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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 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 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.

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.

It has been reported that repeated brief balloon inflation during coronary angioplasty (PTCA) alleviates myocardial dysfunction. However, it has also been reported that PTCA does not induce ischemic tolerance. Six patients with stable angina pectoris were recruited for this study. They were scheduled for PTCA to a significant stenosis of the proximal left anterior descending artery (LAD). All patients had single-vessel coronary artery disease without angiographic evidence of collateral circulation and with normal wall motion. After the stenosis of LAD was dilated by a 30-s inflation, 60 s of balloon inflation was performed five times at 60-s intervals. Left ventricular regional work was determined in the first and fifth inflations, and the data were compared. Regional work of the interventricular septum decreased immediately after the balloon inflation (the first inflation: 5.3 +/- 1.0 --> 0.6 +/- 0.2 mJ/cm3; fifth inflation; 5.3 +/- 1.0 --> 0.6 +/- 0.3 mJ/cm3) and no statistically significant differences were found between the first and fifth inflations. After balloon deflation, the time required for the recovery of regional work was 30s in the fifth inflation, compared with 40 s in the first inflation (at 30 s after deflation, first inflation: 3.6 +/- 1.3 mJ/cm3; fifth inflation: 5.2 +/- 1.2 mJ/cm3). Although repeated balloon inflation did not change the amount of reduction in regional work, it improved the postischemic recovery of regional work. These results suggest ischemic tolerance.

Carvedilol and metoprolol have been reported to be effective in the treatment of patients with chronic heart failure. However, to our knowledge, there have been no studies comparing the effects of the 2 drugs on cardiac function, including cardiac sympathetic nerve activity.We compared 15 patients with dilated cardiomyopathy (DCM) who were receiving carvedilol (group A) with 15 patients with DCM who were receiving metoprolol (group B). Before and after 1 y of treatment, cardiac (123)I-metaiodobenzylguanidine ((123)I-MIBG) uptake was assessed using the total defect score (TDS) and the heart-to-mediastinum (H/M) activity ratio from the delayed images. The New York Heart Association (NYHA) class and echocardiographic left ventricular ejection fraction (LVEF) also were assessed.In both groups, the TDS decreased (in group A, from 25 +/- 14 to 16 +/- 14, P0.01; in group B, from 27 +/- 9 to 19 +/- 10, P0.01), the H/M increased (in group A, from 1.67 +/- 0.31 to 2.01 +/- 0.36, P0.01; in group B, from 1.68 +/- 0.21 to 1.93 +/- 0.32, P0.01), the LVEF increased (in group A, from 31% +/- 10% to 48% +/- 10%, P0.01; in group B, from 28% +/- 9% to 47% +/- 15%, P0.01), and the NYHA functional class improved (in group A, from 2.9 +/- 0.3 to 1.7 +/- 0.5, P0.01; in group B, from 2.8 +/- 0.6 to 1.7 +/- 0.6, P0.01). The change in LVEF was mildly correlated with the change in the TDS in group A (r = 0.41) as well as in group B (r = 0.53). In the patients with a favorable response in the TDS or H/M, the NYHA class improved more than in the patients without a favorable response (P0.05).Carvedilol treatment can improve cardiac function, symptoms, and cardiac sympathetic nerve activity in patients with DCM to a similar extent as metoprolol treatment. The improvement of cardiac function and symptoms is related to the improvement of cardiac sympathetic nerve activity.

New York Heart Association (NYHA) classification is popularly used to evaluate severity of stable chronic heart failure. Since this evaluation depends on subjective symptoms such as dyspnoea or fatigue with exertion, it is not expected to provide a precise reflection of physiologic abnormality. Useful objective indices to evaluate severity of heart failure are peak oxygen uptake (Vo2) and minute ventilation–carbon dioxide output (VE–Vco2) slope, which are derived from cardiopulmonary exercise testing,1 but the required methodology is complex and may not be widely available. Previous studies have shown that plasma brain natriuretic peptide (BNP), a cardiac hormone secreted mainly by cardiac ventricles, increases in chronic heart failure and correlates with haemodynamic abnormalities such as left ventricular dysfunction.2 Although measurement of plasma BNP has been thought of as a simple way to diagnose heart failure,2 it has not been revealed how well plasma BNP concentration predicts severity of heart failure. If exercise tolerance could be shown to correlate with plasma BNP concentration in heart failure, it would enhance this measurement’s value in evaluating heart failure severity. In this study we investigated the relation between plasma BNP concentration and exercise tolerance in patients with chronic stable heart failure. Patients with stable chronic heart failure (neither diuretics nor inotropic drug were changed within two weeks before the study and more than …

Background Adaptive servo-ventilation (ASV) therapy, which is a form of noninvasive positive pressure ventilation therapy and uses an innovative ventilator that has simple operability and provides good patient adherence, potentially has therapeutic benefits—suppression of the deterioration and progression of chronic heart failure (CHF) and a reduction in the number of repeated hospitalizations. Therefore, ASV therapy draws attention as a novel, noninvasive nonpharmacotherapy for patients with CHF owing to its hemodynamics-improving effect, and it is currently being accepted in real-world clinical settings in Japan. However, clinical evidence sufficient for treatment recommendation is lacking because a multicenter, randomized, controlled study of ASV therapy has never been conducted. Methods/Design The present study is a confirmatory, prospective, multicenter, collaborative, open-label, blinded-endpoint, parallel-group, randomized, controlled study. At 40 medical institutions in Japan, 200 Japanese outpatients with mild to severe CHF (age: ≥ 20 years; New York Heart Association classification: greater than or equal to class II) will be randomly assigned to either of the following two study groups: the ASV group, in which 100 outpatients undergo guideline-directed medical therapy and ASV therapy for 24 weeks; and the control group, in which 100 outpatients undergo only guideline-directed medical therapy for 24 weeks. The objective of the present study is to confirm whether the ASV group is superior to the control group concerning the improvement of left ventricular contractility and remodeling, both assessed by two-dimensional echocardiography. Furthermore, the present study will also secondarily examine the effects of ASV therapy on the prognosis and quality of life of patients with CHF. Discussion ASV therapy using the device has the potential to provide therapeutic benefits based on its simple operability and good patient adherence and possesses the potential to improve left ventricular contractility and remodeling. Therefore, the present study is expected to afford more solid scientific evidence regarding ASV therapy as a novel, noninvasive, nonpharmacological, in-home, long-term ventilation therapy for patients with mild to severe CHF. Trial registration UMIN identifier: UMIN000006549, registered on 17 October, 2011. Electronic supplementary material The online version of this article (doi:10.1186/s13063-014-0530-z) contains supplementary material, which is available to authorized users.