubin (p< 0.05). CONCLUSIONS: These results suggest that a high bilirubin level was associated with favorable coronary endothelial function in overweight patients. Further, the anti-inflammatory effects of bilirubin may mediate this effect.

Improvement of autonomic nervous activity by Waon therapy in patients with chronic heart failure.

BACKGROUND AND PURPOSE: We have reported previously that Waon therapy improves cardiac and vascular function, and prognosis of patients with chronic heart failure (CHF). CHF is characterized by generalized sympathetic activation and parasympathetic withdrawal. The purpose of this study was to evaluate the effect of Waon therapy on autonomic nervous activity in patients with CHF. METHODS AND SUBJECTS: Fifty-four patients with CHF, who were receiving conventional therapy for CHF, were divided into Waon therapy and control groups. In the Waon therapy group, 27 patients were treated with medication and Waon therapy. In the control group, 27 patients were treated with only conventional CHF therapy. Cardiac function including cardiac output (CO) and left ventricular ejection fraction (LVEF) was evaluated by echocardiography. The heart rate variability, such as the coefficient of variation of RR intervals (CVRR), the low-frequency (LF) component, high-frequency (HF) component, the LF norm [LF/(LF+HF)], and HF norm [HF/(LF+HF)], were measured at admission and 4 weeks after treatment. RESULTS: Echocardiography demonstrated that CO and LVEF significantly increased after 4 weeks in the Waon therapy group, but did not change in the control group. In the Waon therapy group, CVRR, HF, and HF norm significantly increased 4 weeks after Waon therapy. In addition, the LF/HF ratio and LF norm significantly decreased 4 weeks after Waon therapy. In contrast, these parameters remained unchanged in the control group. Moreover, the HF and HF norm were significantly higher, and the LF/HF ratio and LF norm were significantly lower after 4 weeks of Waon therapy group than after 4 weeks of only conventional therapy. CONCLUSIONS: Waon therapy improved cardiac function and autonomic nervous activity by increasing parasympathetic and decreasing sympathetic nervous activity in patients with CHF.

Effect of Waon therapy on oxidative stress in chronic heart failure.

BACKGROUND: A previous report by our team showed that Waon therapy, using a far infrared-ray dry sauna at 60°C, improves cardiac and vascular function in patients with chronic heart failure (CHF). The purpose of the present study was to clarify the effect of Waon therapy on oxidative stress in CHF patients and investigate its mechanism by animal experiments. METHODS AND RESULTS: Forty patients with CHF were divided into control (n=20) and Waon therapy (n=20) groups. All patients received standard optimal medications for CHF. Waon therapy group was treated with Waon therapy daily for 4 weeks. After 4 weeks of Waon therapy, concentrations of hydroperoxide and brain natriuretic peptide (BNP) decreased significantly (hydroperoxide, 422±116 to 327±88U.CARR, P<0.001; BNP, 402±221 to 225±137pg/ml, P<0.001), and the nitric oxide metabolites increased (71.2±35.4 to 92.0±40.5mmol/L, P<0.05). In contrast, none of these variables changed over the 4-week interval in the control group. Furthermore, animal experiments were performed using TO-2 cardiomyopathic hamsters. On immunohistochemistry, cardiac expression of 4-hydroxy-2-nonenal, a marker of oxidative stress, was decreased in the 4-week Waon therapy compared to untreated hamsters. On Western blotting, cardiac expressions of heat shock protein (HSP) 27, manganese superoxide dismutase and HSP32, which reduce oxidative stress, were significantly upregulated in the 4-week Waon therapy compared to untreated hamsters. CONCLUSIONS: Waon therapy decreases oxidative stress in patients and hamsters with heart failure.

Waon therapy mobilizes CD34+ cells and improves peripheral arterial disease.

BACKGROUND: We previously reported that Waon therapy upregulates endothelial nitric oxide synthase protein, and augments ischemia-induced angiogenesis in mice with hindlimb ischemia, and it improves limb ischemia in patients with peripheral arterial disease (PAD). The aim of this study was to investigate the underlying mechanism of Waon therapy for the treatment of patients with PAD, and to determine whether Waon therapy can mobilize blood-derived progenitor cells. METHODS: 21 consecutive PAD patients received standard medications, and were randomly divided into control (n=10) and Waon therapy groups (n=11). The Waon therapy group received Waon therapy daily for 6 weeks. The control group continued conventional therapy for 6 weeks. Leg pain was scored using a visual analogue scale. The ankle-brachial pressure index (ABPI) and the 6-min walking distance were measured at baseline and 6 weeks after therapy. Frequency of circulating CD34+ progenitor cell numbers was measured by quantitative real-time polymerase chain reaction, and the serum nitrate and nitrite levels were also measured at baseline and 6 weeks after therapy. RESULTS: The leg pain score, ABPI and the 6-min walking distance improved significantly after 6 weeks in the Waon therapy group, but not in the control group. Frequency of circulating CD34+ cells increased after 6 weeks of Waon therapy [2.0 ± 1.2 (×10(-4)) at baseline to 3.9 ± 1.9 (×10(-4)), p=0.015], while it remained unchanged in the control group [1.8 ± 1.8 (×10(-4)) at baseline to 1.2 ± 0.9 (×10(-4))]. Serum nitrate and nitrite levels increased significantly after Waon therapy (29.6 ± 17.6 to 36.0 ± 17.7 µmol/ml, p<0.05), but not in the control group (34.4 ± 9.4 to 38.3 ± 8.8 µmol/ml). CONCLUSION: Waon therapy mobilized circulating endothelial progenitor cells and improved limb ischemia in patients with PAD. Waon therapy is a highly promising therapy for patients with PAD.

Effect of uric acid on coronary microvascular endothelial function in women: association with eGFR and ADMA.

AIM: The aim of this study was to investigate the role of uric acid (UA) in coronary endothelial function via its effects on renal function, other coronary risk factors and asymmetric dimethylarginine (ADMA) in men and women. METHODS: The study population consisted of 194 consecutive patients (119 men and 75 women) without coronary artery disease. The relationships between UA and coronary endothelial function, estimated glomerular filtration rate (eGFR), ADMA or other biochemical or anthropometric parameters were investigated. RESULTS: Monovariate analysis of female participants demonstrated that % change in coronary blood flow (CBF) induced by acetylcholine (ACh) was inversely correlated with UA, ADMA and age (r=-0.32, p<0.01; r=-0.31, p<0.05; r=-0.23, p<0.05, respectively), and positively correlated with eGFR (r=0.27, p<0.05). Stepwise regression analysis showed that UA was the only independent predictor of % change in CBF induced by ACh (F value 4.969, p<0.05). Similar analysis of male participants failed to show significant correlations of these variables except for age in monovariate analysis (r=-0.19, p<0.05). Meanwhile, UA was inversely correlated with eGFR in both men and in women (r=-0.25, p<0.01; r=-0.59, p<0.0001, respectively), and ADMA was positively correlated with UA and inversely correlated with eGFR (r=0.36, p<0.05; r=-0.42, p<0.01, respectively) in women but not in men. CONCLUSION: High concentrations of UA correlate with coronary endothelial microvascular dysfunction in women. Further, serum UA concentration is related to eGFR and ADMA only in women, which may result in impaired endothelial function in resistance coronary arteries in women but not in men.

Enjoying hobbies is related to desirable cardiovascular effects.

An unhealthy lifestyle can increase the risk of cardiovascular disease. However, the mechanism by which lifestyle influences the development of cardiovascular disease remains unclear. Since coronary endothelial function is a predictor of cardiovascular prognosis, the goal of this study was to characterize the effect of enjoying hobbies on coronary endothelial function and cardiovascular outcomes. A total of 121 consecutive patients (76 men, 45 women) with almost normal coronary arteries underwent Doppler flow study of the left anterior descending coronary artery following sequential administration of papaverine, acetylcholine, and nitroglycerin. On the basis of responses to questionnaires, patients were divided into two groups; the Hobby group (n = 71) who enjoyed hobbies, and the Non-hobby group (n = 50) who had no hobbies. Cardiovascular outcomes were assessed at long-term follow-up using medical records or questionnaire surveys for major adverse cardiovascular events (MACE).The average follow-up period was 916 +/- 515 days. There were no significant differences in demographics when comparing the two groups. The percent change in coronary blood flow and coronary artery diameter induced by acetylcholine was significantly greater in the Hobby group than in the Non-hobby group (49% +/- 77% vs 25% +/- 37%, P < 0.05, 4% +/- 13% vs -3% +/- 20%, P < 0.05, respectively). The MACE rate was significantly lower in the Hobby group than in the Non-hobby group (P < 0.01). Enjoyment of hobbies was the only independent predictor of MACE (odds ratio 8.1 [95% confidence interval 1.60, 41.90], P = 0.01) among the variables tested. In the early stages of arteriosclerosis, enjoying hobbies may improve cardiovascular outcomes via its favorable effects on coronary endothelial function.

Relationship between hyperglycemia and coronary vascular resistance in non-diabetic patients.

BACKGROUND: Hyperglycemia upon hospital admission in patients with acute myocardial infarction is associated with the no-reflow phenomenon after successful reperfusion, and increased mortality. However, the mechanism underlying this phenomenon remains unclear. Therefore, the aim of this study was to characterize coronary hemodynamics in a homogenous group of non-diabetic patients without coronary artery disease. METHODS AND RESULTS: A total of 104 consecutive non-diabetic patients (mean age, 62+/-14 years) without coronary artery disease underwent Doppler flow study of the left anterior descending coronary artery. Vascular reactivity was examined by intra-coronary administration of papaverine, acetylcholine (Ach), and nitroglycerin using a Doppler guidewire. Coronary vascular resistance (CVR) was calculated as the mean arterial pressure divided by coronary blood flow (CBF). Baseline CVR was shown as CVR at control and minimal CVR was shown as CVR with papaverine administration. Fasting plasma glucose (FPG) level had a significant, positive correlation with baseline CVR and minimal CVR (r=0.24, p<0.02 and r=0.21, p<0.05, respectively). Hemoglobin A1c (HbA1c) also had a significant, positive correlation with baseline CVR and minimal CVR (r=0.31, p<0.01 and r=0.32, p<0.01, respectively). The percent change in CBF induced by Ach was inversely correlated with HbA1c but not with FPG (r=0.22, p<0.05 and r=0.06, p=0.57, respectively). By contrast, neither FPG nor HbA1c had significant correlation with coronary flow reserve to papaverine. CONCLUSION: These data demonstrate that elevated glucose levels are associated with increases in baseline and minimal coronary vascular resistance. These changes may contribute to unfavorable coronary hemodynamics in non-diabetic patients without coronary heart disease.

Usefulness of the adenosine triphosphate with a sufficient observation period for detecting reconduction after pulmonary vein isolation.

BACKGROUND: Although reconduction after pulmonary vein (PV) isolation is considered to play a key role in the recurrence of paroxysmal atrial fibrillation (AF), there have been few reports regarding the precise time course of early reconduction. Several studies have suggested that transient PV reconduction facilitated by adenosine may predict long-term AF recurrence. This study was designed to clarify the incidence and time course of early reconduction after PVI during the procedure and to confirm whether the use of ATP after a certain observation period was useful to detect early reconduction after PVI. METHODS: In 21 patients (18 males, 56 +/- 11 years) with drug refractory AF, radiofrequency circumferential PV antrum ablation was performed in all 4 PVs. After the completion of isolation, electrograms in each PV were repeatedly recorded (1.98 +/- 0.57 times per PV) using a circular mapping catheter for an observation period of 87 +/- 29 minutes. After isolation of all 4 PVs, 30 mg of adenosine triphosphate (ATP) was administered during isoproterenol infusion. RESULTS: PV electrical isolation was initially achieved in all 81 PVs. During the observation period, 12 (15%) PVs in 10 (48%) of 21 patients exhibited spontaneous reconduction. Among the remaining 69 PVs, 8 (12%) additional PVs had reconduction with the use of ATP. All PV reconduction was successfully eliminated by 4.5 +/- 2.2 additional radiofrequency applications. CONCLUSION: A sufficient observation period and the use of ATP are useful to detect early reconduction after PV isolation.

Waon therapy improves the prognosis of patients with chronic heart failure.

BACKGROUND: We developed a Waon therapy (soothing warm therapy) and have previously reported that repeated Waon therapy improves hemodynamics, peripheral vascular function, arrhythmias, and clinical symptoms in patients with chronic heart failure (CHF). The aim of this study was to investigate the effect of Waon therapy on the prognosis of CHF patients. PATIENTS AND METHODS: We studied 129 patients with CHF in NYHA functional class III or IV who were admitted to our hospital between January 1999 and March 2001. In the Waon therapy group, 64 patients were treated with a far infrared-ray dry sauna at 60 degrees C for 15 min and then kept on bed rest with a blanket for 30 min. The patients were treated daily for 5 days during admission, and then at least twice a week after discharge. In the control group, 65 patients, matched for age, gender, and NYHA functional class, were treated with traditional CHF therapy. The follow-up time was scheduled for 5 years. RESULTS: Recent, complete follow-up data on each patient were obtained. The overall survival rate was 84.5% (Kaplan-Meier estimate). Twelve patients died in the control group and 8 patients died in the Waon therapy group at 60 months of follow-up. Cardiac events due to heart failure or cardiac death occurred in 68.7% of the control group but only 31.3% of the Waon therapy group (P<0.01) at 60 months of follow-up. CONCLUSION: Waon therapy reduced cardiac events in patients with CHF. This therapy is a promising non-pharmacological treatment for CHF.

Beneficial effects of Waon therapy on patients with chronic heart failure: results of a prospective multicenter study.

BACKGROUND: We conducted a prospective multicenter case-control study to confirm the clinical efficacy and safety of Waon therapy on chronic heart failure (CHF). METHODS: Patients (n=188) with CHF were treated with standard therapy for at least 1 week, and then were randomized to Waon therapy (n=112) or a control group (n=76). All patients continued conventional treatment for an additional 2 weeks. The Waon therapy group was treated daily with a far infrared-ray dry sauna at 60 degrees C for 15 min and then kept on bed rest with a blanket for 30 min for 2 weeks. Chest radiography, echocardiography, and plasma levels of brain natriuretic peptide (BNP) were measured before and 2 weeks after treatment. RESULTS: NYHA functional class significantly decreased after 2 weeks of treatment in both groups. Chest radiography also showed a significant decrease of the cardiothoracic ratio in both groups (Waon therapy: 57.2+/-8.0% to 55.2+/-8.0%, p<0.0001; control: 57.0+/-7.7% to 56.0+/-7.1%, p<0.05). Echocardiography demonstrated that left ventricular diastolic dimension (LVDd), left atrial dimension (LAD), and ejection fraction (EF) significantly improved in the Waon therapy group (LVDd: 60.6+/-7.6 to 59.1+/-8.4 mm, p<0.0001; LAD: 45.4+/-9.3 mm to 44.1+/-9.4 mm, p<0.05; EF: 31.6+/-10.4% to 34.6+/-10.6%, p<0.0001), but not in the control group (LVDd: 58.4+/-10.3 mm to 57.9+/-10.4 mm; LAD: 46.3+/-9.7 mm to 46.2+/-10.1 mm; EF: 36.6+/-14.1% to 37.3+/-14.0%). The plasma concentration of BNP significantly decreased with Waon therapy, but not in the control group (Waon: 542+/-508 pg/ml to 394+/-410 pg/ml, p<0.001; control: 440+/-377 pg/ml to 358+/-382 pg/ml). CONCLUSION: Waon therapy is safe, improves clinical symptoms and cardiac function, and decreases cardiac size in CHF patients. Waon therapy is an innovative and promising therapy for patients with CHF.

Comparison of effect between nitrates and calcium channel antagonist on vascular function in patients with normal or mildly diseased coronary arteries.

The comparative long-term antianginal efficacy of long-acting nitrates versus calcium channel antagonists remains unclear. The goal of the present study was to compare the coronary endothelial cell function and coronary artery vasoconstriction between patients with normal or mildly diseased coronary arteries treated with long-acting nitrates or calcium channel antagonists. Forty-two patients suspected to have angina pectoris and with normal or mildly diseased coronary arteries underwent Doppler flow study of the left anterior descending coronary artery. All patients were suspected to have angina pectoris and were receiving either long-acting nitrates (n = 18; Nitrates group) or calcium channel antagonists (n = 24; Ca-antagonists group) for at least 1 year. Vascular reactivity was assessed by intracoronary administration of papaverine, acetylcholine (Ach), and nitroglycerin using a Doppler guidewire. Segments that showed the greatest constrictive response to Ach were used for assessment of vasoconstriction. The percent increase in coronary blood flow (CBF) and coronary artery diameter (CAD) induced by Ach was significantly smaller in the Nitrates group than in the Ca-antagonists group (33% +/- 74% vs 83% +/- 77%, P < 0.05; -3% +/- 16% vs 11% +/- 12%, P < 0.01, respectively). The percent diameter reduction in the region of greatest constrictive response to Ach was significantly greater in the Nitrates group than in the Ca-antagonists group (44% +/- 39% vs 15% +/- 32%, P < 0.02). Long-term treatment with long-acting nitrates may produce less favorable effects on coronary endothelial function and the constrictive response to Ach when compared with long-acting calcium channel antagonists in patients with normal or mildly diseased coronary arteries.

Adiponectin is a better predictor of endothelial function of the coronary artery than HOMA-R, body mass index, immunoreactive insulin, or triglycerides.

BACKGROUND: Previous studies have demonstrated that decreased levels of circulating adiponectin correlate with endothelial dysfunction in peripheral arteries. However, the relationship between adiponectin levels and endothelial function in coronary arteries remains unclear. The goal of the present study was to determine whether circulating adiponectin concentrations are a useful predictor of coronary endothelial function. METHODS: Thirty-six consecutive non-diabetic patients with normal or mildly diseased coronary arteries were enrolled in this study. Coronary endothelial function was evaluated by coronary vascular response to acetylcholine (Ach). The relationship between coronary vasoreactivity and adiponectin or other biochemical or anthropometric parameters was investigated. The predictive value of adiponectin level for assessment of coronary endothelial dysfunction was assessed at the best cut-off point. RESULTS: In a simple regression analysis, log-transformed adiponectin concentrations positively correlated with the percent change in coronary blood flow (CBF) and coronary artery diameter (CAD) induced by Ach (r=0.62, p<0.0001; r=0.63, p<0.0001, respectively). Insulin resistance index (HOMA-R), body mass index, immunoreactive insulin, and triglycerides concentrations also significantly correlated with the percent change in CBF and CAD. However, in a multiple regression analysis, log-transformed adiponectin concentration was the only independent predictor of the percent change in CBF and CAD (p<0.0001; p<0.0001, respectively). Furthermore, patients with adiponectin concentrations <6.3 mg/L demonstrated coronary endothelial dysfunction with high specificity both in terms of CBF and CAD response (85%; 88%, respectively). CONCLUSIONS: Adiponectin is a better predictor of coronary endothelial function than other factors such as HOMA-R, body mass index, immunoreactive insulin, and triglycerides.

Association between Toll-like receptors and the extent and severity of coronary artery disease in patients with stable angina.

OBJECTIVES: Toll-like receptors mediate the innate immune response triggered by pathogen-associated molecular patterns, and atherosclerosis can be considered a state of chronic inflammation whereby immune system cells accumulate within the intima of the arterial wall. The goal of this study was to determine the relation of Toll-like receptors to the extent and severity of coronary artery disease. METHODS: Angiographic vessel score and Gensini score were used to evaluate the extent and severity of coronary atherosclerosis. Sixty-two consecutive patients with stable angina were grouped as follows: those with insignificant (<50%) coronary stenosis (group 1), and those with 1 (group 2), 2 (group 3), or 3-vessel disease (group 4). The expression of Toll-like receptor 1, 2, and 4 on circulating CD14+ monocytes was analyzed by flow-cytometry in all patients. RESULTS: Toll-like receptor 2 had a positive correlation with the vessel score and Gensini score (r=0.46, P<0.001; r=0.32, P<0.02, respectively). Toll-like receptor 4 also positively correlated with the vessel score and Gensini score (r=0.47, P<0.001; r=0.29, P<0.05, respectively). No significant correlation existed between the expression of Toll-like receptor 1 and the vessel score or Gensini score. Further, there was no significant correlation between high-sensitivity C-reactive protein and the vessel score or Gensini score. CONCLUSION: These data suggest that Toll-like receptor 2 and 4 expression correlates with the extent and severity of coronary artery disease.

Elevated levels of brain natriuretic peptide as a predictor of impaired coronary endothelial function in patients with left ventricular remodeling.

BACKGROUND: Plasma levels of brain natriuretic peptide (BNP) correlate with left ventricular remodeling, but the relationship between BNP induction and coronary function remains unclear. OBJECTIVES: The present study assessed BNP production in response to left ventricular enlargement and investigated the relationship between BNP production and coronary vasodilating function in patients with left ventricular remodeling. METHODS: Patients (n = 63) with normal or mildly diseased coronary arteries underwent Doppler flow study of the left anterior descending coronary artery. Vascular reactivity was examined using intracoronary acetylcholine, papaverine and nitroglycerin using a Doppler guidewire. RESULTS: Left ventricular end-diastolic dimension was positively correlated with BNP (r = 0.45, p < 0.001) in all patients. BNP was significantly and inversely correlated with percentage change in coronary artery diameter induced by acetylcholine (r = -0.56, p < 0.001) but not by nitroglycerin (r = -0.20, p = 0.28) in patients with left ventricular end-diastolic dimension > or = 55 mm (n = 32). By contrast, BNP was not significantly correlated with percentage change in coronary artery diameter induced by either acetylcholine or nitroglycerin in patients with left ventricular end-diastolic dimension < 55 mm (n = 31). Further, BNP was not correlated with the percentage change in coronary blood flow induced by acetylcholine or by papaverine in patients with or without left ventricular remodeling. CONCLUSIONS: The elevation in plasma BNP levels that occurs in association with left ventricular enlargement is a predictor of impaired endothelium-dependent vasodilation in conductance coronary arteries.

The effects of repeated thermal therapy for two patients with chronic fatigue syndrome.

OBJECTIVE: This paper describes the successful treatment of two patients with chronic fatigue syndrome (CFS) using repeated thermal therapy. METHODS: Two patients with CFS underwent treatment with prednisolone (PSL), with no satisfactory effect. They were subjected to thermal therapy that consisted of a far-infrared ray dry sauna at 60 degrees C and postsauna warming. The therapy was performed once a day, for a total of 35 sessions. After discharge, these subjects continued the therapy once or twice a week on an outpatient basis for 1 year. RESULTS: Symptoms such as fatigue, pain, sleep disturbance, and low-grade fever were dramatically improved after 15 to 25 sessions of thermal therapy. Although PSL administration was discontinued, the subjects showed no relapse or exacerbation of symptoms during the first year after discharge. The patients became socially rehabilitated 6 months after discharge. CONCLUSIONS: These results suggest that repeated thermal therapy might be a promising method for the treatment of CFS.

Effects of repeated sauna treatment on ventricular arrhythmias in patients with chronic heart failure.

BACKGROUND: The aim of the present study was to determine whether repeated 60 degrees C sauna treatment improves cardiac arrhythmias in chronic heart failure (CHF) patients, because ventricular arrhythmias are an important therapeutic target in CHF. METHODS AND RESULTS: Thirty patients (59+/-3 years) with New York Heart Association functional class II or III CHF and at least 200 premature ventricular contractions (PVCs)/24 h assessed by 24-h Holter recordings were studied. They were randomized into sauna-treated (n=20) or non-treated (n=10) groups. The sauna-treated group underwent a 2-week program of a daily 60 degrees C far infrared-ray dry sauna for 15 min, followed by 30 min bed rest with blankets, for 5 days per week. Patients in the non-treated group had bed rest in a temperature-controlled room (24 degrees C) for 45 min. The total numbers of PVCs/24 h in the sauna-treated group decreased compared with the non-treated group [848+/-415 vs 3,097+/-1,033/24 h, p<0.01]. Heart rate variability (SDNN, standard deviation of normal-to-normal beat interval) increased [142+/-10 (n=16) vs 112+/-11 ms (n=8), p<0.05] and plasma brain natriuretic peptide concentrations decreased [229+/-54 vs 419+/-110 pg/ml, p<0.05] in the sauna-treated group compared with the non-treated group. CONCLUSION: Repeated sauna treatment improves ventricular arrhythmias in patients with CHF.