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BACKGROUND: Minute ventilation/carbon dioxide production (VI‡E/VI‡CO2) is a variable of cardiopulmonary exercise testing (CPET), which is evaluated by arterial CO2pressure and ventilation-perfusion mismatch via invasive methods. This study evaluated substitute non-invasively obtained variables for minimum VI‡E/VI‡CO2(Min) and VI‡E vs. VI‡CO2slope (Slope) and the relationship between Min and Slope.Methods and Results:This study enrolled 1,052 patients with heart disease who underwent CPET and impedance cardiography simultaneously. At first, the correlations between the end-tidal CO2pressure (PETCO2), tidal volume/respiratory rate (TV/RR) ratio, VI‡E and VI‡CO2Y-intercept (Y-int), and cardiac index (CI) and the Min and Slope were investigated. Second, the correlation between Min and Slope was investigated. PETCO2showed the largest correlation value among the 4 variables. These 4 variables could reveal 84.2% and 81.9% of Min and Slope, respectively. Although Slope correlated with Min (R=0.868) and predicted 78.9% of Min, considering these 4 variables, Slope+Y-int was more strongly correlated with Min (R=0.940); the Slope+Y-int revealed 90.6% of the Min relationship in the multiple regression analysis. CONCLUSIONS: Over 80% of the Min and Slope values were revealed with the above-mentioned 4 variables collected non-invasively. The formula, Min∝Slope+Y-int, can reveal >90% of the Min/Slope relationships, and the Y-int may be a crucial factor to clarify the relationship between Min and Slope.

BACKGROUND Many heart failure (HF) guidelines recommend sodium restriction for patients with HF, but the outcome of sodium restriction counseling (SRC) for HF patients is still unknown. We wanted to clarify whether SRC reduces cardiac events in patients with HF.Methods and Results:Overall, 800 patients (77±12 years) who were hospitalized for HF were enrolled. During HF hospitalization, patients received SRC; patients were required to have a salt intake of

Background Exertional dyspnea is a major symptom of heart failure. We investigated the tidal volume (TV)-the respiratory rate (RR) regulation according to the peak O2 uptake (VO2) during cardiopulmonary exercise testing (CPET) for clarifying exercise ventilatory pattern. Methods We enrolled 1111 patients (66 ± 13 years old, 68% men) who had undergone CPET at our hospital. We investigated the relationship between TV and RR and drew the TV/height-RR figure according to the %peak VO2. Results During exercise, TV was greater, illustrated as higher %peak VO2. However, RR was weakly correlated with %peak VO2. Adjusted with age, height, sex, each point of RR, and %peak VO2, TV during exercise highly correlated with age, height, each point of RR, and % peak VO2 (R = 0.726 to 0.821, p Conclusions We identified three ventilatory regularities during exercise. First, TV increases as greater %peak VO2. Second, the line relating TV/height and RR at each reference point during the incremental exercise test converged onto area M. Finally, the TV-RR slope at the early exercise phase was lower in patients with a lower %peak VO2. These ventilatory regularities may assist in elucidating the excise ventilatory pattern and help the diagnosis of exertional dyspnea.

BACKGROUND There is little evidence regarding the effect of outpatient cardiac rehabilitation (CR) on exercise capacity or the long-term prognosis in patients after coronary artery bypass graft surgery (CABG). This study aimed to determine whether participation in outpatient CR improves exercise capacity and long-term prognosis in post-CABG Japanese patients in a multicenter cohort.Methods and Results:We enrolled 346 post-CABG patients who underwent cardiopulmonary exercise testing during early (2-3 weeks) and late (3-6 months) time points after surgery. They formed the Active (n=240) and Non-Active (n=106) CR participation groups and were followed for 3.5 years. Primary endpoint was a major adverse cardiac event (MACE): all-cause death or rehospitalization for acute myocardial infarction/unstable angina/worsening heart failure. Peak oxygen uptake at 3-5 months from baseline was significantly more increased in Active than in Non-Active patients (+26±24% vs. +19±20%, respectively; P

BACKGROUND Cardiopulmonary exercise testing (CPX) is used in the prognostic evaluation of patients with heart failure with reduced ejection fraction (HFrEF). In these patients, the ventilation feedback system is dysfunctional, and overactive peripheral chemoreceptors may be responsible for the early appearance of the respiratory compensation point (RCP) after the anaerobic threshold (AT). The mechanism of RCP appearance remains unknown and very few studies have reported the relationship between RCP and heart failure. We hypothesized that the duration between the RCP and AT (RCP-AT time) can predict the severity of cardiac disorders and prognosis in patients with HFrEF.Methods and Results:We enrolled 143 patients with HFrEF who underwent symptom-limited maximal CPX between 2012 and 2016. During a median follow-up of 1.4 years, cardiovascular death occurred in 45 participants (31%). The patients who died had a significantly shorter RCP-AT time and lower hemoglobin (Hb) levels than those who survived (P

Background We aimed to clarify the predictors of death or heart failure (HF) in elderly patients who undergo transcatheter aortic valve replacement (TAVR).Methods and Results:We prospectively enrolled 83 patients (age, 83±5 years) who underwent transthoracic echocardiography (TTE) and cardiopulmonary exercise testing (CPET) with impedance cardiography post-TAVR. We investigated the association of TTE and CPET parameters with death and the combined outcome of death and HF hospitalization. Over a follow-up of 19±9 months, peak oxygen uptake (VO2) was not associated with death or the combined outcome. The minimum ratio of minute ventilation (VE) to carbon dioxide production (VCO2) and the VE vs. VCO2slope were higher in patients with the combined outcome. After adjusting for age, sex, Society of Thoracic Surgeons score and peak VO2, ventilatory efficacy parameters remained independent predictors of the combined outcome (minimum VE/VO2: hazard ratio, 1.108; 95% confidence interval, 1.010-1.215; P=0.031; VE vs. VCO2slope: hazard ratio, 1.035; 95% confidence interval, 1.001-1.071; P=0.044), and had a greater area under the receiver-operating characteristic curve. The VE vs. VCO2slope ≥34.6 was associated with higher rates of the combined outcome, as well as lower cardiac output at peak work rate during CPET. Conclusions In elderly patients, lower ventilatory efficacy post-TAVR is a predictor of death and HF hospitalization, reflecting lower cardiac output at peak exercise.

Purpose/Method: Aliskiren is a direct renin inhibitor that has been reported to be effective for CHF, but the usefulness of combined therapy with carvedilol and aliskiren has not been reported. Forty-four patients with dilated cardiomyopathy (DCM) were randomized into a group receiving add-on therapy with carvedilol plus aliskiren and another group receiving carvedilol alone for 6 months. Nuclear imagings with (123)I-Metaiodobenzylguanidine (MIBG) and (99m)Tc-Sestamibi were performed. Exercise capacity using a specific activity scale (SAS) and the New York Heart Association (NYHA) class were evaluated. Cardiac sympathetic nerve activity was evaluated by (123)I-MIBG imaging, with the delayed heart-to-mediastinum activity ratio (H/M), delayed total defect score (TDS), and washout rate (WR). Results: Combined add-on therapy with carvedilol and aliskiren improved several parameters much more than carvedilol alone (p

BACKGROUND The increase in stroke volume during inotropic stimulation in patients with heart failure with reduced ejection fraction (HFrEF) is called the "pump function reserve." Few studies have reported on the relationship between pump function reserve and HF prognosis. In HFrEF patients who have pump function reserve, stroke volume increases during exercise. Simply put, the pulse pressure change (∆PP) during cardiopulmonary exercise testing (CPX) is closely related to the prognosis of patients with HFrEF. We hypothesized that ∆PP could predict disease severity and cardiovascular death in patients with HFrEF.Methods and Results:A total of 224 patients with HFrEF who underwent symptom-limited maximal CPX between 2012 and 2016 were enrolled. During a median follow-up of 1.5 years, cardiovascular death occurred in 54 participants (24%). Patients who died demonstrated a lower ∆PP between rest and peak exercise (∆PP [peak-rest]) than those who survived (P

Background The current understanding of ventilator efficiency variables during ramp exercise testing in the normal Japanese population is insufficient, and the responses of tidal volume (VT) and minute ventilation (VE) to the ramp exercise test in the normal Japanese population are not known. Methods A total of 529 healthy Japanese subjects aged 20–78 years underwent cardiopulmonary exercise testing using a cycle ergometer with ramp protocols. VT and VE at rest, at anaerobic threshold, and at peak exercise were determined. The slope of VE versus carbon dioxide (VCO2) (VE vs. VCO2 slope), minimum VE/VCO2, and oxygen uptake efficiency slope (OUES) were determined. Results For males and females in their 20 s, peak VT (VTpeak) was 2192 ± 376 and 1509 ± 260 mL (p Conclusions We have established the normal range of VT and VE responses, the VE vs. VCO2 slope, the minimum VE/VCO2, and the OUES for a healthy Japanese population. Some of these parameters were influenced by weight, height, sex, and age. These results provide useful reference values for interpreting the results of cardiopulmonary exercise testing in cardiac patients.

We investigated the glucagon levels in patients with heart failure (HF), using long oral glucose tolerance test (OGTT).In this prospective observational study, we enrolled 30 undiagnosed diabetes patients (age 69 ± 10 years, 70% males, HbA1c 43 mmol/mol). A 4-h OGTT was performed. Glucose, insulin, and glucagon (radioimmunoassay [RIA] and sandwich ELISA [S-W] methods) were evaluated during 4-h. We compared glucagon levels between HF and non-HF patients.There were 11 HF and 19 non-HF patients. In patients with HF, glucagon (S-W) during 4-h was lower than in patients without HF, with no significant difference. The area under the curve (AUC) of glucagon (RIA) during 4-h was significantly lower among HF patients. Moreover, in patients with reduced left ventricular ejection fraction (LVEF) (40%), AUC glucagon (RIA) was significantly lower than in patients with non-reduced EF (≥40%). However, there was no difference in glucagon values between the high E/e' (≥13.0) and low E/e' (13.0) groups.Although glucagon (S-W) showed no significant difference in patients with and without HF, especially reduced LVEF, glucagon (RIA) secretion was significantly lower in HF patients than in patients without HF. It is suggested that low glucagon secretion might be correlated with low EF.

Hyperglycemia is an established risk factor of coronary artery disease (CAD). However, hyperglycemia with preserved pancreatic β cell function induces hyperinsulinemia to correct the glucose profile and may even result in reactive hypoglycemia (RH), which induces an inflammatory response. In this study, the incidence of RH and its effect on arteriosclerosis were examined in CAD patients with a lengthy oral glucose tolerance test (OGTT).We performed a prospective cross-sectional study on 116 nondiabetic CAD patients [70 ± 9 years, 70% male, HbA1c < 6.5%] using coronary angiography and a 4-hour OGTT. Blood samples were collected prior to and 4 hours after the glucose load to evaluate arteriosclerosis markers. Hypoglycemia following the glucose tolerance test was defined as blood glucose levels < 70 mg/dL. We comparatively examined markers of inflammation and arteriosclerosis between the RH group and the non-RH group.A glucose metabolism disorder was observed in 69% of the patients. Hypoglycemia was observed in 24% (28 individuals) of the patients. All showed a RH pattern with no symptoms. The RH group exhibited significantly elevated insulin levels at 1 hour. Furthermore, a significant increase in the white blood cell (WBC) count during OGTT was observed in the RH group compared with the non-RH group [delta WBC; RH: 4.84 (-4.17-20.75) versus non-RH: -2.17 (-9.23-9.09) %; P = 0.04].Asymptomatic RH and an augmentation of inflammation were observed at an incidence of 24% in CAD patients.

Aims We evaluated whether glucose fluctuation (GF) causes vascular endothelial injury and affects glucometabolic factors during lengthy oral glucose tolerance test (OGTT). Methods We enrolled consecutive 116 patients with coronary artery disease (CAD) who were performed coronary angiography and 4-h OGTT. Blood samples were collected before and 4 h after glucose load to measure endothelial injury factor [von Willebrand factor (vWF) and vWF/a disintegrin-like and metalloproteinase with thrombospondin type-1 motifs 13 (ADAMTS-13) ratio]. GF was defined as maximum – minimum blood glucose levels during 4-h OGTT. We estimated the relationship between GF and glucometabolic factors. Results vWV and vWF/ADAMTS-13 ratio were significantly correlated with GF during 4-h OGTT. GF was significantly correlated with homeostasis model to assess insulin resistance (HOMA-IR) (R = 0.262), Matsuda index (R = −0.405), insulinogenic index (R = −0.336), HbA1c (R = 0.281) and disposition index (R = −0.672). When dividing patients into impaired and preserved category groups according to the average value of GF (122 mg/dL), adjusted to age, sex, HOMA-β, insulinogenic index, HOMA-IR, Matsuda index and HbA1c, disposition index was an independent risk factor for impaired GF [odds ratio (95% confidence interval): 2.87 (1.70–4.83), P Conclusion Pancreatic β cell dysfunction is associated with GF and causes endothelial injury in CAD patients.

BACKGROUND The cardiopulmonary exercise test (CPX) is a tool for evaluating disease severity and limitations in activities of daily living in patients with cardiac disorders. However, few studies have evaluated the association between exercise oscillatory ventilation (EOV) severity and prognosis in heart failure (HF) patients with EOV. EOV severity can be evaluated by detecting endtidal CO2pressure (PETCO2, an indicator of the arterial partial pressure of CO2(PaCO2)) and minute ventilation, which is a reflection of the respiratory response to elevated CO2. We hypothesized that the magnitude of EOV severity can predict the severity and prognosis of cardiac disorders and aimed to validate this hypothesis.Methods and Results:In total, 2,043 patients who underwent symptom-limited maximal CPX between 2010 and 2016 were evaluated. We enrolled 70 patients who had HF with reduced ejection fraction (HFrEF) and EOV. The endpoint was cardiovascular death. During a median follow-up of 4.3 years, 34 participants died (48%). Those who died showed significantly larger EOV loop size and lower hemoglobin (Hb) levels than those who survived (17.3±7.0 cm2vs. 12.8±6.1 cm2, P

The cardiopulmonary exercise test (CPX) is an essential examination for detecting pathophysiological derangement and determining treatment policy because it clarifies not only the changes of hemodynamics but also abnormality in the whole body during exercise where heart disease patients often feel symptoms.To utilize CPX effectively, we must understand each parameter, such as peak oxygen uptake (peak VO2), peak VO2/HR, and VE/VCO2. In addition, comparison of each parameter, for example, peak VO2 and VE/VCO2, and peak VO2 and peak VO2/HR, is useful to detect the pathophysiological abnormalities.In this article, I will describe how CPX should be used in clinical settings.

Background Anaerobic threshold (AT) and peak oxygen uptake ( V ˙ O 2 ) are well known as indicators of severity and prognosis of heart failure. Since these parameters are regulated by many factors, multiple organ dysfunction may occur in chronic heart failure, and these two parameters would vary among patients. However, it is not clear whether AT and peak V ˙ O 2 deteriorate similarly. Therefore, we planned to compare the degree of deterioration of these two parameters using a ratio of AT and peak V ˙ O 2 (%AT/peak), and evaluated its significance in heart failure subjects. Methods One hundred ninety-four stable heart failure patients who had optimal medical treatment for at least 3 months were enrolled. Cardiopulmonary exercise testing, echocardiography, and blood sampling were examined within one week. Since %AT/peak varied from 50.3% to 108.5%, we divided patients into tertiles of %AT/peak [Group A, 50.1–70.0 (n = 112), Group B, 70.1–90.0 (n = 64), Group C, 90.1–110.0 (n = 18)], and compared factors relating with skeletal muscle and heart failure among these 3 groups. Results In Group A, ratio of measured AT against predicted value (%AT) and measured peak V ˙ O 2 against predicted value (%peak V ˙ O 2 ) were similar (80.3 ± 19.0% and 80.4 ± 17.1%, respectively). Peak V ˙ O 2 became lower as %AT/peak increased (Group B; 65.6 ± 14.8%, p Conclusions %AT/peak showed negative correlation with peak V ˙ O 2 . In chronic heart failure, muscle weakness occurs at an early stage, and this can be evaluated using %AT/peak.

BACKGROUND Adaptive servo-ventilation (ASV) therapy is expected to be novel nonpharmacotherapy with hemodynamic effects on patients with chronic heart failure (CHF), but sufficient evidence has not been obtained. METHODS AND RESULTS A 24-week, open-label, randomized, controlled study was performed to confirm the cardiac function-improving effect of ASV therapy on CHF patients. At 39 institutions, 213 outpatients with CHF, whose left ventricular ejection fraction (LVEF) was

Cardiopulmonary exercise testing (CPX) is used to evaluate functional capacity and assess prognosis in cardiac patients. Ventilatory efficiency (VE/VCOA total of 289 Japanese patients underwent CPX using a cycle ergometer with ramp protocols between 2013 and 2014. Among these, 174 patients with a peak VOThe High group had a significantly lower ejection fraction, stroke volume, and cardiac output, and higher brain natriuretic peptide, tricuspid regurgitation pressure gradient, right ventricular systolic pressure, and peak early diastolic LV filling velocity/peak atrial filling velocity ratio compared with the Low group (p's 0.01). In addition, the Low group had a significantly higher prevalence of pleural effusion than did the High group (26 vs 11%, p 0.01).Patients with a relatively greater minVE/VCO

Adaptive servo-ventilation (ASV) therapy using an innovative ventilator—originally developed to treat sleep-disordered breathing (SDB)—is a novel modality of noninvasive positive pressure ventilation and is gaining acceptance among Japanese cardiologists in expectation of its applicability to treat patients with chronic heart failure (CHF) based on its acute beneficial hemodynamic effects. We conducted a multicenter, retrospective, real-world observational study in 115 Japanese patients with CHF, who had undergone home ASV therapy for the first time from January through December 2009, to examine their profile and the effects on their symptoms and hemodynamics. Medical records were used to investigate New York Heart Association (NYHA) class, echocardiographic parameters including left ventricular ejection fraction (LVEF), cardiothoracic ratio (CTR), brain natriuretic peptide (BNP), and other variables. Most of the patients were categorized to NYHA classes II (44.4 %) and III (40.7 %). SDB severity was not determined in 44 patients, and SDB was not detected or was mild in 27 patients. In at least 71 patients (61.7 %), therefore, ASV therapy was not applied for the treatment of SDB. CHF was more severe, i.e., greater NYHA class, lower LVEF, and higher CTR, in 87 ASV-continued patients (75.7 %) than in 28 ASV-discontinued patients (24.3 %). However, SDB severity was not related to continuity of ASV. The combined proportion of NYHA classes III and IV (P = 0.012) and LVEF (P = 0.009) improved significantly after ASV therapy. CTR and BNP did not improve significantly after ASV therapy but showed significant beneficial changes in their time-course analysis (P

This study evaluated the usefulness of cardiac sympathetic nerve activity, estimated by 123I-MIBG scintigraphy, and endothelial function, estimated by flow-mediated dilation (FMD), in the detection of coronary spastic angina (CSA). We compared 78 consecutive patients suspected of CSA with ten age-matched controls. On the basis of a spasm provocation test with acetylcholine, 53 patients were diagnosed as CSA and 25 patients were considered to have chest-pain syndrome (CPS). The total defect score (TDS) by delayed 123I-MIBG scintigraphy was significantly higher in both patient groups than in controls (P

Background:The safety of exercise-based cardiac rehabilitation (CR) has not been investigated in Japan, so a nationwide survey was conducted to investigate the incidence of adverse events (AEs) associated with CR and exercise testing.Methods and Results:In total, 136 hospitals reported operating recovery-phase CR programs, amounting to 383,096 patient-hours of exercise training. The incidence rates of all AEs and life-threatening AEs (LAE: death, cardiac arrest, acute myocardial infarction, cardiac rupture) during exercise sessions were 12 and 1 event/383,096 patient-hours (3.13 and 0.26 events/100,000patient-hours), respectively. When CR programs were categorized as “Formal” in which an exercise prescription based on exercise testing was issued to individual patients or “Non-formal” without exercise prescription, the incidence of AEs during and within the 24 h after an exercise session was significantly lower in the Formal than the Non-formal CR programs (P

Background The responses of heart rate (HR) and blood pressure to the ramp exercise test are not known and the current understanding of peak oxygen uptake and anaerobic threshold (AT) values in the normal Japanese population is insufficient. Methods and results A total of 749 healthy Japanese subjects aged 20–78 years underwent a cardiopulmonary exercise test using a cycle ergometer or treadmill ergometer with ramp protocols. HR, systolic blood pressure (SBP), and oxygen uptake ( V ˙ O 2 ) at rest, at AT, and at peak exercise were determined. HR and SBP at peak exercise in a cycle ergometer and treadmill ergometer test decreased with age. Work rate at peak exercise in a cycle ergometer increased with body weight and decreased with age. V ˙ O 2 / weight at AT and at peak exercise were higher in treadmill ergometer testing than in cycle ergometer testing, and were not affected by exercise protocol. Both of these decreased with age. Conclusions The normal responses of HR and SBP to ramp exercise testing are reported for the first time. AT, peak V ˙ O 2 , and V ˙ O 2 at each stage are shown for a healthy population. Some of these parameters were influenced by weight, gender, and age, as well as mode of exercise and the protocol used. These results provide useful reference values for interpreting the results of cardiopulmonary exercise testing.

Background Myocardial ischemia induces cardiac dysfunction, resulting in insufficient oxygen supply to peripheral tissues and mismatched energy production during exercise. To relieve the insufficient oxygen supply, heart rate (HR) response is augmented; however, beta-adrenergic receptor blockers (BB) restrict HR response. Although BB are essential drugs for angina pectoris, the effect of BB on exercise tolerance in patients with angina has not been studied. The aim of this study was to clarify the importance of HR augmentation to preserve exercise tolerance in patients with angina pectoris. Methods Forty-two subjects who underwent cardiopulmonary exercise testing (CPX) to detect myocardial ischemia were enrolled. CPX was performed until exhaustion or onset of significant myocardial ischemia using a ramp protocol. Subjects were assigned to three groups (Group A: with ST depression during CPX with significant coronary stenosis and taking BB; Group B: with ST depression and not taking BB; Group C: without ST depression and not taking BB). HR response to exercise was evaluated during the following two periods: below and above ischemic threshold (IT). In Group C, it was evaluated during the first 2 min and the last 2 min of a ramp exercise. Results No significant differences were observed among the three groups with regard to patients’ basic characteristics. Below IT, there were no differences in oxygen pulse/watt (O2 pulse increasing rate), HR/watt (ΔHR/ΔWR), and Δ V ˙ O 2 / Δ WR . Above IT, O2 pulse increasing rate was greater in Group A than in Group B. ΔHR/ΔWR was smaller in Group A than in Group B. Δ V ˙ O 2 / Δ WR became smaller in Group A than in Group B. There was no difference in anaerobic threshold, and peak V ˙ O 2 was smaller in Group A than in Group B. Conclusions Restriction of HR response by a BB is shown to be one of the important factors in diminished exercise tolerance.

Background The regional clinical alliance path (RCAP) after discharge from an acute-phase hospital is emerging as a tool for bridging acute-phase treatment and chronic-phase disease management. However, the optimal application of RCAP for acute myocardial infarction (AMI) remains unknown in Japan, and therefore a nationwide survey of hospitals was conducted. Methods and results In 2009, questionnaires were sent to 1,240 cardiology training hospitals authorized by the Japanese Circulation Society. The response rate was 62.9% (780/1,240). Of the 780 responding hospitals, 708 treated AMI, and in these hospitals the number of AMI patients and percutaneous coronary intervention (PCI) procedures performed were, respectively, 59±52 and 200±206 per year. The implementation rate of emergency PCI was high (91%), but that of outpatient cardiac rehabilitation (OPCR) was very low (18%). The implementation rate of RCAP after AMI was significantly lower (10%) than after stroke (57%). Cardiac rehabilitation (CR) was adopted as part of RCAP in only 19% (13/70) of currently operating RCAP programs. Conclusions This first Japanese nationwide survey of RCAP after AMI showed that in contrast to the broad dissemination of acute-phase invasive treatment for AMI, there was infrequent implementation of OPCR, RCAP after AMI, and RCAP including CR. It will be necessary to broaden the use of RCAP after AMI, including OPCR. (Circ J 2016; 80: 1750-1755).

Cardiac fibrosis is an important process of myocardial remodeling. Connective tissue growth factor (CTGF) is a cytokine that plays a key role in the occurrence of progressive fibrosis and excessive scarring. CTGF levels are increased in the failing heart. In addition, sympathetic nerve activity is enhanced in the failing heart, and exacerbates heart failure. To clarify the relation between cardiac sympathetic nerve activity and CTGF, we studied 35 (M/F = 28/7 patients) aged 57 ± 15 years with dilated cardiomyopathy (DCM). Cardiac sympathetic nerve activity was estimated from the total defect score (TDS) and from the H/M ratio and washout rate (WR) on I-123-MIBG imaging. Cardiac symptoms (NYHA class), exercise capacity (specific activity scale: SAS), brain natriuretic peptide (BNP), hemodynamics, and CTGF were assessed. There was a significant correlation between the CTGF and WR on I-123-MIBG (r = 0.45, P = 0.008). Also, a higher plasma CTGF level was associated with a lower SAS score (r = 0.51, P = 0.002), but not the TDS, H/M ratio, or BNP concentration. Moreover, a higher NYHA class and pulmonary artery wedge pressure were associated with a higher plasma CTGF level. The plasma CTGF level can be strongly related with cardiac sympathetic nerve activity in heart failure in DCM patients.

Objectives: Hypertension impairs coronary endothelial cell function, coronary microvascular function and the coronary flow (CF) reserve (CFR). Angiotensin II receptor blockers (ARBs) have been reported to possibly improve coronary endothelial function and coronary microvascular function. The purpose of this study was to determine whether treatment with the ARB olmesartan was more effective for improving CFR than the calcium channel blocker amlodipine. Methods: Twenty patients with untreated essential hypertension (M/F = 13/7, aged 55.6 ± 11.6 years) were randomly assigned to treatment with either olmesartan (n = 10) or amlodipine (n = 10) for 6 months. CF was measured in the proximal left anterior descending artery by magnetic resonance imaging before and during intravenous infusion of adenosine. CFR was calculated as the ratio of the hyperemic to baseline diastolic peak flow before and after 6 months of treatment. Results: The extent of systolic blood pressure reduction was similar in both groups (–40.0 ± 19.1 vs. –48.8 ± 14.7 mm Hg, p = 0.26). The olmesartan group showed significant improvement of CFR (from 1.9 ± 1.0 to 3.1 ± 1.1, p = 0.005), but this did not occur in the amlodipine group. Conclusion: Olmesartan, but not amlodipine, improves CFR in hypertensive patients.

SummaryBackground and purposeHypoglycemia during exercise is a serious problem in diabetic patients during cardiac rehabilitation, whereas normal subjects rarely experience hypoglycemia. Inappropriate glucose uptake by working muscles may be responsible. However, the precise characteristics of glucose uptake during exercise have not been fully studied. We have investigated the effect of acute exercise on glucose uptake in diabetic patients.MethodsNine type 2 diabetic patients (age, 57±6 years; HbA1c, 7.7±1.3%) performed exercise at an intensity of anaerobic threshold for 15min. Glucose utility was determined using euglycemic hyperinsulinemic clamp technique. Glucose infusion rate (GIR) was calculated throughout the exercise and recovery session.ResultsAverage GIR at rest was 3.4±1.6mg/(kgBWmin). Fifteen minutes after starting exercise, it increased significantly (6.6±2.4, p

Summary Background Although patients with heart disease sometimes complain of shortness of breath with rapid and shallow ventilation, its precise characteristics are unclear. We evaluated the relationship between exercise tolerance and the degree of rapidness and shallowness of breathing during exercise. Methods and results Thirty-eight heart disease patients with shortness of breath during daily activity underwent pulmonary function test and cardiopulmonary exercise testing on the same day. Regression line relating tidal volume to respiratory rate (TV/RR slope) during a ramp protocol below the inflection point was regarded as an indicator of rapid ventilation. Tidal volume after the inflection point was regarded as an indicator of shallow ventilation (TV at plateau). TV/RR slope showed weak but significant positive correlation with anaerobic threshold (r = 0.317) and peak V ˙ O 2 (r = 0.302). With V ˙ E vs . V ˙ C O 2 slope, it was negatively correlated (r = −0.528). TV at plateau was strongly correlated with inspiratory capacity (r = 0.641). It also showed strong correlation with anaerobic threshold (r = 0.594), peak V ˙ O 2 (r = 0.550), and V ˙ E vs . V ˙ C O 2 slope (r = −0.390). There was positive correlation between TV/RR slope and TV at plateau (r = 0.647). Conclusions It is suggested that both rapid breathing and shallow breathing are related to impaired exercise tolerance. Shallow breathing is partly determined by the ability of chest expansion.

SummaryBackgroundThis study was designed to evaluate the factors that affect myocardial salvage after percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI).Methods and resultsOne hundred and eighty-three patients with AMI who had undergone successful PCI were recruited for this study. Patients underwent 99mTc-pyrophosphate single photon emission computed tomography (SPECT) on the third day and 99mTc-MIBI SPECT on the sixth day after admission. In the 20 SPECT segments, the summed defect score (TDS) and extent score (ES) of AMI segments were determined and the percentage of the salvaged myocardium was calculated based on the TDS and ES. We performed multivariate analysis to evaluate factors that can affect myocardial salvage. Multivariate analysis was performed among the value of myocardial salvage rate and the 15 clinical variables. Administration of nicorandil (p=0.006), prodromal angina (p

Insulin resistance is associated with various cardiac dysfunctions both molecularly and clinically, including cardiac muscle relaxation and blood flow. Although, these dysfunctions result in heart failure, relationship between insulin resistance and severity of heart failure is not well studied yet. Since severity of chronic heart failure can be determined by exercise tolerance, we attempted to assess the insulin resistance in patients with chronic heart failure and evaluated the relationship between insulin sensitivity and exercise tolerance. We examined nine chronic heart failure patients. Insulin sensitivity was determined with euglycemic hyperinsulinemic clamp technique. Exercise tolerance was assessed using cardiopulmonary exercise testing. There was no correlation between body mass index and insulin sensitivity, while between body fat ratio, significant negative correlation was investigated ( r = −0.463). Insulin sensitivity was negatively correlated with exercise tolerance (with anaerobic threshold, r = 0.548; with peak oxygen uptake, r = 0.581). Insulin sensitivity also showed significant positive correlation with cardiac function during exercise (GIR versus peak oxygen pulse: r = 0.535). Insulin sensitivity is revealed to have some effects on exercise tolerance and cardiac function in patients with chronic heart failure. Insulin resistance seems to be one of the important targets in managing the chronic heart failure.

Background The implementation of cardiac rehabilitation (CR) after acute myocardial infarction (AMI) has not been fully investigated in Japan, so a nationwide survey of hospitals was conducted. Methods and Results Questionnaires were sent in 2004 to a total of 1,875 hospitals in Japan, including all the 859 Japanese Circulation Society (JCS)-authorized cardiology-training hospitals (THs), 311 JCS-associated hospitals (AH), and 705 randomly sampled non-THs (NTHs). The response rate was 59% (1,106/1,875). The percentages of hospitals treating hospitalized AMI patients were 97% in 526 TH, 85% in 194 AH, and 20% in 339 NTH. Although the rates of implementation of emergency percutaneous coronary intervention were very high (92%, 56%, and 4%, respectively), the rates of implementation of recovery phase CR were low (20%, 8%, and 2%, respectively). In addition, patient education programs (23%, 13% and 2%) and formulated exercise prescriptions based on exercise testing (16%, 7% and 1%) were poorly implemented. More importantly, only 9%, 2% and 0% of these hospitals had outpatient CR programs. From these data, the nationwide participation rate in outpatient CR after AMI in Japan was estimated to be only 3.8-7.6%. Conclusion This first nationwide survey demonstrated that, in contrast to the broad dissemination of acute phase invasive treatment for AMI, the implementation of recovery phase CR, especially outpatient CR, is extremely poor in Japan. In addition, patient education programs and exercise prescription based on exercise testing are only poorly implemented. (Circ J 2007; 71: 173 - 179)

Background In a given individual, a consistent relationship exists between oxygen uptake (V˙O2) and heart rate (HR) during exercise. The quotient of V˙O2 and HR (V˙O2/HR) is called the oxygen pulse (O2 pulse), and its value is dependent on stroke volume (SV). However, it is difficult to believe that the O2 pulse would indicate the SV when HR has been modified as with the use of beta-adrenergic receptor blockers (BB). Until now, the effect of BB on peak O2 pulse has not been precisely studied. We tried to clarify the effect of BB on the relationship between O2 pulse and SV. Methods Of 699 consecutive heart disease subjects who performed cardiopulmonary exercise tests (CPX) from 2012 to 2014, we enrolled 430 subjects who had sinus rhythm and could perform CPX until exhaustion. One hundred and fifty-seven subjects were taking BB. SV was evaluated during CPX using impedance cardiography, and we compared the peak O2 pulse with peak SV between patients without BB (Group A) and with BB (Group B). Results The HRs at rest and peak exercise in Group A were greater than those in Group B (74.4 ± 13.0/min vs. 71.8 ± 11.3/min, p

Introduction: Although the prognostic efficacy of out-patient cardiac rehabilitation (OPCR) in patients with coronary artery disease (CAD) has been established in Western countries, it has not been studied in Japan, where both incidence and mortality of CAD are known to be much lower than in Western counties. Methods: To determine the prognostic efficacy of OPCR in Japan, a prospective, controlled, multicenter study of OPCR (J-REHAB) was conducted in 15 hospitals in Japan. A total of 1047 patients hospitalized with cardiac events were prospectively assigned to either OPCR group (n=848) or Non-OPCR group (n=199) according to patient’s preference at the time of hospital discharge. Patients in OPCR group were scheduled to participate in a comprehensive OPCR program for 3 months and Non-OPCR group received usual care. Event-free survivals for cardiac and all-cause death/rehospitalization were assessed according to the initial group assignment and the “prespecified” actual OPCR performance (attendance >=4 times/month and total exercise time >=150 min/week). Results: Patients were followed-up for 416days on average and the follow-up rate was 99.4%. At baseline, patients were 64±11years of age, 85% was male, 58% acute myocardial infarction, with preserved EF (53±13%). By Kaplan-Meier analysis, OPCR group had significantly better event-free survival for cardiac death/rehospitalization (p Conclusions: The first Japanese prospective multicenter J-REHAB study has demonstrated that active participation in OPCR is associated with better event-free survival in CAD patients, independent of baseline clinical characteristics.

Although exercise oscillatory ventilation has emerged as a potent independent risk factor for adverse prognosis in heart failure, it is not well known whether cardiac rehabilitation can improve oscillatory ventilation. In this study, we investigated the magnitude of oscillations in ventilation before and after cardiac rehabilitation in chronic heart failure patients with exercise oscillatory ventilation. Cardiac rehabilitation (5-month program) was performed in 26 patients with chronic heart failure who showed an oscillatory ventilation pattern during cardiopulmonary exercise testing (CPX). After the 5-month rehabilitation program was completed, the patients again underwent CPX. To determine the magnitude of oscillations in ventilation, the amplitude and cycle length of the oscillations were calculated and compared with several other parameters, including biomarkers that have established prognostic value in heart failure. At baseline before cardiac rehabilitation, both oscillation amplitude (R = 0.625, P

Background Two-dimensional speckle tracking (2DST) stress echocardiography detects postischemic myocardial diastolic stunning. However, the use of 2DST at rest for detecting diastolic stunning in ischemia is unclear. Results Thirty-nine patients (age = 65 ± 12 years; male/female = 34/5) with effort angina pectoris that was confirmed by stress myocardial perfusion scintigraphy were enrolled. Ischemic area (I) was determined in the middle LV short axial view using stress myocardial scintigraphy. The area opposite to it was defined as nonischemic area (non-I). Midventricular parasternal short-axis (SAX) radial strains were estimated using 2DST at rest on the following day. LV diastolic function was evaluated using diastolic index (DI, changes in the regional LV radial strain during diastole) and radial strain rate (SR) during early diastolic period. These parameters were compared between I and non-I before and 1 month after percutaneous coronary intervention (PCI) in the I of 3 coronary vessels. For the I, the DI was lower (38 ± 27 vs. 55 ± 27; P = 0.003) and SR was higher (−1.6 ± 0.6 vs. −1.9 ± 0.8; P = 0.007) than in non-I before PCI. One month after PCI, the DI and SR recovered to 53 ± 27 (P = 0.008) and −2.1 ± 0.8 (P = 0.006), respectively. Furthermore, the DI of the LAD and LCX significantly improved (P = 0.0004 and 0.002, respectively); the RCA area showed tendency to improve (P = 0.092), and the SR also improved (P

Adaptive servo-ventilation (ASV) therapy has been reported to be effective for improving central sleep apnea (CSA) and chronic heart failure (CHF). The purpose of this study was to clarify whether ASV is effective for CSA, cardiac sympathetic nerve activity (CSNA), cardiac symptoms/function, and exercise capacity in CHF patients with CSA and Cheyne-Stokes respiration (CSR-CSA). In this study, 31 CHF patients with CSR-CSA and a left ventricular ejection fraction (LVEF) ≤ 40% were randomized into an ASV group and a conservative therapy (non-ASV) group for 6 month. Nuclear imagings with 123I-Metaiodobenzylguanidine (MIBG) and 99mTc-Sestamibi were performed. Exercise capacity using a specific activity scale (SAS) and the New York Heart Association (NYHA) class were evaluated. CSNA was evaluated by 123I-MIBG imaging, with the delayed heart/mediastinum activity ratio (H/M), delayed total defect score (TDS), and washout rate (WR). The ASV group had significantly better (P

Background Functional mitral regurgitation (MR) is common in patients with chronic heart failure (CHF) and left ventricular dysfunction. The severity of CHF is expressed in terms of exercise tolerance, so MR during exercise would affect the severity of heart failure. However, it is not well known how much MR increases during exercise, or if it is related with severity of heart failure. Methods and Results Seventeen subjects underwent dynamic cycle exercise at steady-state levels of 80% and 150% of anaerobic threshold (AT). During each exercise level, the MR jet and left atrial (LA) area were measured, and the degree of MR was expressed as the ratio (MR/LA). The MR/LA increased slightly at 80% AT (rest: 15.5±7.8%, 80% AT: 21.7±9.3%, p

By carrying out an all-electron GW calculation, we firstly obtain quasiparticle energies of C 60 molecule without any experimental information. The amount of computation of GW calculation is propotional to the order of N 6 (N = number of electrons) far more than the case of the standard LDA of N 3 for such a large system. The GW program code has been parallelized using MPI and actual computaions are performed on several supercomputers within the Nanotechnology-VPN under ITBL environment.

Asymmetric expression of Nodal in the lateral plate mesoderm (LPM) plays the major role in left–right (L-R) patterning. A Nodal-responsive enhancer located in the intron 1 (ASE) regulates asymmetric Nodal expression, but it is unknown how Nodal expression is initiated in the left LPM. Here, we have identified a second asymmetric enhancer (left side-specific enhancer, LSE) in the upstream region of mouse Nodal gene. LSE is also located in the corresponding region of human NODAL. L-R specificity of LSE is affected by iv and inv mutations. The requirement of a conserved FoxH1-binding sequence for LSE activity and the dependence of LSE activity on Nodal coreceptor Cryptic indicate that LSE is activated by Nodal signal. However, the mutant mouse lacking LSE does not show obvious L-R patterning defects. These results suggest that Nodal expression in the left LPM is induced by a combination of two Nodal-responsive autoregulatory enhancers, ASE and LSE. Developmental Dynamics 232:1031–1036, 2005. © 2005 Wiley-Liss, Inc.