Age- and sex-stratified normal values for circulatory and ventilatory power during ramp exercise derived from a healthy Japanese population.

Circulatory power (CP) and ventilatory power (VP), obtained by cardiopulmonary exercise testing (CPX), have been suggested to be excellent prognostic markers for heart failure. However, the normal values of these parameters in healthy Japanese populations remain unknown; thus, we aimed to investigate these values in such a population. A total of 391 healthy Japanese participants, 20-78 years of age, underwent CPX with a cycle ergometer with ramp protocols. Systolic blood pressure (SBP), heart rate, oxygen uptake ([Formula: see text]O2) at peak exercise, and the slope of minute ventilation ([Formula: see text]E) versus carbon dioxide ([Formula: see text]CO2) ([Formula: see text]E vs. [Formula: see text]CO2 slope) were measured. CP was calculated by multiplying the peak [Formula: see text]O2 and SBP values, and VP was calculated by dividing the peak SBP value by the [Formula: see text]E versus [Formula: see text]CO2 slope. For males and females, the average CP values were 6119 ± 1280 (mean ± standard deviation) and 4775 ± 914 mmHg·mL/min/kg, respectively (p < 0.001). The average VP values for males and females were 8.0 ± 1.3 and 6.9 ± 1.3 mmHg (p < 0.001). CP decreased with age in both sexes. VP increased with age in females, with no significant change in males. We calculated the normal values for CP and VP in a healthy Japanese population. The results can contribute to the evaluation of patients' CPX results as a reference.

New Formula to Predict Heart Rate at Anaerobic Threshold That Considers the Effects of ß-Blockers in Patients With Myocardial Infarction: MULTI-INSTITUTIONAL RETROSPECTIVE CROSS-SECTIONAL STUDY.

PURPOSE: It is recommended that patients with myocardial infarction (MI) be prescribed exercise by target heart rate (HR) at the anaerobic threshold (AT) via cardiopulmonary exercise testing (CPX). Although percent HR reserve using predicted HRmax (%HRRpred) is used to prescribe exercise if CPX or an exercise test cannot be performed, %HRRpred is especially difficult to use when patients take ß-blockers. We devised a new formula to predict HR at AT (HRAT) that considers ß-blocker effects in MI patients and validated its accuracy. METHODS: The new formula was created using the data of 196 MI patients in our hospital (derivation sample), and its accuracy was assessed using the data of 71 MI patients in other hospitals (validation sample). All patients underwent CPX 1 mo after MI onset, and resting HR, resting systolic blood pressure (SBP), and HRAT were measured during CPX. RESULTS: The results of multiple regression analysis in the derivation sample gave the following formula (R2 = 0.605, P < .001): predicted HRAT = 2.035 × (≥65 yr:-1, <65 yr:1) + 3.648 × (body mass index <18.5 kg/m2:-1, body mass index ≥18.5 kg/m2:1) + 4.284 × (ß1-blocker(+):-1, ß1-blocker(-):1) + 0.734 × (HRrest) + 0.078 × (SBPrest) + 36.812. This formula consists entirely of predictors that can be obtained at rest. HRAT and predicted HRAT with the new formula were not significantly different in the validation sample (mean absolute error: 5.5 ± 4.1 bpm). CONCLUSIONS: The accuracy of the new formula appeared to be favorable. This new formula may be a practical method for exercise prescription in MI patients, regardless of their ß-blocker treatment status, if CPX is unavailable.

Ventilatory efficiency during ramp exercise in relation to age and sex in a healthy Japanese population.

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 (V̇E) 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 V̇E at rest, at anaerobic threshold, and at peak exercise were determined. The slope of V̇E versus carbon dioxide (V̇CO2) (V̇E vs. V̇CO2 slope), minimum V̇E/V̇CO2, 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 < 0.001), peak V̇E (V̇Epeak) was 80.6 ± 18.7 and 57.7 ± 13.9 L/min (sex differences p < 0.001), the V̇E vs. V̇CO2 slope was 24.4 ± 3.2 and 25.7 ± 3.2 (p = 0.035), the minimum V̇E/V̇CO2 was 24.2 ± 2.3 and 27.0 ± 2.8 (p < 0.001), and the OUES was 2452 ± 519 and 1991 ± 315 (p < 0.001), respectively. VTpeak and V̇Epeak decreased with age and increased with weight and height. The V̇E vs. V̇CO2 slope and minimum V̇E/V̇CO2 increased with age, while conversely, the OUES decreased with age. CONCLUSIONS: We have established the normal range of VT and V̇E responses, the V̇E vs. V̇CO2 slope, the minimum V̇E/V̇CO2, 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.

Active Participation in Outpatient Cardiac Rehabilitation Is Associated With Better Prognosis After Coronary Artery Bypass Graft Surgery　- J-REHAB CABG Study.

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<0.05), and the MACE rate was significantly lower in Active than Non-Active patients (3.4% vs. 10.5%, respectively; P=0.02). Multivariate Cox proportional hazard analysis showed that participation in outpatient CR was a significant prognostic determinant of MACE (P=0.03). CONCLUSIONS: This unique study showed that a multicenter cohort of patients who underwent CABG and actively participated in outpatient CR exhibited greater improvement in exercise capacity and better survival without cardiovascular events than their counterparts who did not participate.

Effects of αß-Blocker Versus ß1-Blocker Treatment on Heart Rate Response During Incremental Cardiopulmonary Exercise in Japanese Male Patients with Subacute Myocardial Infarction.

A simplified substitute for heart rate (HR) at the anaerobic threshold (AT), i.e., resting HR plus 30 beats per minute or a percentage of predicted maximum HR, is used as a way to determine exercise intensity without cardiopulmonary exercise testing (CPX) data. However, difficulties arise when using this method in subacute myocardial infarction (MI) patients undergoing beta-blocker therapy. This study compared the effects of αß-blocker and ß1-blocker treatment to clarify how different beta blockers affect HR response during incremental exercise. MI patients were divided into αß-blocker (n = 67), ß1-blocker (n = 17), and no-ß-blocker (n = 47) groups. All patients underwent CPX one month after MI onset. The metabolic chronotropic relationship (MCR) was calculated as an indicator of HR response from the ratio of estimated HR to measured HR at AT (MCR-AT) and peak exercise (MCR-peak). MCR-AT and MCR-peak were significantly higher in the αß-blocker group than in the ß1-blocker group (p < 0.001, respectively). Multiple regression analysis revealed that ß1-blocker but not αß-blocker treatment significantly predicted lower MCR-AT and MCR-peak (ß = -0.432, p < 0.001; ß = -0.473, p < 0.001, respectively). Based on these results, when using the simplified method, exercise intensity should be prescribed according to the type of beta blocker used.

Effect of carvedilol on heart rate response to cardiopulmonary exercise up to the anaerobic threshold in patients with subacute myocardial infarction.

Resting heart rate (HR) plus 20 or 30 beats per minute (bpm), i.e., a simplified substitute for HR at the anaerobic threshold (AT), is used as a tool for exercise prescription without cardiopulmonary exercise testing data. While resting HR plus 20 bpm is recommended for patients undergoing beta-blocker therapy, the effects of specific beta blockers on HR response to exercise up to the AT (ΔAT HR) in patients with subacute myocardial infarction (MI) are unclear. This study examined whether carvedilol treatment affects ΔAT HR in subacute MI patients. MI patients were divided into two age- and sex-matched groups [carvedilol (+), n = 66; carvedilol (-), n = 66]. All patients underwent cardiopulmonary exercise testing at 1 month after MI onset. ΔAT HR was calculated by subtracting resting HR from HR at AT. ΔAT HR did not differ significantly between the carvedilol (+) and carvedilol (-) groups (35.64 ± 9.65 vs. 34.67 ± 11.68, P = 0.604). Multiple regression analysis revealed that old age and heart failure after MI were significant predictors of lower ΔAT HR (P = 0.039 and P = 0.013, respectively), but not carvedilol treatment. Our results indicate that carvedilol treatment does not affect ΔAT HR in subacute MI patients. Therefore, exercise prescription based on HR plus 30 bpm may be feasible in this patient population, regardless of carvedilol use, without gas-exchange analysis data.

Vascular response to biolimus A-9 eluting stent in patients with shorter and prolonged dual antiplatelet therapy: optical coherence tomography sub-study of the NIPPON trial.

Dual antiplatelet therapy (DAPT) with thienopyridine and aspirin is the standard care for the prevention of stent thrombosis. However, the optimal duration and effect of the duration of DAPT on intra-stent thrombus (IS-Th) formation are unknown. The NIPPON study (Nobori Dual Antiplatelet Therapy as Appropriate Duration) was an open label, randomized multicenter, assessor-blinded, trial designed to demonstrate the non-inferiority of shorter (6-month) DAPT to prolonged (18-month) DAPT, after biolimus A9 eluting stent implantation in 3773 patients at 130 sites in Japan. Among them, 101 patients were randomly allocated for an optical coherence tomography (OCT) sub-study to assess the difference of local IS-Th formation between the two groups. In addition to standard OCT parameters, the number of IS-Th formed was counted in each target stent at 8 months. Baseline patient characteristics were not different between the 6- and 18-month groups. IS-Th was detected in 9.8% of the cases and the presence of IS-Th was not significantly different between the two groups (10.9% in 6-month vs. 9.1% in 12-month, P = 0.76). Furthermore, the number of IS-Th formed was not significantly different between the two groups. This OCT sub-study was in line with the main NIPPON study which demonstrated the non-inferiority of 6-month DAPT to 18-month DAPT. Shorter DAPT duration did not promote progressive IS-Th formation at the mid-term time point.

Dual Antiplatelet Therapy for 6 Versus 18 Months After Biodegradable Polymer Drug-Eluting Stent Implantation.

OBJECTIVES: The NIPPON (Nobori Dual Antiplatelet Therapy as Appropriate Duration) study was a multicenter randomized investigation of the noninferiority of short-term versus long-term dual antiplatelet therapy (DAPT) in patients with implantation of the Nobori drug-eluting stent (DES) (Terumo, Tokyo, Japan), which has a biodegradable abluminal coating. BACKGROUND: The optimum duration of DAPT for patients with a biodegradable polymer-coated DES is unclear. METHODS: The subjects were 3,773 patients with stable or acute coronary syndromes undergoing Nobori stent implantation. They were randomized 1:1 to receive DAPT for 6 or 18 months. The primary endpoint was net adverse clinical and cerebrovascular events (NACCE) (all-cause mortality, myocardial infarction, stroke, and major bleeding) from 6 to 18 months after stenting. Intention-to-treat analysis was performed in 3,307 patients who were followed for at least 6 months. RESULTS: NACCE occurred in 34 patients (2.1%) receiving short-term DAPT and 24 patients (1.5%) receiving long-term DAPT (difference 0.6%, 95% confidence interval [CI]: 1.5 to 0.3). Because the lower limit of the 95% CI was inside the specified margin of -2%, noninferiority of short-term DAPT was confirmed. Mortality was 1.0% with short-term DAPT versus 0.4% with long-term DAPT, whereas myocardial infarction was 0.2% versus 0.1%, and major bleeding was 0.7% versus 0.7%, respectively. The estimated probability of NACCE was lower in the long-term DAPT group (hazard ratio: 1.44, 95% CI: 0.86 to 2.43). CONCLUSIONS: Six months of DAPT was not inferior to 18 months of DAPT following implantation of a DES with a biodegradable abluminal coating. However, this result needs to be interpreted with caution given the open-label design and wide noninferiority margin of the present study. (Nobori Dual Antiplatelet Therapy as Appropriate Duration [NIPPON]; NCT01514227).

Prevalence of electrocardiographic abnormalities in young, elite Japanese athletes.

BACKGROUND: The question as to whether or not electrocardiogram (ECG) evaluations should be performed in all athletes is still controversial. So, in this study, the prevalence of electrocardiographic abnormalities was evaluated in young, elite Japanese athletes. METHODS: Subjects included 174 male and 101 female Japanese athletes (mean age, 21.5 years). Sports activities included baseball, basketball, diving, fencing, gymnastics, judo, rhythmic gymnastics, soccer, swimming, tennis, track and field, volleyball, and water polo. A 12-lead resting ECG was recorded and evaluated. We used the criteria for distinctly abnormal ECG patterns as defined by Pelliccia et al. Subjects were divided into 2 groups on the basis of their exercise training type: an endurance training group and a static training group. RESULTS: Twenty six of 174 male subjects (14.9%) and 11 of 101 (10.9%) female subjects presented with abnormal ECG results. ECG abnormalities were observed much more frequently in track athletes compared to athletes of other sporting events. Field players did not present with any ECG abnormalities. Overall, the incidences of ECG abnormalities were statistically lower in the static exercise training group than in the endurance training group both in male and female. High voltage of left ventricle was observed in 114 of 175 male subjects (65.1%), and 27 of 101 female subjects (26.7%). CONCLUSIONS: The prevalence of ECG abnormalities in young, elite, Japanese athletes was comparable to that previously reported by both Western and Asian investigators.

The Relation of Respiratory Muscle Strength to Disease Severity and Abnormal Ventilation During Exercise in Chronic Heart Failure Patients.

BACKGROUND: Breathlessness is a common problem in chronic heart failure (CHF) patients, and respiratory muscle strength has been proposed to play an important role in causing breathlessness in these patients. OBJECTIVES: The aim of this study was to investigate the relation between respiratory muscle strength and the severity of CHF, and the influence of respiratory muscle strength on abnormal ventilation during exercise in CHF patients. PATIENTS AND METHODS: In this case series study, we assessed clinically stable CHF outpatients (N = 66, age: 57.7 ± 14.6 years). The peak oxygen consumption (peak VO2), the slope relating minute ventilation to carbon dioxide production (VE/VCO2 slope), and the slope relating tidal volume to respiratory rate (TV/RR slope) were measured during cardiopulmonary exercise testing. Respiratory muscle strength was assessed by measuring the maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP). RESULTS: The MIP and MEP decreased significantly as the New York Heart Association functional class increased (MIP, P = 0.021; MEP, P < 0.01). The MIP correlated with the TV/RR slope (r = 0.57, P < 0.001) and the VE/VCO2 slope (r = -0.44, P < 0.001), and the MEP also correlated with the TV/RR slope (r = 0.53, P < 0.001) and the VE/VCO2 slope (r = -0.25, P < 0.040). Stepwise multiple regression analysis revealed that age and MIP were statistically significant predictors of the TV/RR and VE/VCO2 slopes (both P < 0.05). CONCLUSIONS: Respiratory muscle strength is related to the severity of CHF, and associated with rapid and shallow ventilation or excessive ventilation during exercise.

Gender-related differences in maximum gait speed and daily physical activity in elderly hospitalized cardiac inpatients: a preliminary study.

Maximum gait speed and physical activity (PA) relate to mortality and morbidity, but little is known about gender-related differences in these factors in elderly hospitalized cardiac inpatients. This study aimed to determine differences in maximum gait speed and daily measured PA based on sex and the relationship between these measures in elderly cardiac inpatients.A consecutive 268 elderly Japanese cardiac inpatients (mean age, 73.3 years) were enrolled and divided by sex into female (n = 75, 28%) and male (n = 193, 72%) groups. Patient characteristics and maximum gait speed, average step count, and PA energy expenditure (PAEE) in kilocalorie per day for 2 days assessed by accelerometer were compared between groups.Gait speed correlated positively with in-hospital PA measured by average daily step count (r = 0.46, P < 0.001) and average daily PAEE (r = 0.47, P < 0.001) in all patients. After adjustment for left ventricular ejection fraction, step counts and PAEE were significantly lower in females than males (2651.35 ± 1889.92 vs 4037.33 ± 1866.81 steps, P < 0.001; 52.74 ± 51.98 vs 99.33 ± 51.40 kcal, P < 0.001), respectively.Maximum gait speed was slower and PA lower in elderly female versus male inpatients. Minimum gait speed and step count values in this study might be minimum target values for elderly male and female Japanese cardiac inpatients.

Influence of exercise-induced pulmonary hypertension on exercise capacity in asymptomatic degenerative mitral regurgitation.

BACKGROUND: Exercise capacity is helpful in the management of patients with mitral regurgitation (MR). However, the determinants of exercise capacity reduction in MR have remained unclear. This study was designed to objectively assess exercise capacity, identify the echocardiographic predictors of exercise capacity, and investigate its impact on development of symptoms in asymptomatic degenerative MR. METHODS: A total of 49 consecutive asymptomatic patients (age, 58.9±13.1 years; 82% males) with at least moderate degenerative MR (effective regurgitant orifice area=0.40±0.14cm(2); regurgitant volume=60.9±19.6mL) underwent the symptom-limited cardiopulmonary exercise testing for assessing exercise capacity (peak oxygen uptake, peak V˙O2; the minute ventilation/carbon dioxide production, V˙E/V˙CO2 slope). All patients also underwent exercise stress echocardiography for detecting exercise-induced pulmonary hypertension (EIPH) defined by systolic pulmonary arterial pressure (SPAP) ≥60mmHg. RESULTS: The mean peak V˙O2 was 22.6±5.1mL/kg/min (86.7±14.1% of age, gender-predicted); peak V˙O2 widely varied (48-121% of predicted), and was markedly reduced (<80.4% of predicted) in 24% of the study patients. The patients with EIPH had lower 2-year symptom-free survival than those without EIPH (p=0.003). The multivariable analysis demonstrated that EIPH was an independent echocardiographic determinant of peak V˙O2 (p=0.001) and V˙E/V˙CO2 slope (p=0.021). Furthermore, the area under curve of age- and gender-adjusted exercise SPAP was 0.88 (95% confidence interval: 0.78-0.97) for reduced exercise capacity. CONCLUSIONS: In asymptomatic moderate to severe degenerative MR, EIPH was independently associated with exercise capacity and predicted the occurrence of symptoms. Exercise stress echocardiography is an important tool in managing patients with asymptomatic degenerative MR.

Impaired ß-cell function attenuates training effects by reducing the increase in heart rate reserve in patients with myocardial infarction.

BACKGROUND: Insulin resistance (IR) is characterized as a metabolic disorder syndrome that is upstream of hypertension, dyslipidemia, and diabetes mellitus (DM). This study investigated exercise training effects on the exercise tolerance and heart rate dynamics in patients with IR or pancreatic ß-cell dysfunction. METHODS: Seventy patients (mean age, 60.1 years) with myocardial infarction (MI) participating in a phase II cardiac rehabilitation program were studied. Patients diagnosed with DM were excluded. Homeostasis model-assessment indices were used to divide patients into three groups - A: IR; B: normal; and C: ß-cell dysfunction. A cardiopulmonary exercise test (CPX) was performed and peak oxygen uptake (V˙O2) was measured. After baseline testing, subjects participated in a supervised, combined aerobic and resistance exercise program. RESULTS: Peak V˙O2 at baseline was comparable among the three groups, and it improved after training in all groups (p<0.05). However, both the increase and percentage increase in peak V˙O2 were smaller in Group C than in Group A (p<0.05). Heart rate (HR) reserve (peak HR-rest HR), and HR recovery immediately 1min after exercise during CPX were calculated in 45 patients who were not taking negative chronotropic agents. Group C alone did not show any significant increase in HR reserve. HR reserve at both baseline and after training had significant positive correlations with peak V˙O2. HR recovery was 1.9 beats/min lower in group C than group A, but this was not significant. HR recovery in group C did not increase after cardiac rehabilitation. CONCLUSION: Impaired HR reserve increase after training in patients with pancreatic ß-cell dysfunction attenuates exercise training effects on functional capacity. Comprehensive treatment including vigorous exercise training will be needed in such prediabetic patients.

Differences in physical performance based on the Geriatric Nutritional Risk Index in elderly female cardiac patients.

BACKGROUND AND AIMS: Little is known about differences in the risk of poor nutritional status as assessed by the Geriatric Nutritional Risk Index (GNRI) in relation to physical performance in elderly female cardiac inpatients. The present study aimed to determine both differences in physical performance based on the GNRI and physical performance cut-off values according to the GNRI in elderly female cardiac inpatients. METHODS: We enrolled 105 consecutive female Japanese inpatients aged ≥65 years (mean age, 74.6 years) with cardiac disease in this cross-sectional study. We divided the patients into two groups according to GNRI: high-GNRI group (≥92 points) (n = 71) and low-GNRI group (<92 points) (n = 34). Handgrip strength (HG), knee extensor muscle strength (KEMS), gait speed (GS), and one-leg standing time (OLST) were assessed as indices of hospital physical performance and compared between the two groups to determine cut-off values of physical performance. RESULTS: After adjustment for age and left ventricular ejection fraction, HG, KEMS, GS, and OLST were significantly lower in the low-GNRI versus high-GNRI group. Cut-off values by ROC curve analysis were 16.2 kgf (AUC = 0.66; p < 0.001) for HG, 34.3 % of body weight (AUC = 0.62; p = 0.04) for KEMS, 1.24 m/s (AUC = 0.72; p < 0.01) for GS, and 8.28 s (AUC = 0.62; p = 0.04) for OLST. CONCLUSION: The risk of poor nutrition, as indicated by a low GNRI, might be a predictor of lower physical performance. Cut-off values determined in this study might be minimum target goals for physical performance that can be attained by elderly female cardiac inpatients.

Relation between VE/VCO2 slope and maximum phonation time in chronic heart failure patients.

This study aimed to determine the relation between the regression slope relating minute ventilation to carbon dioxide output (VE/VCO2 slope) and maximum phonation time (MPT), and the MPT required to attain a threshold value for VE/VCO2 slope of ≤ 34 in chronic heart failure (CHF) patients. This cross-sectional study enrolled 115 CHF patients (mean age, 54.5 years; men, 84.9%). VE/VCO2 slope was assessed during cardiopulmonary exercise testing (CPX). Thereafter, patients were divided into 2 groups according to exercise capacity: VE/VCO2 slope ≤ 34 (VE/VCO2 ≤ 34 group, n = 81) and VE/VCO2 slope > 34 (VE/VCO2 > 34 group, n = 34). For MPT measurements, all patients produced a sustained vowel/a:/ for as long as possible during respiratory effort from the seated position. All subjects showed significant negative correlation between VE/VCO2 slope and MPT (r = -0.51, P < 0.001). After adjustment for clinical characteristics, MPT was significantly higher in the VE/VCO2 ≤ 34 group vs VE/VCO2 > 34 group (21.4 ± 6.4 vs 17.4 ± 4.3 s, F = 7.4, P = 0.007). The appropriate MPT cut-off value for identifying a VE/VCO2 slope ≤ 34 was 18.12 seconds. An MPT value of 18.12 seconds may be a useful target value for identifying CHF patients with a VE/VCO2 slope ≤ 34 and for risk management in these patients.