Effects of Cardiac Rehabilitation With Lumbar-Type Hybrid Assistive Limb on Muscle Strength in Patients With Chronic Heart Failure　― A Randomized Controlled Trial ―

Abstract

Background: Aiming to establish an effective tool in new cardiac rehabilitation programs, we investigated the use of a lumbar-type hybrid assistive limb (HAL) in patients with heart failure (HF) who had difficulty in walking at the usual speed of healthy subjects (≈80 m/min).

Methods and Results: We randomly assigned 28 HF patients (age, 73.1±13.8 years) to perform a sit-to-stand exercise with or without HAL. The sit-to-stand exercise was repeated as many times as possible as cardiac rehabilitation therapy over a period of 6–10 days. We measured 5 parameters before and after the completion of cardiac rehabilitation: B-type natriuretic peptide, Short Physical Performance Battery (SPPB), 6-min walking distance (6MWD), 30-s chair-stand test (CS-30), and isometric knee extensor muscle strength. The SPPB and 6MWD were significantly improved, and the CS-30 score was somewhat improved, after the exercise therapy in both the HAL and non-HAL groups. The knee extensor muscle strength improved significantly in the HAL group (0.29±0.11 to 0.35±0.11 kgf/kg, P<0.01), but showed no change in the non-HAL group (0.35±0.11 to 0.35±0.13 kgf/kg, P=0.40).

Conclusions: The improved knee extensor muscle strength in the HAL group suggests that the lumbar-type HAL may be an effective tool for cardiac rehabilitation in HF patients with frailty, which is a predictor of poor prognosis in HF.

Heart failure (HF) is a growing public health issue with an estimated prevalence of around 37.7 million individuals globally.¹ Cardiac rehabilitation is a comprehensive therapeutic program consisting of exercise therapy, diet, daily life guidance, etc.² Of the components of cardiac rehabilitation, exercise therapy is essential.^2,3 Cardiac rehabilitation is recommended throughout the world as a means of preventing the recurrence and worsening of HF.⁴ Sarcopenia, a condition characterized by qualitative and quantitative impairment of skeletal muscle, commonly afflicts HF patients and contributes to a poor prognosis.⁵ A significant association between sarcopenia and frailty has been reported.⁶ Therefore, an effective approach is indispensable to alleviate sarcopenia and improve the prognosis of frail patients who participate in cardiac rehabilitation programs. The standard rehabilitation programs in patients with chronic HF include walking and bicycle exercise. These exercises are unavailable to many patients, especially those with severe HF in whom skeletal muscle functions are too severely compromised to endure an exercise-based regimen.⁷

Editorial p 68

As the world’s first wearable cyborg, the hybrid assistive limb (HAL) supports, improves, and expands a wearer’s physical functions by detecting bioelectrical signals manifested on the skin surface above the muscles when the wearer tries to generate muscle forces.^8,9 Three types of HAL have been developed so far: a lower limb type, a single joint type, and a lumbar type.^10–12 The lower-limb HAL has been reported to improve gait function in patients with chronic myelopathy,¹³ muscular dystrophy,¹⁴ and spinal cord infarction,¹⁵ and to improve walking ability in adolescents and adults with cerebral palsy.¹⁶ The lumbar-type HAL has the merit of weighing only about 3 kg (battery included), far less than the lower limb type (≈14 kg). The lumbar-type HAL improves lifting performance during repetitive lifting movements by supporting the extension of the hip joint.¹² The lumbar-type HAL is currently used to support nursing care and physical work in the field. In the past several years, the deployment of the lumbar-type HAL for care support has been reported to significantly reduce subjective lumbar fatigue during simulated patient transfer.¹⁷ The lumbar-type HAL also facilitates the stand-up exercise.¹⁸

The sit-to-stand exercise is one of the usual cardiac rehabilitation exercises performed by cardiac patients affected by sarcopenia. There have been no reports, however, on the use of HAL during sit-to-stand exercise in patients with HF. Therefore, we examined the effects of the sit-to-stand exercise performed with support from the lumbar-type HAL in patients with chronic HF.

Methods

Study Subjects

A total of 28 patients with chronic HF who satisfied all of the following criteria⁷ were enrolled:

1. Met health insurance standards of current cardiac rehabilitation (peak oxygen uptake obtained from cardiopulmonary exercise test ≤80 of normal value, left ventricular ejection fraction ≤40, B-type natriuretic peptide (BNP) ≥80 pg/mL) and undergoing exercise therapy at the University of Tsukuba Hospital.

2. Difficulty in walking at the usual speed of healthy subjects (≈80 m/min).

3. Able to consent to enter the study.

4. Aged ≥20 years.

5. Approximate height between 150 and 190 cm, approximate weight within 40–100 kg, and able to wear the HAL.

6. Able to continue hospitalization during the clinical study.

Patients who met any of the following criteria⁷ were excluded from this study.

1. Contraindication to exercise, such as unstable angina, decompensated HF, symptomatic aortic valve stenosis, acute myocarditis, symptomatic hypertrophic obstructive cardiomyopathy, systemic inflammatory disease, or exercise-induced arrhythmia.

2. Unable to perform the sit-to-stand exercise due to orthopedic, central/peripheral nervous-system, or social (behavioral) problem.

3. Medically unstable.

The patients were randomly assigned to either the HAL group or conventional exercise therapy (control) group at a 1 : 1 allocation ratio with the minimization method. The allocation factors were age (age ≥75 or <75 years), sex (male or female), and severity of HF (BNP ≥200 or <200 pg/mL).

The Tsukuba University Clinical Research Review Board approved the study (TCRB18-023). The study protocol was registered with the UMIN Clinical Trials Registry (UMIN000030761) and the Japan Registry of Clinical Trials (jRCTs032180105). All participants gave their written informed consent before enrollment.

Exercise Protocol

The patients in the HAL group performed the sit-to-stand exercise using the lumbar-type HAL (HAL-FB02-SSSJP) for 5–30 min/day (Supplementary Movie). The physical therapist adjusted the power of the assist torque based on the patient’s posture during the sit-to-stand motion. The control group performed the sit-to-stand exercise for the same duration according to the same schedule, but without assistance from the HAL. As a program for cardiac rehabilitation, the sit-to-stand exercise with or without HAL was performed as often as possible over a study period of 6–10 days, up to an upper limit of 30 min/day of exercise therapy. In both groups, the exercise duration was ≈5 min on the first day and gradually increased to suit the patient’s physical fitness and familiarity with the sit-to-stand exercise. The heart rate (HR), systolic and diastolic blood pressures (SBP and DBP), and subjective ratings of exercise intensity on the Borg scale were monitored every minute during the exercise therapy.

On the first day, the patients in the HAL group performed 2 sessions of the sit-to-stand exercise, one with HAL and one without HAL, allowing an interval of approximately 30 min of rest between the sessions. When a participant or investigator judged that the exercise using HAL clearly imposed an excessive load, either due to the weight of the HAL or the physical stress it imposed compared with exercise without the HAL, the participant was immediately excluded from the study. The order of the exercises with and without HAL on the first day alternated according to the order of subjects’ registrations. Both groups performed the exercise therapy in accordance with the “Rehabilitation Guidelines for Cardiovascular Disease Patients” published by the Japanese Circulation Society in 2012.¹⁹

Lumbar-Type HAL System

As reported previously in detail,⁷ the lumbar-type HAL consists of a battery, an exoskeletal frame, power units, lumbar and thigh supporter belts, electrodes, and a sensor of bioelectrical signals.^12,20 When worn around the waist, the device improves the motor function of the trunk and lower limbs, and promotes the voluntary movements of the wearer by generating torque with the power units based on the bioelectrical signals measured on the wearer’s skin. Electrodes attached to the skin covering the lumbar erector spinae muscles can detect the action potentials of nerves and muscles as bioelectrical signals, and thereby sense the wearer’s intention to perform the sit-to-stand movement. These mechanisms enable the HAL device to coordinate the level and timing of the torque to assist the motion of the hip joint. These are innovative technologies based on the hypothesis of an interactive biofeedback mechanism.^21,22

Outcome Measurements

The following parameters were assessed as primary outcome measurements: HR, BP, and subjective ratings of exercise intensity during exercise therapy (Borg scale), number of days from the start of exercise therapy before the patient could walk independently, and number of days from the start of exercise therapy to discharge.⁷ The number of days from the start of exercise therapy before the patient could walk independently was counted only in those who could walk independently at discharge.

As secondary outcome measurements, the following parameters were assessed before and after the exercise therapy: BNP, isometric knee extensor muscle strength, standing ability (30-s chair-stand test: CS-30), 6-min walking distance (6MWD), and Short Physical Performance Battery (SPPB).⁷ The CS-30 is a test to assess a subject’s sit-to-stand ability. The participant is seated in the middle of the chair with his/her arms crossed at the wrists and held against the chest, and asked to complete as many full stands as possible within 30 seconds. The SPPB is a combination of 3 sub-tests, namely, a balance test, walking test, and standing-up test, to evaluate the subject’s lower limb function. Each sub-test is scored on a scale from 0 to 4 points, summing up to 12 points in total. A higher score indicates better lower limb function.

Sample Size

In this study, we aimed to confirm the safety and feasibility of the lumbar-type HAL as a new rehabilitation tool in HF patients. Because there have been no clinical studies comparing a HAL group and non-HAL group of HF patients, the target number of cases was set to a total of 30 cases (15 cases in the HAL group and 15 cases in the control group).

Statistical Analysis

For categorical data, Fisher’s exact test was used to test differences in the baseline variables between the HAL and non-HAL groups. The Wilcoxon signed-rank test was used to compare the outcome measures in each group before and after the completion of the exercise therapy. The Mann-Whitney U test was used to compare the change between groups. All statistical analyses were conducted using SPSS (version 24.0). Statistical significance was set at P<0.05.

Results

The 28 patients enrolled in the study were randomized into 2 groups. No adverse events were observed during the study period in either group; 4 patients (3 in the control group, 1 in the HAL group) were discharged from hospital early for reasons unrelated to the study, and thus were unable to complete the exercise therapy for the pre-defined period of ≥6 days. These patients were excluded from the analysis, and the data on the remaining 24 patients (13 in the HAL group, 11 in the control group) were analyzed (Table 1). Although the patients in the HAL group performed the sit-to-stand exercise both with and without HAL on the first day, none of them experienced excessive load from the exercise with HAL compared with that without HAL. There were no differences between groups in mean age, height, body mass index, left ventricular ejection fraction, New York Heart Association functional class, or BNP. Also, the baseline physical assessment and prevalence of frailty did not differ between groups (Table 2).

Table 1. Clinical Characteristics of the Study Patients

Characteristics	All patients (n=24)	HAL group (n=13)	Control group (n=11)	P value
Male/female	13/11	7/6	6/5	1.00
Age (years)	72.9±14.7	71.0±18.5	75.2±8.9	0.91
Height (m)	160.6±9.8	160.5±10.5	160.8±9.6	0.84
Weight (kg)	54.3±10.2	51.6±8.0	57.5±12.0	0.23
Body mass index (kg/m2)	21.0±3.5	20.0±2.5	22.2±4.1	0.30
LVEF (%)	39.8±19.8	39.9±18.1	39.5±22.6	0.87
NYHA class	2.4±0.6	2.2±0.6	2.5±0.5	0.28
BNP (pg/mL)	816.7±612.0	914.7±614.5	689.4±616.7#	0.41
Etiology
Coronary artery disease	9 (37.5)	4 (30.8)	5 (45.5)	0.67
Valvular heart disease	6 (25.0)	2 (15.4)	4 (36.4)	0.35
Idiopathic dilated cardiomyopathy	3 (12.5)	2 (15.4)	1 (9.1)	1.00
Arrhythmia	2 (8.3)	1 (7.7)	1 (9.1)	1.00
Other cardiac disease	4 (16.7)	4 (30.8)	0	0.09
Creatinine	1.21±0.69	1.21±0.77	1.19±0.61	0.93
Rhythm
Sinus	12 (50.0)	8 (61.5)	4 (36.4)	0.41
Pacing	8 (33.3)	5 (38.5)	3 (27.3)	0.67
Atrial fibrillation	4 (16.7)	0	4 (36.4)	0.03
Medications
β-blocker	14 (58.3)	7 (53.8)	7 (63.6)	0.69
ACEI/ARB	10 (41.7)	7 (53.8)	3 (27.3)	0.24
Diuretic	24 (100.0)	13 (100.0)	11 (100.0)	*
Ca-channel blocker	7 (29.2)	4 (30.8)	3 (27.3)	1.00
Catecholamine	10 (41.7)	4 (30.8)	6 (54.5)	0.40

Data are presented as the mean±SD or n (%) of patients unless otherwise indicated. *No statistics. ^#1 patient in the control group was excluded because of missing data after exercise therapy. ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin-receptor blocker; BNP, B-type natriuretic peptide; LVEF, left ventricular ejection fraction; NYHA class, New York Heart Association functional class.

Table 2. Baseline Physical Assessment and Prevalence of Frailty Patients

	All patients (n=24)	HAL group (n=13)	Control group (n=11)	P value
Physical assessment
Knee extensor muscle strength (kgf/kg)	0.32±0.11	0.29±0.11	0.35±0.11	0.22
CS-30 (n)	5.7±4.6	5.5±5.1	6.0±4.3	0.95
6MWD (m)	185.4±75.9	187.1±69.0	183.4±86.8	0.95
SPPB	6.7±2.7	6.8±2.4	6.6±3.2	0.73
Frequency of frailty components
Weight loss	5 (20.8)	3 (23.1)	2 (18.2)	1.00
Grip strength	19 (79.2)	12 (92.3)	7 (63.6)	0.14
Exhaustion	24 (100)	13 (100)	11 (100)	*
Slow walk	24 (100)	13 (100)	11 (100)	*
Low activity	20 (83.3)	12 (92.3)	8 (72.7)	0.30
No. of frailty components present
0	0 (0)	0 (0)	0 (0)	*
1	0 (0)	0 (0)	0 (0)	*
2	1 (4.2)	0 (0)	1 (9.1)	0.45
3	4 (16.7)	1 (7.7)	3 (27.3)	0.30
4	17 (70.8)	10 (76.9)	7 (63.6)	0.65
5	2 (8.3)	2 (15.4)	0	0.48

Data are presented as the mean±SD or n (%) of patients unless otherwise indicated. *No statistics. 6MWD, 6-min walking distance; CS-30, 30-s chair-stand test; SPPB, Short Physical Performance Battery.

The total number of rehabilitation days in the HAL group, 7.2±1.5 days, did not significantly differ from that in the control group, 6.8±1.3 days (P=0.53). The total number of stand-up exercises at the first session in the HAL group was 61.2±44.2, and did not significantly differ from that in the control group (49.3±31.0, P=0.69). Also, there was no difference in the total number of stand-up exercises at the final session between the groups (117.8±118.9 in the HAL group; 77.8±55.0 in the control group, P=0.33). There was no difference for the total number of stand-up exercises during the study period between groups (629±463 in the HAL group; 485±237 in the control group, P=0.42).

In both groups, no patient performed treadmill or ergometer exercise during the study period. However, in accordance with the “Rehabilitation Guidelines for Cardiovascular Disease Patients”,¹⁹ both groups performed walking along a corridor of the ward, balance exercise, lower limb muscle strengthening exercise, and basic movement exercise, according to the patient’s condition, in addition to the sit-to-stand exercise. There was no difference between groups in the time of these exercises other than the sit-to-stand exercise (53.8±79.3 min in the HAL group; 54.5±53.7 min in the control group, P=0.65). At the start of the study, 6 patients in each group could walk independently. Although 7 patients in the HAL group and 5 patients in the control group could walk under supervision but could not walk independently at the start of the study, 5 patients in the HAL group and 3 patients in the control group acquired independent walking at discharge. For these 8 patients, the number of days from the start of exercise therapy before the patient could walk independently was 7.6±4.6 days in the HAL group and 7.3±0.5 days in the control group (P=0.76). There was no difference between groups in the number of days from the start of exercise therapy to discharge (19.6±14.5 days in the HAL group; 19.8±14.4 days in the control group, P=0.87).

At the first exercise session in the HAL group, HR significantly increased from 85±14 to 95±18 beats/min (P<0.05). However, SBP (from 105±23 to 109±27 mmHg) and DBP (from 63±9 to 62±12 mmHg) did not significantly change. At the first exercise session in the control group, HR significantly increased from 80±12 to 91±10 beats/min (P<0.01), but SBP (from 106±18 to 110±22 mmHg) and DBP (from 69±14 to 65±16 mmHg) did not change. At the final exercise session in the HAL group, HR significantly increased from 80±12 to 99±20 beats/min (P<0.01), and SBP (from 109±30 to 118±31 mmHg, P<0.01) and DBP (from 64±10 to 70±12 mmHg, P<0.01) also significantly increased. At the final exercise session in the control group, HR significantly increased from 80±12 to 88±11 beats/min (P<0.05), but SBP (from 115±19 to 110±19 mmHg) and DBP (from 66±11 to 70±13 mmHg) did not significantly change. There was no significant difference between groups in the Borg scale score at the end of the final exercise session (12.9±1.3 in the HAL group; 12.6±0.5 in the control group).

The knee extensor muscle strength improved significantly in the HAL group, increasing from 0.29±0.11 before the sit-to-stand exercise therapy to 0.35±0.11 kgf/kg (P<0.01) after the therapy (Figure 1), whereas it was unchanged in the control group (0.35±0.11 to 0.36±0.14 kgf/kg, P=0.42). The HAL group showed significantly more improvement in isometric knee extensor muscle strength than the control group (P=0.045). The BNP was significantly improved after the exercise therapy in the HAL group (914.7±614.5 to 501.2±345.7 pg/mL, P<0.01), while that in the control group tended to improve (689.4±616.7 to 466.4±697.7 pg/mL, P=0.059; Figure 2). The CS-30 tended to be higher after the exercise therapy in both groups (HAL group, 5.5±5.1 to 8.2±5.3, P=0.054; control group, 6.0±4.3 to 9.2±6.2, P=0.075; Figure 3). In the HAL group, 6MWD (from 187.1±69.0 to 254.7±110.4 m, P<0.01) and SPPB (from 6.8±2.4 to 8.6±3.0, P<0.05) were significantly improved after the exercise therapy. Also in the control group, 6MWD (from 183.4±86.8 to 239.1±104.3 m, P<0.05) and SPPB (from 6.6±3.2 to 8.5±3.0, P<0.05) were significantly improved after the exercise therapy.

Figure 1.

Isometric knee extensor muscle strength before and after cardiac rehabilitation in the HAL and control groups. HAL, hybrid assistive limb.

Figure 2.

BNP before and after cardiac rehabilitation in the HAL and control groups. The data in one patient in the control group was excluded because of missing data after exercise therapy. BNP, B-type natriuretic peptide; HAL, hybrid assistive limb.

Figure 3.

CS-30 before and after cardiac rehabilitation in the HAL and control groups. CS-30, 30-s chair-stand test; HAL, hybrid assistive limb.

Discussion

This is the first randomized controlled trial to investigate the effects of the use of the lumbar-type HAL in patients with HF. Our results demonstrate that the sit-to-stand exercise with assistance from HAL significantly improved knee extensor muscle strength in the HF patients. The results also suggest that the HAL-assisted exercise may be a safe and feasible cardiac rehabilitation tool, without increasing BNP, in HF patients.

The lumbar-type HAL facilitates the sit-to-stand exercise by supporting hip extension. While being worn, the HAL device measures bioelectrical signals, assesses posture, and calculates the assist torque based on the measurement information and an assist setting by the torque tuner. A power unit arranged at the hip joint outputs the calculated assist torque to assist the wearer’s trunk and hip joint movements. In CVC mode, the device supports motion according to the wearer’s motion intention. The device provides no motion support unless the person tries to move. From another perspective, it only supports motion that resembles the motion pattern of a healthy person. The wearer, therefore, may intuitively adjust his/her body to facilitate the assistance received from the HAL. When the participants in our study performed the sit-to-stand exercise without assistance from the HAL, the exercise probably recruited the muscles of the upper limbs and trunk in order to compensate for the insufficient strength of the lower limbs. Consequently, the control group participants may have found it difficult to perform the exercise naturally and properly with their lower limbs.

Previous studies have suggested that the use of the lumbar-type HAL reduces lumbar muscle activity during repetitive lifting tasks and increases quadriceps muscle activity.²³ Patients with cardiac disease, who have limited mobility, may be able to perform the required exercise more stably, naturally, and accurately when relying on the motion assistance from HAL.⁷ We believe that the lumbar-type HAL improved the knee extensor muscle strength in the HAL group principally by assisting the hip joint. We presume that the increase in lower limb muscle strength resulted not from muscle hypertrophy, but from neurological factors such as an increase in the motor unit discharge rate.²⁴ Exercise using the lumbar-type HAL may have conferred a high motor learning effect by promoting brain, nerve, and muscle activity through the hypothesized mechanism of interactive biofeedback.^21,22

Although there was no significant difference, the number of stand-up exercises in the final session was a little higher in the HAL group than in the control group, which indicated that the patients in the HAL group became accustomed to the HAL and could use it efficiently. Probably, these factors enabled the patients to endure more, and thus increased the BP in the final session in the HAL group.

Sarcopenia is characterized by qualitative and quantitative impairments of the skeletal muscle and is significantly associated with frailty.⁶ An effective approach to alleviating sarcopenia is essential to improving the prognosis of frail patients participating in cardiac rehabilitation programs. Walking and bicycle exercise have become standard rehabilitation programs for patients with chronic HF, but are burdensome and possibly unsuitable for patients with severe HF or severely impaired skeletal muscle function. The sit-to-stand exercise is one of the usual cardiac rehabilitation therapies prescribed for patients who have difficulty in performing aerobic exercise or sarcopenic patients with heart disease. Our results suggest that the lumbar-type HAL may promote exercise therapy in HF patients who have difficulty in walking at the normal speed of healthy subjects. Our results also suggest that patients performing the HAL-assisted exercise over a specific period may be able to improve their lower limb muscle strength more than patients undergoing a standard cardiac rehabilitation program without HAL support. In other words, the lumbar-type HAL may be used as a therapeutic device that secures the sit-to-stand exercise at an early stage of cardiac rehabilitation. In addition to the short-term effects of improving lower limb muscle strength, we propose that the long-term effects of HAL support may include early hospital discharge, prevention of future cardiovascular events, and a reduced risk of rehospitalization. These are topics for future study.

Frailty and HF have been widely researched in conjunction with each other in recent years.^25,26 They have common mechanistic features, such as comorbidities, inflammation, and sarcopenia.²⁶ Management strategies and potential interventions for HF and frailty are required, especially in elderly patients. The Heart Failure Association has redefined its frailty score by dividing it into 4 major domains: clinical, physical and functional, cognitive psychological, and social.²⁷ As such, comprehensive and multidimensional assessments and approaches are required for HF patients with frailty. Matsue et al showed that hospitalized elderly patients with HF were more likely to have physical frailties, social frailties, and cognitive dysfunction.²⁸ These conditions overlapped in their subjects, especially in those of advanced age, and the prognosis worsened as the number of frail domains increased.²⁸ Exercise-based cardiac rehabilitation for HF patients with frailty has recently been found to be associated with a good prognosis.²⁸ Participation in exercise-based cardiac rehabilitation was also associated with a good prognosis in patients with HF with preserved ejection fraction, and across frailty subgroups in whom the efficacy of cardiac rehabilitation had been questioned.²⁹

Study Limitations

The sample size was small. The assessments were not blinded, and thus were potentially open to observer bias. Although not statistically different, the baseline value of knee extensor muscle strength was a little lower and the baseline value of BNP was higher in the HAL group. These differences, which may be due to the small number of subjects, might have affected the present findings. Although we initially set the sample size to a total of 30 cases, we terminated the study after enrolling 28 patients, because of the coronavirus crisis.

Conclusions

Motion assistance from HAL during the sit-to-stand exercise significantly improved muscle strength in HF patients. The lumbar-type HAL may be an effective tool for frailty, a predictor of poor prognosis in HF.

Conflicts of Interest

H. Kawamoto is an Associate Professor of University of Tsukuba, a co-founder, a shareholder, and a part-time director of university venture company CYBERDYNE Inc. (Ibaraki, Japan). Y.S. is an inventor of the world’s first wearable cyborg HAL, a stockholder and the CEO of university venture company CYBERDYNE, the manufacturer of the wearable cyborg HAL. Y.S.’s COI is strictly managed by the board of directors of CYBERDYNE, and by the University of Tsukuba according to the national university rules. Patents of HAL belongs to University of Tsukuba, and CYBERDYNE pays a patent royalty to the University of Tsukuba according to national university rules. CYBERDYNE was not involved in the study design, in the collection, analysis, or interpretation of the data, in the writing of the report, in the financial/non-financial support, or in the decision to submit the paper for publication. This information is fully described in the consent forms. K.A. is a member of Circulation Journal’s Editorial Team. The following authors report no conflicts of interest: H. Kato, H.W., A.K., L.W., K.H., H. Konno, T.M., I.N., A.S., K.A., and M.I.

Funding

This work was supported in part by a grant-in-aid for Scientific Research from the Ministry of Education, Science, and Culture of Japan (JSPS KAKENHI grant no. JP17K09485).

Statement of Ethics

This study was conducted according to the tenets of the Declaration of Helsinki and the ethical guidelines on clinical research. The Tsukuba University Clinical Research Review Board approved this study (TCRB18-023). The study protocol was registered with the UMIN Clinical Trials Registry (UMIN000030761) and the Japan Registry of Clinical Trials (jRCTs032180105). All participants gave their written informed consent before enrollment.

Data Availability

The deidentified participant data will not be shared.

Author Contributions

Conceptualization: A.K. Funding acquisition: A.K. Supervision: A.K., M.I. Methodology, Project administration: H. Kato, H.W., L.W., K. Hayashi, H. Konno, T.M., I.N., A.S. Formal analysis: H. Kato, H.W. Writing – Original Draft: H. Kato, H.W., A.K. Writing – Review & Editing: A.K. Confirm the final manuscript: A.K., L.W., K.H., H. Konno, T.M., I.N., A.S., H. Kawamoto, K.A., Y.S., M.I.

Supplementary Files

Supplementary Movie. Example of the sit-to-stand exercise using the lumbar-type HAL.

Please find supplementary file(s);

http://dx.doi.org/10.1253/circj.CJ-21-0381

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